From a JACI 2012 review:
Chemical structure and cross-reactivity in sulfonamide allergy
Sulfonamides are drugs carrying the SO2-NH2 group. This group is present in many different drugs. Of allergenic relevance are antibacterial sulfonamides (sulfamethoxazole [SMX], sulfadoxine, and sulfapyridine), which are derivatives of sulfanilamides.
Non-sulfanilamide drugs, such as glibenclamide, furosemide, and celecoxib, are not stimulatory and tolerated by patients allergic to sulfanilamides. The term “sulfa allergy” is therefore misleading.
Immunology of sulfanilamide allergies
The mechanism of sulfanilamide hypersensitivity reactions involves:
- frequent T cell–mediated reactions. They are different types and of varying severity - rash (maculopapular exanthem), DRESS, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
- rare IgE reactions - IgE-mediated urticaria and anaphylaxis
- occasional IgG antibody–mediated reactions - hemolytic anemia
One medication can cause reactiobs via different mechanisms. For example, sulfamethoxazole [SMX] can elicit an IgE response, a T cell–mediated response, or both to modified proteins, which can result in different clinical pictures.
SMX can also directly stimulate T cells. This is a typical example of the pharmacologic interaction with immune receptor (p-i) concept. This means that SMX directly binds to the HLA receptor (p-i HLA), T-cell receptor (p-i TCR), or both and thereby elicits T-cell stimulation.
Symptoms of sulfonamide hypersensitivities
Under treatment with sulfonamide antimicrobial agents, 2% of the general population have adverse drug reactions suggestive of an allergic mechanism.
A special problem is the rather high occurrence of a sulfanilamide-related side effect in patients with HIV. Cotrimoxazole was widely in HIV-positive patients and the prevalence of rashes is higher than in the general population.
Two sulfonilamide (amprenavir und fosamprenavir) are used as protease inhibitors in HIV therapy. They induce a high degree of rashes (19-29%), which in 1-3% require to stop therapy.
Sulfanilamides and DRESS
Sulfanilamide allergies include potentially life-threatening reactions, such as SJS/TEN and DRESS. This latter syndrome is also called drug (induced) hypersensitivity syndrome (DHS or DiHS), because not all patients have eosinophilia. DRESS appears typically after a 2-10-week drug exposure.
Patients with DRESS have skin rash, fever, lymph node swelling, hepatitis, or involvement of other organs. Many patients have facial swelling; some have signs of a capillary leak syndrome. More than 70% have marked eosinophilia (often higher than 1 G/L). The lethality is 5-10% and mainly caused by liver failure.
There are some peculiar features that make DRESS a vexing disease:
- recurrent symptoms long after having stopped drug treatment is common. It is often related to reactivation of herpesviruses, in particular human herpesvirus 6, EBV, or CMV.
- intolerance of other drugs/chemicals during the active phase of DRESS: different “innocuous” drugs, such as acetaminophen, can cause flare-ups. Occasionally, even a permanent second drug allergy to a further compound can develop (ie, multiple drug hypersensitivity syndrome).
Diagnosis of sulfonamide hypersensitivity
In the acute phase of an anaphylactic reaction, increased serum tryptase levels (1-4 hours after anaphylaxis) support the diagnosis of an acute allergy. However, these tests do not pinpoint the relevant drug.
An allergy workup is normally recommended 1-6 months after the reaction and it might comprise of skin and in vitro tests.
- The sensitivity of these tests is low, but the specificity is good, which makes a positive result valuable.
Intradermal skin tests might be helpful in both immediate and nonimmediate reactions. SMX at a concentration of 80 mg/mL has been shown to be nonirritating in intradermal tests. However, the sensitivity of intradermally applied SMX in different skin manifestations is not known.
In addition, intradermal skin tests have a small risk for eliciting systemic allergic reactions (mostly mild and transient).
- Patch tests and LTTs are used in Europe in patients with nonimmediate reactions. The latter seems to have a fairly good sensitivity and specificity in lamotrigine- and carbamazepine-induced DRESS.
The risk of a patch test (10% in dimethyl sulfoxide or petrolatum) is negligible; however, its sensitivity seems to be lower than that of late (24 hours) reading of intradermal tests.
LTT seems to be more sensitive and allows also testing compounds in vitro, which are not available for in vivo tests. The test measures the drug-induced proliferation of the patient’s PBMCs during a 6-day culture. However, the LTT is still a rather complex procedure that is not available in many centers.
Treatment od sulfonamide hypersensitivity
The presumably causative drugs should immediately be withdrawn.
- In nonimmediate SMX reactions with mild rashes and no signs of mucosal or extracutaneous symptoms, the cotrimoxazole treatment can be continued or readministered after a “desensitization” protocol. Such “treating through” or “desensitization” is most often used in HIV-positive patients and is successful in 44-79% of cases. It requires monitoring for systemic involvement (fever, eosinophilia, lymphadenopathy, and hepatitis).
- In patients with severe nonimmediate reactions, the T-cell immune system is massively activated, and these patients might temporarily react to many “innocuous” drugs with a flare-up. It is common practice to reduce drug therapy in patients with DRESS as much as possible as long as activated lymphocytes are detectable in the circulation.
- For the treatment of DRESS with severe organ involvements (eg, alanine aminotransferase/aspartate aminotranse level higher than 500 U/L), corticosteroids are used.
Patients with sulfanilamide-induced SJS/TEN are best referred in specialized (eg, burn) centers.
Table 1. Classification of sulfonamides
Sulfanilamides (sometimes refered to as sulflonyl-arylamines)
Antibacterial agents:
Sulfadiazine
Sulfamethoxazole
Sulfisoxazole
Sulfapyridine (in sulfasalazine)
Protease inhibitors:
Amprenavir
Fosamprenavir
----------
Non-sufanilamides
COX-2 inhibitors:
Celecoxib
Etoricoxib
Carbonic anhydrase inhibitors:
Acetazolamide
Brinzolamide
Dorzolamide
Methazolamide
Diuretics:
Bumetanide
Chlorthalidone
Chlorothiazide
Diazoxide
Furosemide
Hydrochlorothiazide
Indapamide
Metolazone
Torasemide
Sulfonylureas:
Chlorpropamide
Glibenclamide
Glimepiride
Glipizide
Glyburide
Tolbutamide
Tolazamide
Other non-sufanilamides:
Ibutilide
Sotalol
Topiramate
Zonisamide
References:
Allergy to sulfonamides. Benno Schnyder, MD, Werner J. Pichler. The Journal of Allergy and Clinical Immunology, Volume 131, Issue 1 , Pages 256-257.e5, January 2013.
http://www.jacionline.org/article/S0091-6749(12)01610-7/fulltext
Showing posts with label Review. Show all posts
Showing posts with label Review. Show all posts
Diagnosis of chronic cough in children
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Pathophysiology of cough:
- large particles reach the upper respiratory structures - removed by coughing unless lodged as foreign body
- small particles reach the bronchioles - removed by mucociliary activity
- smallest particles reach the alveoli - removed by alveolar macrophages by phagocytosis
Cough expels particles from the airway at "the speed of sound."
Acute cough
Defined as cough of less than 4-week in duration. The most common cause is acute upper respiratory infection (URTI). The cough is usually non-productive or minimally productive of sputum (phlegm).
Frequent viral infection (normal frequency is up to 8-10 per year) with acute cough can mimic chronic cough. Acute cough due to repeated viral infections is associated with normal chest X-ray. This type of cough is unresponsive to asthma therapy with ICS or LTRA.
Chronic cough
Defined as cough of greater than 4-week in duration. Evaluation is indicated.
Chronic cough is very common and it is the 5th most frequent cause of patient visits. The most common cause of chronic cough in children is cough-variant asthma.
Cough suppressants (cough syrup) are prescribed on a "massive scale" in children but there is little evidence for efficacy beyond the placebo effect and the natural resolution of the cough.
The current guidelines (see the references at the end of the article) divide chronic cough into specific and nonspecific categories.
Placebo effect can have a considerable impact, Treatment should be based on the etiology of the cough. Adult studies may not be applicable to children, for example, GERD is a common cause in adults but relatively rarer in children, foreign body aspiration should be considered in children.
Chronic productive purulent cough always requires intervention.
Differential diagnosis of cough, a simple mnemonic is GREAT BAD CAT TOM. Click here to enlarge the image: (GERD (reflux), Laryngopharyngeal Reflux (LPR), Rhinitis (both allergic and non-allergic) with post-nasal drip (upper airway cough syndrome, UACS), Embolism, e.g. PE in adults, Asthma, TB (tuberculosis), Bronchitis, pneumonia, pertussis, protracted/persistent bacterial bronchitis (PBB), Aspiration, e.g foreign body in children, Drugs, e.g. ACE inhibitor, CF in children, Cardiogenic, e.g. mitral stenosis in adults, Achalasia in adults, Thyroid enlargement, e.g. goiter, "Thoughts" (psychogenic), Other causes, Malignancy, e.g. lung cancer in adults).
Diagnosis of chronic cough
History - ask about duration (months vs. years), seasonal trends (e.g. allergic asthma triggered by ragweed), times of day when present (night cough could be GERD), associated symptoms, triggers (e.g. exercise in EIB), inhaled foreign body or choking at any age (50% of aspirated foreign bodies have no history), successful and unsuccessful therapies, recent weight loss (ominous sign - cancer or severe infection), recurrent infections (could indicate immune deficiency (PIDD) or ciliary dyskinesia).
Physical examination - assess growth and development for nutritional status and/or obesity, upper respiratory tract for signs of allergic rhinitis (pale boggy trubinates, allergic shiners, Dennie's line), chronic sinus disease, postnasal drip, nasal polyps (CF, PIDD), ear-cough reflex (foreign body in the ear triggers cough in 5% of children).
Specific chronic cough - clinical clues for diagnosis
- auscultatory findings (asthma, CF)
- cardiac abnormalities
- chest pain or dyspnea
- elevated respiratory rate
- chest wall deformity
- digital clubbing
- productive purulent cough (CF, foreign body)
- difficulty with exercise (EIB)
- failure to thrive (CF)
- recurrent bacterial pneumonia (CF, PIDD)
- feeding difficulty - aspiration from the "top" (swallowing problem) or "below" (GERD)
- hemoptysis - never "normal"
- hypoxemia
- immune deficiency
- congenital anomaly
- neurodevelopmental condition - aspiration risk
Nonspecific cough
Evaluation of nonspecific cough:
- chest X-ray - CF, pneumonia. "If you suspect meningitis, do an LP. If you suspect CF, do a sweat test." The current newborn screening identifies 95% of children with CF - this means that 5% of children with CF are not identified at birth and present with symptoms later in life.
- spirometry - asthma
If CXR and spirometry are normal, observe for 1 to 2 weeks.
Treatment of nonspecific cough
Consider prescribing:
- an antibiotic (macrolide) for "wet" productive cough. A 2-week course of amoxycillin clavulanate achieves cough resolution in children with chronic wet cough, supporting the diagnosis of protracted/persistent bacterial bronchitis (PBB, http://goo.gl/4Vmtd).
- a trial of inhaled steroid (ICS) for dry cough
Specific chronic cough
Diagnostic evaluation includes:
- infants and toddlers - chest X-ray and sweat chloride test
- infants and toddlers - evaluate for aspiration - due to either gastroesophageal reflux (GERD) ("bottom") or swallowing disorder ("top")
- infants and toddlers - immunodeficiency studies - quantitative immunoglobulins (IgGAME), nitroblue tetrazolium test (NBT) or even better DHR, complete blood count with differential
- reversible airway obstruction - spirometry if older than 5 years, followed by aerosolized bronchodilator, check for reversible obstruction 15 minutes later. If positive (more than 12% reversibility), treat for asthma.
- older children - chest X-ray, sweat chloride, pulmonary function tests (PFTs), and immunodeficiency studies
- computed tomography (CT) for bronchiectasis, interstitial lung disease (ILD), and congenital lesions. Use a pediatric CT protocol to minimize radiation
- flexible bronchoscopy for microbiological culture and airway assessment
- rigid bronchoscopy (performed by otolaryngologist (ENT) for aspirated foreign body (right mainstem bronchus is the typical place)
Chronic cough causes in children when using a step-by-step approach:
- 25% asthma. Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011).
- 23% prolonged bronchitis, protracted/persistent bacterial bronchitis (PBB) (responds to antibiotics)
- 20% upper airway cough syndrome or UACS (post-nasal drip)
- 5% GERD
- 2% bronchiectasis
Chronic cough causes in children when using "order all test from the beginning" approach. Work-up included chest X-ray, bronchoscopy, pulmonary function tests (PFTs) with bronchial challenge, sweat chloride, pH probe for GERD, and immunoglobulin levels (IgGAME):
- 28% GERD
- 22% allergic rhinitis or post-nasal drip (upper airway cough syndrome, UACS)
- 13% asthma
- 5% infection
- 3% aspiration
- 20% multiple etiologies - this is due to all tests done concurrently
Age-based diagnosis of chronic cough:
- infancy - aspiration, asthma, cystic fibrosis, recurrent respiratory tract infections, passive smoke exposure, congenital heart disease
- early childhood - aspiration, asthma, foreign body aspiration, cystic fibrosis, bronchiectasis, chronic sinusitis
- late childhood and adolescence - asthma, bronchiectasis, cystic fibrosis, infection, foreign body aspiration, active or passive cigarette smoke, psychogenic cough, sinusitis, post-nasal drip
Aspirated (retained foreign body
This can occur at any age. There is a positive initial history only in 30% of cases - the yield can be increased to 50% by focused questioning.
Ask about high risk habits - eating nuts, chewing on pencil eraser, etc.
Imaging: inspiratory-expiratory or bilateral decubitus plain films, CT may be necessary
The ultimate diagnosis and treatment is with rigid bronchoscopy by ENT.
Psychogenic cough (habit cough)
Typically diagnosed in pre-teens and teenagers. It disappears during sleep. Diagnostic evaluation is non-revealing. There is no response to medications (ICS or antibiotics).
Cough-variant asthma
Chronic, persistent cough - without wheezing - may be the only manifestation of asthma. More than 60% bronchial obstruction is needed to produce wheezing - asthma can occur without wheezing - spirometry is required for diagnosis.
Cough-variant asthma presents as dry cough at night. It worsens with exercise (EIA) and nonspecific triggers (cold air).
Cough-variant asthma responds to asthma therapy with ICS.
Cough-variant asthma is diagnosed with pulmonary function testing (PFTs) with response to bronchodilator.
The most common cause of chronic cough in children is cough-variant asthma.
Cough suppressants in children - there are no randomized controlled trials to support efficacy. The suppression could be hazardous, especially with productive cough.
Treat viral-related cough with increased fluid intake and humidity (aerosolized saline, etc.).
The cough suppressant dosing guidelines for adults are imprecise in children. An alternative is throat lozenges ("Halls", etc.).
References
Chronic cough in children – Sally L. Davidson Ward. Audio-Digest Pediatrics, Volume 56, Issue 10, May 21, 2010.
Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chang AB, Glomb WB. Chest. 2006 Jan;129(1 Suppl):260S-283S.
Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Agency for Healthcare Research and Quality.
Related reading
How should one investigate a chronic cough? Cleveland Clinic Journal of Medicine, 2011.
Tips to Remember: Cough in Children. Allergy Tips brochures by AAAAI.
Allergies are bad, sure -- but do you know what happens when your kid inhales a nut. ChicagoTribune.com, 2011.
Green or yellow phlegm likely to be bacterial - confirming beliefs by doctors & patients http://goo.gl/zff8X and http://goo.gl/cwKGs
Diagnostic algorithm for the approach to children with chronic cough. ER, 2011.
Diagnostic Checklist (mobile version) - UToronto and standard web version
Childhood cough - 2012 BMJ review.
Child with chronic cough - WAO interactive case http://goo.gl/yK48I
AInotes - Chronic Cough (Pediatric) http://bit.ly/Ue0g83
Differential diagnosis of chronic cough in children. Allergy and Asthma Proceedings, Volume 35, Number 2, March/April 2014 , pp. 95-103(9) http://buff.ly/1mpq9oy
Figures
Clinical approach from the concept of cough hypersensitivity - figure: http://buff.ly/1Jej9Cq
Video
Chronic Cough - COLA video lecture http://bit.ly/URcUQa:
Published: 11/12/2010
Updated: 11/26/2013
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Pathophysiology of cough:
- large particles reach the upper respiratory structures - removed by coughing unless lodged as foreign body
- small particles reach the bronchioles - removed by mucociliary activity
- smallest particles reach the alveoli - removed by alveolar macrophages by phagocytosis
Cough expels particles from the airway at "the speed of sound."
Acute cough
Defined as cough of less than 4-week in duration. The most common cause is acute upper respiratory infection (URTI). The cough is usually non-productive or minimally productive of sputum (phlegm).
Frequent viral infection (normal frequency is up to 8-10 per year) with acute cough can mimic chronic cough. Acute cough due to repeated viral infections is associated with normal chest X-ray. This type of cough is unresponsive to asthma therapy with ICS or LTRA.
Chronic cough
Defined as cough of greater than 4-week in duration. Evaluation is indicated.
Chronic cough is very common and it is the 5th most frequent cause of patient visits. The most common cause of chronic cough in children is cough-variant asthma.
Cough suppressants (cough syrup) are prescribed on a "massive scale" in children but there is little evidence for efficacy beyond the placebo effect and the natural resolution of the cough.
The current guidelines (see the references at the end of the article) divide chronic cough into specific and nonspecific categories.
Placebo effect can have a considerable impact, Treatment should be based on the etiology of the cough. Adult studies may not be applicable to children, for example, GERD is a common cause in adults but relatively rarer in children, foreign body aspiration should be considered in children.
Chronic productive purulent cough always requires intervention.
Differential diagnosis of cough, a simple mnemonic is GREAT BAD CAT TOM. Click here to enlarge the image: (GERD (reflux), Laryngopharyngeal Reflux (LPR), Rhinitis (both allergic and non-allergic) with post-nasal drip (upper airway cough syndrome, UACS), Embolism, e.g. PE in adults, Asthma, TB (tuberculosis), Bronchitis, pneumonia, pertussis, protracted/persistent bacterial bronchitis (PBB), Aspiration, e.g foreign body in children, Drugs, e.g. ACE inhibitor, CF in children, Cardiogenic, e.g. mitral stenosis in adults, Achalasia in adults, Thyroid enlargement, e.g. goiter, "Thoughts" (psychogenic), Other causes, Malignancy, e.g. lung cancer in adults).
Diagnosis of chronic cough
History - ask about duration (months vs. years), seasonal trends (e.g. allergic asthma triggered by ragweed), times of day when present (night cough could be GERD), associated symptoms, triggers (e.g. exercise in EIB), inhaled foreign body or choking at any age (50% of aspirated foreign bodies have no history), successful and unsuccessful therapies, recent weight loss (ominous sign - cancer or severe infection), recurrent infections (could indicate immune deficiency (PIDD) or ciliary dyskinesia).
Physical examination - assess growth and development for nutritional status and/or obesity, upper respiratory tract for signs of allergic rhinitis (pale boggy trubinates, allergic shiners, Dennie's line), chronic sinus disease, postnasal drip, nasal polyps (CF, PIDD), ear-cough reflex (foreign body in the ear triggers cough in 5% of children).
Specific chronic cough - clinical clues for diagnosis
- auscultatory findings (asthma, CF)
- cardiac abnormalities
- chest pain or dyspnea
- elevated respiratory rate
- chest wall deformity
- digital clubbing
- productive purulent cough (CF, foreign body)
- difficulty with exercise (EIB)
- failure to thrive (CF)
- recurrent bacterial pneumonia (CF, PIDD)
- feeding difficulty - aspiration from the "top" (swallowing problem) or "below" (GERD)
- hemoptysis - never "normal"
- hypoxemia
- immune deficiency
- congenital anomaly
- neurodevelopmental condition - aspiration risk
Nonspecific cough
Evaluation of nonspecific cough:
- chest X-ray - CF, pneumonia. "If you suspect meningitis, do an LP. If you suspect CF, do a sweat test." The current newborn screening identifies 95% of children with CF - this means that 5% of children with CF are not identified at birth and present with symptoms later in life.
- spirometry - asthma
If CXR and spirometry are normal, observe for 1 to 2 weeks.
Treatment of nonspecific cough
Consider prescribing:
- an antibiotic (macrolide) for "wet" productive cough. A 2-week course of amoxycillin clavulanate achieves cough resolution in children with chronic wet cough, supporting the diagnosis of protracted/persistent bacterial bronchitis (PBB, http://goo.gl/4Vmtd).
- a trial of inhaled steroid (ICS) for dry cough
Specific chronic cough
Diagnostic evaluation includes:
- infants and toddlers - chest X-ray and sweat chloride test
- infants and toddlers - evaluate for aspiration - due to either gastroesophageal reflux (GERD) ("bottom") or swallowing disorder ("top")
- infants and toddlers - immunodeficiency studies - quantitative immunoglobulins (IgGAME), nitroblue tetrazolium test (NBT) or even better DHR, complete blood count with differential
- reversible airway obstruction - spirometry if older than 5 years, followed by aerosolized bronchodilator, check for reversible obstruction 15 minutes later. If positive (more than 12% reversibility), treat for asthma.
- older children - chest X-ray, sweat chloride, pulmonary function tests (PFTs), and immunodeficiency studies
- computed tomography (CT) for bronchiectasis, interstitial lung disease (ILD), and congenital lesions. Use a pediatric CT protocol to minimize radiation
- flexible bronchoscopy for microbiological culture and airway assessment
- rigid bronchoscopy (performed by otolaryngologist (ENT) for aspirated foreign body (right mainstem bronchus is the typical place)
Chronic cough causes in children when using a step-by-step approach:
- 25% asthma. Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011).
- 23% prolonged bronchitis, protracted/persistent bacterial bronchitis (PBB) (responds to antibiotics)
- 20% upper airway cough syndrome or UACS (post-nasal drip)
- 5% GERD
- 2% bronchiectasis
Chronic cough causes in children when using "order all test from the beginning" approach. Work-up included chest X-ray, bronchoscopy, pulmonary function tests (PFTs) with bronchial challenge, sweat chloride, pH probe for GERD, and immunoglobulin levels (IgGAME):
- 28% GERD
- 22% allergic rhinitis or post-nasal drip (upper airway cough syndrome, UACS)
- 13% asthma
- 5% infection
- 3% aspiration
- 20% multiple etiologies - this is due to all tests done concurrently
Age-based diagnosis of chronic cough:
- infancy - aspiration, asthma, cystic fibrosis, recurrent respiratory tract infections, passive smoke exposure, congenital heart disease
- early childhood - aspiration, asthma, foreign body aspiration, cystic fibrosis, bronchiectasis, chronic sinusitis
- late childhood and adolescence - asthma, bronchiectasis, cystic fibrosis, infection, foreign body aspiration, active or passive cigarette smoke, psychogenic cough, sinusitis, post-nasal drip
Aspirated (retained foreign body
This can occur at any age. There is a positive initial history only in 30% of cases - the yield can be increased to 50% by focused questioning.
Ask about high risk habits - eating nuts, chewing on pencil eraser, etc.
Imaging: inspiratory-expiratory or bilateral decubitus plain films, CT may be necessary
The ultimate diagnosis and treatment is with rigid bronchoscopy by ENT.
Psychogenic cough (habit cough)
Typically diagnosed in pre-teens and teenagers. It disappears during sleep. Diagnostic evaluation is non-revealing. There is no response to medications (ICS or antibiotics).
Cough-variant asthma
Chronic, persistent cough - without wheezing - may be the only manifestation of asthma. More than 60% bronchial obstruction is needed to produce wheezing - asthma can occur without wheezing - spirometry is required for diagnosis.
Cough-variant asthma presents as dry cough at night. It worsens with exercise (EIA) and nonspecific triggers (cold air).
Cough-variant asthma responds to asthma therapy with ICS.
Cough-variant asthma is diagnosed with pulmonary function testing (PFTs) with response to bronchodilator.
The most common cause of chronic cough in children is cough-variant asthma.
Cough suppressants in children - there are no randomized controlled trials to support efficacy. The suppression could be hazardous, especially with productive cough.
Treat viral-related cough with increased fluid intake and humidity (aerosolized saline, etc.).
The cough suppressant dosing guidelines for adults are imprecise in children. An alternative is throat lozenges ("Halls", etc.).
References
Chronic cough in children – Sally L. Davidson Ward. Audio-Digest Pediatrics, Volume 56, Issue 10, May 21, 2010.
Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Chang AB, Glomb WB. Chest. 2006 Jan;129(1 Suppl):260S-283S.
Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines. Agency for Healthcare Research and Quality.
Related reading
How should one investigate a chronic cough? Cleveland Clinic Journal of Medicine, 2011.
Tips to Remember: Cough in Children. Allergy Tips brochures by AAAAI.
Allergies are bad, sure -- but do you know what happens when your kid inhales a nut. ChicagoTribune.com, 2011.
Green or yellow phlegm likely to be bacterial - confirming beliefs by doctors & patients http://goo.gl/zff8X and http://goo.gl/cwKGs
Diagnostic algorithm for the approach to children with chronic cough. ER, 2011.
Diagnostic Checklist (mobile version) - UToronto and standard web version
Childhood cough - 2012 BMJ review.
Child with chronic cough - WAO interactive case http://goo.gl/yK48I
AInotes - Chronic Cough (Pediatric) http://bit.ly/Ue0g83
Differential diagnosis of chronic cough in children. Allergy and Asthma Proceedings, Volume 35, Number 2, March/April 2014 , pp. 95-103(9) http://buff.ly/1mpq9oy
Figures
Clinical approach from the concept of cough hypersensitivity - figure: http://buff.ly/1Jej9Cq
Video
Chronic Cough - COLA video lecture http://bit.ly/URcUQa:
Published: 11/12/2010
Updated: 11/26/2013
Cellular and Molecular Immunology by Abbas et al: Video Lectures and Q&A
Author: V. Dimov, M.D., Fellow, Creighton University Division of Allergy & ImmunologyReviewer: S. Randhawa, M.D., Fellow, LSU (Shreveport) Department of Allergy & Immunology
The textbook Cellular and Molecular Immunology by Abbas et al. explains the experimental observations that form the basis for the science of immunology.
Some links that may help you to get more out of the textbook are listed below:
Video Lectures, Conferences On-Line Allergy (COLA) by Children's Mercy Hospital
Immunology - Abbas Chapter 5: MHC
Immunology - Abbas Chapter 7: Antigen Receptors and Accessory Molecules
Imuunology - Abbas Chapter 8 - Lymphocyte Development
Immunology: Abbas Chapter 9 - T-cell Activation
Immunology: Abbas Chapter 10 - B-cell Activation
Immunology: Abbas Chapter 11 - Immunologic Tolerance
Immunology: Abbas Chapter 13 - Effector Mechanisms of Cell-Mediated Immunity
Cytokines and Their Receptors
Anticytokine Treatments for Asthma and Rhinitis
Immunology Jeopardy
Principles of Flow Cytometry
The Conferences On-Line Allergy (COLA) is a collaborative venture between the Children's Mercy Hospitals & Clinics section of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology (ACAAI).
Questions and Answers
Abbas MCQ from FIT Corner by ACAAI, 2004.
The questions are posted in a reverse chronological order and you have to scroll to the bottom of the web page in order to see the first chapter.
Image source: Nutrophil, Wikipedia, GNU Free Documentation License.
Published: 02/01/2009
Updated: 03/04/2009
Eosinophilic Esophagitis: Brief Review
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
Eosinophilic esophagitis (EoE) is an eosinophilic inflammation of the esophagus which was first reported in 1978.
IL-5 is the predominant mediators in the EoE inflammation. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.
The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.
Eosinophilic Esophagitis (click here to enlarge the image).
Clinical Manifestations
EoE is a common cause of dysphagia in children. Adult patients are usually men (3:1 M:F) in their 30s or 40s.
Presenting symptoms:
- dysphagia 93%
- food impaction 62%
- heartburn 24%
50-80% of the patients have a history of allergies. A family history of atopic disease is present in 74%.
Peripheral blood eosinophilia
31% have peripheral blood eosinophilia. Blood eosinophilia is not diagnostic and the correlation with disease activity is not established.
Total Immunoglobulin E (IgE)
Serum IgE levels are increased in 55% of patients but total IgE cannot serve as a marker for disease progression or resolution.
Natural History
EoE is a chronic disease with persistent or relapsing symptoms. Esophageal metaplasia (Barrett's esophagus or cardia-type metaplasia) has not been described in EE (different from GERD).
Diagnosis
How to diagnose EoE?
EoE is diagnosed by a biopsy of the esophagus which shows more than 15 eosinophils per HPF. Biopsy specimens should be obtained regardless of the gross appearance of the mucosa.
A peak count of at least 15 intraepithelial eosinophils per HPF is an absolute minimum number to make the diagnosis of EoE. At least 1 HPF must contain at least 15 intraepithelial eosinophils.
Patients with GERD-related esophagitis have fewer than 10 eosinophils per HPF. Any eosinophil number larger than 0 in esophagus is abnormal.
Eosinophils ascend in number as one descends in the GI tract:
0 eosinophils in esophagus
2 eosinophils in stomach
5 eosinophils in small bowel
15-50 eosinophils in large bowel
This eosonophils distribution may have evolved in the evolution to protect the body against parasitic infections ("sitting there waiting for parasites").
Endoscopic findings (abnormal in 91% of patients):
- mucosal fragility 59%
- rings or corrugated lining 49%
- strictures 40%
A corrugated esophagus characterized by fine concentric mucosal rings is a hallmark of EE. One hypothesis explains this by acetylcholine release which contracts muscle fibers in the muscularis mucosae resulting in the formation of concentric esophageal rings.
The rings or corrugated lining make the esophagus look like trachea during EGD. Some authors have called eosinophilic esophagitis "asthma of the esophagus." The changes in esophageal mucosa are reminiscent of airway remodelling in asthma.
Allergic Evaluation
Patients with EoE have a higher incidence (50-80%) of allergic rhinitis, asthma, and atopic dermatitis. Some authors have called eosinophilic esophagitis "asthma of the esophagus." An evaluation by an allergist for other atopic diseases is recommended. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.
- Food allergy: multiple food sensitizations are found in 80% of patients
- Aeroallergens: multiple environmental sensitizations are found in 90% of patients
The presence of allergic rhinitis, sensitization to aeroallergens, or both ranges from 42% to 93% in children with eosinophilic esophagitis. In addition, dietary therapy has a role in EoE treatment. According to the most recent consensus document, children with eosinophilic esophagitis should be evaluated for food and aeroallergen sensitization (Liacouras CC, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011 (July); 128(1):3-20).
Peripheral Cytokines
Eotaxin-3 expression is a promising marker for distinguishing EoE from other causes of esophagitis. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.
Treatment
Currently, there is no FDA-approved treatment for eosinophilic esophagitis. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation (Allergy, 2012).
Some treatment to eosinophilic esophagitis can be summarized by the following mnemonic: SADD
Steroids (local, PO)
Acid suppression with PPI
Diet (6- or 8-food elimination diet)
Dilatation of esophagus (if strictures)
Some experts advise to choose one course of therapy: medical OR diet.
Corticosteroids
Both systemic and topical corticosteroids are effective for therapy of EoE but pathological findings and symptoms reccur when discontinued.
When to use systemic corticosteroids in EoE?
In emergent cases such as dysphagia requiring hospitalization, dehydration because of swallowing difficulties, and weight loss.
Starting dose is 440-880 micrograms per day for children and 880-1760 micrograms per day for adolescents/adults. This regimen is continued for at least 6-8 weeks, depending on the response. Several studies have shown that the eosiniphilic infiltration returns when the swallowed steroids are stopped.
Leukotriene receptor antagonists (Singulair) and cromolyn are not useful for treatment of EE.
How to use steroids for topical treatment of EoE?
Patients should be instructed to use a metered dose inhaler (MDI) without a spacer. MDI is inserted in the mouth and sprayed with lips sealed around the device. The powder is swallowed and not rinsed (just the opposite of using MDI in asthma). Patients should not eat or drink for at least 30 minutes.
Acid Suppression
In patients with EoE, symptoms are unresponsive or only partially responsive to acid blockade with PPIs. PPI therapy is not a primary treatment for EE but rather a co-therapy. Children with eosinophilic esophagitis (EoE) treated with PPIs show an improvement in symptoms despite persistent eosinophilic inflammation. PPI treatment may be useful maintenance therapy in children with EoE (Annals of Allergy&Immunology, 2012).
Dietary Treatment
- Elimination diet (6-food elimination diet: peanut, milk, egg, soy, seafood, wheat)
- Elemental diet
Dietary therapy (specific antigens removal or elemental formula) can be useful in children with EoE. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.
Elemental diet "cures" 95% of EoE but is difficult to implement.
Esophageal Dilatation
Esophageal dilatation is useful for patients with fixed esophageal strictures causing food impaction. Medical therapy should be attempted first.
Monitoring of therapy in EoE
One approach is to perform repeated EGDs with biopsy every 4-6 months until esophageal eosinophilia is resolved.
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
Eosinophilic esophagitis (EoE) is an eosinophilic inflammation of the esophagus which was first reported in 1978.
IL-5 is the predominant mediators in the EoE inflammation. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.
The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.
Eosinophilic Esophagitis (click here to enlarge the image).
Clinical Manifestations
EoE is a common cause of dysphagia in children. Adult patients are usually men (3:1 M:F) in their 30s or 40s.
Presenting symptoms:
- dysphagia 93%
- food impaction 62%
- heartburn 24%
50-80% of the patients have a history of allergies. A family history of atopic disease is present in 74%.
Peripheral blood eosinophilia
31% have peripheral blood eosinophilia. Blood eosinophilia is not diagnostic and the correlation with disease activity is not established.
Total Immunoglobulin E (IgE)
Serum IgE levels are increased in 55% of patients but total IgE cannot serve as a marker for disease progression or resolution.
Natural History
EoE is a chronic disease with persistent or relapsing symptoms. Esophageal metaplasia (Barrett's esophagus or cardia-type metaplasia) has not been described in EE (different from GERD).
Diagnosis
How to diagnose EoE?
EoE is diagnosed by a biopsy of the esophagus which shows more than 15 eosinophils per HPF. Biopsy specimens should be obtained regardless of the gross appearance of the mucosa.
A peak count of at least 15 intraepithelial eosinophils per HPF is an absolute minimum number to make the diagnosis of EoE. At least 1 HPF must contain at least 15 intraepithelial eosinophils.
Patients with GERD-related esophagitis have fewer than 10 eosinophils per HPF. Any eosinophil number larger than 0 in esophagus is abnormal.
Eosinophils ascend in number as one descends in the GI tract:
0 eosinophils in esophagus
2 eosinophils in stomach
5 eosinophils in small bowel
15-50 eosinophils in large bowel
This eosonophils distribution may have evolved in the evolution to protect the body against parasitic infections ("sitting there waiting for parasites").
Endoscopic findings (abnormal in 91% of patients):
- mucosal fragility 59%
- rings or corrugated lining 49%
- strictures 40%
A corrugated esophagus characterized by fine concentric mucosal rings is a hallmark of EE. One hypothesis explains this by acetylcholine release which contracts muscle fibers in the muscularis mucosae resulting in the formation of concentric esophageal rings.
The rings or corrugated lining make the esophagus look like trachea during EGD. Some authors have called eosinophilic esophagitis "asthma of the esophagus." The changes in esophageal mucosa are reminiscent of airway remodelling in asthma.
Allergic Evaluation
Patients with EoE have a higher incidence (50-80%) of allergic rhinitis, asthma, and atopic dermatitis. Some authors have called eosinophilic esophagitis "asthma of the esophagus." An evaluation by an allergist for other atopic diseases is recommended. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.
- Food allergy: multiple food sensitizations are found in 80% of patients
- Aeroallergens: multiple environmental sensitizations are found in 90% of patients
The presence of allergic rhinitis, sensitization to aeroallergens, or both ranges from 42% to 93% in children with eosinophilic esophagitis. In addition, dietary therapy has a role in EoE treatment. According to the most recent consensus document, children with eosinophilic esophagitis should be evaluated for food and aeroallergen sensitization (Liacouras CC, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011 (July); 128(1):3-20).
Peripheral Cytokines
Eotaxin-3 expression is a promising marker for distinguishing EoE from other causes of esophagitis. Both IL-5 and IL-13 cause release of eotaxin which attracts eosinophils.
Treatment
Currently, there is no FDA-approved treatment for eosinophilic esophagitis. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation (Allergy, 2012).
Some treatment to eosinophilic esophagitis can be summarized by the following mnemonic: SADD
Steroids (local, PO)
Acid suppression with PPI
Diet (6- or 8-food elimination diet)
Dilatation of esophagus (if strictures)
Some experts advise to choose one course of therapy: medical OR diet.
Corticosteroids
Both systemic and topical corticosteroids are effective for therapy of EoE but pathological findings and symptoms reccur when discontinued.
When to use systemic corticosteroids in EoE?
In emergent cases such as dysphagia requiring hospitalization, dehydration because of swallowing difficulties, and weight loss.
Topical corticosteroids
Topical corticosteroids are often helpful when used in the setting of EoE, 87% of children respond to topical budesonide.
Topical corticosteroids are often helpful when used in the setting of EoE, 87% of children respond to topical budesonide.
Two inhaled corticosteroids have been used to treat eosinophilic esophagitis - fluticasone and budesonide.
The usual starting dose of budesonide in an adult is a 1 mg ampule mixed with a slurry of artificial sweetener (usually sucralose) using 10 packets, dependent upon taste, and swallowed b.i.d. In a child, 0.5 mg can be used in the same way, mixed with 5 packets.
Fluticasone is typically started at a dose of 440 mcg b.i.d. This can be lowered to 220 mcg b.i.d. subsequently.
Starting dose is 440-880 micrograms per day for children and 880-1760 micrograms per day for adolescents/adults. This regimen is continued for at least 6-8 weeks, depending on the response. Several studies have shown that the eosiniphilic infiltration returns when the swallowed steroids are stopped.
Leukotriene receptor antagonists (Singulair) and cromolyn are not useful for treatment of EE.
How to use steroids for topical treatment of EoE?
Patients should be instructed to use a metered dose inhaler (MDI) without a spacer. MDI is inserted in the mouth and sprayed with lips sealed around the device. The powder is swallowed and not rinsed (just the opposite of using MDI in asthma). Patients should not eat or drink for at least 30 minutes.
Acid Suppression
In patients with EoE, symptoms are unresponsive or only partially responsive to acid blockade with PPIs. PPI therapy is not a primary treatment for EE but rather a co-therapy. Children with eosinophilic esophagitis (EoE) treated with PPIs show an improvement in symptoms despite persistent eosinophilic inflammation. PPI treatment may be useful maintenance therapy in children with EoE (Annals of Allergy&Immunology, 2012).
Dietary Treatment
- Elimination diet (6-food elimination diet: peanut, milk, egg, soy, seafood, wheat)
- Elemental diet
Dietary therapy (specific antigens removal or elemental formula) can be useful in children with EoE. Skin prick testing for foods and environmental allergens (aeroallergen) should be considered in all patients.
Elemental diet "cures" 95% of EoE but is difficult to implement.
Esophageal Dilatation
Esophageal dilatation is useful for patients with fixed esophageal strictures causing food impaction. Medical therapy should be attempted first.
Monitoring of therapy in EoE
One approach is to perform repeated EGDs with biopsy every 4-6 months until esophageal eosinophilia is resolved.
What is the most potent chemokine (chemoattractant) for eosinophils?
(A) IL-5
(B) IL-8
(C) LTB4
(D) eotaxin
(E) IL-4
(F) IL-13
Answer: D.
Eotaxin is the most potent chemoattractant for eosinophils but IL-5 is the most specific stimulant of their production.
References
Eosinophilic Esophagitis. NEJM Images.
Potential pathogenesis and effects of tissue remodeling in patients with EoE. JACI Images, Nov 2011.
Eosinophilic esophagitis: the newest esophageal inflammatory disease. Atkins, D. et al. Nat. Rev. Gastroenterol. Hepatol. 6, 267–278 (2009) (PDF).
Eosinophilic Esophagitis. Harrison's Online.
Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. National Guideline Clearinghouse.
Eosinophilic disorders. JACI, Volume 119, Issue 6, Pages 1291-1300 (June 2007).
Eosinophilic oesophagitis. Alyson Kakakios and Ralf G Heine. MJA 2006; 185 (7): 401.
Eosinophilic Oesophagitis: A Common Cause of Dysphagia in Young Adults? Medscape, 11/2008.
Eosinophilic Esophagitis. NEJM Images.
Potential pathogenesis and effects of tissue remodeling in patients with EoE. JACI Images, Nov 2011.
Eosinophilic esophagitis: the newest esophageal inflammatory disease. Atkins, D. et al. Nat. Rev. Gastroenterol. Hepatol. 6, 267–278 (2009) (PDF).
Eosinophilic Esophagitis. Harrison's Online.
Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. National Guideline Clearinghouse.
Eosinophilic disorders. JACI, Volume 119, Issue 6, Pages 1291-1300 (June 2007).
Eosinophilic oesophagitis. Alyson Kakakios and Ralf G Heine. MJA 2006; 185 (7): 401.
Eosinophilic Oesophagitis: A Common Cause of Dysphagia in Young Adults? Medscape, 11/2008.
Eosinophilic esophagitis after specific oral tolerance induction for egg protein http://goo.gl/fzmip
Video
Eosinophilic Esophagitis. The DAVE Project - Gastroenterology.
Related reading
Proton-Pump Inhibitors (PPIs) Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use http://goo.gl/zANv
Repeating allergy testing in children with eosinophilic esophagitis whose original tests were negative. Ask the Expert, AAAAI, 2011.
Reslizumab (anti-IL5) led to improvements in histology, but not in symptoms in eosinophilic esophagitis. Medscape, 2012.
Eosinophilic Esophagitis treatment strategy relies on 3 D's: drugs, diets, dilation (free full text review), 2012.
Video
Eosinophilic Esophagitis. The DAVE Project - Gastroenterology.
Related reading
Proton-Pump Inhibitors (PPIs) Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use http://goo.gl/zANv
Repeating allergy testing in children with eosinophilic esophagitis whose original tests were negative. Ask the Expert, AAAAI, 2011.
Reslizumab (anti-IL5) led to improvements in histology, but not in symptoms in eosinophilic esophagitis. Medscape, 2012.
Eosinophilic Esophagitis treatment strategy relies on 3 D's: drugs, diets, dilation (free full text review), 2012.
Comments from Twitter
@DrSilge: Dr. Aceves says that they use 0.5 mg budesonide respules in 5 packets, not the 1 mg. If need higher dose, use 10 packets. She states that want the volume for surface area, moreso than the higher concentration of medication.
Dr John Weiner @AllergyNet: Not just hot topic, but burning, summarized superbly by @Allergy
Published: 08/09/2008
Updated: 05/21/2012
Dr John Weiner @AllergyNet: Not just hot topic, but burning, summarized superbly by @Allergy
Published: 08/09/2008
Updated: 05/21/2012
Food Challenges for Diagnosis of Food Allergy
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
A growing numbers of patients present to allergists with laboratory findings of food sensitization and low likelihood of reaction. It is imperative that the allergisst be able to give patients and parents a definitive answer. Clinical history, skin prick testing (SPT), and serum immunoglobulin E (sIgE) levels can only provide data to suggest the likelihood of reaction. The ultimate diagnosis is provided by an oral food challenge (OFC). An open OFC is safe, provided it is carried out in the office of a board-certified allergist. 85% of U.S. allergists perform oral food challenges for diagnosis of food allergy, however only 6% perform more than 10 OFCs per month (JACI, 2011). The duration of the procedure is 3 to 4 hours.
What is a food challenge?
Food challenge is consuming increasing amounts of suspected food at fixed intervals under observation. It is done by feeding gradually increasing doses of the suspected food at 10-30 minutes until a reaction occurs or a normal amount of the food is eaten without causing symptoms. All negative blind challenges end with an open challenge. Oral food challenges are essential to the diagnosis of food allergy.
Oral Food Challenges (click to enlarge the diagram).
3 Types of oral food challenges: DOS:
Double-blind placebo-controlled food challenge (DBPCFC)
Open food challenge (OFC)
Single-blind placebo-controlled food challenge (SBPCFC)
Open food challenge (OFC)
Both the physician and the patient are aware that the patient is eating the suspected food. The challenge food is not disguised in any way. For example, a child with a history of egg allergy is given increasing doses of scrambled egg every 30 minutes until a whole egg is ingested. Generally, OFC is used when the skin testing for the suspected food is negative.
In a retrospective medical record review of open food challenges in 109 patients, 27% of challenges were positive. Reactions were mild to moderate in 92% of positive challenges. Cutaneous reactions occurred in 68% of positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement. Food specific IgE values did not correlate with reaction severity. Interventions included observation or antihistamine only in 92% of positive challenges. No patient received epinephrine or required hospitalization. Negative challenges to milk, peanut, and egg, were predicted by pre-challenge food specific IgE.
Open food challenges are a safe procedure in the office setting for patients selected based on history and food specific IgE approaching negative predictive values.
Single-blind placebo-controlled food challenge (SBPCFC)
The physician is aware of what the patient is being fed, but the patient is not. The suspected food is disguised so the patient is unaware of the contents. For example, a child with a history of egg allergy is given egg hidden in other food.
Double-blind placebo-controlled food challenge (DBPCFC)
Neither the physician nor the patient know what the patient is being fed. The suspected food is disguised in another food. DBPCFC is the gold standard for diagnosing food allergy. DBPCFC is the method of choice for scientific protocols.
DBPCFC’s have taught us that:
- most case histories are inaccurate
- there is short list of foods in 90% of cases
- most children are allergic 1-2 foods only
The final dose of all 3 -- OFC, SBPCFC and DBPCFC, is open and the same -- a normal portion of the suspected food is ingested openly. All negative blind challenges end with an open challenge (OFC).
Clinical reactivity is ruled out once 10 grams of dry food is ingested.
Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to diagnose food allergy because it eliminates both patient and physician bias. In clinical settings though, open food challenge is the most practical test. DBPCFC is not often performed in non-academic allergy setting.
Preparation before food challenge
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction.
The patients should avoid the suspected food for at least 2 weeks (elimination diet).
Antihistamines should be discontinued at least 5 days prior to the challenge. Intravenous access should be obtained in patients with history of severe reactions.
The patient should be without symptoms, and fasting on the day of the challenge.
The procedure is cumbresome and labor intensive. The suspected food is hidden in opaque capsules to elminate taste and smell. Challenge with different foods on different days.
What is the dose in OFCs?
Typical total doses administered during a food challenge: 8-10 g of the dry food, 100 mL of wet food, doubling the amounts for meat or fish.
Food challenge dosing scheme: divide the total challenge into 7 incremental doses: 1%, 4%, 10%, 15%, 20%, 25%, 25% of the total dose.
Graded doses of either a challenge food or a placebo food are administered every 10-30 minutes. Wait for 30 minutes after the last dose. Clinical reactivity is ruled out once 10 grams of dry food is ingested. Most OFCs use doubling doses every 15 minutes until an age-appropriate serving size is administered.
What happens after the final dose in OFC?
All patients should be monitored for at least 2 hours postchallenge and instructed to contact the allergy clinic for any delayed reactions.
Precautions
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction. If there is a history of a severe anaphylactic reaction, do not perform an oral food challenge.
Severity of allergic response is on a continuum:
Subjective --> Objective --> Anaphylaxis --> Death
In asthma, ensure long wash-out periods, FEV1 ≥ 80%, and follow-up with FEV1 hourly for 6 hours after the challenge.
When performed by a board-certified allergist, oral challenge is a very safe procedure. There have been no deaths related to oral food challenge for food allergy, when performed in physician offices, according to literature indexed since 1976.
What happens when the patient "fails" the food challenge?
In a study of 584 food challenges, 43% resulted in an allergic reaction. Of patients who "failed" the challenge, there were 78% cutaneous, 43% gastrointestinal, 26% oral, 26% lower respiratory, and 25% upper respiratory reactions. No patients had cardiovascular symptoms.
There was no difference between foods in the severity of failed challenges or the type of treatment required to reverse symptoms. All reactions were reversible with short-acting antihistamines ± epinephrine, β-agonists, and/or corticosteroids. No children required hospitalization, and there were no deaths.
Other Important Diagnostic Tests in Food Allergy
Skin Prick Tests
Skin prick test (SPT) is the quickest and cheapest test for diagnosing food allergy. SPT can be performed with non-standardized allergens, for example, fresh apple. Some allergists reportedly use themselves as controls to rule out non-IgE mediated reactions.
Positive predictive accuracy of SPT is less than 50%. Negative predictive accuracy is higher than 95%. Negative skin test results essentially confirm the absence of IgE-mediated reactions.
Positive skin prick test or ImmunoCap indicates presence of IgE antibody NOT clinical reactivity (~50% false positive).
Negative skin prick test or ImmunoCap essentially excludes IgE antibody (higher than 95% accuracy).
Patients who passed the OFC without adverse symptoms had significantly smaller SPT wheal size (median, 3 mm vs. 4 mm) and significantly lower sIgE levels to the challenged foods (median, 0.63 kUA/L vs 1.06 kUA/L) as compared with the group that had a reaction during the OFC (JACI, 2011). The majority of reactions, 57%, were cutaneous, 88% were treated with antihistamine alone. Only 1.7% of the challenges required treatment with epinephrine, a rate that is equivalent to systemic reactions to subcutaneous immunotherapy (SCIT).
ImmunoCap Immunoassay (sIgE)
The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:
1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").
2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.
3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").
Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.
ImmunoCAP is a IgE fluoroenzyme immunosorbent assay. The levels vary from 0.1 to 100. The previous threshold was 0.35.
Food specific IgE cut off levels which predict 50% pass rate for challenge tests (Perry et al. JACI 2004):
Food IgE level (KUA/l)
Milk 2
Egg 2
Peanut 2
Wheat 2
ImmunoCAP threshold levels (less than 0.1) are well-established for 4 foods: milk, egg, peanuts and wheat.
The new cut-off threshold is 0.1. Specific IgE level of less than 0.1 predicts a negative food challenge test in most patients. It is important to note that in 10–25% of food allergy reactions, sIgE can be undetectable by blood test (http://buff.ly/1e7HAmY).
Negative ImmunoCAP and negative SPT give a 90% chance of a negative food challenge test. SPT provides a lower threshold than ImmunoCAP.
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Diagnostic algorithm for food allergy: SAD Child:
1. Symptoms: close relation between specific food intake and symptoms, often affect 2 or more organs
2. Allergy testing: skin prick testing or ImmunoCAP.
3. Diagnostic diet: restricted diet leads to symptoms disappearance or significant reduction
4. Challenge - oral food challenge.
Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).
References: Clinical review: ABC of allergies, Food allergy. BMJ 1998;316:1299, figure.
References
Oral food challenge testing for food allergy. JACI, 2009.
Outcomes of office-based, open food challenges in the management of food allergy. JACI, Volume 128, Issue 5 , Pages 1120-1122, November 2011.
Food Allergies. eMedicine.
Risk of oral food challenges. JACI, Volume 114, Issue 5, Pages 1164-1168 (November 2004).
Safety of open food challenges in the office setting. Ann Allergy Asthma Immunol. 2008 May;100(5):469-74.
What is a food challenge? National Jewish Health.
Manifestations of Food Allergy: Evaluation and Management. AFP, 1999.
Overdiagnosis of Food Allergy: IgE and skin-prick testing should be confined to the realm of experts (allergists). Medscape, 2011.
False-negative oral food challenge is a rare occurrence http://goo.gl/VDKY7
PowerPoint Presentations
Food Allergy. Global Resources in Allergy (GLORIA) Module 6.
Food Allergy. Againdra K. Bewtra, M.B.B.S., M.D.
Food Allergy Update. Suzanne S. Teuber, M.D.
Oral Challenge Studies: Purpose, Design and Evaluation. Stefano Luccioli, MD.
Food Allergies in 2006: From The Clinic to The Classroom. Jeffrey M. Factor, MD.
Food Allergy… the nuts and bolts. Tom Gerstner, MD, FRCPC.
Food Allergen Avoidance. V. Dimov, Oct 2008.
Audio and Video
Food Allergy and Additives. Presented by Sami L. Bahna, MD, DrPH. ACAAI Vodcasts 2007 (video).
Challenging children to see if they have overcome a food allergy: a video Health Tip. Plain Dealer, 2010.
Food challenges. National Jewish Health, 2009.
Food challenges. The Today Show, 2009.
When And How Do You Perform Food Challenges? ABC.com.
Food Challenges For Children With Allergies. ABC.com.
General Questions About Food Allergies. ABC.com.
Patients Handouts and Related Reading
The Food Allergy & Anaphylaxis Network.
Putting a face on food allergies - USA Today readers share their stories about dining out with food allergies, 2010.
Milk allergy resolution calculator from CoFAR http://bit.ly/U6TkNS - Mobile version: http://bit.ly/U6TmFn
Twitter comments
@AllergistMommy: Oral challenge uneventful = success! One more person freed from the shackles of peanut allergy!
The Food Challenge Challenge http://buff.ly/Ql0fCh - Remember: No one "fails" a food challenge. The test is either positive or negative.
Published: 07/07/2007
Updated: 05/15/2013
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
A growing numbers of patients present to allergists with laboratory findings of food sensitization and low likelihood of reaction. It is imperative that the allergisst be able to give patients and parents a definitive answer. Clinical history, skin prick testing (SPT), and serum immunoglobulin E (sIgE) levels can only provide data to suggest the likelihood of reaction. The ultimate diagnosis is provided by an oral food challenge (OFC). An open OFC is safe, provided it is carried out in the office of a board-certified allergist. 85% of U.S. allergists perform oral food challenges for diagnosis of food allergy, however only 6% perform more than 10 OFCs per month (JACI, 2011). The duration of the procedure is 3 to 4 hours.
What is a food challenge?
Food challenge is consuming increasing amounts of suspected food at fixed intervals under observation. It is done by feeding gradually increasing doses of the suspected food at 10-30 minutes until a reaction occurs or a normal amount of the food is eaten without causing symptoms. All negative blind challenges end with an open challenge. Oral food challenges are essential to the diagnosis of food allergy.
Oral Food Challenges (click to enlarge the diagram).
3 Types of oral food challenges: DOS:
Double-blind placebo-controlled food challenge (DBPCFC)
Open food challenge (OFC)
Single-blind placebo-controlled food challenge (SBPCFC)
Open food challenge (OFC)
Both the physician and the patient are aware that the patient is eating the suspected food. The challenge food is not disguised in any way. For example, a child with a history of egg allergy is given increasing doses of scrambled egg every 30 minutes until a whole egg is ingested. Generally, OFC is used when the skin testing for the suspected food is negative.
In a retrospective medical record review of open food challenges in 109 patients, 27% of challenges were positive. Reactions were mild to moderate in 92% of positive challenges. Cutaneous reactions occurred in 68% of positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement. Food specific IgE values did not correlate with reaction severity. Interventions included observation or antihistamine only in 92% of positive challenges. No patient received epinephrine or required hospitalization. Negative challenges to milk, peanut, and egg, were predicted by pre-challenge food specific IgE.
Open food challenges are a safe procedure in the office setting for patients selected based on history and food specific IgE approaching negative predictive values.
Single-blind placebo-controlled food challenge (SBPCFC)
The physician is aware of what the patient is being fed, but the patient is not. The suspected food is disguised so the patient is unaware of the contents. For example, a child with a history of egg allergy is given egg hidden in other food.
Double-blind placebo-controlled food challenge (DBPCFC)
Neither the physician nor the patient know what the patient is being fed. The suspected food is disguised in another food. DBPCFC is the gold standard for diagnosing food allergy. DBPCFC is the method of choice for scientific protocols.
DBPCFC’s have taught us that:
- most case histories are inaccurate
- there is short list of foods in 90% of cases
- most children are allergic 1-2 foods only
The final dose of all 3 -- OFC, SBPCFC and DBPCFC, is open and the same -- a normal portion of the suspected food is ingested openly. All negative blind challenges end with an open challenge (OFC).
Clinical reactivity is ruled out once 10 grams of dry food is ingested.
Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to diagnose food allergy because it eliminates both patient and physician bias. In clinical settings though, open food challenge is the most practical test. DBPCFC is not often performed in non-academic allergy setting.
Preparation before food challenge
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction.
The patients should avoid the suspected food for at least 2 weeks (elimination diet).
Antihistamines should be discontinued at least 5 days prior to the challenge. Intravenous access should be obtained in patients with history of severe reactions.
The patient should be without symptoms, and fasting on the day of the challenge.
The procedure is cumbresome and labor intensive. The suspected food is hidden in opaque capsules to elminate taste and smell. Challenge with different foods on different days.
What is the dose in OFCs?
Typical total doses administered during a food challenge: 8-10 g of the dry food, 100 mL of wet food, doubling the amounts for meat or fish.
Food challenge dosing scheme: divide the total challenge into 7 incremental doses: 1%, 4%, 10%, 15%, 20%, 25%, 25% of the total dose.
Graded doses of either a challenge food or a placebo food are administered every 10-30 minutes. Wait for 30 minutes after the last dose. Clinical reactivity is ruled out once 10 grams of dry food is ingested. Most OFCs use doubling doses every 15 minutes until an age-appropriate serving size is administered.
What happens after the final dose in OFC?
All patients should be monitored for at least 2 hours postchallenge and instructed to contact the allergy clinic for any delayed reactions.
Precautions
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction. If there is a history of a severe anaphylactic reaction, do not perform an oral food challenge.
Severity of allergic response is on a continuum:
Subjective --> Objective --> Anaphylaxis --> Death
In asthma, ensure long wash-out periods, FEV1 ≥ 80%, and follow-up with FEV1 hourly for 6 hours after the challenge.
When performed by a board-certified allergist, oral challenge is a very safe procedure. There have been no deaths related to oral food challenge for food allergy, when performed in physician offices, according to literature indexed since 1976.
What happens when the patient "fails" the food challenge?
In a study of 584 food challenges, 43% resulted in an allergic reaction. Of patients who "failed" the challenge, there were 78% cutaneous, 43% gastrointestinal, 26% oral, 26% lower respiratory, and 25% upper respiratory reactions. No patients had cardiovascular symptoms.
There was no difference between foods in the severity of failed challenges or the type of treatment required to reverse symptoms. All reactions were reversible with short-acting antihistamines ± epinephrine, β-agonists, and/or corticosteroids. No children required hospitalization, and there were no deaths.
Other Important Diagnostic Tests in Food Allergy
Skin Prick Tests
Skin prick test (SPT) is the quickest and cheapest test for diagnosing food allergy. SPT can be performed with non-standardized allergens, for example, fresh apple. Some allergists reportedly use themselves as controls to rule out non-IgE mediated reactions.
Positive predictive accuracy of SPT is less than 50%. Negative predictive accuracy is higher than 95%. Negative skin test results essentially confirm the absence of IgE-mediated reactions.
Positive skin prick test or ImmunoCap indicates presence of IgE antibody NOT clinical reactivity (~50% false positive).
Negative skin prick test or ImmunoCap essentially excludes IgE antibody (higher than 95% accuracy).
Patients who passed the OFC without adverse symptoms had significantly smaller SPT wheal size (median, 3 mm vs. 4 mm) and significantly lower sIgE levels to the challenged foods (median, 0.63 kUA/L vs 1.06 kUA/L) as compared with the group that had a reaction during the OFC (JACI, 2011). The majority of reactions, 57%, were cutaneous, 88% were treated with antihistamine alone. Only 1.7% of the challenges required treatment with epinephrine, a rate that is equivalent to systemic reactions to subcutaneous immunotherapy (SCIT).
ImmunoCap Immunoassay (sIgE)
The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:
1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").
2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.
3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").
Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.
ImmunoCAP is a IgE fluoroenzyme immunosorbent assay. The levels vary from 0.1 to 100. The previous threshold was 0.35.
Food specific IgE cut off levels which predict 50% pass rate for challenge tests (Perry et al. JACI 2004):
Food IgE level (KUA/l)
Milk 2
Egg 2
Peanut 2
Wheat 2
ImmunoCAP threshold levels (less than 0.1) are well-established for 4 foods: milk, egg, peanuts and wheat.
The new cut-off threshold is 0.1. Specific IgE level of less than 0.1 predicts a negative food challenge test in most patients. It is important to note that in 10–25% of food allergy reactions, sIgE can be undetectable by blood test (http://buff.ly/1e7HAmY).
Negative ImmunoCAP and negative SPT give a 90% chance of a negative food challenge test. SPT provides a lower threshold than ImmunoCAP.
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Diagnostic algorithm for food allergy: SAD Child:
1. Symptoms: close relation between specific food intake and symptoms, often affect 2 or more organs
2. Allergy testing: skin prick testing or ImmunoCAP.
3. Diagnostic diet: restricted diet leads to symptoms disappearance or significant reduction
4. Challenge - oral food challenge.
Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).
References: Clinical review: ABC of allergies, Food allergy. BMJ 1998;316:1299, figure.
References
Oral food challenge testing for food allergy. JACI, 2009.
Outcomes of office-based, open food challenges in the management of food allergy. JACI, Volume 128, Issue 5 , Pages 1120-1122, November 2011.
Food Allergies. eMedicine.
Risk of oral food challenges. JACI, Volume 114, Issue 5, Pages 1164-1168 (November 2004).
Safety of open food challenges in the office setting. Ann Allergy Asthma Immunol. 2008 May;100(5):469-74.
What is a food challenge? National Jewish Health.
Manifestations of Food Allergy: Evaluation and Management. AFP, 1999.
Overdiagnosis of Food Allergy: IgE and skin-prick testing should be confined to the realm of experts (allergists). Medscape, 2011.
False-negative oral food challenge is a rare occurrence http://goo.gl/VDKY7
PowerPoint Presentations
Food Allergy. Global Resources in Allergy (GLORIA) Module 6.
Food Allergy. Againdra K. Bewtra, M.B.B.S., M.D.
Food Allergy Update. Suzanne S. Teuber, M.D.
Oral Challenge Studies: Purpose, Design and Evaluation. Stefano Luccioli, MD.
Food Allergies in 2006: From The Clinic to The Classroom. Jeffrey M. Factor, MD.
Food Allergy… the nuts and bolts. Tom Gerstner, MD, FRCPC.
Food Allergen Avoidance. V. Dimov, Oct 2008.
Audio and Video
Food Allergy and Additives. Presented by Sami L. Bahna, MD, DrPH. ACAAI Vodcasts 2007 (video).
Challenging children to see if they have overcome a food allergy: a video Health Tip. Plain Dealer, 2010.
Food challenges. National Jewish Health, 2009.
Food challenges. The Today Show, 2009.
When And How Do You Perform Food Challenges? ABC.com.
Food Challenges For Children With Allergies. ABC.com.
General Questions About Food Allergies. ABC.com.
Patients Handouts and Related Reading
The Food Allergy & Anaphylaxis Network.
Putting a face on food allergies - USA Today readers share their stories about dining out with food allergies, 2010.
Milk allergy resolution calculator from CoFAR http://bit.ly/U6TkNS - Mobile version: http://bit.ly/U6TmFn
Twitter comments
@AllergistMommy: Oral challenge uneventful = success! One more person freed from the shackles of peanut allergy!
The Food Challenge Challenge http://buff.ly/Ql0fCh - Remember: No one "fails" a food challenge. The test is either positive or negative.
Published: 07/07/2007
Updated: 05/15/2013
Latex Allergy: Brief Review
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Latex is an emulsion of polymer microparticles and it may be natural or synthetic. Natural rubber latex (NRL) is the milky sap of many plants that coagulates on exposure to air.
Natural rubber latex (NRL) being collected from a "wounded" rubber tree. Image source: Wikipedia, public domain.
Latex is most often referred to the cytoplasmic exudate of the Hevea brasiliensis tree, hence the name Hev b allergens. There are more than 250 latex proteins but only 13 proteins have been characterized and designated as Hev b allergens. Skin prick reactivity to Hev b 5, 6, 7 identifies 93% of workers allergic to latex.
Hevea brasiliensis (Rubber Tree). Image source: Wikipedia, public domain.
Use of universal precautions for prevention of blood-borne infections results in exposure of health care workers to latex proteins via latex gloves. Latex has been around for more than a century but its use exploded with the AIDS epidemic in the 1980s. The material was found to strong enough to hold up after hours of surgery and offered the best protection against blood-borne diseases. The use of gloves increased almost 20 times between 1987 and 1997 (from 12 billion pairs to 200 billion).
Latex allergy, a mind map diagram (click to enlarge).
Risk factors
Risk of latex allergy is related to duration of exposure and cumulative use of latex-containing gloves. Corn starch powder in the gloves acts as an airborne vehicle for adherent latex proteins. There is a well-defined dose-response relationship between duration and numbers of gloves used and prevalence of latex sensitization. For example, in a study of dental hygienist students, none of first-year and 10% of 4th-year students were skin test−positive to latex extract.
Approximately 1% of newly hired health care workers are skin prick test−positive to latex. Hand washing disrupts the skin barrier and facilitate sensitization to latex.
Patients affected by latex allergy are especially those who have been exposed through multiple surgeries.
Symptoms
Less than 1% of the general population is sensitized to latex (the scientifically correct name is natural rubber latex). In contrast, 3-17% of health-care workers are sensitized. Latex may trigger allergic reactions in as many as one in 10 people who are exposed to it. By some estimates, 15% of medical workers are allergic to latex.
“Latex allergy” is defined as presence latex−specific IgE with symptoms of IgE-mediated reaction to latex:
- contact urticaria begins minutes after putting on latex gloves in 11% of sensitized workers
- nasal symptoms and wheezing in 15%. Respiratory symptoms are caused by latex proteins that adhere to cornstarch powder and disperse during glove changes.
Cross-reactions with fruits and vegetables
35% of sensitized patients develop allergic reactions to fruits and vegetables that contain proteins that cross-react with latex allergens:
- bell pepper and olive (Hev b 2)
- kiwi, potato (Hev b 5)
- avocado, banana, chestnut (Hev b 6)
- tomato and potato (Hev b 7)
- wheat
- papaya
- mango
Diagnosis of Latex Allergy
Skin prick test (SPT) with a latex extract is more sensitive and specific than commercial specific IgE immunoassays. However, there are no standardized skin test extracts and the allergists have to prepare the extracts for SPT themselves.
sIgE for latex allergy has much lower sensitivity than previously reported - sensitivity was 35%; specificity 98% (Ann of Allergy, Asthma, Imm, 2012). Sensitivity, specificity, NPV, and PPV of latex-specific IgE assay are 91, 72, 96 and 50%, respectively (http://goo.gl/9gX0F).
An approach to performing a test for immediate hypersensitivity to latex:
1. Prick test with the solution obtained from a soaked latex glove left in saline for one hour. Await 15 minutes.
2. If test 1. is negative, place a wet latex glove on the arm for 15 minutes.
3. If there is no response to test 2., prick through the wet latex glove. Await 15 minutes.
4. Simultaneously draw an ELISA for IgE-anti-latex (ImmunoCAP). Await the results of the ELISA before clearing for the surgical procedure.
Evaluation of patient with possible latex allergy. AAAAI Ask the Expert, 2012.
Treatment
Avoidance of exposure by a transfer to a latex-safe area in the hospital.
Control of ambient exposure by use of non−natural latex gloves and powder-free gloves by co-workers.
Future dental and surgical procedures should be performed in latex-safe facilities. Patients with history of anaphylaxis should be prescribed emergency epinephrine kits.
Johns Hopkins Hospital announced in January 2008 that it plans to end the use of all latex gloves and almost all latex medical products. It has switched to sterile neoprene and polyisoprene gloves for all surgery despite the fact that the new gloves cost 30-50% more.
Latex allergy is rarely seen in the U.S currently due to the diminished use of latex gloves in health care.
References
How to Diagnose Latex AllergyLatex Allergy. AFP, 1998.
Latex Allergy. eMedicine Specialties > Emergency Medicine > Allergy & Immunology, 2008.
Allergy and Immunology MKSAP, 3rd edition.
Latex allergy. Constance H Katelaris. MJA 2006; 185 (6): 339.
Hidden Hazard: Hospitals Target Lurking Latex. WSJ, 02/2008 (subscription may be required).
Latex avoidance in children with spina bifida prevents latex sensitization and latex allergy. http://www3.interscience.wiley.com/journal/123592239/abstract
IgE-mediated latex allergy - An exciting and instructive piece of allergy history.http://goo.gl/i5Tn
Profilin may be a pan-allergen among plants that crossreacts between pollen, fruits, vegetables and latex http://goo.gl/ZUPRQ
Multiple choice questions
Chapter 58: Latex Allergy. Allergy and Immunology Review Corner: Chapter 58 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.
Patient information
Latex Allergy. National Institutes of Health.
Latex allergy. Mayo Clinic staff.
Tips to Remember: Latex allergy. AAAAI.
Related reading
Knowing your allergies can save your life - there are different types of latex allergy. Arizona Daily Sun, 2011.
Anaphylaxis caused by latex surgical gloves immediately after starting surgery. Korean J Anesthesiol. 2010 Dec;59(Suppl):S99-S102.
Latex Allergy in OR Workers Decline - from 14.1% in 1998 to 3.9% in 2009. AAAAI 2011 Meeting.
Latex Medical Gloves: Time for a Reappraisal. Int Arch Allergy Immunol 2011;156:234-246 (DOI: 10.1159/000323892)
Contact dermatitis to latex surgical gloves? There are limited choices for non-latex gloves: vinyl or nitrile. AAAAI, 2011. Hypersensitivity reactions due to nitrile gloves - presence of latex was the cause of the symptoms (JACI, 2012).
Latex immunotherapy: state of the art. Guidelines do not consider allergy to latex as indication to desensitization http://goo.gl/j5UaA
Published: 02/04/2008
Updated: 07/15/2012
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Latex is an emulsion of polymer microparticles and it may be natural or synthetic. Natural rubber latex (NRL) is the milky sap of many plants that coagulates on exposure to air.
Natural rubber latex (NRL) being collected from a "wounded" rubber tree. Image source: Wikipedia, public domain.
Latex is most often referred to the cytoplasmic exudate of the Hevea brasiliensis tree, hence the name Hev b allergens. There are more than 250 latex proteins but only 13 proteins have been characterized and designated as Hev b allergens. Skin prick reactivity to Hev b 5, 6, 7 identifies 93% of workers allergic to latex.
Hevea brasiliensis (Rubber Tree). Image source: Wikipedia, public domain.
Use of universal precautions for prevention of blood-borne infections results in exposure of health care workers to latex proteins via latex gloves. Latex has been around for more than a century but its use exploded with the AIDS epidemic in the 1980s. The material was found to strong enough to hold up after hours of surgery and offered the best protection against blood-borne diseases. The use of gloves increased almost 20 times between 1987 and 1997 (from 12 billion pairs to 200 billion).
Latex allergy, a mind map diagram (click to enlarge).
Risk factors
Risk of latex allergy is related to duration of exposure and cumulative use of latex-containing gloves. Corn starch powder in the gloves acts as an airborne vehicle for adherent latex proteins. There is a well-defined dose-response relationship between duration and numbers of gloves used and prevalence of latex sensitization. For example, in a study of dental hygienist students, none of first-year and 10% of 4th-year students were skin test−positive to latex extract.
Approximately 1% of newly hired health care workers are skin prick test−positive to latex. Hand washing disrupts the skin barrier and facilitate sensitization to latex.
Patients affected by latex allergy are especially those who have been exposed through multiple surgeries.
Symptoms
Less than 1% of the general population is sensitized to latex (the scientifically correct name is natural rubber latex). In contrast, 3-17% of health-care workers are sensitized. Latex may trigger allergic reactions in as many as one in 10 people who are exposed to it. By some estimates, 15% of medical workers are allergic to latex.
“Latex allergy” is defined as presence latex−specific IgE with symptoms of IgE-mediated reaction to latex:
- contact urticaria begins minutes after putting on latex gloves in 11% of sensitized workers
- nasal symptoms and wheezing in 15%. Respiratory symptoms are caused by latex proteins that adhere to cornstarch powder and disperse during glove changes.
Cross-reactions with fruits and vegetables
35% of sensitized patients develop allergic reactions to fruits and vegetables that contain proteins that cross-react with latex allergens:
- bell pepper and olive (Hev b 2)
- kiwi, potato (Hev b 5)
- avocado, banana, chestnut (Hev b 6)
- tomato and potato (Hev b 7)
- wheat
- papaya
- mango
Diagnosis of Latex Allergy
Skin prick test (SPT) with a latex extract is more sensitive and specific than commercial specific IgE immunoassays. However, there are no standardized skin test extracts and the allergists have to prepare the extracts for SPT themselves.
sIgE for latex allergy has much lower sensitivity than previously reported - sensitivity was 35%; specificity 98% (Ann of Allergy, Asthma, Imm, 2012). Sensitivity, specificity, NPV, and PPV of latex-specific IgE assay are 91, 72, 96 and 50%, respectively (http://goo.gl/9gX0F).
An approach to performing a test for immediate hypersensitivity to latex:
1. Prick test with the solution obtained from a soaked latex glove left in saline for one hour. Await 15 minutes.
2. If test 1. is negative, place a wet latex glove on the arm for 15 minutes.
3. If there is no response to test 2., prick through the wet latex glove. Await 15 minutes.
4. Simultaneously draw an ELISA for IgE-anti-latex (ImmunoCAP). Await the results of the ELISA before clearing for the surgical procedure.
Evaluation of patient with possible latex allergy. AAAAI Ask the Expert, 2012.
Treatment
Avoidance of exposure by a transfer to a latex-safe area in the hospital.
Control of ambient exposure by use of non−natural latex gloves and powder-free gloves by co-workers.
Future dental and surgical procedures should be performed in latex-safe facilities. Patients with history of anaphylaxis should be prescribed emergency epinephrine kits.
Johns Hopkins Hospital announced in January 2008 that it plans to end the use of all latex gloves and almost all latex medical products. It has switched to sterile neoprene and polyisoprene gloves for all surgery despite the fact that the new gloves cost 30-50% more.
Latex allergy is rarely seen in the U.S currently due to the diminished use of latex gloves in health care.
References
How to Diagnose Latex AllergyLatex Allergy. AFP, 1998.
Latex Allergy. eMedicine Specialties > Emergency Medicine > Allergy & Immunology, 2008.
Allergy and Immunology MKSAP, 3rd edition.
Latex allergy. Constance H Katelaris. MJA 2006; 185 (6): 339.
Hidden Hazard: Hospitals Target Lurking Latex. WSJ, 02/2008 (subscription may be required).
Latex avoidance in children with spina bifida prevents latex sensitization and latex allergy. http://www3.interscience.wiley.com/journal/123592239/abstract
IgE-mediated latex allergy - An exciting and instructive piece of allergy history.http://goo.gl/i5Tn
Profilin may be a pan-allergen among plants that crossreacts between pollen, fruits, vegetables and latex http://goo.gl/ZUPRQ
Multiple choice questions
Chapter 58: Latex Allergy. Allergy and Immunology Review Corner: Chapter 58 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.
Patient information
Latex Allergy. National Institutes of Health.
Latex allergy. Mayo Clinic staff.
Tips to Remember: Latex allergy. AAAAI.
Related reading
Knowing your allergies can save your life - there are different types of latex allergy. Arizona Daily Sun, 2011.
Anaphylaxis caused by latex surgical gloves immediately after starting surgery. Korean J Anesthesiol. 2010 Dec;59(Suppl):S99-S102.
Latex Allergy in OR Workers Decline - from 14.1% in 1998 to 3.9% in 2009. AAAAI 2011 Meeting.
Latex Medical Gloves: Time for a Reappraisal. Int Arch Allergy Immunol 2011;156:234-246 (DOI: 10.1159/000323892)
Contact dermatitis to latex surgical gloves? There are limited choices for non-latex gloves: vinyl or nitrile. AAAAI, 2011. Hypersensitivity reactions due to nitrile gloves - presence of latex was the cause of the symptoms (JACI, 2012).
Latex immunotherapy: state of the art. Guidelines do not consider allergy to latex as indication to desensitization http://goo.gl/j5UaA
Published: 02/04/2008
Updated: 07/15/2012
Free Lectures and Podcasts in Allergy and Immunology
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of ChicagoReviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Conferences On-Line Allergy (COLA)
Conferences On-Line Allergy (COLA) consists of the bi-weekly presentations at the Children's Mercy Hospitals & Clinics Section of Allergy, Asthma & Immunology. The lectures are very comprehensive and cover most of the spectrum of allergy and immunology. The project could be the video analog of the textbook Middleton's Allergy: Principles and Practice one day.
It is a good idea to download all video files (if allowed by the copyright holder) since many of the webmasters remove them after a certain period of the time. The download cane be done manually or throughiTunes by choosing the "Get all" option from the podcast menu.
Conferences On-Line Allergy (COLA) - free video lectures on allergy and immunology topics by ACAAI, YouTube channel
Allergy and Immunology Lectures at the University of South Florida
USF (University of South Florida, USA) Allergy & Immunology Lecture Series. The 55-minute lectures are recorded in wma format and are best viewed by using Windows Media Player software.
Conferences On-Line Allergy (COLA) - free video lectures on allergy and immunology topics by ACAAI, YouTube channel
Allergy and Immunology Lectures at the University of South Florida
USF (University of South Florida, USA) Allergy & Immunology Lecture Series. The 55-minute lectures are recorded in wma format and are best viewed by using Windows Media Player software.
Podcasts by Journal of Allergy and Clinical Immunology (JACI)
JACI Podcasts highlight recent publications in selected areas, and feature discussions with the authors, editors and other experts: http://www.jacionline.org/content/podcast
WAO Podcasts
Conversations with allergy experts are available as free MP3 files by the World Allergy Organization (WAO). You can subscribe to the RSS feed here: http://www.worldallergy.org/conversations/conversations.xml
The World Allergy Organization (WAO) Journal has a podcast section: Chief Editor Interviews.
Conversations with allergy experts are available as free MP3 files by the World Allergy Organization (WAO). You can subscribe to the RSS feed here: http://www.worldallergy.org/conversations/conversations.xml
ACAAI Conferences
- ACAAI Podcast and Vodcast Library is limited in scope but covers the latest advances in clinical allergy and immunology.
Immunology
The best resource seems to be the immunology course of the University of South Carolina. The lectures can be watched online or downloaded to aniPod/iPhone. Currently, there are 2 courses available -- from the year 2007 and 2008:
- Immunology 2007
- Immunology 2008
Archive of the Immunology Courses from University of South Carolina
Video Lectures in Immunology, LearnersTV.com
Immunology, University of Cambridge
Immunology I & II, MIT OpenCourseWare
Immunology: Lecture Series, Howard Hughes Medical Institute
Asthma
Allergic Rhinitis & Asthma. David Lang, MD. Drexel University College of Medicine Grand Rounds, 2003.
Severe Asthma: Clinical and Pathophysiologic Factors. Sally Wenzel, M.D. Drexel University College of Medicine Grand Rounds, 1999.
Asthma. Podcasts by the supplier of continuing medical education activities PeerView Press.
Allergic Rhinitis
Allergic Rhinitis. Podcasts by the supplier of continuing medical education activities PeerView Press.
Related Resources
Webinar Archives of World Allergy Organization (WAO)
Podcasts in Allergy and Immunology. Allergy Notes, 01/2008.
Immunology Resources: Audio and Video Lectures, PowerPoint Presentations, Q&A
Fellows-in-Training: Review Corner Archive, 2002-2008 by ACAAI
Published: 01/31/2008
Updated: 09/19/2011
Diagnosis of Asthma
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011). Approximately 9% of the U.S. population has asthma - 9% of adult asthmatics have aspirin-exacerbated respiratory disease (AERD) (http://goo.gl/FIeE9).
Asthma is a chronic inflammatory disorder of the airways which causes recurrent episodes of:
- wheezing
- shortness of breath
- chest tightness
- cough
Episodes are associated with variable airflow obstruction that is reversible.
Asthma diagnosis (click to enlarge the image).
History
Symptoms may consist of:
- wheezing
- shortness of breath
- chest tightness
- cough
Cough occurs in most patients with asthma and may be the only symptom in cough-variant asthma.
Link between asthma and allergic rhinitis
Most patients with asthma have rhinitis suggesting the concept of ‘one airway one disease’ or ‘united airways’. However, not all patients with rhinitis present with asthma.
The 1999 WHO workshop ‘Allergic Rhinitis and its Impact on Asthma’ recommended:
- patients with persistent allergic rhinitis should be evaluated for asthma by history, chest examination, and possibly assessment of airflow obstruction before and after bronchodilator
- history and examination of the upper respiratory tract for allergic rhinitis should be performed in patients with asthma
Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs. ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. http://buff.ly/QL1eYI
Physical Examination
The most common sign of airways obstruction (and asthma) is wheezing. Patients with
severe obstruction may not be able move air fast enough to generate vibration and audible wheezing.
Pulmonary Function Tests (PFTs)
Pulmonary function tests (PFTs) are the most objective way to document the diagnosis of asthma.
A mnemonic to remember the different PFTs is SPIROMEtry:
Spirometry
PEFR
Inhalation tests:
Reversibilty of
Obstruction with beta-agonist
Metacholine challenge
Exhaled NO
PFTs (click to enlarge the image).
Spirometry
The patient executes a forced expiratory maneuver by:
1. breathing normally several times
2. exhaling fully followed by a deep inhalation
3. forceful exhalation that should last at least 6 seconds
The phases of spirometry can be remembered by the mnemonic BEIF:
Breath normally x 6 times
Exhale fully
Inhalation (deep)
Forceful exhalation for 6 seconds
There should be no cough, glottic closure or air leak during the forceful exhalation for 6 seconds. The best effort of 3 is used. All efforts should have forced vital capacities (FVC) that are within 5% or 0.1L of each other. Individual volumes are called volumes whereas the combination of volumes is called a capacity.
FEV1/FVC
Decreased in obstruction
Normal or increased in restriction
FEF 25-75
Decreased in obstruction
Normal or increased in restriction
FEV1/FVC
FEF 25-75
R
Regular (normal) or
Raised in
Restriction
FEV1
1ow in both obstructive and restrictive disease
FEV1 is the most commonly used and best-standardized measurement in spirometry. FEV1 is effort-dependent, similary to PEFR.
FEV1 is used to confirm the diagnosis of asthma when airways obstruction
is present by:
- baseline spirometry
- inhalation of a short acting β-agonist
- repeat spirometry in 15-20 minutes to show reversibility of obstruction
BB RR:
Baseline spirometry
Beta-agonist
Repeat spirometry
Reversibilty of obstruction
An improvement in the FEV1 of 12% and 200 mL shows a significant reversibility and is highly specific for asthma
The criteria for reversible bronchoobstruction to diagnose asthma include improvement of 200 ml AND 12 % (not 200 ml OR 12%) after bronchodilation -- both have to be present. The change can be in either FEV1 or FVC.
The test is not very sensitive though. A 12% change in FEV1 is unlikely to be seen in:
- asthmatic patients with normal FEV1
- chronic asthma that has become irreversible because of airways remodeling
Peak Expiratory Flow Rate (PEFR)
PEFR is highly effort dependent, similarly to FEV1. PEFR is less reproducible than FEV1.
Patients should determine their personal best peak flow rather than relying on a chart of predicted peak flows based on height and age. PEFR normally vary about 5%, with the evening values higher than morning values. When asthma is uncontrolled, the normal diurnal variation in PEFR are exaggerated, and the values may vary 20-30%.
Methacholine challenge test
The methacholine challenge test mesaures bronchial hyperreactivity in response to a provoking agent (metacholine).
Bronchial challenges can be performed with:
- methacholine (a cholinergic agonist)
- histamine (used as a positive control in skin prick testing)
- antigen
- cold air (a surrogate for exercise-induced asthma)
95% of patients with asthma have a 20% reduction in FEV1 when given 5 breaths of 25 mg/mL of methacholine.
It is easier to remember the numbers: 5-25-20-5:
5 breaths
25 mg/mL metacholine
20% FEV1 reduction
5% of patients with asthma have a negative test, 95% react to the challenge
Metacholine challenge test has a 95% negative predictive value in excluding asthma. In other words, the utility of metacholine challenge test is to exclude asthma not to diagnose it.
Methacholine challenge test is generally safe.
Relative contraindications:
- FEV1 less than 70% of predicted
- patients taking beta-blockers, e.g. Atenolol
- CAD
- CVA
- HTN
- Bradycardia (can be worsened by cholinergic agents)
Methacholine is more sensitive than mannitol for evaluation of bronchial hyperresponsiveness in children with asthma http://goo.gl/Dh0m
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011). Approximately 9% of the U.S. population has asthma - 9% of adult asthmatics have aspirin-exacerbated respiratory disease (AERD) (http://goo.gl/FIeE9).
Asthma is a chronic inflammatory disorder of the airways which causes recurrent episodes of:
- wheezing
- shortness of breath
- chest tightness
- cough
Episodes are associated with variable airflow obstruction that is reversible.
Asthma diagnosis (click to enlarge the image).
History
Symptoms may consist of:
- wheezing
- shortness of breath
- chest tightness
- cough
Cough occurs in most patients with asthma and may be the only symptom in cough-variant asthma.
Link between asthma and allergic rhinitis
Most patients with asthma have rhinitis suggesting the concept of ‘one airway one disease’ or ‘united airways’. However, not all patients with rhinitis present with asthma.
The 1999 WHO workshop ‘Allergic Rhinitis and its Impact on Asthma’ recommended:
- patients with persistent allergic rhinitis should be evaluated for asthma by history, chest examination, and possibly assessment of airflow obstruction before and after bronchodilator
- history and examination of the upper respiratory tract for allergic rhinitis should be performed in patients with asthma
Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs. ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. http://buff.ly/QL1eYI
Physical Examination
The most common sign of airways obstruction (and asthma) is wheezing. Patients with
severe obstruction may not be able move air fast enough to generate vibration and audible wheezing.
Pulmonary Function Tests (PFTs)
Pulmonary function tests (PFTs) are the most objective way to document the diagnosis of asthma.
A mnemonic to remember the different PFTs is SPIROMEtry:
Spirometry
PEFR
Inhalation tests:
Reversibilty of
Obstruction with beta-agonist
Metacholine challenge
Exhaled NO
PFTs (click to enlarge the image).
Spirometry
The patient executes a forced expiratory maneuver by:
1. breathing normally several times
2. exhaling fully followed by a deep inhalation
3. forceful exhalation that should last at least 6 seconds
The phases of spirometry can be remembered by the mnemonic BEIF:
Breath normally x 6 times
Exhale fully
Inhalation (deep)
Forceful exhalation for 6 seconds
There should be no cough, glottic closure or air leak during the forceful exhalation for 6 seconds. The best effort of 3 is used. All efforts should have forced vital capacities (FVC) that are within 5% or 0.1L of each other. Individual volumes are called volumes whereas the combination of volumes is called a capacity.
FEV1/FVC
Decreased in obstruction
Normal or increased in restriction
FEF 25-75
Decreased in obstruction
Normal or increased in restriction
FEV1/FVC
FEF 25-75
R
Regular (normal) or
Raised in
Restriction
FEV1
1ow in both obstructive and restrictive disease
FEV1 is the most commonly used and best-standardized measurement in spirometry. FEV1 is effort-dependent, similary to PEFR.
FEV1 is used to confirm the diagnosis of asthma when airways obstruction
is present by:
- baseline spirometry
- inhalation of a short acting β-agonist
- repeat spirometry in 15-20 minutes to show reversibility of obstruction
BB RR:
Baseline spirometry
Beta-agonist
Repeat spirometry
Reversibilty of obstruction
An improvement in the FEV1 of 12% and 200 mL shows a significant reversibility and is highly specific for asthma
The criteria for reversible bronchoobstruction to diagnose asthma include improvement of 200 ml AND 12 % (not 200 ml OR 12%) after bronchodilation -- both have to be present. The change can be in either FEV1 or FVC.
The test is not very sensitive though. A 12% change in FEV1 is unlikely to be seen in:
- asthmatic patients with normal FEV1
- chronic asthma that has become irreversible because of airways remodeling
Peak Expiratory Flow Rate (PEFR)
PEFR is highly effort dependent, similarly to FEV1. PEFR is less reproducible than FEV1.
Patients should determine their personal best peak flow rather than relying on a chart of predicted peak flows based on height and age. PEFR normally vary about 5%, with the evening values higher than morning values. When asthma is uncontrolled, the normal diurnal variation in PEFR are exaggerated, and the values may vary 20-30%.
Methacholine challenge test
The methacholine challenge test mesaures bronchial hyperreactivity in response to a provoking agent (metacholine).
Bronchial challenges can be performed with:
- methacholine (a cholinergic agonist)
- histamine (used as a positive control in skin prick testing)
- antigen
- cold air (a surrogate for exercise-induced asthma)
95% of patients with asthma have a 20% reduction in FEV1 when given 5 breaths of 25 mg/mL of methacholine.
It is easier to remember the numbers: 5-25-20-5:
5 breaths
25 mg/mL metacholine
20% FEV1 reduction
5% of patients with asthma have a negative test, 95% react to the challenge
Metacholine challenge test has a 95% negative predictive value in excluding asthma. In other words, the utility of metacholine challenge test is to exclude asthma not to diagnose it.
Methacholine challenge test is generally safe.
Relative contraindications:
- FEV1 less than 70% of predicted
- patients taking beta-blockers, e.g. Atenolol
- CAD
- CVA
- HTN
- Bradycardia (can be worsened by cholinergic agents)
Methacholine is more sensitive than mannitol for evaluation of bronchial hyperresponsiveness in children with asthma http://goo.gl/Dh0m
Methacholine is not as sensitive to diagnose asthma as previously thought, according to a 2011 review published on Medscape (http://goo.gl/ajn0S).
- Creola bodies - clusters of surface epithelial cells
- Charcot-Leyden crystals - a pair of hexagonal pyramids joined at their bases. Normally colorless, they are stained purplish-red by trichrome. They consist of lysophospholipase
Differential Diagnosis of Asthma in Children
C
Children
Congenital conditions
CF
Cystic fibrosis can usually be excluded by:
- negative family history
- normal growth and normal nongreasy stools
- normal CXR
Most children with asthma do not need a sweat chloride or genetic test to rule out cystic fibrosis.
The most common masquerader of asthma is gastroesophageal reflux disease (GERD). GERD triggers wheezing by causing esophagitis rather than aspiration.
Differential Diagnosis of Asthma in Children (click to enlarge the image).
A
Adults
Acquired conditions
Severe asthma in children - different diagnoses and management (click to enlarge the image).
Sputum findings in asthma
- Curschmann’s spirals - corkscrew-shaped twists of condensed mucus
- Creola bodies - clusters of surface epithelial cells
- Charcot-Leyden crystals - a pair of hexagonal pyramids joined at their bases. Normally colorless, they are stained purplish-red by trichrome. They consist of lysophospholipase
Differential Diagnosis of Asthma in Children
C
Children
Congenital conditions
CF
Cystic fibrosis can usually be excluded by:
- negative family history
- normal growth and normal nongreasy stools
- normal CXR
Most children with asthma do not need a sweat chloride or genetic test to rule out cystic fibrosis.
The most common masquerader of asthma is gastroesophageal reflux disease (GERD). GERD triggers wheezing by causing esophagitis rather than aspiration.
Differential Diagnosis of Asthma in Children (click to enlarge the image).
A
Adults
Acquired conditions
Severe asthma in children - different diagnoses and management (click to enlarge the image).
Related reading: Diagnosis of chronic cough in children
Differential diagnosis of asthma in adults
Many congenital conditions are diagnosed before the patient becomes an adult, and therefore the differential diagnosis of asthma in adults consists primarily of acquired conditions.
Beta-blockers can trigger an asthma exacerbation even when used as eye drops for glaucoma or when a selective beta-blocker is taken.
Differential Diagnosis of Asthma in Adults (click to enlarge the image).
References
Allergy and Immunology MKSAP, 3rd edition.
Links between allergic rhinitis and asthma still reinforced. P. Demoly, P. J. Bousquet (2008). Allergy 63 (3), 251–254.
Recently Updated National Institutes of Health Asthma Treatment Guidelines: Important Clinical Applications, Part 2. Medscape, 11/2008.
APDIM E-Learning Task Force: Cardiac Auscultation, Chest X-Rays, Electrocardiograms, Patient Images (Dermatology), Pulmonary Function Tests, 2009.
Postoperative Tracheal Stenosis. NEJM, 01/2010.
Differential diagnosis of asthma in adults
Many congenital conditions are diagnosed before the patient becomes an adult, and therefore the differential diagnosis of asthma in adults consists primarily of acquired conditions.
Beta-blockers can trigger an asthma exacerbation even when used as eye drops for glaucoma or when a selective beta-blocker is taken.
Differential Diagnosis of Asthma in Adults (click to enlarge the image).
References
Allergy and Immunology MKSAP, 3rd edition.
Links between allergic rhinitis and asthma still reinforced. P. Demoly, P. J. Bousquet (2008). Allergy 63 (3), 251–254.
Recently Updated National Institutes of Health Asthma Treatment Guidelines: Important Clinical Applications, Part 2. Medscape, 11/2008.
APDIM E-Learning Task Force: Cardiac Auscultation, Chest X-Rays, Electrocardiograms, Patient Images (Dermatology), Pulmonary Function Tests, 2009.
Postoperative Tracheal Stenosis. NEJM, 01/2010.
Pulmonary Function Testing. Cleveland Clinic Disease Management Online Textbook.
Assessing Lung Function - a Must in Asthma Therapy http://bit.ly/HBWj7I
Audio and Video
Asthma from a pulmonologist perspective, Dr. Muthiah Muthiah. Podcasting Project for the UT Internal Medicine Residency Program.
Video: Dr. Cherry Wongtrakool Discusses Interpretation of Spirometry Values in Obstructive Lung Disease. InsiderMedicine, 03/2008.
Video: Dr. Cherry Wongtrakool Discusses the Interpretation of Post-bronchodilator Test. InsiderMedicine, 03/2008.
Video: Cherry Wongtrakool, MD Discusses Patterns of Restrictive Lung Disease on Spirometry. InsiderMedicine.
Published: 02/03/2008
Updated: 10/08/2012
Assessing Lung Function - a Must in Asthma Therapy http://bit.ly/HBWj7I
Audio and Video
Asthma from a pulmonologist perspective, Dr. Muthiah Muthiah. Podcasting Project for the UT Internal Medicine Residency Program.
Video: Dr. Cherry Wongtrakool Discusses Interpretation of Spirometry Values in Obstructive Lung Disease. InsiderMedicine, 03/2008.
Video: Dr. Cherry Wongtrakool Discusses the Interpretation of Post-bronchodilator Test. InsiderMedicine, 03/2008.
Video: Cherry Wongtrakool, MD Discusses Patterns of Restrictive Lung Disease on Spirometry. InsiderMedicine.
Published: 02/03/2008
Updated: 10/08/2012
Ocular Allergy: Allergic Conjunctivitis and Related Conditions, Brief Review
Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Classification of ocular allergy (click to enlarge the image).
Alphabet "soup": SAC, PAC, AKC, VKC, GPC (click to enlarge the image).
Allergic Conjunctivitis
- AAC
- SAC
- PAC
Keratoconjunctivitis
- Atopic Keratoconjunctivitis (AKC), atopic dermatitis-related, lower eyelid
- Vernal Keratoconjunctivitis (VKC), upper eyelid. See Vernal Keratoconjunctivitis - NEJM images, 2012.
Giant Papillary Conjunctivitis (GPC), contact lenses-related, upper eyelid
Contact dermatoconjunctivitis
All ocular allergies are characterized by bilateral involvement. Sensitization is necessary for all ocular allergies except for giant papillary conjunctivitis.
Most common type of ocular allergy is allergic conjunctivitis (80-90% of all cases).
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
Allergic conjunctivitis
Allergic conjunctivitis is a relatively benign disease that does not threaten vision. Ocular allergy is estimated to affect 20-25% of the population and the incidence is increasing.
Clinical Manifestations
Allergic conjunctivitis is a disease of young adults (average age of onset 20 years).
As with many allergic diseases, symptoms decrease with age.
50% of patients have a personal or family history of other allergic conditions such as allergic rhinitis, atopic dermatitis, and asthma
Signs and symptoms
Itching, tearing, conjunctival edema, hyperemia, watery discharge, burning, and photophobia, eyelid edema.
Laboratory findings
Allergic conjunctivitis is a clinical diagnosis.
Diagnostic Tests in Allergic Conjunctivitis (of academic interest) (click to enlarge the image).
Some tests of academic interest:
- Conjunctival scrapings show eosinophils in 80%
- Tear film and serum IgE levels are elevated
- Tear film mast cell activity is increased - measured by immunoassay for tryptase (unique to mast cells).
But rubbing by itself can result in a significant increase of tryptase in tears.
Conjunctival provocation test (CPT)
CPT is used to study AC and drug efficacies. Before undergoing a CPT, patients must first be skin tested to determine the appropriate allergen for each patient. The allergen extract is applied bilaterally into the conjunctival sac of the eyes.
At baseline, 2 visits (7 days apart) are used to establish the threshold dose of allergen (visit 1) and reproducibility (visit 2).
CPT is a double-blind, randomized test in which the test drug is applied to one eye and placebo to the other.
Types of allergic conjunctivitis
3 categories
- Acute allergic conjunctivitis (AAC)
- Seasonal allergic conjunctivitis (SAC)
- Perennial allergic conjunctivitis (PAC), less common and less severe than SAC
The main difference between SAC and PAC is the timing of the symptoms. SAC symptoms last a specific season. PAC symptoms last throughout the year.
Acute allergic conjunctivitis (AAC)
Sudden-onset hypersensitivity reaction caused by environmental exposure, for example, such as cat dander.
AAC can be severe and debilitating. However, most cases of AAC are self-limited to 24 hours and do not require long-term treatment.
Seasonal allergic conjunctivitis (SAC)
There are several synonyms for SAC: allergic conjunctivitis, hay-fever conjunctivitis, or allergic rhinoconjunctivitis.
SAC is a milder form of ocular allergy than AAC, typically associated with allergic rhinitis (AR).
SAC is most commonly triggered by ragweed or grass pollens.
SAC has a chronic course that corresponds to pollen seasons: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.
Perennial allergic conjunctivitis (PAC)
PAC is a mild chronic allergic conjunctivitis related to year-round indoor allergens, for example, house dust mite (HDM), animal dander, and molds.
PAC is less common and less severe than SAC.
Pathophysiology
All 3 types result from type I IgE–mediated hypersensitivity, same as other atopic diseases.
Conjunctival scrapings show 2 phases (early and late) of the allergic response, same as other atopic diseases affecting the skin, nose and lungs.
The immediate response to allergens is mediated by mast cells, which are normally present in high concentrations in the conjunctiva.
Allergen-IgE crosslinking causes mast cells to release chemical mediators.
Histamine is the mediator of the early response.
Late response consists of cell influx (eosinophils, basophils, and neutrophils) which usually takes 6-10 hours after allergen challenge.
Eosinophils release leukotriene C4, eosinophilic peroxidase, eosinophilic cationic protein, and histamine into the tear fluid.
Diagnosis
The diagnosis of allergic conjunctivitis is usually clinically apparent in the context of typical history and physical examination findings.
The dominant symptom in AC is itching. The eye appears red. Typically, itch is not reported with dry eye.
Laboratory tests are not usually needed to confirm the clinical diagnosis of AC.
Differential diagnosis
- infectious conjunctivitis
- blepharitis
- dry eye
Allergic conditions are often accompanied by pruritus which is not common in infections.
Management
General measures:
- do not to rub the eyes. Eye rubbing causes mechanical mast cell degranulation.
- artificial tears several times a day
- allergen avoidance
- topical antihistamine eye drops
- cool compresses
-avoidance of contact lenses use -- allergens adhere to contact lens surfaces
Dry eyes or tear film insufficiency are extremely common.
Signs of tear film insufficiency include superficial punctate-keratopathy, reduced tear break-up time, and decreased production of tears as measured by the Schirmer's test.
Oral antihistamines can exacerbate tear film insufficiency through decreased tear production (anticholinergic effect).
Punctal plugs may be helpful and can be placed quickly and painlessly by an ophthalmologist.
Allergen avoidance
SAC:
- limit outdoor exposure
- air conditioning
- car and home windows closed
PAC:
- replacement of old pillows and mattresses
- covers for pillows and mattresses
- frequent washing of beddings
- reducing humidity
- frequent vacuuming and dusting of the home
- remove reservoirs of dust: old carpets, old furniture, old curtains or drapes
- if allergic to animal dander, remove the animal from the home
Immunotherapy
Immunotherapy is effective for treatment of allergic rhinoconjunctivitis
One meta-analysis included 15 studies of immunotherapy in patients with ocular allergy symptoms - 12 studies showed benefit -- decreased ocular symptoms scores and medication use.
Immunotherapy is useful treating ocular symptoms that coexist with allergic rhinitis or asthma but the its role in treating isolated ocular allergy is less clear.
Medications
Medications for Allergic Conjunctivitis (click to enlarge the image).
Medications for AAC
Most cases of AAC are self-limited to 24 hours and do not require long-term treatment.
Over-the-counter topical antihistamine/vasoconstrictor
Over-the-counter topical antihistamine/vasoconstrictor can be used to treat symptoms of short-duration (less than 2 weeks):
- Naphazoline/pheniramine maleate (Naphcon-A®, Opcon-A®, Visine-A®)
- Naphazoline/pheniramine phosphate (Vasocon-A®)
Topical vasoconstrictor (decongestants) work within minutes with a duration of 2 hours. Dosing is QID.
Use for longer than 2 weeks can lead to rebound hyperemia.
Antihistamines
Topical antihistamines are faster-acting than oral anthistimines and have little systemic effects.
The combination of a topical antihistamine and a vasoconstrictor works better than either agent alone.
Frequent attacks of AAC (more than 2 days per month) are treated with a dual-action agent (antihistamine/mast cell stabilizer) such as olopatadine.
Pataday® is used qd, Patanol® is used bid for prevention and qid for acute symptoms.
Other topical antihistamines and/or mast cell stabilizers: azelastine (Optivar®), epinastine (Elestat®), pemirolast (Alamast®), and ketotifen (generic).
Ketotifen bid is generic and over-the-counter.
Dual-acting, Antihistamine and Mast Cell–Stabilizing Drugs
These most commonly prescribed eye drops for allergic eye disease: azelastine, olopatadine, and ketotifen.
Medications for SAC and PAC
5 classes of topical drugs:
1. antihistamines
2. mast cell stabilizers, e.g. cromolyn
3. antihistamine/mast cell stabilizer combinations, e.g. olopatadine, ketotifen
4. steroids
5. non-steroidal anti-inflammatory agents (NSAIDs), e.g. ketorolac
Mnemonic for medications for SAC and PAC: MD VANS
Mast cell stabilizers
Dual-acting: antihistamine/mast cell stabilizer
Vasoconstrictors, not recommended
Antihistamines
NSAIDs, only ketorolac, not recommended
Steroids, only loteprednol, by opthalmologist
The treatment of choice for AC is dual–acting eye drops (antihistamine/mast cell stabilizer).
Treatment for SAC should be started 2 weeks prior to the onset of season which cases symptoms: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.
Dual-action agents (topical antihistamines with mast cell stabilizing properties):
- olapatadine (Patanol®, Pataday®)
- azelastine HCl (Optivar®)
- epinastine (Elestat®)
- pemirolast (Alamast®)
- ketotifen (generic)
Ocular antihistamines (eye drops) (click to enlarge the image).
Mast cell stabilizers:
- cromolyn (generic, Opticrom®)
- lodoxamide (Alomide®)
The onset of action of mast cell stabilizers is slow (5-14 days) and the dosing is QID (inconvenient). Cromolyn cannot be used for acute symptoms.
One study compared cromolyn (4%, 4 times daily) for 2 weeks prior to allergen challenge to a single drop of ketotifen (0.025 percent) used just before the allergen challenge. The single drop of ketotifen was more effective.
Oral antihistamines
Oral antihistamines are less effective than topical olopatadine or topical ketotifen.
All antihistamines dry the ocular surface due to their atropine-like effect which decreases tear production of the lacrimal glands.
Oral antihistamines reach a peak serum levels in 0.5-3 hours depending on the drug but a full effects is after several days of use (similar to cromolyn). Oral antihistamines act much slower than topical antihistamines.
Cetirizine may cause sedation in a subset of patients, despite its categorization as non-sedating.
Topical NSAIDs
In theory, NSAIDs block the cyclooxygenase and inhibit the conversion of arachidonic acid to prostaglandins and thromboxanes.
In practice, NSAIDs are less effective than antihistanmines but more effective than placebo. NSAIDs are not recommended for treatment of allergic conjunctivitis.
Ketorolac is the only topical NSAID approved for itching due to AC.
Patients with AR and AC
Olopatadine can be combined with an intranasal steroid (INS). Fluticasone furoate nasal spray is the only intranasal corticosteroid to reduce the ocular symptoms of seasonal allergic rhinitis consistently, JACI, 2010.
When to refer to an ophthalmologist?
- Giant papillae occur on the upper tarsal plate and are described as cobblestoning.
- yellow-white points in the limbus (Trantas dots)
- yellow-white points on the conjunctiva (Horner points)
- corneal “shield” ulcers
- Dennie lines (Dennie-Morgan folds)
Shield ulcers are sterile ulcers which occur where cobblestone papillae are rubbing on cornea.
Children with VKC have measurably longer eyelashes (reaction to ocular inflammation).
VKC is chronic and sight-threatening.
Treatment of Vernal Keratoconjunctivitis
VKC is a sight-threatening disease.
Topical steroids 8 times per day for 7-10 days usually relieves symptoms.
High-dose aspirin therapy has been shown effective (2.4 gm daily)
Topical cyclosporin A (Restasis) has also been used in VKC: Cyclosporine eye drops prevent seasonal recurrences of vernal keratoconjunctivitis in a 2-year study (JACI, 2011).
Giant Papillary Conjunctivitis (GPC)
GPC is linked to chronic exposure to foreign bodies, such as contact lenses. GPC is considered an iatrogenic form of allergic eye disease.
Sensitization not necessary in GCP but is required in all other forms of ocular allergy.
GPC is a chronic inflammation that produces giant papillae (1 mm or greater) on the tarsal conjunctiva of the upper eyelids.
Causes of GPC:
- mechanical trauma secondary to contact lenses
- buildup of protein on the surface of the contact lens causes an allergic reaction
Treatment of Giant Papillary Conjunctivitis
Reduction in the wearing time of contact lenses or total discontinuation is required.
“Artificial tears” help to wash away environmental allergens and lens debris ("protein deposits").
Topical mast cell stabilizers are effective in the treatment of GPC and dual-acting drugs may be the best therapy.
Topical steroids are very effective but should be used only for a short period of time, e.g. 4 times per day for 2-4 days.
Contact lens can be resumed but it often requires a change in the type or material of the contact lenses.
Contact dermatoconjunctivitis
Contact dermatoconjunctivitis is a delayed cell-mediated hypersensitivity reaction (type IV), not an IgE antibody–mediated process.
Contact dermatitis involves the eyelids but can also involve the conjunctivae. Contact dermatitis may be caused by contact lens solutions but a multitude of irritants and allergens have been implicated, for example:
- eye drops, anesthetics, antiviral agents, pilocarpine, timolol
- preservatives in ophthalmic solutions (thiomersal, benzalkonium chloride, chlorhexidine, EDTA)
- cosmetics (eye glosses)
- perfumes
- sunscreens
- adhesives (false eyelashes)
Patch testing is the most useful diagnostic tool for contact dermatoconjunctivitis.
The best treatment is avoidance of the offending agent.
Immunologic Diseases of the Eye
Ocular cicatricial pemphigoid
Peripheral ulcerative keratitis
Episcleritis
Scleritis
Uveitis
List of optometric abbrevations
OU, oculus utro (each eye)
OS, oculus sinister (left eye)
OD, oculus dexter (right eye)
SPK, Superficial punctate keratitis
References
Allergic conjunctivitis. M Reza Dana, MD, MPH, MSc, UpToDate, 16.2, 8/2008.
Chapter 88 – Allergic and Immunologic Diseases of the Eye. Neal P. Barney, Frank M. Graziano. Adkinson: Middleton's Allergy: Principles and Practice, 6th ed.
Allergic Conjunctivitis. Presentation Materials. World Allergy Organization.
Pediatric Ocular Inflammation. Immunology and Allergy Clinic of North America. Volume 28, Issue 1, Pages 169-188 (February 2008).
Chapter 146 – Ocular Allergies. Mark Boguniewicz Donald Y.M. Leung. Kliegman: Nelson Textbook of Pediatrics, 18th ed.
Ocular Allergies. Ask the Expert. AAAAI.
Allergic Conjunctivitis. Ask the Expert. AAAAI.
Allergic conjunctivitis. Handbook of Ocular Disease Management.
Ocular Allergy. Curr Opin Allergy Clin Immunol. 2007; 7(5):424-428. Medscape. Medscape
The Pathophysiology of Ocular Allergy: Current Thinking. C Stephen Foster. Allergy, Volume 50 Issue s21, Pages 6 - 9, 2007.
Online Continuing Education: Ocular Allergy. University of Indiana.
Conjunctivitis, Allergic. Parag A Majmudar, MD. eMedicine.
Allergic rhinoconjunctivitis and differential diagnosis of the red eye. Granet, David. Allergy and Asthma Proceedings, Volume 29, Number 6, 11/12 2008 , pp. 565-574(10).
PowerPoint Presentations
Ocular allergy. V. Dimov, M.D., 09/2008.
Allergic Conjunctivitis. World Allergy Congress.
Allergic Conjunctivitis. MCFP.
Eye diseases and the internist. ACP.
Questions
Review Questions: Pediatric Allergy: Principles & Practices, Chapter 56: Allergic and Immunologic Eye Disease.
Patient information
Patient information: Eye Allergies. WebMD.
Ocular Allergies. Clifford W. Bassett, MD, FAAAAI. Allergy & Asthma Advocate: Summer 2007.
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Classification of ocular allergy (click to enlarge the image).
Alphabet "soup": SAC, PAC, AKC, VKC, GPC (click to enlarge the image).
Allergic Conjunctivitis
- AAC
- SAC
- PAC
Keratoconjunctivitis
- Atopic Keratoconjunctivitis (AKC), atopic dermatitis-related, lower eyelid
- Vernal Keratoconjunctivitis (VKC), upper eyelid. See Vernal Keratoconjunctivitis - NEJM images, 2012.
Giant Papillary Conjunctivitis (GPC), contact lenses-related, upper eyelid
Contact dermatoconjunctivitis
All ocular allergies are characterized by bilateral involvement. Sensitization is necessary for all ocular allergies except for giant papillary conjunctivitis.
Most common type of ocular allergy is allergic conjunctivitis (80-90% of all cases).
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
Allergic conjunctivitis
Allergic conjunctivitis is a relatively benign disease that does not threaten vision. Ocular allergy is estimated to affect 20-25% of the population and the incidence is increasing.
Clinical Manifestations
Allergic conjunctivitis is a disease of young adults (average age of onset 20 years).
As with many allergic diseases, symptoms decrease with age.
50% of patients have a personal or family history of other allergic conditions such as allergic rhinitis, atopic dermatitis, and asthma
Signs and symptoms
Itching, tearing, conjunctival edema, hyperemia, watery discharge, burning, and photophobia, eyelid edema.
Laboratory findings
Allergic conjunctivitis is a clinical diagnosis.
Diagnostic Tests in Allergic Conjunctivitis (of academic interest) (click to enlarge the image).
Some tests of academic interest:
- Conjunctival scrapings show eosinophils in 80%
- Tear film and serum IgE levels are elevated
- Tear film mast cell activity is increased - measured by immunoassay for tryptase (unique to mast cells).
But rubbing by itself can result in a significant increase of tryptase in tears.
Conjunctival provocation test (CPT)
CPT is used to study AC and drug efficacies. Before undergoing a CPT, patients must first be skin tested to determine the appropriate allergen for each patient. The allergen extract is applied bilaterally into the conjunctival sac of the eyes.
At baseline, 2 visits (7 days apart) are used to establish the threshold dose of allergen (visit 1) and reproducibility (visit 2).
CPT is a double-blind, randomized test in which the test drug is applied to one eye and placebo to the other.
Types of allergic conjunctivitis
3 categories
- Acute allergic conjunctivitis (AAC)
- Seasonal allergic conjunctivitis (SAC)
- Perennial allergic conjunctivitis (PAC), less common and less severe than SAC
The main difference between SAC and PAC is the timing of the symptoms. SAC symptoms last a specific season. PAC symptoms last throughout the year.
Acute allergic conjunctivitis (AAC)
Sudden-onset hypersensitivity reaction caused by environmental exposure, for example, such as cat dander.
AAC can be severe and debilitating. However, most cases of AAC are self-limited to 24 hours and do not require long-term treatment.
Seasonal allergic conjunctivitis (SAC)
There are several synonyms for SAC: allergic conjunctivitis, hay-fever conjunctivitis, or allergic rhinoconjunctivitis.
SAC is a milder form of ocular allergy than AAC, typically associated with allergic rhinitis (AR).
SAC is most commonly triggered by ragweed or grass pollens.
SAC has a chronic course that corresponds to pollen seasons: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.
Perennial allergic conjunctivitis (PAC)
PAC is a mild chronic allergic conjunctivitis related to year-round indoor allergens, for example, house dust mite (HDM), animal dander, and molds.
PAC is less common and less severe than SAC.
Pathophysiology
All 3 types result from type I IgE–mediated hypersensitivity, same as other atopic diseases.
Conjunctival scrapings show 2 phases (early and late) of the allergic response, same as other atopic diseases affecting the skin, nose and lungs.
The immediate response to allergens is mediated by mast cells, which are normally present in high concentrations in the conjunctiva.
Allergen-IgE crosslinking causes mast cells to release chemical mediators.
Histamine is the mediator of the early response.
Late response consists of cell influx (eosinophils, basophils, and neutrophils) which usually takes 6-10 hours after allergen challenge.
Eosinophils release leukotriene C4, eosinophilic peroxidase, eosinophilic cationic protein, and histamine into the tear fluid.
Diagnosis
The diagnosis of allergic conjunctivitis is usually clinically apparent in the context of typical history and physical examination findings.
The dominant symptom in AC is itching. The eye appears red. Typically, itch is not reported with dry eye.
Laboratory tests are not usually needed to confirm the clinical diagnosis of AC.
Differential diagnosis
- infectious conjunctivitis
- blepharitis
- dry eye
Allergic conditions are often accompanied by pruritus which is not common in infections.
Management
General measures:
- do not to rub the eyes. Eye rubbing causes mechanical mast cell degranulation.
- artificial tears several times a day
- allergen avoidance
- topical antihistamine eye drops
- cool compresses
-avoidance of contact lenses use -- allergens adhere to contact lens surfaces
Dry eyes or tear film insufficiency are extremely common.
Signs of tear film insufficiency include superficial punctate-keratopathy, reduced tear break-up time, and decreased production of tears as measured by the Schirmer's test.
Oral antihistamines can exacerbate tear film insufficiency through decreased tear production (anticholinergic effect).
Punctal plugs may be helpful and can be placed quickly and painlessly by an ophthalmologist.
Allergen avoidance
SAC:
- limit outdoor exposure
- air conditioning
- car and home windows closed
PAC:
- replacement of old pillows and mattresses
- covers for pillows and mattresses
- frequent washing of beddings
- reducing humidity
- frequent vacuuming and dusting of the home
- remove reservoirs of dust: old carpets, old furniture, old curtains or drapes
- if allergic to animal dander, remove the animal from the home
Immunotherapy
Immunotherapy is effective for treatment of allergic rhinoconjunctivitis
One meta-analysis included 15 studies of immunotherapy in patients with ocular allergy symptoms - 12 studies showed benefit -- decreased ocular symptoms scores and medication use.
Immunotherapy is useful treating ocular symptoms that coexist with allergic rhinitis or asthma but the its role in treating isolated ocular allergy is less clear.
Medications
Medications for Allergic Conjunctivitis (click to enlarge the image).
Medications for AAC
Most cases of AAC are self-limited to 24 hours and do not require long-term treatment.
Over-the-counter topical antihistamine/vasoconstrictor
Over-the-counter topical antihistamine/vasoconstrictor can be used to treat symptoms of short-duration (less than 2 weeks):
- Naphazoline/pheniramine maleate (Naphcon-A®, Opcon-A®, Visine-A®)
- Naphazoline/pheniramine phosphate (Vasocon-A®)
Topical vasoconstrictor (decongestants) work within minutes with a duration of 2 hours. Dosing is QID.
Use for longer than 2 weeks can lead to rebound hyperemia.
Antihistamines
Topical antihistamines are faster-acting than oral anthistimines and have little systemic effects.
The combination of a topical antihistamine and a vasoconstrictor works better than either agent alone.
Frequent attacks of AAC (more than 2 days per month) are treated with a dual-action agent (antihistamine/mast cell stabilizer) such as olopatadine.
Pataday® is used qd, Patanol® is used bid for prevention and qid for acute symptoms.
Other topical antihistamines and/or mast cell stabilizers: azelastine (Optivar®), epinastine (Elestat®), pemirolast (Alamast®), and ketotifen (generic).
Ketotifen bid is generic and over-the-counter.
Dual-acting, Antihistamine and Mast Cell–Stabilizing Drugs
These most commonly prescribed eye drops for allergic eye disease: azelastine, olopatadine, and ketotifen.
Medications for SAC and PAC
5 classes of topical drugs:
1. antihistamines
2. mast cell stabilizers, e.g. cromolyn
3. antihistamine/mast cell stabilizer combinations, e.g. olopatadine, ketotifen
4. steroids
5. non-steroidal anti-inflammatory agents (NSAIDs), e.g. ketorolac
Mnemonic for medications for SAC and PAC: MD VANS
Mast cell stabilizers
Dual-acting: antihistamine/mast cell stabilizer
Vasoconstrictors, not recommended
Antihistamines
NSAIDs, only ketorolac, not recommended
Steroids, only loteprednol, by opthalmologist
The treatment of choice for AC is dual–acting eye drops (antihistamine/mast cell stabilizer).
Treatment for SAC should be started 2 weeks prior to the onset of season which cases symptoms: tree pollens in the spring, grass pollens in the summer, and weed pollens in the late summer and fall.
Dual-action agents (topical antihistamines with mast cell stabilizing properties):
- olapatadine (Patanol®, Pataday®)
- azelastine HCl (Optivar®)
- epinastine (Elestat®)
- pemirolast (Alamast®)
- ketotifen (generic)
Ocular antihistamines (eye drops) (click to enlarge the image).
Mast cell stabilizers:
- cromolyn (generic, Opticrom®)
- lodoxamide (Alomide®)
The onset of action of mast cell stabilizers is slow (5-14 days) and the dosing is QID (inconvenient). Cromolyn cannot be used for acute symptoms.
One study compared cromolyn (4%, 4 times daily) for 2 weeks prior to allergen challenge to a single drop of ketotifen (0.025 percent) used just before the allergen challenge. The single drop of ketotifen was more effective.
Oral antihistamines
Oral antihistamines are less effective than topical olopatadine or topical ketotifen.
All antihistamines dry the ocular surface due to their atropine-like effect which decreases tear production of the lacrimal glands.
Oral antihistamines reach a peak serum levels in 0.5-3 hours depending on the drug but a full effects is after several days of use (similar to cromolyn). Oral antihistamines act much slower than topical antihistamines.
Cetirizine may cause sedation in a subset of patients, despite its categorization as non-sedating.
Topical NSAIDs
In theory, NSAIDs block the cyclooxygenase and inhibit the conversion of arachidonic acid to prostaglandins and thromboxanes.
In practice, NSAIDs are less effective than antihistanmines but more effective than placebo. NSAIDs are not recommended for treatment of allergic conjunctivitis.
Ketorolac is the only topical NSAID approved for itching due to AC.
Patients with AR and AC
Olopatadine can be combined with an intranasal steroid (INS). Fluticasone furoate nasal spray is the only intranasal corticosteroid to reduce the ocular symptoms of seasonal allergic rhinitis consistently, JACI, 2010.
When to refer to an ophthalmologist?
If there is no response to 2-3 weeks of an antihistamine/mast cell stabilizer (olopatadine).
Steroids
Only one topical steroid is currently approved for use in ocular allergy—loteprednol.
Loteprednol 0.2% is Alrex.
Loteprednol 0.5% is Lotemax.
Topical steroids may be considered in refractory patients. Topical steroids can cause serious ocular side effects and should only be used for short "pulse therapy."
Side effects of topical steroids can lead to blindness:
- cataract formation
- elevated intraocular pressure (IOP) and glaucoma
- secondary infections
5% of people respond to steroid eye drop with increased intraocular pressure. Of those with a family history of glaucoma, 20-30% respond with elevated intraocular pressure.
Prednisolone acetate (1 %) and dexamethasone phosphate (0.1 %) have the greatest risk of raising IOP.
"Soft" topical steroids have a much llower risk of increased IOP becase they are inactivated after corneal penetration: Lotemax® (loteprednol), Pred Mild® (prednisolone), FML® (fluorometholone), HMS® (medrysone), and Vexol® (rimexolone).
Atopic Keratoconjunctivitis (AKC)
AKC is a chronic ocular inflammation involving the lower tarsal conjunctiva. VKC affects the upper tarsal conjunctiva. See Vernal Keratoconjunctivitis - NEJM images, 2012.
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
The association between atopic dermatitis and AKC was first described in 1953.
Almost all patients with AKC have atopic dermatitis, and many have asthma. Peak incidence of AKC is 20–50 years of age.
3% of the population is affected by atopic dermatitis. 25% of people with atopic dermatitis have ocular involvement.
Secondary staphylococcal blepharitis is common because of eyelid induration and maceration. Herpetic keratitis occurs in 14-18% of patients.
Keratoconus (noninflammatory progressive thinning of the cornea) occurs in 7-16% of patients.
Treatment of Atopic Keratoconjunctivitis
AKC is a sight-threatening disease.
Topical vasoconstrictor-antihistamine combination may bring transient relief. Dual-acting and mast cell–stabilizing drugs are also recommended.
Topical steroids 8 times per day for 7-10 days are needed to control the symptoms and often lead to an excellent response. Steroid use is transient.
Trichiasis (misdirected eyelashes) must be corrected surgically.
Staphylococcal-associated blepharitis and herpes simplex keratitis requires specific treatments.
Vernal Keratoconjunctivitis (VKC)
VKC is a severe bilateral chronic inflammation of the upper tarsal conjunctiva.
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
VKC is not IgE mediated but occurs most frequently in children with seasonal allergies, asthma, or atopic dermatitis. Males predominate 3:1.
"Vernal" means occurring in spring.
VKC onset is generally before 10 years of age. Without treatment, VKC lasts 2-10 years and usually resolves during puberty. Young men in dry, hot climates (Mediterranean, West Africa) are primarily affected.
VKC signs:
Steroids
Only one topical steroid is currently approved for use in ocular allergy—loteprednol.
Loteprednol 0.2% is Alrex.
Loteprednol 0.5% is Lotemax.
Topical steroids may be considered in refractory patients. Topical steroids can cause serious ocular side effects and should only be used for short "pulse therapy."
Side effects of topical steroids can lead to blindness:
- cataract formation
- elevated intraocular pressure (IOP) and glaucoma
- secondary infections
5% of people respond to steroid eye drop with increased intraocular pressure. Of those with a family history of glaucoma, 20-30% respond with elevated intraocular pressure.
Prednisolone acetate (1 %) and dexamethasone phosphate (0.1 %) have the greatest risk of raising IOP.
"Soft" topical steroids have a much llower risk of increased IOP becase they are inactivated after corneal penetration: Lotemax® (loteprednol), Pred Mild® (prednisolone), FML® (fluorometholone), HMS® (medrysone), and Vexol® (rimexolone).
Atopic Keratoconjunctivitis (AKC)
AKC is a chronic ocular inflammation involving the lower tarsal conjunctiva. VKC affects the upper tarsal conjunctiva. See Vernal Keratoconjunctivitis - NEJM images, 2012.
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
The association between atopic dermatitis and AKC was first described in 1953.
Almost all patients with AKC have atopic dermatitis, and many have asthma. Peak incidence of AKC is 20–50 years of age.
3% of the population is affected by atopic dermatitis. 25% of people with atopic dermatitis have ocular involvement.
Secondary staphylococcal blepharitis is common because of eyelid induration and maceration. Herpetic keratitis occurs in 14-18% of patients.
Keratoconus (noninflammatory progressive thinning of the cornea) occurs in 7-16% of patients.
Treatment of Atopic Keratoconjunctivitis
AKC is a sight-threatening disease.
Topical vasoconstrictor-antihistamine combination may bring transient relief. Dual-acting and mast cell–stabilizing drugs are also recommended.
Topical steroids 8 times per day for 7-10 days are needed to control the symptoms and often lead to an excellent response. Steroid use is transient.
Trichiasis (misdirected eyelashes) must be corrected surgically.
Staphylococcal-associated blepharitis and herpes simplex keratitis requires specific treatments.
Vernal Keratoconjunctivitis (VKC)
VKC is a severe bilateral chronic inflammation of the upper tarsal conjunctiva.
Vernal keratoconjunctivitis and atopic keratoconjunctivitis are potentially sight-threatening.
VKC is not IgE mediated but occurs most frequently in children with seasonal allergies, asthma, or atopic dermatitis. Males predominate 3:1.
"Vernal" means occurring in spring.
VKC onset is generally before 10 years of age. Without treatment, VKC lasts 2-10 years and usually resolves during puberty. Young men in dry, hot climates (Mediterranean, West Africa) are primarily affected.
VKC signs:
- Giant papillae occur on the upper tarsal plate and are described as cobblestoning.
- yellow-white points in the limbus (Trantas dots)
- yellow-white points on the conjunctiva (Horner points)
- corneal “shield” ulcers
- Dennie lines (Dennie-Morgan folds)
Shield ulcers are sterile ulcers which occur where cobblestone papillae are rubbing on cornea.
Children with VKC have measurably longer eyelashes (reaction to ocular inflammation).
VKC is chronic and sight-threatening.
Treatment of Vernal Keratoconjunctivitis
VKC is a sight-threatening disease.
Topical steroids 8 times per day for 7-10 days usually relieves symptoms.
High-dose aspirin therapy has been shown effective (2.4 gm daily)
Topical cyclosporin A (Restasis) has also been used in VKC: Cyclosporine eye drops prevent seasonal recurrences of vernal keratoconjunctivitis in a 2-year study (JACI, 2011).
Giant Papillary Conjunctivitis (GPC)
GPC is linked to chronic exposure to foreign bodies, such as contact lenses. GPC is considered an iatrogenic form of allergic eye disease.
Sensitization not necessary in GCP but is required in all other forms of ocular allergy.
GPC is a chronic inflammation that produces giant papillae (1 mm or greater) on the tarsal conjunctiva of the upper eyelids.
Causes of GPC:
- mechanical trauma secondary to contact lenses
- buildup of protein on the surface of the contact lens causes an allergic reaction
Treatment of Giant Papillary Conjunctivitis
Reduction in the wearing time of contact lenses or total discontinuation is required.
“Artificial tears” help to wash away environmental allergens and lens debris ("protein deposits").
Topical mast cell stabilizers are effective in the treatment of GPC and dual-acting drugs may be the best therapy.
Topical steroids are very effective but should be used only for a short period of time, e.g. 4 times per day for 2-4 days.
Contact lens can be resumed but it often requires a change in the type or material of the contact lenses.
Contact dermatoconjunctivitis
Contact dermatoconjunctivitis is a delayed cell-mediated hypersensitivity reaction (type IV), not an IgE antibody–mediated process.
Contact dermatitis involves the eyelids but can also involve the conjunctivae. Contact dermatitis may be caused by contact lens solutions but a multitude of irritants and allergens have been implicated, for example:
- eye drops, anesthetics, antiviral agents, pilocarpine, timolol
- preservatives in ophthalmic solutions (thiomersal, benzalkonium chloride, chlorhexidine, EDTA)
- cosmetics (eye glosses)
- perfumes
- sunscreens
- adhesives (false eyelashes)
Patch testing is the most useful diagnostic tool for contact dermatoconjunctivitis.
The best treatment is avoidance of the offending agent.
Immunologic Diseases of the Eye
Ocular cicatricial pemphigoid
Peripheral ulcerative keratitis
Episcleritis
Scleritis
Uveitis
List of optometric abbrevations
OU, oculus utro (each eye)
OS, oculus sinister (left eye)
OD, oculus dexter (right eye)
SPK, Superficial punctate keratitis
References
Allergic conjunctivitis. M Reza Dana, MD, MPH, MSc, UpToDate, 16.2, 8/2008.
Chapter 88 – Allergic and Immunologic Diseases of the Eye. Neal P. Barney, Frank M. Graziano. Adkinson: Middleton's Allergy: Principles and Practice, 6th ed.
Allergic Conjunctivitis. Presentation Materials. World Allergy Organization.
Pediatric Ocular Inflammation. Immunology and Allergy Clinic of North America. Volume 28, Issue 1, Pages 169-188 (February 2008).
Chapter 146 – Ocular Allergies. Mark Boguniewicz Donald Y.M. Leung. Kliegman: Nelson Textbook of Pediatrics, 18th ed.
Ocular Allergies. Ask the Expert. AAAAI.
Allergic Conjunctivitis. Ask the Expert. AAAAI.
Allergic conjunctivitis. Handbook of Ocular Disease Management.
Ocular Allergy. Curr Opin Allergy Clin Immunol. 2007; 7(5):424-428. Medscape. Medscape
The Pathophysiology of Ocular Allergy: Current Thinking. C Stephen Foster. Allergy, Volume 50 Issue s21, Pages 6 - 9, 2007.
Online Continuing Education: Ocular Allergy. University of Indiana.
Conjunctivitis, Allergic. Parag A Majmudar, MD. eMedicine.
Allergic rhinoconjunctivitis and differential diagnosis of the red eye. Granet, David. Allergy and Asthma Proceedings, Volume 29, Number 6, 11/12 2008 , pp. 565-574(10).
Updates in the treatment of ocular allergies. Journal of Asthma and Allergy, November 2010, Volume 2010:3 Pages 149 - 158 DOI 10.2147/JAA.S13705 (free PDF).
PowerPoint Presentations
Ocular allergy. V. Dimov, M.D., 09/2008.
Allergic Conjunctivitis. World Allergy Congress.
Allergic Conjunctivitis. MCFP.
Eye diseases and the internist. ACP.
Questions
Review Questions: Pediatric Allergy: Principles & Practices, Chapter 56: Allergic and Immunologic Eye Disease.
Patient information
Patient information: Eye Allergies. WebMD.
Ocular Allergies. Clifford W. Bassett, MD, FAAAAI. Allergy & Asthma Advocate: Summer 2007.
Related reading
Allergy season is here :\ on Flickr
Japanese guideline for allergic conjunctival diseases. Allergol Int. 2011 Mar;60(2):191-203.
Vernal Keratoconjunctivitis - NEJM images, 2012.
Eye Drops for allergic conjunctivitis - why would AAAAI include a homeopathic medications in this list? http://buff.ly/1kPCOgn
Published: 09/25/2008
Updated: 02/02/2012
Vernal Keratoconjunctivitis - NEJM images, 2012.
Eye Drops for allergic conjunctivitis - why would AAAAI include a homeopathic medications in this list? http://buff.ly/1kPCOgn
Published: 09/25/2008
Updated: 02/02/2012
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