Author: V. Dimov, M.D., Allergist/Immunologist at Cleveland Clinic
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
A 72-year-old male was treated for multiple meyeloma 2 years ago. Subsequently, his IgG was found to be 180 mg/dL, IgA 7, IgM and there was insufficient response on the pneumococcus serotypes. At an outside facility, SCIG was started due to poor IV access. There was no history of infections. The diagnosis was secondary immunodeficiency. He has been receiving SCIG (Hizentra) 25 gm every week.
A year later, his IgG is 1200 mg/dL. The reported last dose of SCIG was 3-4 weeks ago (the prescription ran out).
What dose adjustment would you recommend now?
SCIG dose adjustement:
Based on the typical IVIG starting dose of 400 mg/kg/month, the total monthly dose is 400 mg x 65 kg = 26,000 mg (26 g).
According to the Hizentra dosage calculator (Initial recommended dose of Hizentra = 1.53 x Previous IVIg dose(grams)
Number of weeks between scheduled IVIg doses). Based on an IVIg dose of 26grams and 4weeks between IVIg doses, Hizentra weekly dose is: 9.95 g (49.73).
Patient's states the last SCIG dose was 3-4 weeks ago, total IgG is 1200 mg/dL. It is possible that some of the production of IgG by the B cells is recovering.
The recommended new weekly dose of SCIG is 15 g every week. IgG, IgM, IgA levels should be checked in 3 months, just before the SCIG infusion.
SCIG prescription was changed. The infusion nurse was informed.
Mnemonic: Dose of IVIG in PIDD: 4
400-600 mg/kg/month
IgG trough level should be over 400 mg/dL (over 600 mg/dL if bronchiectasis)
4 letter words:
IVIG
CVID
SCID
Starting doses for IVIG: 400 to 600 mg/kg/month for a target trough level of at least 500 mg/dL.
How monitor CVID patients on IVIG?
Immunoglobulin levels at 3-6 month intervals
CBC and CMP yearly
Spirometry yearly
CT chest every 3-4 years - only if lung disease suspected or lung functions not normal
References
Guidelines on Dosing and Treatment Administration for Hizentra Therapy http://buff.ly/1uCZt4Q
Related reading
AInotes - Common Variable Immunodeficiency http://buff.ly/1uCZFky
AInotes - IVIG and Subcutaneous Ig http://buff.ly/1uCZTYP
Published: 07/12/2010
Updated: 03/15/2014
Showing posts with label IVIG. Show all posts
Showing posts with label IVIG. Show all posts
Headache After Treatment with Intravenous Immunoglobulin (IVIG)
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
A 34-year-old Caucasian female is followed by the allergy clinic for common variable immunodeficiency (CVID) and a treatment with intravenous immune globulin (IVIG) was started 4 months ago. She started to have headaches after the second infusion which are progressively getting worse. Her last dose of IVIG was given 2 days ago and since then she had a persistent pounding headache not relieved by Percocet. She denies any symptoms of aseptic meningitis including photophobia, neck stiffness, nausea, or fever. She rates the pain as 8/10.
Past medical history (PMH)
Common variable immunodeficiency (CVID).
Medications
Intravenous immune globulin (IVIG) 400 mg/kg every 4 weeks, Percocet (oxycodone and acetaminophen)
Social history and family history
Not contributory.
Physical examination
Vital signs stable. Normal nose and throat exam. Respiratory system: Clear to auscultation bilaterally. Cardiovascular system: Clear S1, S2. Abdomen: Soft, non-tender, non-distended. Extremities: no edema. Skin: no rashes.Neurological examination: non focal.
What is the most likely diagnosis?
- Headache associated with intravenous immunoglobulin.
- Migraine.
- Aseptic meningitis is in the differential diagnosis but she did not have features of meningitis.
What tests would you suggest?
No additional tests are needed at this time.
What treatment would you suggest?
After verifying that the patient was not pregnant, she was prescribed zolmitriptan (Zomig) 5 mg po x 1, the dose may be repeated 2 hours later. The headache resolved after the second dose.
How to prevent IVIG-related headache?
Post-infusion headaches may be prevented by the following treatments for as long as 72 hours after the infusion is completed
- NSAIDs such as naproxen or ibuprofen
- Prednisone 30 to 60 mg
- cyproheptadine (an antihistamine and serotonin receptor antagonist)
- migraine medications
In this patient, we recommended prednisone 30 mg po x 1 and zolmitriptan (Zomig) 5 mg po x 1 before the infusion.
Other options that may be considered include "splitting" the dose to every 2 weeks and using subcutaneous immunoglobulin rather than IVIG.
Final diagnosis
Headache associated with intravenous immunoglobulin (IVIG) treatment.
Summary
Headache is a common side effect of intravenous immunoglobulin (IVIG) treatment; it usually resolves shortly after completing or slowing the infusion. Aseptic meningitis occurs in up to 17% of patients afterIVIG treatment, with more than 30 cases described in the literature. Aseptic meningitis usually presents with crescendo headache that also causes changes in sensorium or behavioral changes.
Headaches associated with intravenous immunoglobulin may have features of migraine and may be successfully prevented and/or treated with 5-HT1D receptor agonists.
Many patients develop mild headaches during IVIG infusions, which can be prevented or treated with acetaminophen, aspirin, or NSAIDs; and/or by administering the IGIV at a slower rate.
In some cases, the onset may be delayed until 24 to 48 hours after the infusion is completed. The duration of symptoms is generally less than 48 hours, but occasionally, severe headaches lasting as long as 72 hours have been reported.
Mnemonic: Dose of IVIG in PIDD
400-600 mg/kg/month
4 letter words:
IVIG
CVID
SCID
References
Management of the Acute Migraine Headache. AFP, 2002.
Successful Treatment of Headache Related to Intravenous Immunoglobulin With Antimigraine Medications. Alan G. Finkel, MD ; James F. Howard Jr., MD ; J. Douglas Mann, MD. Headache: The Journal of Head and Face Pain, Volume 38 Issue 4, Pages 317 - 321, 2003.
What Can Be Used to Treat Persistent Headache Caused by Aseptic Meningitis? Randolph Warren Evans, MD. eMedicine, 2000.
Published: 04/19/2009
Updated: 08/18/2010
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
A 34-year-old Caucasian female is followed by the allergy clinic for common variable immunodeficiency (CVID) and a treatment with intravenous immune globulin (IVIG) was started 4 months ago. She started to have headaches after the second infusion which are progressively getting worse. Her last dose of IVIG was given 2 days ago and since then she had a persistent pounding headache not relieved by Percocet. She denies any symptoms of aseptic meningitis including photophobia, neck stiffness, nausea, or fever. She rates the pain as 8/10.
Past medical history (PMH)
Common variable immunodeficiency (CVID).
Medications
Intravenous immune globulin (IVIG) 400 mg/kg every 4 weeks, Percocet (oxycodone and acetaminophen)
Social history and family history
Not contributory.
Physical examination
Vital signs stable. Normal nose and throat exam. Respiratory system: Clear to auscultation bilaterally. Cardiovascular system: Clear S1, S2. Abdomen: Soft, non-tender, non-distended. Extremities: no edema. Skin: no rashes.Neurological examination: non focal.
What is the most likely diagnosis?
- Headache associated with intravenous immunoglobulin.
- Migraine.
- Aseptic meningitis is in the differential diagnosis but she did not have features of meningitis.
What tests would you suggest?
No additional tests are needed at this time.
What treatment would you suggest?
After verifying that the patient was not pregnant, she was prescribed zolmitriptan (Zomig) 5 mg po x 1, the dose may be repeated 2 hours later. The headache resolved after the second dose.
How to prevent IVIG-related headache?
Post-infusion headaches may be prevented by the following treatments for as long as 72 hours after the infusion is completed
- NSAIDs such as naproxen or ibuprofen
- Prednisone 30 to 60 mg
- cyproheptadine (an antihistamine and serotonin receptor antagonist)
- migraine medications
In this patient, we recommended prednisone 30 mg po x 1 and zolmitriptan (Zomig) 5 mg po x 1 before the infusion.
Other options that may be considered include "splitting" the dose to every 2 weeks and using subcutaneous immunoglobulin rather than IVIG.
Final diagnosis
Headache associated with intravenous immunoglobulin (IVIG) treatment.
Summary
Headache is a common side effect of intravenous immunoglobulin (IVIG) treatment; it usually resolves shortly after completing or slowing the infusion. Aseptic meningitis occurs in up to 17% of patients afterIVIG treatment, with more than 30 cases described in the literature. Aseptic meningitis usually presents with crescendo headache that also causes changes in sensorium or behavioral changes.
Headaches associated with intravenous immunoglobulin may have features of migraine and may be successfully prevented and/or treated with 5-HT1D receptor agonists.
Many patients develop mild headaches during IVIG infusions, which can be prevented or treated with acetaminophen, aspirin, or NSAIDs; and/or by administering the IGIV at a slower rate.
In some cases, the onset may be delayed until 24 to 48 hours after the infusion is completed. The duration of symptoms is generally less than 48 hours, but occasionally, severe headaches lasting as long as 72 hours have been reported.
Anaphylaxis may occur in patients treated with IVIG who have IgE antibodies against IgA, for example patients with selective IgA deficiency (incidence 1 in 500). Preventive measures include using products with the lowest IgA content and pre-medication with antihistamines or corticosteroids.
Mnemonic: Dose of IVIG in PIDD
400-600 mg/kg/month
4 letter words:
IVIG
CVID
SCID
References
Management of the Acute Migraine Headache. AFP, 2002.
Successful Treatment of Headache Related to Intravenous Immunoglobulin With Antimigraine Medications. Alan G. Finkel, MD ; James F. Howard Jr., MD ; J. Douglas Mann, MD. Headache: The Journal of Head and Face Pain, Volume 38 Issue 4, Pages 317 - 321, 2003.
What Can Be Used to Treat Persistent Headache Caused by Aseptic Meningitis? Randolph Warren Evans, MD. eMedicine, 2000.
Published: 04/19/2009
Updated: 08/18/2010
Selective Immunoglobulin M (IgM) Deficiency
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
A 70-yo Caucasian male (CM) is referred by his primary care physician (PCP) for evaluation for allergic rhinitis/conjunctivitis and chronic sinusitis. He complains of nasal congestion for 25 years which is worse over last 2 years. He has rhinorrhea in spring and fall. He has had 3-4 courses of antibiotics for sinusitis each year for the last 5-7 years.
Past medical history
Diabetes type 2 (DM2), hypertension (HTN).
Medications
Glyburide, amlodipine, Allegra D (fexofenadine and pseudoephedrine) (stopped 5 days ago for skin testing).
Physical examination
Vital signs stable (VSS).
Ears: dull tympanic mebranes (TMs), cerumen present.
Nose: leftward septal deviation, pale boggy turbinates.
Throat: mild cobblestoning.
Lymph: No cervical lymphadenopathy.
Respiratory: CTA (B).
CVS: Clear S1S2.
What tests would you suggest?
Skin prick testing.
CT scan of sinuses.
Would you consider immunodeficiency work-up in this patient?
Immunodeficiency, for example CVID, is in the differential diagnosis of the recurrent episodes of sinusitis in this patient.
Quantitative immunoglobulins were added to the work-up.
What happened?
The CT scan of the sinuses showed pansinusitis, most pronounced in the left maxillary sinus, and moderate leftward deviation of the nasal septum.
Skin prick test was positive for grasses, ragweed, trees, weeds.
We prescribed flunisolide nasal spray qd, saline nasal rinses bid and loratidine qd. He was referred to ENT and a follow-up was arranged in 8 weeks.
What happened next?
The patient came to the follow-up appointment 8 weeks later and reported that he felt 60% better.
His Ig levels were:
The repeated quantitative immunoglobulins showed similar values.
Structure of the pentameric IgM: 1. Base unit, 2. Heavy chains, 3. Light chains, 4. J chain, 5. Intermolecular disulfide bonds. Image source: Wikipedia.
What is the most likely diagnosis?
Selective immunoglobulin M deficiency (SIgMD)
What is the next step in the daignostic work-up of this patient?
Check Anti-ABO antibodies titers. IgM is the antibody against blood group antigens.
Assess biological significance of isolated low IgM level by immunizing the patient with:
- protein vaccines, e.g., tetanus, MMR
- polysaccharide vaccines, e.g. unconjugated Streptococcus pneumoniae
Assess if antigen-specific IgG responses are normal.
How to assess humoral immune response?
Inject patient with Pneumovax 23 (not Prevnar, which is a 7-valent conjugate vaccine). Check anti-polysaccharide IgG antibody to pneumococcus serotypes in 3 weeks. There should be a 3-5 fold increase in the anitbody titer to at least 50% of isotypes.
Which serotypes should be included in the order for Ig?
The same serotypes that were included in the given vaccine. Check the enclosed leaflet for this information. For example, the serotypes included in Pneumovax 23 can be found from the Merck website (PDF):
1 2 3 4 5 6B 7F 8 9N 9V 10A 11A 12F 14 15B 17F 18C 19F 19A 20 22F 23F 33F
How to collect the serum for anti-polysaccharide IgG antibodies?
Collect the serum prior to immunization with Pneumovax 23. Store the pre-immunization serum in the office refrigerator. Give the vaccine. Check the post-immunization serum 3 weeks later. Send both pre- and post-immunization serums to the laboratory at the same time.
The pneumococcal vaccine comprises purified capsular polysaccharide of 23 stereotypes that account for more than 90% of the invasive pneumococcal infections in the USA. It induces anti-polysaccharide IgG antibody levels to most or all of the component polysaccharide antigens in immunocompetent adults. Elderly adults respond equally well to vaccination as do younger adults. The current 23-valent vaccine comprises 25 μg of each of 23 pneumococcal stereotypes (namely, serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F).
The test should be ordered as follows: Pre- and post-IgM and IgG antibody titers to pneumococcal serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F
Final diagnosis
Selective immunoglobulin M deficiency (SIgMD).
What did we learn from this case?
Selective immunoglobulin M deficiency (SIgMD) is a rare form of dysgammaglobulinemia, with an incidence of less than 0.03% in the general population and 1% in hospitalized patients.
Patients with SIgMD are susceptible to infections with encapsulated bacteria, e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae.
Quantitative levels of IgM, IgG, IgA are measured to exclude more common immunodeficiency disorders, such as common variable immunodeficiency and IgA deficiency.
Replacement of IgM is not used since IgM is not a significant component of the commercially available intravenous immunoglobulins.
If defective antigen-specific IgG responses are found after immunization with polysaccharide vaccines, IVIG replacement may be an option.
Five immunoglobulin classes (mind map)
In order of their serum concentrations:
IgG 1000 mg/dL
IgA 200 mg/dL
IgM 150 mg/dL
IgD 4 mg/dL
IgE 0.005 mg/dL (extremely low serum concentration compared to other Ig in (GAMED)
Ig structures. Image source: Wikipedia.
Mnemonics: Adaptive Humoral Immunity: B-cells and Immunoglobulins
There are 5 immunoglobulin classes remembered by the mnemonic GAMED: Ig G, A, M, E, D.
Ig
G
Greatest serum concentration, half-life and number of sub-classes
Ig
M
Macro -- largest Ig
Ig
A
Adhesion prevention
Aggregates -- 2 units linked together
Alternative pathway of complement
Activation
References
Immunoglobulin M Deficiency. Iftikhar Hussain. eMedicine, 2006.
How to Diagnose Common Variable Immunodeficiency (CVID)?
Adaptive Humoral Immunity: B-cells and Immunoglobulins
Mnemonics: Adaptive Humoral Immunity: B-cells and Immunoglobulins
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
A 70-yo Caucasian male (CM) is referred by his primary care physician (PCP) for evaluation for allergic rhinitis/conjunctivitis and chronic sinusitis. He complains of nasal congestion for 25 years which is worse over last 2 years. He has rhinorrhea in spring and fall. He has had 3-4 courses of antibiotics for sinusitis each year for the last 5-7 years.
Past medical history
Diabetes type 2 (DM2), hypertension (HTN).
Medications
Glyburide, amlodipine, Allegra D (fexofenadine and pseudoephedrine) (stopped 5 days ago for skin testing).
Physical examination
Vital signs stable (VSS).
Ears: dull tympanic mebranes (TMs), cerumen present.
Nose: leftward septal deviation, pale boggy turbinates.
Throat: mild cobblestoning.
Lymph: No cervical lymphadenopathy.
Respiratory: CTA (B).
CVS: Clear S1S2.
What tests would you suggest?
Skin prick testing.
CT scan of sinuses.
Would you consider immunodeficiency work-up in this patient?
Immunodeficiency, for example CVID, is in the differential diagnosis of the recurrent episodes of sinusitis in this patient.
Quantitative immunoglobulins were added to the work-up.
What happened?
The CT scan of the sinuses showed pansinusitis, most pronounced in the left maxillary sinus, and moderate leftward deviation of the nasal septum.
Skin prick test was positive for grasses, ragweed, trees, weeds.
We prescribed flunisolide nasal spray qd, saline nasal rinses bid and loratidine qd. He was referred to ENT and a follow-up was arranged in 8 weeks.
What happened next?
The patient came to the follow-up appointment 8 weeks later and reported that he felt 60% better.
His Ig levels were:
| Result mg/dL | Reference range | |
| IgA | 283 | 70 to 400 |
| IgM | 25 | 40 to 230 |
| IgG | 1045 | 700 to 1600 |
The repeated quantitative immunoglobulins showed similar values.
Structure of the pentameric IgM: 1. Base unit, 2. Heavy chains, 3. Light chains, 4. J chain, 5. Intermolecular disulfide bonds. Image source: Wikipedia.
What is the most likely diagnosis?
Selective immunoglobulin M deficiency (SIgMD)
What is the next step in the daignostic work-up of this patient?
Check Anti-ABO antibodies titers. IgM is the antibody against blood group antigens.
Assess biological significance of isolated low IgM level by immunizing the patient with:
- protein vaccines, e.g., tetanus, MMR
- polysaccharide vaccines, e.g. unconjugated Streptococcus pneumoniae
Assess if antigen-specific IgG responses are normal.
How to assess humoral immune response?
Inject patient with Pneumovax 23 (not Prevnar, which is a 7-valent conjugate vaccine). Check anti-polysaccharide IgG antibody to pneumococcus serotypes in 3 weeks. There should be a 3-5 fold increase in the anitbody titer to at least 50% of isotypes.
Which serotypes should be included in the order for Ig?
The same serotypes that were included in the given vaccine. Check the enclosed leaflet for this information. For example, the serotypes included in Pneumovax 23 can be found from the Merck website (PDF):
1 2 3 4 5 6B 7F 8 9N 9V 10A 11A 12F 14 15B 17F 18C 19F 19A 20 22F 23F 33F
How to collect the serum for anti-polysaccharide IgG antibodies?
Collect the serum prior to immunization with Pneumovax 23. Store the pre-immunization serum in the office refrigerator. Give the vaccine. Check the post-immunization serum 3 weeks later. Send both pre- and post-immunization serums to the laboratory at the same time.
The pneumococcal vaccine comprises purified capsular polysaccharide of 23 stereotypes that account for more than 90% of the invasive pneumococcal infections in the USA. It induces anti-polysaccharide IgG antibody levels to most or all of the component polysaccharide antigens in immunocompetent adults. Elderly adults respond equally well to vaccination as do younger adults. The current 23-valent vaccine comprises 25 μg of each of 23 pneumococcal stereotypes (namely, serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F).
The test should be ordered as follows: Pre- and post-IgM and IgG antibody titers to pneumococcal serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F
Final diagnosis
Selective immunoglobulin M deficiency (SIgMD).
What did we learn from this case?
Selective immunoglobulin M deficiency (SIgMD) is a rare form of dysgammaglobulinemia, with an incidence of less than 0.03% in the general population and 1% in hospitalized patients.
Patients with SIgMD are susceptible to infections with encapsulated bacteria, e.g., Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae.
Quantitative levels of IgM, IgG, IgA are measured to exclude more common immunodeficiency disorders, such as common variable immunodeficiency and IgA deficiency.
Replacement of IgM is not used since IgM is not a significant component of the commercially available intravenous immunoglobulins.
If defective antigen-specific IgG responses are found after immunization with polysaccharide vaccines, IVIG replacement may be an option.
Five immunoglobulin classes (mind map)
In order of their serum concentrations:
IgG 1000 mg/dL
IgA 200 mg/dL
IgM 150 mg/dL
IgD 4 mg/dL
IgE 0.005 mg/dL (extremely low serum concentration compared to other Ig in (GAMED)
Ig structures. Image source: Wikipedia.
Mnemonics: Adaptive Humoral Immunity: B-cells and Immunoglobulins
There are 5 immunoglobulin classes remembered by the mnemonic GAMED: Ig G, A, M, E, D.
Ig
G
Greatest serum concentration, half-life and number of sub-classes
Ig
M
Macro -- largest Ig
Ig
A
Adhesion prevention
Aggregates -- 2 units linked together
Alternative pathway of complement
Activation
References
Immunoglobulin M Deficiency. Iftikhar Hussain. eMedicine, 2006.
How to Diagnose Common Variable Immunodeficiency (CVID)?
Adaptive Humoral Immunity: B-cells and Immunoglobulins
Mnemonics: Adaptive Humoral Immunity: B-cells and Immunoglobulins
Interpretation of pneumococcal antibody titers - AAAAI Ask the Expert, 2011.
Cost-effectiveness of Pneumococcal Conjugate Vaccine vs. Polysaccharide Vaccine in Adults: PCV13 was better than PPSV23. JAMA, 2012.
Published: 08/14/2008
Updated: 02/06/2012
Cost-effectiveness of Pneumococcal Conjugate Vaccine vs. Polysaccharide Vaccine in Adults: PCV13 was better than PPSV23. JAMA, 2012.
Published: 08/14/2008
Updated: 02/06/2012
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