Hyperimmunoglobulin E syndrome (Job's syndrome) with acute coccidioidal meningoencephalitis

Authors: Sean Stanga, M.D.; Maria Victoria Dajud, M.D., Blank Children's Hospital
Reviewer: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago

A 4-year-old female was admitted on transfer from a regional medical center for symptoms of nausea, vomiting, dehydration, and complaints of headache and visual changes for approximately four days. Her symptoms had progressively worsened over time and the patient was admitted for suspected meningitis.

Past medical history (PMH)

Past medical history was significant for recurrent upper respiratory infections as well as sinus and skin infections, most notably eczema herpeticum. Previous metabolic and immunologic workup for her symptoms was significant only for an elevated immunoglobulin E, 805 (nl. 0-230 U/mL), and no definitive diagnosis was established at that time.

Medications

No medications.

Allergies

No allergies.

Physical Examination

Fever, nuchal rigidity and photophobia. Dry mucosal membranes and mild tachycardia. The rest of the physical examination was unremarkable.

What is the most likely diagnosis?

Likely bacterial vs. viral meningitis.

What tests would you suggest?

CBC with differential
Comprehensive Metabolic Panel
Urinalysis
Blood Culture
Lumbar Pucture with cell count, differential, culture for bacteria and HSV PCR
Chest X-ray

What happened?

On admission, her WBC count was 12,970/mm3 with 78.5% neutrophils, 12.6% lymphocytes, 6.8% monocytes, 1.9% eosinophils. Hemoglobin, hematocrit, platelets, comprehensive metabolic panel, and urinalysis were all within normal limits. Lumbar puncture was performed which yielded cloudy spinal fluid with 623 white blood cells, and 2 red blood cells. Differential showed 14% neutrophils, 55% lymphocytes, 9% monocytes, and 18% eosinophils. CSF glucose 53, protein 43.2, and Gram stain was negative for microorganisms. Blood culture was negative. Chest x-ray and KUB were normal. CT performed at the outlying regional medical center was negative for any acute intracranial process. HSV PCR along with spinal fluid cultures were obtained and sent.

The patient was initially started on intravenous ceftriaxone for bacterial coverage and acyclovir for possible herpetic meningoencephalitis. On the second day of admission, the patient experienced several simultaneous tonic/clonic seizures that resolved with IV phenytoin. MRI of the brain revealed a small area of infarction within the left basal ganglia and the right superior cerebellar hemisphere. The patient was started on oxycarbazepine for seizure prophylaxis. Immunoglobulin and complement titers were sent. On day three of admission, the patient awoke with severe lethargy, bilateral lower extremity spasticity, right eye ptosis, horizontal nystagmus, and gross left-sided hemiplegia. Repeat MRI demonstrated very large infarcts in the left and right basal ganglia and the right temporal lobe not previously visualized. Blood cultures revealed no growth and HSV PCR was found to be negative on the third day. Immunoglobulin titers revealed an immunoglobulin E of 9147 (nl. 0-230 U/mL). Immunoglobulins A, G, M and complement C3, C4 were within normal limits.

What happened next?

Out of concern for a fungal infectious etiology, the patient was immediately transferred to a tertiary intensive care unit for infectious disease consult. The patient was started on intravenous voriconazole. Further workup and repeat lumbar puncture demonstrated CSF that grew Coccidioides immitus and antifungal therapy was switched to Amphotericin B. The patient recovered well after a prolonged hospital stay and suffered minimal deficits from the acute episodes of stroke. She was discharged on long term fluconazole therapy with extensive rehabilitation therapy in progress.

Final diagnosis

Hyperimmunoglobulin E syndrome (Job's syndrome) with acute coccidioidal meningoencephalitis.

What did we learn from this case?

While the most common source of CNS infection is dissemination from a primary pulmonary infection, our patient in question never manifested any respiratory symptoms or significant radiographic evidence of lung involvement. Her CNS infection likely was the result of a disseminated skin infection given her longstanding history of dermatitis. This patient had an underlying hyperimmunoglobulin E disease pathology which predisposed her to multiple superficial and systemic fungal infections. The fact that her underlying susceptibility to fungemia was not elicited until after severe CNS infection with an invasive fungal pathogen demonstrates the importance of obtaining immunoglobulin titers early in the course of an illness if an immunodeficiency is suspected.

References

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Published: 12/07/2009
Updated: 12/07/2009

1 comment:

Indhrika said...

Thanks for this useful post. Here is some additional information about the "genetics" of this condition that was written by our Genetic Counselor and other genetic professionals: http://www.accessdna.com/condition/Job_Syndrome/214. Thanks, AccessDNA