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

1. Gottfredsson M, Perfect JR. Fungal meningitis. Semin Neurol 2000;20:307-322
2. Bronnimann DA, Adam RD, Galgiani JN, et al. Coccidioidomycosis in the acquired immunodeficiency syndrome. Ann Intern Med 1987;106:372-379
3. Chiller TM, Galgiani JN, Stevens DA. Coccidioidomycosis. Infect Dis Clin North Am 2003;17:41-57, viii
4. Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis 2006;42:103-107
5. Ragland AS, Arsura E, Ismail Y, Johnson R. Eosinophilic pleocytosis in coccidioidal meningitis: frequency and significance. Am J Med 1993;95:254-257
6. Beard JS, Benson PM, Skillman L. Rapid diagnosis of coccidioidomycosis with a DNA probe to ribosomal RNA. Arch Dermatol 1993;129:1589-1593
7. Kleinschmidt-DeMasters BK, Mazowiecki M, Bonds LA, Cohn DL, Wilson ML. Coccidioidomycosis meningitis with massive dural and cerebral venous thrombosis and tissue arthroconidia. Arch Pathol Lab Med 2000;124:310-314
8. de Carvalho CA, Allen JN, Zafranis A, Yates AJ. Coccidioidal meningitis complicated by cerebral arteritis and infarction. Hum Pathol 1980;11:293-296
9. Williams PL, Johnson R, Pappagianis D, et al. Vasculitic and encephalitic complications associated with Coccidioides immitis infection of the central nervous system in humans: report of 10 cases and review. Clin Infect Dis 1992;14:673-682
10. Antony SJ, Jurczyk P, Brumble L. Successful use of combination antifungal therapy in the treatment of coccidioides meningitis. J Natl Med Assoc 2006;98:940-942
11. Capilla J, Clemons KV, Sobel RA, Stevens DA. Efficacy of amphotericin B lipid complex in a rabbit model of coccidioidal meningitis. J Antimicrob Chemother 2007;60:673-676
12. Clemons KV, Sobel RA, Williams PL, Pappagianis D, Stevens DA. Efficacy of intravenous liposomal amphotericin B (AmBisome) against coccidioidal meningitis in rabbits. Antimicrob Agents Chemother 2002;46:2420-2426
13. Li RK, Ciblak MA, Nordoff N, Pasarell L, Warnock DW, McGinnis MR. In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. Antimicrob Agents Chemother 2000;44:1734-1736
14. Proia LA, Tenorio AR. Successful use of voriconazole for treatment of Coccidioides meningitis. Antimicrob Agents Chemother 2004;48:2341
15. Sorensen KN, Sobel RA, Clemons KV, et al. Comparative efficacies of terbinafine and fluconazole in treatment of experimental coccidioidal meningitis in a rabbit model. Antimicrob Agents Chemother 2000;44:3087-3091
16. Tucker RM, Galgiani JN, Denning DW, et al. Treatment of coccidioidal meningitis with fluconazole. Rev Infect Dis 1990;12 Suppl 3:S380-389
17. Tucker RM, Williams PL, Arathoon EG, et al. Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother 1988;32:369-373
18. Kamberi P, Sobel RA, Clemons KV, et al. Comparison of itraconazole and fluconazole treatments in a murine model of coccidioidal meningitis. Antimicrob Agents Chemother 2007;51:998-1003
19. Saitoh A, Homans J, Kovacs A. Fluconazole treatment of coccidioidal meningitis in children: two case reports and a review of the literature. Pediatr Infect Dis J 2000;19:1204-1208

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