COMMENTARY

Literature Commentary by Dr. John G. Bartlett: Unexplained CD4 Cytopenia, July 2007

John G. Bartlett, MD

Disclosures

August 03, 2007

Zonios DI, Falloon J, Huang CY, Chaitt D, Bennett JE. Cryptococcosis and idiopathic CD4 lymphocytopenia. Medicine. 2007;86:78-92. This is a report from the Laboratory of Clinical Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), with a review of 11 patients with cryptococcosis and idiopathic CD4 lymphocytopenia (ICL) combined with 42 similar cases reported from the literature.

A review of the 53 cases showed a median age of 41 years, predominance of central nervous system (CNS) cryptococcosis (meningitis), a median CD4+ cell count of 82/microliter (mcL), and a generally good outcome -- with cures in 42 of 46 (91%) cases. The specifics of the review are summarized in the Table .

Of particular interest in this review are the additional findings in patients with ICL. A review of other opportunistic infections indicated high rates of zoster, a rate that the study authors calculated at 56/1000 person-years compared with 2.1/1000 person-years in the general population. Of note is the observation of only a single case of Pneumocystis jiroveci pneumonia (PCP). Also of note is the long-term follow-up, averaging about 6.6 years, that indicated no explanation for the low CD4+ cell count, including complete absence of lymphomas or other malignancy.

Conclusions: The study authors concluded that cryptococcosis in patients with ICL has a generally favorable outcome; the CD4+ cell counts remain low for long periods; the meningitis appears similar to cryptococcal meningitis encountered with other non-HIV-infected patients; relapses are uncommon; and the need for prolonged prophylaxis with either fluconazole for cryptococcosis relapse or for PCP is "questionable."

Comment: ICL was initially reported in 1993.[1] At the time, it was portrayed as another HIV-like condition that required an aggressive pursuit for cause and management guidance. The condition has remained a mystery, with no clear etiology and sparse evidence of either progressive disease or progression in numbers of cases. The report above from Zonios and colleagues represents one of the best reviews on the subject. This review identifies one of the major clinical presentations, cryptococcal meningitis in the non-HIV-infected patient, with good evidence that this -- along with high rates of zoster -- represent the major clinical manifestations. The standard practice of PCP prophylaxis and prolonged courses of fluconazole to prevent relapse of meningitis are questioned by the review authors on the basis of the experience with these 53 patients.

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