A 53‐year‐old woman presented with vomiting, severe headache, and neck stiffness. She had no recent sick contacts, travel or tick bites. She was without identifiable HIV risk factors or family history of immunodeficiency disorders. Physical examination was notable for fever and meningismus. She had no rashes or neurological deficits. CBC and CMP were unremarkable. CSF revealed pleocytosis and positive Cryptococcal antigen. CD4 count was 32; however, her HIV viral load by both PCR and branched chain assays was negative. CMV, EBV, HTLV‐1/2 serologies were unremarkable. There was no evidence for an underlying autoimmune process, immunoglobulin disturbance, or recent infection. She had no identifiable exogenous therapy capable of suppressing lymphocytes. CT imaging revealed a cavitary left lower lung nodule that was biopsy proven Cryptococcus neoformins and negative for acid‐fast bacilli. CT findings of retroperitoneal lymphadenopathy were found to be reactive on biopsy. She was treated for her cryptococcal meningitis with flucytosine and amphotericin and started on sulfamethoxazole/trimethoprim and azithromycin for primary prevention of opportunistic infections. Subsequent bone marrow biopsy and flow cytometry did not show evidence of a neoplastic disorder or clonal process. Three months following her initial presentation, she continues to have persistent isolated CD4 lymphocytopenia and is being considered for investigational cytokine therapy.
Idiopathic CD4 T‐cell lymphocytopenia (ICL) is a rare condition defined by persistent CD4 lymphocytopenia in the absence of HIV infection or other causes of immunodeficiency. Since the recognition of HIV lymphocytopenia in the 1980s, there have been only 47 documented cases of ICL. Currently, there is no clear understanding of this phenomenon or its natural course. There is evidence that ICL presents in conjunction with coinfections, but it is unclear if the infections are a trigger or consequence of ICL. This case presentation gives a clear description of CD4 loss that has persisted months after resolution of an opportunistic infection. Prognosis depends on the degree and duration of lymphocytopenia and the presence of opportunisitic infections. A prospective study of ICL patients noted that 20% of those with ICL spontaneously resolved their lymphocytopenia within 3 years. Also, there are studies suggesting that those with concomitant CD8 T‐cell loss may benefit from experimental cytokine therapy such as IL‐2.
ICL is a rare heterogeneous condition that is typically diagnosed after an opportunistic infection, most commonly Cryptococcus and nontuberculous mycobacterium. Hospitalists should consider this entity in the setting of opportunisitic infections as further evaluation of t‐lymphocytes could be revealing of ICL. Moreover, hospitalist recognition of this disorder would allow early primary prevention of opportunistic infections and access to investigational cytokine therapies.