Correspondence

The Unturned Stone

N Engl J Med 2005; 352:2140-2141May 19, 2005

Article

To the Editor:

AIDS is a well-known predisposing condition for generalized histoplasmosis, which had been ruled out in the patient described in the Clinical Problem-Solving article by Goulet et al. (Feb. 3 issue).1 Idiopathic CD4+ lymphocytopenia2 is another immunodeficiency state that should be ruled out in such a case. I would like to know what the absolute lymphocyte count and CD4+ count were in this patient. In idiopathic CD4+ lymphocytopenia, several other opportunistic infections, such as cryptococcal meningitis, toxoplasmosis, Pneumocystis carinii pneumonia,3 and disseminated warts, have been described. In general, patients with idiopathic CD4+ lymphocytopenia have stable CD4+ cell counts. Even spontaneous resolution of CD4+ lymphocytopenia has been described. In contrast to the situation with HIV-infected patients, no particular therapy directed against a low lymphocyte count is approved. Patients with idiopathic CD4+ lymphocytopenia may need prophylaxis against other opportunistic infections.

Jayaram S. Bharadwaj, M.D.
Sac-Osage Hospital, Osceola, MO 64776

3 References

1. 1

   Goulet CJ, Moseley RH, Tonnerre C, Sandhu IS, Saint S. The unturned stone. N Engl J Med 2005;352:489-494
   Full Text | Web of Science | Medline

2. 2

   Spira TJ, Jones BM, Nicholson JK, et al. Idiopathic CD4+ T-lymphocytopenia -- an analysis of five patients with unexplained opportunistic infections. N Engl J Med 1993;328:386-392
   Full Text | Web of Science | Medline

3. 3

   Duncan RA, von Reyn CF, Alliegro GM, Toossi Z, Sugar AM, Levitz SM. CD4+ T-lymphocytopenia -- four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med 1993;328:393-398
   Full Text | Web of Science | Medline

Author/Editor Response

Dr. Bharadwaj's comments highlight the importance of searching for an underlying immunodeficiency when an opportunistic infection is found. Idiopathic CD4+ lymphocytopenia is defined by the presence of fewer than 300 CD4+ cells per cubic millimeter or CD4+ cell counts representing less than 20 percent of the total T-cell count in the absence of HIV infection.1 The cause of this condition remains unknown, although some investigators suggest primary failure of regeneration of stem-cell precursors.2 The role of long-term prophylaxis against opportunistic infections in patients with this condition remains unclear.

Our patient had been treated with corticosteroids, which are known to cause relative lymphocytopenia. He had lymphocytopenia, with absolute lymphocyte counts ranging from 400 to 1300 cells per cubic millimeter. In addition to testing for HIV infection, serum immunoglobulin levels were checked to rule out another potential source of immunodeficiency; they were normal. Since our patient had reversible predisposing factors for opportunistic infection (therapy with corticosteroids and infliximab), further testing (including assessment of CD4+ cell counts) and long-term prophylaxis were not recommended. The patient remains in good health without prophylaxis more than 24 months after his hospitalization.

Christopher J. Goulet, M.D.
Claude Tonnerre, M.D.
University of Utah, Salt Lake City, UT 84132
chrisgoulet_98@yahoo.com

2 References

1. 1

   Isgro A, Sirianni MC, Gramiccioni C, Mezzaroma I, Fantauzzi A, Aiuti F. Idiopathic CD4+ lymphocytopenia may be due to decreased bone marrow clonogenic capability. Int Arch Allergy Immunol 2005;136:379-384
   CrossRef | Web of Science | Medline

2. 2

   Smith DK, Neal JJ, Holmberg SD. Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection -- an investigation of cases in the United States. N Engl J Med 1993;328:373-379
   Full Text | Web of Science | Medline