Disseminated histoplasmosis as the first presentation of idiopathic CD4+ T-lymphocytopenia
N Relia, A Kavimandan, S Sinha, SK Sharma
Department of Medicine, AIIMS, New Delhi, India
Department of Medicine, AIIMS, New Delhi
|How to cite this article:|
Relia N, Kavimandan A, Sinha S, Sharma S K. Disseminated histoplasmosis as the first presentation of idiopathic CD4+ T-lymphocytopenia.J Postgrad Med 2010;56:39-40
|How to cite this URL:|
Relia N, Kavimandan A, Sinha S, Sharma S K. Disseminated histoplasmosis as the first presentation of idiopathic CD4+ T-lymphocytopenia. J Postgrad Med [serial online] 2010 [cited 2019 Dec 6 ];56:39-40
Available from: http://www.jpgmonline.com/text.asp?2010/56/1/39/62426
A 39-year-old male presented with a three-month history of low grade fever and cough with expectoration of blood tinged sputum. The patient was a non-smoker and had no history of exposure to birds, visit to forests or caves, recent travel outside his native place or exposure to any person with similar symptomatology. There was no history of high risk behavior or blood transfusion. He had a cachectic look and crackles were audible in right suprascapular region. CT chest revealed bilateral upper lobe fibrocavitatory lesion with consolidation suggestive of an infective etiology [Figure 1]. Sputum examination was negative for bacteria on Gram- and acid fast-staining on three occasions. Based on high population prevalence of tuberculosis in India and a compatible clinical history and radiological evidence, the patient was initiated on anti-tubercular therapy (ATT). There was no significant improvement in his symptoms on ATT and after three weeks of treatment he developed multiple red nodular lesions over the tip of nose, face [Figure 2] and legs. Skin biopsy showed focal areas of necrosis and underlying inflammation rich in histiocytes loaded with intra-cytoplasm organisms morphologically compatible with histoplasma. The diagnosis at this point was revised; ATT stopped and patient started on itraconazole at the dose of 200 mg twice daily.
Considering the possibility of disseminated histoplasmosis, the patient underwent a series of investigations to look for any immune dysfunction and to see other organ involvement. Immunoglobulin levels for IgA, IgG, and IgM were normal. HIV Elisa testing done twice after appropriate counseling and HIV P24 antigen was negative. IgM antibody screening for EBV and CMV were also negative. However, CD4 counts were persistently low at 134/µl and 167/µl tested six weeks apart with normal CD8 counts. Fiber optic Bronchoscopy showed generalized granularity of bronchial wall, mainly in upper and middle lobes with marked narrowing of right upper lobe segments. Bronchial mucosal biopsy revealed multiple epitheloid granulomas without central caseous necrosis.
Computerized tomography (CT) abdomen showed small subcentimetric retroperitoneal lymph nodes without any adrenal, liver and splenic involvement. Bone marrow biopsy also revealed multiple epitheloid granulomas. In the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4 T cells, a diagnosis of disseminated histoplasmosis  with Idiopathic CD4 lymphocytopenia  (ICL) was made. The patient was continued on itraconazole therapy for one year during which cough, fever and skin lesions resolved completely but he continued to have episodes of non-massive hemoptysis with increased frequency and amount. A repeat CT done revealed air crescent sign in the right upper lobe cavity [Figure 3] consistent with fungal colonization and patient tested positive for Aspergillus IgG antibodies. Since patient had no sputum production, a microbiologic identification could not be established and fungal blood cultures were negative. In the absence of constitutional symptoms (except hemoptysis) with underlying lung disease it was thought to represent an Aspergilloma. 
The patient underwent bronchial artery embolization after which his hemoptysis resolved completely. One year later, the patient remained stable with no recurrence of respiratory symptoms or skin lesions or other opportunistic infection. The patient was kept on maintenance antifungal therapy in the form of once daily itraconazole since CD4 count at this time was still low at 148. The persistence of low CD4 count after treatment of histoplasmosis also rules out the possibility of disseminated infection induced transient immunosuppresion.
Idiopathic CD4 lymphocytopenia (ICL) describes a set of patients with reduced numbers of circulating CD4 T lymphocytes (  It is a rare condition  with demographic and immunologic features distinct from those of HIV, making an infectious agent as an unlikely cause of ICL.  Predictably, patients with ICL are prone to opportunistic infections. Cryptococcus has been described as the most common infection in literature followed by Mycobacteriosis and multidermatonal Herpes zoster.  We have reported just the second case of disseminated histoplasmosis in a patient associated with ICL.
Histoplasmosis is a fungal infection caused by soil-based fungus histoplasma capsulatum. In the disseminated form, histoplasmosis is commonly found in immunodeficient individuals such as AIDS, transplant patients and patients with hematological malignancies. AIDS patient tend to be at most risk of severe and progressive disease with CD4 counts less than 150/µl. 
Besides a rare presentation of ICL, this case stresses upon two more important aspects. Firstly, unlike Acquired Immunodeficiency Syndrome (AIDS) related CD4 lymphocytopenia patients with ICL tend to have stable CD4 counts and relatively less severe form of opportunistic disease that responds well to treatment. Secondly, even though tuberculosis is a commonly encountered infection in a developing country like ours; clinicians should retain a high suspicion for the differentials which can closely mimic it, histoplasmosis being one such, especially if there is a less than expected response to ATT or any unexpected clinical event during the course of ATT such as the development of skin lesions in the present case.
|1||Kauffman CA. Histoplasmosis: A clinical and laboratory update. Clin Microbiol Rev 2007;20:115-32. |
|2||Walker UA, Warnatz K. Idiopathic CD4 lymphocytopenia. Curr Opin Rheumatol 2006;18:389-95.|
|3||Amchentsev A, Kurugundla N, Saleh A. Aspergillus-related lung disease. Respir Med CME 2008;1:205-15.|
|4||Busch MP, Valinsky JE, Paglieroni T, Prince HE, Crutcher GJ, Gjerset GF, et al. Screening of blood donors for idiopathic CD4+ T-lymphocytopenia. Transfusion 1994;34:192-7.|
|5||Spira TJ, Jones BM, Nicholson JK, Lai RB, Rowe T, Mawle AC, et al. Idiopathic CD4+ T-lymphocytopenia: An analysis of five patients with unexplained opportunistic infections. N Engl J Med 1993;328:386-92.|