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A Persistent Cutaneous Eruption in a Human Immunodeficiency Virus-Infected Man.

A 33-year-old human immunodeficiency virus (HIV)-positive man was admitted to the hospital with fever, nausea and vomiting, a diffuse cutaneous eruption, shortness of breath, and a persistent cough productive of white sputum. He had lost 27 kg (60 lb) in the previous 6 months. He had initially tested positive for HIV-1 4 years prior to admission, and he had a medical history of asthma, crack cocaine abuse, recurrent oral candidiasis, shingles, and noncompliance with his antiretroviral regimen. Six months prior to admission, he was diagnosed with disseminated histoplasmosis and treated with intravenous amphotericin B and oral itraconazole.

Physical examination revealed a cachectic man with a persistent cough. The patient was febrile to 39.2 [degrees] C (102.5 [degrees] F). Multiple 2- to 3-mm hyperpigmented papules coalesced into large plaques on the patient's cheeks, forehead, chin, and upper arms (Figure 1). Brown macules less than 1 cm were noted on his palms and soles. The oropharynx was mildly erythematous with a white exudate adherent to the hard palate. Multiple, small cervical lymph nodes were noted, but examination of the axillary and inguinal nodes revealed no lymphadenopathy.


The patient's CD4 count was 2/[mm.sup.3], and he was pancytopenic. Radiographs of the chest and a computed tomographic scan of the chest, abdomen, and pelvis were normal.

A 4 x 4-mm punch biopsy of facial skin was performed. The epidermis was normal. Within the dermis were multiple aggregates of faintly basophilic spherules, each measuring approximately 2 to 4 [micro] m in diameter (Figure 2). A minimal lymphohistiocytic inflammatory infiltrate was noted. The spherules were strongly positive for periodic acid-Schiff and Gomori methenamine silver stains.


What is your diagnosis?

Pathologic Diagnosis: Recurrent Acute Disseminated Histoplasmosis in the Acquired Immunodeficiency Syndrome

The tissue culture and 2 blood cultures grew Histoplasma capsulatum. The patient was thought to have had a recurrence of disseminated histoplasmosis. He admitted to poor compliance with his oral antifungal (itraconazole) regimen. Amphotericin B was administered intravenously, and he was treated with oral itraconazole for secondary prophylaxis at discharge.


Histoplasmosis is caused by an infection with the dimorphic fungus H capsulatum var capsulatum, which is found as a soil saprophyte in areas contaminated with bird and bat droppings. This condition occurs in many different areas of the world, but the largest endemic focus is in the southeastern and midwestern United States, where up to 80% to 90% of the population may exhibit a positive intradermal histoplasmin skin test.[1] Acute disseminated histoplasmosis, quite rare before the acquired immunodeficiency syndrome (AIDS) epidemic, is now much more common, occurring in 2.7% to 5% of AIDS patients in nonendemic areas and in up to 27% of AIDS patients in endemic areas of the United States.[2-4] Acute disseminated histoplasmosis often occurs early in the course of HIV infection and is the AIDS-defining illness in at least half of these cases.[5]

In disseminated histoplasmosis, the organism spreads to multiple organs, including the lungs, liver and spleen, lymphoreticular system, bone marrow, and skin. Patients manifest a wasting syndrome and present with persistent fever, weight loss, and frequently chronic respiratory symptoms.[5] The most common presenting signs include hepatosplenomegaly and hematologic abnormalities (anemia, leukopenia, and thrombocytopenia).[5] Cutaneous involvement occurs in less than 25% of patients.[6] The eruption typically appears as 2-mm, erythematous, follicularly centered papules on the face, upper trunk, and extremities. The papules may enlarge to form nodules and plaques, umbilicate to mimic molluscum contagiosum, or progress to shallow ulcerations.[7]

Histologically, the diagnostic feature in cutaneous biopsies is the presence of numerous 2- to 4-[micro]m spores. They may stain weakly with hematoxylin-eosin, but are often positive for methenamine silver stain. Narrow-based budding of the spores may be seen. A brisk lymphohistiocytic infiltrate is typically present, and spores are usually found within macrophages and in giant cells.[8] Less often, there may be a pattern of leukocytoclastic vasculitis with granulomatous changes and areas of focal dermal necrosis.[7] In our patient, the biopsy showed a paucity of inflammation surrounding the aggregates of organisms, and no parasitized histiocytes were noted. This was perhaps due to the profound level of immunosuppression and the inability to mount an appropriate immune response.

The diagnosis is made by identifying the characteristic organisms in biopsies, peripheral blood, or sputum. Care must be taken in differentiating Histoplasma from similar organisms, such as Leishmania, Cryptococcus, and Penicillium marneffei. Histiocytes may also be parasitized by Calymmatobacterium granulomatis and Klebsiella pneumoniae rhinoscleromatis. The presence of Histoplasma should be confirmed by culture. A rising complement-fixation titer may be helpful in diagnosis, but is not always reliable in immunosuppressed patients. Detection of H capsulatum antigen in serum or urine may be more appropriate for patients with AIDS.[9]

Intravenous amphotericin B should be the first-line treatment in the management of disseminated disease. Ketoconazole, fluconazole, and itraconazole have also been used. Recurrence is common in immunosuppressed patients and may be addressed by long-term administration of oral itraconazole.[10]


[1.] Goodwin RA Jr, Des Prez RM. Histoplasmosis. Am Rev Respir Dis. 1978; 117:929.

[2.] Johnson PC, Sarosi GA, Septimus EJ, Satterwhite TK. Progressive disseminated histoplasmosis in patients with the acquired immune deficiency syndrome: a report of 12 cases and a literature review. Semin Respir Infect. 1986;1:1-8.

[3.] Johnson PC, Khardori N, Najjar AF, Butt F, Mansall PWA, Sarosi GA. Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988;85:152-158.

[4.] Wheat LJ, Connolly-Stringfield PA, Baker RL, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore). 1990;69:361-374.

[5.] Sarosi GA, Johnson PC. Disseminated histoplasmosis in patients infected with human immunodeficiency virus. Clin Infect Dis. 1992;14:S60-S67.

[6.] Cohen PR, Bank DE, Silvers DN, Grossman ME. Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients. J Am Acad Dermatol. 1990;23:422-428.

[7.] Eidbo J, Sanchez RL, Tschen JA, EIIner KM. Cutaneous manifestations of histoplasmosis in the acquired immune deficiency syndrome. Am J Surg Pathol. 1993;17:110-116.

[8.] Dumont A, Piche C. Electron microscopic study of human histoplasmosis. Arch Pathol. 1969;87:168.

[9.] Wheat LJ, Kohler RB, Tewari RP. Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimen. N Engl J Med. 1986;314:83-88.

[10.] Wheat J, Hafner R, Wulfsohn M, et al. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1993;118:610-616.

Accepted for publication June 13, 2000.

From the Departments of Medicine (Dermatology) (Drs O'Quinn, Stites, and Boyd) and Pathology (Dr Boyd), Vanderbilt University, Department of Veterans Affairs Medical Center, Nashville, Tenn.

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Article Details
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Author:O'Quinn, Ryan P.; Stites, P. Craig; Boyd, Alan S.
Publication:Archives of Pathology & Laboratory Medicine
Geographic Code:1USA
Date:Apr 1, 2001
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