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Table of Contents 
Year : 2014  |  Volume : 59  |  Issue : 2  |  Page : 182-185
Disseminated cutaneous histoplasmosis, an initial manifestation of hiv, diagnosed with fine needle aspiration cytology

1 Department of Dermatology, North Bengal Medical College, Darjeeling, West Bengal, India
2 Department of Pathology, North Bengal Medical College, Darjeeling, West Bengal, India
3 Department of Dermatology, J.N.M.C. Sawangi, Wardha, Maharashtra, India

Date of Web Publication21-Feb-2014

Correspondence Address:
Sankha Koley
Subhankar Sarani, Bankura-722 101
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.127681

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Acute progressive disseminated histoplasmosis (PDH) may be the initial manifestation of human immunodeficiency virus (HIV). However, cutaneous involvement is very rare. We present an unusual case of acute PDH with multiple diffuse cutaneous papulonodular lesions predominantly on the face, trunk, and upper extremities, diagnosed initially with fine needle aspiration cytology (FNAC). Subsequent serological tests revealed positivity for antibodies for HIV 1 and 2. The cytomorphological features were further confirmed by biopsy and histochemical stains. FNAC is a rapid, cost-effective tool that may be utilized in the diagnosis of papulonodular forms of PDH and for initiating prompt therapy. We discuss the clinical features, clinical differentials, and treatment of the condition.

Keywords: Disseminated cutaneous histoplasmosis, human immunodeficiency virus, fine needle aspiration cytology

How to cite this article:
Koley S, Mandal RK, Khan K, Choudhary S, Banerjee S. Disseminated cutaneous histoplasmosis, an initial manifestation of hiv, diagnosed with fine needle aspiration cytology. Indian J Dermatol 2014;59:182-5

How to cite this URL:
Koley S, Mandal RK, Khan K, Choudhary S, Banerjee S. Disseminated cutaneous histoplasmosis, an initial manifestation of hiv, diagnosed with fine needle aspiration cytology. Indian J Dermatol [serial online] 2014 [cited 2023 Oct 1];59:182-5. Available from:

What was known?
1. Acute progressive disseminated histoplasmosis (PDH) may be the initial manifestation of human immunodeficiency virus (HIV). However, cutaneous involvement is less common (10% of the cases) and almost always associated with systemic complaints.
2. Provisional diagnostic modalities include culture, biopsy, fungal histochemical stains of tissue, aspiration cytology smears of body fluids and serology.

   Introduction Top

Histoplasmosis, the most common endemic mycosis in patients with Acquired Immune Deficiency Syndrome (AIDS), [1] is usually self-limiting or localized in immunocompetent individuals. However, in AIDS patients, it generally occurs as acute progressive disseminated histoplasmosis (PDH). [2] Cutaneous involvement is noted in 10% of PDH [3] and very rarely may be the initial presentation for the diagnosis of AIDS. [4] In the pre-AIDS era, PDH was rare and the cutaneous manifestations were seldom reported. With the increase in patients of AIDS, a range of unusual clinical manifestations of disseminated cutaneous histoplasmosis (DCH) are being noted. Fine needle aspiration cytology (FNAC) is a simple, safe, and rapid technique often used to establish the initial diagnosis of histoplasmosis in tissues [5] but biopsies and culture are necessary for making an accurate diagnosis of the fungal infection. [6]

We report an unusual case of DCH with multiple diffuse nodules and plaques presenting as an initial manifestation of AIDS. The patient was initially diagnosed with the aid of FNAC and treatment was started.

   Case Report Top

A 31-year-old farmer presented with a sudden eruption of papules, nodules, and plaques predominantly on the upper extremities, face, chest and abdomen since three months [Figure 1] and [Figure 2]. A few of the lesions had central umbilication, a few were ulcerated, and a few had pustules over them. Apparently, he was doing well and did not suffer from any serious illness in the recent past. There was no lymphadenopathy or hepatosplenomegaly. He had intermittent fever and occasional viscid cough since six months. The patient was clinically diagnosed as molluscum contagiosum and thoroughly investigated. Routine hemogram was normal except his hemoglobin which was 8 gm%. Chest X-ray showed increased bronchovascular markings with hilar and mediastinal broadening, suggestive of lymph node enlargement. Subsequently, computed tomography (CT) scan of the chest was done to confirm hilar and mediastinal lymphadenopathy. All other biochemical parameters, liver and renal function tests and routine urine and stool examinations were unremarkable. Venereal Disease Research Laboratory (VDRL) test was nonreactive. His serum was positive for antibodies for HIV 1 and 2 by Enzaids HIV 1 + 2 Enzyme-Linked Immunosorbent Assay (ELISA) test kit, Span Diagnostic Ltd., Surat, India. His cluster of differentiation 4(CD4) count was 38 cells/μL.
Figure 1: Disseminated cutaneous histoplasmosis; multiple papules, nodules on face

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Figure 2: Disseminated cutaneous histoplasmosis; multiple papules, nodules on back. Inset: (a) A ruptured macrophage with plenty of intracellular (arrow head) and extracellular yeast forms (hematoxylin and eosin, ×100)

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FNAC from a large nodule on the face yielded a whitish granular aspirate and smears from this showed both extracellular and intracellular fungal profile compatible with morphology of Histoplasma capsulatum [Figure 3]. The fungal spores were mostly oval to round and were 2-4 μm in diameter, with a halo (capsule) around them. The patient was put on highly active antiretroviral therapy (HAART) along with itraconazole 200 mg twice daily.
Figure 3: Ulcerated epidermis with underlying numerous macrophage aggregates (hematoxylin and eosin, ×40); Inset: Plenty of intracellular rounded yeast forms within macrophages (hematoxylin and eosin, ×100)

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Biopsy was taken from a nodule from the back and histopathological examination showed an ulcerated and thinned-out epidermis with underlying numerous macrophages and scattered giant cells in papillary and reticular dermis. There were diffuse lymphocytic infiltrates coupled with a striking number of Periodic Acid Schiff (PAS)-positive yeast forms within the macrophages consistent with H capsulatum [Figure 3]. The aspirated material was innoculated on Sabouraud's dextrose agar and it yielded a fluffy colony on the 13 th day. We could not do a biopsy of the liver and spleen as the patient was not willing.

The lesions disappeared completely in eight weeks. We continued itraconazole 200 mg per day for 10 months more.

   Discussion Top

Histoplasmosis, a fungal infection caused predominantly by H capsulatum var. capsulatum in America and the tropics and H capsulatum var. duboisii in Africa, became an AIDS-defining illness as per the Centers for Disease Control (CDC) in 1987. [7] It has varied presentations such as pulmonary, chronic cavitatory, and PDH (acute and chronic) [8] other than the very rare primary cutaneous form. Acute PDH is usually seen in immunocompromised individuals like those on corticosteroids, those with hematologic malignancies, transplant recipients, or HIV patients. In HIV-infected patients, it is usually associated with advanced immunosuppression in AIDS, with CD4 counts less than 150 cells/μL, with a median CD4 count of 50 cells/μL. [9]

Cutaneous involvement may be seen in all forms of histoplasmosis. Skin lesions can be caused by the fungus itself (papules, plaques, nodules, or ulcers) or by an immune response to the infection (erythema nodosum or erythema multiforme).

Possible diagnostic modalities include culture, biopsy, fungal histochemical stains of tissue, aspiration cytology smears of body fluids, and tests for antigen and antibodies (serology). Culture is the gold standard for diagnosis, but it takes days or even weeks to turn positive and therefore is impractical as a criterion for the initiation of treatment. The antigen tests often show false positivity or negativity. Anti-Histoplasma antibodies may result from previous infections. However, in acute PDH in AIDS, as the fungal burden is high, blood cultures and antigen tests are highly positive (95 and 86%, respectively), [9],[10] and serology is low (83% in immunosuppressed patients compared with 100% of nonimmunosuppressed patients). [10]

Biopsy is a comparatively fast and reliable method, but there is delay in fixation (in formalin) and processing of the tissue. FNAC is a safe, cost-effective (simple and cheap) and rapid technique for initial diagnosis in superficial tissues. It is readily repeatable, useful for multifocal lesions, and causes minimal physical and psychological discomfort to the patient. The simple procedure of FNAC is described in detail in [Table 1]. The outcomes compare well with the results of tissue biopsy when the procedure is performed and interpreted by skilled individuals. [11],[12]
Table 1: Detailed fine needle aspiration cytology procedure

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DCH in AIDS patients may be clinically simulated by deep fungal infections (Cryptococcus neoformans, Penicillium marneffei, and coccidioidomycosis, leishmaniasis, and Pneumocystis jirovecii). H capsulatum is a small, uninucleate dimorphic fungus measuring 2-4 μm in diameter. It is found predominantly intracellularly and is usually present in clusters inside the cytoplasm of macrophages, with a light area surrounding the organism (pseudocapsule). Cryptococci are round capsulated organisms with a thick capsule and show positive capsular staining on Mayer's mucicarmine but negative staining with India ink preparation. The spherical-to-oval yeastlike cells of P. marneffei are often sequestered within mononuclear phagocytes, but do not bud. Instead, this fungus reproduces by schizogony (fission) with the formation of a prominent transverse septum. The gold standard for diagnosing coccidioidomycosis is either a positive culture for Coccidioides immitis or evidence of spherules containing endospores on histopathologic examination. Leishmania will not take PAS stain and is distinguished by a nucleus and bar-shaped kinetoplast within each amastigote. P. jirovecii contain distinct single or paired comma-shaped argyrophilic foci in the walls. The cysts resemble crushed ping-pong balls and are present in aggregates of two to eight (Histoplasma does not form aggregates of spores or cells). The differentials in FNAC are depicted in [Figure 4].
Figure 4: Microscopic differentials of histoplasmosis

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Itraconazole is the drug of choice for both inducing and maintaining remission in mild to moderate histoplasmosis. For disseminated fungal infections, suppressive therapy must be continued to prevent relapse. Earlier, prophylaxis was given lifelong. Recent data suggests that the risk for relapse is rare after 12 months of treatment with a sustained immunologic improvement (CD4 >150/mm 3 ). [13] According to the 2007 guidelines of the Infectious Diseases Society of America (IDSA), AIDS patients with disseminated histoplasmosis on HAART can safely discontinue itraconazole therapy if certain conditions are met [Table 2]. [14] There are documented cases of Immune Reconstitution Inflammatory Syndrome (IRIS) in patients with histoplasmosis, but it is rare and usually mild. So, HAART should not be delayed for that reason. [15] Our patient responded very well to HAART and itraconazole.
Table 2: Conditions for discontinuation of itraconazole therapy in AIDS patients with disseminated histoplasmosis on highly active antiretroviral therapy (Wheat, et al.)[14]

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Histoplasmosis was first reported in India by Panja and Sen in 1954. [16] It is very rare and endemic in certain parts of West Bengal. [17] A prevalence of 9.4% positivity to the histoplasmin-sensitivity test was reported from Calcutta and the vicinity. [18] Acute PDH has been rarely reported from India till 2006, [19] but recently, many cases have been reported from India with HIV infection. [19],[20],[21],[22]

In our case, wide-spread skin lesions along with hilar and mediastinal lymphadenopathy suggested that DCH was secondary to a pulmonary focus. The presence of papules, nodules, and plaques enabled us to do an FNAC. DCH with papulonodular lesions has been rarely reported till now. With a global pandemic status of HIV/AIDS, more and more unusual papulonodular forms of DCH may be noted. FNAC is a simple and inexpensive procedure utilized for rapid diagnosis of the fungus and prompt therapy. This is a very rare case in world literature where the diagnosis of DCH was established with FNAC and a detailed description has been provided here on the clinical features, differential diagnosis, and treatment of the condition.

   References Top

1.Wheat LJ, Chetchotisakd P, Williams B, Connolly P, Shutt K, Hajjeh R. Factors associated with severe manifestations of histoplasmosis in AIDS. Clin Infect Dis 2000;30:877-81.  Back to cited text no. 1
2.Bullock WE. Histoplasma capsulatum. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 4 th ed. London: Churchill Livingstone; 1995. p. 2340.  Back to cited text no. 2
3.Cohen PR, Bank DE, Silvers DN, Grossman ME. Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus infected patient. J Am Acad Dermatol 1990;23:422-8.  Back to cited text no. 3
4.Wheat LJ. Histoplasmosis in the acquired immunodeficiency syndrome. Curr Top Med Mycol 1996;7:7-18.  Back to cited text no. 4
5.Gupta N, Arora SK, Rajwanshi A, Nijhawan R, Srinivasan R. Histoplasmosis: Cytodiagnosis and review of literature with special emphasis on differential diagnosis on cytomorphology. Cytopathology 2010;21:240-4.  Back to cited text no. 5
6.Myers SA, Kamino H. Cutaneous cryptococcosis and histoplasmosis coinfection in a patient with AIDS. J Am Acad Dermatol 1996;34:898-900.  Back to cited text no. 6
7.Leads from the MMWR. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. JAMA 1987;258:1143-54.  Back to cited text no. 7
8.Cirillo-Hyland VA, Gross P. Disseminated histoplasmosis in a patient with acquired immunodeficiency syndrome. Cutis 1995;55:161-4.  Back to cited text no. 8
9.Wheat LJ, Connolly-Stringfield PA, Baker RL, Curfman MF, Eads ME, Israel KS, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: Clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) 1990;69:361-74.  Back to cited text no. 9
10.Williams B, Fojtasek M, Connolly-Stringfield P, Wheat J. Diagnosis of histoplasmosis by antigen detection during an outbreak in Indianapolis. Ind. Arch Pathol Lab Med 1994;118:1205-8.  Back to cited text no. 10
11.Greif J, Marmur S, Schwarz Y, Man A, Staroselsky AN. Percutaneous core cutting needle biopsy compared with fine-needle aspiration in the diagnosis of peripheral lung malignant lesions: Results in 156 patients. Cancer 1998;84:144-7.  Back to cited text no. 11
12.Stewart CJ, Coldewey J, Stewart IS. Comparison of fine-needle aspiration cytology and needle core biopsy in the diagnosis of radiologically detected abdominal lesions. J Clin Pathol 2002;55:93-7.  Back to cited text no. 12
13.McKinsey DS, Wheat LJ, Cloud GA, Pierce M, Black JR, Bamberger DM, et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection. Clin Infect Dis 1999;28:1049-56.  Back to cited text no. 13
14.Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Infectious Diseases Society of America. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 2007;45:807-25.  Back to cited text no. 14
15.Goldman M, Zackin R, Fichtenbaum CJ, Skiest DJ, Koletar SL, Hafner R. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis 2004;38:1485-9.  Back to cited text no. 15
16.Panja G, Sen S. A unique case of histoplasmosis. J Indian Med Assoc 1954;23:257-8.  Back to cited text no. 16
17.Mukherjee AM, Khan KP, Sanyal M, Basu N. Histoplasmosis in India with report of two cases. J Ind Med Assoc 1971;56:121-5.  Back to cited text no. 17
18.Sanyal M, Thammaya A. Skin sensitivity to histoplasmin in Calcutta and its neighborhood. Indian J Dermatol Venereol Leprol 1980;46:94-8.  Back to cited text no. 18
19.Joshi SA, Kagal A, Bharadwaj R, Kulkarni S, Jadhav M. Disseminated Histoplasmosis. Indian J Med Microbiol 2006;24:297-8.  Back to cited text no. 19
[PUBMED]  Medknow Journal  
20.Bhagwat PV, Hanumathayya K, Topkhane RS, Rathod M. Two unusual cases of Histoplasmosis in Human Immunodeficiency Virus infected individuals. Indian J Dermatol Venereol Leprol 2009;75:173-6.  Back to cited text no. 20
[PUBMED]  Medknow Journal  
21.Singh T, Singh Y, Devi K, Mutum S, Singh Y, Singh T. acute disseminated histoplasmosis in a patient with AIDS. Indian J Med Microbiol 1996;14:23-4.  Back to cited text no. 21
22.Wadhwa A, Kaur R, Agarwal S, Jain S, Bhalla P. AIDS related opportunistic mycoses seen in a tertiary care hospital in North India. J Med Microbiol 2007;56:1101-6.  Back to cited text no. 22

What is new?
1. We present an unusual case of acute PDH presenting with multiple diffuse cutaneous papulonodular lesions on the body.
2. DCH was diagnosed with the aid of FNAC, a rapid, cost.effective procedure.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]

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