Indian J Sex Transm Dis Indian J Sex Transm Dis
Official Publication of the Indian Association for the Study of Sexually Transmitted Diseases
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  Table of Contents  
Year : 2022  |  Volume : 43  |  Issue : 2  |  Page : 185-188

Cutaneous manifestations leading to a diagnosis of a case of severe disseminated histoplasmosis in a human immunodeficiency virus-positive child

1 Department of Dermatology, Base Hospital, Lucknow, Uttar Pradesh, India
2 Department of Pathology, Base Hospital, Lucknow, Uttar Pradesh, India
3 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission19-Jun-2022
Date of Acceptance20-Jun-2022
Date of Web Publication17-Nov-2022

Correspondence Address:
Dr. Biju Vasudevan
Department of Dermatology, Armed Forces Medical College, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijstd.ijstd_59_22

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This 9-year-old boy who was human immunodeficiency virus positive since birth presented with raised skin lesions, breathlessness, and cough and was treated as a case of disseminated tuberculosis. When no improvement was seen, he was referred to the dermatologist whose examination revealed papulonodular lesions with crusting over the face and extremities. Based on clinical suspicion of histoplasmosis, investigations done revealed a CD4 count of 3 cells/μL and histopathological features of histoplasmosis along with the disseminated disease. Cutaneous manifestations thus led to an early diagnosis of the case and a good prognostic outcome.

Keywords: Cutaneous, disseminated, histoplasmosis, human immunodeficiency virus

How to cite this article:
Sood A, Raman DK, Sinha A, Vasudevan B. Cutaneous manifestations leading to a diagnosis of a case of severe disseminated histoplasmosis in a human immunodeficiency virus-positive child. Indian J Sex Transm Dis 2022;43:185-8

How to cite this URL:
Sood A, Raman DK, Sinha A, Vasudevan B. Cutaneous manifestations leading to a diagnosis of a case of severe disseminated histoplasmosis in a human immunodeficiency virus-positive child. Indian J Sex Transm Dis [serial online] 2022 [cited 2023 Nov 28];43:185-8. Available from:

   Introduction Top

Disseminated histoplasmosis is an opportunistic infection more commonly occurring in the immunocompromised. In human immunodeficiency virus (HIV)-positive patients, 95% of histoplasmosis occurs as disseminated infection,[1] and is typically seen with a CD4+ cell count of >150/μL.[2] However, >10% of these patients have cutaneous manifestations.[3] We herein present a case of disseminated histoplasmosis with cutaneous manifestations in a 9-year-old boy with HIV infection since birth, who was initially diagnosed as disseminated tuberculosis and later based on the clinical suspicion on dermatological examination and histopathology confirmation was diagnosed as disseminated histoplasmosis. The timely diagnosis was a lifesaver for the child and this article highlights the early diagnosis based on dermatological examination.

   Case Report Top

A 9-year-old male child, infected with HIV since birth (acquired through vertical transmission from mother) presented with complaints of multiple small brownish to black colored, raised, mildly painful lesions over face, upper and lower limbs of 3 weeks' duration. He gave a history of bouts of intermittent dry cough and weight loss for the past 1 month. Associated headache, intermittent fever with chills, generalized weakness, and excessive irritability were present. The patient had been on antiretroviral therapy (ART) since the age of 2 years (abacavir, lamivudine, and efavirenz). His father, mother, and sister were also HIV positive and on ART without any complications.

Sputum acid-fast bacilli was negative and the chest radiograph was normal. Although no evidence of tuberculosis was found during investigations, the patient was empirically started on antitubercular therapy (ATT) by the chest physician, suspecting disseminated tuberculosis based on his fever, cough, breathlessness, skin lesions, and immunocompromised status. However, the patient showed no improvement after 2 weeks of ATT. His fever was unabated and the skin lesions worsened. He was then referred to the dermatologist.

On clinical examination by the dermatologist, the patient was found to have pallor, moderate grade fever, and significant axillary and inguinal lymphadenopathy. Dermatological examination revealed multiple erythematous to hyperpigmented, mildly tender papules and nodules, a few verrucous and some of which had central necrotic areas, distributed symmetrically over face, neck, and upper and lower limbs, with sparing of the trunk [Figure 1] and [Figure 2]. Abdominal examination revealed hepatomegaly while chest examination was unremarkable. Clinical diagnosis of histoplasmosis was suspected based on the skin findings and investigations were ordered.
Figure 1: Clinical image of patient showing the papulonodular and crusted lesions on the face

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Figure 2: Papulonodular lesions on both legs

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The patient was found to have severe anemia hemoglobin (Hb 4.9 mg/dl), thrombocytopenia (96,000/μL), raised liver enzymes (serum glutamic-oxaloacetic transaminase – 92 units/L, serum glutamic-pyruvic transaminase – 86 units/L), raised alkaline phosphatase – 945 units/L, and raised lactate dehydrogenase (1106 units/L). The patient was found to have a CD4 count of only 3 cells/μl.

Chest radiograph and pulmonary function tests were normal. Contrast-enhanced computerized tomography (CECT) chest showed a 7.3 mm × 4.0 mm, subpleural soft-tissue density nodule seen in the posterior segment of the right upper lobe, and a 6 mm calcified granuloma in the left lower lobe. CECT abdomen showed hepatomegaly, enlarged kidneys, and retroperitoneal lymphadenopathy. Fine-needle aspiration cytology from lymph nodes showed nonspecific inflammatory infiltrate.

Histopathology from the skin nodules showed circumscribed necrotic foci in the dermis with occasional histiocytes in the periphery [Figure 3]. Hematoxylin and Eosin stain showed 2–4 μm rounded yeast forms in the necrotic area with a halo around them suggestive of Histoplasma capsulatum and periodic acid–Schiff (PAS) stain showed these yeast forms to be PAS positive [Figure 4]. Fungal culture from the tissue sample confirmed the diagnosis of histoplasmosis [Figure 5].
Figure 3: Histopathology revealing huge granulomatous infiltrate in the dermis with areas of necrosis (H and E, ×100)

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Figure 4: Periodic acid–Schiff stain confirming the presence of Histoplasma capsulatum (PAS STAIN × 400). PAS = Periodic acid–Schiff

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Figure 5: Culture showing the growth of Histoplasma at 37°C

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The patient was started on injection of liposomal amphotericin B at a dose of 100 mg IV daily for 2 weeks along with the continuation of ART. Thereafter, the patient has shifted to oral itraconazole 100 mg twice daily. The patient was also given a blood transfusion once weekly for 2 weeks with a rise in Hb to 7.1 mg/dl. After 2 weeks of therapy, the patient's skin lesions started to resolve and his fever and cough subsided. Liver enzymes and lactate dehydrogenase levels normalized. Repeat CD4 count after a month, however, showed only a mild rise to 8 cells/μl. The patient was discharged on second-line ART and oral itraconazole. A follow-up after 6 months showed that all his skin lesions had completely resolved [Figure 6]. He had no systemic abnormalities and the CD4 count had improved to 300 cells/μL.
Figure 6: Clinical images of the patient 6 months after therapy

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H. capsulatum is a dimorphic fungus that remains in a mycelial form at ambient temperatures and grows as yeast at body temperature in mammals causing histoplasmosis. Although Panja and Sen first reported histoplasmosis from India in 1959,[4] reported cases are few and far between.[5],[6] Progressive disseminated histoplasmosis occurs in 1 per 2000 cases in adults who are immunocompetent and in 4%–27% of infected children, older individuals, and persons who are immunosuppressed.[7]

After initial exposure, the infection is self-limiting and restricted to the lungs in 99% of cases while the remaining 1% progress to either disseminated or chronic disease involving the lungs, liver, spleen, lymph nodes, bone marrow, and less commonly the skin and mucous membranes.[8] Cutaneous lesions may be seen rarely with all forms of histoplasmosis or, rarely, as primary cutaneous histoplasmosis. Cutaneous lesions occur in up to 17% of patients with disseminated histoplasmosis manifesting as papules, pustules, plaques, ulcers, molluscum or wart-like lesions, and rarely erythema nodosum.[9] Cutaneous lesions may be an initial presentation of disseminated histoplasmosis in about 10% of cases and may serve as a marker for acquired immunodeficiency syndrome (AIDS) in endemic areas.[10]

The various drugs used in the treatment of histoplasmosis are amphotericin, itraconazole, ketoconazole, and terbinafine, of which amphotericin B is preferred in severe cases.[11] Suppressive therapy at least for a year must be administered to prevent relapse, especially in immunosuppressed patients. Disseminated histoplasmosis in an immunocompromised host carries a poor prognosis with the untreated acute forms resulting in death within weeks.[12]

This case is unique, due to the florid cutaneous manifestation as an initial manifestation, which has rarely been reported. Even though our patient was symptomatic with fever, cough, and breathlessness, yet there was no evidence of heavy pulmonary infiltration on imaging, and pulmonary function tests and bronchoalveolar lavage evaluation were normal. However, there was heavy cutaneous infiltration as seen in the skin histopathology and this along with the florid cutaneous manifestations could be an early marker for disseminated disease.

This case is being reported to reiterate the need to maintain a high index of suspicion for opportunistic infections such as histoplasmosis in AIDS patients even in nonendemic areas and that a good dermatological examination can help in giving a lead to early diagnosis of this condition which can rapidly become fatal.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Ferreira OG, Cardoso SV, Borges AS, Ferreira MS, Loyola AM. Oral histoplasmosis in Brazil. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:654-9.  Back to cited text no. 1
Kauffman CA. Histoplasmosis: A clinical and laboratory update. Clin Microbiol Rev 2007;20:115-32.  Back to cited text no. 2
Cunha VS, Zampese MS, Aquino VR, Cestari TF, Goldani LZ. Mucocutaneous manifestations of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome: Particular aspects in a Latin-American population. Clin Exp Dermatol 2007;32:250-5.  Back to cited text no. 3
Panja G, Sen S. A unique case of histoplasmosis. J Indian Med Assoc 1954;23:257-8.  Back to cited text no. 4
Viswanathan S, Chawla N, D'Cruz A, Kane SV. Head and neck histoplasmosis – A nightmare for clinicians and pathologists! Experience at a tertiary referral cancer centre. Head Neck Pathol 2007;1:169-72.  Back to cited text no. 5
Rappo U, Beitler JR, Faulhaber JR, Firoz B, Henning JS, Thomas KM, et al. Expanding the horizons of histoplasmosis: Disseminated histoplasmosis in a renal transplant patient after a trip to Bangladesh. Transpl Infect Dis 2010;12:155-60.  Back to cited text no. 6
Kamili QU, Menter A. Atypical presentation of histoplasmosis in a patient with psoriasis and psoriatic arthritis on infliximab therapy. J Drugs Dermatol 2010;9:57-60.  Back to cited text no. 7
Sood N, Gugnani HC, Batra R, Ramesh V, Padhye AA. Mucocutaneous nasal histoplasmosis in an immunocompetent young adult. Indian J Dermatol Venereol Leprol 2007;73:182-4.  Back to cited text no. 8
[PUBMED]  [Full text]  
Sayal SK, Prasad PS, Mehta A, Sanghi S. Disseminated histoplasmosis: Cutaneous presentation. Indian J Dermatol Venereol Leprol 2003;69:90-1.  Back to cited text no. 9
  [Full text]  
Kauffman CA. Histoplasmosis. Clin Chest Med 2009;30:217-25, v.  Back to cited text no. 10
Meyer RD. Treatment of fungal infections in patients with HIV-infection or AIDS. Zentralbl Bakteriol 1994;281:1-7.  Back to cited text no. 11
Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. 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. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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