Unmasking Uncommon-Disseminated Histoplasmosis in a Human Immunodeficiency Virus-Negative Patient

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A 34-year-old male presented with multiple non-itchy, non-tender umbilicated papules over the face, neck, bilateral forearms Figure 1], and thighs for 12 weeks. Painful shallow ulcers covered with yellowish slough on the hard palate and a single centrally ulcerated plaque with serous discharge in the bilateral groin [Figure 2] were present for around 10 weeks.

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Figure 1:

Multiple non-itchy, non-tender umbilicated papules over the face, neck and bilateral forearm.

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Figure 2:

Centrally ulcerated plaques with serous discharge in the bilateral groin surrounded by multiple crusted papules.

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He also complained of fever, loss of appetite, weight loss, and hoarseness of voice for 1 week. The patient had no history of any recent travel.

On examination, enlarged, non-tender, firm, mobile submandibular lymph nodes of size 2*2 cm were palpable. Serological tests for HIV (human immunodeficiency virus), Hepatitis B, and C were negative. The Mantoux test showed induration of 2*2 mm.

Abdominal ultrasound revealed hepatosplenomegaly with a liver of size 16.4 cm and a spleen of 16 cm. Alkaline phosphatase was slightly raised with a value of 272 U/l. A gastroenterology reference was done with the advice of continuing antifungal treatment.

Chest radiograph, HRCT (high-resolution computed tomography) thorax, indirect laryngoscopy, and CT (computed tomography) larynx failed to reveal any abnormality.

On submandibular lymph node FNAC (fine needle aspiration cytology), multiple epithelioid cell clusters with lymphocytes, centrocytes, centroblasts, plasma cells, and neutrophils with degenerated cells lying on a blood-mixed necrotic background, suggestive of necrotising granulomatous lymphadenitis were seen.

Dermatoscopic examination revealed crusted plaque with central brown crust, surrounding yellow-brown structureless area, erythema, and scaling [Figure 3].

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Figure 3:

Dermatoscopy (30x) showing central brown crust (blue arrow), surrounding yellow-brown structureless area (red arrow), scaling (green arrow) and erythema (yellow arrow).

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A biopsy from a papule showed diffuse and nodular dense tuberculoid granulomatous infiltrate made up of lymphocytes, plasma cells, histiocytes, and epithelioid cells with occasional Langhans giant cells with numerous tiny 2–3 mm organisms within vacuoles. Several histiocytes and giant cells showed within their cytoplasm numerous yeast cells of about 2 microns each. PAS (Periodic Acid-Schiff) stain was positive for histoplasmosis [Figure 4].

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Figure 4:

Haematoxylin and eosin stain at 40x showing diffuse and nodular dense tuberculoid granulomatous infiltrate made up of lymphocytes, plasma cells, histiocytes, and epithelioid cells with occasional Langhans giant cells with numerous tiny 2–3 mm organisms within vacuoles (black circles).

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Culture did not reveal any growth.

As our patient was able to take oral medication, he was treated with capsule itraconazole loading dose of 200 mg three times a day for 3 days, then 200 mg/day for 20 weeks, with resolution of lesions.

Darling’s disease, commonly called histoplasmosis, is a systemic fungal infection caused by Histoplasma capsulatum. Inhalation of infectious microconidia during activities causing soil disruption can lead to the disease. The disease can affect skin and mucous membranes, the lungs, or the entire system.^[1] In India, it is mainly seen in West Bengal.^[2] It has been mainly observed among immunocompromised patients. However, more recently, cases are being frequently diagnosed among immunocompetent patients as well.

Diagnosis can be made using a combination of clinical, radiological, and laboratory tests. Although dermatoscopy has a limited role, it can provide valuable clues while examining skin lesions.^[3]

Histoplasmosis can often be confused with other diseases causing umbilicated papules, like cryptococcosis and penicilliosis. Differentiation is often made on histopathology in which cryptococcosis shows multiple spores with thick capsules and narrow bases, whereas in penicilliosis, septum in thin-walled yeast-like cells is seen.^[4]

For histoplasmosis, antifungals like liposomal amphotericin B and itraconazole are the preferred drugs, depending upon the severity of the disease.^[5]

In our case, the patient reacted positively to treatment, as seen by the clearance of skin lesions and significant clinical improvement on subsequent follow-up visits.

Early diagnosis and timely treatment with antifungal agents are essential for successful histoplasmosis management. This case is being reported for its rarity and the fact that cutaneous dissemination of histoplasmosis can occur even without pulmonary involvement.