Progressive disseminated histoplasmosis mimicking acute cutaneous lupus erythematosus in an immunocompetent woman

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A 23-year-old woman presented with fever, malaise, oral ulcers, cutaneous burning on sun exposure, and painful crusted haemorrhagic plaques, localised to sun-exposed sites, for 2 months. Examination revealed multiple, variably sized, discrete to coalescent crusted papules and plaques over her face with distinct sparing of the naso-labial folds [Figure 1]. Her upper chest, arms, forearms, back, buttocks, and thighs were also involved. The papulo-plaques were more coalescent and crusted over her face and discrete over other sites, some being umbilicated. There were large superficial erosions over her lips and buccal mucosa. She was admitted to our inpatient care with working diagnosis of acute cutaneous lupus erythematosus flare, to rule out deep fungal infections because of the unusual umbilicated and centrally crusted papules. She had no other history suggestive of connective tissue disease (CTD) and immunodeficiency. There was no history of cough or other systemic complaints. Her routine blood was normal except for moderate hypochromic, microcytic anaemia and hypoproteinaemia. Anti-nuclear antibody, complement levels and anti-double-stranded DNA levels were within normal limits. The tissue potassium hydroxide (KOH) mount and impression smear on Giemsa stain showed budding yeast cells with surrounding halo, morphologically resembling Histoplasma. Skin biopsy revealed dense lymphocytic infiltrate, foamy histiocytes, plasma cells, and giant cells. Majority histiocytes contained numerous 1-2 µm-sized organisms, most showing surrounding clear space, suggestive of histoplasmosis [Figure 2a]. These are stained positively with periodic acid-schiff (PAS) Stain [Figure 2b] and Gomori-methanamine stain (GMS) [Figure 2c]. Her urine histoplasma antigen was positive, and tissue culture demonstrated growth of Histoplasma capsulatum. HIV 1 and 2 and primary immunodeficiency screen (serum immunoglobulin levels; CD-4, 8, 19, and 20; interferon-gamma receptor 1 (IFN-γR1); interleukin-12 receptor beta 1 (IL-12Rß1) and interleukin (IL-12)) were negative. On systemic screening, contrast-enhanced computed tomography (CE-CT) revealed necrotic mediastinal lymphadenopathy and random sub-centimetric lung nodules, massive hepato-splenomegaly without adrenal involvement. She was started on IV liposomal amphotericin B (3 mg/Kg/day). She became afebrile in 1 day and her skin lesions improved considerably in 2 weeks [Figure 3]. After an initial course of liposomal amphotericin B for 2 weeks, she was shifted to itraconazole 400 mg/day, which will be continued for a year.

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Figure 1:

Before treatment- Crusted papules and plaques over face (distinct sparing of the naso-labial folds and around the mouth).

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Figure 2a:

Foamy histiocytes with 1-2 µm-sized organisms with clear space around (red arrow) (Haematoxylin & eosin, 40x),

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Figure 2b:

Eosinophilic budding yeast cells (black asterix) (PAS-40x).

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Figure 2c:

Black budding yeast cells (Gomory methenamine silver (GMS)-40x).

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Figure 3:

After treatment- Almost complete clearance of skin lesions with residual crust and hyperpigmentation.

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Histoplasmosis is an endemic mycosis, caused by a dimorphic fungus, Histoplasma capsulatum var. capsulatum, causing classical histoplasmosis in the eastern United States and Latin America, and var. duboisii, causing African histoplasmosis in Africa. In the Indian subcontinent rising number of cases have been reported from West Bengal and Uttar Pradesh, and sporadically from other parts of southern India.¹ The infection occurs by inhalation of conidia present in the soil contaminated by bird and bat droppings.² The initial infection is self-limiting and restricted to lungs in 99% of immunocompetent individuals. In the remaining 1%, it disseminates to the lungs, reticulo-endothelial system, and skin and mucous membranes, presenting as acute or chronic pulmonary histoplasmosis or disseminated histoplasmosis. Globally, it is not an uncommon pathogen during immunosuppression, but is being increasingly reported even in immunocompetent hosts. Samaddar et al. reported two cases of disseminated histoplasmosis in immunocompetent patients from Rajasthan with buccal mucosal ulcers, identical to our cases.³ Cutaneous manifestations reportedly occur in 10% to 25% of immunosuppressed patients with disseminated histoplasmosis and are largely non-specific, manifesting as papules, pustules, plaques, ulcers, molluscum or wart-like lesions, local dermatitis, or generalised dermatitis and rarely, erythema nodosum.⁴ Several previous reports have described umbilicated papules as a clue for histoplasmosis.^2,5,6 Cutaneous manifestations of histoplasmosis mimicking skin signs of CTDs have been previously described.⁷ Treatment varies on the extent of dissemination and patient profile. In moderate to severe disseminated Histoplasmosis, the Infectious Disease Society of America (IDSA) recommends intravenous liposomal amphotericin B (3.0 mg/kg) daily for 1–2 weeks, followed by oral itraconazole for a total of at least 12 months.

Our case is special due to its presentation, which closely resembled cutaneous lupus erythematosus in a young, immunocompetent female—an occurrence not previously reported in the literature to our knowledge. This highlights the fact that Histoplasmosis can present with a wide spectrum of clinical manifestations, even in immunocompetent individuals from non-endemic regions. The presence of umbilicated papules was a key diagnostic clue, facilitating early diagnosis and treatment. Timely intervention significantly reduced the mortality risk.