Primary Cutaneous Histoplasmosis Masquerading as Plaque Sarcoidosis in an Immunocompetent Female

Dear Editor, A 48-year-old female, a resident of Delhi, presented with a 2-year history of an asymptomatic enlarging plaque over her forehead [Figure 1]. The lesions initially started as a few asymptomatic, small discrete firm erythematous papules over the forehead, which gradually increased in size and depth over the next 1 year to form a confluent plaque. She had diabetes and hypertension, which were controlled on oral medications. She had no history suggestive of any systemic complaints, prolonged immunosuppression, or immunodeficiency. With a clinical suspicion of infective granulomatous conditions like lupus vulgaris, leishmaniasis, deep fungal infections, and plaque sarcoidosis, punch biopsies for histopathology and microbiological studies were performed. The patient was also evaluated for systemic involvement, particularly in view of strong clinical suspicion of sarcoidosis. Serum angiotensin-converting enzyme, contrast-enhanced computed tomography (CE-CT) chest, urinary calcium, ophthalmology evaluation, and echocardiography (ECG) were performed, which were within normal limits. The skin biopsy, however, showed an atrophic epidermis with dermis showing many epithelioid cell granulomas and many foreign body giant cells along with moderate lymphocytic and histiocytic infiltrate. Periodic acid-Schiff (PAS) staining revealed many small round to ovoid yeast form of fungus, suggestive of histoplasmosis [Figure 2]. Stains for acid-fast bacilli were negative. On microscopy of fungal colonies on calcofluor white staining, showed the presence of yeast cells resembling in morphology Histoplasma capsulatum. Subsequently, fungal culture in standard media confirmed the presence of septate hyphae, micro and macroconidia, and the diagnosis of H. capsulatum was established. The patient denied any direct exposure to birds, but was evaluated systemically for other common possible sites of histoplasmosis. On CE-CT head and neck, chest, and abdomen, there was no oropharyngeal, pulmonary, or pancreatic focus. Serological evaluation for human immunodeficiency virus-1 and -2 was negative, and CD4 counts were within normal limits. The patient was started on 130 mg twice daily doses of supra-bioavailable itraconazole capsules. After 8 weeks of itraconazole intake, there was significant flattening of the plaque [Figure 3]. The patient is still under follow-up and continuing to improve. Histoplasmosis is a mycosis endemic in North America, but the causative agent H. capsulatum is found in the soil globally, especially in bird and bat excretory droppings. Globally, it is not an uncommon pathogen in the immunosuppressed but has been known to cause disease even in immunocompetent individuals. The disease has a wide spectrum of clinical presentations, with primarily pulmonary involvement. On initial exposure to the fungus, the infection is self-limiting and restricted to the lungs in 99% of the individuals, while in the remaining 1%, it progresses to either disseminated or chronic disease involving the lungs, liver, spleen, lymph nodes, bone marrow and sometimes the skin and mucous membranes. The skin lesions of histoplasmosis are nonspecific and arise after dissemination from the primary pulmonary focus.[1] They may occur with all forms of histoplasmosis or, rarely, as primary cutaneous histoplasmosis. Cutaneous manifestations are reported to occur in 10% to 25% of immunosuppressed patients with disseminated histoplasmosis, which can manifest as papules, pustules, plaques, ulcers, molluscum or wart-like lesions, local dermatitis, or generalized dermatitis and rarely, erythema nodosum.[2] Primary cutaneous histoplasmosis can present with nodules, ulcers, abscesses, or molluscum contagiosum-like lesions. It is, in most cases, associated with trauma and possible inoculation of spores through the skin and mucous membranes. The incidence of cutaneous involvement in immunocompetent patients is rare and limited to a few case reports.[3] In the setting of disseminated histoplasmosis in immunocompetent hosts, systemic evaluation of the gastrointestinal tract, adrenal, and oropharynx is required as they are involved in 70-90% of patients. Histoplasmosis is a close mimicker of pulmonary sarcoidosis clinically as well as radiologically. Also, varied and overlapping granulomatous morphological patterns of cutaneous lesions often add to the diagnostic dilemma; hence, high clinical suspicion is needed to pursue diagnostic testing for endemic mycoses, as these infections can be fatal in immunosuppressed patients without appropriate treatment.[4]Figure 1: Erythematous nodulo-plaque with a smooth surface and few satellite papulo-nodules over foreheadFigure 2: (a). The skin biopsy (10x) showing atrophic epidermis and dermis showing many epithelioid cell granulomas with many foreign body giant cells along with moderate lymphocytic and histiocytic infiltrate. (b). Skin biopsy (40x) showing an epithelioid granuloma with multiple Langhans-type giant cells. (c). PAS staining (40x) showing many small round to ovoid yeast forms (encircled) of fungus, suggestive of histoplasmosisFigure 3: Lesions after 8 weeks of therapyOur case was an immunocompetent individual from a non-endemic region presenting with an unusual morphology of localized primary cutaneous histoplasmosis mimicking plaque sarcoidosis, which has not been reported previously to the best of our knowledge. The case also highlights the clinical and histopathological overlap of cutaneous lesions of sarcoidosis and histoplasmosis, which warrants microbiological testing in granulomatous cutaneous lesions. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.