Leonine facies and hoarseness in disseminated histoplasmosis: A diagnostic pitfall

Case report

A 56-year old immuno-competent male from Uttar Pradesh, India, presented with progressive weight loss, hoarseness of voice and cutaneous lesions over the face, trunk and genitalia for three months. He kept domestic pigeons and had initially received homeopathic treatment for his ailments without relief.

On examination, leonine facies, genital nodules, and diffuse violaceous indurated ulcers with central necrosis were noted, along with widespread scaling across the trunk and extremities. Small, firm, non-umbilicated nodules were present on the scrotum and penile shaft (Fig. 1(a)-(c)).

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Figure 1.

(a) Confluent, crusted, infiltrated nodules and plaques over the forehead, nose, and malar regions with partial effacement of normal facial contours, clinically consistent with leonine facies; (b) Indurated ulcer with violaceous margins and central necrosis over the trunk, surrounding skin shows fine white scales; (c) Multiple firm nodules distributed over the scrotal skin; (d) Sagittal T2 images of 56 years old male showing oedematous thickened epiglottis (red arrow) and ary-epiglottic fold showing heterogenous T2 hyper intensity; (e) PAS-stained skin section showing numerous oval-to-round intracellular fungal spores measuring 2–4 µm, prominently highlighted in magenta within histiocytes (PAS, ×200); (f) Post-treatment resolution of facial plaques and nodules with improvement in skin texture; (g) Healed indurated ulcer over the lower abdomen showing post-inflammatory hyper-pigmentation and scarring, post treatment; (h) Complete resolution of scrotal nodules post-treatment.

All routine investigations were within normal limits. An MRI scan of the neck revealed bilateral oedematous, nodular thickening of the false vocal cords, epiglottis and aryepiglottic folds (Fig. 1(d)). Laryngoscopy and laryngeal biopsy were not performed due to patient's refusal.

Urine antigen testing using the IMMY Clarus Histoplasma galactomannan EIA kit showed a markedly elevated value of 45.1 EIA units (reference: negative ≤1 EIA unit). Histopathological examination of skin biopsies from facial and truncal lesions revealed ill-defined epithelioid granulomas, chronic inflammatory infiltrates and numerous intracellular yeast-like organisms highlighted by periodic acid–Schiff stain (Fig. 1(e)). Although fungal cultures from the skin tissue were negative, a polymerase chain reaction (PCR) targeting the mitochondrial small subunit ribosomal ribonucleic acid gene (SSU rRNA) confirmed the presence of Histoplasma capsulatum DNA.

Thus, a diagnosis of disseminated histoplasmosis with probable laryngeal involvement could be established. Treatment was started with liposomal amphotericin B (3 mg/kg/day) for 14 days, followed by oral itraconazole (200 mg bd) for maintenance, according to the Infectious Diseases Society of America guidelines. ¹ Marked improvement was observed in the cutaneous, mucosal and laryngeal lesions after a treatment duration of 12 months (Fig. 1(f)-(h)).

Discussion

Histoplasmosis is a systemic mycotic infection caused by Histoplasma capsulatum, a dimorphic fungus that exists as two distinct species pathogenic to humans: H. capsulatum var. capsulatum and H. capsulatum var. duboisii. Although endemic in eastern India, it is underdiagnosed in non-endemic regions owing to its wide clinical spectrum.

We assume our patient acquired the infection through inhalation of fungal spores from soil contaminated by pigeon droppings. Disseminated histoplasmosis typically affects immuno-compromised individuals, but increasing reports of disease occurring in immuno-competent hosts from non-endemic regions, such as our case, highlight the need for broader clinical suspicion.

Cutaneous lesions can mimic conditions such as leprosy, sarcoidosis, deep mycoses, and cutaneous lymphoma. ² We found only two published reports of concurrent cutaneous and laryngeal disease: an HIV-positive patient with disseminated histoplasmosis manifesting as supraglottitis ulceration and umbilicated nodules lesions in the context of immune reconstitution inflammatory syndrome, ³ and an immuno-competent individual with facial plaques and a proliferative lesion on the left vocal cord, in whom the diagnosis was made solely on the basis of a skin biopsy. ⁴

Facial infiltration may rarely result in a leonine facies, typically linked to lepromatous leprosy, making this a possible diagnostic pitfall. Genital involvement and diffuse scaling in disseminated histoplasmosis are uncommon. While ulcers, epididymo-orchitis, posthitis and Fourniers gangrene have all been described, the presence of intact nodules over the penis and scrotum, as seen in our patient, has been rarely documented. ²

The reverse transcriptase quantitative PCR targeting the mitochondrial SSU rRNA gene is a rapid and reliable diagnostic tool for disseminated histoplasmosis, particularly when conventional cultures are negative or non-contributory, as also observed in our case. ⁵

Our case highlights the diagnostic challenges of disseminated histoplasmosis in an immuno-competent host from a non-endemic region.

Patient consent statement

Written informed consent was obtained from the patient(s) for the publication of their clinical details and any accompanying images, including facial photographs. The patient has consented to the publication of these images in both print and online formats, understanding that while efforts will be made to conceal their identity, complete anonymity cannot be guaranteed.