Syphilis of Fungal world: Novel Skin Manifestations of Histoplasmosis in an Immunocompetent Host.

A case of chronic disseminated cutaneous histoplasmosis with unusual skin manifestations in an immunocompetent host is reported. Presence of cutaneous ulcers, linear erythematous plaques, skin coloured atrophic plaques and recurrent self-limiting oral ulcers in a single patient has not been documented in literature so far. Diagnosis was established by identifying small intracellular yeast-like cells of Histoplasma in tissue smear and skin biopsy. Leishman stained tissue smear proves to be an easy and simple procedure for diagnosis of histoplasmosis.

What was known?

Cutaneous histoplasmosis can manifest in a bewildering array of clinical types and variation. Thus, it has been called the syphilis of fungal world.

Introduction

Histoplasmosis, also known as Darling's disease, is a systemic fungal infection caused by the dimorphic fungus, Histoplasma capsulatum. Infection is acquired by inhalation of conidia from soil contaminated by bird or bat excreta. Histoplasmosis can manifest in a bewildering array of clinical types and variation and has been called the syphilis of fungal world. We report a case of chronic disseminated cutaneous histoplasmosis with varied skin lesions in an immunocompetent host. Presence of cutaneous ulcers, linear erythematous plaques, skin coloured atrophic plaques and recurrent self-limiting oral ulcers in a single patient has not been documented in literature so far.

Case Report

A 74-year-old male, woodcutter by occupation, residing in a non-endemic area in South India, presented with multiple painful ulcers over face and oral mucosa and asymptomatic reddish raised lesions over neck and trunk of 5 days duration. There was history of recurrent episodes of self-healing ulcers over lower lip and soft palate for the past 10 years, and multiple asymptomatic skin coloured lesions over forearm and trunk for these years, which were not preceded by any other type of skin lesions. He had taken antitubercular treatment, 20 years back for chronic cough. On examination, multiple ulcers of varying size with well-defined, irregular margin were seen on forehead, periorbital area, chin and left anterior axillary fold. Linear erythematous crusted plaques were present over neck and trunk. Multiple skin coloured atrophic plaques were present over forearm, trunk and thighs [Figure 1]. Erosions were present over the buccal mucosa and soft palate. Systemic examination was unremarkable. Hemogram was normal. Serological tests for syphilis and HIV were negative. Leishman stained tissue smears from ulcers and erythematous crusted plaques revealed budding organism with peripheral halo [Figure 2]. Biopsies from these lesions and the skin coloured atrophic plaques showed parasitized macrophages, containing small round yeast-like organisms with a surrounding halo suggestive of Histoplasma capsulatum, which was confirmed by Gomori Methenamine Silver (GMS) stain [Figure 3]. Smears taken from oral mucosa stained with Papanicolaou also showed budding organisms. Fungal culture done in Sabouraud dextrose agar did not yield organism. Serological tests could not be done due to financial constraints. Chest X-ray showed calcification of right upper lobe. Fasting serum cortisol level was normal. Patient was diagnosed with chronic disseminated cutaneous histoplasmosis and started on itraconazole 200 mg twice in a day. Skin lesions resolved within 6 weeks of therapy [Figure 4].

Figure 1

Varied morphological lesions: (a) Ulcerated plaques of varying size over forehead, periorbital area and cheeks; (b) Linear erythematous plaques over upper chest and crusted lesions over anterior axillary fold; (c) Atrophic plaques over thigh; (d) Linear atrophic plaque forearm

Figure 2

Tissue smears from ulcers and erythematous crusted plaques showing budding organism with peripheral halo. (Leishman stain, ×400)

Figure 3

Histology showing (a) Heavy dermal inflammatory infiltrate containing poorly formed granulomas and many giant cells, Hematoxylin and eosin stain, original magnification ×40; (b) Intracellular and extracellular yeast-like organisms with a surrounding halo, GMS stain, original magnification ×100

Figure 4

Healed lesions after 6 weeks of antifungal therapy

Discussion

Samuel Taylor Darling first recognized histoplasmosis in Panama in 1905.[1] There are 2 varieties of Histoplasma capsulatum that are pathogenic to man: H. capsulatum var. capsulatum and H. capsulatum var. duboisii. There is a third variety that is an equine pathogen, H. capsulatum var. farciminosum. H. capsulatum var. capsulatum occurs worldwide with endemic foci in Central and North America, whereas H. capsulatum var. duboisii is restricted to African subcontinent.[2] Panja and Sen reported the first case of disseminated histoplasmosis from India in 1954.[3] Among the forms of histoplasmosis reported from India, disseminated histoplasmosis is the least common.[4] Infection is acquired by inhalation of conidia from soil contaminated by bird or bat excreta. The risk factors for acquiring the infection include occupational and recreational activities in old buildings, bridges and caves.[2] Being a woodcutter, our patient had occupational exposure to multitude of trees inhabited by birds. Though any person can acquire infection through inhalation, disseminated infection occurs in patients with defective cellular immunity.[1] Histoplasmosis manifests in a bewildering array of clinical types and variation. Thus, it has been called the syphilis of fungal world.[5] A myriad of lesions such as macules, papules, plaques, pustules, ulcers, abscesses and purpuric lesions have been described in histoplasmosis.[6] Molluscum contagiosum-like, erysipelas-like,[6] pyoderma gangrenosum-like,[7] ecthyma-like,[8] rosacea-like[9] and exfoliative forms[6] are the rare manifestations reported. Our patient, who was an immunocompetent elderly male, presented with diverse skin lesions including well defined irregular ulcers, linear erythematous crusted plaques, and skin coloured atrophic plaques. Verma S.B. reported the first case of chronic disseminated cutaneous histoplasmosis presenting as linear erythematous plaques with central ulceration over the neck and upper chest in an immunocompetent host.[10] We also observed similar linear orientation of erythematous plaques over the neck and trunk. We suspect this could be a specific manifestation of chronic disseminated cutaneous histoplasmosis in immunocompetent host. Another unique feature in our patient was the presence of skin coloured atrophic plaques, from which we demonstrated the organism. This type of lesion has not so far been documented in literature. Mucosal involvement is a common presenting feature of disseminated histoplasmosis.[1] Our patient gave history of recurrent self-healing oral ulcers for about 10 years. Most skin lesions of histoplasmosis arise following dissemination from a pulmonary focus and the only evidence of lung involvement could be calcification, which is indistinguishable on X-ray from tuberculosis. In our patient, history of chronic cough and chest X-ray finding of pulmonary calcification could have been due to pulmonary histoplasmosis, which might have been erroneously treated as tuberculosis. Diagnosis of histoplasmosis was established by identifying small intracellular yeast-like cells of Histoplasma in tissue smear and skin biopsy. In our case, Leishman stained tissue smear proves to be an easy and simple procedure for diagnosis. The choice of therapy depends on the severity of illness.[1] For patients with localized or few disseminated lesions, oral itraconazole of 200-400 mg daily is highly effective. Intravenous amphotericin B up to 1 mg/kg daily is recommended for patients with widespread and severe infections. Our patient showed excellent response to itraconazole.

What is new?

Presence of cutaneous ulcers, linear erythematous plaques, skin coloured atrophic plaques and recurrent self-limiting oral ulcers in a single patient is reported. Skin coloured atrophic plaques, from which we demonstrated the organism in our patient is a type of lesion that has not so far been documented in literature.