Multiple keratotic papulonodular lesions in a human immunodeficiency virus-negative patient

A 52-year-old Bangladeshi female patient presented to the dermatology clinic, in Kuwait, with a painful ulcer and two skin abscesses on her neck accompanied by multiple keratotic papulonodular lesions located in the right mandibular area of her face. The lesions had appeared 3 weeks before, and had gradually increased in size. The patient also mentioned loss of weight, 4 kg in 2 months, with loss of appetite. She did not complain of night sweats, but had a chronic cough with clear sputum. Her medical history revealed that she was diagnosed with haemoglobin E trait since childhood. She had been infected with pulmonary tuberculosis in Bangladesh 25 years ago.

The patient's vital signs were normal except for elevated temperature (37.3°C). Skin examination revealed a unilateral right mandibular distribution of keratotic papulonodular skin lesions, some of which coalesced to form plaques. These lesions also involved the pre- and postauricular areas. One ulcer measuring 1.5 × 2 cm and two skin abscesses were present in the right lateral neck (Figure 1). No other skin lesions were seen in the other parts of the body. Multiple tender cervical lymph nodes were also observed. Abdominal examination revealed hepatomegaly. The rest of systemic examination was otherwise normal.

Laboratory investigations revealed mild anaemia (haemoglobin = 10.2), eosinophilia, and an elevated erythrocyte sedimentation rate. HbA1C level is 5.7%. Repeated HIV test was negative. Acid-fast bacillus staining and culture from sputum specimen were negative. The chest radiograph was unremarkable. A high-resolution CT chest showed atelectatic bands in the right upper lobe. Tissue culture for tuberculosis was negative. Extractable nuclear antigen panel was negative for autoantibodies. A skin biopsy was taken (Figure 2).

Histoplasmosis is an infection caused by the fungus H. capsulatum, which is present in contaminated soil and materials containing bat and bird waste. Histoplasmosis is rare in immunocompetent individuals, and is rarely reported in Kuwait.¹ Histoplasmosis is classified in four types according to its clinical manifestations: asymptomatic (95%), acute pulmonary, chronic pulmonary, and disseminated.² Disseminated histoplasmosis particularly affects the reticulohistiocytic system. The liver, spleen, pancreas, and intestines, are often affected. Hence, patients with disseminated histoplasmosis may exhibit a range of clinical manifestations, including fever, anorexia, weight loss, cough, vomiting, diarrhoea, abdominal pain, and hepatosplenomegaly.

Up to 17% of patients with disseminated histoplasmosis develop cutaneous lesions that are diverse and nonspecific and are caused either by the fungus, which causes papules, plaques, nodules, or ulceration, or by an immune response to the infection, such as erythema nodosum or erythema multiforme.³ The face, trunk, and extremities are the most commonly affected anatomical locations.⁴ Our patient had a localized facial distribution of lesions that extended to the lateral neck region, involving the pre- and postauricular regions but did not cause hearing problems. One case report revealed a comparable distribution of localized ulcerative lesions and affecting the external auditory canal.⁵

Different cutaneous manifestations of histoplasmosis are observed depending on the immune status of the patient. For example, cutaneous manifestations of histoplasmosis are significantly more common and polymorphic in immunocompromised individuals, particularly those with HIV/AIDS. Papules and pustules are often seen in the initial presentations of histoplasmosis, whereas plaques and ulcers are seen in more severe forms, particularly in disseminated cases. Vegetating lesions can also arise due to the hematogenous dissemination of the fungus, leading to a large number of lesions. Additionally, in immunocompromised patients, lesions may present as acneiform papules, nodules, gummas, or ulcers with a granulomatous base. In some cases, they may resemble molluscum contagiosum or wart-like lesions.^{6, 7} In contrast, cutaneous histoplasmosis is rare in immunocompetent individuals and usually results from the direct inoculation of the fungus through the skin. It can manifest as nodules, ulcers, or abscesses, often following trauma such as thorn pricks.⁸

Histopathologically, histoplasmosis is characterised by the presence of 2–4 µm sized yeast cells that divide by budding within the cytoplasm of macrophages and, in some cases, giant cells. H. capsulatum spores are visible in sections stained with hematoxylin and eosin as well as special stains such as periodic acid Schiff, Giemsa, and methenamine silver stains. The spores appear as round or oval bodies surrounded by a transparent space that was at first interpreted as a capsule, hence the name H. capsulatum. Granulomatous inflammation, sometimes with caseation necrosis can also be seen.^{1, 4, 9}

Leishmaniasis, Penicillium marneffei, and Cryptococci neoformans infections are all possible differential diagnoses of histoplasmosis. Leishmania can be visualized using Giemsa stain, which highlights the amastigotes distinctly from Histoplasma yeasts. The identification of the kinetoplast is a key feature in confirming leishmaniasis.¹⁰ The yeast forms of P. marneffei are characterized by their septate appearance; they replicate via binary fission, whereas H. capsulatum divides via budding. Cryptococci are encapsulated, spherical to oval yeasts measuring 5–10 μm in diameter. They are easily ruled out by Grocott methenamine-negative staining.⁹

To ensure an optimal outcome, disseminated histoplasmosis should be treated early with amphotericin B. Oral itraconazole is only recommended for patients with mild-to-moderate disease and as a step-down therapy following initial treatment with amphotericin B.¹¹

Rawan Almutairi: Manuscript writing; manuscript reviewed and edited; conceptualization. Khaled Alobaid: Manuscript reviewed and edited; data curation and investigation. Humoud Al-Sabah: Conceptualization; data curation and investigation. Ahmed Attia: conceptualization; data curation and investigation. Atlal Allafi: Conceptualization; data curation and investigation; supervision.

The authors declare no conflicts of interest.

All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable.