Nodular lesions of the buttock for 20 years: the challenge of chromoblastomycosis in non-endemic settings

Abstract

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.

Background

Chromoblastomycosis is a neglected tropical disease (NTD) with significant morbidity in endemic countries. It is rarely seen outside of this setting and can be easily missed. It should be considered in patients with atypical skin lesions, which do not respond to treatment and who have lived in or travelled to tropical countries. Biopsy for fungal staining and culture is key. We present a case of a buttock lesion present for over 20 years diagnosed as chromoblastomycosis where inoculation likely occurred during childhood.

Case presentation

A man in his 50s was referred to the infectious diseases clinic with multiple nodular lesions on his left buttock. These had started as a small, single lesion over 20 years previously. Over time the lesion enlarged but had progressed rapidly over the preceding 12 months with pruritus, bleeding and new lesions developing. The patient was born in Kerala, India, but had lived and worked in the UK for the last 14 years as a chef. Other than type 2 diabetes mellitus, he had no other previous medical history. Examination revealed a large verrucous plaque 6×2.5 cm in size on the left buttock with multiple small and varied nodular satellite lesions and hyperpigmentation (figure 1). Some of the lesions were excoriated. A skin biopsy performed by the referring dermatologist was reported to show a granulomatous dermatosis (figure 2), suggestive of possible infective aetiology which had prompted the referral to a tertiary infectious disease clinic. A second opinion was sought from a histopathologist with a specialist interest in infection.

Figure 1.

Left buttock lesions at presentation.

Figure 2.

Dermal granulomas, some with central necrosis. H&E, x100.

Investigations

On H&E stained sections, in addition to dermal granulomas, pseudoepitheliomatous hyperplasia was seen at low magnification suggesting a deep mycosis. On review of high-power magnification images, Medlar bodies (figure 3) were demonstrated confirming chromoblastomycosis. A repeat punch biopsy was performed and sent to the UK Mycology Reference Laboratory (MRL) for fungal culture and pan-fungal PCR. Pan-fungal PCR performed on formalin-fixed tissue was negative, likely representing reduced sensitivity in this context. However, culture of fresh tissue isolated a pigmented fungus, morphologically a Fonsecaea species, which was identified as Fonsecaea monophora using Matrix-assisted laser desorption/ionisation with time-of-flight mass spectrometry and by ribosomal DNA sequencing using pan-fungal PCR primers.^{1 2} This confirmed the diagnosis of chromoblastomycosis.

Figure 3.

High-power view of the pigmented Medlar bodies with typical ‘copper pennies’ appearance. H&E, x400.

Differential diagnosis

Granulomatous dermatoses have infectious and non-infectious aetiologies. Tuberculous granulomas were suspected given the regional endemicity and slow onset. Other infectious causes in the differential included leprosy, leishmaniasis, actinomyces, syphilis and cutaneous mycoses.

Non-infectious causes such as squamous cell carcinoma and mycosis fungoides were excluded on histology; sarcoidosis remained possible but unlikely given the site.

Medlar bodies identified by an experienced pathologist are pathognomonic of chromoblastomycosis and confirmed the diagnosis.

Treatment

The patient was commenced on empirical oral terbinafine 250 mg/day, pending sensitivities. Susceptibility testing by Clinical & Laboratory Standards Institute broth microdilution indicated sensitivity to amphotericin B, isavuconazole, itraconazole, posaconazole and voriconazole (minimum inhibitory concentrations in mg/L were 0.5, 0.06, 0.25, 0.06 and 0.06, respectively) and he was switched to oral itraconazole 400 mg/day. Susceptibility testing for terbinafine is not performed at the MRL due to high minimum inhibitory concentrations in vitro despite published data suggesting in vivo efficacy.³

Outcome and follow-up

The patient was unable to tolerate 400 mg/day however due to lethargy, which interfered with his work, therefore the dose was reduced to 300 mg/day and then 200 mg/day, which he was able to tolerate. Itraconazole trough levels were subtherapeutic on 200 mg/day, therefore his dose was increased back to 300 mg/day. His skin lesions improved initially with reduced pruritus and cessation of bleeding. He remained on this therapy for 17 months, however the lesions ultimately began to increase in size (see figure 4). He was switched to oral voriconazole and topical terbinafine on advice of the MRL. Several months later, the patient went abroad for surgical excision although there was evidence of recurrence within the surgical scars at subsequent review (see figure 5). Treatment with oral voriconazole and topical terbinafine continues.

Figure 4.

Lesions after 17 months of medical management.

Figure 5.

Lesions after surgical excision.

Discussion

Chromoblastomycosis is a chronic granulomatous implantation mycosis of the skin and subcutaneous tissue caused by melanised fungi of the order Chaetothyriales. It is considered to be on the same spectrum as other melanised fungal infections such as mycetoma and phaeohyphomycosis; however, it is associated with distinct fungi of the genera Fonsecaea, Cladophialophora, Phialophora, Rhinocladiella and Exophiala. It is confined to the subcutaneous tissue and rarely penetrates fascia or bone.⁴ It is classified by the WHO as a NTD and is associated with significant morbidity, including stigma and discrimination. The highest prevalence is in tropical and subtropical climates with South and Central America (particularly Brazil), the Caribbean islands, India, China, Japan, Madagascar, South Africa and Australia accounting for the majority of cases.⁵ Within India, where our patient acquired it, the state of Kerala reports the greatest number of cases nationally.⁶ Cases in Europe are rare but autochthonous infection has been reported, both in Mediterranean and temperate regions.⁵ Within the UK, eight cases have been reported in the literature to date, beginning with a report of a plaque-like lesion on the elbow of a Jamaican man by Crow and Riddell in 1954; all cases have been imported.^7–14 The fungi are present in soil, plants and decomposing wood, and inoculation is initiated by any trauma to the skin; 90% of cases affect men 20–60 years old that do manual work in rural agricultural areas or work with environmental materials (farmers, miners, etc). Lack of protective footwear or gloves, poor hygiene and poor access to healthcare all contribute to the burden borne by the poorest populations. Contrary to many fungal infections, chromoblastomycosis usually affects immunocompetent individuals.⁴

Clinically the disease manifests initially as a cutaneous papule or nodule on an area of common trauma such as feet, knees, hands, elbows and lower limbs that goes on to develop into a verrucous or granulomatous plaque.⁴ With time, several lesions can coalesce and form a multinodular mass, and multiple lesions may exist as discrete islands scattered within unaffected skin, as seen in our patient (figure 1). The time from inoculation to the onset of the initial lesion varies but is usually weeks to months. Lesions can evolve over time, spreading contiguously or by de novo satellite lesions through auto-inoculation. There are usually no constitutional symptoms. If left untreated, the lesions can progress relentlessly over years and cause deformity, secondary infection, lymphoedema and malignant transformation to squamous cell carcinoma.⁴ Diagnosis requires the visualisation of Medlar bodies, a characteristic thick-walled and septated fungal body, in tissue of an affected lesion (figure 3). Skin biopsy is recommended for histopathological examination of tissue with H&E and Gomori-Grocott staining, for fungal culture, and to assess for coinfections and other differential diagnoses. Direct examination and culture of skin scrapings using potassium hydroxide or Calcofluor white can also be used. Culture of samples on appropriate media is important as this will allow speciation; Fonsecaea may be less sensitive to antifungals than other species.⁴

Treatment can be challenging and is usually prolonged. There are no comparative or randomised trial data to aid clinicians and what does exist rests on descriptive case studies and expert opinion. Various physical, topical and systemic treatments exist, but these depend on the site and extent of infection. Physical methods such as surgical excision (which provides the most effective cure for small lesions), cryotherapy, heat therapy and laser therapy have been used. Topical therapy with imiquimod has been reported but is not routine.⁴ Antifungals are the mainstay of therapy, but the optimal choice of agent is not known. What evidence there is, suggests that standard therapy should begin with itraconazole, but terbinafine, posaconazole or voriconazole are also options.¹⁵ These may be used alone or can be combined with physical treatments. Duration is determined by clinical response; most will respond within 8–10 months but can take over a year and beyond.¹⁶

Learning points.

• The diagnosis of chromoblastomycosis can be challenging in countries where it is not endemic and rarely seen.

• A high index of suspicion elicited from a history of travel to an endemic region and early dialogue with a histopathologist and infection specialist are vital.

• Prolonged antifungal therapy alone, or in combination with local treatments, is necessary for cure.

• Worldwide, chromoblastomycosis remains a debilitating disease for patients and a therapeutic challenge for clinicians.

Ethics statements

Patient consent for publication

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