The Diagnosis of Fungal Neglected Tropical Diseases (Fungal NTDs) and the Role of Investigation and Laboratory Tests: An Expert Consensus Report.

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs.

Diagnosis and Management of Fungal Neglected Tropical Diseases In Community Settings-Mycetoma and Sporotrichosis.

BACKGROUND: This is a retrospective, analytic observational study where we describe cases of sporotrichosis and mycetoma from Acapulco General Hospital and Community Dermatology Mexico C.A. over 25 years. Analysis of environmental features that favour the development of such diseases has been made, as well as the limitations in the study and treatment of such diseases in resource poor settings. METHODS: We reviewed the information on 76 sporotrichosis and 113 mycetoma patients out of a total of 14,000 consultations at Acapulco General Hospital and from Community Dermatology clinics. We analysed the epidemiological and mycological characteristics and the investigations used for diagnosis such as direct examination, culture, intradermal test reactions, and biopsy. RESULTS: In total 91 confirmed cases of actinomycetoma, 22 of eumycetoma and 76 of sporotrichosis have been identified including diagnostic studies for both diseases and their treatment. DISCUSSION: The results obtained have been analysed and interpreted in patients with mycetoma and sporotrichosis in the state of Guerrero, México, along with limitations in their management in areas with limited economic and logistical resources. The prevalence of mycetoma in our setting is compared with other centres where patients from all over the country are seen. The possible causes for variations in prevalence in specific areas has been looked for, in one of the poorest states of the Mexican Republic.

Report of 73 cases of cutaneous sporotrichosis in Mexico

Abstract: We report 73 cases of cutaneous sporotrichosis from the Community Dermatology program, at the central and mountain areas of the state of Guerrero, Mexico. A similar number of cases was found between children and adults, mostly peasants and school-age children with rural occupations. Upper limbs were the mostly affected and the predominant clinical form was lymphocutaneous (56.16%). All cultures corresponded to Sporothrix schenckii (sl). Treatment was done with potassium iodide in 54 patients, achieving clinical and mycological cure in all cases.

Eumycetoma.

Eumycetoma is caused by different fungi. Madurella mycetomatis, Madurella grisae, and Scedosporium apiospermum are the most common causative agents. This disease is more frequent on the lower extremities but can also be present in other areas. The diagnosis is made by direct microscopic examination and histologic study, which should show hyphae and vesicles characteristic of the fungi. Etiologic identification of the species of the fungus is sometimes difficult by culture and biopsy specimen; in these cases, molecular techniques can help to identify the infecting organism. Treatment has been with amphotericin B, which is now seldom used due to its side effects and limited success. The best therapeutic choice is surgical removal of the lesion, followed by medical treatment. This includes antifungals such as the azoles, ketoconazole and itraconazole; in resistant cases, posaconazole and voriconazole are currently recommended. In particular, the combination of terbinafine and itraconazole can elicit a good result in some cases.

Eumycotic mycetoma caused by Madurella mycetomatis successfully treated with antifungals, surgery, and topical negative pressure therapy.

We report a 21-year-old farmer with a 4-year history of a nodular plaque with fistulas and induration of adjacent skin. The lesion had been treated surgically at another hospital, but recurred 2 years later. Black, charcoal-like grains were observed draining through the fistulas. A biopsy specimen showed brown grains with filaments in an abscess surrounded by macrophages, giant cells, and lymphocytes. Culture demonstrated small white colonies of Madurella mycetomatis. The patient was treated with itraconazole for 6 months, followed by surgery. TNP was initiated in the immediate post-operative period, and copious granulation tissue was observed within 1 week. Autologous skin grafting was performed, and itraconazole was continued for an additional 3 months. Although necrosis of the graft ensued, the functional result was acceptable. The patient appeared free of disease at 18 months of follow-up. Eumycotic mycetoma is an infectious and inflammatory process that occurs after traumatic inoculation of fungi through the skin. Surgery is the treatment of choice, but successful reconstruction may be challenging and recurrence is common. Topical negative pressure (TNP) promotes the formation of granulation tissue, which facilitates closure of deep wounds and chronic ulcers. This case illustrates that eumycotic mycetoma is difficult to treat. Whether TNP contributed to the successful outcome cannot be proven but, given the generally poor response of eumycetoma to therapy, we suggest that the role of TNP in the management of this disease merits attention.

Giant onychomatricoma: report of two cases with rare clinical presentation.

BACKGROUND: Onychomatricoma was reported for the first time by Baran and Kint as a rare nail matrix tumor with specific clinical and histologic features, including a macroscopic appearance of filiform digitations originating from the nail matrix which are inserted in the nail plate.(1) The appearance of the lesion may resemble that of an "anemone." All previous reports have been mostly from Europe, with only one case from North America. These are the first case reports from Mexico. They show rare clinical characteristics, in particular tumor involving the entire nail matrix. METHODS: Two cases are presented: Case 1, a 59-year-old man with a 2-year history of deformity of the entire nail apparatus of the right thumb, clinically suggestive of onychomatricoma; Case 2, a 45-year-old woman with a 3-year history of gradual nail dystrophy, initially misdiagnosed as onychomycosis and treated unsuccessfully for several months with antimycotics by a general physician. In both cases, the entire nail plate was affected and, because of the clinical appearance, nail exploration and excisional biopsy of the tumors at the nail matrix were performed. RESULTS: During nail matrix surgical exploration, including avulsion of the nail plate, characteristic digitiform projections that were firmly attached to the nail plate were observed. In both cases, the entire nail matrix was affected, producing a giant form of onychomatricoma. Hematoxylin and eosin stain showed characteristic filiform projections that corresponded to the clinical appearance, with elongated epithelium from the nail matrix and fibromyxoid stroma with multiple basophilic cells, and typical clefts in between. CONCLUSIONS: Onychomatricoma has a classical clinical appearance; however, it is difficult to identify, as it is not until surgery, when the typical filiform projections are more visible, that the diagnosis can be made. Onychomatricoma is a rare tumor. The involvement of the entire nail matrix, with secondary nail dystrophy, in both cases presented here makes them interesting case reports of this unusual form of tumor.

Scalp metastases of a renal cell carcinoma.

An 80-year-old man presented with a localized tumor of the right occipital scalp. The tumor was a 1-cm, bright red-purple, ulcerated, and crusted exophytic nodule on a smooth base (Figure 1). The lesion had grown asymptomatically over 18 months except for profuse bleeding induced by minimal trauma. It was extirpated with the clinical diagnosis of pyogenic granuloma vs. renal metastasis to the scalp. The patient's medical history included a transurethral prostatic resection 3 years earlier and, 1 year later, a right nephrectomy for a 2-kg kidney tumor verbally reported as "benign." The patient also had a 2-year history of untreated high blood pressure. Histopathologically, the excised tissue was an exo-endophytic nodule of a solid form composed of pleomorphic neoplastic cells with abundant clear cytoplasm, surrounded by fibrous collagen septae, blood vessel proliferation, and areas of hemorrhage (Figures 2 and 3). The histopathologic diagnosis of metastatic renal cell carcinoma was supported by immunohistochemistry with positive epithelial membrane antigen staining (Figure 4). Cytokeratins 7 and 20 were nonreactive. Laboratory studies revealed hematuria and elevated creatinine and urea nitrogen levels, but no malignant cells were observed in five urinary cytologies. Renal ultrasound showed the presence of two simple cysts in the left kidney and data compatible with chronic inflammatory disease.