Fine needle aspiration of nodular cystic swelling showing a rare melanized fungus Medicopsis romeroi: A case report.

A young woman on long term corticosteroid therapy presented with a discrete hyperpigmented nodular cystic swelling on her upper thigh to the buttock region. There was history of discharging sinuses however at presentation the lesion was painless nondischarging. The lesion was subjected to fine-needle aspiration. The cytological smears on routine and special stains showed branching, septate fungal hyphae present extracellularly and intracellularly. The background showed dense mixed inflammation and granulomatous inflammation. The aspirated material was further subjected to culture. A nonsporulating melanized fungus was obtained and a culture isolate was sent for molecular characterization. Medicopsis romeroi, a rare melanized fungus belonging to the order Pleosporales was isolated on Internal transcribed spacer sequencing.

The Phytopathogenic Fungus Pallidocercospora crystallina-Caused Localized Subcutaneous Phaeohyphomycosis in a Patient with a Homozygous Missense CARD9 Mutation.

PURPOSE: In the past decade, an increasing number of otherwise healthy individuals suffered from invasive fungal infections due to inherited CARD9 mutations. Herein, we present a patient with a homozygous CARD9 mutation who was suffering from localized subcutaneous phaeohyphomycosis caused by the phytopathogenic fungus Pallidocercospora crystallina which has not been reported to cause infections in humans. METHODS: The medical history of our patient was collected. P. crystallina was isolated from the biopsied tissue. To characterize this novel pathogen, the morphology was analyzed, whole-genome sequencing was performed, and the in vivo immune response was explored in mice. Whole-exome sequencing was carried out with samples from the patient's family. Finally, the expression and function of mutated CARD9 were investigated. RESULTS: A dark red plaque was on the patient's left cheek for 16 years and was diagnosed as phaeohyphomycosis due to a P. crystallina infection. Whole-genome sequencing suggested that that this strain had a lower pathogenicity. The in vivo immune response in immunocompetent or immunocompromised mice indicated that P. crystallina could be eradicated within a few weeks. Whole-exome sequencing revealed ahomozygous missense mutation in CARD9 (c.1118G>C p.R373P). The mRNA and protein expression levels were similar among cells carrying homozygous (C/C), heterozygous (G/C), and wild-type (G/G) CARD9 alleles. Compared to PBMCs or neutrophils with heterozygous or wild-type CARD9 alleles, however, PBMCs or neutrophils with homozygous CARD9 alleles showed impaired anti-P. crystallina effects. CONCLUSION: Localized subcutaneous phaeohyphomycosis caused by P. crystallina was reported in a patient with a homozygous CARD9 mutation. Physicians should be aware of the possibility of a CARD9 mutation in seemingly healthy patients with unexplainable phaeohyphomycosis.

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Mycology - an update. Part 1: Dermatomycoses: causative agents, epidemiology and pathogenesis.

Dermatomycoses are caused most commonly by dermatophytes. The anthropophilic dermatophyte Trichophyton rubrum is still the most frequent causative agent worldwide. Keratinolytic enzymes, e.g. hydrolases and keratinases, are important virulence factors of T. rubrum. Recently, the cysteine dioxygenase was found as new virulence factor. Predisposing host factors play a similarly important role for the development of dermatophytosis of the skin and nails. Chronic venous insufficiency, diabetes mellitus, disorders of cellular immunity, and genetic predisposition should be considered as risk factors for onychomycosis. A new alarming trend is the increasing number of cases of onychomycosis - mostly due to T. rubrum - in infancy. In Germany, tinea capitis is mostly caused by zoophilic dermatophytes, in particular Microsporum canis. New zoophilic fungi, primarily Trichophyton species of Arthroderma benhamiae, should be taken into differential diagnostic considerations of tinea capitis, tinea faciei, and tinea corporis. Source of infection are small household pets, particularly rodents, like guinea pigs. Anthropophilic dermatophytes may be introduced by families which immigrate from Africa or Asia to Europe. The anthropophilic dermatophytes T. violaceum, T. tonsurans (infections occurring in fighting sports clubs as "tinea gladiatorum capitis et corporis") and M. audouinii are causing outbreaks of small epidemics of tinea corporis and tinea capitis in kindergartens and schools. Superficial infections of the skin and mucous membranes due to yeasts are caused by Candida species. Also common are infections due to the lipophilic yeast fungus Malassezia. Today, within the genus Malassezia more than 10 different species are known. Malassezia globosa seems to play the crucial role in pityriasis versicolor. Molds (also designated non-dermatophyte molds, NDM) are increasingly found as causative agents in onychomycosis. Besides Scopulariopsis brevicaulis, several species of Fusarium and Aspergillus are found.

Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases.

Failure of desmosomal adhesion with ensuing keratinocyte separation - a phenomenon called acantholysis - can result from genetic, autoimmune or infectious proteolytic causes. Rare hereditary disorders of desmosomal formation have been identified in animals. Familial acantholysis of Angus calves and hereditary suprabasal acantholytic mechanobullous dermatosis of buffaloes appear to be similar to acantholytic epidermolysis bullosa of human beings. A genetic acantholytic dermatosis resembling human Darier disease has been rarely recognized in dogs. In autoimmune blistering dermatoses, circulating autoantibodies bind to the extracellular segments of desmosomal proteins and induce acantholysis. Autoantibodies against desmoglein-3 are found in canine pemphigus vulgaris and paraneoplastic pemphigus. Autoantibodies against desmoglein-1 have been rarely detected in dogs with pemphigus foliaceus. When circulating autoantibodies target desmogleins-1 and -3, mucocutaneous pemphigus vulgaris develops in dogs. Finally, several infectious agents can release proteases that cleave desmosomal bonds. In superficial pustular dermatophytosis of dogs and horses, Trichophyton hyphae colonize the stratum corneum, and acantholysis presumably develops because of proteases secreted by the dermatophytes. In exudative epidermitis of piglets, Staphylococcus bacteria - usually Staphylococcus hyicus- release exfoliatin toxins that bind to and specifically cleave desmoglein-1. Any of the above mechanisms can result in impairment of desmosomal function with subsequent acantholysis. The end point of adhesion failure is identical among these diseases: there is cleft formation where desmosomes are affected. The similarity of mechanisms explains why clinical and microscopic skin lesions overlap between entities, thus leaving clinicians and dermatopathologists with the conundrum of determining whether the acantholysis is of genetic, autoimmune or infectious origin.

Toll-like receptor 2 (TLR2) mediates intracellular signalling in human keratinocytes in response to Malassezia furfur.

Toll-like receptors (TLRs) are crucial players in the innate immune response to microbial invaders. The lipophilic yeast Malassezia furfur has been implicated in the triggering of scalp lesions in psoriasis. The aim of the present study was to assess the role of TLRs in the defence against M. furfur infection. The expression of the myeloid differentiation factor 88 (MyD88) gene, which is involved in the signalling pathway of many TLRs, was also analysed. In addition, a possible correlation of antimicrobial peptides of the beta-defensin family to TLRs was tested. Human keratinocytes infected with M. furfur and a variety of M. furfur-positive psoriatic skin biopsies were analysed by RT-PCR, for TLRs, MyD88, human beta-defensin 2 (HBD-2), HBD-3 and interleukin-8 (IL-8) mRNA expression. When keratinocytes were infected with M. furfur, an up-regulation for TLR2, MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated cells. The same results were obtained when psoriatic skin biopsies were analysed. The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M. furfur-induced expression of these molecules. These findings suggest the importance of TLRs in skin protection against fungi and the importance of keratinocytes as a component of innate immunity.

Estudo de associação entre antígenos leucocitários humanos e doença de Jorge Lobo / Study of the association between human leukocyte antigens and Jorge Lobo's disease

A doença de Jorge Lobo é uma micose cutânea/subcutânea de evolução crônica, causada pelo fungo Lacazia loboi. Devido às características epidemiológicas e poucos estudos relacionados aos aspectos imunológicos dessa doença, o objetivo do trabalho foi investigar uma possível associação das especificidades HLA de classe II em 21 pacientes portadores da doença de Jorge Lobo, comparando com indivíduos sadios de mesma etnia. As tipificações HLA foram realizadas pelo método de PCR-SSP. O resultado não revelou qualquer tipo de associação entre os antígenos HLA e doença de Jorge Lobo. Embora sem significância estatística, foi observada a diminuição da freqüência do antígeno HLA-DR7 no grupo dos pacientes em relação aos controles (0 por cento x 18 por cento), sugerindo uma associação negativa (protetora) entre HLA-DR7 e doença de Jorge Lobo. Contudo, estudos devem ser continuados, objetivando melhor entendimento nos mecanismos envolvidos na suscetibilidade e/ou proteção dessa doença.

[Antifungal agents in dermatophytic disease: failure of griseofulvin, ketoconazole and itraconazole]. / Les antifungiques dans la maladie dermatophytique: échec de la griséofulvine, du kétoconazole et de l'itraconazole.

The dermatophytic disease is a rare, severe affection caused by banal dermatophytes. A genetically predisposed basis could explain the frequent failure of antifungal therapeutics. We report here the case of a 28-year-old male. Despite 2 years of griseofulvin, 23 months of ketoconazole and 8 months of itraconazole, the therapeutic failure was evident: circinate herpes, papulo-nodules, vegetating plaques, ulceration, superficial and profound adenopathies, cerebral involvement, and deterioration of the general state. The correction of the immuno-deficient state combined with antifungals could be the best therapy.

Microepidemia de dermatofitose por Microsporum canis: aspectos de saúde pública / Microepidemy of dermatophytosis by Microsporum canis: public health aspects

Os autores chamam a atençäo para aspectos epidemiológicos num surto familiar de dermatofitose por M. canis. Eles enfatizan a importancia da busca da fonte de infecçäo na tentativa de reduzir a magnitude do reservatório animal