Inappropriate Use of Steroids in Superficial Dermatophytosis: An Uncommon Case of Erythroderma.

Erythroderma is a dermatological emergency presenting with generalized erythema and scaling involving <90% of the body surface.1 There are various causes of erythroderma, such as psoriasis, atopic dermatitis, phytophotodermatitis, pityriasis rubra pilaris, pemphigus foliaceus, cutaneous T-cell lymphoma, and drug eruptions.2 However, erythroderma induced by dermatophytosis is encountered rarely. We, here, describe a case of erythroderma developed secondary to extensive dermatophytosis.

Zoonotic Majocchi's Granuloma of the Vulva.

A healthy 32-year-old woman presented to clinic with tender pruritic lesions of 2-month duration at the vulva and lesions for weeks on the shins. She was treated with topical corticosteroids and intravenous vancomycin without significant improvement. On examination, dozens of follicular hemorrhagic papulopustules were detected at the suprapubic area and vulva (Figure 1). Similar but less prominent lesions were observed on the shins as well. Biopsies of the vulva and shin revealed a follicular inflammatory infiltrate of neutrophils, histiocytes, and lymphocytes as well as fungal hyphae within the follicular infundibulum and hair shafts, consistent with Majocchi's granuloma (MG). Gram and Fite-Faraco staining, direct immunofluorescence, and bacterial culture were negative. Tissue culture grew Trichophyton mentagrophytes, which was identified using sequence analysis of the D1/D2 region of the 28s rDNA. Minimum inhibitory concentrations for terbinafine, ketoconazole, and itraconazole were determined, with terbinafine having the lowest concentration. Additional history revealed that shortly prior to commencement of her clinical manifestations, the patient had acquired a pet guinea pig with eruptions and hair loss (Figure 2). The patient was prescribed ketoconazole cream and terbinafine, 250 mg daily, with almost immediate improvement. Based on clinical response, the patient remained on terbinafine and ketoconazole cream for 6 months. Her skin remained clear 4 months after discontinuing all antifungals. Based on the results of patient's culture, a veterinarian treated her guinea pig successfully with systemic terbinafine and miconazole lotion.

A Case of Tinea Faciei due to Trichophyton indotineae with Steroid Rosacea Related to Topical Over-The-Counter Drugs Purchased Outside of Japan.

A Filipino woman in her forties had facial erythema that was being self-treated with over-the-counter (OTC) drugs purchased outside of Japan. The drugs included clobetasol propionate, antibiotic, and antifungal components. Her facial erythema symptoms were worse during summertime. KOH direct examination of annular erythema was positive for fungal hyphae and negative for Demodex folliculorum. Fungal culture revealed Trichophyton indotineae based on internal transcribed spacer sequence analysis. Minimal inhibitory concentration for terbinafine was 0.06 µg/mL. We made a diagnosis of tinea faciei with steroid rosacea. We treated the patient with oral itraconazole. Physicians should be aware of increasing T. indotineae infections and increasing self-medication using topical OTC steroids combined with antifungals and antibiotics not only in India but also among foreign people living in other countries such as Japan.

Deep dermatophytosis caused by Trichophyton rubrum in an elderly patient with CARD9 deficiency: A case report and literature review.

Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

Deep-seated dermatophytosis caused by Trichophyton rubrum in patient with Becker muscular dystrophy.

Trichophyton rubrum is a common fungal pathogen that usually causes superficial infection limited to epidermis only, so called dermatophytosis. However in immunocompromised patients, dermatophytosis can be exceptionally more invasive with extensive lesions involving deep tissues and generating sometimes systemic course. We report the case of a 43-year-old heart transplanted man, who presented with multiple deep-seated nodules and papules in the inguinal areas and in the buttocks. Involvement of Trichophyton rubrum was confirmed by culture, DNA sequencing and histological examination that showed granulomatous inflammatory infiltrates with the presence of hyphae in the dermis. Antifungal therapy with oral terbinafine for four weeks was successful; in spite of initial remnant atrophic scars, the lesions were completely cleared after four month evolution. Deep-seated invasive dermatophytosis is rare, but should be considered with immunocompromised conditions, especially when history of previous superficial dermatophytosis is present.

Erythroderma combined with deeper dermal dermatophytosis due to Trichophyton rubrum in a patient with myasthenia gravis: first case report and literature review.

BACKGROUND: Dermatophytes are the most common causative pathogens of mycoses worldwide and usually cause superficial infections. However, they can enter deep into the dermis lead to invasive dermatophytosis such as deeper dermal dermatophytosis on rare occasions. Erythroderma is a severe dermatological manifestation of various diseases resulting in generalized skin redness, but erythroderma due to fungi infections is barely reported. In this article, we reported the first case of erythroderma combined with deeper dermal dermatophytosis due to Trichophyton rubrum (T. rubrum) in a patient with myasthenia gravis. CASE PRESENTATION: A 48-year-old man was hospitalized because of erythema with scaling and nodules covering his body for a month. The patient had a history of myasthenia gravis controlled by regularly taking prednisolone for > 10 years and accompanied by onychomycosis and tinea pedis lasting > 8 years. Based on histopathological examinations, fungal cultures, and DNA sequencing results, the patient was finally diagnosed with dermatophyte-induced erythroderma combined with deeper dermal dermatophytosis caused by T. rubrum. After 2 weeks of antifungal treatment, the patient had recovered well. CONCLUSIONS: This case report shows that immunosuppressed patients with long histories of superficial mycoses tend to have a higher risk of developing invasive dermatophytic infections or disseminated fungal infections. Dermatologists should be alert to this condition and promptly treat the superficial dermatophytosis.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

Association of Kallikrein Related Peptidase 3 (KLK3) gene with dermatophytosis in the UK biobank cohort.

BACKGROUND: In a previous genome wide association study (GWAS) of UK Biobank (UKB) data, we identified one susceptibility locus, tubulointerstitial nephritis antigen (TINAG), with genome wide significance for dermatophytosis. We used genotype calls from file UKB22418. These data are derived directly from Affymetrix DNA microarrays but are missing many genotype calls. Using computationally efficient approaches, UKB has entered imputed genotypes into a second dataset, UKB22828, increasing the number of testable variants by over 100-fold to 96 million variants. METHODS: In the current study, we used UKB imputed genotypes in UKB22828 to identify dermatophytosis susceptibility loci. To identify cases of dermatophytosis, we used ICD10 code B35, which covers tinea barbae, tinea capitis, tinea unguium, tinea manuum, tinea pedis, tinea corporis, tinea imbricata, tinea cruris, other dermatophytoses and dermatophytosis, unspecified. We used PLINK, a whole-genome association analysis toolset, to analyse the UKB22828 chromosome files. RESULTS: GWAS summary (Manhattan) plot of the meta-analysis association statistics highlighted two susceptibility loci, TINAG and Kallikrein Related Peptidase 3 (KLK3), with genome wide significance for dermatophytosis. KLK3, also known as prostate specific antigen (PSA), belongs to a subclass of serine proteases with a variety of physiological functions. CONCLUSION: KLK3 may be a dermatophytosis susceptibility gene. KLK3 could affect risk of dermatophytosis, since kallikreins are necessary for normal homeostasis of the skin.

Cytomorphological findings of Trichophyton rubrum infection in an elderly hypertensive woman.

Trichophyton is a dermatophytic fungi causing superficial skin infections which affects outermost layer of the epidermis, stratum corneum, and mainly involves feet, groin, scalp, and nails. Invasion into the dermis occurs mainly in immunocompromised patients. A 75-year-old hypertensive female presented with a nodular swelling on the dorsum of right foot for 1 month. The swelling was 1.0 × 1.0 cm and gradually progressive in nature. FNAC revealed many thin filamentous branching and fungal hyphae along with foreign body granulomas and suppurative acute inflammation. The swelling was excised and sent for histopathological examination which confirmed the above findings. Periodic Acid Schiff stain showed fungal hyphae in both cytology smear as well as histopathology section. On fungal culture, microconidia with septate hyphae suggestive of Trichophyton rubrum was seen. Trichophytons mainly affect immunocompromised and diabetic patients, however, may present as nodular lesions without any history of superficial dermatophytosis as seen in the present case. The characteristic cytological picture helped to clinch the diagnosis in this case and facilitated further management.

Dermatologic Diseases of Four-Toed Hedgehogs.

Dermatologic diseases are frequently diagnosed in the four-toed hedgehog. Common clinical signs include spine loss, scales and crusts, pruritus, alopecia, and masses. Caparinia tripilis, family Psoroptidae, is the most common mite affecting hedgehogs, and is diagnosed via light microscopy. Dermatophytosis from Trichophyton erinacei infection is a common zoonotic dermatologic disease in pet hedgehogs. Diagnosis is through fungal culture. Neoplasia is another major cause of dermatologic diseases in four-toed hedgehogs. The diagnostic approach typically begins with a fine-needle aspirate but often requires a biopsy for a definitive diagnosis.

Treatment recalcitrant cases of tinea corporis/cruris caused by T. mentagrophytes - interdigitale complex with mutations in ERG11 ERG 3, ERG4, MDR1 MFS genes & SQLE and their potential implications.

BACKGROUND: Recalcitrant dermatophyte infections are being reported from various parts of the world due to varied causes including strain variation, steroid misuse, SQLE mutations, and variable quality of itraconazole pellet formulations. The oral drug preferred in endemic areas is itraconazole, to which MIC levels remain low, and clinical failures to itraconazole reported defy a sound scientific explanation. OBJECTIVES: The objective of the study was to conduct a proteomic and genomic analysis on isolates from therapeutically recalcitrant case with isolation of gene mutations and enzymatic abnormalities to explain azole failures. METHODS: Trichophyton mentagrophyte interdigitale complex strains were isolated from seven clinically non-responding tinea corporis/cruris patients, who had failed a sequential course of 6 weeks of terbinafine 250 mg QD and itraconazole 100 mg BID. After AFST 1 strain, KA01 with high MIC to most drugs was characterized using whole genome sequencing, comparative proteomic profiling, and total sterol quantification. RESULTS: Sterol quantification showed that the standard strain of Trichophyton mentagrophytes (MTCC-7687) had half the ergosterol content than the resistant KA01 strain. Genomic analysis revealed mutations in SQLE, ERG4, ERG11, MDR1, MFS genes, and a novel ERG3 mutation. Proteomic analysis established the aberrant expression of acetyl Co-A transferase in the resistant strain and upregulation of thioredoxin reductase and peroxiredoxin. CONCLUSION: Our findings demonstrate possible reasons for multidrug resistance in the prevalent strain with mutations in genes that predict terbinafine (SQLE) and azole actions (ERG4, ERG11, ERG3) apart from efflux pumps (MDR1, MFS) that can explain multidrug clinical failures.

Molecular study of feline dermatophytosis and Toll-like receptor 2 and 4 gene expression in their lesions.

BACKGROUND: Pattern recognition receptors (PRRs) as the recognition of pathogenic fungal structures induce the secretion of cytokines by immune systems. Toll-like receptors (TLRs) 2 and 4 are the main PRRs that recognize fungal components. AIM: The present study aimed to assess the presence of dermatophyte species in symptomatic cats in a region of Iran and to investigate the expression of TLR-2 and 4 in cat lesions with dermatophytosis. METHODS: A total of 105 cats suspected of dermatophytosis with skin lesions were examined. Samples were analysed by direct microscopy using potassium hydroxide (20%) and culture on Mycobiotic agar. Dermatophytes strains were confirmed by the polymerase chain reaction (PCR) amplification and then sequencing of the Internal Transcribed Spacer rDNA region. Also, for pathology and real-time PCR studies, skin biopsies were taken by sterile single-use biopsy punch from active ringworm lesions. RESULTS: Dermatophytes were found in 41 felines. Based on the sequencing of all strains, Microsporum canis (80.48%, p < 0.05), Microsporum gypseum (17.07%) and Trichophyton mentagrophytes (2.43%) were the dermatophytes isolated from cultures. Cats under 1 year (78.04%) revealed a statistically significantly higher prevalence of infection (p < 0.05). Gene expression by real-time PCR revealed the increased TLR-2 and 4 mRNA levels in skin biopsies of cats with dermatophytosis. CONCLUSIONS: M. canis is the most prevalent dermatophyte species isolated from feline dermatophytosis lesions. Increased expression of TLR-2 and TLR-4 mRNAs in cat skin biopsies suggests that these receptors are involved in the immune response by recognizing dermatophytosis.

Querión Celso, dermatofitosis del cuero cabelludo infantil / Kerion Celsi, dermatophytosis of the scalp in young boy

Resumen Querión Celso es una micosis ocasionada por hongos dermatofitos que daña el cuero cabelludo principalmente a niños y en raras ocasiones a adultos. La forma de infección para los humanos proviene de los animales y del suelo y se relaciona con mala higiene personal, hacinamiento en las viviendas, condiciones de subdesarrollo y pobreza. Se presenta un caso de un niño de 9 años con una úlcera de 7 cm de diámetro en el cuero cabelludo y en forma de placa circular que presentaba material purulento, pelo quebradizo y un área alopécica. Al inicio, se abordó de manera terapéutica como una infección bacteriana; posteriormente, se solicitó estudio micológico que evidenció una coinfección por el microorganismo Microsporum gypseum. Se le confirmó el diagnóstico de tiña capitis con afección inflamatoria y se le prescribió griseofulvina, lo que resultó en una curación completa.

Abstract Kerion Celsi is a mycosis caused by dermatophyte fungi that mostly affects children and rarely adults, causing damage to the scalp. The form of infection for humans comes from animals and the soil. The infection is related to poor personal hygiene, overcrowded homes, underdeveloped conditions, and poverty. A case of a 9-year-old boy with a 7cm diameter ulcer on the scalp and in the form of a circular plaque that presented purulent material, brittle hair and an alopecic area is presented. Initially it was therapeutically addressed as a bacterial infection, a mycological study was requested, which showed coinfection by the microorganism Microsporum gypseum, the diagnosis of tinea capitis with inflammatory condition was confirmed, and Griseofulvin was prescribed, resulting in complete cure.

Case Report: Disseminated Vegetating Plaques Occurring over Chronic Recalcitrant Dermatophytosis in an Immunocompromised Patient.

Blastomycosis-like pyoderma (BLP) is an uncommon tissue response possibly to bacterial infection that presents as vegetative skin lesions usually in immunocompromised patients. Staphylococcus aureus is the most frequent pathogen implicated in BLP. Here, we report the case of a 32-year-old man who had ulcerative vegetating lesions on extremities for 3 months over preexisting recalcitrant tinea lesions. The patient was hypertensive with a history of chronic graft rejection after renal transplantation 8 months earlier and was on long-term immunosuppressants. Investigations revealed anemia, mild hyperglycemia, and elevated serum creatinine. Histopathology showed suppurative and fibrosing perifolliculitis with moderate pseudocarcinomatous hyperplasia and the culture of biopsy specimen demonstrated growth of Escherichia coli and Citrobacter koseri. The diagnosis of BLP overlying dermatophytoses was made. The skin lesions improved completely with parenteral antibiotics. Local immune dysregulation by dermatophytoses along with iatrogenic immunosuppression may have favored this rare pyoderma.

Case report: Severe deep ulcer on the left abdomen mimicking mycosis fungoides caused by Trichophyton tonsurans in a patient with novel CARD9 mutation.

Dermatophytosis is the most common type of superficial fungal infection caused by dermatophytes. Occasionally, the fungus invades deep into the dermis or other tissues, causing deep dermatophytosis. Deep dermatophytosis is often associated with Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in patients. Here, we report the first case of deep dermatophytosis with a rare mycosis fungoides manifestation caused by T. tonsurans in a patient with a novel mutation in exon 4 of CARD9. The condition presented with heterozygous K196E mutation, which leads to deficiency of innate and adaptive immune responses in the patient, and caused intractable severe lesions. The patient received treatment with multiple antifungal drugs and was ultimately alleviated by posaconazole. These findings extend the pathogen spectrum of deep dermatophytosis linked with CARD9 deficiency and enriched their phenotypic spectrum.