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Trichophyton(T.)mentagrophytesnow accounts for an overwhelming majority of clinical cases in India, a new “Indian genotype” (T. mentagrophytes ITS genotype VIII)having been isolated from skin samples obtained from cases across a wide geographical distribution in this country. The conventional diagnostic methods, like fungal culture, are, however, inadequate for diagnosing this agent. Thus, molecular methods of diagnosis are necessary for proper characterization of the causative agent. The shift in the predominant agent of dermatophytosis fromT. rubrumtoT. mentagrophytes, within a relatively short span of time, is without historic parallel. The apparent ease of transmission of a zoophilic fungus among human hosts can also be explained by means of mycological phenomena, like anthropization.

A severe outbreak of highly virulent and multi-resistant dermatophytosis by species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India. The correct identity of the etiologic agent is a much-debated issue. In order to define species limits, a taxonomic study was undertaken combining molecular, morphological, and physiological characteristics as evidence of classification. Molecular characteristics show that T. mentagrophytes s. str. and T. interdigitale s. str. can be distinguished with difficulty from each other, but are unambiguously different from the Indian genotype, T. indotineae by sequences of the HMG gene. The entities were confirmed by multilocus analysis using tanglegrams. Phenotypic characters of morphology and physiology are not diagnostic, but statistically significant differences are observed between the molecular siblings. These properties may be drivers of separate evolutionary trends. Trichophyton mentagrophytes represents the ancestral, homothallic cloud of genotypes with a probable geophilic lifestyle, while T. indotineae and T. interdigitale behave as anthropophilic, clonal offshoots. The origin of T. indotineae, which currently causes a significant public health problem, is zoonotic, and its emergence is likely due to widespread misuse of antifungals.

Dermatophytosis has attained unprecedented dimensions in recent years in India. Its clinical presentation is now multifarious, often with atypical morphology, severe forms and unusually extensive disease in all age groups. We hesitate to call it an epidemic owing to the lack of population-based prevalence surveys. In this part of the review, we discuss the epidemiology and clinical features of this contemporary problem. While the epidemiology is marked by a stark increase in the number of chronic, relapsing and recurrent cases, the clinical distribution is marked by a disproportionate rise in the number of cases with tinea corporis and cruris, cases presenting with the involvement of extensive areas, and tinea faciei.

Lichen simplex chronicus (LSC) of the vulva is an acquired, persistent, severely itchy dermatosis usually located in easily reachable areas of the body like the extremities, nape of the neck, and genitalia. It also has a strong association with atopy and is said to be initiated and perpetuated by the itch-scratch-itch cycle. Two cases of rugose labia as the sole presentation of LSC of vulva are being presented.

Background The Indian ITS genotype VIII T. mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyzes the first step of ergosterol biosynthesis. Objectives Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T. mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population. Methods Growth in fluconazole or terbinafine containing medium was analyzed using a microplate-laser-nephelometry (MLN)-based growth assay. Results Ala 448 Thr erg1 single mutants were terbinafine sensitive but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance. Conclusion The new Indian T. mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.

A rather quick change in epidemiological shift from Trichophyton rubrum to Trichophyton mentagrophytes (ITS genotype VIII), several changes in clinical presentation of superficial dermatophytoses and the the response/ the lack of it, makes this current epidemic very interesting and novel. We present here some of the relatively less discussed variants that have been described under the broad terms of tinea corporis and tinea faceie. Many of them are found to occur uncharacteristically frequently and some in areas that were never described. We describe some representative cases of female genital dermatophytoses, periumblical and periocular dermatophytosis and discuss some unusual variants like those showing sole involvement of the ear (tinea auricularis), lip (tinea labialis) and superficial dermatophytosis of the scalp skin.

A 19-year-old man with granulomatosis with polyangiitis (Wegener's disease) presented with hemorrhagic facial nodules mimicking severe inflammatory acne (acne fulminans) as one of the first symptoms of the disease. The lesions were earlier treated as nodulocystic acne with isotretinoin without any benefit. Complete resolution was seen with pulsed methylprednisolone and oral prednisolone and mycophenolate mofetil thereafter. He also developed acute onset of severe pustular eruption of the face and a destructive ulcer of the auricle on two separate occasions. Facial lesions mimicking severe inflammatory acne, not responsive to standard treatment, may be a marker for more severe systemic disease such as Wegener's disease/granulomatosis with polyangiitis.

Introduction Superficial dermatophytoses constitute a common and growing problem in India. However, the associated impact on the affected individuals’ quality of life (QoL) has rarely been investigated. Aim To assess the quality of life of patients with different dermatophytoses. Material and methods Among 100 consecutive Indian patients with dermatophytosis, 76% agreed to participate. The diagnosis was established upon the typical clinical manifestation and direct microscopic mycological examination (10% KOH). Dermatology Life Quality Index (DLQI) was utilized to assess QoL impairment. Participants evaluated the presence and intensity of itch during the last 3 days using Numeral Rating Scale (NRS). Results A combination of tinea corporis and tinea cruris was diagnosed most commonly (52.6%), followed by tinea cruris alone (21%) and tinea corporis alone (13.2%). The mean duration of the disease was assessed as 6.3 ±18.0 months. The mean DLQI score was 8.2 ±5.1 points. A very large and extremely large effect on the DLQI was reported by 26.3% of patients, moderate by 40.8%, whereas small by 29%, with females being more heavily affected than males (9.3 ±5.2 and 7.1 ±4.7 points, respectively) (p = 0.038). Patients with a combination of tinea corporis, tinea cruris and tinea faciei demonstrated the lowest QoL (11.0 ±4.5 points). Additionally, a significant correlation between impairment of QoL and itch intensity (mean NRS score: 6.8 ±1.8 points) (r = 0.37; p < 0.002) was documented. Moreover, there was a trend towards lower QoL in patients who have been previously treated with topical agents containing corticosteroids. Conclusions Superficial dermatophytoses are associated with a moderate impact on QoL of the affected subjects.

We report four cases of ulcerated striae following misuse of fixed dose combinations creams containing clobetasol propionate with antifungal and antibacterial agents.

BACKGROUND Itch is an integral part of clinical picture of superficial dermatophytoses which constitute a common and growing problem in India. OBJECTIVES The study aimed to evaluate the prevalence, intensity and clinical characteristics of itch in superficial dermatophytosis. METHODS The data concerning disease history and clinical type of dermatophytosis were obtained. The presence and various characteristics of itch were documented. Numerical Rating Scale (NRS) was utilized to assess the worst intensity of itch during the last 3 days and during the course of the disease. 4-Item Itch Questionnaire was utilized to assess itch extent, intensity, frequency and associated sleep impairment, while quality of life (QoL) impairment was assessed via Dermatology Life Quality Index. RESULTS Ninety-nine patients with direct microscopic confirmation of dermatophytosis were included in the study. In 46.5% of subjects, the coexistence of tinea corporis and tinea cruris was noted, followed by tinea cruris (25.2%) and tinea corporis (13.1%). The majority of patients reported itch in the last 3 days (99%) and complained of itch limited to skin lesions (89.9%). According to NRS, the mean intensity of worst itch in the last 3 days was 6.8 ± 1.8 points. Severe and very severe itch was reported by 74.7% of patients. Itch was an isolated sensation in 34.3% of subjects, while 46.9% reported associated burning sensation. Itch was frequently exacerbated by sweating, hot temperature and wearing tight clothes. Difficulties in falling asleep and sleep awakenings were reported by 34.3% and 54.6% of subjects, respectively. Itch negatively influenced the well-being of patients and its intensity correlated with QoL impairment. CONCLUSIONS Itch is an important symptom in superficial dermatophytoses and is associated with negative impact on sleep and carries a significant psychosocial burden. Acknowledging its presence is necessary in a holistic approach to these patients.

Ein 6 Monate alter weiblicher Saugling aus Bahrain litt an einer ausgepragten Dermatomykose des gesamten Integuments. Die topische Behandlung mit Terbinafin uber 2 Monate fuhrte zu keinerlei Besserung. An der Dermatophytose erkrankte erwachsene Familienmitglieder und Kinder wurden im Heimatland ebenfalls ohne Erfolg topisch und auch systemisch – mit Voriconazol – antimykotisch behandelt. Die mykologische Diagnostik wahrend eines Urlaubsaufenthaltes in Deutschland erbrachte den Nachweis des zoophilen Dermatophyten Trichophyton (T.) mentagrophytes. Mittels Sequenzierung der „internal transcribed spacer“(ITS)-Region der rDNA (ribosomale Desoxyribonukleinsaure) des Pilzes lies sich der neu beschriebene Genotyp VIII innerhalb der Spezies T. mentagrophytes identifizieren. Dieser Genotyp von T. mentagrophytes ist der Haupterreger der aktuellen Epidemie von chronischen therapierefraktaren Dermatophytosen in Indien. Von einer Ubertragung dieses indischen Dermatophytengenotyps in andere Lander im Rahmen der Globalisierung muss ausgegangen werden. Ein wesentlicher Teil dieser indischen T.-mentagrophytes-Stamme ist zudem in vitro und genetisch – Punktmutationen der Squalenepoxidase (SQLE) – resistent gegenuber Terbinafin. Fur das hier untersuchte T.-mentagrophytes-Isolat aus Bahrain bestatigte sich in der SQLE-Mutationsanalyse der Nachweis der Punktmutation TTC/TTA, die fur die F397L-Aminosauresubstitution des Enzyms steht. Der Stamm war zudem in vitro resistent gegen Terbinafin. Diese Punktmutation ist im hohen Mase mit einer In-vitro-Resistenz des Dermatophyten gegenuber Terbinafin assoziiert. Das Madchen wurde erfolgreich rein topisch mit Miconazol, dann auch im Wechsel mit Ciclopiroxolamin behandelt. Es handelt sich hier um die erste Beschreibung einer Infektion durch einen Terbinafin-resistenten T.-mentagrophytes-Stamm vom ITS-Genotyp VIII aus Indien in Deutschland.

Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole.

We report 16 patients of tinea cruris who presented with an asymptomatic red scrotum due to fixed dose combination creams containing antifungal agents and topical steroids applied to the thighs as a treatment of tinea cruris. The erythema resolved upon starting appropriate treatment with single molecule antifungal creams and oral antifungal drugs in about six weeks' time in majority of cases. We propose that this clinical presentation may be akin to red scrotum syndrome (RSS). Due to its asymptomatic nature in most of the cases, we propose that this could be a forme fruste of RSS.

One of the canonical features of the current outbreak of dermatophytosis in India is its unresponsiveness to treatment in majority of cases. Though there appears to be discordance betweenin vivoandin vitroresistance, demonstration ofin vitroresistance of dermatophytes to antifungals by antifungal susceptibility testing is essential as it may help in appropriate management. The practical problem in the interpretation of antifungal susceptibility testing is the absence of clinical breakpoints and epidemiologic cutoff values. In their absence, evaluation of the upper limit of a minimal inhibitory concentration of wild type isolates may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility. In the current scenario, most of the cases are unresponsive to standard dosages and duration of treatment recommended until now. This has resulted in many ex-cathedra modalities of treatment that are being pursued without any evidence. There is an urgent need to carry out methodical research to develop an evidence base to formulate a rational management approach in the current scenario.

We present a series of three kidney transplant patients developing epidermoid cysts after receiving oral tacrolimus for long-term prevention of rejection of the allograft. Cyclosporin A has been known to show this cutaneous adverse drug reaction, but this is the first series of patients with epidermoid cysts following tacrolimus to the best of our knowledge.

Background An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. Objectives The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. Patients/methods We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. Results Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. Conclusions The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.

A 17 year old male patient with no known history of a consanguineous marriage of the parents was referred to one of us (SV) by a nephrologist for erythroderma. He was earlier treated for nephritic syndrome with gradually worsening edema and proteinuria over a period of one week with a marginally raised creatinine. (2.4 mg/d). After four weeks of treatment with 0.5 mg/kg prednisolone in a tapering dose and diuretics the patient had a normal kidney function, normal electrolytes but a subnephrotic range proteinuria. According to the parents the boy was ‘covered in scales’ on the 3rd day of birth and the condition persists till date. He had a short stature (1.47 meters) with coarse facial features. This article is protected by copyright. All rights reserved.

A 6 month-old-female infant from Bahrain visiting Germany with her family for a holiday was seen by us for extensive dermatophytosis of the back, buttocks, chest and groins. Topical treatment by terbinafine for over 2 months was not successful. Other family members including adults and children were treated in Bahrain with topical antifungals and oral voriconazole which was not helpful. Mycological examination performed in Germany revealed the detection of the zoophilic dermatophyte Trichophyton (T.) mentagrophytes. The newly described genotype VIII within the species T. mentagrophytes was identified by sequencing of the "internal transcribed spacer" (ITS) region of the fungal rDNA. This genotype of T. mentagrophytes is the main causative agent of the current epidemic of chronic recalcitrant dermatophytoses in India. Transmission of this Indian genotype of T. mentagrophytes to other countries due to globalization is a serious issue to be considered. Moreover, a significant percentage of these Indian T. mentagrophytes strains are resistant to terbinafine both in vitro and by the way of genetic point mutations in the squalene epoxidase (SQLE) gene. Some are also found to be partially resistant against itraconazole and voriconazole. The point mutation TTC/TTA was found by SQLE mutation analysis in this particular T. mentagrophyte isolate from Bahrain. This point mutation is closely associated with F397L amino acid substitution of the enzyme indicative of in vitro resistance of the dermatophyte against terbinafine. The girl was successfully treated by topical miconazole and later by ciclopirox olamine. This is the first report on an infection due to a terbinafine-resistant T. mentagrophytes strain of the ITS genotype VIII from India in Germany.