Clinico-mycological and therapeutic updates on cutaneous dermatophytic infections in the era of Trichophyton indotineae.

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses.

Comparison of outcomes of azathioprine, leflunomide and allergen avoidance in patients with patch test-positive pigmented contact dermatitis: a randomized comparative study.

BACKGROUND: Pigmented contact dermatitis (PCD) is a noneczematous form of allergic contact dermatitis characterized by dermal hyperpigmentation. Allergen avoidance is the cornerstone of therapy, but it is difficult to achieve. The use of immunosuppressives seems rational, but data are lacking. OBJECTIVES: To compare outcomes with azathioprine (AZA), leflunomide and allergen avoidance (AA) in patients with PCD. METHODS: A comparative study was conducted on 28 patients with patch test-positive PCD who were randomly allocated to one of three treatment groups: AZA 2 mg kg-1 daily for 24 weeks + AA (n = 10); leflunomide (LEF) 20 mg daily for 24 weeks + -AA (n = 8); AA alone (n = 10). Patients were followed up for an additional 24 weeks. The Dermal Pigmentation Area and Severity Index (DPASI) score and Hindi Melasma Quality of Life scale (MELASQOL) were used to assess hyperpigmentation and quality of life (QoL). respectively. RESULTS: Hair colorants (n = 12) and paraphenylenediamine (n = 8) were the most common allergens. Mean (SD) DPASI score decreased from 30.97 (3.69), 32.35 (3.90) and 31.86 (3.47) to 13.78 (4.25), 21.67 (2.99) and 20.64 (3.82) at 48 weeks in the three groups, respectively (P < 0.001); the maximum percentage decline was seen with AZA (56%). Mean (SD) MELASQOL score was reduced in the three treatment groups from 48.0 (6.46), 46.75 (3.69) and 46.6 (4.65) to 19.6 (6.98), 24.5 (5.80) and 24.0 (5.49), respectively, at 48 weeks (P < 0.001). Reductions in DPASI and Hindi MELASQOL scores were significantly correlated. The most frequent adverse event was transaminitis in both the AZA and LEF groups. CONCLUSIONS: Patients on AZA achieved a statistically significantly greater reduction in DPASI and MELASQOL score; therefore, AZA may fulfil an unmet need in PCD treatment. An objective reduction in hyperpigmentation was paralleled by an improvement in QoL score, reiterating the need for active management of this disease.

Use of tofacitinib in baricitinib-refractory atopic dermatitis: An example of JAK inhibitor switching.

Atopic dermatitis (AD) is predominantly mediated by a T-helper 2 immune system response. While JAK inhibitors have gained treatment approval for AD, data regarding interclass efficacy and therapeutic rationale is lacking. We report a patient with recalcitrant AD who failed baricitinib but demonstrated an excellent response to the pan-JAK inhibitor tofacitinib.

A prospective real-world study evaluating serum levels of arginine and cysteine in women with chronic telogen effluvium: do we really need blanket prescription of amino acid supplementation?

Amino acids form a major component of hair fibres and are prescribed routinely in the form of nutritional supplements in patients with chronic telogen effluvium (CTE). Such a practice is based on assumption of a nutritional deficiency state in such patients. In this prospective study, we evaluated the serum levels of cysteine and arginine in 30 women with CTE and in healthy controls. We found no significant difference between the two groups in terms of serum arginine levels. Cysteine levels were higher in patients with CTE (P < 0.001). No correlation was found between levels of serum amino acids (cysteine and arginine) and either diet type (vegetarian or not) or body mass index, and no significant correlation between levels of the two amino acids and severity of disease. Our work suggests that arginine and cysteine deficiency is not present in women with CTE. Supplementation is unlikely to be of any benefit in nutrient-replete populations and only adds to the cost of therapy.

Adjunctive use of saturated solution of potassium iodide (SSKI) with liposomal amphotericin B (L-AMB) in mucormycosis achieves favorable response, shortened dose and duration of amphotericin: A retrospective study from a COVID-19 tertiary care center.

PURPOSE: Second wave of COVID-19 pandemic was associated with an unprecedented rise in cases of mucormycosis, treatment of which has been challenging owing to the availability and side effects associated with amphotericin. METHODS: All patients presenting with rhino-orbital cerebral mucormycosis (ROCM) following COVID-19 infection between April 2021 to June 2021 were included in this retrospective interventional study. Primary objective was to assess the clinical response with combination of intravenous liposomal amphotericin B (4-5 mg/kg/day) and saturated solution of potassium iodide (SSKI) given orally along with surgical debridement. RESULTS: Twenty-five patients of ROCM were treated with the regimen. Mean age and fasting blood sugar levels were 53.48 years and 239.64 mg/dL respectively. All patients had history of intake of steroids with a mean daily dose of 86.39 mg of prednisolone equivalent. 88% of patients had a "proven" diagnosis of mucormycosis. Cultures were positive in 52% of patients with Rhizopus arrhizus as the predominant species. The mean daily dose of amphotericin received was 268 mg/day with a mean duration of 9.52 days. Mean daily dose of SSKI was 2.57 g. 21 patients (84%) had stabilization of disease at week 8 and achieved cure at the end of treatment whereas the mortality rate was 16%. Factors that significantly affected outcome were eye and central nervous system (CNS) involvement on presentation. CONCLUSION: SSKI, with its remarkably low cost and safety profile, makes it a potential adjuvant drug that may help achieve the twin benefits of shortened duration and dose of LAMB.

Checkerboard Analysis To Evaluate Synergistic Combinations of Existing Antifungal Drugs and Propylene Glycol Monocaprylate in Isolates from Recalcitrant Tinea Corporis and Cruris Patients Harboring Squalene Epoxidase Gene Mutation.

Recalcitrant dermatophytic infections of the glabrous skin (tinea corporis/cruris/faciei) pose a huge challenge to health care systems. Combinations of oral and topical drugs may potentially improve cure rates, but the same has never been objectively assessed for this condition in laboratory or clinical studies. The present study was undertaken with the aim of identifying synergistic combinations of oral and topical antifungals by testing clinical isolates obtained from patients with recalcitrant tinea corporis/cruris. Forty-two patients with tinea corporis/cruris who had failed oral antifungals or had relapsed within 4 weeks of apparent clinical cure were recruited. Twenty-one isolates were identified by sequencing (all belonging to the Trichophyton mentagrophytes/T. interdigitale species complex) and subjected to antifungal susceptibility testing (AFST) and squalene epoxidase (SQLE) gene mutation analysis. Finally, five isolates, four with underlying SQLE gene mutations and one wild-type strain, were chosen for checkerboard studies using various combinations of antifungal agents. Most isolates (n = 16) showed high MICs of terbinafine (TRB) (0.5 to >16 µg/ml), with SQLE gene mutations being present in all isolates with MICs of ≥0.5 µg/ml. Synergistic interactions were noted with combinations of itraconazole with luliconazole, TRB, and ketoconazole and propylene glycol monocaprylate (PGMC) with luliconazole and with the triple combination of PGMC with luliconazole and ketoconazole. In vitro synergistic interactions provide a sound scientific basis for the possible clinical use of antifungal combinations. Hence, these synergistic combinations may be tested for clinical utility in the wake of rising resistance among dermatophytic infections of the glabrous skin.

A case of orofacial granulomatosis evolving into Melkersson Rosenthal syndrome in a child treated with a steroid free regimen of Clofazimine and Minocycline.

Orofacial granulomatosis (OFG) is a rare disorder with varied etiological, immunological and infectious mechanisms implicated and is believed to be a umbrella term which includes Melkersson Rosethal syndrome (MRS). We describe a 17 year old female who was diagnosed with OFG and was successfully treated with a combination of minocycline and clofazimine without oral steroids with significant improvement within 1 month of therapy.

Predicting a therapeutic cut-off serum level of itraconazole in recalcitrant tinea corporis and cruris-A prospective trial.

BACKGROUND: With rising resistance to terbinafine, and consistently high MICs to fluconazole and griseofulvin, itraconazole is being increasingly used as a first line drug for tinea corporis/cruris. However, inadequate clinical responses are often seen with it in spite of in vitro susceptibility. This is possibly related to a variable pharmacokinetic profile of itraconazole. The drug serum levels associated with the therapeutic outcome have not been defined in dermatophytic infections. METHODS: Forty treatment naïve patients with tinea corporis/cruris were randomised to one of the three dose groups (100, 200 and 400 mg/day) of itraconazole. The drug serum levels of 21 of these patients were obtained after 2 weeks of treatment and correlated with the final clinical outcome and in vitro antifungal susceptibility data. RESULTS: Trichophyton indotineae was identified by sequencing of ITS region of rDNA and TEF1α. All isolates were sensitive to itraconazole (Minimum Inhibitory Concentration (MICs) range: 0.06-0.5 µg/ml), while MICs to terbinafine were uniformly high (range 8-32 µg/ml). Thirty-seven patients (92.5%) achieved complete cure, while three failed treatment. Serum levels achieved with 400 mg/day were significantly higher than levels with 100 or 200 mg dose. All patients with itraconazole serum levels of >0.2 µg/ml were cured, while two out of the 10 patients with serum levels <0.2 µg/ml failed treatment. CONCLUSIONS: Therapeutic failures are uncommon with itraconazole, and the prevalent strain in India has low itraconazole MICs. Treatment failure is likely with itraconazole serum levels of <0.2 µg/ml, while levels >0.2 µg/ml are consistently associated with a positive therapeutic outcome.

Hematohidrosis of the mid-face and hands treated with oral oxybutynin.

Hematohidrosis is a rare condition characterized by blood in the sweat. We report a case of hematohidrosis of the mid-face and hands in a 13-year-old girl who was treated successfully with oral oxybutynin and discuss the therapeutic rationale.

Iatrogenic Cushing's syndrome due to topical steroid abuse in a child with Psoriasis presenting as septicaemia.

Psoriasis vulgaris is a chronic inflammatory disorder that affects the skin and joints. Mild disease is treated with topical corticosteroids (CS) which forms the first line of treatment for localized disease. While it is well established that prolonged use of oral or parenteral corticosteroids can lead to iatrogenic Cushing's syndrome and suppression of hypothalamic pituitary axis; development of these complications secondary to use of topical CS is rarely described. Since steroids have anti-inflammatory properties, their prolonged use can lead to increased susceptibility to develop bacterial and fungal infections. We hereby report a 11-year-old female with psoriasis who presented with septicaemia and features of iatrogenic Cushing's syndrome due to treatment with topical corticosteroids for 2 years. Presentation of ICS as septicemia due to topical steroid use in this age group or in a psoriatic patient has not been described in the literature so far. Patient also developed hypertension and osteopenia, which are known adverse effects of corticosteroids; but occur rarely due to topical corticosteroids.

Lichenoid drug reaction due to anti-tubercular therapy presenting as erythroderma.

First-line anti-tubercular therapy (ATT) is very effective in management of tuberculosis and is usually well tolerated. Varied spectrum of cutaneous adverse drug reactions is associated with ATT, of which lichenoid drug eruption (LDR) constitutes approximately 10% of the cases. However, LDR presenting as erythroderma is very rare. Here, we report a case of exfoliative dermatitis secondary to LDR which developed after 5 months of ATT.

A prospective study of anti-mullerian hormone and other ovarian and adrenal hormones in adult female acne.

Polycystic ovarian syndrome (PCOS) diagnosis in adult female acne (AFA) is tough owing to unreliable ultrasonography in virgins or obese females and inconsistent hyperandrogenemia. We analyzed hormones in AFA and established a diagnostic cut-off value of anti-mullerian hormone (AMH) for PCOS. Female acne patients aged ≥25 years were assessed with total testosterone (TT), sex hormone binding globulin (SHBG), free androgen index (FAI), AMH, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Rotterdam's criteria defined PCOS. AMH was measured (Access AMH assay) to calculate the diagnostic cut off value using receiver operating characteristic (ROC) curve. Of 120 cases, 25.83% had PCOS. This group had significant clinical hyperandrogenism, truncal and adolescent acne, polycystic ovarian morphology (PCOM), and raised hormones (AMH, TT, FAI, LH, and LH/FSH). AMH levels were significantly higher in the PCOS group (6.91 ± 3.85 ng/mL) and positively correlated with TT, FAI, 17OHP, LH, and LH/FSH ratio. AMH at >5.1 ng/mL (sensitivity-70.97% and specificity-82.02%) predicted PCOS and correlated with PCOM. AMH (>5.1 ng/mL) is useful for diagnosing PCOS and surrogate for hyperandrogenemia and PCOM. Its correlation with hormones in non PCOS AFA highlights its sensitivity to diagnose endocrinological derangements.

A prospective study on patterns of topical steroids self-use in dermatophytoses and determinants predictive of cutaneous side effects.

Nonprescription use of topical corticosteroids (TCS) is a significant concern. This can lead to cutaneous adverse effects, altered morphology of skin disorders and chronicity of cutaneous infections. To record and analyze the patterns of TCS use in patients with tinea corporis/cruris and analyze factors determining the development of cutaneous side effects. Hundred patients with a clinical diagnosis of tinea corporis/cruris who could recall the TCS preparation/s used were included. The TCS usage patterns were recorded and analyzed. Most patients had used very potent TCS (n = 66). Most reported using TCS intermittently for duration ranging from 1 to 4 weeks (n = 78). Relapse of symptoms occurred within 1 to 2 weeks of stopping TCS, triggering reuse. Cutaneous adverse effects were present in 44 patients (striae [n = 29], hypo/depigmentation [n = 11], skin thinning [n = 8], hypertrichosis [n = 1], tinea pseudoimbricata [n = 1]). There was a significant correlation between presence of cutaneous adverse effects and the total duration of TCS use (P = .0016), duration of disease (P = .016), and total amount of TCS used (P = .012). Use for >60 days and of >32 g were associated with 89% and 96.3% (respectively) probability of developing cutaneous adverse effects. Self-use of TCS is a worrisome trend. Intermittent use is a plausible reason for development of cutaneous side effects in only 44% patients.

Antifungal resistance in dermatophytes: Recent trends and therapeutic implications.

Dermatophytoses or tinea refers to superficial fungal infection of keratinized tissues. Although generally considered easy to treat, recalcitrant infections, presenting as extensive and difficult to treat tinea corporis and cruris, are on the rise in some parts of the world. The situation demands an understanding of the pharmacokinetic and pharmacodynamic properties of the available antifungals against dermatophytes and the possible contribution of drug resistance and other factors to the present scenario. In this review, we provide the readers a comprehensive account of the available literature on in-vitro and in-vivo resistance to clinically used antifungals among dermatophytes. We have also added, in brief, the relevant skin pharmacokinetics of important systemic drugs. The established and postulated mechanisms of drug resistance are discussed and aspects on lack of in vivo correlation of in vitro resistance are presented. Finally, the lacunae in our existing knowledge on the topic and the arenas for future research are highlighted.

Relevant diagnostic implications of the therapeutic challenge with antitubercular therapy in an unusual case of sarcoidosis mimicking lupus vulgaris.

Cutaneous manifestations in sarcoidosis are seen in 25-35% of patients with systemic disease and may be the sole manifestation in few patients. It is known that isolated cutaneous sarcoidosis is a great mimicker and can be easily misdiagnosed as other granulomatous conditions especially lupus vulgaris in regions with high burden of tuberculosis (TB). Here we present a case with cutaneous sarcoidosis who was initially misdiagnosed and treated as bifocal lupus vulgaris with antitubercular therapy (ATT) for 6 months. This nonresponsiveness to therapy prompted us to investigate the patient further for other differentials, failing which a diagnosis of cutaneous sarcoidosis was made and the patient was treated with oral steroids and methotrexate with complete clearance of lesions after 14 weeks of therapy. Our case reemphasizes the value of therapeutic trial of ATT in diagnosis of cutaneous TB and highlights the remarkable clinical mimic of sarcoidosis with lupus vulgaris.

Microcystic lymphatic malformation in a child and his mother.

A 3-year-old boy presented to us with swelling of the right upper lip and the surrounding perioral area with the multiple clear fluid-filled grouped vesicles on the mucosal surface. The patient's mother had a similar swelling located at the same anatomic location extending to the cheek and the ala of nose on the same side. Magnetic resonance imaging and histopathological examination were suggestive of microcystic lymphatic malformation (LM) in both mother and child. Although an autosomal recessive inheritance pattern has been reported for isolated cystic hygromas, no familial case of microcystic LM has been reported previously.

Correlation of In Vitro Susceptibility Based on MICs and Squalene Epoxidase Mutations with Clinical Response to Terbinafine in Patients with Tinea Corporis/Cruris.

Recalcitrant dermatophytoses are on the rise in India. High MICs of terbinafine (TRB) and squalene epoxidase (SQLE) gene mutations conferring resistance in Trichophyton spp. have been recently documented. However, studies correlating laboratory data with clinical response to TRB in tinea corporis/cruris are lacking. For this study, we investigated the clinicomycological profile of 85 tinea corporis/cruris patients and performed antifungal susceptibility testing by CLSI microbroth dilution and SQLE mutation analysis of the isolates obtained and correlated these with the responses to TRB. Patients confirmed by potassium hydroxide (KOH) mounting of skin scrapings were started on TRB at 250 mg once a day (OD). If >50% clinical clearance was achieved by 3 weeks, the same dose was continued (group 1). If response was <50%, the dose was increased to 250 mg twice a day (BD) (group 2). If the response still remained below 50% after 3 weeks of BD, the patients were treated with itraconazole (ITR; group 3). Overall, skin scrapings from 64 (75.3%) patients yielded growth on culture. Strikingly, all isolates were confirmed to be Trichophyton interdigitale isolates by internal transcribed spacer (ITS) sequencing. Thirty-nine (61%) of the isolates had TRB MICs of ≥1 µg/ml. Complete follow-up data were available for 30 culture-positive patients. A highly significant difference in modal MICs to TRB among the three treatment response groups was noted (P = 0.009). Interestingly, 8 of the 9 patients in group 3 harbored isolates exhibiting elevated TRB MICs (8 to 32 µg/ml) and SQLE mutations. The odds of achieving cure with TRB MIC < 1 µg/ml strains were 2.5 times the odds of achieving cure with the strain exhibiting MIC ≥1 µg/ml.

Exploring the combination of SSKI and topical heparin in a case of erythema nodosum migrans.

Erythema nodosum migrans (subacute nodular migratory panniculitis) is an uncommon type of panniculitis characterized by migrating subcutaneous nodules or plaque on the lower extremity. There are a very few cases of Erythema nodosum migrans reported and thus its appropriate treatment modality is not defined. We describe a case of a 30-year-old male with idiopathic erythema nodosum migrans which was manifest centrifugally spreading, slightly morpheaform erythematous plaque on the lower left leg. The patient was diagnosed initially and treated as a case of furunculosis with poor clinical response. The skin biopsy showed features consistent with subacute nodular panniculitis. Saturated Solution of Potassium Iodide along with topical Heparin successfully treated the patient, when the conventional treatment modalities failed. In a morpheaform centrifugally expanded plaque, erythema nodosum migrans should be kept in mind in the differential diagnosis, especially in the lower extremities in cases of unknown etiology.

Complete cure of Fusarium solani sp. complex onychomycosis with Qs NdYAG treatment.

The incidence of non dermatophytic mould (NDM) onychomycosis (OM) has been steadily increasing Fusarium spp is the most common cause of NDM OM in most geographical locations. Fusarium spp and other NDMs are largely resistant to commonly used anti-fungals. The successful use of laser and light based devices has been demonstrated in dermatophytic OM, but there is no previous report of their successful use in any NDM OM. We describe a patient with OM caused by Fusarium solani spp, who was clinically (with a normal appearing nail) and mycologically (with negative microscopy and culture on repeated samples) cured of her infection following treatment with 2 sessions of Qs NdYAG (532nm and 1064nm) given 1 month apart.