Clinical Use of Super Bioavailable Itraconazole for the Management of Dermatophytosis: Consensus Statement by Dermatologists from India via the Modified Delphi Technique.

INTRODUCTION: Super bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as inter-individual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50mg and the United States as 65mg and in India as 50mg, 65mg, 100mg, and 130mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis is insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. METHODS: Sixteen dermatologists, (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ) formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. RESULTS: A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130mg once daily and if not tolerated, 65mg twice daily. The preferred duration for treating naïve dermatophytosis is 4-6 weeks and that for recalcitrant dermatophytosis is 6-8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. CONCLUSION: Expert opinions indicate that overall clinical experience with SB ITZ is better than that with CITZ.

Comparative Efficacy and Safety of Super-Bioavailable Itraconazole-130 mg Once Daily in Obese and Non-Obese Patients of Glabrous Tinea.

Background: Obesity is considered one of the risk factors for dermatophytosis and warrants systemic therapy. Itraconazole is the most commonly used antifungal, but owing to pharmacokinetic challenges, super-bioavailable itraconazole (SITZ) was approved globally, recently. For the management of dermatophytosis in obese patients, there are mixed opinions regarding the dosing of systemic antifungals. Materials and Methods: This study was conducted to compare the efficacy and safety of SITZ-130 mg once daily in glabrous tinea or dermatophytosis in obese and non-obese patients for a total duration of 10 weeks on 87 eligible patients. Efficacy and safety assessments were done at weeks 3 and 6 with follow-up at week 10 for relapse. The primary objective was to assess the proportion of patients achieving complete cure at week 6 with the assessment of safety, clinical, and mycological cure rates as secondary objectives. Results: Out of 87 patients, 80 were considered for analysis. At week 6, 22/35 (63%) and 33/45 (73%) patients in obese and non-obese groups were completely cured (P = 0.47). Similarly, there was no statistically significant difference for mycological and clinical cure in both the groups (P = 0.17 and P = 0.61, respectively). Four patients in the obese group (18% of completely cured), while one patient in the non-obese group (3% of completely cured), relapsed within 4 weeks of completion of treatment (P = 0.14). The therapy was well tolerated by both groups, with only one patient in the non-obese group experiencing pruritus. Conclusion: SITZ-130 mg once daily achieved desired and similar clinical response in obese patients as of non-obese patients suffering from dermatophytosis, and hence, a higher dose may not require in obesity.

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.

Mucocutaneous manifestations of COVID-19-associated mucormycosis: A retrospective cross-sectional study.

Background Cutaneous mucormycosis has shown a significant upsurge during the COVID-19 pandemic. Due to the rapid progression and high mortality of cutaneous mucormycosis in this context, it is important to identify it early. However, very few studies report detailed clinical descriptions of cutaneous mucormycosis in COVID-19 patients. Objectives To describe mucocutaneous lesions of COVID-19-associated mucormycosis based on clinical morphology and attempt to correlate them with radiological changes. Methods A retrospective cross-sectional study was conducted at a tertiary care centre from 1st April to 31st July 2021. Eligibility criteria included hospitalised adult patients of COVID-19-associated mucormycosis with mucocutaneous lesions. Results All subjects were recently recovering COVID-19 patients diagnosed with cutaneous mucormycosis. One of fifty-three (2%) patients had primary cutaneous mucormycosis, and all of the rest had secondary cutaneous mucormycosis. Secondary cutaneous mucormycosis lesions presented as cutaneous-abscess in 25/52 (48%), nodulo-pustular lesions in 1/52 (2%), necrotic eschar in 1/52 (2%) and ulcero-necrotic in 1/52 (2%). Mucosal lesions were of three broad sub-types: ulcero-necrotic in 1/52 (2%), pustular in 2/52 (4%) and plaques in 1/52 (2%). Twenty out of fifty-two patients (38%) presented with simultaneous mucosal and cutaneous lesions belonging to the above categories. Magnetic resonance imaging of the face showed variable features of cutaneous and subcutaneous tissue involvement, viz. peripherally enhancing collection in the abscess group, "dot in circle sign" and heterogeneous contrast enhancement in the nodulo-pustular group; and fat stranding with infiltration of subcutaneous tissue in cases with necrotic eschar and ulcero-necrotic lesions. Limitations The morphological variety of cutaneous mucormycosis patients in a single-centre study like ours might not be very precise. Thus, there is a need to conduct multi-centric prospective studies with larger sample sizes in the future to substantiate our morphological and radiological findings. Conclusions COVID-19-associated mucormycosis patients in our study presented with a few specific types of mucocutaneous manifestations, with distinct magnetic resonance imaging findings. If corroborated by larger studies, these observations would be helpful in the early diagnosis of this serious illness.

Role of Cyclosporine (CsA) in Immuno-dermatological Conditions.

Cyclosporine (CsA) is a calcineurin inhibitor that acts selectively on T cells. It has been used in dermatology since 1997 for its US Food and Drug Administration indication of psoriasis and off-label for various other inflammatory skin conditions, including atopic dermatitis, alopecia areata, urticaria, lichen planus and many others in pediatric, adults as well as in pregnant women. However, clinicians' preferences for management differ, which may have a bearing on the treatment selection. Hence, the purpose of this review is to outline the role of CsA in various skin conditions through consensus statement from six national experts in the field of dermatology.

Therapeutic Inertia in the Management of Psoriasis: A Quantitative Survey Among Indian Dermatologists and Patients.

Purpose: The primary objective of the study was to understand the therapeutic inertia in treatment and management of plaque psoriasis among dermatologists, along with determining the preferred treatment choices for management of plaque psoriasis; it also included the resulting treatment satisfaction among patients. The secondary objective was to identify the gaps in terms of knowledge and attitude among dermatologists and the expectations of patients. Patients and Methods: A multicentre, cross-sectional quantitative survey was conducted among dermatologists and patients with moderate to severe plaque psoriasis across India. The interviews were conducted either face to face or via telephone between September and November 2020, using structured and validated questionnaires based on specific themes. The data obtained were statistically analysed, wherever applicable. Results: Overall, 207 adult patients with moderate-to-severe plaque psoriasis and 303 dermatologists were interviewed. Post experiencing symptoms, 44% of the patients visited general physicians for treatment and there was an average 7.8-month delay by the patients to consult a dermatologist. Approximately one-fourth of patients used home remedies before seeking medical help. One-third of dermatologists used the Psoriasis Area and Severity Index (PASI) for assessing the disease severity. Majority of dermatologists preferred combination therapy for their patients. The lack of quick resolution and side effects were the major reasons for changing the treatment. Overall, only 35% of the patients complied to current treatment. Satisfaction with existing forms of therapies was highest for mild plaque psoriasis (62%) as confirmed by dermatologists, while 52% of the overall patients were satisfied with their therapy. Majority of the patients (64%) affirmed living with plaque psoriasis impacted their lives. Conclusion: This first-of-its-kind survey in India highlighted the gaps in terms of the disease journey between dermatologists and patients. The survey emphasises the need for shared decision-making and may benefit dermatologists in suggestive modifications of the treatment algorithm and disease management in clinical settings.

The Use of Apremilast in Psoriasis: An Indian Perspective on Real-World Scenarios.

Apremilast, an oral phosphodiesterase-4 inhibitor, is approved for use in the management of psoriasis and psoriatic arthritis. Although its efficacy and safety have been well established in clinical studies, in real-world settings, different practice scenarios have been reported. This review paper serves to evaluate clinical real-world scenarios and aspects of treatment for which the information in the literature was considered to be lacking or controversial. Following a literature review, a panel of five dermatologists with expertise in psoriasis considered five scenarios; namely, the positioning of apremilast in psoriasis, its use in difficult-to-treat areas, special conditions and populations, safety, dose titration and dose in maintenance therapy. These were then assessed with psoriasis experts in India using a web-based questionnaire. A total of 28 questions were discussed regarding these scenarios. According to the responses, apremilast is effective in stable mild to moderate psoriasis as monotherapy and in severe psoriasis in combination. Also, a positive response was received with regard to its effectiveness in difficult locations such as the scalp, palms and soles. To reduce adverse effects, prolonged titration therapy over 4 weeks is required and lower doses can be prescribed to maintain remission. Apremilast therapy should be continued for a minimum of 8 weeks once initiated to achieve the desired results, and the total duration of therapy should be about 24 weeks for better efficacy. It is also effective in many other cases, such as obese patients, patients with hepatitis B or C and HIV, or patients on polypharmacy. It was also reported that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. Overall, apremilast is an attractive option for the individualized treatment of psoriasis owing to its favorable safety profile, its ease of oral administration without the need for screening or ongoing laboratory monitoring, and its positive impact on symptoms and lesions in difficult-to-treat areas.

Etiological prevalence and antifungal sensitivity patterns of dermatophytosis in India - A multicentric study.

BACKGROUND: The prevalence of dermatophytes varies with season, geographical area, socio-economic factors and effective management strategies. AIMS: The aim of the study was to assess the prevalence of pathogenic dermatophytes, clinical types of dermatophyte fungal infection, and in vitro antifungal drug susceptibility testing against dermatophytes. METHODS: Three hundred and ninety five patients with dermatophytosis were enrolled from five cities (Mumbai, Delhi, Lucknow, Kolkata and Hyderabad) across India. All patients were subjected to clinical examination and investigations, including potassium hydroxide microscopy, fungal culture and antifungal drug susceptibility testing. RESULTS: Trichophyton rubrum was the most common species identified (68.4%), followed by T. mentagrophytes (29.3%). Within species, T. mentagrophytes was prevalent in humid environmental conditions (Mumbai and Kolkata), whereas T. rubrum was prevalent in noncoastal areas (Delhi, Lucknow and Hyderabad). Tinea corporis (71.4%) and tinea cruris (62.0%) were the common clinical types observed. antifungal drug susceptibility testing data indicated that minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC-90) was lowest for griseofulvin (0.25-3.0 µg/mL). Among oral antifungals, the mean MIC of itraconazole was within the range (0.84 [0.252] µg/ mL), whereas high mean MIC values were reported for terbinafine (0.05 [0.043] µg/mL). Among topical agents, lowest mean MIC values were reported for luliconazole (0.29 [0.286] µg/mL), eberconazole (0.32 [0.251]) µg/mL and amorolfine (0.60 [0.306]) µg/mL. LIMITATIONS: Lack of correlation between in vitro antifungal susceptibility and clinical outcome and absence of defined MIC breakpoints. CONCLUSION: T. rubrum was the most common, followed by T. mentagrophytes as an emerging/codominant fungal isolate in India. Tinea corporis was the most common clinical type of dermatophytosis. Mean MIC of terbinafine was above the reference range, while it was within the range for itraconazole; griseofulvin had the lowest mean MIC. Luliconazole presented the lowest mean MIC values across cities.

Unusual non-trophic ulcerations in leprosy: A case series of 17 patients.

Non-neuropathic ulcers in leprosy patients are infrequently seen, and atypical presentations are prone to misdiagnosis. We evaluated diagnosed cases of leprosy between January 2017 and January 2020 for the presence of cutaneous ulceration, Ridley-Jopling subtype of leprosy, reactions and histologic features of these ulcerations. Treatment was given as WHO recommended multi-bacillary multi-drug therapy. We found 17/386 leprosy patients with non-neuropathic ulcers. We describe three causes - spontaneous cutaneous ulceration in lepromatous leprosy (one nodular and one diffuse), lepra reactions (five patients with type 1; nine with type 2, further categorised into ulcerated Sweet syndrome-like who also had pseudoepitheliomatous hyperplasia, pustulo-necrotic and necrotic erythema nodosum leprosum) and Lucio phenomenon (one patient). Our series draws attention towards the different faces of non-neuropathic ulcers in leprosy, including some atypical and novel presentations.

Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.

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.

Expert consensus on the management of Androgenetic Alopecia in India.

Androgenetic alopecia (AGA), also known as androgenic or pattern alopecia, is a frequently reported disorder that affects both the sexes, with a higher incidence generally reported in men. AGA has immense psychological effects on the patient, irrespective of the age or stage of baldness. This consensus document has been developed taking into account the opinions of leading experts in the field of dermatology. The objective of this article is to provide the dermatologists with an evidence-based platform for choosing efficacious and safe therapy for patients with AGA. This review articulately summarizes the key opinions of the experts on all aspects of treatment for the effective management of AGA.

Expert consensus on the management of Telogen Effluvium in India.

Alopecia, a frequently reported problem, severely impacts the quality of life of patients and is often associated with loss of confidence and low self-esteem. Several conditions such as telogen effluvium (TE), anagen effluvium, diffuse type of alopecia areata, female pattern hair loss, hair shaft abnormalities, loose anagen hair syndrome, and congenital atrichia or hypotrichosis are associated with hair loss. The actual prevalence rate of TE is not reported since most cases are subclinical in nature. Further, since women get more distressed by hair fall and promptly seek treatment, they tend to be over-represented. However, both genders can suffer from this condition if triggering factors are present. This consensus paper was developed by taking into account opinions of renowned experts in the field and is hoped to serve as an evidence-based platform for selecting efficacious and safe therapy for patients with TE. This review presents a synopsis of the key opinions of experts on all aspects of treatment and effective management of this condition.

The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes-A molecular study.

The disease burden of chronic-relapsing and therapy-refractory superficial dermatophytosis dramatically increased in India within the past 5-6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR-ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)-1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte-positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR-ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte-positive showing 151 (93.21%) T mentagrophytes- and 11 (6.79%) T rubrum-positive samples. In this study, we show for the first time a dramatic Indian-wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes "Indian ITS genotype" that might be disseminated Indian-wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.

Diagnosis and Management of Chronic Pruritus: An Expert Consensus Review.

The aim of this study is to formulate the best clinical practice in the diagnosis and management of chronic pruritus (CP). We searched PubMed, EMBASE, Scopus, Web of Science, and the WHO's regional databases, for studies on "Diagnosis and management of chronic pruritus" from January 1, 2014, to July 31, 2015. We included programmatic reports and hand-searched references of published reviews and articles. Two independent reviewers screened articles and extracted data. We screened 87 of 95 studies that contained qualitative data. Avoid: Dry climate, heat, alcohol compress, ice packs, frequent bathing and washing, intake of very hot and spicy food, intake of alcohol, contact with irritant substances, excitement, strain and stress, and allergens. Using: Mild nonalkaline soaps, moisturizers, bathing oils, lukewarm water while bathing, soft cotton clothing and night creams/lotions, relaxation therapy, autogenic training, psychosocial education, educating patients to cope with itching and scratching, and educational programs. Especially use of moisturizers is considered important. In addition, symptomatic treatment options include systemic H1 antihistamines and topical corticosteroids. Symptomatic therapy directed toward the cause (hepatic, renal, atopic, polycythemia, etc.). If refractory or cause is unknown, consider capsaicin, calcineurin inhibitors for localized pruritus and naltrexone, pregabalin, ultraviolet therapy, Cyclosporine for generalized itching. CP is quite frequent finding associated with skin and systemic diseases in the overall population. It is known to significantly affect quality life score of an individual and also adds burden on the health-care cost. A specific recommendation for treatment of CP is difficult as a result of varied and diverse possibility of underlying diseases associated with CP.