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

Super-bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as interindividual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50 mg and the USA as 65 mg and in India as 50 mg, 65 mg, 100 mg, and 130 mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis are insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. 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%. A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130 mg once daily and if not tolerated, 65 mg 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. Expert clinicians reported that the overall clinical experience with SB ITZ was better than that with CITZ.

A single-centre prospective study comparing efficacy and safety of apremilast with cyclosporine in moderate to severe atopic dermatitis.

BACKGROUND: Apremilast regulates several pro-inflammatory signals involved in atopic dermatitis (AD). METHODS: A randomized, open-labelled study was conducted at a tertiary care centre in India. Fifty patients with AD of >1 year duration were randomly assigned in a 1:1 ratio to receive either apremilast (30 mg twice daily after initial titration) or cyclosporine (5 mg/kg/day) for 24 weeks, followed by a 12-week follow-up period. Primary outcome was mean percentage change in Eczema Area and Severity Index (EASI) from baseline to week 24. Secondary outcome measures were proportion of patients achieving EASI 75, EASI 90, ≥2-point improvement in Investigator's Global Assessment (IGA), SCORing Atopic Dermatitis (SCORAD) 75 at week 24 and percentage of patients experiencing ≥1 adverse effect (AEs). RESULTS: Mean percentage change in EASI (standard deviation) was -67.79% [22.44] in the apremilast treatment group and -83.06% [21.20] in the cyclosporine treatment group (p < 0.05). At week 24, 52.38% of patients in the apremilast group and 78.26% in the cyclosporine group achieved EASI 75 (p < 0.05); 14.29% in the apremilast group and 52.17% in the cyclosporine group achieved EASI 90 (p < 0.05) and 80.95% in the apremilast group and 82.60% patients achieved ≥2 point reduction in IGA (p > 0.05). 57.14% of patients achieved SCORAD 75 in the apremilast group and 69.56% in the cyclosporine group (p > 0.05). Mean time taken to achieve EASI 75 in the apremilast group was 4.50 ± 4.62 weeks, while it was 3.96 ± 3.43 weeks in the cyclosporine group (p > 0.05). Incidence of AEs was 28.57% in the apremilast group and 21.74%) in the cyclosporine group. CONCLUSIONS: Apremilast demonstrated lesser efficacy in comparison to cyclosporine; it has the advantage of a favourable safety profile and requires no laboratory monitoring.

Naftifine: A Topical Allylamine for Superficial Dermatophytosis.

Dermatophytosis is a very common public health problem with high prevalence. Dermatophytes are a highly specialized set of filamentous fungi, which are adapted to keratinized tissues of humans and animals. Dermatophytosis is the most common fungal infection worldwide, affecting approximately 20-25% of the world's population. The etiological agents of dermatophytosis, called dermatophytes, change with geography and socioeconomic status. Trichophyton rubrum (T. rubrum) is the prime species for skin and nail infections followed by T. mentagrophytes/ T. interdigital complex. There is a shift from T. rubrum to T. mentagrophytes in India for superficial fungal infections. In order to deal with fungal infections, treatment strategies involve the use of systemic antifungals and/or topical antifungal agents. Naftifine is a synthetic allylamine antifungal first reported in 1974 and in 1985 became the first commercially available allylamine. The highly lipophilic nature of allylamine allows efficient penetration and reasonably high concentrations in the stratum corneum (SC) and hair follicles. Naftifine is fungicidal as well as fungistatic. The higher efficacy rates of allylamines over imidazoles for the treatment of fungal infections, even for months after cessation of treatment, is thought to be due to their fungicidal effect, as well as to potentially greater keratin binding and slower release from the SC. The effectiveness of naftifine is also demonstrated against various bacteria belonging to both gram-negative and gram-positive classes. The antiinflammatory property of naftifine has been reported in various preclinical studies where it has been shown to target the prostaglandin pathway. Naftifine 1 and 2% gel and cream is approved by The United States Food and Drug Administration (USFDA), recently naftifine has been approved in India by the Indian regulatory authority Drug Controller General of India (DCGI) for the treatment of dermatophytosis. Naftifine 2% also appears to be a promising treatment, requiring fewer applications than the 1% formulation. Naftifine appears to be effective in a single dose and has a shorter treatment duration than azoles. Naftifine demonstrated its efficacy and safety in various clinical studies of tinea infections. Naftifine offers a very useful and promising option for treating dermatophytosis.

Long-term efficacy and safety analysis of single cycle of biosimilar rituximab in pemphigus: A retrospective study of 76 patients from India.

Pemphigus poses a therapeutic challenge and rituximab is increasingly used in its treatment. Long-term data regarding efficacy and safety of rituximab in pemphigus is limited. This study was a retrospective analysis of 76 pemphigus patients with primary endpoint being the percentage of patients achieving complete remission (CR) on/off therapy. Secondary endpoints were time to relapse, mean cumulative dose of prednisolone after rituximab infusion, mean duration of follow up, and adverse events to rituximab if any. A total of 62 (82.7%) attained complete remission on/off treatment, out of which 42 were off therapy. Mean interval between rituximab administration and complete remission off treatment was 6.9 ± 3.7 months. Complete remission off treatment was sustained for a mean duration of 21.4 ± 17.8 months before relapse. Over a mean follow-up duration of 42.7 ± 24.9 months (median 41, maximum 83 months), 22 of 62 patients (35.5%) who had achieved complete remission after the first cycle of rituximab relapsed. A mean total cumulative dose of 8716.3 ± 10533.8 mg prednisolone was prescribed over a mean duration of 18.05 ± 15.64 months after the first cycle of rituximab. Adverse events were noted in 18 out of 76 patients (23.7%) which included infusion reactions (n = 3), minor infections (n = 7), transitory disease flare (n = 6), and mortality (n = 2). No statistically significant correlation was found between remission/relapse rates and age, gender or pemphigus subtype. This study substantiates the long-term efficacy and safety of single cycle of rituximab in pemphigus.

Efficacy and safety of basic fibroblast growth factor (bFGF) related decapeptide solution plus Tacrolimus 0.1% ointment versus Tacrolimus 0.1% ointment in the treatment of stable vitiligo.

Vitiligo is common acquired pigmentary disorder affecting skin of 1% of the world population, India 3% to 8% incidences approximately. Treatment is tough challenge. The combination treatments have proven beneficial due to different mechanisms. There is need to find drug targeting different mechanisms of action. Test medicine is decapeptide derived from basic Fibroblast Growth Factor (bFGF) treating vitiligo. The current study was to compare efficacy and safety of BFGF related decapeptide solution plus Tacrolimus 0.1% (M + T) Ointment versus Tacrolimus monotherapy 0.1% (T) Ointment in patients with stable vitiligo. The randomized, open label, comparative, prospective, multicentre study in patients with stable vitiligo was conducted. The primary endpoint was improvement in extent of repigmentation in target lesion after 12 months of treatment from baseline. The secondary endpoints were extent of repigmentation at end of 6 months, patient global assessment (PGA) and safety at end of 6 months. This shows interim analysis results. Total 94 patients were randomized to M + T (n = 40) and T (n = 44), 10 patients were lost to follow up. Extent of repigmentation (>50%) was significantly greater at end of 8 weeks in M + T group 22.5% (p ≤ .05) while 6.8% in T group. In grade of repigmentation, significant difference (p ≤ .05) was observed, M + T had better grade. PGA was significantly greater (p ≤ .05) in M + T-group than T. All these parameters showed significant improvement in M + T-group than group T at end of 6 months. No adverse events were reported during the study. It is an interim analysis report so complete data is not available for analysis. Addition of bFGF related decapeptide solution to Tacrolimus gave better results than Tacrolimus alone therapy. It also has a favorable safety profile and was well tolerated.

Streptococcal pharyngitis, rheumatic fever and rheumatic heart disease: Eight-year prospective surveillance in Rupnagar district of Punjab, India.

BACKGROUND: Rheumatic fever (RF)/rheumatic heart disease (RHD) continue to be a neglected public health priority. We carried out a registry-based control project, prospective surveillance and sample surveys to estimate the burden of disease. METHODS: We trained healthcare providers and established a surveillance system for the 1.1 million population of Rupnagar district in Punjab. In sample surveys conducted among schools, physicians examined the sampled children. Children with a cardiac murmur were investigated by echocardiography. Throat swabs were obtained from a sub-sample, and group A streptococci (GAS) were identified and emm typed by standard laboratory methods. We estimated the morbidity rates for RF/RHD from surveillance data and school surveys using a correction factor to account for under-registration of cases in the registry. RESULTS: A total of 813 RF/RHD cases were registered from 2002 to 2009. Of the 203 RF and 610 RHD cases, respectively, 51.2% and 36.7% were males. In the age group of 5-14 years, RF was more common (80%) than RHD (27%). The prevalence of RF/RHD in 5-14-year-old students was 1.0/1000 (95% CI 0.8-1.3). The school survey indicated that about two-thirds of the RF/RHD cases were enrolled in the hospital-based registries. Based on the school survey, the prevalence of RF/RHD was estimated to be 143/100,000 population. In the registry, the annual incidence of acute RF was estimated to be at least 8.7/100 000 children in the age group of 5-14 years. The prevalence of GAS was 2% (13/656) in children with sore throat and 0.5% (14/2920) among those not having sore throat. Typing of 27 GAS revealed 16 emm types. We estimate that about 1000 episodes of GAS pharyngitis lead to one episode of acute RF. CONCLUSION: RF/RHD continue to be a public health problem in Punjab, India.

Syphilis: Is it Back with a Bang?

Background: Syphilis was brought under control with the advent of penicillin. However, in recent times, a rise in the incidence of syphilis has been reported by Centers for Disease Control and Prevention (CDC). Aim: To study the clinical and epidemiological profile of patients with syphilis attending sexually transmitted infection (STI) clinic at tertiary care center. Materials and Methods: Observational, cross-sectional analysis of sociodemographic, clinical, and investigational data of all syphilis patients visiting STI clinic from August 2019 to July 2021 was done and analyzed. Results: Out of 1330 STI patients that attended the clinic, 15.04% (n = 200) were diagnosed with syphilis, among them 72% (n = 144) were males, and 28% (n = 56) were females, with male-to-female ratio of 2.5:1. Of these 24.5% (n = 49) had primary, 44.5% (n = 89) had secondary, 30.5% (n = 61) had latent, and 0.50% (n = 1) had congenital syphilis. Among secondary syphilis patients, rash was the most common presentation seen in 43 patients, followed by condyloma lata in 30, palmoplantar syphilis in 17, oral mucous patch in 3, and iridocyclitis in 3 patients. Human immunodeficiency virus (HIV) was positive in 16.5% (n = 33). Herpes genitalis was the most common coinfection among 25 patients who were diagnosed with mixed venereal disease. RPR titer was positive in all 200 patients, with 1:16 titer being most common. Conclusion: India is experiencing a new trend in the prevalence of syphilis, mainly due to the changes in risk behavior, misconceptions, and social stigma associated with STIs, improved laboratory diagnosis, and increased public awareness. Particularly secondary and latent stages have shown a rising trend over the past few years. Awareness about safe sexual practices and contraception is very important to control the current resurgence.

A prospective comparative study of efficacy and safety of 15% trichloroacetic acid peel, 35% glycolic acid peel and Q-switched Nd-YAG laser in patients of macular amyloidosis.

Background: The unappealing appearance of skin in macular amyloidosis (MA) interferes with the patient's quality of life, and treating the condition has been challenging. Aims and Objectives: To compare the efficacy and safety of 15% trichloroacetic acid (TCA) peel, 35% glycolic acid (GA) peel, and Q-switched Nd-YAG Laser in MA. Materials and Methods: Open, prospective study was conducted over 2 years, where after fulfilling the criteria, randomization was done into three groups. Group A: 15% TCA peel; Group B: 35% GA peel; Group C: Q-switched Nd-YAG Laser. Procedures were repeated at monthly intervals for six sittings. On each visit, patients were scored on the following parameters: color score, visual analog score (VAS), physician global assessment (PGA) scale, subjective improvement, and adverse effects. Results: A total of 75 patients (25 patients in each group) completed the treatment. The mean age of study-population was 35.68 ± 9.8 years, with female to male ratio of 11.5:1. The mean change in color score (1.68) was more by Group A, followed by Group C (1.4), followed by Group B (1.16). Similar results were noted by subjective improvement, VAS, and PGA. Adverse events were more in Group A, followed by Group C, followed by Group B. No patient showed permanent adverse events. Conclusion: TCA-peel showed superior results over Nd-YAG laser and glycolic-acid peel. TCA-peel being cost-effective with excellent acceptability should be considered a treatment modality.

Clinico- Therapeutic Study of Stevens Johnson Syndrome-Toxic Epidermal Necrolysis and Prognostic Significance of SCORTEN in Indian Patients.

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening dermatological emergencies. SCORTEN (SCORe of toxic epidermal necrolysis) is a validated score to predict mortality; however, there is a paucity of data to determine its usefulness in the Indian population. Objective: To evaluate the accuracy of SCORTEN as a prognostic marker in SJS-TEN. Methods: A prospective observational study was conducted at a tertiary care hospital for two years. SCORTEN was calculated on days one and three of admission. The actual death rates were compared to the predicted rates as estimated by the SCORTEN by standardised mortality ratio analysis (SMR). Results: Of 40 cases included in the study, the mean age was 36.2 ± 14 years (range 11-65) with the male: female ratio being 1.67:1. Antibiotics (37.5%) were the most common group followed by anticonvulsants (22.5%). Comorbidities were observed in 60% of cases, with epilepsy (17.5%) and HIV (human immunodeficiency virus) infection (12.5%) being common. On univariate analysis, heart rate > 120/min, epidermal detachment > 10% BSA, and Se HCO3 (bicarbonate) <20 mmol/L were associated significantly with the death of the subjects (P < 0.05). The observed mortalities were 4.34%, 0, 0 and 80% for SCORTEN 0-1 (3.2%), 2 (12.1%), 3 (35.8%) and 4 (58.3%) respectively when compared to expected mortality. SMR of SJS was 0.69 and of TEN was 1.49. Conclusion: SCORTEN gave an overestimation of mortality in patients with lower scores and an underestimation of mortality in patients with higher scores in our study. Minor refinements based on the study population may increase the predictive accuracy of the original scale.

Delphi Consensus Statement on the Role of Probiotics in the Treatment of Atopic Dermatitis.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczematous lesions. Important factors in the etiopathogenesis of AD include genetic predisposition, epidermal barrier dysfunction, immune dysregulation, and gut and skin dysbiosis. Probiotics could be a potential preventive strategy for allergies including AD through immune system modulation as well as enhancement of the epithelial barrier integrity. To further understand the role of probiotics in the management of AD, a Knowledge, Attitude, and Practices (KAP) survey was conducted. Materials and methods A steering committee comprising nine experts formulated consensus recommendations on the role of probiotics in the management of AD and associated flare-ups through the use of the Knowledge, Attitude, and Practices questionnaire while analyzing literature reviews and responses from a national panel consisting of 175 members. The evidence strength and quality were evaluated based on the Agency for Healthcare Research and Quality (AHRQ) criteria. The acceptance of expert opinions as recommendations was considered upon receiving an endorsement from ≥70% of the panelists, as indicated by a Likert scale. Results The national panel emphasized that the improvement in nutritional status, immunomodulatory properties, and beneficial effects on the gastrointestinal (GI) tract and skin support the use of probiotics in AD. The panel agreed that probiotics should be a part of the complementary therapy in the management of AD and associated flare-ups. Mostly, a probiotics supplementation duration of eight to 12 weeks is preferred by dermatologists. Probiotics, when used as an adjuvant therapy, may serve as a strategy to reduce steroid usage or maintenance therapy in high-risk cases with flares. Conclusion A Delphi-mediated KAP response provides a real-life approach to the use of probiotics in the management of AD. It suggests that probiotics could be useful as an adjuvant therapy in the management of AD and associated flare-ups when used along with traditional treatment.

A Rare Case of Congenital Herpes Simplex Virus Infection with Therapeutic Response to Acyclovir.

A 1-day-old pre-term female child delivered by lower segment cesarean section was referred for hypo-pigmented skin lesions over trunk since birth. After 3 days, the neonate developed vesicles and pustules. The mother gave a history of fluid-filled genital lesions at the 12th week of gestation. The diagnosis of neonatal herpes infection was suspected clinically, which was confirmed by polymerase chain reaction, and the lesions resolved following injectable acyclovir.

The Enigma of Periorificial Desquamating Lesions in a Child.

Biotinidase deficiency (BD) is a rare autosomal recessive, vitamin-responsive inborn error of metabolism associated with a wide spectrum of dermatological, neurological, auditory, and metabolic abnormalities. This case report reiterates that a high index of suspicion in childhood diseases with periorificial desquamation can lead to timely detection and active intervention in BD.

A Prospective, Randomized, Comparative Study of Topical Minocycline Gel 4% with Topical Clindamycin Phosphate Gel 1% in Indian Patients with Acne Vulgaris.

Acne vulgaris is characterized by inflammatory and non-inflammatory skin lesions with a high prevalence among adolescents in India. Not enough studies are reported on the use of topical antibiotics for the management of acne in the Indian population. The proposed study aims to compare the efficacy and safety of topical minocycline gel 4% with topical clindamycin gel 1% in the Indian population. A randomized, open-label, double-arm study was planned at two centers in India. One hundred patients were enrolled and randomized equally to two treatment arms. The drugs were applied once daily, preferably at the same time each day. The number of inflammatory and non-inflammatory lesions, as well as the investigator's global assessment (IGA), were obtained at the baseline and on weeks 3, 6, 9, and 12. The change in these parameters from baseline to week 12 was compared between the two treatment arms. A tolerability assessment was also performed on selected parameters. The age of patients ranged between 14 and 31 years, with female preponderance in each arm. On week 12, the percent change in inflammatory and non-inflammatory lesions in the minocycline 4% arm was significantly higher than in the clindamycin 1% arm (p < 0.0001). The IGA treatment success was significantly higher in the minocycline arm compared to the clindamycin arm on weeks 9 and 12, with p-values of 0.001 and 0.015, respectively. Tolerability assessment revealed significantly improved parameter performance in the minocycline arm compared to the clindamycin arm. On subgroup analysis, in adolescents, minocycline was found to be more efficacious than clindamycin. The comparative assessment resulted in a significantly improved performance of minocycline gel 4% compared to clindamycin gel 1% in the Indian population, thus making it a preferred choice for the treatment of moderate-to-severe acne in India.

Presentation of Hansen's disease as Lucio phenomenon in an Indian male.

Lucio phenomenon is a reactional state described in patients with Lucio leprosy and in a few cases of lepromatous leprosy; it is rarely seen outside Mexico and Central America. We report a case of 35-year old labourer who presented with clinical features classical of Lucio phenomenon without any pre-existing cutaneous nodules or infiltrative lesions of either Lucio or lepromatous leprosy. This case report demonstrates the need to consider Lucio phenomenon in patients presenting with clinical features of medium vessel vasculitis even in areas not endemic for Lucio leprosy.

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.