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.

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.

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.

A Clinical-Mycological Study of Dermatophytosis in Western India with Focus on Antifungal Drug Resistance as a Factor in Recalcitrance.

Background: Dermatophytosis have assumed epidemic proportions in India. Antifungal drug resistance solely cannot explain disease magnitude and changing epidemiology. Objectives: Aim of this study was to analyse clinical-mycological aspects of dermatophytosis, and estimate contribution of drug resistance in clinical recalcitrance. Methods: This single-centre observational, cross-sectional, descriptive study was done in tertiary centre of western India after ethical approval, enrolling dermatophytosis patients of all ages and sex. After history and examination, KOH mount and culture in modified SDA medium was done. Culture positive isolates were subjected to E-strip antifungal susceptibility method to test MIC for Terbinafine, Itraconazole, Fluconazole and Griseofulvin. Results: Total 300 patients were included, with mean age of 33.83±27.5 years and male-to-female ratio of 1.22:1; tinea corporis et cruris being commonest, 39.33% (n=118). Only 11.67% (n=35) were treatment naïve, having classical annular morphology. History of topical steroid abuse was found in 81.67% (n=245), with pseudoimbricate lesions in 70.61% (n=173). 86.67% (n=260) had KOH positivity while 83.33% (n=250) had culture positivity: Trichophyton mentagrophytes 45.6% (n=114), followed by Trichophyton rubrum in 34.4% (n=86). A total of 265 patients fit into definition of recalcitrance, from which 12.45%, i.e., 33 isolates showed in-vitro fluconazole resistance. 14.33% (n=43) cases were chronic, 37% (n=111) persistent, 46% (n=138) recurrent while 17% (n=51) had relapse in their disease course. Steroid abuse was the commonest denominator. Conclusion: Role of antifungal resistance in recalcitrant dermatophytosis remains debatable. Stopping steroid abuse, which is often the commonest culprit, with adherence to standard antifungal therapy remains the paradigm in management.

Comparative Efficacy of Super Bioavailable Itraconazole Capsules 50 mg vs 65 mg Twice Daily in the Management of Glabrous Tinea.

Introduction: Owing to pharmacokinetic challenges of itraconazole, super-bioavailable itraconazole (SB) was developed and recently approved in strengths of 50mg and 65mg. But comparative study was lacking between these two strengths in glabrous tinea (dermatophytosis) management. Hence, this study was planned to compare the efficacy of both these strengths in dermatophytosis. Methods: One hundred eligible patients were enrolled in this prospective, randomized, clinical study during May-2022 to September-2022 at tertiary hospital in Ahmedabad in adults. Efficacy and safety assessments were done at week-3 and 6 with follow up at week-10 for relapse. Primary objective was to assess the proportion of patients achieving complete cure at week-6 following treatment in both the groups. Secondary outcomes compared safety, clinical and mycological cure rates. Results: Of the 100 patients enrolled, 98 patients (50 in SB-50mg and 48 in SB-65mg group) included in the final analysis. At week 6, 20 patients (40%) and 30 patients (62.5%) achieved complete cure (p < 0.05) in SB-50mg and SB-65mg groups, respectively. In completely cured patients, relapse was reported in 3 (15%) and 5 (17%) patients of SB-50mg and SB-65mg groups, respectively (p = 1). A significant difference was noted in clearance of symptoms and lesions in SB-65mg group (p < 0.05). Moreover, similar results were also obtained in sub-group analysis of recalcitrant dermatophytosis. Both the treatments were found to be safe and well tolerated with no discontinuation. Conclusion: Study result concluded the superiority of SB-65mg over SB-50mg in terms of cure rate and resolution of symptoms in dermatophytosis management.

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.

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.

A Comparative, Three-Arm, Randomized Clinical Trial to Evaluate the Effectiveness and Tolerability of Bilastine vs Fexofenadine vs Levocetirizine at the Standard Dose and Bilastine vs Fexofenadine at Higher Than the Standard Dose (Up-Dosing) vs Levocetirizine and Hydroxyzine (in Combination) in Patients with Chronic Spontaneous Urticaria.

INTRODUCTION: Though second-generation antihistamines (SGAH) are first-line drugs in chronic spontaneous urticaria (CSU), 50% of patients do not respond to them. In such patients, guidelines recommend either up-dosing of SGAH or combination of different antihistamines. However, the studies comparing these treatment regimens are limited. METHODS: In this comparative, three-arm study, CSU patients were randomized to receive standard dose of either bilastine, fexofenadine, or levocetirizine for 2 weeks. After 2 weeks of treatment, non-responders received double dose of either bilastine or fexofenadine, while hydroxyzine 25 mg once daily was added in the levocetirizine group. Patients were primarily evaluated for improvement in CSU, quality of life, and somnolence. RESULTS: A total of 110 patients with CSU were recruited. At the end of 4 weeks, 33/39, 26/35, and 22/36 patients in the bilastine, fexofenadine, and levocetirizine groups showed improvement in urticaria symptoms. At week 2, there was no statistical difference in urticaria activity score (UAS7) improvement between any of the groups; however, at week 4, there was a statistical difference between the bilastine and levocetirizine groups (p<0.05). Somnolence was significantly lower in the bilastine group (p<0.05). Bilastine was statistically significant (p<0.05) in the improvement of quality of life as compared to both groups. No major adverse events were reported during study period; however, bilastine was associated with significantly lower levels of AEs compared to levocetirizine (p<0.05). CONCLUSION: Two-fold up-dosing of bilastine improves CSU symptoms without compromising safety as compared to two-fold up-dosing of fexofenadine and combination of first- and second-generation antihistamines.

Real-world Efficacy and Safety of Apremilast Monotherapy in the Management of Moderate-to-severe Psoriasis.

INTRODUCTION: Apremilast is the new oral drug in the management of moderate-to-severe plaque psoriasis with well-established effectiveness and safety in long-term clinical trials and a few real-world studies. However, its effectiveness and safety in Indian setup have not been reported yet. MATERIALS AND METHODS: This was retrospective, single-center, longitudinal, observational cohort study where the total study period was 24 weeks. Effectiveness parameters were the proportion of patients achieving psoriasis area and severity index (PASI) 50, 75, 90, and 100 response at week 16 and 24. Safety was measured as the proportion of patients reporting ≥1 adverse event (AE) during the study period. RESULTS: Data of a total of 70 patients were included in our study. At week 16, 76.92%, 41.53%, 15.38%, and 6.15% patients achieved PASI 50, 75, 90, and 100, respectively. At week 24, 81.53%, 58.46%, 29.23%, and 10.76% patients achieved PASI 50, 75, 90, and 100, respectively. Mean percentage reduction in PASI was 67% at week 24 and DLQI score was reduced significantly to 3.4 from mean baseline DLQI score of 10.8 (P < 0.001). 40% of patients reported ≥1 AE during the study period. 5 out of 70 patients discontinued apremilast due to AE. Nausea was most common AE reported by 21.4% patients followed by diarrhea (18.57%), headache (17.4%), vomiting (8%), weight loss (7.69%), myalgia (6.15%), and gastritis (6.15%). Most of the AEs were of mild-to-moderate severity. CONCLUSION: The results of this study support the long-term use of apremilast monotherapy as an efficacious and safe treatment option for the management of moderate-to-severe plaque psoriasis.

Apremilast in People Living with HIV with Psoriasis Vulgaris: A Case Report.

Psoriasis is a chronic papulosquamous skin disease that involves immune-mediated cutaneous inflammation and keratinocyte hyperproliferation. The associated immunosuppression in people living with HIV (PLHIV) with psoriasis poses a challenge to the clinician as therapeutic options are limited. Until now, there have been no documented case of apremilast therapy for HIV-associated psoriasis in India. Here, we report a case of HIV-associated psoriasis who achieved Psoriasis Area and Severity Index (PASI) 100 with apremilast therapy.