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.

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.

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.

Photoaging: Reversal of the Oxidative Stress Through Dietary Changes and Plant-Based Products.

Redox flagging represents all life processes, and maintaining a physiological level of antioxidants is essential for the legitimate working of the cell. Genetics and environmental triggers are two major culminating factors for skin aging, both chronological and photoaging. The latter, however, relies principally upon the level of ultraviolet radiation (UVR) exposure and the skin phototype. Apart from causing DNA damage, UVR also stimulates the receptors present in keratinocytes as well as fibroblasts. This in turn leads to the breakdown of collagen and a breach in the generation of new collagen. It is speculated that the breakdown of collagen in the dermis is ensured by the defective restoration that ultimately hampers the structural integrity of skin, leading to wrinkled and atrophic skin. The skin has an admixture of various endogenous antioxidants that work synergistically with vitamins and minerals to maintain cellular equilibrium. Although, their role in safeguarding the cells against the detrimental effects induced by UVR is still questionable and requires further research. However, the advancement in the biology of skin has led to the development of strategies that aim at skin rejuvenation and retarding the progression of photoaging and its visible signs. Photoaging in this article is reviewed in light of current concepts in pathogenesis and its prevention. In addition, the article focuses on both prevailing and forthcoming treatment strategies primarily through plant-based products that will help slow down the process of photoaging.

Psoriasis: A Primer for General Physicians.

Psoriasis is a multisystem, polygenic, inflammatory condition that typically causes changes in the skin. Although there is a significant genetic component, environmental factors like infections can have a significant impact on triggering the disease. A major part of the pathogenesis of psoriasis is played by the Interleukin (IL) IL23/IL17 axis along with the immune-related cells mainly macrophages and dendritic cells (DCs). Additionally, the role of various cytokines along with the toll-like receptors has also been pointed out in immunopathogenesis. These have been supported by the efficacy of biological therapies including TNF alpha inhibitors and inhibitors of IL17 and IL23. We have summarized the topical as well as systemic therapies for psoriasis including biologics. The article throws light on a few emerging therapeutic options like modulators of sphingosine 1-phosphate receptor 1 and Rho-associated kinase 2 inhibitors.

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 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.

Prevalence of Thyroid Dysfunction in Patients With Hepatitis C.

INTRODUCTION: Hepatitis C has been linked to a multitude of autoimmune disorders, including rheumatoid arthritis, thyroid disease, cryoglobulinemia, immune thrombocytopenic purpura, systemic lupus erythematosus, and Sjögren's syndrome. In this study, efforts were made to draw a parallel between hepatitis C and thyroid dysfunction. METHODS: This case-control study was conducted between June 2020 and March 2021 in the gastroenterology ward of a tertiary care hospital. We enrolled 300 hepatitis C-positive patients in this study through consecutive convenient non-probability sampling. In addition, 300 patients without hepatitis C were signed up as a control group. Blood sampling for thyroid function tests was conducted via phlebotomy from the cubital vein and the samples were dispatched to the laboratory for further study. RESULTS: The control group had more euthyroid patients as compared to patients with hepatitis C (74.6% vs. 89.6%; p-value: <0.01). Hepatitis C patients had more cases of primary hypothyroidism compared to the control group (10.6% vs. 4.6%; p-value: 0.005). Similarly, patients with hepatitis C had a higher prevalence of subclinical hypothyroidism compared to the control group (6.0% vs. 1.3%; p-value: 0.002). CONCLUSION: Hepatitis C patients have a high frequency of thyroid dysfunction, particularly primary hypothyroidism and subclinical hypothyroidism. Therefore, it is important to ensure regular screening for early prognosis and avoid treatment modalities that are known to cause thyroid abnormalities.

Effect of Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 on Acute Watery Diarrhea: A Randomized Double-Blind Placebo-Controlled Study in Indian Children.

PURPOSE: To assess the effect of combination probiotic Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 in outpatient management of acute watery diarrhea in children. METHODS: A randomized double-blind placebo-controlled study was conducted in 180 participants aged six months to five years with acute mild to moderate diarrhea. All were enrolled from six centers across India and centrally randomized to receive S. boulardii CNCM-I 3799 and B. subtilis CU-1 or a placebo along with oral rehydration salts and zinc supplementation. Each participant was followed up for three months to assess recurrence of diarrhea. RESULTS: The mean duration of diarrhea in the probiotic and placebo groups were 54.16 hours and 59.48 hours, respectively. The difference in the duration of diarrhea in those administered with probiotic or placebo within 24 hours of diarrhea onset was 25.21 hours. Furthermore, the difference in duration of diarrhea was 13.84 hours (p<0.05) for participants who were administered with probiotics within 48 hours. There were no significant differences in the stool frequencies between the two arms. After three months, 15% in the probiotic group and 18.5% in the placebo group reported episodes of diarrhea. The mean duration of diarrhea was considerably lower in the probiotic group, 31.02 hours versus 48 hours in placebo (p=0.017). CONCLUSION: S. boulardii CNCM-I 3799 and B. subtilis CU-1 combination was effective in reducing the duration of diarrhea when administered within 48 hours of diarrhea onset. Similarly, it reduced recurrence of diarrhea and its intensity in the subsequent three months.

Study of maternal outcome in referral obstetric cases in a tertiary care centre.

INTRODUCTION: To identify the pattern of Obstetric referral to our hospital and the primary reasons for referral, so as to implement measures to reduce unnecessary referrals and to reduce maternal mortality and morbidity. METHOD: All the referred cases for obstetrics indications above 20 weeks were analysed for cause of referral, their condition and outcome for a period of 6 months from January 2016 to June 2016. RESULTS: According to our study out of a total of 10172 delivered patients, 1014 (9.96%) cases were referred patients. Maximum cases i.e. 713 (70. 3%) were in the age group of 21-30. Most of the cases 678 (66.86%) did not receive any treatment at referral hospital before being referred. Only 27.52% patients were referred with referral slips/chit etc., having adequate information and 40.24% of cases were delayed referrals. 183 (18.04%) patients required intensive care unit admission. CONCLUSION: The present study showed that illiteracy and ignorance of female regarding healthcare requirements and poor infrastructure came out to be a major contributor of poor pregnancy outcome. Timely referral is crucial for a satisfactory maternal and fetal outcome. To reduce the number of unnecessary referrals and to reduce burden on tertiary care hospitals, health care workers should be trained in essential and emergency obstetric care which will help in reducing morbidity and mortality.