A Clinico-Epidemiological Study of Cutaneous Adverse Drug Reactions in a Tertiary Care Centre of Eastern India.

Background: Adverse drug reactions (ADRs) are major problems in the drug therapy. Cutaneous adverse drug reactions (CADRs) are the most common ADRs. The pattern of CADRs differs among various drugs. Aims: To record various morphological patterns of CADRs and their causal relationships among patients attending in a tertiary care centre. Materials and Methods: An observational, cross-sectional, clinical study was conducted for a duration of one and a half years in a tertiary care centre in eastern India. Patients presenting with suspected CADRs were included if drug identity could be ascertained. Clinical profiling and drug history were recorded, and causality assessment was carried out as per the Naranjo scale. Result: The commonest CADR in our study was fixed drug eruption (FDE) 48.61%, followed by SJS-TEN spectrum 16.66%, maculopapular rash 11.11% and so on. Severe cutaneous adverse drug reactions (SCARs) such as SJS, TEN, SJS-TEN Overlap, AGEP and DRESS accounted for 18 cases (25%). The most common culprit drugs were antimicrobials (54.16%), followed by nonsteroidal anti-inflammatory drugs (15.27%) and anticonvulsants (12.5%). Most of the CADRs were in probable category. Conclusion: The pattern of CADRs and the drugs causing them in our study population are similar to some previous studies but somewhat different from most of the previous Indian studies. The incidence of SCARs was significantly higher than in previous other studies in India and abroad.

A Clinico-Epidemiological Study of Fixed Drug Eruption with a Special Focus on the Causative Agent and the Clinical Patterns.

Background: Fixed drug reaction (FDE) is characterized by the development of well-circumscribed, round, erythematous macules and plaques on cutaneous or mucosal surface following ingestion of the offending drug. Aim and Objectives: To study the etiological agents responsible for FDE and to study the clinical patterns of FDE due to different drugs. Materials and Methods: It was a hospital-based observational cross-sectional clinical study. The study period was 24 months. Fifty patients were included. The study was done after a literature search, hypothesis generation, protocol write-up, ethical submission, ethical clearance, patient enrollment, data collection, data analysis, and research. The patients were selected on the basis of the Naranjo scoring system. The patients with a history of combination drug intake were not included in the study. Results: A total of 0.11% patients presented with FDE in the study period. Out of them, 52% of the patients belonged to 20-39 years age group, having sex ratio of 1.6:1. About 64% of the patients presented with multiple lesions, whereas 36% had a single lesion. A total of 46% patients presented with first episode and 54% had recurrent episodes. The mean time intervals of first and subsequent episodes were 6.5 days and 4.3 hours, respectively. Also, 16% patients had a history of herpes infection. Extremities were more affected followed by trunk and mucosa. Fluoroquinolones were the most common etiological agent found in 56% patients having cutaneous (48%) and mucosal lesions (14%). The most common drug was norfloxacin (36%) followed by both paracetamol (12%) and metronidazole (12%). Fluoroquinolones were the most common drugs implicated in bullous lesions and generalized bullous FDE. Limitations: The study population was small and the study was for a limited period of time. Conclusion: The patient should be aware of the offending drug and opt for any alternative agent after visiting the physician.

Socio-cultural and financial issues against breast cancer screening behaviour among eligible Indian women: evidence for action.

PURPOSE: Breast cancer, a common malignancy in Indian women, is preventable and curable upon early diagnosis. Screening is the best control strategy against breast cancer, but its uptake is low in India despite dedicated strategies and programmes. We explored the impact of socio-cultural and financial issues on the uptake of breast cancer screening behaviour among Indian women. METHODS: Breast cancer screening-uptake and relevant social, cultural, and financial data obtained from the National Family Health Survey (NFHS) round 5 were used for analysis. We studied 399,039 eligible females to assess their breast cancer screening behavior and determine the impact of socio-cultural and financial issues on such behavior using multivariable logistic regression. RESULTS: Most participants were 30-34-year-old (27.8%), educated to the secondary level (38.0%), and 81.5% had bank accounts. A third (35.0%) had health insurance, and anaemia was the most common comorbidity (56.1%). Less than 1.0% had undergone breast cancer screening. Higher age, education, urban residence, employment, less privileged social class, and access to the Internet and mass media were predictors of positive screening-uptake behavior (p < 0.05). Mothers of larger number of children, tobacco- and alcohol-users, the richer and having health insurance had negative uptake behavior (p < 0.05). CONCLUSION: A clear impact of socio-cultural and financial factors on breast cancer screening behavior is evident among Indian women. Therefore, apart from the ongoing health system strengthening efforts, our findings call for targeted interventions against prevailing misconceptions and taboos along with economic and social empowerment of women for the holistic success of India's cancer screening strategy.

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.

Use of Janus kinase inhibitors in atopic dermatitis - an update.

Atopic dermatitis is among the cutaneous inflammatory disorders whose pathophysiology is thought to be influenced by the JAK-STAT intracellular signalling system. The effectiveness of systemic and topical Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis has been shown in clinical trials and case studies. At present, oral abrocitinib (Cibinqo), oral upadacitinib (Rinvoq), oral baricitinib (Olumiant) and topical ruxolitinib (Opzelura) have approval from the US-FDA for their use in the treatment of atopic dermatitis. The efficacy and safety of oral and topical Janus kinase inhibitors for the treatment of atopic dermatitis have been reviewed in this article.

Current Burden of Atopic Dermatitis in India: A Systematic Literature Review.

Atopic dermatitis (AD) is a common chronic dermatological condition affecting ~10% of adults and ~20% of the paediatric population in high-income countries. There is a lack of comprehensive understanding of the disease burden of AD in India. In this systematic review, the primary objective was to review epidemiological data on AD in India based on articles published between 2011 and 2021. The secondary objective was to assess the disease burden from economic and quality of life (QoL) perspectives. A literature search was conducted using the PubMed and Google Scholar databases using predefined search strings. Relevant studies published in English on AD between 2011 and 2021 were included. This review included 11 articles, of which nine reported demographic and clinical characteristics. The reported prevalence ranged from 3.1% to 7.21% among the paediatric population, up to 16 years of age. The prevalence of AD ranged from 0.98% to 9.2% in studies including paediatric and adult patients. The cost of medications was reported to be the major contributor to the economic burden associated with AD. Mental illnesses such as depression and anxiety were frequently reported in association with AD. Although AD is a common disorder affecting all age groups, there is a lack of substantial epidemiological data. None of the current studies covers the entire country. Hence, studies with a wider geographic scope covering all aspects of disease burden are required to help clinicians and policymakers to understand the disease burden and devise appropriate preventive and management strategies.

Topical Therapy in Psoriasis.

Psoriasis is a chronic condition that progresses in remitting and relapsing phases. Most of these patients have mild-to-moderate illness, which can be managed with topical medications or could be thought of as continuing therapy after remission. Potential therapeutic efficacy is offered, and systemic treatment's negative side effects are constrained. Topical therapies have recently advanced in tandem with recent advancements in our understanding of psoriasis. To improve the quality of life of patients, appropriate knowledge and application of these topical agents are crucial.

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.

Disease Assessment in Psoriasis.

Researchers are making all out efforts worldwide, to find a serological marker to monitor the disease severity and/or measure efficacy of the drug. There are many potential molecular targets being investigated as a candidate marker. However, till date there has been no significant breakthrough. Thus, various scoring systems have been devised to evaluate the disease severity in psoriasis. In spite of constant revisions of the scores being currently used, from time to time. None of the scores yet satisfy all the validation criteria desired of an ideal scoring system. And this is partly also because of the fact that the psoriasis has such a huge range of clinical variants. Nevertheless, in the recent past, significant progress has been made in this direction.

Biologics and Biosimilars in Psoriasis.

Psoriasis is a chronic, debilitating, relapsing, inflammatory dermatosis, which affects approximately 2-3% of the population. The burgeoning research on pathogenesis of psoriasis has opened up new directions in management of this common condition. The introduction of biologics has given additional elements to the arsenal of psoriatic disease treatments. TNF-α inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, CD-6 inhibitor proved highly efficient and have a good safety profile in numerous clinical trials. Biosimilar drugs are structurally almost similar to their reference biologic and are also made from living organism. Long-term follow-up and post-marketing surveillance are required to understand, long-term efficacy, adverse events of these powerful potent molecules.

Psoriasis and its Association with Metabolic Syndrome.

Psoriasis is a multifactorial, chronic, immune-mediated inflammatory condition. Psoriasis often goes beyond the skin, nails and scalp and involves the eyes (uveitis), joints (arthritis) and several metabolic derangements, as seen in various studies. It is strongly associated with features of the metabolic syndrome (MetS) like hypertension, obesity, dyslipidaemia, type 2 diabetes, insulin resistance and non-alcoholic fatty liver disease. Amongst various skin diseases, MetS has the strongest association with psoriasis. The risk of having MetS is almost doubled in patients with psoriasis as compared to healthy individuals. Both conditions share a common pathophysiological background in terms of genetics, inflammatory markers, lifestyle choices, etc. The association of psoriasis with MetS is clinically important as it influences the prognosis, quality of life and choice of treatment. Systemic conventional drugs should be used with caution in such patients, as their long-term use may contribute to metabolic impairment. The treating dermatologist should be aware of such associations and their implications, and a more holistic approach should be taken to manage psoriasis where equal importance is given to lifestyle and dietary modifications and comorbid conditions, in addition to the pharmacological therapy so as to decrease the burden of the disease for both the patient and the health system.

Morbidity pattern and health-care seeking among women domestic workers: Perspective from an Indian metropolis.

Background: Domestic work being unrecognized as a formal form of occupation in India, workers are often deprived of basic social security, including access to proper health care. Self-negligence coupled with societal neglect makes them vulnerable to injury and a variety of illnesses. Objectives: We aimed to study the morbidity pattern of women domestic workers residing in a slum area of Kolkata, West Bengal, India. Materials and Methods: An observational descriptive cross-sectional study was carried out by interviewing and clinically examining 106 randomly selected women domestic workers. Results: The majority (82.08%) had health complaints: heart burn being most common (40.57%). Musculoskeletal and dermatological issues were common. Anemia (31.25%) was a common prediagnosed morbidity. Pallor (33.96%) and dental caries (31.13%) were common; 50.94% reported workplace injury. Of those having complaints, 77.36% sought health care, 59.43% of whom relied on health facilities. Lack of time (54.05%), felt need (35.14%) and money (21.62%) affected adequate care seeking. Participants with cardiorespiratory complaints tended to visit health facilities significantly more (P < 0.05). Conclusion: Health vulnerabilities and neglectful behavior among domestic workers are evident, making the need to sensitize them about their health risks and ways to overcome such issues very vital. Awareness should also be generated about government health schemes to encourage timely health checkup and necessary intervention.

A Cross-Sectional Study of the Levels of Cytokines IL-6, TNF-α, and IFN-γ in Blood and Skin (Lesional and Uninvolved) of Vitiligo Patients and their Possible Role as Biomarkers.

Introduction: Vitiligo is a multifactorial disorder, most often explained by the autoimmune hypothesis. The objective of this study is to measure the levels of cytokines IL-6, TNF-α, and IFN-γ in the blood and skin (lesional and uninvolved) of vitiligo patients and to compare it with that of age-matched controls. Methods: IL-6, TNF-alpha, and IFN-gamma cytokines were measured with a BioRad 6110 ELISA reader. We compared the levels of these cytokines in generalized versus localized vitiligo and stable versus unstable vitiligo. We also correlated cytokine levels in blood/lesion/uninvolved skin with body surface area (BSA) involvement and Vitiligo Disease Activity (VIDA) scoring. Result: Forty-three participants, each with vitiligo and control, were analyzed. The values of TNF-α and IL 6 in sera were significantly higher in the vitiligo group compared with the controls (p < 0.001), whereas INF-γ was significantly lower in the vitiligo group than the control group. TNF-α, INF-γ levels when compared between blood, lesional skin, and normal skin in all vitiligo patients were found to be significant (p < 0.001). Conclusion: We conclude vitiligo is strongly associated with increased levels of TNF-α and IL 6.

The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry.

BACKGROUND: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). OBJECTIVE: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. METHODS: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. RESULTS: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71-14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4-20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4-59.96], aOR 37.57 [95%CI 1.05-871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16-207.49], aOR 45.75 [95%CI 4.54-616.22]). CONCLUSIONS: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.

Low-dose Oral Minoxidil in the Treatment of Alopecia: Evidence and Experience-based Consensus Statement of Indian Experts.

Alopecia is a highly prevalent condition worldwide including in India. There are different types of alopecia with differing etiology, presentation, and hence treatment. Androgenetic alopecia represents the most common form of hair loss affecting male as well as female population termed as male and female pattern hair loss, respectively. Several treatment options are available for the treatment of alopecia with often unsatisfactory results resulting in psychological distress among such patients. Topical minoxidil is known to be effective in the treatment of alopecia. However, oral minoxidil is not currently approved for the treatment of alopecia. This expert consensus is prepared to provide guidance to the clinicians regarding the use of oral minoxidil in the treatment of alopecia. Extensive literature review was performed to prepare the draft consensus which was then revised based on the suggestions and comments from the experts. The final draft was circulated to the experts for review and approval. This consensus document provides overview of evidence related to oral minoxidil and consensus from the experts for its use in the treatment of minoxidil.

A Cross-Sectional Study to Evaluate the Alteration of Cytokine Expression and Activation of Inflammatory Pathway in Response to NOD1 and NOD2 Signal in Leprosy.

Introduction: Leprae bacilli are identified as foreign by pattern recognition receptors (PRRs) present in the microbes but absent in the host. The Nucleotide oligomerization domain (NOD)-like receptor (NLR) family comprises the nucleotide-binding oligomerisation domain (NOD1 and NOD2) proteins, which are two well-known PRRs. The objectives of this study were to study the expression of cytoplasmic NOD1 and NOD2 in the pathogenesis of leprosy and the serum level of expressed cytokines and to measure the messenger Ribonucleic Acid (mRNA) expression. Methods: Clinically suspected Hansen's patients were analysed for 4 years. Newly diagnosed leprosy patients were considered leprosy disease control (LDC). The cases with active or new lesions and an increase in Bacteriological index (BI) by at least 2 + after 12 months of completion of Multidrug therapy (MDT) were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (healthy control (HC)). enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of five human cytokines in serum, including three pro-inflammatory cytokines (Tumor necrosis factor (TNF)-α, Interferon gamma (IFN-γ) and IL-6), one anti-inflammatory cytokine (IL-10) and one chemokine (IL-8). Quantitative expression of receptor genes (NOD1 and NOD2) and cytokine genes (TNF-α, IFN-γ, IL-6, IL-10 and IL-8) was evaluated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We studied NOD1 and NOD2 expression in the tissues through fluorescence immunohistochemistry. Differential NLR intracellular expression on peripheral blood monocytes (PBMs) and their response to stimulation with specific ligands (lipopolysaccharide (LPS) and muramyl dipeptide (MDP)) were studied. Results: A significant difference in the expression of the NOD1 gene was observed in unstimulated monocytes of the LDC and LDR cases when compared to HC. The NOD2 transcript level was significantly higher in stimulated monocytes from LDC and LDR patients than in similarly stimulated cells from HC. The LDC patients had a significantly higher level of pro-inflammatory cytokines as compared to the HC. Conclusion: In conclusion, this study has demonstrated the expression of both cytokines and chemokines in response to NLR activation in the skin of leprosy patients.

Real-World Indian Experience of Switchover to Bilastine 40 mg/day in CSU Patient Refractory to Other Antihistamines at Double Dose.

Background: Although second-generation antihistamines (SGAHs) are recommended as first-line drugs in chronic spontaneous urticaria (CSU), symptom relief has been reported in <50% of patients at licensed doses and up to fourfold dosing is recommended for these patients. Bilastine (SGAH), at licensed doses and higher doses, is efficacious in CSU. However, large-scale real-world data is scarce. Objectives: To report the real-world evidence of the safety and effectiveness of bilastine at a double dose (40-mg per day) in CSU management. Materials and Methods: In this retrospective questionnaire-based study carried out from February 2022 to July 2022, a pre-validated questionnaire was used to gather data on patients with CSU in dermatology practice from 62 centres across India. Adult patients of either gender diagnosed with CSU and switched over to bilastine 40 mg/day due to a non-satisfactory response (UCT score <12) to other antihistamines at double dose were considered for analysis. Based on UCT scores, patients were classified as responders (UCT ≥12) and non-responders at follow-up assessment at 2 weeks as compared to baseline. Results: 177 patients with a mean disease duration of 2.11 ± 1.48 years were included in the final analysis, with 53% females and 47% males. At the end of two weeks, 74/177 (42%) patients were classified as responders, and 103/177 (58%) were non-responders to Bilastine 40 mg/day. The mean change of UCT score from 5.0 ± 2.2 at baseline to 8.08 ± 5.41 (62% improvement) was significant (P < 0.001). Sedation was reported by ten patients without any discontinuation of treatment. Conclusion: Bilastine 40 mg/day was effective and well-tolerated in controlling CSU symptoms refractory to antihistamines at double doses.

Intermittent or Sequential Topical Tacrolimus in Atopic Dermatitis: Systematic Review and Meta-Analysis.

Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an immunomodulator), belongs to the class of calcineurin inhibitors, with promising efficacy in AD. We performed this systematic review to obtain an up-to-date coverage map of controlled clinical trials of sequential or intermittent treatments with TCI as a therapeutic intervention for AD. Articles of interest were retrieved from PubMed, Google Scholar, and EMBASE published between between January 2000 and March 2023. Key words were "calcineurin inhibitors," "corticosteroids," "atopic dermatitis," "pruritus," "sequential," "intermittent" and "consecutive" while fixed language search consisted of "Intermittent topical calcineurin inhibitors AND topical corticosteroids AND atopic dermatitis OR eczema" AD patients who were administered sequential and/or intermittent applications of TCI for management of atopic eczema were included. Outcome measures included but were not limited to Scoring of Atopic Dermatitis (SCORAD) and the Eczema Area Severity Score (EASI). Four clinical trials were considered for the purpose of review. A total of 101 patients with AD were analysed. The risk of bias was low in two studies, while the other two had an unclear risk of bias. Overall, pooled data from two trials revealed that sequential therapy with TCS/TCI was comparable to monotherapy or emollients, as the test for overall effect determined was non-significant with a p-value of 0.33. The two studies were highly heterogeneous, as indicated by a very high I2 of 92% and an extremely significant p-value (p=0.0005). Sequential therapy with TCS and TCIs was effective and well tolerated in the management of AD and it may be considered an important treatment approach during the initial period.