Cutaneous-immuno-neuro-endocrine (CINE) system: A complex enterprise transforming skin into a super organ.

Skin is now emerging as a complex realm of three chief systems viz. immune system, nervous system, and endocrine system. The cells involved in their intricate crosstalk, namely native skin cells, intra-cutaneous immune cells and cutaneous sensory neurons have diverse origin and distinct functions. However, recent studies have explored their role beyond their pre-defined functional boundaries, such that the cells shun their traditional functions and adopt unconventional roles. For example, the native skin cells, apart from providing for basic structural framework of skin, also perform special immune functions and participate in extensive neuro-endocrine circuitry, which were traditionally designated as functions of cutaneous resident immune cells and sensory neurons respectively. At the cellular level, this unique collaboration is brought out by special molecules called neuromediators including neurotransmitters, neuropeptides, neurotrophins, neurohormones and cytokines/chemokines. While this intricate crosstalk is essential for maintaining cutaneous homeostasis, its disruption is seen in various cutaneous diseases. Recent study models have led to a paradigm shift in our understanding of pathophysiology of many such disorders. In this review, we have described in detail the interaction of immune cells with neurons and native skin cells, role of neuromediators, the endocrine aspect in skin and current understanding of cutaneous neuro-immuno-endocrine loop in one of the commonest skin diseases, psoriasis. An accurate knowledge of this unique crosstalk can prove crucial in understanding the pathophysiology of different skin diseases and allow for generation of targeted therapeutic modalities.

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.

Delay in diagnosis is the most important proximate reason for mortality in hereditary angio-oedema: our experience at Chandigarh, India.

BACKGROUND: Hereditary angio-oedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of nonpruritic subcutaneous and/or submucosal oedema. Laryngeal oedema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for the management of HAE, mortality was as high as 30%. Mortality has significantly declined in countries where first-line treatment options are available and patients can access these therapies. There is a paucity of literature on the outcomes of patients with HAE in developing countries where availability of and access to first-line treatment options are still a challenge. OBJECTIVES: To report our experience on mortality in patients with HAE and to report factors associated with the death of these patients. METHODS: We carried out a record review of all patients diagnosed with HAE between January 1996 and August 2022. Families with HAE who had reported the death of at least one family member/relative from laryngeal oedema were studied in detail. RESULTS: Of the 65 families (170 patients) registered in the clinic, 16 families reported the death of at least one family member/relative from laryngeal oedema (total of 36 deaths). Of these 16 families, 14 reported that 1 or more family members had experienced at least 1 attack of laryngeal oedema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid, while the remaining 35 patients were not diagnosed with HAE at the time of their death. At the time of death of all 36 patients, at least 1 other family member had symptoms suggestive of HAE, but the diagnosis was not established for the family. CONCLUSIONS: To our knowledge, this is the largest single-centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. The delay in diagnosis is the most important reason for mortality.

Emerging role of topical Janus kinase inhibitors in dermatological disorders: a review.

Janus kinase (JAK) refers to a family of tyrosine kinases that are involved in the production of proinflammatory mediators in response to various extracellular signals. The JAK-signal transducer and activator of transcription (STAT) pathway is an appealing target in many inflammatory illnesses as this pathway modulates immune cell activation and T-cell-mediated inflammation in response to several cytokines. The practical considerations of prescription for topical and oral JAK inhibitors (JAKis) in atopic dermatitis, vitiligo and psoriasis have been covered in prior publications. Currently, the US Food and Drug Administration has approved the topical JAKi ruxolitinib for atopic dermatitis and nonsegmental vitiligo. None of the remaining first- or second-generation topical JAKis have been approved for topical application in any dermatological indications so far. For this review, the PubMed database was searched using 'topical' and 'JAK inhibitor' or 'Janus kinase inhibitor' or the names of individual drug molecules as the keyword in the title with no date limits. The description of topical JAKi usage in dermatology from the literature was evaluated in each abstract. The current review concentrates on emphasizing the rising use of topical JAKis in both approved and off-label dermatological applications for both old and novel conditions.

Cross-sectional study to estimate the prevalence and risk factors of nonalcoholic fatty liver disease in children and adolescents with psoriasis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent comorbidity in adult patients with psoriasis, but there is a paucity of data on NAFLD in paediatric patients with psoriasis. AIM: To estimate the prevalence of NAFLD in children and adolescents with psoriasis compared with age- and sex-matched healthy controls (HCs) and to evaluate risk factors for NAFLD in paediatric psoriasis. METHODS: This was a cross-sectional study performed from July 2019 to December 2020 in a single tertiary care centre, which enrolled 52 children/adolescents aged 2-18 years diagnosed with psoriasis at least 6 months previously, and 52 HCs matched for age and sex. Anthropometric, metabolic and radiological assessment was performed for all participants. NAFLD prevalence was determined by liver enzyme (serum glutamic pyruvic transferase) levels, ultrasonography, shear wave elastography and aspartate aminotransferase/platelet index. Multivariate analysis was performed to determine the independent risk factors for NAFLD. RESULTS: The frequency of NAFLD was found to be 28·8% in patients with paediatric psoriasis compared with 3·8% in HCs. Logistic regression showed that greater disease severity (Psoriasis Area and Severity Index ≥ 10), obesity and decreased high-density lipoprotein cholesterol (HDL-C) level were independently associated with NAFLD, and thus can be considered risk factors for NAFLD. CONCLUSION: Patients with paediatric psoriasis have a higher prevalence of NAFLD compared with HCs. Children who are obese or have moderate to severe psoriasis or decreased HDL-C levels are at a higher risk of developing NAFLD.

Comparison between methotrexate and apremilast in Psoriatic Arthritis-a single blind randomized controlled trial (APREMEPsA study).

To compare the efficacy of methotrexate and apremilast in psoriatic arthritis (PsA). This Single blinded (physician), parallel group, randomized controlled trial was conducted at a single centre between October 2019 and December 2020. Adult PsA patients (age > 18 years), fulfilling CASPAR criteria, not on methotrexate/apremilast in last 3 months and never receiving bDMARDs or, JAK inhibitors, having active articular disease (one or more swollen joint or, having one or more tender entheseal point) were recruited. Primary outcome measure was rate of major cDAPSA response at week 24 and secondary outcome measures were ACR 20 response, change in PASI score, Maastricht enthesitis score, Leeds dactylitis index, and health assessment questionnaire-disability index (HAQ-DI) and number of adverse events at week 24 between methotrexate and apremilast groups. A total of 31 patients were recruited (15 in the apremilast arm and 16 in the methotrexate arm) amongst whom 26 patients completed 24 weeks follow up (13 patients in the apremilast arm and 13 patients in the methotrexate arm). Median cDAPSA score at baseline was 23 (9) in the apremilast group and 20 (21) in the methotrexate group. No difference in major cDAPSA response at week 24 was observed between apremilast and methotrexate arm (20% vs. 37.5%; p = 0.433). In the secondary outcome measures, there was no significant differences between both the groups. Both the drugs were safe without any serious adverse events. There was no significant difference between methotrexate and apremilast in terms of efficacy as measured by cDAPSA and ACR20 responses.

Correlation of plasma levels of itraconazole with treatment response at 4 weeks in chronic dermatophytosis: Results of a randomised controlled trial.

BACKGROUND: Itraconazole in varying doses and duration is being frequently used for the management of dermatophytosis. There is a scarcity of studies on the bioavailability of various itraconazole brands available in the market. AIMS AND OBJECTIVES: The aim of this study was to determine the plasma concentration of itraconazole of various brands and its correlation with clinical efficacy in chronic dermatophytosis. MATERIALS AND METHODS: One hundred patients with chronic dermatophytosis with age >18 years were studied at the outpatient clinic of our tertiary care hospital. Plasma itraconazole level was estimated on Week 2 and Week 4 after randomly dividing the patients into Groups A, B and C who received cap itraconazole 100 mg twice a day of innovator, multinational and local generic brands, respectively, for 4 weeks. Both efficacy (cure, partial cure or no cure), safety and recurrence were compared between the three groups. RESULTS: At 4 weeks, number of patients classified as 'cured' were 10/26 (38.4%) in Group A, 5/22 in Group B (22.7%) and 3/21 (14.2%) in Group C (p = .002). Mycological cure rates at Week 4 in Groups A, B and C were 21 (80.8%), 17 (81.0%) and 5 (26.3%), respectively (p = .006). Plasma levels of itraconazole were comparable between the three groups at Week 2 and Week 4. No statistically significant correlation was found between itraconazole levels and treatment response in any of the groups at 4 weeks. Incidence of adverse effects and recurrence rates was also similar among the three groups. CONCLUSION: Cure rates for chronic dermatophytosis were poor with all three itraconazole brands at 4 weeks of treatment. Higher cure rates were obtained with innovator drug as compared to multinational and local generic brands at 4 weeks. Plasma levels of the three drugs were however similar, indicating that factors other than serum bioavailability are at play in determining response of chronic dermatophyte infections to oral itraconazole.

Comparison of overall efficacy and safety of oral versus subcutaneous methotrexate in severe psoriasis.

Subcutaneous (SC) methotrexate (MTX) is considered to be associated with a higher and predictable linear bioavailability as compared to oral MTX. Although various studies have reported SC MTX to be safe and effective in psoriasis, prospective head-to-head comparative trials on oral versus SC MTX are limited. To compare the efficacy and safety of SC versus oral MTX in severe psoriasis. It was a prospective, single-blinded, randomized controlled trial, in 100 eligible, adult patients of severe psoriasis randomized into two groups. Group-A (n = 50) patients were started on oral MTX at a full dose of 0.3 mg/kg/week (maximum 25 mg/week) given for 12 weeks or till achieving PASI90 [90% reduction in Psoriasis Area Severity Index (PASI) from baseline], whichever was earlier and group-B (n = 50) patients received SC MTX in the same dose and duration. MTX was then tapered gradually at 5 mg every 2 weeks and stopped. All patients were followed-up for 24 weeks post-treatment with monthly assessment of PASI and Dermatology Life Quality Index (DLQI) scores. Baseline demographic profiles of patients in both the groups were comparable. The mean ± SD baseline PASI scores were group-A: 15.1 ± 3.2 versus group-B:15.7 ± 3.3 (p = 0.35). The number of patients that achieved PASI90 at or before 12 weeks of treatment was numerically higher in group-B (39/50, 78%) versus group-A (31/50, 62%; p = 0.08) and the time to achieve PASI90 was significantly lesser (p < 0.001).Also, the percentage(%) decline in DLQI was significantly higher in group-B(p = 0.003). The overall side-effect profile was comparable between groups (p = 0.31), but the frequency of gastrointestinal side-effects was significantly less in group-B (p = 0.04). Among those patients who achieved a PASI90 response by week12, relapse rates were comparable during the subsequent 24-week follow-up period [group-A: 12/31 (39%), group-B: 11/39 (28%), and p-value = 0.33]. SC MTX results in a significantly faster achievement of PASI90 and greater reduction in DLQI as compared to oral MTX in patients who are candidates for systemic therapy with a comparable safety profile. CTRI/2018/01/011373, date of registration: 15 January, 2018; trial registered prospectively.

Evolving utility of apremilast in dermatological disorders for off-label indications.

Apremilast, a small molecule that acts by inhibition of the phosphodiesterase-4 enzyme, has been approved by the US Food and Drug Administration for the management of psoriatic arthritis, plaque psoriasis and Behçet disease. The drug has drawn much interest from practising dermatologists in view of its exceptional safety profile and prescription convenience, as evident by the recent surge of literature describing its off-label indications. This review was carried out with the aim of summarizing the literature on off-label use of apremilast in dermatology, in order to guide clinicians regarding currently available evidence. The PubMed database was searched using 'apremilast' as a keyword in the title. Abstracts were individually screened to determine whether there was a description of an off-label use of apremilast in dermatology within the article. Randomized controlled trial data were available for vitiligo, alopecia areata, hidradenitis suppurativa and atopic dermatitis. Case series and case reports describing apremilast were also reviewed. Owing to its broad spectrum of immunomodulatory activity, apremilast may be useful in several chronic inflammatory skin diseases recalcitrant to conventional therapies, either alone or in combination with other drugs. Further studies are needed to establish its role in various dermatological indications.

A multicentric study on dermoscopic patterns and clinical-dermoscopic-histological correlates of basal cell carcinoma in Indian skin.

BACKGROUND: Literature on the dermoscopic patterns of basal cell carcinoma (BCC) in India is limited. AIM: To describe the dermoscopic pattern and dermoscopic-histopathological correlation in a large cohort of patients with BCC from India, with a particular focus on skin of colour (SOC). METHODS: This retrospective study was conducted under the aegis of the Dermatoscopy Society of India. Clinical details were collected, and two lead authors independently analysed dermoscopic images of BCC for a predefined set of characteristics. Histopathological slides/blocks were reviewed, and dermoscopic-histological correlation attempted. RESULTS: In total, 143 patients with BCC and skin phototypes IV-VI were included. The mean largest BCC diameter was 3.10 ± 3.68 cm and there was a significant but weak association between duration and largest dimension of the lesion (Spearman ρ = 0.33, P < 0.01). Nearly half of the cases were diagnosed with pigmented BCC and the most common histological subtype was nodular BCC (37.9%). Dermoscopically, blue-grey dots and arborizing vessels were the most common features (60.0%). Pigmentary changes were found in the majority of cases, and included blue-white veil, blue-grey ovoid nests and maple leaf-like areas. A third of our patients had short linear telangiectasia, polymorphic vessels and regular dotted vessels, and another third exhibited a dermoscopic rainbow effect. Arborizing vessels were significantly more common with micronodular (78.9%) and nodular variants (74.1%, P = 0.05), whereas regular dotted vessels (68.4%, P = 0.04), blue-white veil (84.2%, P = 0.02) were significantly associated with micronodular variant. CONCLUSION: The dermoscopic patterns of blue-white veil and regular dotted vessels are indicators towards micronodular BCC in SOC and can help in prioritizing treatment.

Fibromyalgia influences health-related quality of life and disease activity in psoriatic arthritis.

Fibromyalgia syndrome (FMS) is common in patients of psoriatic arthritis (PsA), but the magnitude of its impact is uncertain. This cross-sectional study evaluated the impact of FMS on health-related quality of life (HRQoL) and disease activity in PsA. Adults classified with PsA (CASPAR criteria) at the rheumatology and dermatology outpatient clinics of PGIMER, Chandigarh, India between January 2014 and June 2015 were recruited. All patients were assessed for FMS using the 2010 ACR criteria. Health-related quality of life was assessed using PROMIS-HAQ, HAQ-pain, HAQ-health and revised fibromyalgia impact questionnaire (FIQR). Disease activity measures (SJC, TJC, BASDAI, enthesitis, dactylitis, PASI) and PROMIS-HAQ were correlated with measures of FMS [FIQR, symptom severity scale (SSS) score and widespread pain index (WPI)]. Multivariate regression analyses were used to identify predictors of PROMIS-HAQ and FMS. Out of 106 PsA patients screened, 102 [50 (49%) females; mean age 43.8 (12.4) years] were included. 19 (18.3%) had FMS. Patients of PsA with FMS had significantly (p < 0.05) higher TJC (14 vs 7), SJC (10 vs 5), BASDAI (6.1 vs 4.1) and enthesitis (53 vs 33%), but no difference in dactylitis, severity of skin disease and disease duration. A significant positive correlation of measures of FMS (FIQR, SSS and WPI) with SJC, TJC and BASDAI was noted. PROMIS-HAQ, HAQ-pain and HAQ-health were significantly worse (p < 0.001) in patients of PsA with coexisting FMS. Presence of FMS was found to be an independent predictor of worse PROMIS-HAQ. Female gender and higher TJC independently predicted presence of FMS. To conclude, FMS is an important contributor towards poor HRQoL in patients of PsA and is associated with higher values of joint disease activity measures.

A multicentric clinical and epidemiological study of chronic and recurrent dermatophytosis in India.

BACKGROUND: There has been an alarming increase in the prevalence of chronic, recurrent and steroid modified dermatophytosis of the glabrous skin in the recent years in India. There is paucity of literature on the magnitude of this major public health problem. OBJECTIVE: To estimate the prevalence of dermatophytosis and clinico-epidemiological features of chronic and recurrent dermatophytosis (CRD) across India and to evaluate the associated risk factors. METHODS: This is a multicentric descriptive cross-sectional study conducted in 13 centres situated across India in two phases during dry and rainy seasons. All consecutive patients presenting with dermatophytosis were screened during the study period of 14 consecutive working days. Patients with CRD of the glabrous skin as per the case definition were included after exclusion of isolated hair and nail infections. Demography, clinical findings and results of potassium hydroxide wet mount were recorded. RESULTS AND CONCLUSION: A total of 41,421 patients were screened, out of which 7174 (17.31%) patients had glabrous dermatophytosis. CRD was observed in 1999 (27.86%) patients with 78.08% and 21.95% of chronic and recurrent dermatophytosis, respectively. Family history was present in 50.03% of patients. History of sharing of fomites was present in 50.37% of them. Synthetic tight clothes were worn by 43.47%, while 50.9% gave history of misuse of topical corticosteroid creams. Multiple site involvement was common (69.58%) with tinea cruris (79.99%) and tinea corporis (75.69%) being the most common clinical types. CRD is associated with sharing of fomites, topical corticosteroid misuse and involvement of multiple sites.

Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India.

BACKGROUND: There is paucity of literature on long-term follow-up of patients with hereditary angioedema (HAE) from developing countries. OBJECTIVE: This study was carried out to analyze the clinical manifestations, laboratory features, and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019. METHODS: Data were retrieved from medical records of Paediatric Immunodeficiency Clinic, Postgraduate Institute of Medical Education and Research, Chandigarh, India. RESULTS: Median age at onset of symptoms was 6.25 years (range 1-25 years), and median age at diagnosis was 12 years (range 2-43 years). Serum complement C4 level was decreased in all patients. All patients had low C1-esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long-term prophylaxis (attenuated androgens or tranexamic acid (TA) or a combination of the 2). Life-threatening episodes of laryngeal edema were managed with fresh-frozen plasma (FPP) infusions. We recorded one disease-related mortality in our cohort. This happened in spite of long-term prophylaxis with stanozolol and TA. CONCLUSIONS: We report largest single-center cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents, and FPP may be used for management of HAE in resource-limited settings.

Sociodemographic characteristics and spectrum of Malassezia species in individuals with and without seborrhoeic dermatitis/dandruff: A comparison of residents of the urban and rural populations.

Seborrhoeic dermatitis/dandruff (SD/D) is a common, persistent, relapsing inflammatory condition affecting the areas rich in sebaceous glands. SD/D is widely prevalent in India but Malassezia species implicated are not well studied. To estimate the prevalence and spectrum of Malassezia species causing SD/D and understand the sociodemographic characteristics of SD/D in rural and urban populations, a total of 200 SD/D patients and 100 healthy controls (HC) from both rural and urban backgrounds were enrolled in this study. SD/D severity was clinically graded as mild, moderate, severe, and very severe. The isolates were identified by phenotypic characters and confirmed by ITS2 PCR-RFLP and sequencing of the ITS region of rDNA. Severe (59%) and very severe (71%) form of SD/D was higher in the rural population compared to the urban population (P = .004). The isolation rate of Malassezia was significantly higher in overall SD/D patients scalp (82%) compared to HC (67%) (P = .005). From the scalp of SD/D patients, M. globosa (36.2%) was predominantly isolated followed by M. restricta (31.3%), M. furfur (15.7%), a mixture of M. globosa and M. restricta (12%) or M. arunalokei (4.8%). Similarly, M. globosa (49.3%) was predominately isolated from the scalp of HC followed by M. restricta (22.4%). M. restricta was significantly higher in the scalp of SD/D patients compared to HC and/or nasolabial fold of both SD/D patients and HC (P = .0001). Our findings indicate that M. restricta has a high association with SD/D. More severe disease frequency was observed in the rural population. PRECIS: Dandruff is associated with Malassezia restricta and very severe cases are higher in rural population, probably due the poor hygiene. Moderate to severe hair loss and itching were strongly associated with dandruff. Use of soaps to cleanse scalp appears to be better than shampoo in preventing dandruff.

Clinical profile, long-term follow-up and outcome of juvenile systemic scleroderma: 25 years of clinical experience from North-West India.

OBJECTIVES: To describe the clinical profile, long-term follow-up and outcome of juvenile systemic scleroderma (JSSc) from a tertiary care referral hospital in North-West India. METHODS: A review of case records was performed and children with JSSc (disease onset <14 years of age) were analysed. Diagnosis was based on the Paediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSSc. RESULTS: Forty patients (28 girls and 12 boys; F:M ratio= 2.3:1) were diagnosed with JSSc (including 22 children with overlap) in the last 25 years. Mean age at symptom onset was 7.75±3.19 years with a mean delay in diagnosis of 2.275±2.09 years. Raynaud's phenomenon was seen in 26/40 (65%) patients at presentation. Lung involvement was noted in 40% patients. Methotrexate was the most commonly used therapy, followed by oral prednisolone. Patients without overlap had higher incidence of cutaneous ulcers as compared to patients with overlap (55% vs. 18%; p-value: 0.01). Patients with overlap required significantly higher oral prednisolone (81% vs. 22%), methotrexate (72% vs. 38%) and hydroxychloroquine (54% vs. 5%) while cyclophosphamide (13% vs. 44%) and azathioprine (9% vs. 44%) were used relatively less in this group. Mortality was 15% at a mean follow-up of 51.75 months. Infections were noted to be the most common cause of death. There was no significant difference in the mortality between patients with and without lung disease or patients with or without overlap. CONCLUSIONS: We describe the largest single-centre cohort with longest follow-up of juvenile systemic scleroderma from India.

Comparison of the efficacy and safety of minocycline and clofazimine in chronic and recurrent erythema nodosum leprosum-A randomized clinical trial.

Management of chronic/recurrent erythema nodosum leprosum (ENL) is challenging. The majority of these patients become steroid-dependent and suffer from the adverse effects of long-term corticosteroid use. Minocycline has shown promising results in a small series of chronic/recurrent ENL patients. The aim of this study was to compare the efficacy and safety of minocycline and clofazimine in patients with chronic/recurrent ENL. In this prospective randomized clinical trial, 60 participants with chronic/recurrent ENL were randomized (1:1) to receive either minocycline 100 mg once daily or clofazimine 100 mg thrice daily for 12 weeks along with prednisolone according to WHO protocol and followed up for 6 months. The outcome measures were mean time for initial control of ENL, proportion of patients having a recurrence of ENL, mean time for recurrence after initial control, additional prednisolone requirement, and frequency of adverse events. Initial control of ENL was achieved earlier in the minocycline group as compared to the clofazimine group (2.97 ± 1.9 weeks vs. 4 ± 1.96 weeks, respectively; p-0.048). The number of participants having ENL flares/recurrences during the study period was comparable in both groups (71.4% in clofazimine vs. 55.2% in minocycline group; p-0.2). The participants in the minocycline group remained in remission for a longer duration after initial control of ENL as compared to the clofazimine group (p-0.001). Mean additional prednisolone dose required for control of ENL flares/recurrences was also comparable in both groups (p-0.09). The minocycline group had fewer side effects than the clofazimine group (p-0.047). Minocycline led to a rapid and sustained improvement of ENL episodes with fewer adverse events showing a superior efficacy to clofazimine.

Dermatoscopic assessment of treatment response in patients undergoing autologous non-cultured epidermal cell suspension for the treatment of stable vitiligo: A prospective study.

There is lack of literature on serial dermatoscopic assessment in patients undergoing non-cultured epidermal cell suspension (NCES) for treatment of stable vitiligo. This prospective study was conducted to evaluate the role of serial dermatoscopy in assessing disease stability and predicting repigmentation rates in vitiligo patients undergoing NCES. Dermatoscopic assessment of target lesions were done at baseline and post-NCES at week 4, 8, 12, 16, and 24. Patches obtaining >90% repigmentation at 24 weeks were categorized to have obtained excellent repigmentation. The dermatoscopic features of target lesions that showed clinical signs of disease activity anytime during the follow-up period were compared to those maintaining clinical stability throughout. Twenty-six vitiligo patients with 52 patches, clinically stable for atleast 1 year were recruited. At follow-up, six patches showed clinical signs of instability. Five patches in the unstable group developed satellite lesions by week 16, compared to none in the stable group (p < 0.05). Excellent repigmentation was achieved in 29 out of 52 patches. Appearance of normal reticular pigment network at 8 weeks was a positive predictor of excellent response (OR = 10.5, CI 1.2-89.7), whereas, altered pigment network at 12, 16, and 24 weeks and telangiectasias at 12 and 16 weeks significantly reduced the odds of excellent repigmentation.

Teledermatology during the COVID-19 pandemic: Experience at a tertiary care centre in North India.

BACKGROUND: Teledermatology has evolved as a valuable option to outpatient visits during the current pandemic. We set up a smartphone-based hybrid model of teledermatology services providing direct care to patients at our center. To analyse patient and physician-experience and acceptability for teledermatology over a 6-month-period, along with clinicodemographic profile of patients. METHODOLOGY: Single-center, retrospective study conducted from May 20, 2020 to October 31, 2020. Patient satisfaction level for teledermatology was assessed on a 4-point scale and compared with the satisfaction level during their previous physical visits prior to COVID-19 pandemic. A physician assessment form was utilised to record the experience of dermatologists while providing teledermatology services. RESULTS: Of 7530 patients registered, a successful consult was provided to 6125 patients (81.34%). Average number of teleconsultations/day rose from 23.60 in May 2020 to 77.96 in October 2020. Mean age of patients availing teledermatology services was 33.60 ± 16.99 years. Average distance to care and travel time were 100.90 ± 171.77 km and 135 ± 222.32 min, respectively. A definitive diagnosis could be ascertained in 5724 patients (93.45%) and in-person visit was recommended to 133 patients (2.2%). Out of 6125 patients, 5229 could be contacted for feedback, 935 (18.18%), 2230 (42.65%), 1749 (33.45%), and 300 patients (5.70%) reported being very satisfied, satisfied, partially satisfied, and unsatisfied, respectively. Of 1914 patients, who had availed in-person OPD facilities prior to the pandemic, 914 patients (49.62%) preferred in-person visits. Of 34 dermatologists surveyed, 88.2% felt comfortable providing teleconsultations and 82.4% felt the need to continue teledermatology services in the upcoming months. CONCLUSIONS: Overall, teledermatology is a valid alternative for in-person dermatology visits during the current crisis; helping with initial triage and further patient management. Further refinement of the process could lead to even more acceptability.

Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry: Protocol standardisation, comparison and database expansion for faster and reliable identification of dermatophytes.

BACKGROUND: Accurate and early identification of dermatophytes enables prompt antifungal therapy. However, phenotypic and molecular identification methods are time-consuming. MALDI-TOF MS-based identification is rapid, but an optimum protocol is not available. OBJECTIVES: To develop and validate an optimum protein extraction protocol for the efficient and accurate identification of dermatophytes by MALDI-TOF MS. MATERIALS/METHODS: Trichophyton mentagrophytes complex (n = 4), T. rubrum (n = 4) and Microsporum gypseum (n = 4) were used for the optimisation of protein extraction protocols. Thirteen different methods were evaluated. A total of 125 DNA sequence confirmed clinical isolates of dermatophytes were used to create and expand the existing database. The accuracy of the created database was checked by visual inspection of MALDI spectra, MSP dendrogram and composite correlation index matrix analysis. The protocol was validated further using 234 isolates. RESULT: Among 13 protein extraction methods, six correctly identified dermatophytes but with a low log score (≤1.0). The modified extraction protocol developed provided an elevated log score of 1.6. Significant log score difference was observed between the modified protocol and other existing protocols (T. mentagrophytes complex: 1.6 vs. 0.2-1.0, p < .001; T. rubrum: 1.6 vs. 0.4-1.0, p < .001; M. gypseum:1.6 vs. 0.2-1.0, p < .001). Expansion of the database enabled the identification of all 234 isolates (73.5% with log score ≥2.0 and 26.4% with log scores range: 1.75-1.99). The results were comparable to DNA sequence-based identification. CONCLUSION: MALDI-TOF MS with an updated database and efficient protein extraction protocol developed in this study can identify dermatophytes accurately and also reduce the time for identifying them.

Immunological response and clinical profile in patients with recurrent dermatophytosis.

BACKGROUND: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host. OBJECTIVES: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis. METHODS: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed. RESULTS: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ+ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17+ cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4+ cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis. CONCLUSIONS: Reduced IFN-γ+ , Th1, IL-17+ and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.