Whole-body and targeted narrowband ultraviolet B phototherapy effectively stabilize acral vitiligo with negligible repigmentation beyond wrists and ankles: Results from a split-body randomized controlled trial.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy promotes stability and repigmentation in vitiligo. No studies have compared targeted NB-UVB with whole-body NB-UVB in treatment of acral vitiligo. OBJECTIVES: This randomized split-body study compared whole-body NB-UVB with targeted NB-UVB in inducing stability and repigmentation in acral vitiligo. METHODS: Thirty-two patients with bilaterally symmetrical acral vitiligo lesions (distal to elbows and knees) were recruited. Patients received whole-body NB-UVB treatment, with one hand and one foot shielded until elbow and knee, followed by targeted NB-UVB treatment on the shielded side. Patients were assessed at 4-week intervals for 24 weeks using Vitiligo Disease Activity (VIDA) score, Vitiligo Skin Activity Score (VSAS), Vitiligo Area Scoring Index (determined through fingertip method, using the method to calculate facial-VASI) and degree of repigmentation. RESULTS: After 12 weeks, 87.5% of patients achieved a VIDA score of 3, with none having active disease at 24 weeks. Over 50% repigmentation was observed in 42.2% and 37.5% of limbs in whole-body and targeted groups, respectively (p = .95). No improvement in F-VASI scores of hands and feet (distal to wrist and ankles) was noted with either modality over the 24-week period. CONCLUSION: Our study showed comparable repigmentation rates between whole-body and targeted NB-UVB groups. Limited effectiveness of phototherapy in repigmentation of hands and feet underscores an important therapeutic gap.

A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Background: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. Objective: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. Methods: This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. Results: C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. Conclusions: IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

A prospective observational study validating the CET score as a screening tool in suspected DRESS syndrome.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic severe cutaneous adverse reaction that may be potentially life-threatening. Recently, a simple scoring system for the early screening of DRESS patients was derived by combining hsCRP levels, the eosinophil count, and the total body surface area (CET score). The objectives of this study were validating the CET score, and calculating its lead time advantage and cost-benefits compared to RegiSCAR scoring. METHODS: This is a prospective observational case-control study, where 110 consecutive patients diagnosed with drug-induced maculopapular exanthema (MPE) were recruited during the 18 months of the study period. Patients were classified as cases (DRESS) and controls (MPE) using RegiSCAR score cut-off 2 (possible DRESS). They were also simultaneously screened using the CET score, based on which patients were classified as positive or negative. They were subsequently followed up on Day 15 for a second comparison and assessment of lead time and at 3 and 6 weeks to evaluate clinical response. RESULTS: Seventy cases and 40 controls were recruited. At a cut-off of >2.12, the CET score had a sensitivity of 94.3%, a specificity of 60%, a positive predictive value (PPV) of 80.5%, and a negative predictive value (PPV) of 85.7%. The median delay in diagnosing DRESS using RegiSCAR was around 14.5 hours. There was a median cost benefit of 12.1 USD in favor of the CET score. CONCLUSIONS: The CET score had good diagnostic performance in screening DRESS patients with a lead time of 14.5 hours and fewer costs incurred.

Delays in diagnosis is the commonest proximate reason for mortality in hereditary angioedema: our experience at Chandigarh, India.

BACKGROUND: Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of non-pruritic subcutaneous and/or submucosal edema. Laryngeal edema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for management of HAE, the mortality used to be as high as 30%. The mortality has significantly reduced in countries where first-line treatment options are available and patients can access these therapies. There is paucity of literature on the outcomes of patients with HAE in developing countries where availability and access to first-line treatment options is still a challenge. OBJECTIVE: To report our experience with mortality in patients with HAE and to report factors associated with death of these patients. METHODS: We carried out a record review of all patients diagnosed to have HAE between January 1996 and August 2022. Families with HAE who had reported death of at least one family member/relative because of laryngeal edema were studied in detail. RESULTS: Of the sixty-five families (one hundred and seventy patients) registered in the clinic, sixteen families reported death of at least one family member/relative because of laryngeal edema (total thirty-six deaths). Of these sixteen families, fourteen families reported that one or more family members had experienced at least one attack of laryngeal edema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid while remaining thirty-five patients were not diagnosed to have HAE at the time of their death. At the time of death of all thirty-six patients, at least one other family member had symptoms suggestive of HAE but the diagnosis was not established for the family. CONCLUSIONS: This is the largest single centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. Delay in diagnosis is the commonest reason for mortality.

Covid-19 Vaccination and Chronic Urticaria: A Paradigm Study.

Background: Multiple vaccines were introduced during 2020-2021 to combat Covid-19 pandemic, being one of the successful vaccine programmes in the present era. Very few studies are available on status of chronic urticaria (CU) post Covid-19 vaccination. Aim: The aim of this study was to study effect of Covid-19 vaccination on our urticaria cohort. Materials and Methods: In this retrospective study, case records of CU patients registered in urticaria clinic, who had received any type of Covid-19 vaccine during the interval of March 2021-2022 were retrieved. Patients were classified as 'vaccine induced urticaria' (VIU) when CU developed for first time post-vaccination and 'vaccine exacerbated urticaria' (VEU) when administration of vaccine exacerbated disease activity in previously diagnosed CU. Results: Overall, 353 CU patients registered with us during this period, 265 had received atleast one dose of a Covid-19 vaccine, of which 12 reported VEU (ten of whom had received adenovirus vector vaccine), and three patients were diagnosed with VIU (all had received inactivated virus vaccine). Mean vitamin D3 levels were significantly higher in patients who had VEU as compared to those CU patients without exacerbation (p = 0.003). Significant correlation was observed between level of concern regarding adverse effects of vaccination, pre-vaccination, and post-vaccination urticaria activity score (UAS-7), (Pearson correlation coefficient = 0.66, P = 0.007) in both VEU and VIU. Urticaria symptoms were controlled in 75% and 66.6% patients, respectively, of VEU and VIU, after one month of initiating standard antihistamine treatment. Conclusion: Hence, we conclude that though Covid-19 vaccines can trigger CU, standard treatment protocols control disease activity in most patients.

Management of hereditary angioedema in resource-constrained settings: A consensus statement from Indian subcontinent.

Hereditary angioedema (HAE) is an uncommon disorder characterized clinically by recurrent episodes of nonitchy subcutaneous and/or submucosal swellings. The estimated prevalence of HAE is ~ 1: 10,000 to 1: 50,000. There are no prevalence data from India, however, estimates suggest that there are 27,000 to 135,000 patients with HAE in India at present. The majority of these, however, remain undiagnosed. Replacement of plasma-derived or recombinant C1-esterase inhibitor (C1-INH) protein, administered intravenously, is the treatment of choice during the management of acute episodes of angioedema (i.e., "on-demand treatment") and is also useful for short-term prophylaxis (STP) and long-term prophylaxis (LTP). This has been found to be effective and safe even in young children and during pregnancy. Until recently, none of the first-line treatment options were available for "on-demand treatment," STP or LTP in India. As a result, physicians had to use fresh frozen plasma for both "on-demand treatment" and STP. For LTP, attenuated androgens (danazol or stanozolol) and/or tranexamic acid were commonly used. These drugs have been reported to be useful for LTP but are associated with a significant risk of adverse effects. Intravenous pd-C1-INH, the first-line treatment option, is now available in India. However, because there is no universal health insurance, access to pd-C1-INH is a significant challenge. HAE Society of India has developed these consensus guidelines for India and other resource-constrained settings where plasma-derived C1-INH therapy is the only available first-line treatment option for the management of HAE and diagnostic facilities are limited. These guidelines have been developed because it may not be possible for all patients to access the recommended therapy and at the recommended doses as suggested by the international guidelines. Moreover, it may not be feasible to follow the evaluation algorithm suggested by the international guidelines.

Chronic spontaneous urticaria and metabolic syndrome: a relationship conundrum.

Chronic spontaneous urticaria (CSU) and metabolic syndrome (MetS) are associated with low-grade inflammation. Despite intensive research and various hypothesis, there is lack of specific pathomechanisms of urticaria. Previous studies have suggested low-grade inflammation in obesity which may be linked to urticaria. However, there is limited literature on association of MetS and CSU. So, this study was conducted to evaluate the association of MetS and its components in patients with CSU. This was a hospital-based and cross-sectional cohort study in which 481 patients of CSU and 240 age- and gender-matched controls were recruited. MetS was defined using the revised National Cholesterol Education Program Adult Treatment Panel III. BMI, waist circumference, blood pressure, fasting blood sugar, plasma insulin, and lipid profile were measured after overnight fasting. Pearson's Chi-squared test was used to calculate significance. Logistic regression analysis was done to assess MetS as a predictor of CSU. All patients were started on antihistamines according to the severity of the disease. CSU patients comprised 220 men (45.7%) and 261 women (54.3%) with 97 patients (20.12%) qualifying criteria for metabolic syndrome compared with 73 (30.42%) controls without any significant difference (p = 0.177). CSU was significantly associated with a higher prevalence of central obesity (p = 0.003) but CSU patients with central obesity did not have a higher urticaria activity score (p = 0.727) or serum IgE levels (p = 0.359). In conclusion, our study found an increased association of central obesity with CSU that was not related to the severity of urticaria. This is of significance as obesity is the most prevalent and first component of MetS to be developed. There was no increase in the overall prevalence of MetS in patients with CSU. The increased association of obesity and urticaria in our study can be partially explained by the role of antihistamines in modulation of metabolic pathway and appetite. Future research into the same can give better insights and thus can aid in better management options in CSU patients.

Extramammary Paget's disease of vulva and metastatic adenocarcinoma: A rare conundrum.

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma. To increase awareness and knowledge regarding this rare dermatosis, we hereby reported a case of ulcerated plaque on genitalia.

Altered levels of lymphocyte enhancer-binding factor-1 modulates the pigmentation in acral and non-acral lesions of non-segmental vitiligo patients: a follow-up-based study in North India.

BACKGROUND: Lymphocyte enhancer-binding factor-1 (LEF1) is responsible for melanocyte proliferation, migration and differentiation and its downregulation may result in depigmentation in vitiligo. Narrowband UVB (NB-UVB) phototherapy is known to enhance melanocyte migration from hair follicles to lesional epidermis; hence, it may have a role in the upregulation of LEF1. OBJECTIVES: We intended to assess the expression of LEF1 both before and after NB-UVB therapy and correlate it with the extent of re-pigmentation. MATERIALS AND METHODS: In this prospective cohort study, 30 patients of unstable non-segmental vitiligo were administered NB-UVB phototherapy for 24 weeks. Skin biopsies were obtained from acral and non-acral sites in all patients, both prior to initiation and after completion of phototherapy and LEF1 expression was measured. RESULTS: Amongst the 16 patients who completed the study, at 24 weeks, all patients achieved > 50% re-pigmentation. However, > 75% re-pigmentation was achieved in only 11.1% of acral patches, whereas it was achieved in a significantly higher number of non-acral patches (66.6%) (p = 0.05). A significant increase was observed in the mean fluorescent intensity of the LEF1 gene in both acral as well as non-acral areas at 24 weeks as compared to baseline (p = 0.0078), However, no difference was observed between acral and non-acral lesions in the LEF1 expression at 24 weeks or the change in LEF1 expression from baseline. CONCLUSION: LEF1 expression modulates the re-pigmentation of vitiligo lesions after treatment with NBUVB phototherapy.

Biologicals in Treatment of Chronic Urticaria: A Narrative Review.

Chronic urticaria is a common inflammatory skin disease affecting around 0.5-1% of the world's population. The disease has a chronic indolent course which significantly affects the patient's quality of life. Urticaria pathogenesis involves cross-linking of immunoglobulin E (IgE) on mast cells causing degranulation which occurs by various pathways which leads to development of wheals and angioedema. The first-line treatment for chronic urticaria is non-sedating second-generation H1 antihistamines (AHs). After the advent of anti-IgE monoclonal antibody omalizumab, the response rate in resistant urticaria has improved significantly without any major adverse events. Other biologicals such as anti-IgE, anti-IL-5, anti-IL-1, anti-IL-17, and anti-CD20 monoclonal antibodies are under trial. These biologicals have better efficacy and safety profile as compared to conventional immunosuppressants. Even with the advances in the last decade, recurrence after stopping the therapy is common, and there is a need for better understanding of the pathogenesis and the drugs acting on the key pathways involved in urticaria. In this review, we provide the role of several biologicals in the treatment of chronic urticaria.

A randomized, open-label study to compare two different dosing regimens of oral tranexamic acid in treatment of moderate to severe facial melasma.

Oral tranexamic acid (TXA) demonstrates promising results in melasma management. However, no clear consensus on the dosing and duration of maintenance doses of TXA therapy in melasma exists. In this study, we intend to evaluate and compare the efficacy of two different TXA dosing regimens in patients with melasma using the mMASI score. This was a randomized, open-label study wherein 50 patients (age > 18 years) with moderate to severe melasma were randomized into group A (250 mg TXA twice a day) and group B (500 mg TXA twice a day). Treatment was administered for 12 weeks and later followed up 4-weekly for next 12 weeks. The primary outcome measure was proportion of patients achieving 75% reduction in modified Melasma area and severity index (mMASI-75) at 12 weeks from baseline, reduction in mMASI and melasma quality of life (MelasQOL) score at 12 and 24 weeks. To assess the rate of relapse by end of 12 weeks post-treatment. Among 50 patients, proportion of patients achieving mMASI-75 at 12 weeks were 20% and 25% in group A and B, respectively (p-0.71). Both groups showed a significant reduction in mean mMASI (4.8 ± 2.2 in group A and 6.8 ± 3.4 in group B; p-0.02) at 12 weeks of treatment. mMASI remained stable after 12 weeks of follow-up and was 4.9 ± 2.43 and 4.93 ± 2.85 in group A and B, respectively (p-0.97). The mean percentage reduction in MelasQOL in group A and B were 41.8 ± 15.3 and 29.5 ± 21.5, respectively (p-0.03). No adverse effects were observed in both groups. Relapse rates was very less and comparable between both groups. Thus, we conclude that both dosing regimens showed comparable efficacy in terms of mMASI reduction at 12-weeks and the improvement achieved was well maintained even after 12-weeks of discontinuing treatment with very few patients relapsed. Hence, lower doses of TXA are equally effective and safe compared to higher doses and not all patients might require tapering or dosing maintenance.

A prospective observational study to sequentially determine the dermoscopic features of vitiligo and its association with disease activity in patients on medical treatment: Dermoscopy and disease activity in vitiligo.

Prospective data on correlation between dermoscopic features of vitiligo and disease activity are scarce. This study was conducted to sequentially determine the dermoscopic features of vitiligo and to evaluate their association with disease activity. A cohort of 30 patients with 60 active vitiligo patches on medical therapy was subjected to sequential clinical and dermoscopic examination at four weekly intervals till 16 weeks. Disease activity at each visit was assessed using serial clinical photographs and modified vitiligo activity severity index. The dermoscopic images were merged and analysed for a predefined set of dermoscopic parameters by two blinded dermatologists. Paired analysis of dermoscopic features was done between baseline, and stabilized vitiligo patches at 12 and 16 weeks. Pigment network changes (absent and reduced pigment network, p < .001), perifollicular depigmentation (p = .02), ill-defined margins (p = .04) and satellite lesions and micro-Koebner phenomenon (p < .001) were associated with active vitiligo while perifollicular repigmentation (p < .001) was associated with stabilizing and repigmenting vitiligo. Satellite lesions and micro-Koebner's phenomena were suggestive of unstable disease irrespective of site of target lesion, while perifollicular repigmentation was suggestive of stabilized/repigmenting disease only at non-acral sites. We found sequential dermoscopy to be useful to assess disease activity and potential for repigmentation in localized vitiligo.

A Delphi consensus on the nomenclature and diagnosis of lichen planus pigmentosus and related entities.

BACKGROUND: Although well known in clinical practice, research in lichen planus pigmentosus and related dermal pigmentary diseases is restricted due to lack of consensus on nomenclature and disease definition. AIMS AND OBJECTIVES: Delphi exercise to define and categorise acquired dermal pigmentary diseases. METHODS: Core areas were identified including disease definition, etiopathogenesis, risk factors, clinical features, diagnostic methods, treatment modalities and outcome measures. The Delphi exercise was conducted in three rounds. RESULTS: Sixteen researchers representing 12 different universities across India and Australia agreed to be part of this Delphi exercise. At the end of three rounds, a consensus of >80% was reached on usage of the umbrella term 'acquired dermal macular hyperpigmentation'. It was agreed that there were minimal differences, if any, among the disorders previously defined as ashy dermatosis, erythema dyschromicum perstans, Riehl's melanosis and pigmented contact dermatitis. It was also agreed that lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis did not differ significantly apart from the sites of involvement, as historically described in the literature. Exposure to hair colours, sunlight and cosmetics was associated with these disorders in a significant proportion of patients. Participants agreed that both histopathology and dermatoscopy could diagnose dermal pigmentation characteristic of acquired dermal macular hyperpigmentation but could not differentiate the individual entities of ashy dermatosis, erythema dyschromicum perstans, Riehl's melanosis, lichen planus pigmentosus and pigmented contact dermatitis. LIMITATIONS: A wider consensus involving representatives from East Asian, European and Latin American countries is required. CONCLUSION: Acquired dermal macular hyperpigmentation could be an appropriate conglomerate terminology for acquired dermatoses characterised by idiopathic or multifactorial non-inflammatory macular dermal hyperpigmentation.