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.

Prescribing practices of tranexamic acid for melasma: Delphi consensus from the Pigmentary Disorders Society.

Introduction There is ambiguity regarding usage of tranexamic acid for melasma in India, be it in its pre-administration evaluation, administration route, dosing or monitoring. Hence, we conducted this study to understand various tranexamic-acid prescribing patterns and provide practical guidelines. Materials and methods A Google-form-based questionnaire (25-questions) was prepared based on the key areas identified by experts from the Pigmentary Disorders Society, India and circulated to practicing dermatologists across the country. In rounds 2 and 3, the questionnaire was re-presented to the same group of experts and their opinions were sought. The results of the practitioners' survey were denoted graphically alongside, to guide them. Consensus was deemed when at least 80% of respondents chose an option. Results The members agreed that history pertaining to risk factors for thromboembolism, cardiovascular and menstrual disorders should be sought in patients being started on oral tranexamic-acid. Baseline coagulation profile should be ordered in all patients prior to tranexamic-acid and more exhaustive investigations such as complete blood count, liver function test, protein C and S in patients with high risk of thromboembolism. The preferred oral dose was 250 mg orally twice daily, which can be used alone or in combination with topical hydroquinone, kojic acid and sunscreen. Repeated dosing of tranexamic-acid may be required for those relapsing with melasma following initial tranexamic-acid discontinuation. Coagulation profile should ideally be repeated at three monthly intervals during follow-up, especially in patients with clinically higher risk of thromboembolism. Treatment can be stopped abruptly post improvement and no tapering is required. Limitation This study is limited by the fact that open-ended questions were limited to the first general survey round. Conclusion Oral tranexamic-acid provides a valuable treatment option for melasma. Frequent courses of therapy may be required to sustain results and a vigilant watch is recommended for hypercoagulable states during the course of therapy.

A randomized prospective study to assess the role of topical tacrolimus as preventive therapy in unstable acral vitiligo.

BACKGROUND: Acral vitiligo is a significantly distressing condition and tends to be treatment-resistant. The occurrence of new lesions on acral areas further causes greater psychological trauma. Topical tacrolimus has been widely used in the management of vitiligo and its role in preventing flares in other dermatoses such as atopic dermatitis has been well documented. OBJECTIVES: To assess the role of topical tacrolimus as preventive therapy in unstable acral vitiligo. MATERIALS AND METHODS: In this single-centre randomized prospective study, 60 patients aged 16-60 years having unstable acral vitiligo with symmetrical lesions were enrolled and randomized (1:1) into two groups. Patients in group A were instructed to apply topical tacrolimus 0.1% ointment on both vitiliginous and normal skin while patients in group B were instructed to apply topical tacrolimus 0.1% ointment only on vitiliginous skin for 6 months. Only the distal hand till the wrist joint was chosen for observation. Vitiliginous patches were assessed monthly for 6 months for a change in the number of lesions and total area involved, extension of preexisting lesions and adverse effects if any. RESULTS: A reduction in the number of lesions was observed in both groups. The decrease in the number of lesions in group A was 5.6% as compared to 2.3% in group B (p-0.001). The decrease in depigmented area in group A was 10.5% as compared to 4.6% in group B (p-0.048). Treatment failure was seen in 11 out of 60 (18.3%) patients. CONCLUSION: Tacrolimus 0.1% ointment application showed effectiveness in preventing the appearance of new lesions in unstable acral vitiligo and hastening the repigmentation when applied on both lesional and perilesional skin in vitiligo.

Oral mycophenolate mofetil in the treatment of acquired dermal macular hyperpigmentation: An open-label pilot study.

BACKGROUND: Literature on treating acquired dermal macular hyperpigmentation is sparse. AIMS AND OBJECTIVES: To assess treatment response of mycophenolate mofetil in patients having acquired dermal macular hyperpigmentation. MATERIAL AND METHODS: In this open-label, pilot study, patients of acquired dermal macular hyperpigmentation affecting at least the face and/or neck were included. Each participant was treated with mycophenolate mofetil 2 g/day for 24 weeks, with a follow-up of 12 weeks. Two aspects of disease severity were measured: activity (appearance of new lesions/extension of existing lesions), and degree of hyperpigmentation (measured using 'dermal pigmentation area and severity index'). Patient satisfaction was assessed on a scale of 0-10. RESULTS: Forty-three of 46 patients who were prescribed mycophenolate, completed the study (40 females, 6 males; mean disease duration 2.8 ± 1.4 years). Amongst 20 (43.5%) patients with active disease, stability was achieved in 17, after a mean duration of 6.1 ± 2.5 weeks (range 4-12 weeks; median 4; IQR 4 weeks). Mean dermal pigmentation area and severity index at baseline was 18.8 ± 7.1 and decreased to 13.7 ± 6.3 at 24th week (27.5 ± 14.7%; P < 0.001). A significant decreasing trend in dermal pigmentation area and severity index (P < 0.001) was observed, and first significant difference from baseline was noted at the 16th week (P 0.008). Less than 10%, >10-20%, >20%-30%, >30%-40%, >40%-50%, and >50% reduction in dermal pigmentation area and severity index was observed in 8, 5, 4, 15, 10 and 1 patients/patient respectively. The maximum mean grade of pre-treatment dermatoscopic severity was 3 ± 0.7, and decreased to 2.1 ± 0.8 on the face (P < 0.001) and 2.4 ± 0.7 on the neck (P < 0.001) post-treatment. There were 9 (20.1%) non-responders. Self-assessment scores of the rest of the patients fell in the range of moderate/fair improvement (>5 to 7). No significant correlation was seen between patient satisfaction score and degree of reduction in dermal pigmentation area and severity index (r -0.39). Three developed adverse effects (leucopenia, n = 1; transaminitis and hyperbilirubinemia, n = 2) that resolved following discontinuation of mycophenolate. CONCLUSION: Mycophenolate mofetil appears to be a promising treatment option in acquired dermal macular hyperpigmentation.

A prospective study to assess the efficacy of various surgical modalities in treatment of stable vitiligo patches over resistant sites.

BACKGROUND: Despite advances in surgical management of vitiligo, lesions on acral areas and bony prominences remain treatment refractory. There is lack of literature on the treatment efficacy of various surgical modalities over these treatment refractory sites. OBJECTIVE: To compare the efficacy of three common methods of grafting in vitiligo in known resistant areas. METHODS: A single-center interventional clinical trial involving 30 patients of stable vitiligo (disease stability ≥1 year) located over bony prominences and acral areas. All patients were treated with noncultured epidermal cell suspension (NCES), suction blister epidermal grafting (SBEG), and mini punch grafting (MPG) on three separate patches. Extent of repigmentation was assessed at 12 and 24 weeks, color matching and patient satisfaction were evaluated at 24 weeks. RESULTS: Among 30 participants, 22 (73%) were females, mean age was 27.4 (±10.7) years, and the majority (93.3%) had nonsegmental vitiligo. At 12 weeks, repigmentation >75% was noted in 56.6, 60, and 16.6% of patches treated by NCES, SBEG, and MPG, respectively. At 24 weeks, results remained the same in both the NCES and SBEG groups, while the number of patches with >75% repigmentation increased to 23.3% in the MPG group. The difference in repigmentation rate between NCES and MPG as well as between SBEG and MPG achieved statistical significance. Color matching of treated area and patient satisfaction were better in NCES and SBEG groups compared to MPG. CONCLUSION: NCES and SBEG are superior to MPG with reasonably good efficacy and can be offered as a therapeutic modality for stable vitiligo patches over these sites.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

A clinico-demographic study of 344 patients with lichen planus pigmentosus seen in a tertiary care center in India over an 8-year period.

BACKGROUND: Lichen planus pigmentosus (LPP) is an acquired disorder of hyperpigmentation affecting certain racial and ethnic groups. OBJECTIVE: To retrospectively analyze the demographic and clinical characteristics of LPP. METHODS: Clinical and demographic records of all LPP patients attending our pigmentary clinic from January 2011 to June 2018 were reviewed. RESULTS: Data of 344 LPP patients (229 females) were analyzed. Affected females had significantly higher age at onset (P < 0.002) but lesser disease duration at presentation (P < 0.001) as compared to males. Significant positive correlation between body surface area involvement and disease duration was observed (r = 0.72). Personal history of atopy and accompanying autoimmune diseases were observed in 49 (14.24%) and 45 (13.08%) patients, respectively. Observed morphological patterns of LPP included diffuse (n = 193, 56.1%); reticular (n = 45, 13.1%); blotchy (n = 41, 11.9%); and follicular (n = 28, 8.1%). All the patients had a chronic and indolent course of disease with approximately half (49.2%) reporting satisfactory improvement with treatment. CONCLUSION: This is the largest clinico-demographic study till date on LPP. A longer disease duration was associated with more widespread disease. Although the disease improved over time as per patient and physician global assessment, a complete clearance was rarely attained.

A prospective study to validate various clinical criteria used in classification of leprosy: a study from a tertiary care center in India.

BACKGROUND: Various clinical criteria are used to categorize leprosy patients into paucibacillary (PB) and multibacillary (MB), thus aiding in appropriate treatment. However, comprehensive studies validating these criteria are minimal. AIMS: To assess sensitivity and specificity of different clinical criteria individually and in combination for classifying leprosy into PB/MB spectrum. METHOD: A prospective study was conducted wherein 50 newly diagnosed, untreated leprosy cases were recruited and classified into PB and MB using the following clinical criteria: number of skin lesions (NSL), number of body areas affected (NBAA), and size of largest skin lesion (SLSL). Patients with pure neuritic leprosy, diffuse macular type of lepromatous leprosy, and with reactions were excluded. Sensitivity and specificity of these clinical criteria in classification was calculated taking histopathological findings as gold standard. RESULTS: Among 50 patients, 37 were males and 13 were females with a mean age of 32.08 ± 16.55 years. The sensitivity and specificity of NSL, NBAA, and SLSL was 94.74 and 87.1%, 94.74 and 61.29%, and 73.68 and 16.13%, respectively. Combining all three criteria, the sensitivity increased to 100%, but specificity decreased drastically to 12.9%. The ROC curve for NSL, NBAA, and SLSL showed a cutoff of ≥6 skin lesions, ≥3 body areas affected, and ≤2 cm lesion to classify as MB. CONCLUSION: The current WHO system of leprosy classification based on NSL seems to be best among available clinical criteria. Uniform and sensible application of this criteria itself assures appropriate categorizing and leprosy treatment with reasonable sensitivity and specificity.

Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm.

BACKGROUND: Vitamin D (Vit.D) deficiency has been reported in alopecia areata (AA). Downregulation of Vitamin D receptor (VDR) on hair follicles is associated with reduced hair growth. OBJECTIVE: To correlate serum Vit.D levels with severity, pattern, and duration of AA, and density of VDR expression over hair follicles in AA patients. METHODS: Prospective study including 30 AA patients and 30 healthy controls. Clinical details and serum Vit.D measurement and scalp biopsy for histopathology and VDR expression was performed in patients and controls at baseline and after 6 months of treatment of AA. RESULTS: Mean age of patients and controls was 28.9 ± 9.96 and 31.17 ± 9.43 years, respectively. Mean SALT score in patients was 35.8 ± 27.5 with a median disease duration of 48 weeks. Mean serum Vit.D levels was 7.65 ± 4.50 ng/ml and 15.8 ± 11.47 ng/ml in patients and controls, respectively. Twenty-nine (96.7%) patients were Vit.D deficient (<20 ng/ml), compared to 22 (73.3%) controls (P = 0.001). Serum Vit.D levels inversely correlated with severity of the disease (r = -256), P = 0.17, and duration of disease but did not correlate with pattern of AA and VDR expression in tissue samples. VDR expression was reduced in all patients and was normal in controls. Inverse correlation of VDR was noted with presence of inflammation on histology (P = 0.02). VDR upregulation post treatment was seen only in 13% of patients and demonstrated no correlation with response to treatment. CONCLUSION: Vit.D deficiency in AA correlates inversely with disease severity and duration. VDR expression is reduced in AA and inversely correlate with inflammation histologically but does not correlates with serum Vit.D levels, severity, pattern, or duration of illness.

Dermatoscopic evaluation and histopathological correlation of acquired dermal macular hyperpigmentation.

BACKGROUND: Acquired dermal macular hyperpigmentation (ADMH) is a hypernym encompassing Riehl's melanosis, lichen planus pigmentosus, and ashy dermatoses that show significant clinicopathological overlap. We sought to describe the dermatoscopic features of ADMH and correlate them with histopathological findings. METHODS: This was a prospective observational study performed in two phases. A detailed clinical and dermatoscopic examination was performed, and skin biopsies were obtained in 51 patients. Two dermatologists and a blinded dermatopathologist studied archived dermatoscopic images and histopathology specimens, respectively. RESULTS: Dermatoscopic features noted were (i) pigment structures; dots (82.4%), globules (66.7%) and blotches (56.9%) that spared the eccrine and hair follicle openings; (ii) telangiectasia (82.4%); (iii) accentuation of the normal pseudoreticular pigmentary network (33.3%); (iv) owl's eye structures (15.7%). Four dermatoscopic grades of disease severity were identified: grade 1 - dotted; grade 2 - Chinese letter; grade 3 - reticulate; and grade 4 - diffuse. Density of melanin incontinence on histopathology correlated positively with size of pigment structures (r = 0.7, P < 0.000) and grades of disease severity (r = 0.75, P < 0.000) on dermatoscopy. CONCLUSION: Increasing grades of disease severity can be detected dermatoscopically, which correlate well with histopathological features. A carefully performed dermatoscopy aids in better patient counseling regarding disease severity.

Long-term follow-up and epidemiological trends in patients with pretibial myxedema: an 11-year study from a tertiary care center in northern India.

INTRODUCTION: Pretibial myxedema (PTM) is a rare manifestation of Graves' disease. There is paucity of data regarding long-term follow-up and response to treatment in PTM. MATERIALS AND METHODS: Retrospective study wherein 30 patients of PTM presenting during 2001-2011 attending dermatology and endocrinology outpatient departments were analyzed. RESULTS: Among 30 patients with PTM, 12 were males and 18 females with a ratio of 1 : 1.5 males/females. Four morphological forms were identified: plaques (18 patients), diffuse non-pitting edema of both lower legs (five), nodules (five), and elephantiasis lesions (two). Eighty percent were diagnosed with hyperthyroidism before the development of dermopathy. Twenty-six patients presented with ophthalmopathy. Fourteen patients with plaque had an excellent response to topical clobetasol propionate ointment and attained complete resolution by 3.6 years. Out of 16 patients treated with combination therapy, which included nine treated with topical corticosteroids/intralesional triamcinolone and seven treated with oral, intralesional, and topical corticosteroids, nine attained complete resolution in the lesions by 3.4 years, and none relapsed anytime during four years of post-treatment follow-up. However, the remaining patients (elephantiasis and diffuse forms) failed to achieve complete resolution. CONCLUSIONS: Plaques and nodules are common variants with a favorable clinical response to topical and intralesional corticosteroid; elephantine and diffuse forms responded poorly to therapy. Studies analyzing larger cohorts of patients with PTM and their long-term follow-up are limited, hence more such studies are required.

Nevus lipomatosus superficialis unseen or unrecognized: a report of eight cases.

BACKGROUND: Nevus lipomatosus superficialis (NLS) is a unique developmental anomaly or nevoid form of lipoma characterized by the ectopic presence of mature adipocytes in reticular dermis. The condition is rare; apart frrom isolated case reports, there are no large case series dealing with the clinicoepidemiologic characteristics and posttreatment long-term follow-up in patients with NLS and little published information on treatment outcome. OBJECTIVE: To study the clinicoepidemiologic characteristics and long-term posttreatment follow-up in patients with NLS. METHODS: This was an 11-year retrospective study analyzing disease characteristics and treatment outcome in eight patients with NLS. RESULTS: There were eight (six males, two females) patients with NLS, of whom three were children. The classic variant of NLS was the predominant presentation. One patient demonstrated a combination of both classic and solitary variants. Most patients, especially those with solitary variants, were commonly misdiagnosed before presenting to us. Four patients, including two with the solitary variant, one each with the classic and the combined type, underwent surgical resection without any recurrence over 8 years of follow-up. CONCLUSIONS: The rare nature of the disorder, which is commonly misdiagnosed, and the absence of long-term follow-up data prompted us to share our experience about NLS to increase its awareness among health care providers.

Características clínicas y resultados en pacientes de lepra multibacilares (MB) tratados con 12 meses de MDT-MBR OMS: análisis retrospectivo de 750 pacientes de una clínica para lepra en un hospital especializado del norte de la india / No disponible

Antecedentes: La pauta de 12 meses de multiterapia (MDT) pauta multibacilar (MBR) fue implantada en la India en 1998, pero todavía adolece de información fiable sobre su posible eficacia. Objetivo: Evaluar la eficacia de la MDT MBR de 12 meses en apcientes multibacilares (MB) en nuestro centro. Metodología: Es un estudio retrospectivo que analiza las historias clínicas de 1210 pacientes registrados en la clínica para lepra de nuestra institución desde 1999 hasta 2010. Se observó un elevado Índice Bacteriano (IB) ≥ 3+, en 313 pacientes en el momento del registro. Cuatrocientos un pacientes experimentaron leproreacciones (54,9%9. ENL recurrente sólo se detectó en 14 pacientes incluso 5 años después de haber recibido el alta. La correlación clínico-histológica se examinó en 361 (49,5%) de los pacientes. Durante el periodo de seguimiento desde 9 meses a 10 años, casi todos los pacientes presentaron una aclaración evidente de sus lesiones cutáneas, incluyendo la mejoría histopatológica. Solo recidivaron 13 (1.7%). Conclusiones: Todos los pacientes respondieron sin problemas a la pauta MDT-MBR de 12 meses sin efectos adversos destacables. El índice total de recidivas fue de sólo 1,7%. Por tanto, la recomendación de la MDT MBR de 12 meses para todos los pacientes MB es robusta y práctica (AU)

Backgorund: Shortened (12 months) multidrug multibacillary regimen (MDT MBR) was implemented in India in 1998, however there is yet a paucity of crucial data on its long term outcome. Objetive. To assess the efficacy of 12 months MDT MBR in multibacillary (MB) patients at our centre. Design:This eas a retrospective study undertaken analyzing the clinic records of 1210 patients registered at the leprosy clinic of our institute form 1999-2010. Results. 730 MB patients were treated with 12 months MDT MBR over this period. High bacillary index (BI) ≥ 3+, was observed in 313 patients at the time of registration. Four hundred and one (54,9%) patients experienced lepra reactions. Recurrent ENL was observed in only 14 patients which manifested even after 5 years of stopping treatment. Clinico-histological correlation was noted in 361 (49,5%) patients. During follow up period ranging from 9 months to 19 years, nearly all patients had clearance of skin lesions including histopathological/bacteriological improvement. Only 13 (1.7%9 patients relapsed. Conclusions: all patients responded well with 12 months MDT MBR without significant side effects. The overall relapse rate was only 1.7%. Thus, the recommendation for 12 months MDT MBR for all MB patients is robust and operationally practical, a decision which seems logical (AU)