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.

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 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.

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.