Transmission patterns of C1-INH deficiency hereditary angioedema favors a wild-type male offspring: Our experience at Chandigarh, India.

BACKGROUND: Deficiency of C1-inhibitor (C1-INH) protein, caused by pathogenic variants in the Serpin family G member 1 (SERPING1) gene, is the commonest pathophysiological abnormality (in ∼95 % cases) in patients with hereditary angioedema (HAE). C1-INH protein provides negative control over kallikrein-kinin system (KKS). Although the inheritance of the HAE-C1-INH is autosomal dominant, female predominance has often been observed in patients with HAE. OBJECTIVE: To analyze the risk of transmission of SERPING1 gene variant from father or mother to their offspring. METHODS: Pedigree charts of 42 families with a confirmed diagnosis of HAE-C1-INH and a pathogenic variant in the SERPING1 gene were analysed. Patients with HAE who had had at least one child were included for analyses to assess the risk of transmission from the father or mother to their offspring. RESULTS: Overall, 49 % (189/385) of all offspring inherited the genetic defect. In the subgroup analyses, 54.8 % (90/164) female offspring and 44.8 % (99/221; p < 0.02) male offspring inherited the genetic defect. Inheritance of the genetic defect was significantly lower in male offspring. Fathers with SERPING1 gene variant had a statistically significant skewed transmission of the wild type to the male offspring as compared to the variant (57.8 % wild type vs. 42.1 % variant; p < 0.02), whereas no statistically significant difference was found when a father transmitted the variant to a female offspring. Mothers with SERPING1 gene variant had no statistically significant difference in variant transmission to male or female offsprings. CONCLUSION: Results of the study suggest that the transmission pattern of SERPING1 gene variant favours the transmission of wild-type alleles in males, especially when the father is the carrier; hence, overall, fewer males and more female offspring inherited the variant. This could be because of a selection of wild-type male sperms during spermatogenesis, as the KLK system has been reported to play a crucial role in the regulation of spermatogenesis. Although, a similar pattern was observed in the maternal transmission of the SERPING1 gene variant; the difference was not statistically significant, likely because of a small sample size.

Vitiligo: Translational research and effective therapeutic strategies.

This is an exciting phase of vitiligo research with the current understanding of vitiligo pathogenesis and its translation to successful treatment. The pathogenetic origin of vitiligo revolves around autoimmunity with supporting role from many other factors like oxidative stress, inherent melanocyte defects, or defective keratinocytes and fibroblasts. Vitiligo can be classified into segmental or non-segmental depending upon the clinical presentation, or it can be classified as progressing or stable based on the activity of the disease. Vitiligo treatments need to be stratified depending upon which type of vitiligo we are treating and at which phase the vitiligo patient presents to us. There are two different aims of treatment of vitiligo. The first involves rescuing the melanocytes from the damage to arrest the depigmentation. The second strategy focuses on replenishing the melanocytes so that successful repigmentation is achieved. It is also important to maintain the disease in a stable phase or prevent relapse. As stability in non-segmental vitiligo is a dynamic process, maintenance of the stability of repigmentation is also an important consideration in the management of vitiligo. In this review, we shall briefly discuss the current options and future insight into the management of vitiligo.

Metastatic Crohn Disease: A Clinicohistological Appraisal From a Tertiary Care Center in India.

BACKGROUND: Granulomatous dermatitis due to noncontiguous involvement of Crohn disease (CD) of the gut has been described as metastatic CD (MCD). MCD is the rarest form of cutaneous manifestations of CD. This study aims to analyze the clinicohistological features of MCD in a tertiary care center of India. MATERIALS AND METHODS: A retrospective review of patients diagnosed clinically and histologically with MCD over past 5 years was performed. Data on cutaneous features, histological findings, and response to treatment were collected. RESULTS: Twelve patients (3 men and 9 women) with a mean age of 29 years were identified. All women had vulval involvement in the form of edema (80%), ulceration (60%), and fistula (20%). Among the 3 men, 2 had perineal and scrotal swelling and ulcer, whereas the third patient presented with leg ulcer. Intestinal CD was already diagnosed in 50% patients (5/10) at cutaneous presentation, whereas it was diagnosed subsequently in 30% (3/10) cases. Histological examination revealed nonnecrotizing granulomatous inflammation in the dermis in 11 patients (92%). Additional histological features included eosinophilic infiltrate (58%), panniculitis (33%), and vasculitis (33%). The patients were treated with various combinations of oral prednisolone, metronidazole, minocycline, azathioprine, and subcutaneous adalimumab with partial relief. CONCLUSION: MCD shows a wide spectrum of clinical presentation, with anogenital involvement being the most common. Histology reveals nonnecrotizing granulomas in the dermis in majority of the cases. The diagnosis is extremely challenging in patients without gastrointestinal involvement at presentation, and thus, a high index of suspicion is imperative.

Combination of Follicular and Epidermal Cell Suspension as a Novel Surgical Approach in Difficult-to-Treat Vitiligo: A Randomized Clinical Trial.

Importance: Epidermal cell suspension (ECS) and follicular cell suspension (FCS) are successful surgical modalities for the treatment of stable vitiligo. However, repigmentation in generalized and acrofacial vitiligo and over acral or bony sites (eg, elbows, knees, iliac crests, and malleoli), which are difficult to treat, is challenging. Objective: To study the efficacy of transplanting a combination of autologous, noncultured ECS and FCS (ECS + FCS) compared with ECS alone in stable vitiligo. Design, Setting, and Participants: A prospective, observer-blinded, active-controlled, randomized clinical trial was conducted at a tertiary care hospital, with treatment administered as an outpatient procedure. Thirty participants who had stable vitiligo with symmetrical lesions were recruited between October 18, 2013, and October 28, 2016. All of the lesions were resistant to medical modalities with minimum lesional stability of 1 year. Intent-to-treat analysis was used. Interventions: ECS + FCS was prepared by mixing equal amounts (in cell number) of FCS with ECS. After manual dermabrasion, ECS was applied to 1 lesion and ECS + FCS was applied to the anatomically based paired lesion of the same patient. No adjuvant treatment was given. Main Outcomes and Measures: Patients were followed up at 4, 8, and 16 weeks by a blinded observer and extent of repigmentation, color match, pattern of repigmentation, patient satisfaction and complications were noted. Both the visual and the computerized image analysis methods were used for outcome assessment. Cell suspensions were assessed post hoc for OCT4+ stem cell counts using flow cytometry; expression of stem cell factor and basic fibroblast growth factor was evaluated using quantitative relative messenger RNA expression. Results: Of the 30 patients included in the study, 18 (60%) were women; mean (SD) age was 23.4 (6.4) years. Seventy-four percent of the lesions (62 of 84) were difficult-to-treat vitiligo. ECS + FCS showed superior repigmentation outcomes compared with ECS: extent (76% vs 57%, P < .001), rapidity (48% vs 31%, P = .001), color match (73% vs 61%, P < .001), and patient satisfaction (mean [SD] patient global assessment score, 23.30 [6.89] vs 20.81 [6.61], P = .047). Melanocyte stem cell counts (2% in ECS + FCS vs 0.5% in ECS) as well as expression of basic fibroblast growth factor (11.8-fold) and stem cell factor (6.0-fold) were higher in ECS + FCS suspension (P<.05 for both). Conclusions and Relevance: The findings from this study establish ECS + FCS as a novel approach in vitiligo surgery for attaining good to excellent repigmentation in a short period with good color match, even in difficult-to-treat vitiligo. Trial Registration: ctri.nic.in Identifier: CTRI/2017/05/008692.

Evidence-based Review, Grade of Recommendation, and Suggested Treatment Recommendations for Melasma.

Treatment of melasma is known to be less satisfactory, often incomplete, and relapse is frequent. Although many treatment options are available, they are either known to be unsafe on long-term use or their long-term safety profile is unknown. Patients often use various drugs, even topical steroid-based preparation without any medical supervision for long period of time, making the skin unsuitable for many of the drugs available. Thus, there has been gross disparity among the treating physician about what drugs and what regimen are best suitable for various categories of melasma patients and in different situations. With this background, numerous newer drugs, mostly combinations of some proprietary molecules or even unknown plant extracts, have flooded the market for the management of melasma. Information on efficacy or safety of these products are almost unknown. Studies on Asian people, especially Indian population, are far less commonly available. Therapeutic guideline for use on Indian patients with melasma is almost missing. Extrapolation of data from Caucasian people for use on Asian people may not be scientifically justifiable because Caucasian and Asian people are known to have inherent difference in their response as well as tolerance to the drugs used for melasma. With this background, we have extensively evaluated, following a strict, scientifically designed protocol, all the available studies on melasma management till May 2016 and prepared this document on level of evidence, grade of recommendation and suggested therapeutic guideline for melasma as per the method proposed by Oxford Centre of Evidence-Based Medicine. Various ethical, social, logical, regional, and economic issues in the context of Indian and similar populations were given due importance while preparing the suggested therapeutic recommendation.

Noninvasive treatment of keloid using customized Re-188 skin patch.

Keloids are developed as fibrotic scar at the site of surgery or trauma and often enlarge beyond the original scar margins. Re-188 colloid coated customized patch was superficially fixed onto the lesion for 3 hrs. The same patch was reapplied on the lesion on third day for 3 hrs. The patients were followed up at 1, 3,6 and 12 months post treatment. The size and elevation of the keloid lesion was reduced after treatment. The total radiation dose from the patch (day-1 and day-3) was 100 Gy/mCi of Re-188. The radioactive patch treatment of keloids is noninvasive, painless and safe with prolonged outcome.

Comparison of bacillary index on slit skin smear with bacillary index of granuloma in leprosy and its relevance to present therapeutic regimens.

BACKGROUND: As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB) versus multibacillary (MB) regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called "PB" cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS) versus bacillary index of granuloma (BIG). AIMS: To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy. MATERIALS AND METHODS: This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS) where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines. RESULTS: The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases. CONCLUSION: This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent "under-treatment" of so called PB cases, which may actually warrant MB regimens.

Addisonian pigmentation and vitamin B12 deficiency: a case series and review of the literature.

Skin changes associated with vitamin B12 deficiency are common. In most cases, patients present primarily with systemic involvement (eg, megaloblastic anemia and/or neurologic effects), and additional cutaneous changes related to the diagnosis are noted as incidental findings. The role of vitamin B12 deficiency in the etiology of Addisonian pigmentation has not been well studied. We discuss the importance of testing vitamin B12 levels in patients who present for evaluation of generalized hyperpigmentation. Various cutaneous changes associated with vitamin B12 deficiency also are reviewed.