Janus-kinase inhibitors in dermatology: A review of their use in psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease.

Recent studies on molecular pathways have elucidated novel therapeutic approaches in inflammatory and autoimmune skin disorders. Specifically, the dysregulation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) cascade plays a central role in the pathogenesis of many skin conditions. JAK inhibitors, with their ability to selectively target immune responses, are potential treatment options. Using the National Library of Medicine, we provide a comprehensive review of the use of United States Food and Drug Administration (FDA)-approved and emerging JAK or tyrosine kinase 2 (TYK2) inhibitors in a wide range of dermatologic conditions, including psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease. In patients with psoriasis, oral deucravacitinib (TYK2 inhibitor) has been approved as a once-daily therapy with demonstrated superiority and efficacy over apremilast and placebo and tolerable safety profiles. In patients with vitiligo, topical ruxolitinib (JAK1 inhibitor) is approved as a twice-daily treatment for repigmentation. The efficacy of several other JAK inhibitors has also been demonstrated in several clinical trials and case studies for systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease. Further investigations with long-term clinical trials are necessary to confirm their utility in treatment and safety for these diseases.

Comparative study of the efficacy and safety of two grafting procedures (an automated epidermal harvesting system and non-cultured epidermal cell suspension) in the treatment of stable vitiligo.

Background The non-cultured epidermal cell suspension method is a well-established but tedious grafting modality in the management of stable vitiligo. Recently a more user-friendly automated epidermal harvesting system has been introduced. Aim This was a pilot study to compare the efficacy and safety outcomes of the above two grafting procedures. Study design The study was a single-blinded split-body randomised controlled trial. After scientific and ethical clearance, the trial was registered with CTRI (CTRI/2018/05/014225). Thirty consenting patients of stable vitiligo with 60 near-symmetrical patches were recruited. Block randomisation was done using computer-generated randomisation software and each patch was allocated either of the two grafting modalities. Efficacy was assessed by the Physician Global Assessment Scale on serial images and pain by the Numerical Rating Pain Scale. Results and conclusion The non-cultured epidermal cell suspension was found to be an overall statistically superior technique to the automated epidermal harvesting system in terms of efficacy (re-pigmentation). Both donor and recipient site complications were significantly less with the automated epidermal harvesting system grafting and this method had the distinct advantage of being a painless and easy technique with minimal recovery time. A novel observation was that a good colour match and near-complete re-pigmentation occurred in patients with a darker skin colour with both techniques. Limitations The main limitation of our study was the small sample size. Also, the size of the treated patches was limited such that they could be covered by the 5 × 5 cm size of the automated epidermal harvesting system blade. However, a larger area can be covered with multiple sessions.

Association between exonic polymorphisms of human leukocyte antigen-G gene and non-segmental vitiligo in the Korean population.

Background Vitiligo is a pigmentary skin disorder characterised by a chronic and progressive loss of melanocytes. Although several theories have been suggested to the pathogenesis of vitiligo, an autoimmune process leading to melanocyte destruction appears most likely. Human leukocyte antigen-G is a non-classic, major histocompatibility complex Class I molecule that plays an important role in the suppression of the immune response. Several recent studies have provided evidences that polymorphisms in the human leukocyte antigen-G gene might be related with autoimmune diseases. Objectives The aim of this study was to decide whether exonic single nucleotide polymorphisms in human leukocyte antigen-G contribute to the risk of developing non-segmental vitiligo in the Korean population. Methods To evaluate the associations between exonic single nucleotide polymorphisms (rs1630223 [Ala5Ala] and rs12722477 [Leu134Ile]) of human leukocyte antigen-G and vitiligo, 244 patients with vitiligo and 398 healthy controls were recruited. Genotyping was performed using Fluidigm 192.24 Dynamic Array with EP1 (Fluidigm Corp., CA). The SNP type assay (Fluidigm Corp., CA), which employs allele-specifically designed fluorescences (FAM or VIC) primers and a common reverse primer was applied and the data were analysed using the EP1 single nucleotide polymorphisms genotyping analysis software to obtain genotype calls. Results Two exonic single nucleotide polymorphisms (rs1630223 and rs12722477) exhibited significant associations with susceptibility and remained a statistically significant association following Bonferroni correction. These two single nucleotide polymorphisms were located within a block of linkage disequilibrium. Haplotypes G-C and A-A comprising rs1630223 and rs12722477 demonstrated a significant association with non-segmental vitiligo. Limitations The protein expression level of patients with vitiligo and controls was not studied and a replication study of the genetic association in an independent group was not managed. Conclusion Our results suggest that exonic human leukocyte antigen-G polymorphisms (rs1630223 and rs12722477) are associated with the development of non-segmental vitiligo.

Non-venereal genital dermatoses and their impact on quality of life-A cross-sectional study.

BACKGROUND: Lesions on the external genitalia could be venereal or non-venereal. Non-venereal genital dermatoses are common and may cause considerable anxiety to patients, particularly if noticed after sexual intercourse. However, this aspect has not been studied much till now. OBJECTIVES: Our study proposes to describe the profile of non-venereal genital dermatoses and determine their impact on quality of life both social and sexual, using the dermatology life quality index questionnaire. METHODS: We recruited patients aged 18 years and above, who were diagnosed to have non-venereal genital dermatoses during the study period. A detailed history was obtained and clinical examination done with relevant investigations when necessary. The dermatology life quality index was assessed and graded in all patients using Finlay dermatology life quality index questionnaire. RESULTS: A total of 293 patients with non-venereal genital dermatoses were seen and 25 different dermatoses were observed. Men 242(82.6%) outnumbered women. The commonest age group affected was 31-50 years 144(50%). Chronic inflammatory dermatoses 135(41.6%) constituted the majority of cases. Scrotal dermatitis 46(15.7%), lichen simplex chronicus 37(12.6%), vitiligo 31(10.6%) were seen most frequently. In the study group, 111(37.9%) patients had moderate and 133(45.4%) had large impact on the quality of life. Erectile dysfunction was seen in 48(19.8%) men and 9(3.7%) had premature ejaculation. A significant effect on dermatology life quality index was found with increasing age (P = 0.007), positive marital status (P = 0.006), history of unprotected sex (P < 0.001), history of recurrences (P = 0.002) and venereophobia. (P = 0.008). LIMITATIONS: The number of women in the study group was less compared to men and we could not ascertain the type of sexual dysfunction in them. CONCLUSION: Non-venereal genital dermatoses are common, more so among men. They have a significant impact on the quality of life of the individual. Recognizing and addressing this problem will help in managing these patients effectively.

Family vitiligo impact scale: A scale to measure the quality-of-life of family members of patients with vitiligo.

BACKGROUND: Vitiligo places a significant psycho-social burden on caregivers and family members. AIMS: The aim of the study was to develop and preliminarily validate a scale to measure the psychosocial impact of vitiligo on adult family members. METHODS: Themes that emerged from qualitative interviews and a focus group discussion with family members were used to generate items for a preliminary scale, followed by pre-testing and scale development. The new scale was then tested with two comparator scales and a global question. RESULTS: A preliminary scale with 32 items was pilot tested on 30 participants. Following this, the scale was condensed to 16 items in 12 domains that were administered to 159 participants. Scale scores ranged from 0 to 48 with a mean of 19.75 ± 12.41. The scale had excellent internal consistency with Cronbach's alpha coefficient of 0.92 (0.70-0.95) and also showed good test-retest reliability at two weeks (r = 0.946). The scale showed criterion, convergent and known group validity. LIMITATIONS: It was conducted in a large teaching hospital which may have resulted in selection of patients with persistent or progressive disease and more worried family members. Vitiligo is highly stigmatized in our country and the performance of the scale may need to be evaluated in other communities and cultures as well where stigma is less oppressive. CONCLUSION: Family Vitiligo Impact Scale appears to be an easy-to-complete, reliable and valid instrument to measure the psychosocial impact of vitiligo in family members of patients. It may be useful as an outcome measure in both clinical and research settings.

Psychosocial burden of lichen planus pigmentosus is similar to vitiligo, but greater than melasma: A cross-sectional study from a tertiary-care center in north India.

BACKGROUND: Lichen planus pigmentosus can have a negative impact on the quality of life; however, this has not been studied in detail. OBJECTIVES: To study the quality of life in patients with lichen planus pigmentosus and compare it with patients with vitiligo and melasma. METHODS: This was a cross-sectional study conducted in a tertiary-care center in north India from January 2018 to May 2019. Patients ≥ 18 years of age with lichen planus pigmentosus (n = 125), vitiligo (n = 113) and melasma (n = 121) completed the Dermatology Life Quality Index (DLQI) questionnaire and answered a global question on the effect of disease on their lives. In addition, patients with vitiligo completed the Vitiligo Impact Scale (VIS)-22 questionnaire, while those with lichen planus pigmentosus and melasma filled a modified version of VIS-22. RESULTS: The mean DLQI scores in patients with lichen planus pigmentosus, vitiligo and melasma were 10.9 ± 5.95, 9.73 ± 6.51 and 8.39 ± 5.92, respectively, the difference being statistically significant only between lichen planus pigmentosus and melasma (P < 0.001). The corresponding mean modified VIS-22/VIS-22 scores were 26.82 ± 11.89, 25.82 ± 14.03 and 18.87 ± 11.84, respectively. This difference was statistically significant between lichen planus pigmentosus and melasma, and between vitiligo and melasma (P < 0.001 for both). As compared to vitiligo, patients with lichen planus pigmentosus had a significantly greater impact on "symptoms and feelings" domain (P < 0.001) on DLQI, and on "social interactions" (P = 0.02) and "depression" (P = 0.04) domains on VIS-22. As compared to melasma, patients with lichen planus pigmentosus had significantly higher scores for "symptoms and feelings," "daily activities," "leisure" and "work and school" domains of DLQI, and all domains of VIS-22. Female gender was more associated with impairment in quality of life in patients with lichen planus pigmentosus, while lower education, marriage, younger age and increasing disease duration showed a directional trend. LIMITATIONS: Use of DLQI and modified version of VIS-22 scales in the absence of a pigmentary disease-specific quality-of-life instrument. CONCLUSION: Patients with lichen planus pigmentosus have a significantly impaired quality of life. The psychosocial burden of lichen planus pigmentosus is quantitatively similar to that of vitiligo, but significantly greater than melasma.