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.

Low dose oral glucocorticoid therapy in lichen planus: A retrospective cohort study.

Background There are various topical and systemic treatment options for the management of lichen planus. However, it is often difficult to achieve long-term disease control and many of the common therapies may be associated with unwanted side effects. Aims To evaluate the effectiveness of 8 mg oral methylprednisolone administered daily in lichen planus by the analysis of medical records. Methods In this retrospective cohort study, we compared the rates of improvement between two groups of patients. The first group received 8 mg oral methylprednisolone daily for at least one month. In the second group, patients with similar parameters to the first group (age, sex, disease manifestation) but without systemic glucocorticoid therapy were included. Fisher's exact test was used to compare the rates of remission in the two groups. Results In the daily oral methylprednisolone (n = 24) and no systemic corticosteroids (n = 16) groups, 23 (95.8%) and 6 (37.5%) patients achieved partial or complete remission, respectively. The frequency of improvement was significantly higher in patients who received oral methylprednisolone (P < 0.0001). Limitations Limitations of this study include its retrospective design and the relatively small sample size. Conclusion Low dose oral glucocorticoid therapy may be an effective option for the systemic treatment of lichen planus. Based on our results and previous studies, instead of higher doses, longer therapy duration with low doses should be considered.

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.

The role of autophagy-related gene 9B in lichen planus.

BACKGROUND: Lichen planus (LP) is an idiopathic, chronic, relapsing, inflammatory, autoimmune dermatological disease. The etiopathogenesis of LP is still unclear. Autophagy is a strictly regulated lysosomal degradation pathway that is crucial for maintaining intracellular homeostasis and normal development. The dysregulation of autophagy-associated genes was recognized to increase the susceptibility to multiple diseases, including inflammation, autoimmune disorders and cancer. AIMS: Our study aimed to detect the expression of autophagy-related gene 9 b (ATG9B) in LP patients compared to normal control persons to investigate the possible role of autophagy in pathogenesis of this disease. METHODS: This case-control study included 30 LP patients and 30 age-, gender-matched healthy controls. Four millimeters punch skin biopsies were obtained from LP lesions and from the controls and they were kept in lysis solution for the stability of the studied parameters and were kept frozen at -80°C till analysis of ATG9B using real-time polymerase chain reaction. RESULTS: The level of ATG9B in lesional skin of LP was significantly decreased compared to normal control persons (P < 0.01); also, there was a non-significant relation between ATG9B level and age, sex, duration and family history among LP patients. LIMITATIONS: Limited number of patients included in our study (30 patients). CONCLUSION: Autophagy may play a role in the pathogenesis of cutaneous LP.

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.

Lichen Planus Severity Index: A new, valid scoring system to assess the severity of cutaneous lichen planus.

INTRODUCTION: Lichen planus is a chronic autoimmune inflammatory disorder. At present, there is a lack of any specific scoring system to judge the severity of cutaneous lichen planus. Hence, a study was undertaken to establish and validate a system to define the severity of cutaneous lichen planus, i.e. Lichen Planus Severity Index. MATERIALS AND METHODS: SETTING: Skin outpatient department, Krishna Institute of Medical Sciences, Karad. MODEL: The formulation model was Psoriasis Area Severity Index (PASI) and the validation model was Onychomycosis Severity Index (OSI). PARTICIPANTS: The consensus group included two dermatologists and two dermatology residents with special interest in lichen planus and a statistician. Results of the consensus group were compared with a preliminary reproducibility group of two dermatologists and four dermatology residents. Later, reliability assessment was carried out by two groups: 1. Twenty-one dermatologists scored 20 photographs of four patients of lichen planus after being trained to use Lichen Planus Severity Index. 2. Six doctors (three experts and three randomly selected physicians) evaluated ten real-world patients of lichen planus in skin outpatient department. The physicians were blind to the scores assigned by experts. STEPS TO CALCULATE SCORE: There are five morphological types of lesions seen in lichen planus, namely, erythematous papule, violaceous papule, violaceous plaque, hyperpigmented hypertrophic papule and plaque and postinflammatory hyperpigmentation. Total involved body surface area is determined and a body surface area factor is assigned. Area involvement factor for each of these morphological lesions is calculated and multiplied with the respective multiplication factor. Sum of all the products gives the lesion severity score. Product of lesion severity score with the body surface area factor gives the final Lichen Planus Severity Score. RESULTS: There was no significant difference between the scores of consensus group and preliminary reproducibility group. Both assessment groups showed high reliability. (Group 1: Cronbach alpha = 0.92, ICC = 0.85; Group 2: Cronbach's alpha = 0.99, ICC = 0.92). The correlation between Lichen Planus Severity Index and the standard Physician Global Assessment score was found to be positive (correlation coefficient = 0.73). LIMITATIONS: : The system is tedious and requires a steep learning curve. Possible uses of Lichen Planus Severity Index are yet to be explored and validated. CONCLUSION: Lichen Planus Severity Index is a new reproducible tool to grade the severity of lichen planus.

Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case-control study.

BACKGROUND: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. OBJECTIVE: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. METHODS: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. RESULTS: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. LIMITATIONS: The main limitation of this study is the small sample size due to the time limitation and financial constraints. CONCLUSION: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India.

BACKGROUND: Lichen planus is a common chronically relapsing autoimmune skin condition with poorly understood etiology. Apart from cellular immunity, presence of various antibodies has been hypothesized. Various studies have found the presence of serum anti-nuclear antibody, anti-mitochondrial antibody, anti-desmoglein 1 and 3 antibodies, anti-keratinocyte antibody and anti-thyroglobulin antibody in patients of cutaneous and oral lichen planus. AIM: To study the prevalence of autoantibodies and the clinical spectrum of disease in an Indian patient subpopulation with lichen planus. METHODS: A cross-sectional epidemiological study comprising 100 lichen planus patients was conducted in the dermatology outpatient department of Seth G.S Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India. Serum concentrations of circulating anti-nuclear antibodies, anti-desmoglein 1 antibody, anti-desmoglein 3 antibody, anti-keratinocyte antibodies, anti-mitochondrial antibodies and anti-thyroglobulin antibodies were determined by indirect immunofluorescence. Pairs of groups were compared using "Student's t-test" for normally distributed continuous data. The "χ2-test" was used for the categorical variables as needed. Statistical significance was set at P < 0.05. RESULTS: It was found that 65 (65%) patients showed the presence of at least one of the six autoantibodies that we studied, while 35 (35%) tested negative for all six of them. Positivity of anti-keratinocyte antibody in 26 (26%), anti-nuclear antibody in 22 (22%), anti-desmoglein 1 antibody in 19 (19%), anti-desmoglein 3 antibody in 16 (16%), anti-mitochondrial antibody in 9 (9%) and anti-thyroglobulin antibody in 6 (6%) patients was detected. It was observed that 55 (71.4%) patients of cutaneous lichen planus, 6 (46.1%) patients of mucosal lichen planus and 4 (40%) patients of cutaneous and mucosal lichen planus overlap showed presence of at least one autoantibody. CONCLUSION: This study provides the serological parameters of a population of lichen planus from western India. Presence of autoantibodies in lichen planus suggests the possible role of humoral immunity in lichen planus. Identifying antibodies linked to lichen planus may help in identifying suitable diagnostic tests and therapeutic targets. Well-controlled studies with larger sample size are the need of the hour to confirm the role of humoral immunity in lichen planus. LIMITATIONS: Studies with a larger number of patients as well as controls should be undertaken to further evaluate the role of autoantibodies in lichen planus.