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.

Successful long-term thalidomide therapy for discoid lupus erythematosus-lichen planus overlap syndrome.

Although thalidomide is a U.S. Food and Drug Admistration (FDA) approved medication for erythema nodosum leprosum and multiple myeloma, it has many off-label uses, including for discoid lupus erythematosus (DLE), Behçet's disease, apththous ulcers in HIV patients, and prurigo nodularis. Herein, we present a patient with an overlap of discoid lupus erythematosus and lichen planus who was successfully treated with thalidomide for over 19 years without significant side effects. We propose that some of the most common side effects, including peripheral neuropathy, numbness, parasthesias, sedation, and constipation, can be avoided at lower doses, typically less than 100mg/day.

Thalidomide: an experience in therapeutic outcome and adverse reactions.

BACKGROUND: The US FDA-approved thalidomide for the treatment of chronic recurrent/severe erythema nodosum leprosum. Thalidomide is also useful in many other inflammatory dermatological conditions where patients have exhausted other treatment options. METHODS: The beneficial and adverse clinical effects of thalidomide were studied in 25 patients suffering from different inflammatory dermatological conditions that were poorly controlled with conventional therapies. RESULTS: Thalidomide was found to be effective in various inflammatory dermatological diseases other than chronic recurrent erythema nodosum leprosum such as Behçet's disease, disseminated and hypertrophic discoid lupus erythematosus, erosive lichen planus, discoid lupus erythematosus-lichen planus overlap, recurrent aphthous stomatitis and prurigo nodularis. Deep vein thrombosis due to thalidomide occurred in 20% of these patients and appears to be a significant side effect. CONCLUSION: Thalidomide appears promising in a number of inflammatory dermatological conditions and will probably find new usages in future. The treating physicians need to be wary of the thrombo-embolic complications due to thalidomide especially when glucocorticoids or other chemotherapeutic agents such as doxorubicin, gemcitabine, 5-fluorouracil or dexamethasone-cyclophosphamide pulse therapy are being used concomitantly, and in patients of metastatic renal carcinoma, myelodysplastic syndrome or multiple myeloma receiving thalidomide/chemotherapy. Antiphospholipid or anticardiolipin antibodies appear to be other possible risk factors for this complication.

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration-approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçet's syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

Complete resolution of generalized lichen planus after treatment with thalidomide.

Thalidomide has gained an infamous history due to severe birth defects observed in patients who had taken the drug to control nausea during pregnancy. The medication was withdrawn from the market because of its teratogenicity, but was approved by the FDA in 1998 for the treatment of erythema nodosum leprosum. However, thalidomide has been employed with success by dermatologists for a host of off-label uses including the treatment of lichen planus. Currently, no clinical trials or studies exist to evaluate the efficacy of using thalidomide to treat lichen planus, but case reports have been published in the medical literature supporting its therapeutic benefits. TNF-alpha is among the many cytokines that have been implicated in the pathogenicity of lichen planus. It is thought that thalidomide acts.

Talidomida: su importancia en terapéutica dermatológica; ensayo continuado en varias entidades / Thalidomide: its importance in dermatological theraphy; continuous assay in many identities

Para estudiar la efectividad de la Talidomida en patologías dermatológicas diferentes de la reacción leprosa, se seleccionaron 4 pacientes que acudían a la consulta externa del Instituto de Biomedicina (Caracas). Un paciente con Líquen plano hipertrófico; un paciente con Eritoma Multiforme, uno con aftas orales recurrentes y un paciente con Lupus Subagudo y manifestacines cutáneas de Lupus Eritematoso Discoideo Crónico (LEDC). Los cuatro pacientes tenían en común la ausencia parcial o total de respuesta a los tratamientos convencionales para estas afecciones. En todos los casos se observó una buena a excelente respuesta al uso de la Talidomida. La Talidomida debe quedar a la disposición del Dermatólogo para el tratamiento de la reacción leprosa, aftosis recurrente, líquen plano, LEDC y tal vez para algunos otros casos muy seleccionados tomando en cada caso las precauciones necesarias con el fin de evitar los riesgos de teratogénesis y posible neuropatía

Thalidomide therapy. An open trial

In an open trial, 35 patients suffering from a variety of dermatologic conditions were treated with thalidomide. The drug was shown to be a valuable addition to the therapeutic armamentarium; however, the occurrence of a peripheral neuropathy will limit its use just as its teratogenic side effects have done for many years.