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.

Systemic lupus erythematosus: review of synthetic drugs.

INTRODUCTION: Synthetic drugs are prescribed for nearly all patients with systemic lupus erythematosus (SLE), a multisystem autoimmune disease, to ameliorate symptoms and positively influence outcome. While only 2 biologic agents have been approved for the treatment of SLE, synthetic drugs are still the mainstay of therapy in SLE. The highly variable and unpredictable course of SLE poses a challenge for physicians as to what drug(s) should be prescribed for which patient. AREAS COVERED: Previous and recent studies have evaluated several synthetic drugs in the treatment of SLE. This article reviews currently available evidence for the efficacy and safety of synthetic drugs in SLE and discusses future treatment perspectives. EXPERT OPINION: Hydroxychloroquine should be considered an anchor drug in SLE because of the multiple beneficial effects of this agent. When patients present with persistent disease activity despite hydroxychloroquine therapy or need higher dosages and/or prolonged use of glucocorticoids (GCs), additional immunosuppressants should be promptly prescribed. Based on available evidence, azathioprine and mycophenolate mofetil are the drugs of first choice. Determination of a 'safe' GC dose for chronic daily use is of major importance and should be subject of further studies in large patient populations.

Borderline tuberculoid leprosy in childhood onset systemic lupus erythematosus patient.

Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.

Lupus and leprosy: beyond the coincidence.

Systemic lupus erythematous (SLE) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. Disease flares have been mostly associated with parvovirus B19, cytomegalovirus, EBV and Mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ANA, anti nDNA and anti-ß2-GPI mainly in lepromatous leprosy. Mycobacterium leprae not only may determine symptoms that mimic lupus flares, including autoantibodies production, but could also act as a trigger for lupus reactivation; however, its association is still not fully explored. As demonstrated for tuberculosis, it is quite possible that molecular mimicry may also be involved in the interface of these two diseases. Some studies reported shared epitopes among idiotypes derived from 8E7 and TH9 lepromatous antibodies and those obtained from SLE patients, and it could partially explain the triggering phenomenon of SLE caused by M. leprae. We report and discuss three Brazilian patients whose disease was inactive and presented disease flares concurrently with the diagnosis of leprosy.

Talidomida y análogos de talidomida / Thalidomide and analogous

La talidomida se introdujo en la década del '50 como droga hipnótica, sedante y antiemética, especialmente indicada en mujeres gestantes durante el primer trimestre del embarazo. Se asociaron al uso del fármaco graves anormalidades congénitas y polineuropatías, por lo que se la retiró del mercadoen los años '60. Posteriormente se comprobaron propiedades inmunomoduladoras en pacientes con eritema nudoso lepromatoso, así como también efectos antiinflamatorios como lupus eritematoso discoide, enfermedad de Behcet, úlceras aftosas en pacientes con SIDA, enfermedad crónica injerto contra huésped, mieloma múltiple y neoplasia de órganos sólidos. Actualmente, con el desarrollo de nuevos fármacos análogos de la talidomida, que conservan sus propiedades terapéuticas sin presentar teratogenicidad, su aplicación futura es más promisoria

Talidomida y análogos de talidomida / Thalidomide and analogous

La talidomida se introdujo en la década del 50 como droga hipnótica, sedante y antiemética, especialmente indicada en mujeres gestantes durante el primer trimestre del embarazo. Se asociaron al uso del fármaco graves anormalidades congénitas y polineuropatías, por lo que se la retiró del mercadoen los años 60. Posteriormente se comprobaron propiedades inmunomoduladoras en pacientes con eritema nudoso lepromatoso, así como también efectos antiinflamatorios como lupus eritematoso discoide, enfermedad de Behcet, úlceras aftosas en pacientes con SIDA, enfermedad crónica injerto contra huésped, mieloma múltiple y neoplasia de órganos sólidos. Actualmente, con el desarrollo de nuevos fármacos análogos de la talidomida, que conservan sus propiedades terapéuticas sin presentar teratogenicidad, su aplicación futura es más promisoria (AU)

Dexamethasone-cyclophosphamide pulse therapy in systemic lupus erythematosus.

BACKGROUND AND AIMS: Therapy systemic lupus erythematosus (SLE) has been generally discouraging. Methyl-prednisolone pulse therapy has been used for various connective tissue disorders. We used intravenous dexamethasone cyclophosphamide pulse therapy to treat SLE. METHODS: Fourteen patients (10 females and 4 males) between the age of 15-48 years with definite or classical clinical criteria laid by American Rheumatism Association criteria were treated by Dexamethasone-Cyclophosphamide pulse (DCP) therapy at our center. RESULTS: It was possible to induce a complete clinical remission with DCP therapy in most of the patients thereby offering them life free from disease and drugs. The side effects commonly observed with conventional daily dose regimen of corticosteroids were not present or were mild. CONCLUSIONS: Almost all patients had good response after 3-4 pulses to allow them a normal life style. Fever, malar rash and oral ulceration responded early but photosensitivity, discoid rash, alopecia and joint pains took some more time.

Thalidomide: a re-look.

Thalidomide was synthesized in 1954 in erstwhile West Germany and marketed as a sedative in over 46 countries until the early 1960s. Owing to serious teratogenic effects, the drug was withdrawn from the market in 1961. A chance observation suggested the utility of thalidomide in erythema nodosum leprosum (ENL). After many controlled and uncontrolled trials were published, the World Health Organization recommended its use in ENL. The Food and Drug Administration, USA approved it for use in ENL in July 1998. Only established and well-defined studies conducted to substantiate the efficacy of thalidomide have been included in this review. Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered. Once the anti-inflammatory, immuno-modulatory, anti-TNF-alpha and anti-angiogenic properties of thalidomide were discovered, it was also tried in AIDS and related wasting, apthous ulcers, microsporidiosis and Kaposi's sarcoma. Thalidomide has no clinical place as an immunosuppressant in solid organ transplantation. However, it has a therapeutic role in graft-verus-host-disease. Among the dermatological conditions, thalidomide has been found to be effective in systemic lupus erythematosus, discoid lupus erythematosus, actinic prurigo and prurigo nodularis. Used correctly, it is a safe and effective medicine (except for its teratogenic potential and delayed neuropathy) in a variety of disease conditions.

Coexistent leprosy and lupus erythematosus.

We present a patient who, while under therapy with systemic corticosteroids to control lupus erythematosus, noted lesions of leprosy (Hansen's disease) on her elbow and knee. The corticosteroids may have played a role in the emergence of the leprosy. Leprosy should be considered in the differential diagnosis of cutaneous lesions with sensory loss to hasten diagnosis and therapy.