Treatment of sarcoidosis with cutaneous involvement with tofacitinib

Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids and there are no approved steroid-sparing medications. There is emerging evidence that Janus kinase (JAK) inhibitors, which inhibit JAK-dependent cytokine activity, may hold promise in sarcoidosis. In this open-label trial, 10 patients with recalcitrant sarcoidosis with cutaneous involvement were treated with tofacitinib 5 mg twice daily. There was no washout period and patients were permitted to continue, taper, or discontinue other treatments. The primary outcome was the change in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) activity score after 6 months. Change in internal organ disease activity was also assessed using total lesion glycolysis (TLG) determined by full-body positron emission tomography. A mean reduction in the CSAMI activity score of 82.7% was observed, with 6 patients showing a complete response. Internal organ response data was available in 8 patients; a decrease in TLG of ≥50% was noted in 5 patients, with complete or near complete resolution in 3 (>98% reduction in TLG). Patients were generally able to significantly taper or discontinue their baseline immunosuppressive regimen, which included prednisone in 5 patients. Single cell RNA-sequencing, bulk RNA-sequencing, and high-throughput proteomic analyses were performed on skin and blood as a function of treatment in order to delineate changes in immunologic signals with therapy. We identified CD4+ T cell derived IFN-gamma as a central cytokine driver of sarcoidosis and inhibition of its activity was achieved with tofacitinib and correlated closely with clinical improvement. Tofacitinib appears to have impressive activity in treatment of sarcoidosis and likely acts by inhibiting IFN-gamma, larger, controlled studies are warranted.

A case of chronic cough due to sarcoidosis

Sarcoidosis is a multisystemic, chronic granulomatous disease of unknown aetiology that often affects the lungs. Diagnosis and treatment of sarcoidosis can be strenuous. Patients may be asymptomatic or experience cough, dyspnoea, fatigue, unintentional weight loss or night sweats. Computed tomography is valuable in the diagnosis of sarcoidosis. The typical histopathological lesion of sarcoidosis is granuloma without caseous necrosis in the involved organs. As tuberculosis is endemic in our region, clinicians should not forget this great mimicker. The cornerstone of treatment of sarcoidosis is corticosteroids but newer agents such as steroid-sparing agents and biological agents are available. We report a case of pulmonary sarcoidosis presenting with chronic cough.

ERS clinical practice guidelines on treatment of sarcoidosis

BackgroundThe major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin, or other manifestations. While glucocorticoids (GC) remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. GC-sparing alternatives are available. The presented treatment guideline aims to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations.Materials and MethodsA European Respiratory Society Task Force (TF) committee composed of clinicians, methodologists, and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations.ResultsThe TF committee delivered twelve recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac, and neurologic disease as well as fatigue. One PICO question regarding small fiber neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation.ConclusionsThere are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment.MessageAn evidence based guideline for treatment of sarcoidosis is presented. The panel used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life.

Sarcoidosis and Primary Biliary Cholangitis- An Overlap

Primary Biliary Cholangitis (PBC) is a chronic progressive autoimmune cholestatic liver disease. Sarcoidosis is a multisystem chronic granulomatous disease. Both diseases are known to affect the liver causing granulomas. Sarcoidosis commonly involves the skin while PBC is associated with autoimmune skin disorders. Diagnosis of PBC requires biochemical, serological and histological confirmation. Steroids are used in the treatment of sarcoidosis. The role of steroids in the treatment of PBC is not completely established. In this case report, authors present the case of a 31-years-old female diagnosed as sarcoidosis based on granulomatous lesions in skin biopsy with concurrent PBC diagnosed on basis of serology and liver biopsy.

The role of vitamin D in sarcoidosis

After the initial description of extrarenal synthesis of 1,25-dihydroxyvitamin D (1,25-(OH)2D) three decades ago, extensive progress has been made in unraveling the immunomodulatory roles of vitamin D in the pathogenesis of granulomatous disorders, including sarcoidosis. It has been shown that 1,25-(OH)2D has dual effects on the immune system, including upregulating innate immunity as well as downregulating the autoimmune response. The latter mechanism plays an important role in the pathogenesis and treatment of sarcoidosis. Vitamin D supplementation in patients with sarcoidosis has been hampered owing to concerns about the development of hypercalcemia and hypercalciuria given that extrarenal 1-α hydroxylase is substrate dependent. Recently, a few studies have cast doubt over the mechanisms underlying the development of hypercalcemia in this population. These studies demonstrated an inverse relationship between the level of vitamin D and severity of sarcoidosis. Consequently, clinical interest has been piqued in the use of vitamin D to attenuate the autoimmune response in this disorder. However, the development of hypercalcemia and the attendant detrimental effects are real possibilities. Although the average serum calcium concentration did not change following vitamin D supplementation, in two recent studies, hypercalciuria occurred in one out of 13 and two out of 16 patients. This review is a concise summary of the literature, outlining past work and newer developments in the use of vitamin D in sarcoidosis. We feel that larger-scale placebo-controlled randomized studies are needed in this population. Since the current first-line treatment of sarcoidosis is glucocorticoids, which confer many systemic adverse effects, and steroid-sparing immunosuppressant treatment options carry additional risks of adverse effects, adjunct management with vitamin D in combination with potent anti-osteoporotic medications could minimize the risk of glucocorticoid-induced osteoporosis and modulate the immune system to attenuate disease activity in sarcoidosis.

Evaluation of the efficacy and safety of methotrexate in progressive sarcoidosis: a retrospective observational study

Sarcoidosis is epithelioid cell granulomatosis of unknown etiology. All the schemes of its treatment are of a recommendatory nature. Methotrexate (MTT) is considered a second-line drug in the treatment of sarcoidosis.Methods. A retrospective observational study of patients with progressive sarcoidosis (n = 104), treated with MTT once a week, was carried out. Clinical, laboratory, functional and radiation parameters were evaluated with an interval of 3 months ≤ 1 year.Results. The use of MTT was accompanied by an improvement in the radiation picture (64.1% by the end of the year), an improvement not only in spirometry parameters, starting from the 3rd month (54.7%), but also in the general condition of the patients (63.8% – at the 6th month). Adverse reactions with drug withdrawal were most often observed (15.4%) during the first 3 months, and subsequently their frequency decreased.Conclusion. According to the results of the study, it was shown that methotrexate can be recommended for further use in progressive sarcoidosis, as well as in patients, who have previously received systemic glucocorticosteroids.