Refractory Cutaneous Dermatomyositis With Severe Scalp Pruritus Responsive to Apremilast.

ABSTRACT: Dermatomyositis (DM) is a subset of idiopathic inflammatory myopathy with characteristic cutaneous manifestations and muscle weakness. Conventional treatments for DM include glucocorticoids and other immunosuppressive or immunomodulatory agents including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, and intravenous immunoglobulin. Refractory patients require more aggressive or novel therapies. Apremilast has not been studied for the management of refractory cutaneous DM. We report a case of a patient with refractory DM with severe scalp pruritus treated with apremilast who demonstrated significant improvement in her skin disease and complete resolution of scalp pruritus.

Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib.

OBJECTIVES: Some patients with cutaneous DM demonstrate incomplete responses to conventional therapy while some, including those with extra-cutaneous manifestations, experience disease recurrences. Janus kinase/signal transducers and activators of transcription pathway inhibition has been reported to mitigate IFN signalling, which is thought to contribute to disease pathogenesis in DM. Four cases of refractory DM responsive to tofacitinib have been reported in the literature. Our case series investigated the use of tofacitinib in refractory cutaneous DM. METHODS: Our case series includes four subjects with refractory DM who received tofaticinib after failure of several immunosuppressive and immunomodulatory agents. RESULTS: All four subjects responded well to tofacitinib with significant improvement in cutaneous and extra-cutaneous manifestations. CONCLUSION: Tofacitinib can improve cutaneous and inflammatory articular manifestations in refractory DM.

Development of Pulmonary Hypertension in Over One-Third of Patients With Th/To Antibody-Positive Scleroderma in Long-Term Follow-Up.

OBJECTIVE: This study was undertaken to describe clinical manifestations in patients with Th/To antibody-positive systemic sclerosis (SSc) during long-term follow-up. METHODS: We performed a case-control study involving anti-Th/To antibody-positive patients with SSc who were newly referred to the University of Pittsburgh Medical Center and the Pittsburgh Scleroderma Center from 1980 to 2015. For every case, 2 anti-Th/To antibody-negative SSc patients (the first 2 consecutively seen after a case) were used as controls. Long-term disease manifestations and survival were then compared between cases and controls. RESULTS: A total of 204 anti-Th/To antibody-positive SSc patients and 408 controls were identified. The cohort had a mean ± SD age of 52 ± 12.9 years, and 76% of individuals were women. Anti-Th/To antibody-positive patients more often presented without skin thickening (P < 0.0001) and had a higher rate of pulmonary hypertension (PH) (P < 0.0001) and interstitial lung disease (P = 0.05) compared to anti-Th/To antibody-negative SSc controls. Anti-Th/To antibody-positive SSc patients also had less frequent muscle and joint involvement than anti-Th/To antibody-negative SSc controls (P < 0.0001). After a median clinical follow-up period of 6.1 years (interquartile range 2.4-12.7), 38% of anti-Th/To-positive patients had developed PH compared to 15% of anti-Th/To antibody-negative SSc controls (P < 0.0001). The rate of PH classified as World Health Organization (WHO) Group 1 pulmonary arterial hypertension [PAH] was 23% in anti-Th/To-positive patients compared to 9% in anti-Th/To antibody-negative SSc controls (P < 0.0001). After adjusting for age and sex, anti-Th/To antibody positivity was associated with a hazard ratio (HR) of 3.3 (95% confidence interval 2.3-4.9) for increased risk of developing PH at 10 years of follow-up from the first scleroderma center visit. CONCLUSION: This is the largest cohort of patients with anti-Th/To antibody-positive SSc with long-term follow-up data. The very high rate (38%) and associated independent risk of anti-Th/To antibody-positive patients developing PH in follow-up, particularly in WHO Group 1 PAH patients, is striking. Patients presenting with limited skin involvement should be tested for Th/To antibodies, and if present, careful monitoring for PH is warranted.

Superporous hydrogels for cartilage repair: Evaluation of the morphological and mechanical properties.

Despite extensive research in the design of biomaterials for articular cartilage repair, there remains a need for the development of materials with the mechanical compliance to function synergistically with healthy cartilage, but porous enough to allow for tissue integration. In this study, superporous hydrogels of poly(vinyl alcohol) and poly(vinyl pyrrolidone) were prepared using a novel technique consisting of a double emulsion process. The hydrogel emulsions were physically cross-linked by freeze-thaw cycling. The hydrogels had a high degree of porosity, determined using environmental scanning electron microscopy, a technique superior to any method that involves dehydrating the samples. Increasing the volume of organic solvent increased porosity, due to cross-linking of the hydrogel solution around the droplets in the emulsion, leaving pores where the organic solvent was present. Poly(lactic-co-glyclic acid) microparticles formed and were embedded in the matrix. The mechanical properties, measured in confined creep and in unconfined, uniaxial compression, were similar to native articular cartilage. The permeability of the samples was unaffected by changing solvent content, despite changes in porosity. These materials are good candidates for tissue engineering of cartilage because they can mimic mature cartilage mechanically while providing a porous matrix through which cells can migrate and proliferate.

Semi-degradable scaffold for articular cartilage replacement.

Existing technologies have not met the challenge of designing a construct for the repair of focal cartilage defects such that it mimics the mechanical properties of and can integrate with native cartilage. Herein we describe a novel construct consisting of a non-degradable poly-vinyl alcohol (PVA) scaffold to provide long-term mechanical stability, interconnected pores to allow for the infiltration of chondrocytes, and poly-lactic glycolic acid (PLGA) microspheres for the incorporation of growth factors to enhance cellular migration. The objective of this study was to characterize the morphological features and mechanical properties of our porous PVA-PLGA construct as a function of PLGA content. Varying the PLGA content was found to have a significant effect on the morphological features of the construct. As PLGA content increased from 10% to 75%, samples exhibited a 6-fold increase in average percentage porosity, an increase in average microsphere diameter from 8 to 34 microm and an increase in average pore diameter from 29 to 111 microm. The effect of PLGA content on aggregate modulus and permeability was less profound. Our findings suggest that that morphology of the construct can be tailored to optimize cellular infiltration and the dynamic mechanical response. The experiments herein presented were conducted at the Hospital for Special Surgery.