Tofacitinib therapy in refractory inflammatory myositis: a retrospective cohort study of 41 patients.

OBJECTIVES: To evaluate the efficacy and safety of tofacitinib in treatment-refractory inflammatory myositis in a real-world clinical setting. METHODS: All patients with refractory inflammatory myositis treated with tofacitinib from a single urban center in Vancouver, British Columbia, Canada, were included from June 2016 to December 2022. The medical records of these patients were retrospectively reviewed. RESULTS: A total 41 patients were included, 23 with classic dermatomyositis (DM), 12 with amyopathic DM (ADM) and 6 with polymyositis (PM) phenotype. The patients failed an average of 4-5 non-steroidal immunosuppressants before initiation of tofacitinib. In the classic DM and ADM group, tofacitinib offered clinically and statistically significant cutaneous improvement. In all myositis patients including the PM phenotype, no meaningful muscle strength response to tofacitinib was observed. 53.7% of the patients discontinued tofacitinib due to lack of benefit or death. Of the 19 patients who remained on tofacitinib at the conclusion of this study, tofacitinib demonstrated clinically and statistically significant improvement in cutaneous disease activity. CONCLUSION: Tofacitinib appears to be highly effective in targeting cutaneous manifestations in classic DM and ADM; however, minimal benefit in muscle strength in the DM or PM phenotype were observed.

Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant.

Anti-melanoma differentiation-associated protein 5 (anti-MDA5) is a subset of dermatomyositis associated with respiratory complications, in which rapidly progressive interstitial lung disease (RPILD) is commonly cited, and spontaneous pneumomediastinum (SPM) is a rare complication. In medical literature, aggressive immunosuppressive therapy has been the mainstay of anti-MDA5-associated SPM management. Here, we report the first MDA5 case with SPM which was successfully treated with a double-lung transplant. We present a 48-year-old male who presented with multiple constitutional symptoms such as fevers, weight loss, malaise, and arthralgias, in association with erythroderma over the ears and fingers. Imaging of the chest demonstrated peripheral airspace disease, and myositis-specific serology returned positive for anti-Jo1 (medium-positive), anti-Ro52 (high-positive), and anti-MDA5 (weak-positive) autoantibodies. Therefore, the patient was begun on immunosuppressive therapy as the leading diagnosis included autoimmune myositis, possibly antisynthetase syndrome with interstitial lung disease (ILD). A year later, the patient presented with progressive shortness of breath, widespread macular erythematous facial rash, and new erythematous ulcerations over the fingertips. Imaging demonstrated a new SPM at this juncture. As the patient's respiratory status continued to decline despite the use of immunosuppressive agents, a double-lung transplant was performed. Therefore, we propose that lung transplantation should be considered early in MDA5-SPM.

Epidemiology and Treatment of Peripheral Neuropathy in Systemic Sclerosis.

OBJECTIVE: The epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc. METHODS: A systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy. RESULTS: This systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35-32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig. CONCLUSION: All-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.

Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results.

BACKGROUND: Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. METHODS: Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016-July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. RESULTS: We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives.In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives.Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7-189.2, p < 0.001) and strong positive (versus weak positive) results (4.4, 2.3-8.3, p < 0.001). CONCLUSIONS: We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.

Risk of Myocardial Infarction and Stroke in Newly Diagnosed Systemic Lupus Erythematosus: A General Population-Based Study.

OBJECTIVE: To estimate the future risk and time trends of newly diagnosed myocardial infarction (MI), ischemic stroke, or both (cardiovascular disease [CVD]) in individuals with systemic lupus erythematosus (SLE). METHODS: Using a population-based database that includes all residents of British Columbia, Canada, we conducted a matched cohort study of all patients with incident SLE and up to 10 age-, sex-, and entry time-matched individuals from the general population. We compared incidence rates (IRs) of MI, ischemic stroke, or CVD (i.e., MI or ischemic stroke) between the 2 groups according to SLE disease duration. We calculated hazard ratios (HRs), adjusting for confounders. RESULTS: Among 4,863 individuals with SLE (86% female, mean age 48.9 years), the IRs of MI, stroke, and CVD were 6.4, 4.4, and 9.9 events per 1,000 person-years, respectively, versus 2.8, 2.3, and 4.7 events per 1,000 person-years in the comparison cohort. Compared with non-SLE individuals, the fully adjusted multivariable HRs among SLE patients were 2.61 (95% confidence interval [95% CI] 2.12-3.20) for MI, 2.14 (95% CI 1.64-2.79) for stroke, and 2.28 (95% CI 1.90-2.73) for CVD. The age-, sex-, and entry time-matched HRs for MI, stroke, and CVD were highest during the first year after SLE diagnosis: 5.63 (95% CI 4.02-7.87), 6.47 (95% CI 4.42-9.47), and 6.28 (95% CI 4.83-8.17), respectively. CONCLUSION: Patients with SLE have an increased risk of cardiovascular events, particularly during the first year after diagnosis. Increased vigilance in monitoring for these potentially fatal outcomes and their modifiable risk factors is recommended in this patient population.

Septic arthritis of the pubic symphysis from Pseudomonas aeruginosa: reconsidering traditional risk factors and symptoms in the elderly patient.

A high-functioning 82-year-old man presented with lower lumbar pain and pubic tenderness. On admission he was afebrile with a normal white count. A grossly elevated C reactive protein was noted. CT scan of the pelvis showed a fluid collection anterior to the pubic symphysis and to the right of the midline measuring 2.0 × 2.2 cm. Pseudomonas aeruginosa was cultured from the fluid collection. The patient had no history of intravenous drug use, pelvic surgeries, malignancies or trauma. We report what we believe is the first documented case of P aeruginosa infection of the pubic symphysis in an elderly patient that did not have any of the traditional risk factors associated with neither P aeruginosa septic arthritis nor infections of the pubic symphysis. Instead, we propose that phimosis with chronic infection of the foreskin and balanitis may have led to septic arthritis.