Impact of dysphagia and its severity on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathies other than inclusion body myositis.

OBJECTIVE: To investigate the impact of dysphagia on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis. METHODS: We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time-to-event analyses were used, including Kaplan-Meier curves with log-rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models. RESULTS: Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non-dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non-dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age-adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36-1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69-3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non-severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases. CONCLUSION: The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia.

Baseline clinical features predicting macrophage activation syndrome in patients with systemic adult-onset Still's disease receiving interleukin-6 inhibitor treatment.

AIM: Macrophage activation syndrome (MAS), a severe complication of systemic adult-onset Still's disease (AOSD), has been reported to occur during interleukin-6 (IL-6) inhibitor treatment. However, predictors for MAS development are unknown. Therefore, this study investigated predictive features for MAS development after starting IL-6 inhibitor treatment in systemic AOSD patients. METHOD: In a single-center retrospective study involving systemic AOSD patients who were refractory to high-dose glucocorticoids with immunosuppressants and started IL-6 inhibitor treatment between April 2008 and March 2020, we compared the baseline clinical features between patients who developed AOSD flare with MAS features (MAS group) and those who did not (non-MAS group) during IL-6 inhibitor treatment. RESULTS: Only tocilizumab was used as an IL-6 inhibitor. Six of 14 refractory systemic AOSD patients developed AOSD flares with MAS features during tocilizumab treatment, including 4 who developed them shortly after initiation. The MAS group had significantly lower neutrophil counts, fibrinogen, and higher IL-18/C-reactive protein (CRP) ratio at starting tocilizumab (baseline) than the non-MAS group. Before starting tocilizumab, neutrophil counts were trending downward and upward in the MAS and non-MAS groups, respectively, with significant differences in changes. Receiver operating characteristic analysis showed that baseline neutrophil counts and fibrinogen and their changes before tocilizumab treatment and baseline IL-18/CRP ratio had significant discriminatory abilities for subsequent MAS development. CONCLUSION: We identified baseline laboratory features associated with MAS development after initiating an IL-6 inhibitor in refractory systemic AOSD patients. These features may reflect the suppression of IL-6 signaling, and further suppression of IL-6 signaling might trigger early-onset MAS.

Improvement of Chronic Rhinosinusitis and Reduction of the Myeloperoxidase-Antineutrophil Cytoplasmic Antibody Titer in a Patient with Eosinophilic Granulomatosis with Polyangiitis by Additional Mepolizumab.

A case of eosinophilic granulomatosis with polyangiitis (EGPA) in which chronic rhinosinusitis (CRS) was improved with a reduction in the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer after the addition of mepolizumab is reported. A 55-year-old woman with EGPA receiving prednisolone 5 mg/day developed CRS with increases in the eosinophil count and the MPO-ANCA titer. Although it improved with prednisolone 15 mg/day in addition to mizoribine 150 mg/day, because azathioprine could not be taken orally due to side effects, it relapsed after prednisolone was tapered to 5 mg/day. There was no exacerbation of other vasculitis symptoms such as mononeuropathy multiplex. The patient was treated with additional mepolizumab 300 mg every 4 weeks, which resulted in the improvement of CRS and marked reductions of the eosinophil count and MPO-ANCA titer, and the reduction of prednisolone to 2 mg/day. Furthermore, even after tapering mepolizumab to 200 mg every 4 weeks, her condition remained stable without relapse of EGPA and without increases in the eosinophil count and MPO-ANCA titer. The clinical course of mepolizumab treatment in this patient suggests that the IL5-dependent inflammatory cascade is one of the factors contributing to the increase in MPO-ANCA in EGPA.

Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of Adult-Onset Still's Disease with Liver Failure with No Response to Tocilizumab Therapy.

A 21-year-old woman with refractory systemic flare of adult-onset Still's disease with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus, and tocilizumab, was successfully treated with additional use of etanercept. Etanercept at a dose of 50 mg weekly was partially effective but could not reduce the dose of concomitant betamethasone from 5 mg/day. Etanercept at a dose of 75 mg weekly could lead her to clinical remission and enabled successful tapering off the corticosteroids and discontinuation of etanercept. Normalization of serum C-reactive protein and interleukin 6 and persistent elevation of serum tumor necrosis factor α under the treatment with high-dose corticosteroids and immunosuppressants suggest that tumor necrosis factor α was more deeply involved than at least interleukin 6 in the pathogenesis of refractoriness of the disease in this patient, and these findings might be indicative of potential efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an interleukin 6 inhibitor.