Ernste, Floranne C.

Abstract Objective To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. Methods We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. Results We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren’s syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren’s syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. Conclusions IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren’s syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.

ObjectiveTo determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades.MethodsThe previously identified population‐based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970–1999 was extended to include patients with incident PsA during 2000–2017. Age‐ and sex‐specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported.ResultsThere were 164 incident cases of PsA in 2000–2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age‐ and sex‐adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2–9.8) and was higher in men (9.3 [95% CI 7.4–11.3]) than women (7.7 [95% CI 5.9–9.4]) in 2000–2017. Overall incidence was highest in the 40–59 years age group. The incidence rate was relatively stable during 2000–2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970–1999 when a 4%‐per‐year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5–207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970–1999 and 41% in 2000–2009 to 54% in 2010–2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61–1.15]).ConclusionThe incidence of PsA in this predominantly White US population was stable in 2000–2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.

AbstractBackgroundAnti‐cytosolic 5′‐nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results.MethodsWe first searched for patients, seen in our clinics, tested for anti‐cN1A antibodies between December 2015 and December 2019. We identified 92 patients who were diagnosed with sIBM, according to the 2011 ENMC or Griggs et al criteria. Thereafter, we reviewed and compared the clinical and investigational findings of these patients in relation to their antibody status.ResultsAnti‐cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value, or presence of myotonic discharges on EMG. Anti‐cN1A antibody positive patients appeared to have more frequent auto‐aggressive inflammation on muscle biopsy but not as an isolated myopathological feature.ConclusionsOur study showed that anti‐cN1A antibody positive and negative sIBM patients have similar clinical features and disease severity. Anti‐cN1A antibodies in our sIBM cohort did not correlate with any studied clinical or laboratory parameter and, therefore, were of limited value in the patient's assessment.

Systemic sclerosis (SSc) is characterised by non-inflammatory vasculopathy, autoimmunity and widespread fibrosis. While the presence of antineutrophil cytoplasmic antibodies (ANCAs) has been reported in SSc, their association with ANCA-associated vasculitis is exceedingly rare. Myeloperoxidase ANCA is more common than proteinase-3 ANCA, and glomerulonephritis is the most common clinical presentation of ANCA-associated vasculitis in SSc. ANCAs have been associated with the adverse disease outcomes in SSc, including higher mortality per recent reports. A 65-year-old man with diffuse cutaneous SSc for 6 years presented with new-onset peripheral neuropathy. Workup revealed a positive proteinase-3 and cytoplasmic ANCA, and histopathology confirmed an inflammatory vasculitic neuropathy. The patient was successfully treated with rituximab. Our case highlights the importance of checking ANCA in SSc at baseline, given the risk of disease-related complications, even years later. Tissue biopsy is often warranted for confirmation of vasculitis and prompt treatment can optimise long-term outcomes.

» Treatment of the patient with rheumatoid arthritis affecting the hand and wrist can be a challenging endeavor. Optimal management for best outcomes includes careful collaboration between providers managing the medical treatment of the disease, therapists, hand surgeons, and the patient. » In this review, we present a challenging clinical scenario with input from key voices from various medical fields to provide a balanced and unbiased diagnosis and treatment recommendation for a patient with complex rheumatoid pathology affecting her hand and wrist.

ObjectiveType I interferon (IFN) is important to systemic lupus erythematosus (SLE) pathogenesis, but it is not clear how chronic elevations in IFN alter immune function. We compared cytokine responses after whole blood stimulation with Toll‐like receptor (TLR) agonists in high‐ and low‐IFN SLE patient subgroups.MethodsSLE patients and nonautoimmune controls were recruited, and SLE patients were categorized as either high or low IFN. Whole blood was dispensed into tubes coated with lipopolysaccharide (LPS), oligonucleotides with cytosine‐guanine repeats, Resiquimod, IFN‐α, and IFN‐α + LPS. Cytokine production in patient sera and after whole blood TLR stimulation was measured by multiplex assay, and type I IFN was assessed using a functional assay.ResultsCirculating plasmacytoid dendritic cell numbers were specifically reduced in high‐IFN SLE patients and not in low‐IFN SLE patients. In serum, we observed that the correlations between cytokines in serum differed to a much greater degree between the high‐ and low‐IFN groups (P < 0.0001) than the absolute cytokine levels differed between these same groups. In stimulated conditions, the high‐IFN patients had less cytokine production in response to TLR ligation than the low‐IFN SLE patients. LPS produced the most diverse response, and a number of interactions between type I IFN and LPS were observed.ConclusionWe find striking differences in resting and stimulated cytokine patterns in high‐ vs. low‐IFN SLE patients, which supports the biological importance of these patient subsets. These data could inform personalized treatment approaches and the pathogenesis of SLE flare following infection.

Necrotising autoimmune myopathy (NAM) is an immune-mediated myopathy that may be associated with statin use, malignancy or an autoimmune connective tissue disease, but it can also be idiopathic. Anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is an extremely rare side effect of statin use, occurring in approximately 2–3 out of every 100 000 patients who use statins. Patients typically present with subacute proximal muscle weakness and creatine kinase levels >10 times the upper limit of normal. The diagnosis is suggested by muscle biopsy showing necrotic fibres with minimal inflammation along with positive anti-HMGCR antibodies. Treatment nearly always requires multiple immunosuppressive agents, the earlier use of which is associated with improved outcomes. Reports of statin-induced NAM leading to heart failure are limited. We present the case of a 69-year-old woman with statin-induced NAM who presented with acute systolic heart failure. Early initiation of high-dose corticosteroids and IVIG resulted in significant improvement in her symptoms.