Emergency medicine updates: Acute diverticulitis.

INTRODUCTION: Acute diverticulitis is a condition commonly seen in the emergency department (ED). Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this disease. OBJECTIVE: This paper evaluates key evidence-based updates concerning acute diverticulitis for the emergency clinician. DISCUSSION: Diverticulitis is a complication of diverticulosis and most commonly affects the sigmoid and descending colon in Western countries. History and examination can suggest the diagnosis, with abdominal pain and tenderness in the left lower quadrant being the most common symptom and sign, respectively. Change in bowel habits and fever may also occur. Laboratory testing may demonstrate leukocytosis or an elevated C-reactive protein. Imaging options can include computed tomography (CT) of the abdomen and pelvis with intravenous contrast, magnetic resonance imaging (MRI), or ultrasound (US), though most classification systems for diverticulitis incorporate CT findings. While the majority of diverticulitis cases are uncomplicated, complications may affect up to 25% of patients. Treatment of complicated diverticulitis requires antibiotics and surgical consultation. Antibiotics are not required in select patients with uncomplicated diverticulitis. Appropriate patients for supportive care without antibiotics should be well-appearing, have pain adequately controlled, be able to tolerate oral intake, be able to follow up, have no complications, and have no immunocompromise or severe comorbidities. CONCLUSIONS: An understanding of literature updates can improve the ED care of patients with acute diverticulitis.

More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.

Objective: To study disease severity and response to therapy in a large cohort of patients with anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)-associated myositis. Methods: Muscle strength, creatine kinase levels and treatments were assessed in anti-HMGCR-positive patients at each clinical visit. Univariate and multivariate analyses were used to analyse the influence of clinical characteristics on strength and the change in strength over time. Whole exome sequencing was performed in a subset of patients. Results: . Among 50 patients followed for ⩾2 years, only 22 (44%) reached full strength with immunosuppressive therapy; even among those with full strength, 55% continued to have CK levels in excess of 500 IU/l and only three could be tapered off immunosuppressive therapy. Both univariate and multivariate analysis showed that patients who were older at disease onset were stronger at all time points (P < 0.001) and improved faster (P < 0.008) than younger patients; a history of statin exposure was not independently associated with the improvement rate. Younger patients were more likely to have refractory disease (P = 0.02) than older patients. Among eight refractory patients with DNA available for testing, whole exome sequencing did not reveal pathogenic mutations in known dystrophy genes. The risk of cancer was not increased in anti-HMGCR myositis patients compared with the general population. Conclusions: Anti-HMGCR myositis is usually a chronic disease requiring long-term immunosuppression. Although younger patients had more severe disease and a worse prognosis than older patients, they did not have evidence of a known co-existing muscular dystrophy to explain their persistent, and sometimes progressive, muscle weakness.

Longitudinal Course of Disease in a Large Cohort of Myositis Patients With Autoantibodies Recognizing the Signal Recognition Particle.

OBJECTIVE: Patients with immune-mediated necrotizing myopathy (IMNM) often have autoantibodies recognizing the signal recognition particle (SRP) or HMG-CoA reductase (HMGCR). Here, we studied a cohort of anti-SRP patients to identify factors associated with disease severity and clinical improvement; we also compared the severity of weakness in those with anti-SRP versus anti-HMGCR autoantibodies. METHODS: All anti-SRP patients in the Johns Hopkins Myositis Cohort from 2002 to 2015 were included. Longitudinal information regarding proximal muscle strength, creatine kinase (CK) levels, and immunosuppressive therapy was recorded at each visit. Univariate and multivariate multilevel regression models were used to assess prognostic factors influencing recovery. Strength in the anti-SRP patients was compared to strength in 49 previously described anti-HMGCR subjects. RESULTS: Data from 37 anti-SRP patients and 380 total clinic visits were analyzed. Younger age at onset was associated with more severe weakness at the first visit (P = 0.02) and all subsequent visits (P = 0.002). Only 50% of patients reached near-full or full strength after 4 years of treatment, and most of these continued to have elevated CK levels. Rituximab appeared to be effective in 13 of 17 anti-SRP patients. Anti-SRP patients were significantly weaker than those with anti-HMGCR autoantibodies (-1.3 strength points; P = 0.001). CONCLUSION: Younger age at onset is associated with more severe weakness in anti-SRP myositis. Furthermore, even among anti-SRP patients whose strength improved with immunosuppression, most had ongoing disease activity as demonstrated by elevated CK levels. Finally, anti-SRP patients were significantly weaker than anti-HMGCR patients, providing evidence that these autoantibodies are associated with distinct forms of IMNM.

Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum.

OBJECTIVE: Autoantibodies against melanoma differentiation-associated protein 5 (MDA-5) have been described in several Asian dermatomyositis (DM) cohorts, often associated with amyopathic DM and rapidly progressive interstitial lung disease (ILD). A recent study of a DM cohort seen at a US dermatology clinic reports that MDA-5 autoantibodies are associated with a unique cutaneous phenotype. Given the widening spectrum of clinical findings, we evaluated the clinical features of anti-MDA-5-positive patients seen at a US myositis referral center. METHODS: One hundred sixty DM patients were screened for MDA-5 autoantibodies by immunoprecipitation and antibody titers were analyzed in longitudinal serum samples. Anti-MDA-5-positive patients were evaluated for the presence of additional myositis autoantibodies. Patient clinical characteristics were compared by retrospective chart review. RESULTS: MDA-5 was targeted in 11 (6.9%) of 160 patients with DM. Of these, 9 presented with a symmetric polyarthropathy, 6 demonstrated overt clinical myopathy, and 8 had ILD. Eight anti-MDA-5-positive patients exhibited the clinical attributes of the antisynthetase syndrome in the absence of Jo-1 or other antisynthetase autoantibodies. MDA-5 autoantibody titers did not correlate with clinical course. CONCLUSION: MDA-5 autoantibodies are found in DM patients presenting with a symmetric polyarthritis, clinically similar to rheumatoid arthritis. These patients often have features of the antisynthetase syndrome, but in the absence of antisynthetase autoantibodies. Most anti-MDA-5-positive patients had overt clinical myopathy and ILD. The latter, while occasionally severe, typically resolved with immunosuppressive therapy. In this cohort, the MDA-5 phenotype is frequently a clinical mimic of the antisynthetase syndrome and is not associated with rapidly progressive ILD.

Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.

OBJECTIVE: Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti-HMGCR antibody levels with disease activity. METHODS: Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR-positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin-exposed and 5 statin-unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated. RESULTS: Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin-exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin-exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any patient. CONCLUSION: In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin-exposed patients had significant improvements in CK levels and strength whereas statin-unexposed patients did not, suggesting a phenotypic difference between statin-exposed and statin-unexposed anti-HMGCR-positive patients.