Faculty Bibliography

Extra-intestinal manifestations are frequent complications of the classical inflammatory bowel diseases, Crohn's disease and ulcerative colitis. However, in addition to the classical diseases, there is a spectrum of conditions, often termed "microscopic colitis", in which extra-intestinal manifestations are less well described. Our objective was to review the literature regarding the extra-intestinal manifestations complicating microscopic colitis and describe the association with systemic autoimmune rheumatic diseases. A comprehensive search and review of peer-reviewed English-language and international journals and reports was completed based on key terms, including "microscopic colitis", "lymphocytic colitis", "collagenous colitis", "inflammatory bowel disease", "extraintestinal manifestations", and the specific disease associations utilizing the PubMed Central database and MEDLINE. A broad spectrum of rheumatologic manifestations has been reported in patients with microscopic colitis. The identification of rheumatoid arthritis and limited scleroderma as co-morbidities with microscopic colitis was noteworthy. Inflammatory arthropathy was frequently seen in microscopic colitis, usually preceding or occurring in conjunction with the onset of gastrointestinal symptoms. A variety of presentations of associated arthritis were reported: migratory, symmetric or asymmetric, peripheral or axial, oligoarticular or polyarticular, erosive or non-erosive. There was a high incidence of autoantibodies in these patients, supporting a potential autoimmune association. On the basis of these anecdotal reports, we would suggest development of a clinical registry to help define the incidence of extra-intestinal manifestations and systemic autoimmune rheumatic diseases among microscopic colitis patients to help elucidate shared predispositions, pathogenic mechanisms and therapeutic opportunities.

Although autoimmune manifestations can be associated with various lymphomas, they are distinctly unusual with primary cutaneous anaplastic large cell lymphoma (PCALCL). We present the case of a 76-year-old woman who, over the course of 2 years, presented with a variety of autoimmune disorders including minimal change disease and focal glomerulosclerosis, visual loss due to retinal vasculitis, immune mediated thrombocytopenia, autoimmune hemolytic anemia, and inflammatory polyarthritis in conjunction with elevated rheumatoid factor, cryoglobulins, and hypocomplementemia. She ultimately developed PCALCL that took an aggressive course and to which she ultimately succumbed. Our case adds to the growing literature demonstrating autoimmune manifestations associated with a variety of lymphoid malignancies. We propose that immune dysregulation can predispose patients to the development of both autoimmune and lymphoproliferative disease. Suspicion of underlying malignancy in patients presenting with otherwise unexplained autoimmune phenomena may prompt earlier diagnosis.

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjögren's syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (± 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for ≥ 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA.

The objectives of this analysis were to assess the prevalence of Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA) and to compare baseline characteristics of patients with RA with and without SS. Adult patients with RA from a large observational US registry (Corrona RA), with ≥ 1 visit for assessment of SS status between 22 April 2010 and 28 February 2018, were considered. Patients with RA with versus without SS were compared. SS status was determined from a yes/no variable and reported at enrollment into the Corrona RA registry and follow-up visits. Outcomes were unadjusted prevalence of SS in patients with RA, prevalence of SS by RA disease duration, and baseline characteristics in patients with RA by SS status. Of 24,528 eligible patients, 7870 (32.1%) had a diagnosis of RA and SS. The unadjusted overall rate for SS prevalence in patients with RA was 0.30 (95% confidence interval 0.29, 0.31). SS prevalence increased with increasing RA duration. Patients with RA with versus without SS were more likely to be older, female, and seropositive; had a longer RA duration; higher disease activity; and a higher incidence of comorbidities (hypertension, cardiovascular disease, malignancies, and serious infections), erosive disease, and subcutaneous nodules at index date. Patients with RA and SS had a higher disease burden than those with RA only. The prevalence of SS increased as duration of RA increased. RA with SS was associated with seropositivity, more severe RA, extra-articular manifestations, and comorbidities.Key Points• The overall prevalence of SS among patients with RA was 30%.• The prevalence of SS increased with increasing RA disease duration.• Identifying specific clinical characteristics of patients with RA with SS, such as a greater incidence of extra-articular manifestations and comorbidities, may help clinicians to better characterize this patient population.

Human parvovirus B19 (B19V) is well known for its infectivity. However, the risk for communicability to previously unexposed healthcare professionals is controversial. We report here a small outbreak of B19V infection among physicians and family members in an adult rheumatology practice that occurred after providing care for a patient with B19V arthropathy. As B19V-infected patients who demonstrate findings of erythema infectiosum or viral arthritis are generally beyond the period of transmissability, strict handwashing and droplet precautions remain imperative when there is contact with potentially pre-symptomatic family members.

Malignant catatonia represents a potentially life-threatening presentation of catatonia that typically includes fever, autonomic instability, and cardiovascular collapse. Failure to respond to benzodiazepines, particularly with an increase in catatonic signs, should raise suspicion for the presence of malignant catatonia. Here, we report the first case of malignant catatonia as the initial manifestation of systemic lupus erythematosus (SLE) presenting in a 15-year-old girl who developed progressive catatonia that was resistant to immunosuppressive therapy with pulse corticosteroids, intravenous immunoglobulin (IVIg), and cyclophosphamide and required electroconvulsive therapy for clinical improvement. Catatonia in SLE is reviewed and contrasted with other types of autoimmune encephalopathies, anti-NMDAR antibody encephalitis, and Hashimoto encephalopathy (HE), highlighting the diagnostic considerations and clinical challenges.

At the intersection of atopy and autoimmunity, we present a patient with seronegative rheumatoid arthritis (RA) who developed hypereosinophilia, without evidence of other etiologies, as she became rheumatoid factor (RF) positive. Although the magnitude of eosinophilia in patients with RA has been thought to reflect the severity or activity of the RA, in our patient, eosinophilia developed at a time when the patient's synovitis was well controlled. Although eosinophilia may reflect associated drug hypersensitivity, discontinuation of the medications utilized to control our patient's disease, adalimumab and methotrexate, did not promote clinical improvement. Probably the most curious aspect of our patient was the concomitant development of rheumatoid factor seropositivity in the setting of previously seronegative RA. The temporal relationship between the development of peripheral eosinophilia and seroconversion suggests a possible connection between these events. We speculate that the T cell cytokine production that can induce eosinophilia may simultaneously activate RF production.

The aim of this review is to analyze the available literature regarding the neuropsychiatric (NP) disturbances associated with corticosteroid (CS) therapy; to determine the nature, severity, and frequency of these NP symptoms; and to identify the various risk factors involved in the development of CS-induced NP disturbances. We searched the available literature since the advent of corticosteroid therapy (1950) utilizing the PubMed database ( www.pubmed.gov). Primary articles were identified, and they and their pertinent references were reviewed. Due to potential confusion between NP manifestations of CS therapy and central nervous system (CNS) involvement of systemic lupus erythematosus (SLE), a condition often treated with CS, a brief review of NP manifestations of SLE was also performed. The presentation of CS-induced neuropsychiatric disorders (CIPD) can be quite varied with depression, hypomania, and overt psychosis being the most common manifestations. CIPD can also include bipolar affective changes, delirium, panic attacks, agoraphobia, obsessive-compulsive disorder, anxiety, insomnia, restlessness, fatigue, catatonia, reversible dementia-like cognitive changes, impaired memory, and concentration. No factors have been identified that allow for the accurate prediction of development of CIPD. A dose-dependent relationship (increased risk when the daily prednisone-equivalent dose is >/=40 mg) has been observed in most cases of CIPD, although there have been case reports with lower doses, alternate-day therapy, and even inhaled CS. Women are more commonly affected with most symptoms occurring in the first 6 weeks of starting treatment. SLE has been the only specific illness that has been linked to a greater risk of CIPD and the NP manifestations of SLE may mimic those of CIPD, with most occurring in the first year of diagnosis. Antiribosomal P, antineuronal, or antiphospholipid antibodies are frequently seen in patients with SLE developing CIPD. Imaging and EEG abnormalities, the coexistence of non-CNS manifestations of SLE, and the presence of serious disturbances in memory and concentration are more suggestive of NP-SLE than CIPD. Although NP symptoms associated with the use of CS generally resolve with discontinuation of the medication, prophylaxis with lithium, and treatment with antidepressants, anticonvulsants and electroconvulsive therapy for severe mania and depression have been reported with successful outcomes. A greater understanding of the underlying mechanism of CIPD, risk factors involved, treatment options, and the distinguishing features from NP-SLE will ultimately lead to more directed therapy for such patients.

BACKGROUND: Orbital inflammatory disease can complicate many systemic inflammatory disorders, including sarcoidosis, vasculitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis and scleroderma, but has not been reported with spondyloarthropathies. OBSERVATIONS: The authors describe a 29-year-old woman who developed orbital myositis, in addition to anterior uveitis, sacroiliitis and peripheral arthritis, as a complication of an underlying HLA-B27 related spondyloarthropathy, which responded temporarily to corticosteroid therapy and more completely to adalimumab. CONCLUSIONS: The patient reported herein presents with orbital inflammation as an extra-articular manifestation of HLA-B27 associated undifferentiated spondyloarthropathy. We propose that enthesitis is the likely mechanism of orbital inflammation in this patient.