Rheumatologic associations of microscopic colitis: A narrative review.

Extraintestinal manifestations (EIMs) 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' (MC), in which EIMs are less well described. Our objective was to review the literature regarding the EIMs complicating MC and describe their 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', and '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 MC. The identification of rheumatoid arthritis and limited scleroderma as comorbidities with MC was noteworthy. Inflammatory arthropathy was frequently seen in MC, 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, and 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 the development of a clinical registry to help define the incidence of EIMs and systemic autoimmune rheumatic diseases among MC patients to help elucidate shared predispositions, pathogenic mechanisms, and therapeutic opportunities.

Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and Sjögren's syndrome enrolled in a large observational US registry.

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.

Spontaneous Remission of Acquired Generalized Lipodystrophy Presenting in the Postpartum Period.

Acquired generalized lipodystrophy (AGL) is a rare condition characterized by the diffuse loss of adipose tissue resulting in hyperglycemia, severe insulin resistance, and sequelae of metabolic disease. Here, we report the case of a 32-year-old woman who developed uncontrolled hyperglycemia and significant weight loss within 2 months postpartum. Upon endocrine evaluation, she was found to have generalized loss of adiposity, hypoleptinemia, and persistent hyperglycemia despite aggressive insulin administration. Glycemic response was obtained with U-500 intramuscular insulin, pioglitazone, and metformin-sitagliptin. At 14 months postpartum, the patient achieved spontaneous remission with normoglycemia off medication and restoration of adipose tissue deposition. Autoimmune workup revealed positive antinuclear antibodies (ANA) and anti-U1-ribonucleoprotein (anti-U1-RNP) titers, suggestive of an autoimmune etiology to her condition. This case of AGL represents the first reported case of spontaneous remission and the first to develop in the postpartum period.

Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus.

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.

Nodular Sarcoid Myositis Treated With Hydroxychloroquine Monotherapy.

Clinically significant granulomatous inflammation of skeletal muscle in sarcoidosis is rare. Glucocorticoids are generally considered the first-line treatment of sarcoidosis, but due to their side effect profile, the addition of steroid-sparing regimens has become increasingly more common. We report a patient with nodular sarcoid myositis who was successfully treated with antimalarial hydroxychloroquine alone. Whereas antimalarials have been reported to be an effective treatment of various organ involvement in sarcoidosis, to our knowledge, this is the first report of hydroxychloroquine monotherapy successfully treating nodular sarcoid myositis. Hydroxychloroquine monotherapy may be a reasonable initial treatment option for nodular sarcoid myositis and other forms of muscular sarcoidosis, as well as for other non-acute organ-threatening manifestations of the disease.

Etanercept therapy for psoriatic arthritis in the presence of recurrent non-Hodgkin lymphoma.

Tumor necrosis factor inhibitors (TNFi) have established efficacy in psoriasis and psoriatic arthritis; however, there are concerns regarding the risk of lymphoma with their use. Although current data suggest that this risk is not increased with TNFi treatment, there are no data on the risk of recurrence of previously treated lymphoma under TNFi therapy. Herein, we describe a 46-year-old man with recurrent non-Hodgkin lymphoma whose refractory psoriatic arthritis was effectively treated for 5.5 years with the TNFi etanercept, initiated just 7 months after achieving lymphoma remission, without recurrence of non-Hodgkin lymphoma. However, he subsequently died 6.5 years later of pancreatic adenocarcinoma.

Spontaneous resolution of apparent radiation associated retroperitoneal fibrosis.

A 70-year-old man was diagnosed with retroperitoneal fibrosis (RPF) complicated by ureteral obstruction 4 months after finishing radiotherapy for prostate cancer. He was treated conservatively with ureteral stent placement. After 3 months, computed tomography scan of the abdomen revealed resolution of RPF without any medical or surgical interventions. Although an uncommon event, the possibility of spontaneous resolution of RPF, as demonstrated by this and previously reported cases, has led some to encourage conservative management.

Autoimmune Manifestations as the Harbinger of Primary Cutaneous Anaplastic Large Cell Lymphoma.

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.

Evolving connective tissue disease influenced by splenectomy: beneath the sword of Dameshek.

In years past, there was concern that splenectomy could lead to dissemination of occult systemic lupus erythematosus. Clinical studies subsequently effectively refuted that concept. However, there remains uncertainty regarding the role of the spleen in autoimmune diseases and the effect of splenectomy on their course. We present a case of a 56-year-old woman with autoimmune hepatitis and rheumatoid arthritis, without clinical or serologic features of lupus, who developed glomerulonephritis and antiphospholipid syndrome subsequent to an elective splenectomy. Literature review was performed to identify examples of the effect of splenectomy on other autoimmune diseases. Splenectomy has been linked with the development of new autoimmune phenomenon, alterations in the clinical course of patients with prior autoimmune disease, such as in our patient, and in a progressive redistribution of memory B cells that may influence autoimmune disease activity and may have been involved in the alteration in our patient's clinical course.

Malignant Catatonia as the Presenting Manifestation of Systemic Lupus Erythematosus.

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.

Healthcare-Associated Transmission of Parvovirus B19 Arthropathy.

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.

Prevalence of Sjögren's syndrome associated with rheumatoid arthritis in the USA: an observational study from the Corrona registry.

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.

Spondyloarthropathy after ampullary carcinoma resection: "post-Whipple" disease.

The development of bowel-bypass syndrome complicating the Whipple procedure for biliary tract carcinoma is described here for the first time. A 56-year-old HLA-B27 + man, treated with excision of adenocarcinoma of the ampulla of Vater, developed an undifferentiated spondyloarthropathy, initially unresponsive to nonsteroidal anti-inflammatory drugs and doxycycline, but eventually controlled with sulfasalazine and tapered corticosteroids. This condition represents another example of a rheumatic syndrome occurring after disruption of gastrointestinal tract continuity and likely development of small bowel bacterial overgrowth.

Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis.

The anti-inflammatory effects of both n-3 and n-6 polyunsaturated fatty acids (PUFA) have been demonstrated in vitro and in many disease states, in particular in the treatment of rheumatoid arthritis. The benefit of n-3 PUFA supplementation has been documented in animal models of periodontal inflammation and a trend towards reduced inflammation has been seen in human experimental gingivitis. The purpose of this study was to examine the potential anti-inflammatory effects of PUFA supplementation, by administration of fish oil as a source of the n-3 PUFA, eicosapentaenoic acid, and borage oil as a source of the n-6 PUFA, gamma-linolenic acid (GLA), to adults with periodontitis. Thirty adult human subjects with periodontitis were administered either fish oil 3000 mg daily; borage oil 3000 mg daily; fish oil 1500 and borage oil 1500 mg daily, or placebo. The modified gingival index, the plaque index (PI), periodontal probing depths and beta-glucuronidase levels in gingival crevicular fluid were measured at baseline and after 12 weeks of treatment. Improvement in gingival inflammation was observed in subjects treated with borage oil (P<0.016), with a trend apparent in subjects treated with fish oil or a combination of PUFA. There was no statistically significant improvement in PI, although a trend was apparent in those receiving borage oil. Improvement in probing depth was seen in those subjects treated with either fish oil alone or borage oil alone, but statistical significance was only seen for the comparison of borage oil and placebo (P<0.044). No change was seen in gingival crevicular fluid (GCF) beta-glucuronidase levels. The use of borage oil supplementation, a source of the n-6 PUFA, GLA, can have beneficial effects on periodontal inflammation. n-6 PUFA supplementation seemed to offer more impressive results than either n-3 PUFA supplementation or the combination of lower doses of the two supplements. Additional studies will be necessary to more fully assess the potential of these agents to favorably affect periodontal inflammation.

Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis.

Rheumatoid arthritis (RA) and adult periodontitis share common pathogenetic mechanisms and immunologic and pathological findings. One oral pathogen strongly implicated in the pathogenesis of periodontal disease, Porphyromonas gingivalis, possesses a unique microbial enzyme, peptidylarginine deiminase (PAD), the human equivalent of which has been identified as a susceptibility factor for RA. We suggest that individuals predisposed to periodontal infection are exposed to antigens generated by PAD, with de-iminated fibrin as a likely candidate, which become systemic immunogens and lead to intraarticular inflammation. PAD engendered antigens lead to production of rheumatoid factor-containing immune complexes and provoke local inflammation, both in gingiva and synovium via Fc and C5a receptors.

Hypereosinophilia and seroconversion of rheumatoid arthritis.

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.

Alopecia areata universalis complicating daclizumab therapy for uveitis.

Alopecia areata (AA) is a complication of biologic therapy with several anti-tumor necrosis factor (TNF) inhibitors and efalizumab for the treatment of various autoimmune diseases. We report the case of a 51-year-old woman who developed AA universalis while undergoing treatment with daclizumab, an immunosuppressive biologic therapy, administered for treatment of inflammatory ocular disease. Although immunomodulatory agents that function by interfering with T helper cell stimulation are expected to impede autoimmune-related processes, we believe that daclizumab may be causally related to the development of AA.

Orbital inflammatory disease: unusual presentation of enthesitis in an HLA-B27 spondyloarthropathy.

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.