Imaging in Rheumatic Immune-related Adverse Events.

Since their introduction, immune checkpoint inhibitors have revolutionized cancer treatment by harnessing the body's own immune system as a defense against tumor growth. The downside of activating the immune system is the development of immune-related adverse events (irAEs), which mimic autoimmune disease of various organ systems. The musculoskeletal system is an uncommon, but substantial one for patients and can lead to long-term pain and disability that affects their quality of life. This review summarizes recent literature on imaging forms utilized for diagnosis and assessing treatment response in rheumatic irAEs.

Paget Disease as a Rare Mimicker of Giant Cell Arteritis.

Paget disease (PD) is a skeletal disorder that is characterized by excessive osteoclast activity and subsequent increased osteoblast activity that leads to disorganized bone formation. Here, we report a case of a patient whose symptoms initially raised concern for giant cell arteritis (GCA), but further clinical examination ultimately led to an alternative diagnosis.

Mitral Valve Echodensities in a Young-Adult Female with Relapsing Polychondritis, Transiently Positive Lupus Anticoagulant, and Systemic Embolism.

Background: Valvular strands seen on echocardiography carry a wide differential diagnosis and may not always have a clear etiology despite taking clinical context into account. The decision of whether to provide anticoagulation for these lesions can be challenging. Case Presentation. A young adult female with an extensive rheumatologic history involving relapsing polychondritis and positive lupus anticoagulant presents to the emergency department with a discolored and painful right toe, as well as right auricular pain and swelling. Initial work-up revealed a possible splenic infarct, vasculitis of the right lower extremity, and mitral valve echodensities on echocardiography, without evidence of infective endocarditis. Due to concern that nonbacterial thrombotic endocarditis may be the cause of the patient's thromboembolic event, her valvular lesions were treated with low molecular weight heparin while awaiting serial imaging. When follow-up echocardiography showed no change in the size of her mitral valve lesions, which would be most consistent with Lambl's excrescences, the care team still faced a decision about which long-term anticoagulation to prescribe. This patient of childbearing age wished to avoid the teratogenicity and long-term monitoring associated with warfarin therapy. Although warfarin was the preferred agent for the patient's rheumatologic comorbidities, she elected to receive enoxaparin therapy for long-term thromboembolism prophylaxis. Conclusions: Even when accounting for clinical context, valvular lesions seen on echocardiography often have uncertain etiology and may require time and serial imaging to determine which treatment to pursue. When long-term anticoagulation is provided for females of childbearing age, shared decision-making with consideration of the patient's personal priorities and comorbidities is essential.

Racial/ethnic disparities in the risk of preterm birth among women with systemic lupus erythematosus or rheumatoid arthritis.

OBJECTIVE: In a large multi-racial/ethnic cohort of women, we examined racial/ethnic disparities in preterm birth (PTB) risk stratified by autoimmune rheumatic disease (ARD) type, which included systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Birth records linked to hospital discharge data of singleton births in California from 2007 to 2012 were leveraged for a retrospective cohort study including women with SLE or RA. The relative risk of PTB (< 37 versus ≥ 37 weeks' gestation) was compared among different racial/ethnic groups (Asian, Hispanic, Non-Hispanic (NH) Black, and NH White) and stratified by ARD type. Results were adjusted for relevant covariates using Poisson regression. RESULTS: We identified 2874 women with SLE and 2309 women with RA. NH Black, Hispanic, and Asian women with SLE were 1.3 to 1.5 times more likely to have PTB compared to NH White women. NH Black women with RA were 2.0 to 2.4 times more likely to have PTB compared to Asian, Hispanic, or NH White women. The NH Black-NH White and NH Black-Hispanic disparity in PTB risk was significantly higher in women with RA compared to SLE or the general population. CONCLUSION: Our findings highlight the racial/ethnic disparities for risk of PTB among women with SLE or RA and highlight that several of the disparities are higher for women with RA compared to those with SLE or the general population. These data may provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth, particularly among women with RA. Key Points • There is an unmet need for studies that evaluate racial/ethnic disparities in birth outcomes specifically in women with RA or SLE. • This is one of the first studies describing racial/ethnic disparities in PTB risk for women with RA, and to draw conclusions regarding Asian women in the USA with rheumatic diseases and PTB. • These data provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth among women with autoimmune rheumatic diseases.

Mediation of Adverse Pregnancy Outcomes in Autoimmune Conditions by Pregnancy Complications: A Mediation Analysis of Autoimmune Conditions and Adverse Pregnancy Outcomes.

OBJECTIVE: Autoimmune conditions are associated with an increased risk of adverse pregnancy complications and outcomes, suggesting that pregnancy complications may mediate the excess risk. We performed a causal mediation analysis to quantify the mediated effects of autoimmune conditions on adverse pregnancy outcomes. METHODS: We queried a California birth cohort created from linked birth certificates and hospital discharge summaries. From 2,963,888 births, we identified women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and inflammatory bowel disease (IBD). Pregnancy complications included preeclampsia/hypertension, gestational diabetes mellitus, and infection in pregnancy. Adverse pregnancy outcomes were preterm birth, cesarean delivery, and small for gestational age. We performed a mediation analysis to estimate the total effects of each autoimmune condition and adverse pregnancy outcome and the indirect effects through pregnancy complications. RESULTS: All 4 autoimmune conditions were associated with preterm birth and cesarean delivery, and RA, SLE, and IBD were associated with offspring that were small for gestational age. The strongest mediator of RA, SLE, and psoriasis was preeclampsia/hypertension, accounting for 20-33% of the excess risk of preterm births and 10-19% of excess cesarean deliveries. Gestational diabetes mellitus and infections generally mediated <10% of excess adverse pregnancy outcomes. Of the 4 autoimmune conditions, selected pregnancy complications mediated the least number of adverse pregnancy outcomes among women with IBD. CONCLUSION: We found evidence that some excess risk of adverse pregnancy outcomes is mediated through pregnancy complications, particularly preeclampsia/hypertension. Quantifying excess risk and associated pathways provides insight into the underlying etiologies of adverse pregnancy outcomes and can inform intervention strategies.

Impact of autoimmune rheumatic diseases on birth outcomes: a population-based study.

Objectives: Autoimmune rheumatic diseases (ARDs) affect women of childbearing age and have been associated with adverse birth outcomes. The impact of diseases like ankylosing spondylitis and psoriatic arthritis (PsA) on birth outcomes remains less studied to date. Our objective was to evaluate the impact of ARDs on preterm birth (PTB), congenital anomalies, low birth weight (LBW) and small for gestational age (SGA), in a large cohort of women. Methods: We conducted a propensity score-matched analysis to predict ARD from a retrospective birth cohort of all live, singleton births in California occurring between 2007 and 2012. Data were derived from birth certificate records linked to hospital discharge International Classification of Diseases, ninth revision codes. Results: We matched 10 244 women with a recorded ARD diagnosis (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, PsA); ankylosing spondylitis and juvenile idiopathic arthritis (JIA) to those without an ARD diagnosis. The adjusted OR (aOR) of PTB was increased for women with any ARD (aOR 1.93, 95% CI 1.78 to 2.10) and remained significant for those with RA, SLE, PsA and JIA. The odds of LBW and SGA were also significantly increased among women with an ARD diagnosis. ARDs were not associated with increased odds of congenital anomalies. Conclusion: Consistent with prior literature, we found that women with ARDs are more likely to have PTB or deliver an SGA infant. Some reassurance is provided that an increase in congenital anomalies was not found even in this large cohort.

Comparison of thoracic duct ligation plus subphrenic pericardiectomy with or without cisterna chyli ablation for treatment of idiopathic chylothorax in cats.

OBJECTIVE To compare duration of surgery, recurrence rate, and survival time between cats with idiopathic chylothorax treated with thoracic duct ligation (TDL) plus subphrenic pericardiectomy (SPC) and those treated with TDL, SPC, and cisterna chyli ablation (CCA). DESIGN Retrospective case series with nested cohort study. ANIMALS 22 client-owned cats surgically treated for idiopathic chylothorax from 2009 through 2014. PROCEDURES Patient and surgery data were collected from the medical records. Recurrence of chylothorax and survival time were assessed by medical record review and client interview. Comparisons were made between cats treated with TDL plus SPC (TDL-SPC group) and those treated with TDL, SPC, and CCA (TDL-SPC-CCA group). RESULTS 15 cats were treated with TDL plus SPC, and 7 were treated with TDL, SPC, and CCA. Median duration of surgery was significantly briefer for the TDL-SPC group (80 minutes; range, 55 to 175 minutes) than for the TDL-SPC-CCA group (125 minutes; range, 105 to 205 minutes). Five cats (2 in the TDL-SPC group and 3 in the TDL-SPC-CCA group) had persistent pleural effusion 4 weeks after surgery. Chylothorax recurred in 2 cats (1/group). Median survival time in the TDL-SPC group was 774 days (range, 3 to 2,844 days) and in the TDL-SPC-CCA group was 380 days (range, 11 to 815 days); these values did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Addition of CCA to the surgical treatment approach for cats with idiopathic chylothorax was associated with a significantly longer duration of surgery with no better outcome than achieved with TDL plus SPC alone.

Hydralazine-associated vasculitis: Overlapping features of drug-induced lupus and vasculitis.

INTRODUCTION: Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. METHODS: Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record. RESULTS: 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography. CONCLUSIONS: Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition.

Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis.

Eosinophilic fasciitis (EF) is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α.