Megan L. Krause

Update on Diffuse Alveolar Hemorrhage and Pulmonary Vasculitis

Diffuse alveolar hemorrhage is a clinical syndrome that can be a manifestation of multiple different causes. Identification of the underlying etiology is of utmost importance and dictates treatment. Pulmonary vasculitis including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of diffuse alveolar hemorrhage. For AAV, treatment includes induction followed by maintenance therapy. Rituximab has an increasing role in the treatment of AAV.

Perioperative management of the patient with rheumatoid arthritis

A multidisciplinary approach is required to care for patients with rheumatoid arthritis (RA) in the perioperative period. In preparation for surgery, patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA. Treatment of RA is with immunomodulatory medications, which present unique challenges for the perioperative period. Currently, there is no consensus on how to manage disease modifying antirheumatic drug (DMARD) therapy in the perioperative setting. Much of the data to guide therapy is based on retrospective cohort data. Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists. Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication. Special attention is required at the time of surgery for potential need for stress dose steroids. Further, there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease. There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery. However, history and exam alone cannot be relied upon to identify cervical spine disease. Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis, necessitating particular vigilance in postoperative follow up. This review summarizes available evidence regarding perioperative management of patients with RA.

Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know:

Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease of synovial joints, can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. Because it can affect women in their reproductive years, care of pregnant women with RA requires a delicate balance of maintaining disease control while limiting potential toxicity to the fetus and neonate. While most women experience a substantial improvement in disease activity during pregnancy, for some women their RA remains active. It can even manifest itself for the first time during pregnancy or early in the post-partum period. Optimizing disease control prior to conception is key, but utilizing disease-modifying treatments effectively and safely throughout pregnancy and lactation requires open dialogue and shared decision making. This review provides evidence-based recommendations for use of disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers to guide rheumatologists in their care of pregnant and lactating women with RA and serves as a guide to counsel male patients with RA on family planning decisions.

Patterns of interstitial lung disease and mortality in rheumatoid arthritis

Objective. To characterize a cohort of patients with RA who have interstitial lung disease (ILD) and to assess the utility of previously developed mortality staging systems [gender, age, lung physiology (GAP) and ILD-GAP]. Methods. All patients with RA and ILD seen at the Mayo Clinic from 1998 to 2014 were identified and manually screened for study inclusion. RA disease characteristics and pulmonary findings including high-resolution CT and pulmonary function testing were evaluated. Survival was estimated using Kaplan–Meier methods. GAP and ILD-GAP models were evaluated using c-statistics and standardized incidence ratios. Results. The study included 181 patients with RA-associated ILD (96% Caucasian; 48% females; 37% never-smokers). The mean age at ILD diagnosis was 67.4 years (S.D. 9.9). The median time from RA diagnosis to ILD was 4.9 years (range −10.9–48.1). The median follow-up was 3.1 years (range 0.01–14.8). Age, RA disease duration and low initial diffusing capacity for carbon monoxide were predictive of premature mortality in multivariate modelling. Sex, smoking status, obstructive lung disease, seropositivity and erosive disease were not associated with mortality. The 5-year survival rate was 59.7% (95% CI 51.5, 69.2). Survival did not differ between usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia (P = 0.42). The GAP model performed well in this cohort for both discrimination and calibration (c-statistic 0.71, standardized incidence ratio 0.97). Conclusion. In this large single-centre cohort of patients with RA-ILD, most patients were seropositive and had a history of smoking. ILD most commonly occurred after the RA diagnosis. Mortality was high and did not differ among the types. The GAP model may be useful in assessing mortality risk.

Progressive Decline of Lung Function in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Interstitial lung disease (ILD) is associated with substantial morbidity in rheumatoid arthritis (RA), but very little is known about its long‐term progression. This study was undertaken to investigate the progression of pulmonary disease using a large single‐center cohort of patients with RA‐associated ILD.

Differentiating scleroderma renal crisis from other causes of thrombotic microangiopathy in a postpartum patient

Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and scleroderma renal crisis (SRC) all present with features of thrombotic microangiopathy. Distinguishing among these entities is critical, however, as treatments differ and may be mutually exclusive. We describe the case of a 25-year-old woman with an undefined mixed connective tissue disease who presented 6 weeks post-partum with fever, transient aphasia, thrombocytopenia, hemolytic anemia, and acute kidney injury eventually requiring initiation of hemodialysis. Renal biopsy revealed thrombotic microangiopathy. Renal function did not improve despite immediate initiation of plasma exchange, and an angiotensin-converting enzyme (ACE) inhibitor was initiated following discontinuation of plasma exchange. At last follow up, she remained dialysis dependent. Due to the myriad causes of thrombotic microangiopathy and potential for diagnostic uncertainty, the patient’s response to therapy should be closely monitored and used to guide modification of therapy.

Assessing Immune Function by Profiling Cytokine Release from Stimulated Blood Leukocytes and the Risk of Infection in Rheumatoid Arthritis

Persons with rheumatoid arthritis (RA) suffer a high burden of infections, but currently no biomarkers are available to identify individuals at greatest risk. A prospective longitudinal study was therefore conducted to determine the association between the responsiveness of ex vivo cytokine production and 6-month risk of infections. Infections were identified by billing codes and validated by medical record review. At baseline, the release of 17 cytokines by peripheral blood mononuclear cells in response to stimulation, or media alone, was measured using multiplexed cytokine analysis. Production of IL-2, IL-8, IL-10, IL-17, TNF-α, IFN-γ, and GM-CSF, induced by various conditions, was significantly associated with the occurrence of infections. A multivariable prediction model based on these data provided new information on the risk of infection beyond standard assessments of disease activity, severity, and treatment. Future studies could utilize this information to devise new biomarkers for the prediction of infection in patients with RA.

Population-based study of outcomes of patients with juvenile idiopathic arthritis (JIA) compared to non-JIA subjects

OBJECTIVE Evaluate healthcare utilization and occurrence of comorbidities in a population-based cohort of patients of juvenile idiopathic arthritis (JIA) with an age- and sex-matched comparator group. METHODS Prevalent cases of JIA in 1994-2013 were identified in Olmsted County, Minnesota, along with age- and sex-matched non-JIA comparators. Surgeries, hospitalizations, pregnancies, and comorbidities were identified by medical record review. Poisson methods were used to generate rate ratios (RR) with 95% confidence intervals (CI) to compare outcomes between JIA and non-JIA cohorts separately during childhood (age < 18 years) and adulthood (age ≥ 18 years). RESULTS A total of 89 JIA and 89 non-JIA comparators were identified [64% female; mean (SD) age 8.6 (5.1) years at JIA incidence/index date and mean follow-up in childhood 6.3 (4.4) years for JIA; similar for comparators]. Among them, 38 pairs had follow-up into adulthood with mean follow-up of 8.0 (5.5) years for JIA. Children with JIA were more likely to have joint surgery (RR = 3.93, 95% CI: 1.18-24.94), non-joint surgery (RR = 1.90, 95% CI: 1.05-3.67), and hospitalizations (RR = 2.25, 95% CI: 1.04-5.53) than non-JIA comparators. As adults only joint surgeries remained significantly different (RR = 8.5, 95% CI: 2.27-120.1). Depression during childhood was more common in JIA (RR = 2.49, 95% CI: 1.01-6.13). There were no differences in educational achievement, employment status, or pregnancy outcomes between the 2 groups. CONCLUSIONS In a population-based cohort, inpatient healthcare utilization is higher for patients with JIA including surgery and hospitalization during childhood but not extending into adulthood. Understanding long-term comorbidities and healthcare needs for patients with JIA is necessary to provide comprehensive care.

Juvenile Idiopathic Arthritis in Olmsted County, Minnesota, 1960–2013

To evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994–2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960–2013.

Juvenile Idiopathic Arthritis in Olmsted County 1960‐2013

To evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994–2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960–2013.