Association Between Rheumatic Autoantibodies and Immune-Related Adverse Events.

BACKGROUND: Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs. PATIENTS AND METHODS: Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS). RESULTS: A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019). CONCLUSIONS: Pre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.

Challenges of caring for transgender and gender diverse patients with rheumatic disease: presentation of seven patients and review of the literature.

PURPOSE OF REVIEW: As perspectives on sex and gender identity have evolved, there has been an increase in the practice of transgender medicine. Within rheumatology, however, there is a dearth of information about rheumatic disease in transgender and gender diverse (TGGD) individuals. This is important, as sex hormones affect the etiopathogenesis and expression of autoimmune diseases. We therefore sought to identify TGGD patients with rheumatic disease, review their clinical courses, and appraise existing literature about this population. RECENT FINDINGS: Of 1053 patients seen at the Los Angeles County and University of Southern California Medical Center from 2019 through 2021, five transgender men and two transgender women with rheumatic disease were identified. Most patients' disease courses were not overtly impacted by gender affirming hormone therapy (GAHT). Six of seven patients had psychosocial barriers to care. Our systematic review found 11 studies with 11 transgender women and two transgender men. In 12 of 13 patients, GAHT possibly modulated the patients' rheumatic disease. SUMMARY: Our observations suggest GAHT need not be a strict contraindication in TGGD patients with rheumatic disease. TGGD patients often face significant psychosocial barriers. Additional information about this population and empathy toward their health disparities are needed.

Chronic Pain in Patients with Rheumatoid Arthritis.

PURPOSE OF REVIEW: Chronic pain is highly prevalent in patients with rheumatoid arthritis (RA) and can cause various physical and psychological impairments. Unfortunately, the appropriate diagnosis of chronic pain syndromes in this population can be challenging because pain may be primary to RA-specific inflammation and/or secondary to other conditions, typically osteoarthritis (OA) and fibromyalgia (FM). This disparity further poses a clinical challenge, given that chronic pain can often be discordant or undetected with standard RA-specific surveillance strategies, including serological markers and imaging studies. In this review, we provide a robust exploration of chronic pain in the RA population with emphasis on epidemiology, mechanisms, and management strategies. RECENT FINDINGS: Chronic pain associated with RA typically occurs in patients with anxiety, female sex, and elevated inflammatory status. Up to 50% of these patients are thought to have chronic pain despite appropriate inflammatory suppression, typically due to peripheral and central sensitization as well as secondary OA and FM. In addition to the standard-of-care management for OA and FM, patients with RA and chronic pain benefit from behavioral and psychological treatment options. Moreover, early and multimodal therapies, including non-pharmacological, pharmacological, interventional, and surgical strategies, exist, albeit with varying efficacy, to help suppress inflammation, provide necessary analgesia, and optimize functional outcomes. Overall, chronic pain in RA is a difficult entity for both patients and providers. Early diagnosis, improved understanding of its mechanisms, and initiation of early, targeted approaches to pain control may help to improve outcomes in this population.

Challenges of caring for homeless patients with rheumatic and musculoskeletal disorders in Los Angeles.

Homelessness is a public health crisis. Homeless individuals have significantly worse health outcomes than the general population. We have begun examining challenges of caring for homeless patients with rheumatic and musculoskeletal diseases. Difficulties include physical environment, food and financial insecurity, access to healthcare, low health literacy, and comorbid mental illness, and substance abuse. Based on known prevalences of rheumatic and musculoskeletal diseases (RMSDs), we extrapolate that there are thousands of homeless with rheumatoid arthritis (RA), systemic lupus erythematosus, psoriatic arthritis, gout, and osteoarthritis. We present preliminary observations of disparities in the care of homeless patients with RA seen at the Los Angeles County Medical Center of the Keck School of Medicine of the University of Southern California. They tended to be African American males, missed appointments, utilized emergency services frequently, tended not to be on medications, and exhibited severe disease. We reviewed the available literature on homelessness and homeless healthcare to consider what further studies might be helpful and what interventions might improve the care of patients with RMSDs. We identified several aspirational and practical recommendations. These include ensuring access to healthcare for the homeless (indeed for all); reducing disparities through policy, tailored care, and enhanced social services; and recognizing and treating disease early. Developing better approaches for the care of these homeless has obvious and important implications for other underserved populations needing rheumatologic care, patients with early arthritis, or situations where rheumatologists are unavailable. We believe that physicians have a special responsibility to mitigate inequities in this particularly disadvantaged population.

Outpatient fluoroquinolone prescribing patterns before and after US FDA boxed warning.

OBJECTIVES: Fluoroquinolones are routinely overprescribed for uncomplicated urinary tract infection (uUTI), acute sinusitis, and acute bronchitis. In 2016, the United States (US) Food and Drug Administration (FDA) updated the boxed warning on fluoroquinolones, recommending against their use as first-line agents for the routine pharmacologic management of uUTI, acute sinusitis, and acute bronchitis in patients who have other treatment options. The primary objective of this study was to determine if the 2016 expanded boxed warning was associated with decreased fluoroquinolone prescription rates for these three diagnoses. METHODS: We retrospectively reviewed antibiotics prescribed at a single, large, academic outpatient center for these three diagnoses between January 2013 and May 2018. Interrupted time series analysis was used to compare the rate of fluoroquinolone prescriptions before and after the May 2016 FDA boxed warning. RESULTS: A total of 10 087 antibiotic prescriptions for these three diagnoses were examined. There was no significant change in fluoroquinolone prescription rates after the FDA boxed warning. The majority of inappropriate fluoroquinolone prescriptions were given for the management of uUTI. CONCLUSION: The 2016 US FDA boxed warning against fluoroquinolone use for uUTI, acute sinusitis, and acute bronchitis was not associated with a statistically significant reduction in the rate of fluoroquinolone prescriptions for these diagnoses. Additional research is needed to define how US FDA boxed warnings may be incorporated into broader antibiotic stewardship programs to decrease overuse of fluoroquinolones and avoid adverse effects of the drug class, including Clostridioides difficile infections and emergence of resistant organisms.

Acute Cardiac Events in Patients With Severe Limb Infection.

Recent studies have shown an association between infections, such as influenza, pneumonia, or bacteremia, and acute cardiac events. We studied the association between foot infection and myocardial infarction, arrhythmia, and/or congestive heart failure. We analyzed the records of 318 consecutive episodes of deep soft tissue infection, gangrene, and/or osteomyelitis in 274 patients referred to a vascular surgery service at a tertiary center. We identified 24 acute cardiac events in 21 of 318 (6.6%) episodes of foot infection or foot gangrene. These 24 events included 11 new myocardial infarctions (3.5%), 8 episodes of new onset or worsening congestive heart failure (2.5%), and 5 new arrhythmias (1.6%). Tachycardia and systemic inflammatory response syndrome were associated with acute cardiac events ( P < .05 for each). The 1-year survival of patients with acute cardiac events was 50.4%, significantly lower than the 91.7% 1-year survival of patients without acute cardiac events ( P < .0015). Acute cardiac complications are not uncommon among patients presenting with severe foot infection and are associated with a high 1-year mortality. Primary care physicians, cardiologists, and vascular and orthopedic surgeons must keep a high index of suspicion for the occurrence of an acute cardiac event.

Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren syndrome or systemic lupus erythematosus in BALB/c mice.

Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used. Group I was immunized with Ro60. Groups II to IV were immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively. Group V controls received Freund's adjuvant. A rapid abrogation of tolerance to Ro60/La antigens occurred in mice immunized with HNE-modified Ro60, especially in the low and medium HNE-Ro60 groups. Lymphocytic infiltration and significantly high decrement in salivary flow (37%) compared to controls was observed only in the high HNE-Ro60 group, suggesting induction of a Sjögren syndrome-like condition in this group. Anti-dsDNA occurred only in mice immunized with medium HNE-Ro60. This group did not have a significant decrement in salivary flow, suggesting induction of a systemic lupus erythematosus-like manifestation in this group. Significantly high antibodies to Ro60 were found in saliva of mice in the low and medium HNE-Ro60 and the Ro60 groups, as well as anti-HNE Ro60 in the low and medium HNE-Ro60 groups. Understanding the mechanism of this differential induction may help discriminate between these two autoimmune diseases.