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.

Reflecting on the immunopathology of arthritis associated with inflammatory bowel disease: what do we know and what should we know?

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is clinically closely associated with arthritis. Three major arthritis clinical subtypes have been described, peripheral arthritis type 1 (PeA1), peripheral arthritis type 2 (PeA2), and axial spondyloarthritis (axSpA). While genetic overlaps between IBD and arthritis have been defined, detailed pathophysiology for these three major subtypes of arthritis in patients with IBD has only recently begun to be established. The genetic and molecular mechanisms distinguishing axial and peripheral arthropathies in patients with UC and CD need to be better described. Understanding the pathophysiology for PeA1, PeA2, and axSpA in the settings of both UC and CD is necessary to provide the fundamental biology underlying the clinical phenotypes in IBD arthritis. This has been attempted for CD-associated spondyloarthritis, differentiating this from both CD and axSpA, while observing unique peripheral blood mononuclear cells linking gut inflammation to joint disease. We should know more about the processes by which immune cells are perturbed in these disorders, how they translocate to joints, how they are activated, what other molecules and mediators are involved, and how gut microbes and microbial products damage joints. Information from such studies are needed to elucidate whether distinctions between IBD-related peripheral and axSpA are clinically meaningful. IBD-related peripheral and axSpA studies are needed to elucidate whether distinctions between peripheral and axSpA are clinically meaningful, to better understand immunopathogenesis, and to develop novel targeted therapies.

Challenges of caring for homeless patients with inflammatory arthritis: 12-month follow-up observations and identification of certain barriers to care.

Homelessness is a public health crisis and there is a paucity of information about patients with rheumatic disease experiencing homelessness. We sought to develop approaches to improve care for this unique patient population. We previously reported observations on 17 homeless patients with inflammatory arthritis (15 rheumatoid arthritis (RA), 2 psoriatic arthritis (PsA)). We obtained follow-up information from our original 17 patients and compared this to data summarized and published about them from 12 months previously. We also created and administered a 100-question needs assessment survey. Follow-up 12-month clinical information was available from 13/17 homeless and 13/17 non-homeless controls. Homeless patients remained less well with more disease than non-homeless patients-poorer access to clinic appointments (80% vs 91%, p < 0.05), more emergency services use (20 vs 5 ED visits), less DMARDs use (43% vs 100%, p < 0.01), and more steroid use (29% vs 0%, p < 0.01). Homeless patients also had higher inflammatory markers than non-homeless patients (ESR 32 vs 26 mm/h and CRP 17 vs 5 mg/L), although these findings were not statistically significantly different. Seventy-eight percent of homeless patients were stable, 14% improved, and 7% worse; 21% had stable controlled and 57% stable active disease vs 62% and 0% of non-homeless (p < 0.01). Among the homeless, 6 (4 RA, 2 PsA) completed the survey, 2 declined, and 9 could not be reached. All 6 had found housing although all still had housing insecurity; 4 (67%) were homeless in the past. Three out of six (50%) obtained housing from social assistance during hospitalization following disease exacerbation while homeless. The average monthly income was $873. 5/6 (83.3%), were unable to work due to health, and were in considerable pain that adversely impacted their physical and mental health and ability to perform ADLs. Their perceived "greatest need" included dental care, physical therapy, knee surgery, employment, socialization secondary to isolation, and stable housing. Our understanding of the unique challenges of patients with rheumatic disease experiencing homelessness is improved, but not complete. Strengthened collaboration between street medicine providers and rheumatologists is necessary to improve care for homeless patients, especially given poorer outcomes compared with non-homeless counterparts. Key Points • We report 12-month follow-up information from our original 17 homeless patients with inflammatory arthritis (related in this journal in 2021) and their responses to an extensive needs assessment survey designed to identify barriers to care. • Homeless patients with inflammatory arthritis continued to have worse disease outcomes, use more corticosteroids and less DMARDs, and be seen less often in rheumatology clinics and more frequently in emergency departments than their non-homeless counterparts. • Survey data indicated that social assistance during hospitalization was a key area where healthcare providers could intervene to provide housing security for homeless patients and improve outcomes. Patients perceived "greatest needs" went beyond housing and rheumatological care and critically included access to social/specialty services. • Street medicine is the direct delivery of healthcare to people experiencing homelessness wherever they reside. Our observations, obtained in collaboration with street medicine colleagues, suggest important and salutary opportunities for this partnership to improve care for these particular patients.

Coincident Kikuchi-Fujimoto's disease and adult-onset Still's disease: report of a patient from an uncommonly affected population and case-directed systematic review.

Kikuchi-Fujimoto's disease (KFD) and adult-onset Still's disease (AOSD) are rare idiopathic inflammatory conditions of unknown etiology. Ten prior instances of KFD and AOSD occurring together have been reported in the medical literature. These overlaps, together with certain distinguishing clinical and laboratory characteristics in these co-occurrences, offer insight into the pathophysiology of both of these rare disorders. Too, examination of these cases may help improve the diagnostic evaluation and care of patients afflicted with these rare diseases. We therefore report an additional patient with KFD and AOSD occurring in a middle-aged Hispanic female patient and perform a systematic literature review using the PubMed/MEDLINE and Embase databases to further analyze and compare prior identified cases. Our observations in our index case complement and expand previous reports, including new demographic and diagnostic features not seen in prior cases of overlap. Indeed ours is the first in a patient of Hispanic ethnicity, with retroperitoneal lymphadenopathy, as well as with a skin biopsy consistent with AOSD. Each of the reviewed cases of co-occurrence met the diagnostic criteria for both KFD and AOSD. This finding, in the setting of unique clinical and diagnostic manifestations that are not typically seen in either disease entity alone, suggests the presence of an overlap syndrome. Also, many of the shared clinical features and symptomatic responses to targeted therapies implies a similar, yet still poorly understood, pathophysiologic pathway for the two diseases.

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.

Certain perspectives about the use of corticosteroids for managing hospitalized patients with rheumatic diseases.

The administration of cortisone to a bedridden patient with rheumatoid arthritis (RA) 70 years ago was a transformative event in modern medicine. We have since struggled to balance the near-miraculous anti-rheumatic with the yet all-too-frequent devastating side effects of glucocorticoids (GC). With the current availability of newer disease-modifying and biologic anti-rheumatic agents, we were rather surprised to note that 94% of sick hospitalized patients with systemic rheumatic diseases at our medical center were on corticosteroids during a 3-month observation period. Comparing contemporary with past practices from historical references, we confirmed a perhaps paradoxical trend of increasing steroid usage in certain contexts over the years. Sixty-seven percent of our hospitalized lupus patients were started on GC of greater than 30 mg prednisone equivalent compared with 50% in the 1950s. Seventy-five percent of our RA inpatients had their GC dose increased on discharge. Both (2/2) our new RA patients were started on GC, compared with 69% in the 2000s and just 36% in the 1990s. This likely reflects both improved abilities to keep sick patients alive and inability of other anti-rheumatic therapies to consistently induce or sustain disease remission compared with the usually highly efficacious yet inexpensive GC in these particular patients. Administration of glucocorticoids to ill, often infected, patients with systemic rheumatic diseases remains more art than science. Current perspectives view glucocorticoids as considerably less salutary than previously thought; we are still challenged to keep our patients from developing preventable complications. These observations emphasize the need for more and better therapeutic alternatives to glucocorticoids. There are now several examples-disease-modifying and biologic medications for RA and biologics for lupus and vasculitis-that suggest the possibility of caring for our patients without the historical reliance on corticosteroids. We have made enormous progress since steroids were first offered to a patient with RA in 1948. We are hopeful the future will bring us interventions of comparable or better efficacy that are safer.

Rituximab use as induction therapy for lupus nephritis: a systematic review.

OBJECTIVE: Rituximab (RTX) has important usage in rheumatoid arthritis and vasculitis. There remains a need for more, better, and safer treatments for patients with lupus nephritis (LN). RTX has been trialed in such patients without definitive conclusions about its effectiveness. As a role for RTX has not been clearly established for LN, we carried out a systematic review and analysis. METHODS: We identified 31 studies of RTX for class I-VI LN, and assessed complete renal response (CRR) and partial renal response (PRR) using criteria including serum creatinine, proteinuria, and urinary sediment. Due to differences in the pediatric presentation of the disease, studies focusing on pediatric patients were excluded. RESULTS: One randomized controlled trial (RCT) showed superiority of RTX+cyclophosphamide (CYC) versus CYC alone (64% vs. 21% CRR and 19% vs. 36% PRR). Six prospective and retrospective studies utilizing RTX monotherapy found 66% CRR or PRR in all patients. Eleven studies that investigated RTX in combination with CYC or mycophenolate mofetil (MMF) also found 66% CRR or PRR in all patients. In total, the CRR for Caucasian, East Asian, and Hispanic patients were 77%, 38%, and 28%, respectively. CONCLUSIONS: RTX appeared to benefit certain LN patients, but most studies were not randomized or properly controlled, were heterogeneous in design, subjects, and LN types, and were not comparable, and must therefore be interpreted cautiously. RTX alone may not deplete B cells sufficiently for the perturbations of LN. In addition, RTX may induce responses differently among patients of different ethnic and racial backgrounds. Furthermore, there were wide variations in the baseline characteristics of the patients, namely LN class, time course of disease, age, and prior immunosuppressive use. We suggest a prospective RCT in patients aged 18-65 years with class IV LN. Ideally, the patients would not have received prior immunosuppression and would better represent different ethnicities. The treatment groups would be RTX, RTX+belimumab, CYC, and MMF groups, with pulse-dose steroids during induction followed by maintenance steroids and MMF. The CRR and PRR would be assessed at 12 and 24 months. This or a similar study might clarify RTX's role in the treatment of LN.

Elevated serum globulin gap as a highly reliable marker of elevated erythrocyte sedimentation rate in patients with systemic rheumatic diseases.

OBJECTIVE: Serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are the two most commonly used markers of inflammation in clinical practice. Reducing the need for these tests could lead to considerable cost savings without sacrificing the quality of patient care. METHODS: The electronic medical records of patients with systemic rheumatic diseases seen between May 2015 and June 2017 in the rheumatology clinics at a single academic medical center were retrospectively reviewed. Correlations and receiver operator characteristic (ROC) curves between serum CRP level and ESR vs serum globulin gap (the difference between levels of total protein and albumin) and albumin-to-globulin (A:G) ratio were determined. RESULTS: In two independent cohorts (discovery: 263 subjects, 446 entries; validation: 438 subjects, 1959 entries), the globulin gap and A:G ratio correlated (p < 0.001) with CRP level and ESR, with correlation coefficients being greater for ESR than for CRP level. ROC curve analyses demonstrated better area-under-curve for ESR than for CRP level. The percentages of entries with elevated globulin gap (≥4.0 g/dl) and low A:G ratio (<0.8) were ∼8.4% and ∼2.6%, respectively, and each had a positive predictive value of ≥0.960 for elevated ESR. Among patients with high globulin gap, the change in globulin gap over time faithfully reflected changes in ESR. CONCLUSION: In the subset of systemic rheumatic disease patients who harbor an elevated globulin gap, the ESR is almost always elevated. This novel observation sets the conceptual foundation and rationale for subsequent prospective studies that assess whether ESR testing in this subset of rheumatic disease patients could be reduced without sacrificing patient care. Ultimately, ordering an ESR test may often be unnecessary, thereby resulting in cost savings.

Has Rheumatology Become a More Attractive Career Choice? Comparison of Trends in the Rheumatology Fellowship Match From 2008 to 2013 With Those From 2014 to 2017.

OBJECTIVE: Rheumatology has previously been a less attractive career choice than other internal medicine (IM) subspecialties. Recent fellowship data from the National Resident Matching Program (NRMP) has suggested that this may have changed. Therefore, we evaluated the current attractiveness of rheumatology as a career choice and compared it with other medical subspecialties. METHODS: Data from the NRMP from 2008 to 2017, the 2015 American College of Rheumatology workforce study, and Medscape physician salaries from 2010 to 2017 were used to determine annual numbers of fellowship applicants, availability of positions, and post-fellowship salary trends. Data from 2008 to 2013 were compared with those from 2014 to 2017, and rheumatology was compared with other IM subspecialties. RESULTS: The total number of annual fellowship applicants to rheumatology for 2008-2013 decreased by 3% (average annual mean ± SEM percentage change of -1.9 ± 2.6%), from 251 to 244 applicants. However, for 2014-2017, annual rheumatology applications increased by 44% (average annual mean ± SEM percentage change of 20.7 ± 10.5% [P = 0.03]), from 230 to 332 applicants. Other nonprocedural and procedural IM subspecialties did not exhibit a similar increase. For rheumatology, the increases in the ratio of annual applicants to positions (P = 0.02) and in the percentage of US medical graduates applying (P = 0.03) were statistically significant, and mean post-fellowship salary also rose. CONCLUSION: The aforementioned observations suggest that rheumatology has become a more attractive career choice since 2014. We speculate that the increasing popularity of the field is multifactorial, likely reflecting lifestyle, job satisfaction and availability, influence of mentors, and other elements. This salutary and exciting potential opportunity for rheumatology should be exploited.

Should a patient with rheumatoid arthritis be a kidney donor?

We cared for a woman with sero-positive rheumatoid arthritis (RA), in clinical remission on oral methotrexate (MTX) and hydroxychloroquine, who wished to donate a kidney to a brother with end-stage renal disease (ESRD). We could find scant literature about this unusual clinical circumstance, and therefore review pertinent aspects of renal disease in RA, perioperative medical management, maintenance of disease remission, outcomes for RA patients who have donated kidneys, and relevant ethical issues. Renal complications in RA are not uncommon, with as many as 50% of patients at risk of reduced eGFR. This reflects anti-rheumatic and analgetic medication use (non-steroidal anti-inflammatory drugs, acetaminophen, DMARDs [cyclosporine and, historically, D-penicillamine and gold compounds], and others), glomerulitis, interstitial nephritis, complicating Sjogren's syndrome, vasculitis, or amyloidosis, and/or emergence of an "overlap" syndrome or other rheumatic disorder. The literature suggests that MTX need not be interrupted for surgery. The risk of perioperative infection to our patient would be low and remission should be sustained. We are aware of one study of six patients with RA who donated kidneys; they experienced no complications, ESRD, or deaths after a median follow-up of 8.2 years. Our ethical responsibilities are to balance patient autonomy of decision-making while assuring clinical beneficence and minimizing potential maleficence. Our perspective was that it would not be unreasonable to support this patient donating a kidney if, when fully informed, that remained her wish.

Advice for my chief resident.

I have been privileged to have served as a division of rheumatology chief and/or program director for 18 years and as a department of medicine chair and medicine residency program director for another 22 years. During the latter, I collected and codified advice for my chief residents. Selected highlights are presented as follows.