Missed opportunities for treatment of inflammatory arthritis and factors associated with non-treatment: An observational cohort study in United States Veterans with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

OBJECTIVE: To identify factors associated with non-treatment with biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) during the 12 months after initial inflammatory arthritis (IA) diagnosis. METHODS: We identified Veterans with incident IA diagnosed in 2007-2019. We assessed time to treatment with Kaplan-Meier curves. We identified associations between non-treatment and factors relating to patients, providers, and the health system with multivariate Generalized Estimation Equation (GEE) log-Poisson. Subgroup analyses included IA subtypes (rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondylitis [AS]) and timeframes of the initial IA diagnosis (2007-11, 2012-15, and 2016-19). RESULTS: Of 18,318 study patients, 40.7 % did not receive treatment within 12 months after diagnosis. In all patients, factors associated with non-treatment included Black race (hazard ratio, 95 % confidence interval: 1.13, 1.08-1.19), Hispanic ethnicity (1.14, 1.07-1.22), Charlson Comorbidity Index ≥2, (1.15, 1.11-1.20), and opiate use (1.09, 1.05-1.13). Factors associated with higher frequency of DMARD treatment included married status (0.86, 0.81-0.91); erosion in joint imaging report (HR: 0.86, 0.81-0.91); female diagnosing provider (0.90, CI: 0.85-0.96), gender concordance between patient and provider (0.91, CI: 0.86-0.97), and diagnosing provider specialty of rheumatology (0.53, CI: 0.49-0.56). CONCLUSION: A high proportion of Veterans with IA were not treated with a biologic or non-biologic DMARD within one year after their initial diagnosis. A wide range of factors were associated with non-treatment of IA that may represent missed opportunities for improving the quality of care through early initiation of DMARDs.

Predictors of Thirty-Day Hospital Readmissions in Systemic Lupus Erythematosus in the United States: A Nationwide Study.

OBJECTIVE: To evaluate independent risk factors for readmission and to determine the major reasons for readmission in a nationally representative sample of patients with systemic lupus erythematosus (SLE). METHODS: We used the Nationwide Readmissions Database to identify adults with SLE who were discharged from hospital to home during January-November of 2016 and 2017. Thirty-day all-cause readmissions were identified. A multivariable adjusted survey-specific logistic regression model was used to identify factors associated with readmission. RESULTS: A total of 132,400 hospitalized adults with SLE were discharged home during the study period; 88.3% were female, with a median age of 51.0 years (interquartile range 38.7-61.9 years). Of these, 18,973 individuals (14.3%) were readmitted within 30 days of discharge from their index hospitalization. In multivariable analyses, the factors associated with the highest odds for readmission were autoimmune hemolytic anemia (odds ratio [OR] 1.86 [95% confidence interval (95% CI) 1.51-2.29]), glomerular disease (OR 1.27 [95% CI 1.19-1.36]), pericarditis (OR 1.35 [95% CI 1.14-1.60]), heart failure (OR 1.34 [95% CI 1.24-1.44]), age 18-30 years (OR 1.28 [95% CI 1.17-1.41] versus age ≥​65 years), and Medicare (OR 1.20 [95% CI 1.13-1.28]) and Medicaid insurance (OR 1.26 [95% CI 1.18-1.34]). Sepsis (7.6%), SLE (7.4%), heart failure (3.5%), and pneumonia (3.2%) were among the most common causes for readmission. CONCLUSION: In this nationally representative study of SLE readmissions, the strongest risk factors for 30-day readmission were younger age, SLE-related manifestations, and public insurance. These results identify patient groups with SLE that would benefit from postdischarge interventions designed to reduce hospitalizations and improve health outcomes.

Association of rheumatoid arthritis with mortality in chronic kidney disease: a cohort study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD) as well as with an increased risk of chronic kidney disease (CKD), also a known cardiovascular risk factor. However, it is not known if RA is a predictor of adverse outcomes in patients with CKD. We hypothesized that among a cohort of patients with CKD, RA would be associated with an increased risk of mortality. MATERIALS AND METHODS: We conducted a retrospective study of 3939 participants with CKD from the prospective Chronic Renal Insufficiency Cohort (CRIC) study. The primary outcome of interest was all-cause mortality. Secondary outcomes included CKD progression (defined as end-stage kidney disease or 50% decline in estimated glomerular filtration rate), cardiovascular endpoints, and composite of myocardial infarction, cerebrovascular accident, heart failure, or death. Multivariable Cox proportional hazards regression was utilized, adjusting for potential confounders including age, sex, race/ethnicity, body mass index, current smoker, and education. RESULTS: The study cohort included 83 participants with RA on a disease modifying anti-rheumatic drug (DMARD). In the adjusted analysis, CKD-RA status was significantly associated with an increased risk of death (adjusted HR, aHR, 1.73 (1.27, 2.35)) and composite outcome (aHR 1.65 (1.27-2.15)) even after adjusting for traditional risk factors. Similar statistically significant associations were observed between CKD-RA and other secondary outcomes except for CKD progression. CONCLUSION: RA was associated with higher mortality among individuals with CKD but not progressive renal decline. Further studies evaluating the mechanisms behind this association are needed. Key Points • Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD) as well as with an increased risk of chronic kidney disease (CKD), also a known cardiovascular risk factor. However, it is not known if RA is an independent predictor of adverse outcomes in patients with CKD • In this study, we observed that CKD patients with RA experience higher mortality as well as an increased risk of CVD compared to patients with CKD without comorbid RA • These data provide rationale for more aggressive monitoring for CVD in patients with CKD and RA. They also underscore the need for determining which interventions can help decrease the burden of mortality in these patients.

Safety of immune checkpoint inhibitors in patients with cancer and pre-existing autoimmune disease.

BACKGROUND: Patients with pre-existing autoimmune disease (AD) have been largely excluded from clinical trials of immune checkpoint inhibitors (ICI), so data on safety of ICIs among patients with pre-existing AD are relatively limited. There is a need for deeper understanding of the type and management of complications from ICI in patients with pre-existing AD. We sought to investigate the safety of ICIs in patients with pre-existing ADs as well as factors associated with AD flare. METHODS: Consecutive patients with pre-existing AD who received monotherapy as well as combination of ICI therapies at our institution from September 2015 through September 1st, 2018 were identified. Clinical information was abstracted via manual chart review. Clinical factors associated with AD flare were determined using multivariable logistic regression. RESULTS: A total of 42 patients were identified of whom 12 developed AD flare. All flares were treated with oral or topical corticosteroids, while a patient with flare of rheumatoid arthritis was treated with tofacitinib and another patient with Crohn's flare was treated with infliximab. Female sex, smoking status, higher age at the start of ICI therapy, cancer type, such as melanoma and lung cancer as compared to other cancers, were not significantly associated with AD flare, however, patients with underlying rheumatologic AD were noted to have a five times greater likelihood of flare as compared to other non-rheumatologic AD. Nine patients developed new immune related adverse events (IRAEs) unrelated to underlying AD, such as inflammatory poly-arthropathy, neuropathy, hypothyroidism, diarrhea, lichenoid drug eruptions, which were managed with oral and/or topical corticosteroids. ICI was stopped in six patients due to AD flare, in four patients due to IRAE flare (out of which one resumed ICI after resolution of IRAE). CONCLUSIONS: In patients with pre-existing AD treated with ICI, AD flare occurred in 28% of patients and were managed successfully with corticosteroids alone or with additional disease-modifying therapies. ICI could be considered in patients with AD, but with very close monitoring and preemptive multidisciplinary collaboration.

Approaching Reactive Arthritis Associated With Poor Prognostic Factors: A Case Report and Literature Review.

The aim of this paper is to review and discuss the background, common manifestations, differential diagnosis, and current treatment practices of reactive arthritis. The focus will be on the choice of therapy in patients with poor prognostic factors. A PubMed search was performed in March 2020 on reactive arthritis and revealed 137 articles. Fourteen case reports and four large-scale studies that are pertinent for discussion in terms of treatment of reactive arthritis over the past five years are reported along with poor prognostic markers. The first choice of therapy regardless of the number of poor prognostic markers is non-steroidal anti-inflammatory drugs (NSAIDs). The second choice of therapy appeared to be glucocorticoids in the oral as well as intra-articular forms. No correlation was detected between the need for systemic steroids and the number of poor prognostic factors present. The third choice of therapy appears to be disease-modifying anti-rheumatic drugs (DMARDs) (such as sulfasalazine) and their increasing use can be demonstrated over time. Novel therapies such as adalimumab have also been shown to be used and this shows a strong correlation with an increased number of poor prognostic factors. Reporting of these case reports and review of literature contribute to knowing more about reactive arthritis and help keep us up to date with newer therapies available when patients do not respond to conventional therapy. It was notable that the increased number of poor prognostic factors and non-responders have shown increased use of tumor necrosis factor inhibitors (TNFI) such as adalimumab.

Leukocytoclastic Vasculitis: An Early Skin Biopsy Makes a Difference.

Leukocytoclastic vasculitis (LCV) is an uncommon condition with a broad differential diagnosis. Although the clinical history, physical examination, and laboratory workup are pivotal when formulating a differential diagnosis of LCV, a skin biopsy is required in most cases to elucidate the cause. The diagnostic yield of a skin biopsy increases within the first 24 to 48 hours of the lesion onset indicating the importance of obtaining a prompt skin sample. We present the case of a 60-year-old man who presented to the emergency department with a three-day history of fevers, headaches, and a painful skin rash. He endorsed rhinorrhea and sore throat a week ago. Physical examination was notable for an erythematous papular rash with palpable violaceous purpura located mainly at the distal right leg and thigh. He also complained of painful bilateral hand edema. His complete blood count and chemistries were unremarkable. His C-reactive protein was 147 mg/L (normal value <8 mg/L), and sedimentation rate was 51 mm (normal value <15 mm). Immunoglobulin A was 509 mg/dL (normal value 82-460 mg/dL). Further workup including viral hepatitis serologies, antinuclear antibodies, complements, antineutrophil cytoplasmic antibodies, cryoglobulins, rheumatoid factor, and blood cultures yielded negative results. Therefore, it was believed that his rash was likely associated with his recent upper respiratory infection. A skin biopsy done on the first day of admission was positive for LCV without immunoglobulin A deposition. He was managed with prednisone and anti-inflammatory medications with improvement of his rash.

A Rare Case of Clear Cell Adenocarcinoma of the Cervix with No Intrauterine Diethylstilbestrol Exposure.

Cervical cancer is the fourth most common cancer in females. Clear cell adenocarcinoma of the cervix is an uncommon histological variant and is usually seen with intrauterine exposure to diethylstilbestrol. A 28-year-old female with no intrauterine exposure to diethylstilbestrol presented with postcoital bleeding. A pelvic exam revealed a cervical mass. Imaging confirmed the cervical mass and positron emission tomography scan showed an increased uptake in the cervical mass as well as the para-aortic and pelvic lymph nodes. Biopsy showed a clear cell carcinoma of the cervix. She was treated with cisplatin and paclitaxel for eight cycles and concurrent radiation therapy. She had a complete response to therapy and has been in complete remission nine months from the end of therapy. There are no clear guidelines for the treatment of clear cell carcinoma with current therapy based on the treatment of squamous and non-clear cell adenocarcinoma. Cisplatin and paclitaxel could be an option, given the successful treatment of the patient in our case.

Elevated C-reactive Protein and Role of Steroids in Cocaine-associated Levamisole-induced Vasculitis.

Levamisole is a common contaminant in cocaine and has led to the emergence of an entity known as levamisole-induced vasculitis (LIV). There is no consensus on the management of this condition. We describe a patient who presented with acute on chronic LIV who was treated with pulse dose steroids. We aim to discuss the diagnosis and current management options for LIV. We have compared seven case reports that have measured C-reactive protein (CRP) and compared the CRP levels, site involved, dose, and mode of steroid administration. We postulate that elevated CRP may warrant steroid therapy over conservative management and could lead to a possible decreased hospital stay.

Spontaneous Tumor Lysis Syndrome Due to Endometrial Carcinoma.

Spontaneous tumor lysis syndrome (TLS) is a rare condition in solid tumors, particularly in endometrial carcinoma. Spontaneous TLS occurs without the use of cytotoxic therapy but is observed particularly in hematologic malignancies. Given the high morbidity and mortality associated with spontaneous TLS, it is crucial to identify and treat it promptly. There have been only four cases of spontaneous TLS reported to date in the literature from a uterine source. We present a 59-year-old female with a recently diagnosed endometrial carcinoma with neuroendocrine features by dilation and curettage who presented to the hospital with somnolence, decreased oral intake, and lower abdominal pain of three days duration. She was found to have sepsis secondary to endometritis and spontaneous tumor lysis syndrome by clinical and laboratory definitions (hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia). Signs of disease progression were found such as worsening retroperitoneal lymphadenopathy that corresponded with the suspected increased tumoral activity. We report the case of a solid tumor (endometrial) presenting with spontaneous TLS, which highlights the importance of the early identification and initiation of treatment.

Idiopathic Granulomatous Mastitis-A Mystery Yet to be Unraveled: A Case Series and Review of Literature.

Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.

Statin-Associated Necrotizing Myopathy: A Feared Complication.

Statins are a group of frequently-prescribed drugs with proven cardiovascular risk-benefit. The most common adverse effects include weakness and myalgias. However, prescribers need to be aware of a less common complication, statin-associated necrotizing myopathy, which can occur at any time during the treatment course and has been found to be <0.1% of adverse effects. High suspicion is warranted when patients taking statins develop weakness and myalgia. Increased risk of muscle injury has been observed when using gemfibrozil in combination with statins and should be avoided. We present a case of an elderly male with chronic use of combination lipid-lowering agents who initially presented with proximal weakness. He was diagnosed with statin-associated necrotizing myopathy and subsequently developed rapid end-stage renal disease in the setting of severe rhabdomyolysis. The case report discusses the work-up of proximal muscle weakness with focus on the importance of early recognition and prompt management of rhabdomyolysis to avoid life-threatening complications.

Nivolumab-induced hepatitis: A rare side effect of an immune check point inhibitor.

Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3-6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.