Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

INTRODUCTION: In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. METHODS: This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18 years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12 months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12 months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. RESULTS: Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4 years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12 months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. CONCLUSIONS: Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

Knee Arthrocentesis in Adults.

Arthrocentesis of the knee is a procedure in which a needle is inserted into the knee joint, and synovial fluid is aspirated. An arthrocentesis can be diagnostic or therapeutic. Synovial fluid may be removed for testing to determine the nature of the knee effusion. If septic arthritis is suspected, urgent arthrocentesis before initiation of antibiotic treatment is indicated. Moreover, arthrocentesis can also aid in diagnosing crystal-induced arthritis such as gout or pseudogout, or non-inflammatory arthritis such as osteoarthritis. Identifying the cause of the knee effusion can guide treatment. Furthermore, removing fluid from a knee can reduce intraarticular pressure to decrease pain and improve range of motion. There is no absolute contraindication to performing this procedure, but in selecting the needle entry site, an area of skin that is infected should be avoided. Therefore, caution should be exercised when a patient presents with suspected cellulitis over the knee joint to avoid the potential risk of causing iatrogenic septic arthritis. A knee that has undergone arthroplasty should be assessed for arthrocentesis by an orthopedic surgeon. Arthrocentesis of the knee is typically performed with the patient supine. The site for needle insertion is marked, and then the skin is disinfected. After a local anesthetic is administered, a needle is inserted along the pathway that was anesthetized. Synovial fluid is aspirated, and then the needle is withdrawn. Pressure is applied until any bleeding stops. The synovial fluid can be analyzed for infection and inflammation but cannot directly confirm a diagnosis of internal derangement or autoimmune causes of arthritis. In addition to the history and physical examination, laboratory findings and imaging can clarify the etiology of a knee effusion.

Atypical Sjögren's Syndrome Initially Presenting as Lymphocytic Interstitial Pneumonitis followed by Immune Thrombocytopenia.

BACKGROUND: Sjögren's syndrome is an autoimmune disease characterized primarily by decreased exocrine gland function leading to eye and mouth dryness. Extraglandular manifestations occur less frequently. Case Report. A 74-year-old man with hypertension was admitted with productive cough and fever. On physical examination, he had bilateral lower lung decreased breath sounds. A chest radiograph showed bibasilar patchy infiltrate. Laboratory studies revealed hemoglobin of 11.9 g/dL, white blood cell count of 16,000/uL, and platelet count of 250,000/uL. Empiric antibiotic therapy was begun for suspected community acquired pneumonia, and then he was discharged home. However, his cough recurred. Chest computed tomography demonstrated adenopathy throughout the mediastinum and multiple ill-defined patchy groundglass opacities with a lower lobe prominence. He underwent a transbronchial biopsy to rule out malignancy; however, it showed lymphocytic interstitial pneumonitis. Antinuclear antibody was 1 : 80 homogeneous, and anti-SSA antibody was 6.3 AI (normal <1.0 AI). The patient was treated with prednisone 20 mg/day with marked improvement in his symptoms. Repeat chest computed tomography showed decreased groundglass opacities and decreased mediastinal lymph nodes. After more than a year, he was readmitted due to petechiae on his buccal mucosa and a platelet count of 2000/µL. The patient was started on prednisone 80 mg/d and intravenous immunoglobulin 80 g/d for 2 consecutive days. The platelet count eventually increased to 244,000/µL. CONCLUSION: We report a rare presentation of Sjogren's syndrome manifesting as acute lymphocytic interstitial pneumonitis and followed by immune thrombocytopenia. Both extraglandular manifestations responded well to corticosteroid therapy.

A Rare Case of Concomitant Septic Arthritis, Osteomyelitis, and Pyomyositis Caused by Salmonella.

A common causative organism in osteomyelitis in sickle cell disease is Salmonella. Septic arthritis and muscle infection due to Salmonella are much less common. We present a case of a 28-year-old woman with sickle cell disease who presented with left shoulder and elbow pain for two days. Physical examination revealed swelling of the left upper arm. The patient was initially treated for a sickle cell pain crisis. On hospital day 4, the patient developed a fever. She empirically started intravenous vancomycin and cefepime before her blood culture showed Salmonella. Subsequently, the antibiotic was changed to ceftriaxone. Synovial fluid analysis of the left shoulder revealed a white blood cell count of 53,250/mm3 with mostly neutrophils, and this led to a presumptive diagnosis of septic arthritis. She underwent a left shoulder arthroscopic irrigation and debridement. The synovial fluid culture was negative. Magnetic resonance imaging (MRI) revealed osteomyelitis in the left humerus, a 4.4 x 5 cm intramuscular abscess near the distal anterior humerus, and pyomyositis. Percutaneous abscess drainage was done. The patient was discharged home on ceftriaxone but returned 12 days later with worsening pain in her shoulder. Repeat MRI showed a complex glenohumeral joint effusion. She had an incision and drainage of her left shoulder. The patient was discharged on an eight-week course of ceftriaxone. Prompt diagnosis and early treatment are essential in reducing the mortality and morbidity associated with these joint, bone, and muscle infections.

A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection.

BACKGROUND: Colchicine has been used in conditions such as periodic febrile illness, acute pericarditis, and gouty arthritis, all having a common hyperinflammatory response as seen in moderate to severe forms of coronavirus disease 2019 (COVID-19). This project was carried out during the rapid surge of cases in New York City, and the goal was to assess the efficacy of colchicine in treating patients with COVID-19. METHODS: Patients admitted to two distinct pulmonary oriented floors of the BronxCare Hospital Center were compared. Patients on one floor were given colchicine in addition to standard of care, while control patients from another floor received only standard of care. Patients who had at least two separate timepoint measurements for at least two out of four serum inflammatory markers (C-reactive protein (CRP), D-dimer, ferritin, or lactate dehydrogenase (LDH)) were selected for the final comprehensive analysis. RESULTS: An initial analysis performed on all patients, irrespective of the availability of two timepoint inflammatory markers, revealed a lower mortality (49.1% versus 72.9%, P = 0.002), a lower percentage of intubations (52.8% versus 73.6%, P = 0.006), and a higher discharge rate (50.9% versus 27.1%, P = 0.002), in the patients who received colchicine. Patients in the final comprehensive analysis groups (34 in the colchicine group and 78 in the control group) had a similar prevalence of comorbid medical conditions, except for renal failure, which was higher in the control group (65.3% versus 35.2%, P = 0.015). HTN (71.8% versus 52.9%, P = 0.053) and DM (51.3% versus 32.4%, P = 0.064) were also more prevalent in the control group, although the difference was not statistically significant. Patients who received colchicine had a lower mortality than the control group (47.1% versus 80.8%, P = 0.0003), lower rate of intubations (47.1% versus 87.2%, P < 0.0001), and a higher discharge rate (52.9% versus 19.2%, P = 0.0003). Patients in the colchicine group also showed a more significant decrease in inflammatory markers for D-dimer (P = 0.037), CRP (P = 0.014), and ferritin (P = 0.012). CONCLUSIONS: Our study demonstrates that colchicine improved outcomes in patients with COVID-19 receiving standard of care therapy. Future randomized, placebo-controlled clinical trials to assess the potential benefit of colchicine in COVID-19 are warranted.

Post-chikungunya rheumatic disorders in travelers after return from the Caribbean.

BACKGROUND: Due to increasing concerns about post-chikungunya (pCHIK) rheumatic disorders in Latin America we aimed to evaluate its occurrence in travelers returning to NYC from the Caribbean. METHOD: Patients diagnosed with chikungunya (CHIK) during 2014 at the Bronx-Lebanon Hospital Center (Bronx, NewYork) were identified by reviewing laboratory and electronic medical records. Patients and caregivers of pediatric patients were interviewed by phone ≥9 months after the CHIK diagnosis to survey for chronic symptomatology and current health care needs. Reported chronic musculoskeletal complaints were categorized according to validated criteria. RESULTS: A total of 28 patients (54% females, median age [range] of 51.5 [0, 88] years) diagnosed with CHIK at our center were identified. Most (82%) had returned from the Dominican Republic. Nineteen (68%) patients were successfully contacted at a median (range) of 13 (9, 16) months since the acute diagnosis. A third (37%) reported ongoing complaints related to CHIK including joint pain (32%), muscle pain (32%), and joint swelling (26%). A presumptive diagnosis of pCHIK chronic inflammatory arthritis (n = 4) and pCHIK musculoskeletal disorder (n = 3) was established. CONCLUSIONS: A third of travelers with CHIK acquired in the Caribbean may be at risk for developing persistent symptoms suggestive of pCHIK rheumatic disorder.

Neutrophil gelatinase-associated lipocalin is instrumental in the pathogenesis of antibody-mediated nephritis in mice.

OBJECTIVE: The mechanism by which anti-DNA antibodies mediate lupus nephritis has yet to be conclusively determined. Previously, we found that treatment of mesangial cells with anti-DNA antibodies induced high expression of neutrophil gelatinase-associated lipocalin (NGAL), an iron-binding protein up-regulated in response to kidney injury. We undertook this study to determine whether NGAL is instrumental in the pathogenesis of nephritis, is induced as part of repair, or is irrelevant to damage/repair pathways. METHODS: To investigate the role of NGAL in antibody-mediated nephritis, we induced nephrotoxic nephritis by passive antibody transfer to 129/SyJ and C57BL/6 mice. To determine if NGAL up-regulation is instrumental, we compared the severity of renal damage in NGAL wild-type mice and NGAL-knockout mice following induction of nephrotoxic nephritis. RESULTS: We found that kidney NGAL expression, as well as urine NGAL levels, were significantly increased in mice with nephrotoxic nephritis as compared to control-injected mice. Tight correlations were observed between NGAL expression, renal histopathology, and urine NGAL excretion. NGAL-knockout mice had attenuated proteinuria and improved renal histopathology compared to wild-type mice. Similarly, following nephritis induction, NGAL injection significantly exacerbated nephritis and decreased survival. NGAL induced apoptosis via caspase 3 activation and up-regulated inflammatory gene expression in kidney cells in vitro and when injected in vivo. CONCLUSION: We conclude that kidney binding of pathogenic antibodies stimulates local expression of NGAL, which plays a crucial role in the pathogenesis of nephritis via promotion of inflammation and apoptosis. NGAL blockade may be a novel therapeutic approach for the treatment of nephritis mediated by pathogenic antibodies, including anti-glomerular basement membrane disease and lupus nephritis.

Diffuse calcifications of the spleen: a novel association with systemic lupus erythematosus.

OBJECTIVES: While anatomical and physiological changes in the spleen are reported in systemic lupus erythematosus (SLE), a complex autoimmune disease that can affect most organ systems, calcifications have not been described as a characteristic feature. We report 4 lupus patients with extensive splenic calcifications with no apparent cause except for their primary disease. The relevant literature on calcifications of the spleen in SLE is also reviewed. METHODS: Four lupus patients with extensive splenic calcifications are described, identified by radiologists at 2 large urban academic centers. In addition, the relevant literature was reviewed (PubMed search 1947 through May 2010) using the following terms: "lupus," "spleen," and "calcified," "calcification," "calcifications," or "microcalcifications." English-language case reports and series were selected. RESULTS: Four lupus patients were found to have a unique pattern of splenic calcifications. The age range was 36 to 73 years. Two of the patients were women, and 1 of these had SLE and limited systemic sclerosis. On reviewing the literature, 6 additional cases of lupus and splenic calcifications were found, 1 of which had pathologic assessment of the spleen on autopsy. The incidence of infection was apparently not increased in affected patients. CONCLUSIONS: A unique pattern of calcifications of the spleen may be found in lupus patients, which can suggest the diagnosis of the underlying connective tissue disease. Whether splenic calcification can predispose to hyposplenism remains to be determined. While the exact significance of diffuse splenic calcification is still unknown, this unique radiologic finding may be a result of the disease process itself.

Prolactin, systemic lupus erythematosus, and autoreactive B cells: lessons learnt from murine models.

The predominant prevalence of autoimmune diseases in women of reproductive age has led to the investigation of the effects of sex hormones on immune regulation and in autoimmune diseases, in particular the prototypic systemic autoimmune disease lupus. The female hormone prolactin has receptors beyond the reproductive axis including immune cells, and it is thought to promote autoimmunity in human and murine lupus. Induced hyperprolactinemia in experimental lupus models, regardless of gender, exacerbates disease activity and leads to premature death. Prolactin treatment in mice that are not prone to develop lupus leads to the development of a lupus-like phenotype. Persistent mild-moderate hyperprolactinemia alters the selection of the naïve B cell repertoire. Recent studies demonstrate that prolactin impairs all three mechanisms of B cell tolerance induction (negative selection, receptor editing, and anergy) and thereby contributes to the pathogenesis of autoimmunity. The effects of prolactin are genetically determined as shown by the differential response to the hormone in the different mice strains. Bromocriptine, a drug that inhibits prolactin secretion, abrogates some of the immune effects of this hormone. Further research is required to elucidate molecular mechanisms involved in immune effects of prolactin and to develop novel targeted treatments for SLE patients with prolactin-responsive disease.

Sex and autoantibody titers determine the development of neuropsychiatric manifestations in lupus-prone mice.

Emotional disturbances are among the most common neuropsychiatric manifestations of SLE, a systemic autoimmune disease with a strong female predominance. In this study, we evaluated young MRL/lpr mice, directly comparing males and females. MRL/lpr females exhibited significant depression as early as 5 weeks (at which time elevated levels of autoantibodies were already present), as compared to MRL/lpr males, where depression was noted only at 18 weeks. Depression was significantly correlated with autoantibodies against nuclear antigens, NMDA receptor, and ribosomal P. Our results are consistent with a primary role of autoantibodies in the pathogenesis of early neuropsychiatric deficits in this lupus model, which translate into gender-based differences in clinical phenotype.

B-cell-directed therapies in systemic lupus erythematosus.

OBJECTIVE: Owing to their ability to promote the onset and flares of systemic lupus erythematosus (SLE), B-cells are now established as key players in the pathogenesis of the disease, and, therefore, have become a major therapeutic focus in SLE. In this article, we review the literature on B-cell-directed therapies for SLE focusing on B-cell depletion, B-cell tolerance, costimulatory signals, and cytokines that affect B-cell survival and activation. METHODS: The clinical trials reviewed in this article were accessed from the PubMed database (www.pubmed.gov) and Clinical Trials database (www.clinicaltrials.gov) through an English language search of the literature published between January 2002 and March 2007. Keywords included the following terms: B-cells, SLE, and therapy. RESULTS: Seventeen completed clinical trials enrolling 973 patients and 5 ongoing studies with anticipated enrollment of 785 patients were reviewed. Novel SLE therapies that target B-cells directly or indirectly were included. B-cell-depleting therapies with the monoclonal antibodies rituximab and epratuzumab have shown good therapeutic results. On the contrary, the well-studied B-cell tolerogen LJP 394 has not demonstrated much clinical benefit. Studies targeting costimulatory pathways have shown variable results; clinical trials with anti-CD40L antibody were terminated because of thromboembolic events, whereas studies targeting the B7-CD28 pathway seem promising. Anticytokine agents against B-lymphocyte stimulator (BLyS), interleukin (IL)-10, IL-6, and interferon alpha (IFN-alpha) are the newcomers that need further evaluation in the treatment of SLE. CONCLUSIONS: Progress in technology has led to the variety of B-cell-directed therapies. In contrast to general immunosuppressants, novel treatments that interfere with specific aspects of B-cell functions create the possibility of developing targeted therapeutic approaches for specific subpopulations of lupus patients.