Coexistent Relapsing Polychondritis and Clinically Amyopathic Dermatomyositis: A Rare Association of Autoimmune Disorders.

Relapsing polychondritis (RPC) is an uncommon autoimmune systemic disease characterized by recurrent inflammation of the cartilage tissue. It can occur alone or in association with other autoimmune diseases, vasculitis, or hematologic disorders. However, the association of RPC with dermatomyositis is extremely rare. Herein, we present a case of a 38-year-old man who developed concurrent RPC and clinically amyopathic dermatomyositis (CADM) manifested by auricular chondritis, nasal chondritis, polyarthritis, gottron papules, fingertip papules, skin biopsy consistent with dermatomyositis, and positive antimelanoma differentiation-associated gene 5 (MDA5) antibodies. RPC features resolved with corticosteroids, but CADM manifestations were resistant to corticosteroids, cyclophosphamide, azathioprine, and hydroxychloroquine. Subsequent therapy with rituximab was effective to control CADM manifestations. This case highlights the importance of recognizing CADM as part of the autoimmune diseases linked with RPC and maintaining a high level of awareness to initiate effective therapy to avoid the long-term complications associated with these conditions.

Monarticular rheumatoid arthritis of the elbow.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by symmetric inflammatory polyarthritis. However, RA limited to a single joint is extremely rare. Here, we report a middle-aged woman who presented with insidious right elbow arthritis. She had no other peripheral joint pain, tenderness or swelling. She had high-positive anti-cyclic citrullinated peptide antibodies. An MRI of the right elbow showed capsular distension, joint effusion and bone marrow oedema. Synovial biopsy revealed hyperplasia with lymphoplasmacytic infiltrate consistent with RA. Therapy with methotrexate 7.5 mg orally weekly was effective to control her inflammatory arthritis. This case highlights the relevance of synovial tissue analysis for patients presenting with chronic inflammatory monarthritis when the cause is not clinically evident, and the importance of considering RA even in the absence of polyarticular involvement. Delayed diagnosis and treatment of inflammatory monarthritis can lead to joint destruction and disability.

Clinical Manifestations and Outcomes in Disease-Modifying Antirheumatic Drug-Naive Adult Patients with Chronic Chikungunya Arthritis.

Most studies on chronic chikungunya virus (CHIKV) arthritis include patients treated with disease-modifying antirheumatic drugs (DMARDs), likely altering the expression of clinical manifestations and outcome. Therefore, we sought to evaluate the clinical features and correlates in DMARD-naive patients with chronic CHIKV arthritis. We conducted a case-control study in adult patients with serologically confirmed CHIKV infection in Puerto Rico. Demographic features, clinical manifestations, comorbidities, disease activity (per Clinical Disease Activity Index [CDAI]), functional status (per Health Assessment Questionnaire Disability Index [HAQ-DI]), and pharmacologic treatment were ascertained. Patients with and without chronic CHIKV arthritis were compared. Furthermore, a sub-analysis was performed among patients with chronic CHIKV who presented with mild disease activity versus moderate-to-high disease activity at study visit. In total, 61 patients were studied; 33 patients had chronic arthritis and 28 had resolved arthritis. Patients with chronic arthritis had significantly more diabetes mellitus, chronic back pain, and fever, tiredness, and myalgias on the acute phase. The mean (SD) HAQ score was 0.95 (0.56), and 57.6% had moderate-to-high disease activity. Patients with moderate-to-high disease activity had higher scores in overall HAQ-DI and HAQ-DI categories (dressing and grooming, arising, hygiene, reaching, and activities) than in those with mild activity. In conclusion, in this group of DMARD-naive patients with chronic CHIKV arthritis, nearly 58% had moderate-to-high disease activity and had substantial functional disability. Diabetes mellitus, chronic back pain, and some manifestations on acute infection were associated with chronic CHIKV arthritis.

Clinical impact of hydroxychloroquine dose adjustment according to the American Academy of Ophthalmology guidelines in systemic lupus erythematosus.

OBJECTIVE: The American Academy of Ophthalmology recommends a maximum hydroxychloroquine (HCQ) dose of ≤5.0 mg/kg/day to reduce the risk of HCQ-induced retinopathy. To determine if this dose adjustment would have an impact on the clinical course of SLE, we compared outcome measures in a cohort of patients with SLE before and after adjusting HCQ dose. METHODS: Sixty Puerto Ricans with SLE (per 1997 American College of Rheumatology criteria) treated with HCQ who were changed to HCQ ≤5.0 mg/kg/day were studied. Visits were ascertained every 6 months for 2 years before and 2 years after HCQ dose adjustment (baseline visit). Disease activity (per Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), SLE exacerbations, emergency room visits, hospitalisations, disease damage (per Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), corticosteroids exposure, prednisone dose and immunosuppressive drugs exposure were determined before and after HCQ dose change. RESULTS: At baseline visit, the mean age was 43.8±15.1 years. All patients were women. The mean disease duration was 13.8±9.1 years. After HCQ dose adjustment, patients required a lower prednisone dose when compared with visits before HCQ dose reduction. No significant differences were observed for mean SLEDAI scores, lupus exacerbations, emergency room visits, hospitalisations, disease damage and exposure to immunosuppressive drugs before and after HCQ dose adjustment. CONCLUSIONS: This study suggests that adjustment of daily HCQ dose to ≤5.0 mg/kg/day of actual body weight does not have a significant impact on the short-term and mid-term outcomes in this group of patients with SLE.

Efficacy of Cyclosporine in the Induction and Maintenance of Remission in a Systemic Lupus Erythematosus Patient Presenting with Macrophage-Activating Syndrome.

Macrophage-activating syndrome (MAS) is a rare condition characterized by dysfunctional macrophage activation leading to overproduction of cytokines and phagocytosis of erythrocytes, leukocytes, and platelets. MAS is associated with infectious diseases, malignancies, and autoimmune rheumatic disorders. Herein, we present a 22-year-old Hispanic woman with SLE who was hospitalized because of a three-week history of fever, fatigue, polyarthralgia, nausea, and abdominal pain. Initial laboratories showed severe pancytopenia with marked elevation of liver enzymes and ferritin levels. Bone marrow biopsy revealed macrophages with engulfed erythrocytes consistent with MAS. The patient was treated with high-dose corticosteroids, intravenous immunoglobulins, and cyclosporine 3 mg/kg/day. She had a remarkable clinical response to this therapy. She was continued on cyclosporine, and prednisone dose was gradually decreased to 7.5 mg daily without experiencing recurrent disease. She remained in full clinical remission for 12 months. Our case, together with other reports, suggests that combination therapy with corticosteroids, immunoglobulins, and cyclosporine appears to be effective for patients with SLE-associated MAS. Furthermore, cyclosporine seems to be a good drug for maintenance of remission.

Severe systemic inflammatory response syndrome immediately after spinal surgery in a patient with axial gout.

We report a 55-year-old man with gouty arthritis who developed a 3-month history of low back pain, gradual lower extremities weakness and urinary incontinence. Lumbar MRI showed an exophytic lesion at L3-L4. Immediately after spinal decompression surgery, he developed fever, disorientation, polyarthritis, acute kidney injury and leucocytosis. He was treated with multiple antimicrobial agents for presumed spinal abscess but did not improve. Multiple body site cultures were negative. Aspiration of the sacroiliac joint revealed the presence of monosodium uric acid crystals. A diagnosis of acute gout was done, and he was treated with high-dose intravenous methylprednisolone and colchicine. Within 48 hours, he had a remarkable clinical improvement. At discharge, neurological and laboratory abnormalities had resolved. Awareness of risk factors for axial gout and a high degree of suspicion are important to establish a prompt diagnosis and treatment to prevent severe complications as seen in this case.

Efficacy of immunosuppressive treatment in a systemic lupus erythematosus patient presenting with inclusion body myositis.

Inclusion body myositis (IBM) is an inflammatory myopathy that is generally unresponsive to immunosuppressive drugs. The coexistence of IBM with other autoimmune connective tissue diseases is rare. We present a case of a 76-year-old woman with systemic lupus erythematosus (SLE) who developed proximal muscle weakness of lower extremities and mild elevation of serum creatine kinase (CK) at 495 U/L. Muscle biopsy showed changes of endomysial inflammation and rimmed vacuoles consistent with IBM. She was treated with prednisone 40 mg daily and methotrexate 12.5 mg weekly. One month later, her physical examination showed minimal proximal weakness of lower extremities. CK levels decreased to 44 U/L. Prednisone dose was gradually decreased to 5.0 mg daily. She remained stable with normal CK levels during a follow-up period of 10 months. This case, together with other reports, suggests that IBM in the setting of SLE represents a different subtype that can benefit from immunosuppressive treatment.

Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome.

Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI ≤ 24.9 kg/m(2) (nonoverweight/obese) and BMI ≥ 25 kg/m(2) (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS.

Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.

OBJECTIVES: Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. METHODS: Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. RESULTS: The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10(-4), OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10(-7), OR 0.71; case-only pmeta=1.9×10(-4), OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. CONCLUSIONS: These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.

Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort.

The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0 (7.9) years; 2127 (91.6%) were women. Anti-Sm antibodies were present in 579 (24.9%) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud's phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.

Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression.

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.

Limited systemic sclerosis initially presenting with mesenteric panniculitis.

Mesenteric panniculitis pertains to a group of uncommon disorders named sclerosing mesenteritis that present with different levels of inflammation and fibrosis of the small bowel mesentery. It is associated with abdominal surgeries, trauma, malignancies, infections and connective tissue diseases. To the best of our knowledge, no cases of sclerosing mesenteritis have been reported in patients with systemic sclerosis. We present a case of a 61-year-old woman who had incidental CT findings of mesenteric panniculitis. Diagnosis was confirmed by biopsy that showed fat necrosis. On further review she had a 1-year history of Raynaud's phenomenon. Physical examination showed sclerodactyly. She had elevated anticentromere antibodies and skin biopsy was consistent with scleroderma. She was diagnosed with limited systemic sclerosis and was treated with D-penicillamine. After 6 years of follow-up, the mesenteric panniculitis and systemic sclerosis both remained stable. This case highlights the importance of considering rheumatic diseases in the differential diagnosis of sclerosing mesenteritis.

Factors associated with tender point count in Puerto Ricans with fibromyalgia syndrome.

OBJECTIVE: To examine the factors associated with fibromyalgia syndrome (FMS) tender point count (TPC) in a group of Hispanic patients from Puerto Rico. METHODS: A cross-sectional study was performed in 144 FMS patients as determined using American College of Rheumatology [ACR] classification). Sociodemographic features, clinical manifestations, comorbidities, and pharmacologic agents were determined during the study visit. Tender points were assessed as described in the ACR classification for FMS. A t-test and one-way ANOVA test were used to examine the relationships between continuous, dichotomous, and nominal variables. RESULTS: The mean (standard deviation, [SD]) age of the FMS patients in this study was 50.2 (9.9) years; 95.1% were females. The mean (SD) TPC was 15.0 (4.7). Dysmenorrhea, the sicca syndrome, subjective swelling, increased urinary frequency, shortness of breath, headache, constipation, paresthesia, cognitive dysfunction, arthralgia, tiredness, morning stiffness, depression, and anxiety were associated with higher TPC. No associations were seen between socio-demographic features and FMS pharmacologic therapies. CONCLUSION: In this group of Puerto Ricans with FMS, TPC was associated with several FMS symptoms and comorbidities. This study suggests that TPC may be a simple and effective tool for assessing disease severity in FMS patients.

Infective endocarditis initially presenting with a dermatomyositis-like syndrome.

Infective endocarditis (IE) may present with rheumatological manifestations such as myalgias, arthralgias, arthritis and back pain. However, muscle inflammation is rare. We present a case of a 68-year-old Hispanic man who presented with 1-month history of tiredness, weight loss, fever, myalgias, muscle weakness and dysphagia to solid food. On physical examination he had severe weakness in the proximal upper and lower extremities, and erythematous eruption involving the upper eyelids, neck and metacarpophalangeal joints. Creatine kinase levels were markedly elevated at 15 809 U/L. MRI of the right thigh revealed intermuscular and intramuscular oedema. Muscle biopsy showed acute necrotising suppurative perimyositis. Blood cultures were positive for methicillin-resistant Staphylococcus aureus. A transoesophageal echocardiogram revealed vegetations in the pulmonic valve. All clinical manifestations were resolved completely with broad-spectrum antibiotics. This case suggests that IE should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.

Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a strong genetic component. African-Americans (AA) are at increased risk of SLE, but the genetic basis of this risk is largely unknown. To identify causal variants in SLE loci in AA, we performed admixture mapping followed by fine mapping in AA and European-Americans (EA). Through genome-wide admixture mapping in AA, we identified a strong SLE susceptibility locus at 2q22-24 (LOD=6.28), and the admixture signal is associated with the European ancestry (ancestry risk ratio ~1.5). Large-scale genotypic analysis on 19,726 individuals of African and European ancestry revealed three independently associated variants in the IFIH1 gene: an intronic variant, rs13023380 [P(meta) = 5.20×10(-14); odds ratio, 95% confidence interval = 0.82 (0.78-0.87)], and two missense variants, rs1990760 (Ala946Thr) [P(meta) = 3.08×10(-7); 0.88 (0.84-0.93)] and rs10930046 (Arg460His) [P(dom) = 1.16×10(-8); 0.70 (0.62-0.79)]. Both missense variants produced dramatic phenotypic changes in apoptosis and inflammation-related gene expression. We experimentally validated function of the intronic SNP by DNA electrophoresis, protein identification, and in vitro protein binding assays. DNA carrying the intronic risk allele rs13023380 showed reduced binding efficiency to a cellular protein complex including nucleolin and lupus autoantigen Ku70/80, and showed reduced transcriptional activity in vivo. Thus, in SLE patients, genetic susceptibility could create a biochemical imbalance that dysregulates nucleolin, Ku70/80, or other nucleic acid regulatory proteins. This could promote antibody hypermutation and auto-antibody generation, further destabilizing the cellular network. Together with molecular modeling, our results establish a distinct role for IFIH1 in apoptosis, inflammation, and autoantibody production, and explain the molecular basis of these three risk alleles for SLE pathogenesis.

Rheumatology practice profiles in teaching and community settings in Puerto Rico: implications to subspecialty training.

BACKGROUND: University-based fellowship training programs may not always provide the required experience to manage common and less complex medical conditions usually seen at the community setting. Few studies have addressed this concern. OBJECTIVE: The purpose of this study was to compare the demographic features, diagnoses, and rheumatologic procedures in patients seen at the University of Puerto Rico Medical Sciences Campus Adult Rheumatology Training Program practice and 3 community-based rheumatology practices in Puerto Rico. METHODS: Claim forms submitted to health care insurance companies in 2007 from the university and community practices were evaluated. Demographic parameters, primary diagnoses (per International Classification of Diseases, Ninth Revision), medical visits, and rheumatologic procedures (per Current Procedural Terminology 4) were examined. Variables were analyzed by χ and Student t tests. RESULTS: A total of 11,373 claim forms were reviewed: 1952 from the university setting and 9421 from the community-based practices. Younger age and female sex were more common in visits from the university-based setting. Autoimmune diseases were reported more commonly at the university setting (65.3% vs 37.6%, P < 0.001). Conversely, osteoarthritis (24.4% vs 9.8%, P < 0.001), fibromyalgia syndrome (7.4% vs 1.9, P < 0.001), and regional rheumatic pain syndromes (7.2% vs 1.4%, P < 0.001) were seen more frequently at community practices. Hospital/emergency room visits (11.8% vs 0.3%, P < 0.001) were more frequent at the university setting, whereas joint (13.3% vs 2.9%, P < 0.001) and periarticular injections (6.2% vs 1.7%, P < 0.001) were performed more frequently at the community practices. CONCLUSIONS: Several differences were found in the profile of demographic parameters, diagnoses, medical visits, and rheumatologic procedures between patients seen at the University of Puerto Rico Medical Sciences Campus rheumatology practice and 3 community-based practices. Efforts may be required to diversify and increase the exposure of rheumatology fellows to patients with conditions commonly seen at the community setting.

Impact of managed care health insurance system for indigent patients with rheumatoid arthritis in Puerto Rico.

The aim of this study was to determine the clinical outcome among indigent patients with rheumatoid arthritis (RA) in Puerto Rico receiving their healthcare in a managed care system, as compared with non-indigent patients treated in fee-for-service settings. A cross-sectional study was conducted in 214 Puerto Ricans with RA (per American College of Rheumatology classification criteria). Demographic features, health-related behaviors, cumulative clinical manifestations, disease activity (per disease activity score 28), comorbid conditions, functional status (per Health Assessment Questionnaire), and pharmacologic profile were determined. Data were examined using uni- and multivariable (logistic regression) analyses. The mean (standard deviation (SD)) age of the study population was 56.6 (13.5) years; 180 (84.1 %) were women. The mean (SD) disease duration was 10.8 (9.6) years. Sixty-seven patients were treated in the managed care setting, and 147 patients received their healthcare in fee-for-service settings. In the multivariable analyses, RA patients treated in the managed care setting had more joint deformities, extra-articular manifestations, arterial hypertension, type 2 diabetes mellitus, cardiovascular events, fibromyalgia syndrome, and poorer functional status while having a lower exposure to biological agents than those treated in fee-for-service settings. Efforts should be undertaken to curtail the gap of health disparities among these Hispanic patients in order to improve their long-term outcomes.