Polyarticular Joint Research Articles

Isolated Adrenocorticotropic Hormone Deficiency Presenting With Arthritis: A Case Report.

This case report describes a case of isolated adrenocorticotropic hormone (ACTH) deficiency that presented with arthritis. Initial investigations, including blood tests, imaging, and musculoskeletal ultrasonography, did not confirm to any specific connective tissue disease, making it initially difficult to identify the cause of the arthritis. Subsequent adrenal crisis led to the diagnosis of isolated ACTH deficiency through comprehensive endocrine evaluation. The patient's musculoskeletal symptoms were resolved following corticosteroid replacement therapy together with generalized symptoms. This report highlights isolated ACTH deficiency as a rare but one of the causes of polyarticular joint pain and underscores the importance of considering endocrine disorders in the differential diagnosis of unexplained arthritis, particularly when accompanied by systemic symptoms.

Patient clusters identified by machine learning from a pooled analysis of the clinical development programme of secukinumab in psoriatic arthritis, ankylosing spondylitis and psoriatic arthritis with axial manifestations.

To identify patient clusters based on baseline demographics and clinical indicators. Pooled baseline demographics and clinical data of secukinumab-treated patients from ten Phase III studies in psoriatic arthritis (PsA; FUTURE 1-5 and MAXIMISE), ankylosing spondylitis (AS; MEASURE 1-4), were analysed by machine learning (ML) algorithms. The longitudinal responses of secukinumab 300 mg versus 150 mg were investigated across the clusters and three clinical indicators of tender joints, swollen joints and enthesitis. 3907 patients were grouped into eight distinct clusters based on patient demographics and baseline clinical characteristics. Patients with PsA and axial manifestations (MAXIMISE) were overrepresented in clusters 6-8. Patients in cluster 6 (mean age 48 years; 46% male) were overweight with pronounced psoriasis, higher articular burden in knees, shoulders, elbows and wrists. Patients in cluster 7 (mean age 47 years; 53% male) were less overweight with lower polyarticular joint counts and tenderness of the joints of the feet, wrists and hands. Patients in cluster 8 were predominantly with AS (mean age 43 years; 64% male) with a mean body mass index of 27.3 kg/m2, oligoarthritis and high prevalence of spinal pain. Patients with PsA (FUTURE) were overrepresented in clusters 1-5. Longitudinal analysis showed improvements with secukinumab 300 mg versus 150 mg in clusters 6 and 8 for tender joint counts, and cluster 7 for swollen joint counts. PsA clusters obtained by ML in pooled dataset indicate phenotypical heterogeneity of patients with PsA and axial manifestations and overlapping features across the spondyloarthritis spectrum.

Reversible Bilateral Basal Ganglia and Brainstem Lesions in Neuropsychiatric Systemic Lupus Erythematosus: A Case Report

<p>The pathophysiology behind neuropsychiatric SLE (NPSLE) remains poorly understood and its clinical and radiological manifestations are highly varied. In this report, we present a complex case of an adolescent female patient with a three-week history of systemic symptoms (fever, nausea, vomiting, weight-loss, polyarticular joint pain), progressive motor weakness, tremor, and altered mental status. Physical examination was significant for oromandibular and cervical dystonia rigidity, and general weakness with imposed right-sided hemiparesis. A head MRI demonstrated bilateral hyperintense lesions of the basal ganglia and brainstem, SS without restricted diffusion. The patient was diagnosed with NPSLE, lupus nephritis, electrolyte imbalance, severe hypoalbuminemia, lupus cardiomyopathy, autoimmune hemolytic anemia, pulmonary tuberculosis, and sepsis. The patient was given treatment in the ICU with pulse dose corticosteroids, intravenous antibiotics, intravenous immunoglobulins (IVIg), and supportive treatment with correction of hematologic and electrolyte abnormalities. Her condition improved rapidly. Full alertness was regained, and symptoms of oromandibular dystonia, tremor, and weakness diminished significantly. A follow-up MRI three weeks later revealed complete disappearance of lesions, which we attribute to resolution of the inflammatory process in the brain.</p>

Similarities and differences between gouty arthritis and rheumatoid arthritis—an interesting case with a short look into the literature

Gout often presents as acute arthritis but may also present with chronic joint inflammation. For the diagnosis of an acute gout attack with its typical symptoms, the differentiation towards a bacterial joint infection is critical and mandatory. The detection of intracellular uric acid crystals in the synovial fluid of affected joints is important for the initial diagnosis of gout. In the case of a chronic course with polyarticular joint involvement, the differentiation from other inflammatory rheumatic diseases such as rheumatoid arthritis (RA) can be challenging. The case presented here is of interest because the patient initially had characteristic clinical symptoms of tophaceous gout including a typical medical history—even though rheumatoid factor and anti-citrullinated protein antibodies (anti-CCP) were positive. The course of the disease and the critical evaluation of all findings also, and most interestingly, including histological results finally suggested a main diagnosis of RA.

Abstract 14073: Hypercalcemia Induced Reversible LBBB

Background: Parathyroid hormone (PTH) and calcitriol are the two hormones responsible for calcium and phosphate homeostasis. PTH exerts its effect on the renal tubular calcium reabsorption and bone resorption. PTH secretion is modulated by calcium acting on the sensitive calcium-sensing receptor on the parathyroid cells. Primary hyperparathyroidism has been linked to hypertension and valvular calcification. Structural changes are also seen including elevated left ventricular mass, diastolic dysfunction and myocardial calcification. Case presentation: A 61-year old female with hyperlipidemia and osteoporosis presented with polyarticular joint pain and diffuse myalgia noted to have elevated PTH of 90 pg/ml and elevated Ca of 10.1 mg/dl. Her calcium levels has ranged from 10.1 to 11.2 mg/dl and her PTH ranged from 90 to 113 pg/ml. She had a negative sestamibi scan, and thyroid ultrasound showed fusiform lesion measuring 0.82 x 0.36 in the right posterior neck suspicious for a parathyroid adenoma with the plan made for resection. The diagnosis at this time was primary hyperparathyroidism induced hypercalcemia. She developed exertional dizziness and was found to have a new LBBB and reduced ejection fraction of 40-45% with a small fixed defect in the septal area which was attributed to the LBBB. She was initiated on metoprolol succinate 25 mg, irbesartan 75 mg, atorvastatin 40 mg and aspirin 81 mg because of the reduced systolic function. SPECT was negative for ischemia with a fixed decreased uptake of the septum. She underwent right lower parathyroid excision on 11/2021 with normalization of calcium to 9.4 mg/dl and PTH to 9 pg/ml with resolution of the LBBB and systolic function in 2/2021 improving to 48%. Discussion: Calcium plays a key role in cardiac excitation, depolarization, repolarization, and also coupling of these signals to mechanical contraction via calcium induced calcium release and myofibril cross linking. In this case, calcium was only mildly elevated to cause a partial conduction defect. Literature is lacking on whether there is a threshold level for calcium that predisposes to varying degrees of conduction disease. This case also highlights the temporal nature of symptom resolution following parathyroid surgery with resolution of the LBBB.

PSAT012 Endogenous Hypercortisolism Concealing an Autoimmune Disease

Abstract Background Endogenous hypercortisolism may mask symptoms of autoimmune diseases by suppressing immune responses. These conditions can flare upon resolution of hypercortisolism. We report a case of a patient with adrenal Cushing's syndrome (CS) who was diagnosed with seropositive rheumatoid arthritis (RA) after resolution of hypercortisolism post adrenalectomy. Clinical Case A 38-year-old woman presented with a two-year history of a 30-pound weight gain, purple striae, acne, easy bruising, and worsening anxiety. Evaluation was consistent with an ACTH-independent CS: cortisol 33 ug/dL (3-17), ACTH <1 pg/mL (7.2-63.3), DHEA-S 53 ug/dL (45-270), elevated 24-hour urine free cortisol 354.1 ug/day (<45), and an abnormal 1mg dexamethasone suppression with cortisol 23 ug/dL and dexamethasone level 215.1 ng/dL (140-295). CT abdomen revealed bilateral adrenal nodules: right 2.3cm×2.9cm with HU of 19 and left 2.1cm×2.3cm with HU of -16 consistent with bilateral macronodular hyperplasia. A laparoscopic right adrenalectomy and a left cortical-sparing adrenalectomy was performed with the goal of preventing adrenal insufficiency by preserving sufficient adrenal cortex tissue. She was discharged on a hydrocortisone taper following perioperative stress doses. While on hydrocortisone 15mg in the morning and 5mg in the afternoon, no evidence of hypothalamus-pituitary-adrenal (HPA) axis recovery was seen: cortisol <1 ug/DL with ACTH 2.5 pg/mL. Electrolytes and plasma renin activity remained normal. However, once glucocorticoids were tapered to a physiologic dose, she experienced fatigue, diffuse muscle aches, polyarticular joint pain, swelling, and stiffness concerning for an underlying inflammatory disorder. Rheumatology evaluation was consistent with seropositive RA: cyclic citrullinated peptide >200 units (<200) and rheumatoid factor 34 IU/mL (0-14) in the setting of tenosynovitis of her wrists and fingers. Her symptoms rapidly improved on methotrexate 15mg weekly and prednisone 20mg daily. Prednisone was then tapered by 5mg every 2 weeks to physiologic, 5mg daily, without issues while continuing methotrexate. Repeat assessment of her HPA axis is pending. Conclusion Untreated CS with hypercortisolism may mask autoimmune diseases by suppressing inflammation until the hypercortisolism is reversed, and patients no longer have endogenous glucocorticoid excess. The incidence of new onset autoimmune diseases after treatment of CS is not well described in the literature. One single center retrospective analysis of 147 CS patients found 9 cases of patients developing autoimmune diseases such as thyroiditis and vasculitis after treatment of their CS. Here we add to these described cases with the uncovering of RA after normalization of cortisol levels. It is important for clinicians to distinguish activation of autoimmune disorders after CS is treated from manifestations of glucocorticoid withdrawal postoperatively. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

KNEE SYNOVIAL OSTEOCHORNDROMATOSIS: CASE REPORT, SAUDI ARABIA

A rare benign condition known as synovial osteochondromatosis is characterized by the development of several cartilaginous nodules in the synovial joint. It is a monoarticular or polyarticular joint disease, that is easily diagnosed with radiographs. We decided to present this case as its infrequently seen in our arthroplasty clinic and accidentally found during routine images when the patient presented with pain and limited range of motion.

KNEE SYNOVIAL OSTEOCHORNDROMATOSIS: CASE REPORT, SAUDI ARABIA

A rare benign condition known as synovial osteochondromatosis is characterized by the development of several cartilaginous nodules in the synovial joint. It is a monoarticular or polyarticular joint disease, that is easily diagnosed with radiographs. We decided to present this case as its infrequently seen in our arthroplasty clinic and accidentally found during routine images when the patient presented with pain and limited range of motion.

Association of skin lesion severity with clinical features of psoriatic arthritis

Objective: To investigate the relationship between psoriasis severity and clinical features in psoriatic arthritis (PsA). Methods: Patients were recruited from the Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021, and data were collected including the baseline demographic characteristics, various clinical manifestations (including arthritis, nail disease, comorbidities), laboratory tests[including erythrocyte sedimentation rate(ESR), C-reactive protein (CRP)], health assessment questionnaire (HAQ). Body surface area (BSA) and psoriasis area and severity index (PASI) were selected for the tools of assessment of cutaneous psoriasis. Patients were divided to two groups, including the severe psoriasis group (BSA>10%) and the non-severe psoriasis group (BSA≤10%). Disease assessment included ankylosing spondylitis disease activity score (ASDAS), disease activity score 28 (DAS28) and disease activity in psoriatic arthritis (DAPSA). Results: 1 074 eligible patients with PsA were recruited, and 106 (9.9%) had severe psoriasis. Compared with non-severe psoriasis group, the severe psoriasis group had more peripheral joint involvement (including patients with ever or current peripheral arthritis, 94.3% vs. 85.6%), more polyarticular joint involvement (including patients with current peripheral arthritis, 74.0% vs. 58.2%), more axial joint involvement (51.4% vs. 39.9%), more nail disease (72.6% vs. 61.4%), more frequency of smoking (20.2% vs. 18.7%), and higher proportion of hypertension (23.4% vs. 14.4%). In addition, the severe psoriasis group had higher level of ESR [33(10, 70) mm/1h vs. 20(9, 38) mm/1h] and CRP [18.6(5.0, 60.8) mg/L vs. 7.0(2.4, 18.1) mg/L], higher values of DAS28-ESR (4.5±1.7 vs. 3.7±1.5), DAS28-CRP (4.2±1.5 vs. 3.4±1.4), ASDAS-ESR (3.5±1.4 vs. 2.6±1.2), and ASDAS-CRP(3.4±1.6 vs. 2.5±1.2), higher scores of HAQ [0.6(0.1, 1.0) vs. 0.3(0.0, 0.8)]. Conclusion: Patients with PsA with severe psoriasis bore a heavier disease burden. Therefore, clinicians were supposed to pay more attention to them. In addition to skin lesions, they should also focus on examination of other clinical manifestations, such as joints and nails.

A Case Report of Male Systemic Lupus Erythematous with Antinuclear Antibodies-Negative: A Challenging Diagnosis

Systemic lupus erythematosus (SLE) is a connective tissue disease of unknown etiology that predominantly affects women of childbearing age. We report a case of male systemic lupus erythematous with antinuclear antibodies and typical clinical presentations of multiple skin lesions, polyarticular joint pain, fatigue, anorexia, and hair loss. Full evaluations were used to establish a diagnosis of SLE. The lower prevalence of SLE among males and antinuclear antibody-negative patients poses a great challenge for diagnosis. Therefore, as primary care doctors, we need to have a high suspicion of systemic lupus erythematous even in male and antinuclear antibody-negative patients. Thus, early treatment may help patients improve their quality of life.

Neisseria meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis

• Septic Arthritis is a medical emergency with a high mortality and morbidity. • Early recognition of Septic Arthritis is crucial to preserve joint integrity. • Primary Meningococcal Arthritis can present with atypical clinical features. • PCR testing can prove invaluable in identifying bacterial DNA. • Neisseria Meningitidis is a fastidious organism not easy to culture. Septic Arthritis is a medical emergency with a significant mortality and morbidity. Infection usually occurs via haematogenous seeding of microorganisms or via injury, such as trauma or surgery. The aim of management is to minimise the risk of irreversible joint damage and to preserve function. Septic arthritis is usually bacterial in origin, most commonly Staphylococcus aureus , but Mycobacteria or fungi can also be responsible. Neisseria meningitidis is an aerobic Gram-Negative Diplococcus that normally inhabits the naso and oropharynx and has the potential to cause meningitis, septicaemia, septic arthritis and endocarditis. We present the case of a 63 year old lady admitted with bilateral knee pain and swelling, lower limb rash and a fever who was initially managed as a Reactive Arthritis but subsequent Polymerase Chain Reaction (PCR) molecular analysis revealed capsular group B N. meningitidis in bilateral knee aspirates. We discuss the diagnostic challenges in differentiating Septic Arthritis from inflammatory arthritis, and the role of PCR molecular analysis in that process.

O11 Neisseria Meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis

O11 <i>Neisseria Meningitidis</i> as a cause of isolated bilateral polyarticular native knee joint septic arthritis

RECURRENT PLEURAL EFFUSION: THE INITIAL PRESENTATION OF RHEUMATOID ARTHRITIS

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pleural effusion is an uncommon complication of rheumatoid arthritis (RA), affecting roughly 2-3% of patients. Rheumatoid pleural effusions are typically observed in patients with an existing diagnosis of RA and are seldom the first manifestation of this disease. CASE PRESENTATION: A 48-year-old Hispanic man with no significant past medical history presented to the emergency department (ED) with three weeks of non-productive cough, pleuritic chest pain, and shortness of breath with exertion. On initial presentation, vital signs were within normal limits. Physical exam was remarkable for decreased breath sounds bilaterally with increased prominence in the right lower lobe, dullness to percussion of the right lower lobe, and no crackles. Laboratory studies were notable for mild leukocytosis with a neutrophilic predominance. Computed tomography (CT) angiography of the chest revealed a right sided pleural effusion with compressive atelectasis of the right lower lobe and patchy consolidation of the right middle lobe. The patient underwent right sided thoracentesis with removal of 200 ml of fluid. Pleural fluid analysis demonstrated 19% eosinophils, a glucose of 21 mg/dL, and a lactate dehydrogenase (LDH) of 856 units/L. Cytology was unremarkable. His presentation was attributed to a parapneumonic effusion and he was was discharged on oral antibiotics. He ultimately returned to the ED 9 days later with a similar clinical presentation. Repeat CT of the chest revealed recurrence of the right sided pleural effusion. A chest tube was placed with removal of 500 mL of cloudy yellow fluid. Pleural fluid analysis was remarkable for 7% eosinophils, glucose of 40 mg/dL, LDH of 600 units/L, and a pH of 8.0. Cytology displayed mixed inflammatory cells. Pleural fluid was suggestive of RA pleurisy. Further laboratory workup revealed RA titers of 1:32, A-DNA of 10.0 IU/mL, positive antinuclear antibody, and cyclic citrullinated peptide of 289.4 U/mL. The patient had no symptoms of polyarthritis. Patient was treated with prednisone and methotrexate with complete resolution of symptoms. DISCUSSION: RA should be considered as an etiology in unexplained cases of exudative pleural effusion, particularly when pleural fluid analysis shows low glucose, low pH, and high LDH. Pathognomonic cytologic features of rheumatoid pleuritis include the presence of large, elongated macrophages, giant multinucleated cells, and granular background material. CONCLUSIONS: Rheumatoid pleural effusions can occur before, concurrently with, or after the onset of joint symptoms. Thus, clinicians should not exclude the diagnosis of RA in patients without the typical symptoms of polyarticular joint disease. REFERENCE #1: Chou CW, Chang SC. Pleuritis as a presenting manifestation of rheumatoid arthritis: diagnostic clues in pleural fluid cytology. Am J Med Sci. 2002;323(3):158-161. REFERENCE #2: Rodriguez-Zarco E, Vallejo-Benitez A, Otal-Salaverri C. Pleural Effusion Associate with Rheumatoid Arthritis: Diagnostic Clues. J Cytol. 2019;36(4):222-223. DISCLOSURES: No relevant relationships by Gustavo Avila, source=Web Response No relevant relationships by Jessica Baek, source=Web Response No relevant relationships by Mauricio Hernandez Zuniga, source=Web Response No relevant relationships by Renuka Reddy, source=Web Response No relevant relationships by Claudia Tejera Quesada, source=Web Response

Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.

Arthritis mutilans in juvenile idiopathic arthritis.

These hand photographs of a woman aged 42 years old, who has had persisting polyarticular joint pain over decades, show severe foreshortening of the fingers with telescoped skinfolds (figure A). She had a history of polyarticular joint pain complicated with general fatigue and fever, whereby the fatigue and fever persisted for over a month when she was 7 years old (in 1985). Based on currently available criteria from the International League of Associations for Rheumatology for the classification of juvenile idiopathic arthritis, these symptoms were consistent with rheumatoid factor negative polyarticular arthritis or systemic arthritis.

Epidemiological study of bone and joint injury based on urban medical insurance database

To estimate the prevalence rate of bone and joint injury in China and to describe the three-dimension distribution of the disease (area, time and people). Based on a cross-sectional design, a retrospective study was conducted by using Chinese basic medical insurance database from January 1, 2013 to December 31, 2017 to analyze the epidemiological characteristics of bone and joint injury. The prevalence rate of bone and joint injury in each city was calculated, and then using meta-analyses to estimate the pooled prevalence of each area and the whole country. The pooled prevalence rates were compared among the different groups of populations, in terms of geographical area, time and population characteristics (age and gender). A total of 28 419 264 subjects were included in this study, including 705 793 patients with bone and joint injury. From 2013 to 2017, in Chinese basic medical insurance database, the overall prevalence rate of bone and joint injury was 141.5(95%CI: 90.4－203.7) per 10 000 population, and the prevalence rates of non-specific or polyarticular disease, knee disease, and shoulder disease were 101.6 (95%CI: 63.5－148.4)per 10 000 population, 22.5(95%CI:15.1－31.4)per 10 000 population and 10.9 (95%CI: 6.4－16.4)per 10 000 population. The prevalence rates varied across the areas, the highest rate was observed in North China, with the prevalence of 310.6 (95%CI: 12.6－989.7) per 10 000 population, and the lowest rate was observed in Southwest China, with the prevalence of 59.0 (95%CI: 37.5－85.2) per 10 000 population. The prevalence rate of bone and joint injury increased over the study period, from 111.1 (95%CI: 56.0－182.5)per 10 000 population in 2013 to 175.5 (95%CI: 116.8－245.5)per 10 000 population in 2017. The prevalence of bone and joint injury in the female population was 149.1 (95%CI: 94.2－215.9) per 10 000 population, which was higher than that of men [133.6(95%CI: 86.2－190.9) per 10 000 population]. The higher prevalence of knee disease, unspecified or polyarticular disease, and bone and joint injury were observed in people aged 60 years and older, while the prevalence of shoulder disease peaked in 40－59 years old people [20.6 (95%CI: 12.5－30.5) per 10 000 population]. This study reported a relative low prevalence of bone and joint injury in China from 2013 to 2017. The prevalence increased over the study period, and the highest prevalence rate was observed in North China. The prevalence rate showed differences among different groups of populations, and higher rates were observed in females and people aged 60 years and older.

Atypical arthritis in a toddler: beware, save the heart

Acute rheumatic fever still poses a dreadful threat to pediatric morbidity and mortality. A 2 year old toddler presented to us with non migratory polyarticular joint pain and swelling. General physical and systemic examination was normal. Local examination revealed swelling and tenderness of multiple small and large joints. Further evaluation fulfilled Modified Jones criteria and she was diagnosed to have acute rheumatic fever. Other close differentials were simultaneously ruled out. Child was started on naproxen because of aspirin toxicity. There was significant response for therapy and complete resolution of joint involvement was noted on follow up. We report this case to emphasize the fact that rheumatic fever might have bizarre clinical presentation and may also affect infants and toddlers deviating the typical age of onset. There is a need for earliest possible initiation of adequate management and follow up to prevent permanent cardiac complications. This warrants high index of suspicion even in uncommon age group.

A CASE OF RHEUMATOID ARTHRITIS WITH VALVULAR AND VOCAL CORD INVOLVEMENT

Chronic inflammatory polyarticular joint pain is the most common presenting feature of rheumatoid arthritis (RA). Apart from it, other system involvement symptoms and signs are frequently associated. We are reporting a case of RA that presented as a respiratory case, was diagnosed to have valvular heart disease and was eventually diagnosed as RA with cardiovascular involvement along with the unique and rarely reported laryngeal involvement causing loss of voice temporarily.

Pharmacologic Management of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune, systemic inflammatory disease whose hallmark is symmetrical, polyarticular joint involvement. There is characteristic synovial membrane inflammation and proliferation with potential joint and periarticular structure destruction resulting in pain, joint destruction, deformity, and loss of function. Systemic symptoms can occur in RA; they can sometimes antedate evident joint manifestations and include fatigue, weakness, low-grade fever, and generalized malaise. RA occurs predominantly in women, with a peak onset between the fourth and sixth decades of life. All ethnic groups can be affected, although Native American populations tend to have higher rates of prevalence while Asian populations seem to have lower rates. The prevalence of RA in the United States has been estimated at around 1% [1]. RA results in increased morbidity and mortality. The increased morbidity includes significantly increased rates of myocardial infarction, stroke, infection, and lymphoma. It has also been estimated that RA results in mortality rates up to 27% higher than in the general population [2]. Life expectancy can be significantly reduced in patients with RA, although estimates vary widely [3]. The medical and societal costs of RAin the United States have been estimated at $9 billion per year [4]. These estimates fail to account for intangible costs, such as impact on the family as daily life is modified to accommodate the needs of the person with RA. The lifetime costs for a patient with RA have been said to rival those of entities such as stroke or cardiovascular disease [5].

Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies.

Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-α) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.