Reactive arthritis as a rare complication of intravesical bacillus Calmette-Guérin treatment: Report of two cases.

Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is recommended for non-muscle-invasive bladder cancer after transurethral resection. BCG-associated musculoskeletal adverse events are rare. We report two cases of BCG reactive arthritis that were unusually severe and refractory. These describe two male patients who presented with polyarthritis after BCG exposure. Ultrasonography-guided glucocorticoid injections, high-dose systemic glucocorticoids and the institution of sulfasalazine were required for achievement of remission. Bacillus Calmette-Guérin reactive arthritis can present as polyarthritis of small and medium joints or as mono-oligoarthritis of asymmetrical ankles and knees, frequently associated with tenosynovitis and enthesitis. The mechanism by which BCG promotes arthralgia and arthritis is poorly understood. The most well-accepted theory is that the BCG antigens migrate to different peripheral tissues, including the joints. There is also a lack of knowledge regarding risk factors, with possible genetic factors playing a role. As the two presented cases show, BCG-induced reactive arthritis should be considered in the differential diagnosis of arthritis and refractory tenosynovitis in BCG-exposed patients.

Reactive arthritis following COVID-19: clinical case presentation and literature review.

Reactive arthritis (ReA) is a clinical condition typically triggered by extra-articular bacterial infections and often associated with the presence of HLA-B27. While ReA has traditionally been associated with gastrointestinal and genitourinary infections, its pathogenesis involves immune and inflammatory responses that lead to joint affections. The emergence of COVID-19, caused by SARS-CoV-2, has prompted studies of plausible associations of the virus with ReA. We present a case of ReA in a patient who survived COVID-19 and presented with joint affections. The patient, a 31-year-old man, presented with lower limb joints pain. SARS-CoV-2 was confirmed by PCR testing during COVID-19-associated pneumonia. Following a thorough examination and exclusion of all ReA-associated infections, a diagnosis of ReA after COVID-19 was confirmed. In addition, this article encompasses a study of similar clinical cases of ReA following COVID-19 reported worldwide.

Azacitidine as a rare cause of reactive arthritis in a patient with acute myeloid leukemia.

INTRODUCTION: Azacitidine (AZA), a demethylating agent, is one of the mainstay treatments for patients with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) who are ineligible for curative allogeneic stem-cell transplantation and is recommended as first-line treatment in multiple countries. While arthralgia and myalgia have been commonly reported as side effects, the incidence of drug-induced reactive arthritis has only been reported twice so far. CASE REPORT: We present a retrospective overview of a clinical case of a 71-year-old patient that developed new cytopenias on a background of Chronic Lymphocytic Leukaemia and was diagnosed with therapy-associated AML. His treatment included an indefinite course of AZA to induce remission and optimise long-term survival which resulted in a satisfactory haematological response. However, after his ninth AZA cycle, he presented to the emergency department with knee swelling and erythema and conjunctivitis. MANAGEMENT AND OUTCOMES: Arthrocentesis of the knee revealed reactive arthritis with no crystal or organism growth. His symptoms were managed effectively with conservative management including NSAIDs, analgesia and temporary immobilization for joint rest. The adverse drug reaction probability score in our study was calculated as six and adverse drug reaction was thus assigned to the "probable" category. CONCLUSION: We report a case that points to AZA as a probable cause of arthritis flares in MDS patients. The current limitation of this study is the lack of available data, future reviews and research will aid in providing stronger evidence of a correlation between arthritis and AZA treatment.

Does post-COVID reactive arthritis exist? Experience of a tertiary care centre with a review of the literature.

BACKGROUND: Rheumatological manifestations following COVID-19 are various, including Reactive Arthritis (ReA), which is a form of asymmetric oligoarthritis mainly involving the lower limbs, with or without extra-articular features. The current case series describes the clinical profile and treatment outcome of 23 patients with post-COVID-19 ReA. METHODS: A retrospective, observational study of patients with post-COVID-19 arthritis over one year was conducted at a tertiary care centre in India. Patients (n=23) with either a positive polymerase chain reaction test for SARS-CoV2 or an anti-COVID-19 antibody test were included. Available demographic details, musculoskeletal symptoms, inflammatory markers, and treatment given were documented. RESULTS: Sixteen out of 23 patients were female. The mean age of the patients was 42.8 years. Nineteen patients had had symptomatic COVID-19 infection in the past. The duration between onset of COVID-19 symptoms and arthritis ranged from 5 to 52 days with a mean of 25.9 days. The knee was the most involved joint (16 out of 23 cases). Seven patients had inflammatory lower back pain and nine had enthesitis. Most patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and steroids - either depot injection or a short oral course. Three patients required treatment with hydroxychloroquine and methotrexate which were eventually stopped. No relapse was reported in any of the patients. CONCLUSION: On combining our data with 21 other case reports of ReA, a lower limb predominant, oligoarticular, asymmetric pattern of arthritis was seen with a female preponderance. The mean number of joints involved was 2.8. Axial symptoms and enthesitis were often coexistent. Treatment with NSAIDs and intra-articular steroids was effective. However, whether COVID-19 was the definitive aetiology of the arthritis is yet to be proven.

[Reactive arthritis]. / Reaktive Arthritis.

Reactive arthritis Abstract. Reactive Arthritis is a sterile, inflammatory arthritis that is typically preceded by a bacterial gastrointestinal or urogenital infection occurring one to four weeks previously. The typical pattern is an asymmetric oligoarthritis most common affecting the lower extremities. Similar to other spondyloarthropathies, enthesitis, dactylitis, and sacroiliitis can occur as well as extra-articular manifestations, such as conjunctivitis, anterior uveitis, oral ulcers, circinate balanitis, and keratoderma blennorrhagicum. The treatment of "triggering" infection with antibiotics is the first therapeutic goal, especially for Chlamydia trachomatis. For arthritis NSAIDs are the treatment of first choice, followed by intraarticular or oral glucocorticosteroids. DMARDs (Sulfasalzine, TNF-alpha inhibitors) are reserved for refractory cases. Over 50% of the patients have a self-limited course lasting two to six months, 30% have recurrent episodes, and 10-20% have a chronic course requiring immunosuppressive therapy.

Reactive arthritis occurring after COVID-19 infection: a narrative review.

PURPOSE: Reactive arthritis is acute aseptic arthritis occurring 1 to 4 weeks after a distant infection in a genetically predisposed individual. It may occur after COVID-19 infection. We summarize, in this article, the current findings of reactive arthritis following COVID-19 infection. METHODS: A literature search has been performed from December 2019 to December 2021. We included case reports of reactive arthritis occurring after COVID-19 infection. We collected demographic, clinical, and paraclinical data. RESULTS: A total of 22 articles were reviewed. There were 14 men and 11 women with a mean age of 44.96 + 17.47 years. Oligoarticular involvement of the lower limbs was the most frequent clinical presentation. The time between arthritis and COVID infection ranged from 6 to 48 days. The diagnosis was based on clinical and laboratory findings. The pharmacological management was based on non-steroidal anti-inflammatory drugs in 20 cases. Systemic or local steroid therapy was indicated in 13 patients. Sulfasalazine was indicated in two cases. Alleviation of symptoms and recovery were noted in 22 cases. The mean duration of the clinical resolution was 16 + 57 days. CONCLUSION: The diagnosis of reactive arthritis should be considered in patients with a new onset of arthritis following COVID-19 infection. Its mechanism is still unclear.

Knowledge and Perceptions of Reactive Arthritis Diagnosis and Management Among Healthcare Workers During the COVID-19 Pandemic: Online Survey.

BACKGROUND: Reactive arthritis (ReA) is an often neglected disease that received some attention during the coronavirus disease 2019 (COVID-19) pandemic. There is some evidence that infection with severe acute respiratory syndrome coronavirus 2 can lead to "reactive" arthritis. However, this does not follow the classical definition of ReA that limits the organisms leading to this condition. Also, there is no recommendation by any international society on the management of ReA during the current pandemic. Thus, a survey was conducted to gather information about how modern clinicians across the world approach ReA. METHODS: An e-survey was carried out based on convenient sampling via social media platforms. Twenty questions were validated on the pathogenesis, clinical presentation, and management of ReA. These also included information on post-COVID-19 arthritis. Duplicate entries were prevented and standard guidelines were followed for reporting internet-based surveys. RESULTS: There were 193 respondents from 24 countries. Around one-fifth knew the classical definition of ReA. Nearly half considered the triad of conjunctivitis, urethritis and asymmetric oligoarthritis a "must" for diagnosis of ReA. Other common manifestations reported include enthesitis, dermatitis, dactylitis, uveitis, and oral or genital ulcers. Three-fourths opined that no test was specific for ReA. Drugs for ReA were non-steroidal anti-inflammatory drugs, intra-articular injections, and conventional disease-modifying agents with less than 10% supporting biological use. CONCLUSION: The survey brought out the gap in existing concepts of ReA. The current definition needs to be updated. There is an unmet need for consensus recommendations for the management of ReA, including the use of biologicals.

Evaluation of clinical and paraclinical findings in patients with reactive arthritis caused by giardiasis: A systematic review.

INTRODUCTION: The aim of this study was to systematically review the clinical and paraclinical findings in patients with reactive arthritis (ReA) caused by giardiasis. METHODS: In this study, papers describing ReA in patients with giardiasis were found after searching in international databases including MEDLINE/PubMed, Web of Science, Scopus, and ScienceDirect up to 2021. Google Scholar was also searched to find more articles. RESULTS: Finally, 16 studies met the inclusion criteria with reporting 115 patients, ranging in age from 19 months to 49 years. This disease was more reported in children and adolescents than adults. The most frequently involved joints with arthritis were the knee and ankle followed by the hip, wrist, elbow, shoulder, axial skeleton, metatarsophalangeal, and proximal interphalangeal. The most common extra-articular symptoms included diarrhea, allergic symptoms, and abdominal pain. CONCLUSION: The signs and symptoms of ReA caused by giardiasis can be various, from moderate to severe manifestations. Also, they can be similar to some other diseases, so it is recommended that physicians and specialists have more knowledge about this disease to treat patients with a correct diagnosis.

Reactive arthritis after SARS-CoV-2 infection.

SARS-CoV-2 has been recognised as a potential trigger of inflammatory arthritis in individuals with inflammatory rheumatic diseases as well as in previously unaffected individuals. However, new-onset arthritis after COVID-19 is a heterogeneous phenomenon that complicates differential diagnosis. For example, acute arthritis with features of viral arthritis has been reported after COVID-19, as has crystal-induced arthritis. Arthritides mimicking reactive arthritis (ReA) have also been described, but these patients often do not fulfil the typical features of ReA: several reports describe cases of patients older than 45 years at the onset of arthritis, and the characteristic genetic feature of ReA, HLA-B27, is rarely found. Because viral infections are much less likely to cause ReA than bacterial infections, and respiratory infections are rarely the cause of ReA, it is currently unknown whether SARS-CoV-2 can cause true ReA. Here, we report the case of a 30-year-old patient who presented with acute pain, swelling and redness in the left metatarsophalangeal (MTP) joint and ankle 7 days after resolution of a SARS-CoV-2 infection. Diagnostics revealed arthritis of the MTP2, synovitis of the upper ankle with significant joint effusion and peritendinitis of the flexor tendons. Based on the clinical manifestations and diagnostic test results, ReA appeared to be the most likely cause. A screening for typical ReA-associated infections was negative. The patient was treated with NSAIDs and intra-articular and systemic glucocorticoids. At a follow-up visit after discontinuation of glucocorticoids, the patient was symptom-free. Overall, we observed a ReA with typical clinical, genetic and patient characteristics after SARS-CoV-2 infection, and we conclude that a direct association with COVID-19 is highly plausible.

Clinical profiles of post-infectious arthritis and transient synovitis of the hip in children.

BACKGROUND: Acute inflammatory arthritides can present as a result of immune reaction following infections. Post-infectious arthritis and transient synovitis of the hip in children are included in this disease entity. The aim of this study was to describe the clinical profiles of post-infectious arthritis and transient synovitis of the hip in Thai children. METHODS: A retrospective review was performed at a tertiary care hospital in Bangkok, Thailand from January 2005 to July 2017. RESULTS: Eighty-six patients (56 boys and 30 girls) were included in this study. Mean age was 8.4 ± 4.8 years. Reactive arthritis was diagnosed in two patients (2.3%) following Salmonella spp. and Chlamydia trachomatis infections. Post-streptococcal reactive arthritis was present in 10 patients (11.6%). Transient synovitis of the hip was found in 30 patients (34.9%). Forty-four patients (51.2%) were clinically diagnosed with post-infectious arthritis. Mono/oligoarthritis was the most common clinical profile (84.9%). The distribution of lower-extremity involvement was as follows: hip, 47.6%; knee, 46.5%; and ankle joints, 30.2%. The documented preceding illness consisted mostly of upper respiratory tract symptoms (30.2%). Non-steroidal anti-inflammatory drugs were prescribed for 70 patients (81.4%). CONCLUSION: Mono/oligoarthritis of the lower extremity was the main clinical profile. Preceding viral illness was documented in one-third of children. Reactive arthritis was rarely seen.

[A Case of Reactive Arthritis after BCG Intravesical Infusion Therapy Successfully Treated with Salazosulfapyridine].

The patient was a 70-year-old woman who underwent transurethral resection of bladder tumor in May 2020. She was diagnosed with urothelial carcinoma (high grade, pT1 by pathology). We started bacillus Calmette-Guerin (BCG) intravesical infusion (80 mg Tokyo strain) in August of the same year after a second transurethral resection. Pain during urination persisted during the administration of BCG, and it worsened after the completion of six doses. The patient was hospitalized with back and neck pain and difficulty in physical movement. At the time of admission, bilateral conjunctivitis was observed. The patient was diagnosed with reactive arthritis associated with BCG intravesical injection therapy, as three typical symptoms were observed (bilateral conjunctivitis, urethritis, polyarthritis). The patient was treated with prednisolone and non-steroidal anti-inflammatory drugs for arthritis, but the symptoms did not improve. We administered salazosulfapyridine and her reactive arthritis improved.

Reactive arthritis following treatment with intravesical Bacillus Calmette-Guerin for papillary carcinoma of bladder.

A man in his 60s developed reactive arthritis following treatment with intravesical Bacillus Calmette-Guerin (iBCG) for papillary carcinoma of bladder. Evaluation revealed leucocytosis and raised inflammatory markers. HLA B27 was positive. Based on the temporal relationship, it was attributed to BCG-related reactive arthritis. iBCG was stopped. Treatment with non-steroidal anti-inflammatory drugs (NSAIDS) and glucocorticoids were ineffective. Prolonged course of disease-modifying antirheumatic drugs (DMARDS) was required which aided in alleviation of symptoms and sustained remission. Intravesical BCG therapy is a treatment for bladder cancer. It is rarely associated with reactive arthritis, which responds to discontinuation of iBCG and treatment with NSAIDS and/or short-term glucocorticoids. iBCG-related reactive arthritis commonly has an acute/subacute course. Chronic arthritis as observed in our case requiring prolonged treatment with DMARDS is rare.

Association of Corticosteroid Treatment With Outcomes in Pediatric Patients With Bacterial Meningitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: Controversy has arisen among the overall benefit and potential risks in the use of corticosteroids for the treatment of pediatric bacterial meningitis. This systematic review and meta-analysis aims to provide evidence of the use of corticosteroids in the treatment of bacterial meningitis in children. METHODS: Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and other databases) were searched from inception until March 9, 2021. Randomized clinical trials focused on corticosteroids as adjuvant therapy in pediatric bacterial meningitis were considered eligible. The primary outcomes were hearing loss and neurologic sequelae. Secondary outcomes were mean days before resolution of fever, mortality, secondary fever, and reactive arthritis. Fixed- or random-effects models were used to evaluate the association between corticosteroids therapy and outcomes by calculating risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data extraction, and risk assessment. FINDINGS: Twenty-nine studies with 3433 patients were included. An obvious benefit was found in the treatment of corticosteroids in hearing loss (RR = 0.62; 95% CI, 0.47-0.81; I² = 17%; P = 0.0006). No benefit was found in the rate of neurologic sequelae. However, obvious benefit was found in the low-dosage subgroup (0.6 mg/kg per day) (RR = 0.60; 95% CI, 0.47-0.77; I² = 0%; P < 0.0001) but not in the high-dosage subgroup (0.8 mg/kg per day). An increasing rate of secondary fever was found when using corticosteroids (RR = 1.29; 95% CI, 1.10-1.51; I² = 13%; P = 0.001). Corticosteroids could significantly decrease the mean days before resolution of fever (MD = -1.48; 95% CI, -1.79 to -1.17; I² = 84%, P < 0.00001). No difference was found in the rate of mortality and reactive arthritis. IMPLICATIONS: The findings of this study suggest that the administration of corticosteroids is associated with reduced hearing loss and neurologic sequelae especially in children using a low dose of corticosteroids. Benefits also included a reduction in the mean number of days before resolution of fever.

Comparison of immune checkpoint inhibitor-induced arthritis and reactive arthritis to inform therapeutic strategy.

INTRODUCTION: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is a relatively new disease entity caused by ICI agents during cancer therapy. Reactive arthritis (ReA) is a well-known disease entity caused by urogenital or gastrointestinal bacterial infection or pneumonia. In this sense, ICI-IA and ReA are both defined by a reaction to a well-specified causal event. As a result, comparing these diseases may help to determine therapeutic strategies. METHODS: We compared ICI-IA and ReA with special focus on pharmacological management. Specifically regarding treatment, we conducted a literature search of studies published in the PubMed database. Inclusion criteria were studies on treatment with non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GC), or disease modifying antirheumatic drugs (DMARDs) in ICI-IA or ReA. During systematic selection, 21 studies evaluating ICI-IA and 14 studies evaluating ReA were included. RESULTS: In ICI-IA, prospective and retrospective studies have shown effects of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid (GC), sulfasalazine (SSZ), methotrexate (MTX), hydroxychloroquine (HCQ) and TNFi. In ReA, retrospective studies evaluated NSAIDs and GC. A randomized controlled trial reported the effect of SSZ, and a retrospective study reported the effect of MTX and SSZ in combination with tumor necrosis factor alpha inhibition (TNFi). For both entities, small case reports show treatment effects of interleukin 6 receptor inhibition (IL-6Ri). DISCUSSION: This literature review identified both similarities and differences regarding the pathogenesis and clinical features of ReA and ICI-IA. Studies on treatment reported effectiveness of NSAIDs, GC, MTX, SSZ and TNFi in both diseases. Further, small case reports showed effects of IL-6Ri.

Rheumatologic Manifestations of Post SARS-CoV-2 Infection: A Case Series.

BACKGROUND: It has been over a year since the first documented case of the COVID-19 virus was recorded. Since then, our understanding of this virus has continually evolved, however, its wide-ranging effects are still unfolding. Similar to previously studied viral infections, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has been shown to lead to a degree of autoimmunity in patients who are recovering from its effects. Due to its effects on the innate immune system, such as the toll-like receptors and complement system, a varying degree of proinflammatory markers can become widespread in those who continue to recover from the virus. This case series offers a unique perspective on how COVID-19 has had dramatic effects on those already suffering from inflammatory rheumatic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, or fibromyalgia. As the ever-lasting effects of COVID-19 are still unfolding, this case series is one of few to discuss the development and changes of patients with rheumatic conditions. This study hopes to encourage larger studies to be conducted on the effects of COVID- 19 on autoimmune conditions. CASE PRESENTATION: Seven patients were identified with new manifestations of rheumatic conditions, which included 3 cases of rheumatoid arthritis, 2 cases of polymyalgia rheumatica, 1 case of reactive arthritis, and 1 case of cutaneous lupus. Post-COVID syndrome was also diagnosed in 7 other patients. Patients with rheumatoid arthritis presented with symptoms 4-5 weeks after being diagnosed with COVID-19. Symptoms of polyarticular joint pain, swelling, and morning stiffness were reported in this group. These patients were treated with disease-modifying anti-rheumatic drugs and experienced an improvement in symptoms on follow-up. Two cases of polymyalgia rheumatica were identified in patients that were previously diagnosed with COVID-19 six weeks prior. One patient had no significant past medical history and the other patient had a history of rheumatoid arthritis, which was well controlled. These patients experienced weakness and tenderness in the proximal joints with elevated levels of ESR and CRP. They were treated with prednisone and showed improvement. Reactive arthritis was diagnosed in 1 patient who presented with swelling in both hands and wrists 2 days after being diagnosed with COVID-19. This patient began to experience symptoms of reactive arthritis 2 days after resolution of initial COVID-19 symptoms and this persisted for 3 months. The patient was managed with methylprednisolone injections and NSAIDs, which improved her symptoms. Post-COVID syndrome was identified in 7 patients. All patients were female and had a history of well-controlled fibromyalgia. Patients generally experienced fatigue, headaches, and memory fog, which had variable onset from a few days and up to 4 weeks after being diagnosed with COVID-19. One patient had a complete recovery of her symptoms at follow-up 3 months after the initial presentation. The other 6 patients continued to report symptoms of post-COVID syndrome at follow-up. Patients were managed with lifestyle modifications and their previous fibromyalgia treatment. CONCLUSION: While cases of COVID-19 continue to rise, complications of this disease are still being discovered. Those who initially recover from COVID-19 may experience new-onset rheumatic conditions, worsening of previously diagnosed rheumatic conditions, or post-COVID syndrome. As we continue to learn more about the effects of COVID-19, the awareness of these manifestations will play a key role in the appropriate management of these patients.

Infectious mimics of rheumatoid arthritis.

Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.