Expanding the spectrum of reactive arthritis (ReA): classic ReA and infection-related arthritis including poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA.

Reactive arthritis (ReA) is a form of sterile arthritis that occurs secondary to an extra-articular infection in genetically predisposed individuals. The extra-articular infection is typically an infection of the gastrointestinal tract or genitourinary tract. Infection-related arthritis is a sterile arthritis associated with streptococcal tonsillitis, extra-articular tuberculosis, or intravesical instillation of bacillus Calmette-Guérin (iBCG) therapy for bladder cancer. These infection-related arthritis diagnoses are often grouped with ReA based on the pathogenic mechanism. However, the unique characteristics of these entities may be masked by a group classification. Therefore, we reviewed the clinical characteristics of classic ReA, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA. Considering the diversity in triggering microbes, infection sites, and frequency of HLA-B27, these are different disorders. However, the clinical symptoms and intracellular parasitism pathogenic mechanism among classic ReA and infection-related arthritis entities are similar. Therefore, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA could be included in the expanding spectrum of ReA, especially based on the pathogenic mechanism.

Reactive arthritis after COVID-19.

A previously healthy 53-year-old man was hospitalised for 12 days due to COVID-19 with shortness of breath. A few days after discharge from hospital, the patient developed fever and severe pain in several joints in the lower extremities. The pain was so severe that the patient was unable to stand on his feet. Synovial fluid from the right-side knee contained a high number of polynuclear cells and a few mononuclear cells. Microscopy, culture and PCR tests for bacterial infection were all negative. Furthermore, the patient tested negative for rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen (HLA)-B27. Thus, the condition was compatible with reactive arthritis. The condition improved markedly after a few days' treatment with non-steroid anti-inflammatory drugs and prednisolone.

Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic Escherichia coli (DEC).

OBJECTIVES: Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Escherichia coli (DEC) and development of reactive arthritis (ReA) and other reactive musculoskeletal (MSK) symptoms among international travellers. METHODS: A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires (pretravel, post-travel and 3-week follow-up). A multiplex quantitative PCR assay was deployed to detect five DEC comprising enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, enterohaemorrhagic E. coli and enteroinvasive E. coli and Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio cholerae. Multivariate analysis was employed to identify factors predisposing to MSK symptoms. New post-travel MSK symptoms reported by participants with DEC were assessed by phone interviews and, if needed, clinically confirmed. RESULTS: From among the total of 224 volunteers who returned all questionnaires and stool specimens, 38 (17.0%) reported MSK symptoms. Multivariate analysis revealed that acquisition of DEC was associated with MSK symptoms (OR 3.9; 95% CI 1.2 to 13.3). Of the 151 with only-DEC, four (2.6%) had ReA, two (1.3%) reactive tendinitis and three (2.0%) reactive arthralgia. ReA was mostly mild, and all patients with ReA were negative for human leucocyte antigen B27. Antibiotic treatment of travellers' diarrhoea did not prevent development of MSK symptoms. CONCLUSION: A total of 17% of volunteers reported post-travel MSK symptoms. DEC acquisition was associated with an increased risk of developing them, yet the ReA incidence remained low and the clinical picture mild. Antibiotic treatment did not protect against development of MSK symptoms.

Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis.

AIMS: Intrathecal injection of morphine presents analgesic and antiedematogenic effects in rats. However, it is unknown whether tramadol, which possess a mixed mechanism of action, can also produce analgesic and antiedematogenic effects similarly. MAIN METHODS: Male Wistar rats received carrageenan and LPS in the right knee joint. Tramadol (10 µg) was injected intrathecally 20 min before articular LPS injection. Incapacitation and articular edema were measured 5 h after LPS stimulation. Synovial fluid was collected for leukocyte counting and western blot analysis. Whole joint and lumbar spinal cord were also collected for histology and immunohistochemistry, respectively. Intrathecal pretreatments groups were with the NKCC1 blocker bumetanide, TRPV1 agonist resiniferatoxin, µ-opioid receptor antagonist CTOP and serotonergic neurotoxin 5,7-DHT, all previously to tramadol. KEY FINDINGS: Tramadol treatment caused the reduction of incapacitation and edema. It also reduced c-Fos protein expression in the spinal cord dorsal horn and slightly reduced TNF-α levels in synovial fluid, but neither reduced cell migration nor tissue damage. Bumetanide and resiniferatoxin prevented the analgesic and antiedematogenic effects of tramadol. CTOP prevented the analgesic and the antiedematogenic effects, but 5,7-DHT prevented only tramadol-induced analgesia. SIGNIFICANCE: Spinal NKCC1 cotransporter and peptidergic peripheral afferents seem to be important for the analgesic and antiedematogenic effects of tramadol, as well as µ-opioid receptor. However, the monoamine uptake inhibition effect of tramadol seems to be important only to the analgesic effect.

An overview of reactive arthritis.

Reactive arthritis, also known as Reiter syndrome, is a spondyloarthropathy that typically follows a urogenital or gastrointestinal infection, and is characterized by conjunctivitis, urethritis, and arthritis. The frequency of reactive arthritis in the United States is estimated at 3.5 to 5 patients per 100,000. Physician assistants (PAs) can manage the condition; therefore, they should be familiar with the disease's signs and symptoms, diagnostic criteria, and treatment regimens. Without proper management, reactive arthritis can progress to a chronic destructive arthritis. Prompt recognition of the condition is key to early intervention and a better patient outcome with fewer complications.

A rare cause of oligoarthritis with septic presentation.

A 33-year-old man presented with new-onset, asymmetric, migratory oligoarthritis in the setting of several weeks of nausea and vomiting, diarrhoea, fevers and dysuria. He was initially treated in the inpatient setting with broad-spectrum antibiotics due to concern for an evolving sepsis presentation. Arthrocentesis of a large right knee effusion revealed inflammatory synovial fluid without findings suggestive of septic arthritis. Human leucocyte antigen B27 was positive and, taken together with the antecedent history of gastroenteritis, dysuria and inflammatory oligoarthritis, the clinical diagnosis was most consistent with reactive arthritis. Antibiotics were discontinued. His treatment course proved refractory to non-steroidal anti-inflammatory drugs and intra-articular and systemic glucocorticoid therapy with concurrent use of sulfasalazine and ultimately necessitated treatment with a tumour necrosis factor alpha inhibitor.

A bicentre retrospective study of features and outcomes of patients with reactive arthritis.

OBJECTIVE: Reactive arthritis (ReA) is a sterile arthritis following an extra-articular infection, usually of the gastrointestinal or genitourinary tract. The aim of this study was to assess the incidence and the clinical and therapeutic characteristics of ReA and to compare them with those of a historical cohort. We hypothesised that improved hygiene together with prevention and treatment of sexually transmitted infections may have decreased the incidence of ReA. METHODS: All patients with ReA diagnosed in the University Hospital Centres of Lyon Sud and Besançon from January 2002 to December 2012 were included in the study retrospectively and were compared with ReA patients diagnosed from January 1986 to December 1996 in the same two hospitals. Medical records were reviewed, clinical features, treatments and outcomes were analysed and diagnoses were compared with international diagnostic criteria. RESULTS: Twenty-seven patients were included between 2002 and 2012 compared with 31 between 1986 and 1996. The overall incidence of ReA in patients hospitalised in the rheumatology department did not change, although the current evolution is more severe with development of chronic disease in the form of more frequent spondyloarthritis. While the incidence of Chlamydiae trachomatis has decreased, new microbes are now found to be involved. CONCLUSIONS: ReA still exists and its incidence has been stable over the last 30 years. However, ReA currently more often progress to spondyloarthritis. Our study also highlights the need for diagnostic criteria that accurately detect ReA.

Musculoskeletal manifestations of Ebola virus.

The 2014 West African Ebola virus disease outbreak shocked the world as it swept through the region leaving Guinea, Liberia and Sierra Leone struggling to gain control. As the largest Ebola virus disease outbreak to date, there are more survivors in its wake than ever before, with a spectrum of health problems requiring management. Here we review various musculoskeletal manifestations of the virus that can occur both during and after the infection, and consider possible pathogenesis.

Reactive Arthritis.

Reactive arthritis is classified as a spondyloarthropathy. Current concepts of disease suggest an infectious trigger, followed by inflammatory arthritis. Several mechanisms have been proposed to explain the interaction of host susceptibility and microorganism. Diagnosis relies on a compatible clinical syndrome and microbiologic confirmation of the pathogen. Antibiotic therapy seems useful in Chlamydia-triggered arthritis. The role of antibiotics in arthritis triggered by enteric pathogens is less clear. The role of tumor necrosis factor alpha inhibitors in therapy is evolving. Many patients have a course limited to a few months, but others experience extraarticular disease and more prolonged courses.

Reiter's syndrome postintravesical Bacillus Calmette-Guérin instillations.

Intravesical Bacillus Calmette-Guérin (BCG) has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC) of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1), and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.

Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy.

In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+) CD69(+) IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5-6·5) versus 1·5 (1·0-2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5-130·7) versus 19·25 (6-41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39-20·42) versus 0·72 (0·048-9·15) ng/ml, P < 0·05], interleukin (IL)-17 [28·60 (6·15-510·86) versus 11·84 (6·83-252·62) pg/ml, P < 0·05], IL-23 [70·19 (15-1161·16) versus 28·25 (> 15-241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03-273·36) versus 10·17 (0·004-190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA.

Modes of presentation of reactive arthritis based on the affected joints.

INTRODUCTION: Reactive arthritis is an autoimmune condition that occurs as a reaction against an infection site elsewhere in the body. Reactive arthritis affects mostly young ages, mainly group age 20-40 y.o., mostly males with ratio 2:1 against females, sometimes 3:1, and even 14:1. The purpose of the study was to observe the mode of illness presentation based on the number of affected joints. MATERIAL AND METHODS: During the 01.03.2012 - 01.03.2014 in the Clinic for Rheumatology and O.S.I.R. "Vendenisi - AL" in Besiana have been examined, elaborated and hospitalized 100 patients with reactive arthritis, out of them 66 males and 34 females. Patients underwent necessary laboratory, hematological, biochemical, and immunological examinations. Subsequently each affected joint has been examined based on the propedeutics rules (inspection, palpation and assessment of the level of motility), as well as x ray examination. RESULTS: From 100 examined patients 66% were males and 34% females respectively. 11% of them were in the 10-20y.o. group age, 30% belonged to group age 21-30 y.o., 24% of patients to 31-40 y.o. group age, 30% to 41-50 y.o. group age, and 5% of patients to the group age over the 51 year old. Regarding the affected articulations and modes of illness presentation, we've obtained the following results: Knee was affected in 64.7% female and 52,12% male patients respectively, T/C joint in 50% female and 57.57% male patients, MTPH joint in 41.11% female and 48.48% male patients respectively, and R/C joint in 44.11% female and 48.48% male patients respectively. Oligoarticular type is seen in 73% male and 70% female patients. Monoarticular type is seen in 14% male and 13% female patients, and poliarticular type is seen in 10% male and 14% female patients respectively. Results from our study have revealed that: reactive arthritis is more frequent in males than females in ratio 2:1 in the infections of urogenital infection, 3:1 in nasopharyngeal infections, and similar in infections of enteral origin. CONCLUSION: Reactive arthritis mostly attacks young ages 20-40 y.o., while over the age of 50 and below the age of 20 is rarely seen. First reactive arthritis attack in males occurs earlier than in females. Most affected joints are: knee, talocrural joint, metatarsophalangeal (MTPH) joint, radiocarpal (R/C) joint, and proximal interphalanteal (PIPH) joint. Oligoarticular mode of illness presentation is 2.5 more frequent than mono and poliarticular mode of illness presentation.

Poncet's disease with high titers of rheumatoid factor and anti-citrullinated peptide antibodies mimicking rheumatoid arthritis.

Reactive arthritis accompanying tuberculosis (TB), also known as Poncet's disease, is a rare condition. In the present report, we describe the case of a patient with Poncet's disease, who presented with high titers of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), which mimicked rheumatoid arthritis (RA). A 69-year-old man with a childhood history of chronic left gonitis suffered from right knee arthritis for 3 years. Chronic monoarthritis in his right knee and positive results obtained on interferon-gamma release assay were suggestive of tuberculous arthritis. However, there was no evidence of TB infection. Moreover, the high titers of RF and ACPA suggested a diagnosis of RA. Surprisingly, the culture of a small sample from his bony ankylosed left knee that had no focal signs of infection, exhibited a positive result for TB infection. Thus, based on these findings, the patient was diagnosed with Poncet's disease. His symptoms improved after initiation of anti-TB therapy, which supported the accuracy of the diagnosis. In addition, we analyzed the characteristics of Poncet's disease by conducting a literature review, and identified that the presence of extra-articular manifestation and negative results for RF and ACPA tests were the features that facilitated distinguishing between typical Poncet's disease and RA; however, since tuberculous patients occasionally exhibit positive results for ACPA tests, the differential diagnosis is essential in ACPA-positive arthritic patients.

Poncet's disease (tubercular rheumatism) - a case report.

Poncet's disease is a rare condition in childhood. It occurs due to immunological reaction to tubercular protein resulting in reactive arthritis and manifest with polyarthritis associated with features of active tuberculosis. We are reporting a case of Poncet's disease that was initially treated as a case of Juvenile Idiopathic Arthritis (JIA) without any improvement. The diagnosis was made clinically from history and physical findings with supportive radiological findings and confirmed by granulomatous changes on FNAC. Our patient improved dramatically after treatment with anti-tubercular drugs. Though very rare, Poncet's disease should be strongly considered in the differential diagnosis of fever and polyarthritis of obscure cause, especially in tubercular endemic countries like ours.

[Changes of the hemodynamics, heart structure and functional state in patients with reactive arthritis].

Our investigation showed for the patients with reactive arthritis typical is hyperkinetic type of haemodynamic, and also structural changes of the heart which manifestate by interventricular partition's thickness as a result of inflammatory edema and it's valve consolidation frequently whithout expressed blood regurgitation, and diastolic dysfunction's development of the left and right heart ventricles in hypertrophic type with disorders of their active relaxation and growth their chamber's rigidity. These changes, probably, evidence about development of the inflammatory cardiopathy in these patients and can be preconditions of the heart failure.