EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.

BACKGROUND: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. METHODS: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. RESULTS: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies. CONCLUSION: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

Skin inflammation associated with arthritis, synovitis and enthesitis. Part 2: rheumatoid arthritis, reactive arthritis, Reiter's syndrome, Lyme borreliosis, dermatomyositis and lupus erythematosus.

Syndromes associated with concurrent skin and joint inflammation frequently pose a therapeutic challenge for both dermatologists and rheumatologists. In part 1 of this review, we discussed psoriatic arthritis as well as the autoinflammatory disorders SAPHO syndrome, Still's disease and Behçet's disease. Part 2 will address rheumatoid arthritis, reactive arthritis, Reiter's syndrome and Lyme borreliosis. In addition, we will discuss dermatomyositis and lupus erythematosus, two common autoimmune disorders that frequently present with both cutaneous and joint involvement. For each of the aforementioned disorders, we will highlight aspects of epidemiology, pathogenesis, clinical presentation, diagnosis and treatment.

Hypertrophic osteoarthropathy mimicking a reactive arthritis: a case report and review of the literature.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and periosteal tissues of the extremities. It can be a rare hereditary disease (pachydermoperiostosis) or can be secondary to various diseases, though mostly lung malignancies. Here, we report an unusual clinical presentation of HOA. CASE PRESENTATION: A 77-year-old man presented with fever, diarrhea, and an oligoarthritis involving the left knee and the ankles. Since left knee synovial fluid aspiration revealed an aseptic synovitis and Clostridium Difficile toxin was detectable in stool samples, a reactive arthritis secondary to a Clostridium Difficile induced colitis was initially suspected. However, the presence of a worsened digital clubbing and the lack of a good clinical response to steroid therapy led us to perform a radionuclide bone scanning, which revealed HOA. This turned out to be associated with a lepidic predominant lung adenocarcinoma, which was clinically and radiologically difficult to distinguish from a relapse of pneumonia. CONCLUSION: Consistent with the literature, HOA tends to have a variable clinical presentation, mimicking that of various rheumatic diseases. This clinical case shows that HOA can present as a presumptive acute reactive arthritis, and it highlights the importance of patient's follow-up in the differential diagnosis of inflammatory arthritis, especially when a worsened digital clubbing is present.

[Update on reactive arthritis]. / Update zur reaktiven Arthritis.

The following review summarizes the evidence on reactive arthritis (ReA), focussing on the latest relevant work on epidemiology, diagnosis, pathogenesis, and treatment. ReA is a joint inflammation that develops after a primary, extra-articular infection; the infection often involves the urogenital or gastrointestinal system, and less frequently the respiratory tract. The microbial agent causing the primary infection and triggering the arthritis cannot be cultured from the synovial compartment by standard methods; however, bacterial antigens or nucleic acids originating from Chlamydia trachomatis and other microbes can be detected within joint material. ReA occurs worldwide with a prevalence of 40/100,000 and an incidence of 5/100,000. The arthritis develops within days or weeks after the primary infection and usually affects the lower extremities. A dactylitis of the toes is highly typical, while axial or extra-articular manifestations are less common. The disease subsides in many cases within weeks or months, however relapses can occur and chronic forms are described in 30 % of patients.Antibiotic treatment is recommended for the active primary infection. Treatment of ReA focuses on alleviation of signs and symptoms. Severe and chronic forms require the use of immunomodulatory agents.

Acute arthritis of the hip--case series describing emergency physician performed ultrasound guided hip arthrocentesis.

We report two cases of acute hip arthritis where arthrocentesis was able to be performed rapidly, at the bedside by the emergency physician using ultrasound guidance, expediting diagnosis and patient care. In the first case, the patient, who was 23 weeks pregnant, was diagnosed with septic hip arthritis, taken for operative washout of the joint and did very well postoperatively with no pregnancy or other complications. In the second case, the patient was determined to have a noninfectious etiology and also did well. Skilled ultrasound guidance allows hip arthrocentesis to be performed by the treating clinician, decreasing the time to diagnosis and definitive care.

Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease.

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient's skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

Spondyloarthropathies: new directions in etiopathogenesis, diagnosis and treatment.

The spondyloarthropathies (SpA) are a group of inflammatory rheumatic diseases affecting the spine, peripheral joints and nonarticular structures. Often referred to as "seronegative" due to the absence of rheumatoid factor, SpA include ankylosing spondylitis (AS), reactive arthritis (ReA), enteropathic (IBD) associated arthritis, psoriatic arthritis (PsA), as well as undifferentiated, and juvenile SpA. A broad and overlapping spectrum of disease presentations creates difficulties in determining an initial diagnosis. In the last 10 years treatment options have expanded.

[Outlook of surgical treatment of servicemen with pathology of knee joint in the specialized orthopedo-traumatology department].

Analyzed data from annual reports of major trauma districts, chiefs of departments of hospitals and centers and reviewed the frequency and structure of surgical interventions on the knee, made in the last 5 years (2005-2010) in health care facilities the Defense Ministry. The frequency of the most typical injuries and diseases of the knee joint in different categories of servicemen. An integrated laboratory and endoscopic examination of patients with reactive arthritis, associated with latent urogenital infection and how the underlying disease and disease associated surgical pathology knee. Formulated evidence-based recommendations for improving the organization of surgical treatment of soldiers with the pathology of the knee.

The value of blocking IL-6 outside of rheumatoid arthritis: current perspective.

PURPOSE OF REVIEW: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune response and induces acute phase response. Despite the important physiological activities of IL-6, dysregulated overproduction of IL-6 is pathologically involved in various immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA). A series of clinical studies of tocilizumab, a humanized anti-IL-6 receptor (IL-6R) antibody, for patients with RA refractory to conventional therapy or anti-tumor necrosis factor therapy have demonstrated the clinical benefit of IL-6 blockade in RA. On the other hand, there is now accumulating evidence that tocilizumab is therapeutically effective for patients with a number of IMIDs other than RA. This review focuses on the perspective of IL-6 blockade therapy for such IL-6-related IMIDs outside of RA. RECENT FINDINGS: A considerable number of case reports and preclinical studies have shown the benefit of IL-6 blockade therapy in various IMIDs such as systemic lupus erythematosus, adult-onset Still disease, Takayasu arthritis, polyarteritis nodosa, systemic sclerosis, reactive arthritis, dermatomyositis, and polymyositis. SUMMARY: Blocking IL-6 with tocilizumab can be a therapeutic option for patients with various IMIDs in which overproduction of IL-6 plays a pathological role. Future clinical studies investigating the safety and efficacy will elucidate the clinical benefits of IL-6 blockade therapy for such diseases.

[Spondyloarthritides]. / Spondyloarthritiden.

The spondyloarthritides (SpA) are an interrelated group of rheumatic diseases that are characterized by common clinical symptoms and genetic similarities. The most important subtype is ankylosing spondylitis (AS), which is now considered part of axial spondyloarthritis. Important clinical features of the SpA are inflammatory back pain (IBP), asymmetric peripheral oligoarthritis, predominantly of the lower limbs, enthesitis, and specific organ involvement such as anterior uveitis, psoriasis and chronic inflammatory bowel disease. For clinical purposes, five subgroups are differentiated: AS, psoriatic SpA (PsSpA), reactive SpA (ReSpA), SpA associated with inflammatory bowel disease (SpAIBD) and undifferentiated SpA (uSpA). AS usually starts in the sacroiliac joints at a mean age of 26 years, affecting men slightly more frequently than women. SpA are genetically linked (90% of cases), the strongest contributing factor being HLA B27.Conventional radiography remains the gold standard for diagnosis in the axial skeleton. The new ASAS classification criteria have helped to improve the early diagnosis of SpA, with MRI and early HLA B27 determination playing an important role.

Reactive Arthritis Provoked by Campylobacter jejuni Enterocolitis Mimicking Prosthetic Joint Infection: A Case Report.

CASE: A 59-year-old man with previously well-functioning partial knee replacement was admitted with a warm, swollen, and painful knee. The clinical presentation was consistent with prosthetic joint infection (PJI), but the synovial fluid analysis was negative for microbial growth. Further discussion revealed earlier Campylobacter jejuni enterocolitis that subsequently provoked reactive arthritis (ReA) mimicking PJI. The patient was treated with oral naproxen and intra-articular injection of triamcinolone and recovered completely without antibiotics or surgery. After 29 months, the knee is functioning normally. CONCLUSION: ReA is rare but should be included in the differential diagnosis of PJI.

Invasive Group A streptococcal postpartum endometritis associated with multi-organ infarctions: an uncommon case presentation and literature review.

Background: Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective: To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation: This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A ß-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion: STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.

Health care utilization in patients with spondyloarthropathies.

OBJECTIVE: To study health care utilization in veterans with SpAs. METHODS: In a postal survey of 70,508 veterans in Veterans Integrated Service Network (VISN)-13 from 1 October 1996 to 31 March 1998, demographics, smoking status and performance of activities of daily living (ADLs) were queried. Databases provided ICD-9 codes for AS, PsA and ReA; comorbidities; demographics; and health care utilization post-survey in respondents. Multivariable linear/logistic regression compared out- and inpatient health care utilization in SpA vs non-SpA, and its predictors in SpA. RESULTS: A total of 1001 veteran respondents had diagnoses of SpA: AS, n = 154; PsA, n = 814; ReA, n = 33. Veterans with AS, PsA and ReA, respectively, had significantly higher adjusted annual medical specialty (2.8, 3.6 and 3 vs 1.5; P < 0.0001), surgical care (3.3, 2.7 and 3.2 vs 1.9; P < 0.0001) and primary care visits (3.4, 3.0 and 2.3 vs 2.7, P = 0.024). Multivariable-adjusted analyses showed that more ADL limitations and higher comorbidity were associated with higher in- and outpatient health care utilization in PsA and none of the predictors were significantly associated with utilization in AS. CONCLUSIONS: After adjustment for differences in demographics and comorbidities, more outpatient health resource utilization was observed in SpA patients. Further studies should focus on what leads to this increase in utilization, and whether any modifiable factors can be introduced to reduce health care utilization in PsA patients.

Evolving patterns of reactive arthritis.

OBJECTIVE: To characterize rheumatologists' perspectives on evolving trends of reactive arthritis (ReA). METHODS: After ethics approval, 548 members of the Canadian Rheumatology Association were surveyed with 37 questions covering their demographic information, subspecialty, level of experience, practice setting and opinions on prevalence, treatment, and causes of ReA. Results were analyzed with descriptive statistics. RESULTS: Ninety-seven responded to the survey (18% response rate); 66 fully completed it. Nearly half of respondents believed that the incidence of ReA is declining and causes of ReA may be changing. Physicians reported that most of the ReA cases in their practices were caused by an unknown organism, sexually transmitted, or gastrointestinal infection. Full triad ReA increased the chance of recurrence according to their impressions. Common investigations in ReA included inflammatory markers, HLA-B27, chlamydia and gonorrhea testing, stool cultures, synovial fluid analyses, SI joint imaging. ReA treatment included NSAIDs, intra-articular corticosteroid injections, and DMARDs. Two-thirds said they used TNF alpha inhibitors in chronic ReA occasionally or more frequently. CONCLUSION: ReA may be decreasing in frequency and severity in Canada. Changes could be due to less food borne illness, cleaner water, or more rapid treatment of sexually transmitted infections. The cause is often unknown in clinical practice.Key Points• Reactive arthritis (ReA) is likely decreasing in prevalence and severity.• Patients with classic trial of arthritis, urethritis, and conjunctivitis are more likely to have recurrent and/or chronic ReA.• The causal organisms are often not detected and seem to be changing over time.

Ankylosing spondylitis and reactive arthritis in the developing world.

Spondylarthropathies revolve around the strongest known contributing factor, HLA-B27. However, the role of HLA-B27 remains unclear. Its subtypes are reported here in the particular context of developing countries. Non-MHC factors are also being described. The role of immunity is being elucidated. Cytokine expression has been proved to play a major role in ankylosing spondylitis (AS). Recently shown are IL23R, which encodes a critical cytokine receptor in the TH17 subset of T cells, and ARTS1, loss of function of which could have pro-inflammatory effects. This constitutes a major breakthrough in the understanding of AS which could potentially lead to a therapy. New imaging techniques and therapies have substantially improved the earlier diagnosis and management of the disease. However, criteria for an early diagnosis remain to be settled. Such criteria are particularly important for developing countries where they could help in decreasing the socioeconomic burden of the disease.

[Radon therapy in medical rehabilitation of patients with seronegative spondyloarthritis. An open controlled study].

Radon therapy of seronegative spondylitis in 213 patients proved much more efficient than symptomatic drug therapy due to its beneficial effect on peripheral arthritis and enthesitis. It stimulated cellular immunity and improved the quality of life in patients with seronegative spondyloarthritis to a higher degree compared with medicamentous treatment.

Evolution over thirty years of the profile of inpatients with reactive arthritis in a tertiary rheumatology unit.

Reactive arthritis (ReA) is sterile arthritis occurring after extra articular bacterial infection. The aim of this study was to analyze, over 30 years, clinical, biological and imaging characteristics as well as therapeutic management of new cases of ReA, comparing two periods. METHODS: retrospective monocentric study, data of all the patients followed in our unit between January 1st 1984 and April 2014 with the diagnosis or ReA were analyzed (clinical and biological features, management and outcome), and compared between two periods: from January 1984 to December 1993, and from January 2004 to December 2013. RESULTS: Sixty two patients fulfilling international diagnosis criteria were analyzed. There was no significant difference between the two periods in number of new cases, clinical presentation, biological data or outcome. Changes in therapeutic management were obvious with occurrence of anti TNF in the recent period. CONCLUSION: Reactive arthritis is still a current rheumatologic problem in a developed country, with a need of early and tailored rheumatologic management.

Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis.