Management of postinfectious inflammatory arthritis.

PURPOSE OF REVIEW: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management. RECENT FINDINGS: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded. SUMMARY: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.

Extra-articular Manifestations of Chikungunya.

Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Pathogenesis of chronic chikungunya arthritis: Resemblances and links with rheumatoid arthritis.

Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.

Extra-articular Manifestations of Chikungunya

ABSTRACT Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.

Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the family Togaviridae and genus Alphavirus that causes an acute febrile illness, chikungunya fever, which is transmitted to humans by Aedes species mosquitoes. During acute illness, patients have high fever, polyarthralgias or polyarthritis, maculopapular rash, headache, and myalgia that lasts for days to weeks. Following resolution of acute infection, a significant proportion of patients develop chronic chikungunya arthritis that can resemble rheumatoid arthritis. In this review, we first consider the historical background of infectious causes of inflammatory arthritis, and then the pathogenic and clinical manifestations of chronic chikungunya arthritis as a rheumatoid arthritis mimic. We believe that chronic chikungunya arthritis may be a postinfectious inflammatory process, and that an understanding of the parallels and differences between chronic chikungunya arthritis and rheumatoid arthritis may offer insights into better diagnosis and treatment of both diseases.

Brief report: the disability of chronic chikungunya arthritis.

In 50% of patients, chikungunya fever (CHIKF) is followed by arthritic pain that is often chronic, painful, and disabling. To better define the spectrum of pain and disability in chronic CHIK arthritis (CCA), we evaluated 35 consecutive CCA patients seen in a Brazilian rheumatology clinic, using a pain Visual Analog Scale and the Health Assessment Questionnaire Disability Index. In our patients, pain and disability levels were of the same magnitude as are seen in other serious rheumatic diseases. The mean score for 19 patients with moderate disability was 1.42± 0.20 (median 1.37). The median HAQ-DI score for the entire group was 1.25. These findings underscore the morbidity imposed by CCA and the urgent need for improvements in management.

The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis.

Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, polyarthritis, morning stiffness, joint edema, and erythema. Chronic CHIK arthritis (CCA) often causes severe pain and associated disability. The pathogenesis of CCA is not well understood. Proposed hypotheses include the persistence of a low level of replicating virus in the joints, the persistence of viral RNA in the synovium, and the induction of autoimmunity. In this review, we describe the main hypotheses of CCA pathogenesis, some of which support methotrexate (MTX) treatment which has been shown to be effective in preliminary studies in CCA.

Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review.

OBJECTIVE: Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis. METHODS: A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov. RESULTS: Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non-controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001). CONCLUSION: The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo-controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.