Reactive arthritis after COVID-19: a case-based review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 19 (COVID-19) pandemic, which is deeply affecting the whole world. In this new case for the scientific world, scientists are investigating the etiopathogenesis of viral infection-induced damage and have started to focus on the short and long-term immune system effects and alterations after SARS-CoV-2 infection. The case is here reported of a 53-year-old female patient with acute monoarthritis after SARS-CoV-2 infection, who responded adequately to 150 mg/day diclofenac treatment, and the available case reports are comprehensively reviewed. With the focus on arthritis after SARS-CoV2 infection, which emerges as a new pathological condition associated with COVID-19, it was aimed to examine the possible immunological mechanisms of post-COVID-19 arthritis based on the current data on SARS-CoV-2 and the known pathogenetic background of viral arthritis.

A case report of monoarthritis in a COVID-19 patient and literature review: Simple actions for complex times.

RATIONALE: COVID-19 presentation is multifaceted and up to 44% of patients affected by COVID-19 experience musculoskeletal complaints, mostly in the form of diffuse aspecific arthromyalgias. Nevertheless, only a few cases of arthritis following SARS-CoV2 infection are reported. PATIENT CONCERNS: A 27-year-old man affected by nail psoriasis presented with monoarthritis 2 weeks after being diagnosed with COVID-19. DIAGNOSES: Diagnostic work-up and differential diagnosis were made difficult by patient isolation, absence of lab tests, and his visit via telemedicine, even though signs of first metacarpophalangeal joint involvement were clear. INTERVENTIONS: Due to the inefficacy of acetaminophen and nonsteroidal anti-inflammatory drugs, the patient was prescribed oral steroids with a rapid benefit. OUTCOMES: The patient's response to oral steroid was prompt and maintained even after therapy tapering. Even so, a formal diagnosis was not possible due to a difficult diagnostic work-up and lack of a long-term follow-up. LESSONS: Like many other viral diseases, SARS-CoV2 can play as a causative agent or as a trigger for inflammatory arthritis development in predisposed individuals.

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.

Hand-Foot and Mouth Disease and Reactive Arthritis: An Unusual Paediatric Case.

Reactive arthritis is defined as arthritis that occurs during or after an extraarticular infection. It is mostly difficult to determine the causative agent that causes inflammation in the joints. Initially, salmonella, shigella, chlamydiaand yersinia were considered to be pathogenic agents. But recently, in addition to demonstrated viral and bacterial agents, there are also other cases of reactive arthritis after vaccinations with Rubella and Influenza. Herein a 3-year old boy is reported with reactive arthritis of left knee that developed shortly after hand-foot and mouth disease. This report represents the first detailed description of a paediatric case in literature with reactive arthritis following hand-foot and mouth disease.

Prevalence of Post-Chikungunya Infection Chronic Inflammatory Arthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the percentage of patients who would develop chronic inflammatory rheumatism (CIR) following chikungunya (CHIK) virus disease. METHODS: We conducted a systematic review of the literature in 3 databases (PubMed, Science Citation Index, and Scopus) to identify studies assessing the proportion of patients who progress to CHIK-CIR. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence intervals (95% CIs). A 2-tailed alpha level of 5% was used for hypothesis testing. Measures of heterogeneity, including Cochran's Q statistic, the I2 index, and the tau-squared test, were calculated and reported. Subgroup analyses were conducted by type of study and country, by studies evaluating chronic arthritis, and by studies with ≥200 patients and followup ≥18 months. Publication bias was assessed using a funnel-plot. RESULTS: Up to June 15, 2015, our literature search yielded 578 citations. The pooled prevalence of CHIK-CIR in 18 selected studies among 5,702 patients was 40.22% (95% CI 31.11-49.34; τ2 = 0.0838). From studies derived from India, prevalence was 27.27% (95% CI 15.66-38.88; τ2 = 0.0411), while from France, prevalence was 50.25% (95% CI 25.38-75.12; τ2 = 0.1797). The prevalence of CHIK chronic arthritis was 13.66% (95% CI 9.31-18.00; τ2 = 0.0060). Considering just those studies with ≥200 patients assessed, prevalence was 34.14% (95% CI 23.99-44.29; τ2 = 0.0525). In studies with a followup ≥18 months, prevalence was 32.13% (95% CI 22.21-42.04; τ2 = 0.0453). CONCLUSION: According to our results in the most conservative scenario, approximately 25% of CHIK cases would develop CHIK-CIR (34% if we just consider the most representative studies), and 14% would develop chronic arthritis.

[PCR-based detection of pathogens in clinical rheumatology]. / Polymerasekettenreaktion-gestützte Erregerdiagnostik in der Rheumatologie.

In the differential diagnostics of autoimmune-mediated rheumatic diseases, rheumatologists often have to consider infections (e. g. Lyme arthritis) or reactive diseases (e. g. reactive arthritis after urogenital bacterial infections). Furthermore, infections with an atypical presentation or caused by atypical pathogens (opportunistic infections) can complicate the immunosuppressive therapy of autoimmune diseases. For this purpose not only conventional microbiological culture methods but also PCR-based methods are increasingly being applied for the direct detection of pathogens in clinical specimens. The aim of this overview is to present commonly used PCR methods in the clinical practice of rheumatology and to describe their benefits and limitations compared to culture-based detection methods.

Mercury Exposure in a Riverside Amazon Population, Brazil: A Study of the Ototoxicity of Methylmercury

Introduction Mercury poisoning causes hearing loss in humans and animals. Acute and long-term exposures produce irreversible peripheral and central auditory system damage, and mercury in its various forms of presentation in the environment is ototoxic. Objective We investigated the otoacoustic emissions responses in a riverside population exposed to environmental mercury by analyzing the inhibitory effect of the medial olivocochlear system (MOCS) on transient otoacoustic emissions (TEOAE). Methods The purpose of the research was to evaluate the entire community independently of variables of sex and age. All of the participants were born and lived in a riverside community. After otolaryngologic evaluation, participants were received tympanometry, evaluation of contralateral acoustic reflexes, pure tone audiometry, and recording of TEOAEs with nonlinear click stimulation. Hair samples were collect to measure mercury levels. Results There was no significant correlation between the inhibitory effect of the MOCS, age, and the level of mercury in the hair. Conclusions The pathophysiological effects of chronic exposure may be subtle and nonspecific and can have a long period of latency; therefore, it will be important to monitor the effects of mercury exposure in the central auditory system of the Amazon population over time. Longitudinal studies should be performed to determine whether the inhibitory effect of the MOCS on otoacoustic emissions can be an evaluation method and diagnostic tool in populations exposed to mercury. .

[SPECIES COMPOSITION OF INFECTIOUS FACTORS THAT CAUSE THE REACTIVE ARTHRITIS DEVELOPMENT AND THEIR EFFECT ON ARGINASE-NO-SYNTHASE REGULATORY SYSTEM OF PERIPHERAL BLOOD LYMPHOCYTES].

The own observations results of urogenital, gastrointestinal and nasopharyngeal infectious factors that cause the development of reactive arthritis (PeA) are being presented. The greatest contribution to the development of this disease make Chlamidia trachomatis (36%), Streptococcus haemolyticus (pyogenes) (19%) and hepatitis viruses B and C (10%). As a result of the research a number of kinetic parameters of arginase and NO-synthase reactions in peripheral blood lymphocytes of patients with reactive arthritis was identified. The authentic increase of arginase activity in 3.3 times and eNO-synthase activity decrease by 1,9 times in peripheral blood lymphocytes of patients with PeA, compared to practically healthy donors were determined. Increased activity of arginase and iNO-synthase of lymphocytes indicates changes in immune cells functional activity, which may be due to impaired metabolic and regulatory processes in these cells caused by a bacterial or viral infection.

Spondyloarthritis in sub-Saharan Africa.

Spondyloarthritis (SpA) is generally uncommon in sub-Saharan Africa, in part because of the rarity of HLA-B27 in this region. However, the relationship between HLA-B27 and SpA, particularly ankylosing spondylitis (AS), is complex. Despite the HLA-B 27:05 risk allele occurring in some West African populations, associated AS is not seen. In fact, most patients with AS are HLA-B27-negative, although there is emerging evidence that another class I HLA molecule, HLA-B 14:03, is associated with AS in black Africans. The Assessment of SpondyloArthritis International Society criteria for detecting early axial disease are of limited value in sub-Saharan Africa, because of both the rarity of HLA-B27 and very limited access to magnetic resonance imaging. Reactive arthritis (ReA), psoriatic arthritis, and undifferentiated SpA are seen mainly in the context of HIV infection, although the exact effect of the virus in the pathogenesis of arthritis is unclear. In Zambia, ReA is associated with the HLA-B*57:03 allele, which is paradoxically also associated with slow progression of HIV infection. HIV-associated ReA has a more protracted and aggressive course than standard ReA. Enthesitis-related arthritis is more common in children infected with HIV by vertical mother-to child transmission. Use of TNF inhibitors for axial disease is problematic, mainly because of cost, but also because of potential safety problems, especially reactivation of tuberculosis.

Mannose binding lectin is required for alphavirus-induced arthritis/myositis.

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3(-/-) mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis.

Protracted rheumatic manifestations in travelers.

BACKGROUND: Travel returnees may complain of protracted rheumatic symptoms, but there are sparse data regarding their causes. We aimed to describe travelers returning with new rheumatic symptoms. METHODS: We conducted a retrospective analysis of Israeli travelers who were referred to the Sheba Medical Center from January 2005 to January 2010 with prolonged (>4 weeks) nontraumatic arthralgia or arthritis. RESULTS: During 5 years, 14 patients (7 men and 7 women) with posttravel arthritis/arthralgia were seen. A total of 5 patients were diagnosed with reactive arthritis, and 9 were diagnosed with rheumatic symptoms related to infection with Alphaviruses: Chikungunya virus or Ross River virus. Some disability remained for several months in most cases, but only 1 case of reactive arthritis eventually evolved to a chronic spondyloarthropathy. CONCLUSIONS: Travel-related arthritis may persist even several months after the exposure. Assessing patients' travel history may help in the evaluation of some cases with rheumatic manifestations. Their prognosis may be better than that of autoimmune arthritides.

[Lamivudine treatment of a HBs antigen positive man with reactive arthritis]. / Lamivudinbehandling af en hepatitis Bs- antigen-positiv patient med reaktiv artritis.

A 46-year-old man who was HBs antigen positive since childhood had painful talocrural arthritis that was considered re-active to HBs antigen. Lamivudine treatment was started and HBV-DNA disappeared from the blood, and the joint swellings disappeared. HBe antibody disappeared after eight months. After one year and nine months lamivudine was discontinued, resulting in a flare of the hepatitis after 56 days: HBV-DNA rose to 40 million copies per ml and HBe antigen became positive. Lamivudine was reinstituted, resulting in normalization of ALAT and lowering of HBV-DNA under detection level.

The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease.

OBJECTIVE: The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of >200 mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients suggests that treatment with anti-TNF-alpha therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.

Frequency of recent parvovirus infection in patients examined for acute reactive arthritis. A study with combinatorial parvovirus serodiagnostics.

OBJECTIVE: To determine the causative role of human parvovirus B19 as a preceding infection in patients examined for acute reactive arthritis (ReA). METHODS: Sixty adult patients with acute arthritis were screened for evidence of triggering infections. In all patients, cultures of stool specimens and of Chlamydia trachomatis in urethra/cervix, and/or bacterial serology were studied. The timing of primary infection of human parvovirus B19 was determined by measurement in serum of VP2-IgM, VP2-IgG, epitope-type specifity of VP2-IgG, and avidity of VP1-IgG. RESULTS: Median time from onset of joint symptoms to the rheumatological consultation was five weeks (range 1-62). Of the 60 patients, 35 fulfilled the diagnostic criteria for ReA; in the remaining, the diagnosis was unspecified arthritis (UA). Thirty-six patients had antibodies for the B19 virus. Occurrence of these antibodies did not differ significantly between ReA and UA groups (P = 0.61). Of these 36 patients, 34 had a pre-existing immunity to the B19 virus. Of the two other patients, one had rash and self-limiting polyarthritis with serological evidence of B19 primary infection, and the other had arthritis of the lower extremities with serological evidence of a convalescence period after the B19 primary infection. The latter patient also had antibodies to Yersinia, with a clinical picture typical for ReA. CONCLUSION: In patients examined for acute ReA, the frequency of recent B19 virus infection was 3.3% (2 out of 60). The diagnostic utility of the presented methodology, by using a single serum sample, was evident.

Infection and musculoskeletal conditions: Viral causes of arthritis.

Several viruses cause postinfectious arthritis. The disease is a typical manifestation of arthritogenic alphaviruses, rubella virus and human parvovirus B19. In addition, arthritis is not uncommon after infection by HIV, cytomegalovirus, hepatitis B virus, hepatitis C virus, or Epstein-Barr virus (EBV). Also prolonged arthritis may result from viral infections, particularly with alphaviruses and human parvovirus B19. Viruses such as EBV and B19 may have significant roles in initiating chronic arthropathies, which in some cases may be indistinguishable from rheumatoid arthritis.

Infection and musculoskeletal conditions: Rheumatologic complications of HIV infection.

The pandemic caused by the human immunodeficiency virus (HIV) has entered its second quarter-century, with 40 million people now affected worldwide - particularly in Africa, where the impact has been most devastating. A complex array of rheumatic disease manifestations has been described, including diseases specific to HIV infection such as HIV-associated arthritis and the diffuse infiltrative lymphocytosis syndrome; other conditions which occur prominently in HIV-positive individuals include vasculitis, reactive and psoriatic arthritis and HIV-associated polymyositis, opportunistic musculoskeletal infections, and finally disorders that were originally ameliorated by HIV infection, such as rheumatoid arthritis and lupus. Effective antiretroviral treatment ameliorates many of these disorders; however, the introduction of highly active antiretroviral treatment (HAART) has introduced a new spectrum of disorders and new challenges confronting the clinician, including osteonecrosis, rhabdomyolysis, and, with immune reconstitution, the appearance de novo of a variety of autoimmune disorders and phenomena.

Human immunodeficiency virus related reactive arthritis in Zambia.

OBJECTIVE: To characterize the clinical, radiological, and diagnostic features of reactive arthritis (ReA) in indigenous Black Zambians with human immunodeficiency virus (HIV) infection. METHODS: Consecutive patients attending an arthritis clinic over a 5-year period were studied prospectively. Those who satisfied diagnostic criteria for ReA were analyzed. RESULTS: In total, 170 patients satisfied the ESSG criteria for ReA; 71 (45 men, 26 women) had one or more extraarticular manifestations; 30% had enteroreactive and 14% uroreactive disease. Only 59% of patients had the diagnostic features of ReA at presentation. The initial diagnosis was undifferentiated spondyloarthropathy (uSpa) in 20%, other ReA in 14%, and "arthritis alone" in 7%. Of 65 (42 men, 23 women) patients tested, 94% were HIV-positive (91% men, 100% women). In those with HIV, the arthritis was predominantly polyarticular, lower limb-predominant, and progressive; 58% of 33 with persistent disease had erosions of foot and/or hand joints (average disease duration, 24.4 mo); 6 of 10 showed early radiological spine or sacroiliac joint changes (average duration 47.7 mo). Anterior uveitis occurred in 33% of patients, while keratoderma blenorrhagicum and stomatitis occurred in 14.3% and 9.5%, respectively, of patients with enteroreactive ReA. Uroreactive ReA was more common in women. There were no significant differences in the clinical, diagnostic, or radiographic features between men and women or between those with or without a known preceding trigger. CONCLUSION: HIV associated ReA in Black Zambians frequently follows an accelerated course with a strong tendency to relapse, develop early erosions and joint deformity, and become chronic. The clinical, diagnostic, and radiographic features are indistinguishable from those described in the conventional (HLA-B27 related) disease, although our HIV-positive patients have a high overall frequency of uveitis, keratoderma, and onycholysis.