key: cord-0795349-266eluef
authors: Slouma, Maroua; Mhemli, Takoua; Abbes, Maissa; Triki, Wafa; Dhahri, Rim; Metoui, Leila; Gharsallah, Imen; Louzir, Bassem
title: Rheumatoid arthritis occurring after coronavirus disease 2019 (COVID-19) infection: Case based review
date: 2022-03-04
journal: Egyptian Rheumatologist
DOI: 10.1016/j.ejr.2022.03.001
sha: 0cb26a94840b2149cbe164b0dfd598ca7187954e
doc_id: 795349
cord_uid: 266eluef

Introduction Rheumatoid arthritis (RA) is a multifactorial disease. Genetic predisposition and environmental triggers including infections are the major players of autoimmunity. We present a case of rheumatoid arthritis occurring after the coronavirus disease 2019(COVID-19) infection.Case presentation: A 72-year-old woman with a medical history of hypertension and atrial fibrillation presented for a 2-month history of bilateral symmetric polyarthritis starting 2 weeks after asymptomatic COVID-19 infection. Physical examination showed swelling and tenderness of the metacarpophalangeal and proximal interphalangeal joints, wrists, and knees. She had increased inflammatory biomarkers (C-reactive protein:108 mg/L, erythrocyte sedimentation rate: 95mm, alpha-2 and gamma-globulins, interleukin 6: 16.5 pg/mL). Immunological tests revealed positive rheumatoid factor (128 UI/mL), anti-cyclic citrullinated peptide antibodies (200UI/mL), anti-nuclear antibodies (1:320), and anti-SARS-CoV-2 IgG (12.24U/mL). She had the genotype: HLA-DRB1*04:11, HLA-DQB1*03:01, and HLA-DQB1* 03:02. Hands and feet radiographs did not show any erosion. Ultrasonography showed active synovitis and erosion of the 5th right metatarsal head. The diagnosis of RA was made. The patient received intravenous pulses of methylprednisolone (250 mg/day for 3 consecutive days) then oral corticosteroids (15mg daily) and methotrexate (10 mg/week) were associated, leading to clinical and biological improvement.Conclusion: Despite its rarity, physicians should be aware of the possibility of the occurrence of RA after COVID-19 infection. This finding highlights the autoimmune property of this emerging virus and raises further questions about the pathogenesis of immunological alterations.

Clinical manifestations of coronavirus disease 2019 (COVID-19) may include fever, arthralgia, myalgia, respiratory and digestive symptoms, with varying degrees of severity [1] .A syndrome of dysregulated immune overactivation may be associated,leading to several complications [2] .Since its outbreak, many reports have been published suggesting the occurrence of immunological changes and autoimmunity [3] .If musculoskeletal symptoms, such as non-specific arthralgia and myalgia,are frequent during COVID-19 infection, the risk of rheumatic diseases seems to be also increased after this infection [4] .Rheumatologists stated that the low rate of acceptability of COVID-19 vaccine is alarming and should stir further interventions to reduce the levels of vaccine hesitancy [5] . Furthermore, rheumatoid arthritis (RA) patients faced remarkable difficulty to obtain their medications with subsequent change in their disease status. The challenges of the pandemic have hastened changes in the way health care is delivered [6] . We report the case of seropositive rheumatoid arthritis (RA) occurring after COVID-19 infection.

A 72-year-old woman with a body-massindex of 26 kg/m 2 and a medical history of hypertension and atrial fibrillation, was diagnosed with asymptomatic COVID-19 infection.

The diagnosis was confirmed by a positive nasopharyngeal swab by RT-PCR for SARS-CoV-2 that was performed as she had exposure to a confirmed case of COVID-19 (her husband).

She received Azithromycin(500 mg orally daily the first day, followed by 250 mg daily for 4 days), paracetamol, vitamin D, C, and zinc supplementation.An informed consentwas obtained from the patient for the publication of this case report.

Three months later, she presented to our departmentwith a 2-month history of inflammatory The diagnosis of seropositive rheumatoid arthritis (RA) was made according to the 2010 American Congress of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria [7] .The patient received intravenous pulses of methylprednisolone (250 mg/day for 3 consecutive days). Then, methotrexate was initiated with a weekly dose of 10 mg associated with oral corticosteroids (prednisone 15 mg/day for 7 days then 10 mg daily).

During the follow-up, the IL-6 level has become within the normal range (4pg/mL). The CRP level decreased at 16 mg/L and the ESR at 40 mm. The Disease activity score using ESR fell from 6.08 (high disease activity) to 4.2 (moderate disease activity) after a follow-up of 15 days.

The pathogenesis of RA is multifactorial, including genetic, environmental, hormonal, and immunological factors. The HLA has been recognized as the strongest genetic risk factor for RA development accounting for 60% of genetic susceptibility. Indeed, HLA-DRB1 alleles (DRB1*0101, DRB1*0401, DRB1*0404,and DRB1*0405) are encountered in >80% of patients with RAand code for a sequence of amino-acids called the "shared epitope". External factors such as smoking and infectionsinteract with this genetic background and contribute to an uncontrolled immune response and the production of ACPA [8] .

It has been suggested that transient infection-dependent pathways contribute to the onset and perpetuation of this autoimmunity. It has been demonstrated that respiratory viral infections were associated with a higher number of incident RA.The parainfluenza, coronavirus, and metapneumovirus were the most implicated viruses in the occurrence of RA [9] .We herein report a case of a 72-year-old womanwho presented withRA following a COVID-19 infection.

Emerging data showed that COVID-19 infection may induce autoimmunity. It has been reported to trigger numerous autoimmune diseases such as Guillain-Barré syndrome, systemic lupus erythematosus, dermatomyositis, myelitis, autoimmune hemolytic anemia and vasculitis [4, 10] .

In fact, SARS-CoV-2 infection can lead to dysregulation of the immune system via three mechanisms : (i)molecular mimicry as a result of immunological similarities shared between the virus and self-antigens with cross-reactive immune response, (ii) activation of autoreactive immune T cells due to bystander activation, and (iii) persistent immune activation [11] .Moreover, COVID-19 infection induces the recruitment of inflammatory cells and the secretion of pro-inflammatory cytokine levels (IL-1, IL-6, IL-10, and TNF-α) [2] , particularly in severe cases. Besides, hyperinflammatory syndrome with immune overreaction has been reported in patients with COVID-19 and was described as a cytokine storm [2] .Furthermore, post-COVID-19 autoimmunity can also be explained by lymphopenia causing transient immunosuppression and loss of self-tolerance [12] . Table 1 

Clinical Characteristics of Coronavirus Disease 2019 in China

Immune responses during COVID-19 infection

Immunomodulation in COVID-19

Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: Case-based review

Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt

Impact of COVID-19 pandemic on rheumatoid arthritis from a Multi-Centre patient-reported questionnaire survey: influence of gender, rural-urban gap and north-south gradient

Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Respiratory viral infections and the risk of rheumatoid arthritis

Microscopic polyangiitis associated with coronavirus disease-2019 (COVID-19) infection in an elderly male

Autoimmune and rheumatic musculoskeletal diseases as a consequence of SARS-CoV-2 infection and its treatment

The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals

Onset of rheumatoid arthritis after COVID-19: coincidence or connected?

First flare of ACPA-positive rheumatoid arthritis after SARS-CoV-2 infection