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LETTER TO EDITOR
Ahead of print publication  

Successful use of tofacitinib in reactive arthritis following COVID-19 infection


 Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, Odisha, India

Date of Submission08-Oct-2021
Date of Acceptance28-Nov-2021
Date of Web Publication01-Jul-2022

Correspondence Address:
Debashis Maikap,
Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar - 751 024, Odisha
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_231_21



How to cite this URL:
Padhan P, Maikap D. Successful use of tofacitinib in reactive arthritis following COVID-19 infection. Indian J Rheumatol [Epub ahead of print] [cited 2022 Aug 20]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=349454



Dear Editor,

A 55-year-old male presented with complaints of low-grade fever, sore throat, dry cough, severe tiredness, myalgia, anorexia, and loss of taste sensation for last 5 days. There was no history of diarrhea and vomiting. He had no prior known past medical history or recent vaccination. At presentation, his pulse rate was 84 beats/min, blood pressure was 110/70 mmHg, and temperature was 101°F with a respiratory rate of 18 beat/min. His oxygen saturation at room air was 97%. Physical examination, including chest examination, was unremarkable. His laboratory investigation revealed hemoglobin 12 g/dL, TLC count of 5200/mm3, and platelet count of 2 lakh/mm3. His C-reactive protein (CRP), D-dimer, and serum ferritin levels were 15 mg/L, 0.66 mcg/mL, and 450 ng/mL, respectively. His chest radiograph was normal. Nasopharyngeal swab for COVID-19 by reverse transcription–polymerase chain reaction (RT-PCR) was positive. He was treated symptomatically with paracetamol and antihistamines. He was advised for self-quarantine for 14 days. He was monitored telephonically and remained clinically stable with no episode of hypoxia.

One month later, he presented to us with complaints of fever, fatigability, and pain and swelling of right knee followed by left knee of duration 1 week. He had no history of low back pain, skin lesions, or recent diarrhea. He had no family history of psoriasis, inflammatory bowel disease (IBD), or spondyloarthritis. On physical examination, he was febrile (100°F). His vital signs were normal. Joint examination revealed warmth, swelling, and tenderness over his both knees. He had enthesitis in his left achilles tendon. The spine examination was normal. Other system examination was normal. His repeat quantitative RT-PCR for nasal and throat swabs was tested negative for COVID-19. Laboratory investigation revealed leukocytosis (Total leukocyte count (TLC) 12,500/mm3) and thrombocytosis (5.2 lakh/mm3). Liver and renal function test results were normal. Hepatitis B and C human immunodeficiency virus (HIV) screenings were negative. His rheumatoid factor, anti-CCP(cyclic citrullinated peptide) (anti-CCP), antinuclear antibodies, antimyeloperoxidase antibodies, antiproteinase 3 antibodies, and HLA-B27 were negative. His acute-phase reactants CRP and erythrocyte sedimentation rate (ESR) were elevated (CRP 200 mg/L [normal <6 mg/L] and ESR 125 mm [normal: 0–20 mm] in 1st h). Urine PCR for gonococcus and Chlamydia trachomatis were negative. Synovial fluid aspirate from the right knee was turbid with 23,778/mm3 white blood cell count with 90% neutrophils and no crystals. Synovial fluid gram stain and culture were negative. COVID-19 could not be detected by RT-PCR in synovial fluid. His serum immunoglobulin G antibody against spike protein for COVID-19 was positive.

A diagnosis of post-COVID reactive arthritis (ReA) was made. He was started on naproxen 500 mg bid for 15 days along with intra-articular triamcinolone with partial relief. His knee arthritis and fever along with raised inflammatory markers persisted (CRP: 66 mg/L, ESR: 88 mm/h). He also received diclofenac 50 mg twice a day for 2 weeks. He had history of sulfa allergy; hence, oral methotrexate (15 mg/week) was added as a disease-modifying drug instead of sulfasalazine along with prednisolone 10 mg/day. There was a minimal clinical improvement with persistently raised CRP and ESR even after 2 months. In view of persistent arthritis, tofacitinib, a JAK1/JAK3 inhibitor, was given at a dose of 5 mg twice daily which was started after ruling out latent TB infection. One week later, he became afebrile with a rapid reduction in joint pain and swelling. On follow-up after 1 month, his arthritis resolved completely with a normalization of acute-phase reactants [Table 1].
Table 1: Disease activity score and treatment response

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Postviral ReA following COVID-19 is rare with few reported cases in the literature.[1],[2],[3] Most common viruses responsible for arthritis are chikungunya, parvovirus B19, hepatitis B and C, and HIV. Mechanisms for viral-induced arthritis are hypothesized into three categories: direct virus mediated pathology (rubella, parvovirus, enteroviruses, HIV, and chikungunya virus); immune complex mediated (chronic hepatitis B); and immune activation due to persistent viral infection (HIV). Our case is the index case of the use of tofacitinib in a case of post-COVID-19 ReA. The underlying mechanism for COVID-19-related arthritis is yet to be understood.[4]

In our case, a direct viral infection of joints is highly unlikely in view of negative synovial fluid test for COVID-19, but ReA is a possibility due to a gap of 4 weeks between COVID-19 and onset of arthritis. This hypothesis of ReA is based on the involvement of pro-inflammatory markers (interleukin-6 [IL-6], IL-17, and tumor necrosis factor-α) which play a role in cytokine storm in COVID-19.[3],[5]

Since the emergence of COVID-19, only nine cases of acute arthritis without any background history of inflammatory arthritis have been reported in the literature.[6]  Achilles tendinitis More Details or enthesitis was present in two patients similar to our case. HLA-B27 genetic testing was performed and negative (or not reported to be positive) in two cases like our case. Most reported cases of COVID-19-associated ReA are males with mono- or oligoarthritis of lower limbs 1–4 weeks following viral infection. Joint fluid is sterile as in our case.[1],[7] Most of the cases showed a favorable outcome with nonsteroidal anti-inflammatory drugs treatment and intra-articular corticosteroid injections.[3] Our case did not respond to conventional therapies and treatment with tofacitinib resulted in prompt recovery within 1 month, and he is doing well at 6-month follow-up [Figure 1].
Figure 1: Clinical course of the patient

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As post-COVID ReA is rare, it is important to distinguish acute-onset inflammatory arthritis related to COVID-19 infection from preexisting autoimmune disease flare triggered by COVID-19.

Informed consent

Written informed consent for publication was obtained from the patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ono K, Kishimoto M, Shimasaki T, Uchida H, Kurai D, Deshpande GA, et al. Reactive arthritis after COVID-19 infection. RMD Open 2020;6:e001350.  Back to cited text no. 1
    
2.
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-32.  Back to cited text no. 2
    
3.
Wendling D, Verhoeven F, Chouk M, Prati C. Can SARS-CoV-2 trigger reactive arthritis? Joint Bone Spine 2021;88:105086.  Back to cited text no. 3
    
4.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 4
    
5.
Schett G, Manger B, Simon D, Caporali R. COVID-19 revisiting inflammatory pathways of arthritis. Nat Rev Rheumatol 2020;16:465-70.  Back to cited text no. 5
    
6.
Conway R, Konig MF, Graef ER, Webb K, Yazdany J, Kim AH. Inflammatory arthritis in patients with COVID-19. Transl Res 2021;232:49-59.  Back to cited text no. 6
    
7.
Yokogawa N, Minematsu N, Katano H, Suzuki T. Case of acute arthritis following SARS-CoV-2 infection. Ann Rheum Dis 2021;80:e1017.  Back to cited text no. 7
    


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