Dear Editor, ReA, a subtype of SpA, is a sterile inflammatory arthritis, predominantly
involving the lower extremities. It usually occurs 1–3 weeks after a remote mucosal
infection (gastrointestinal or genitourinary). It is also known as Reiter’s syndrome
in the presence of the classical triad: urethritis in men and cervicitis in women,
ocular inflammation (conjunctivitis or uveitis) and arthritis of large joints. Chlamydia
trachomatis, Campylobacter, Salmonella, Shigella and Yersinia are a few of the common
bacterial infections that can cause ReA [1]. A few other bacteria and viruses have
also been associated with the pathogenesis of ReA. The novel coronavirus, severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) as a cause of ReA has been reported
previously in six cases [2–7]. Here, we report a case of ReA after SARS-CoV-2 infection.
Written informed consent was obtained from the patient.
A 27-year-old female was hospitalized after 2 days of fever and body aches. On evaluation,
SARS-CoV-2 RT-PCR from a nasopharyngeal swab was positive, and CT imaging of the chest
showed bilateral peripheral ground glass opacities COVID-19 Reporting and Data System
(CO-RADS-4). Other laboratory parameters during hospitalization showed leucopenia
(3200/mm3), elevated CRP (114 mg/l) and D-dimer (three times upper normal limit),
and normal levels of lactate dehydrogenase, ferritin and IL-6. She was diagnosed with
coronavirus disease 2019 (COVID-19) pneumonia and received 1 mg/kg CS in the form
of oral methylprednisolone and favipiravir. Oxygen saturation was well maintained
on room air throughout the disease course. Fever subsided on day 3 of hospitalization,
and she was discharged on day 8 with tapering doses of CS. Two weeks after testing
positive for SARS-CoV-2 infection, while on 0.25 mg/kg of CS, she developed acute
onset arthritis in both lower extremities and relatively mild arthritis in the small
joints of the right hand. She did not have any history of recent diarrhoea, cervicitis
or uveitis.
On examination, bilateral knee, ankle and midfoot joints were extremely tender and
swollen. Mild tenderness was also noted in the small joints of the right hand (wrist,
MCP and PIP joints). The rest of the physical examination was normal. RT-PCR for SARS-CoV-2
was negative. RF was positive in low titres. ACPA, ANA and HLA-B27 were negative.
A probable diagnosis of ReA secondary to SARS-CoV-2 infection was made. She received
NSAID and additionally required oral opioid analgesic to manage the pain. CS was gradually
tapered and stopped over next 3 weeks. At 4-week follow-up, the arthritis had improved
significantly, allowing withdrawal of opioid analgesic and tapering of NSAID.
Although ReA causes asymmetric oligoarthritis in the lower extremities, a mild form
of upper limb arthritis can also occur, as seen in our patient [6]. In contrast to
this, Danssaert et al. [5] reported arthritis of unilateral hand joints without involvement
of lower extremities. Liew et al. [4] described a patient with acute right knee arthritis
manifesting 3 days after fever and simultaneously being positive for SARS-CoV-2 infection.
Schenker et al. [6] and De Stefano et al. [7] described cases of ReA associated with
cutaneous vasculitis and psoriatic skin lesions, respectively. The patient reported
by Ono et al. [2] had severe respiratory distress requiring mechanical ventilation,
whereas respiratory involvement was milder in the other five patients [3–7], including
our patient. All these cases are summarized in Table 1.
Table 1
Reported cases of possible reactive arthritis after SARS-CoV-2 infection
Parameter
Ono et al. [2]
Saricaoglu et al. [3]
Liew et al. [4]
Danssaert et al. [5]
Schenker et al. [6]
De Stefano et al. [7]
Our case
Age, years
50
73
47
37
65
30
27
Sex
Male
Male
Male
Female
Female
NA
Female
Onset of ReA after SARS-CoV-2 infection, days
22
14
Simultaneous
12
˃10
20
14
Musculoskeletal manifestations
Ankles, right Achillis enthesitis
Hands, feet
Knee
Hand
Knees, ankles, wrists
Right elbow
Knees, ankles, feet, hand
Other manifestations
–
–
Balanitis
–
Cutaneous vasculitis
Psoriatic skin lesions
–
RF
−
−
NA
−
−
−
+
ACPA
−
−
NA
NA
−
−
−
HLA-B27
−
NA
NA
NA
+
−
−
ANA
−
NA
NA
+
−
−
−
Arthrocentesis
No crystals, sterile
NA
No crystals, sterile
NA
NA
No crystals
Not done
Radiograph
Normal
Normal
Normal
NA
NA
NA
Not done
Treatment
NSAID, IA CS
NSAID
NSAID, IA CS
Opioid, gabapentin
CS
NSAID, topical CS for skin
NSAID, opioid
NA: not available.
Other manifestations of ReA include inflammatory back pain, dactylitis, enthesitis,
tendinitis and bursitis. There are no specific laboratory tests for ReA, and diagnosis
relies on the typical clinical presentation with detection of the triggering infection
[8]. Arthritis persists for >6 months in 30–50% of patients [1]. The most effective
treatment for ReA is NSAID. IA glucocorticoid can be used for mono- or oligoarticular
disease. In chronic cases, SSZ can be effective when started within 3 months of disease
onset [8].
Our patient developed lower limb predominant inflammatory arthritis, 2 weeks after
SARS-CoV-2 infection. The presence of RF in low titres was possibly attributable to
an immune response to the recent infection. The classical clinical picture, a preceding
infection, absence of other autoantibodies, absence of autoimmunity in the family
and response to NSAID, supported the diagnosis of ReA.
This case, along with previously reported cases, suggest SARS-CoV-2 infection as an
aetiology in the pathogenesis of ReA. More observations are required to strengthen
this association.
Key message
• ReA should be considered in patients with acute arthritis after SARS-CoV-2 infection.
Funding: No specific funding was received from any funding bodies in the public, commercial
or not for-profit sectors to carry out the work described in this manuscript.
Disclosure statement: The authors have declared no conflicts of interest.
Data availability statement
The authors confirm that the data supporting the findings of this study are available
within the article.