The database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with serologically confirmed coronavirus infection and subsequent flares of their rheumatic disease. A flare was defined as new signs of arthritis (or uveitis) after a period of inactive disease.
Inclusion criteria were: 1) a diagnosis of juvenile idiopathic arthritis according to ILAR criteria [6], 2) flare of the disease in close temporal correlation to a confirmed infection with SARS-CoV-2, and 3) no change to treatment after the last flare-up of the disease until the current flare. Explicitly excluded were patients who reduced or stopped medication as a consequence of diagnosis of infection with SARS-CoV-2, and subsequently developed a flare of their rheumatic disease. All patients were required to show negative antigen testing (SARS-CoV-2 Rapid Antigen Test, Roche, Grenzach-Wyhlen, Germany) and PCR testing (Vivalytic SARS‑CoV‑2 PCR-Test, Bosch Healthcare, Waiblingen, Germany) prior to admission, and patients in whom a preceding infection was suspected received quantitative determination of SARS-CoV-2-IgG by ELISA.
In 988 cases with JIA admitted from July 2020 until June 2021 to the German Center for Pediatric and Adolescent Rheumatology, serology for COVID-19 was determined in 178 cases. Of these, 13 samples were positive. Five patients had no signs of arthritis flare but a recent history of other symptoms compatible with infection with SARS-CoV-2. Two had signs of arthritis flare after discontinuation of medication following the diagnosis of COVID-19. The remaining five patients with flare after infection with SARS-CoV-2, despite no change in medication, are presented here (Table 1).
Patient cases
Case 1
is a seven-year-old girl diagnosed with extended oligoarthritis at the age of two years and ten months with arthritis in knees, ankles and, in the course of the disease, the left subtalar joint and both temporomandibular joints. She had been treated with methotrexate and later with adalimumab. Medication was stopped approximately 18 months ago and she continued well without clinical signs of arthritis.
She presented with swelling of the right ankle for several weeks. Approximately three weeks prior to admission, several cases of COVID-19 disease were diagnosed in the family but the patient had no clinical signs and repeatedly negative antigen tests. On admission, she tested highly positive for SARS-CoV-2-IgG, but negative for IgM antibodies and PCR and antigen testing.
Case 2
is a 17-year-old adolescent male who had been diagnosed with rheumatoid-factor negative polyarthritis at the age of 11 years and six months. He was treated with intraarticular steroid injections, methotrexate and in the course of his disease, etanercept, adalimumab and tocilizumab. He was switched to baricitinib 6 months prior to admission and experienced a complete response. However, he presented with arthritis in both ankle and subtalar joints three weeks after COVID-19 disease, with inapparent clinical symptoms diagnosed by antigen testing after his brother had developed a symptomatic infection with SARS-CoV-2.
Case 3
is a nine-year-old girl who had been diagnosed with rheumatoid-factor negative arthritis at the age of ten months. She was initially treated with methotrexate, intraarticular steroid injections, and etanercept was added at age three years. She had occasional mild flares, the last one at age seven years where dosage was adjusted.
She presented with arthritis in both knees and the left ankle, both ongoing for three months. This had developed shortly after a COVID-19 disease of the whole family (confirmed by antigen testing at that time) where she had fever and mild diarrhea.
Case 4
is an 18-year-old adolescent male who had been diagnosed with enthesitis associated arthritis at age 11 years. He was treated with methotrexate, hydroxychloroquine and low-dose prednisolone until medication was stopped at the age of 17 years. He continued well without medication until he developed an infection with SARS-CoV-2, with positive antigen test, with signs of infection in the upper respiratory tract, vertigo and loss of taste. He developed increasing joint pains shortly thereafter and presented three months later with confirmed arthritis in the right knee, both wrists, ankles and several finger joints.
Case 5
is a 15-year-old adolescent female who had been diagnosed with extended oligoarthritis starting at age three. She was treated with multiple intraarticular steroid joint injections and methotrexate, but was started on etanercept at age nine due to ongoing arthritis. At age ten she developed uveitis of the left eye, when she was switched first to adalimumab, then infliximab, and then due to antibodies to both, to tocilizumab. Due to ongoing arthritis she was switched to golimumab at age 13 which, together with methotrexate, led to lasting remission. She presented approximately 18 months later, four weeks after COVID-19 disease, confirmed by antigen test, with arthritis in both wrists, hips, knees, ankles and the right temporomandibular joint.