Sex: F
Vaccine: COVID19
Symptoms: Aldolase, Anti-cyclic citrullinated peptide antibody, Antibody test, Antineutrophil cytoplasmic antibody, Antineutrophil cytoplasmic antibody positive
Clinical narrative: Systemic lupus erythematosus; This is a literature report.  A 68-year-old patient without history of autoimmune conditions presented to the emergency department with bilateral proximal upper and lower extremity muscle weakness, stiffness, and pain. She received the first dose of the Pfizer-BioNTech COVID-19 vaccine 2 days prior to symptom onset and 7 days prior to hospital presentation. Initially, she developed a mild headache and experienced soreness at the injection site that resolved the day after vaccination. Two days after receiving the vaccine, she developed acute onset of bilateral shoulder pain, morning stiffness that lasted at least 30 min, and weakness that started in her right shoulder and then progressed to her left shoulder. She also developed bilateral antero-lateral hip pain radiating into her thighs, stiffness and weakness. Over the course of a week, the muscle weakness and pain became so profound, that she was unable to ambulate. During her hospitalization, she did not experience fever, headache, jaw claudication, scalp tenderness, chest pain, rash, other muscle involvement, or respiratory symptoms. Patient reported intentional 47-pound weight loss over the last couple of months. On examination, she had tenderness and 3/5 proximal muscle strength at the hip and shoulder girdles. She had tenderness with active and passive range of motion. She could not get out of bed without assistance. Laboratory studies showed reactive ANA with positive titer 1:640 and presence of cytoplasmic pattern, ESR greater than 130 mm/h, CRP 15.9 mg/dl, and total CPK 23 IU/L. The patient tested negative for Covid-19 but Covid-19 antibodies were positive. Further serological work up was negative for RF, anti-CCP, anti-SSA, and anti-SSB antibodies. Complement levels, vitamin D, TSH, and morning cortisol were normal. She had a positive p-ANCA with anti-MPO specificity; however, CT of the chest/sinuses, and urinalysis were unremarkable. She had no features suggestive of vasculitis. CT of the chest, abdomen and pelvis were performed to rule out malignancy, which were all negative. She underwent MRI of the cervical, thoracic, and lumbar spine that showed disc disease with mild impingement at C3-C4 with moderate central canal stenosis, these findings did not explain patient's symptoms. By the time she was admitted to the hospital, lumbar puncture was performed at outside facility due to concern of possible Guillain-Barre. The neurology team did not consider Guillain-Barre as a possible working diagnosis given her physical examination was not consistent with it. Her lumbar puncture was normal: WBC 1, RBC 4, protein 39, and glucose 58, with negative gram stain. Serum electrophoresis showed no evidence of monoclonal proteins. Initial clinical manifestations pointed towards a possible presentation of polymyalgia rheumatica (PMR). For this reason, she received prednisone 20 mg daily and described a "90% improvement" in her muscle weakness and pain on the following day. Muscle strength and tenderness on range of motion in shoulders and hips girdles almost normalized after 2 days of prednisone. Her repeat inflammatory markers after a short interval of 3 days on prednisone were ESR 112 mm/h and CRP 7.7 mg/dl. She was discharged home on a prednisone taper of 20 mg daily for 2 weeks, with instructions to taper by 5 mg every 2 weeks. Three weeks after discharge, patient's muscle weakness, pain and stiffness had continued to improve. Follow-up blood work was noted for decreased inflammatory markers with ESR 55 mm/h, CRP 52.6 mg/dl. However, 2 months later, she experienced recurrent symptoms, developing significant joint pain in shoulders, wrists, hips, knees, and ankles along with morning stiffness lasting all day. She endorsed swelling in her ankles and metacarpophalangeal joints as well as a rash on her forearm and palm of hands. More extensive work-up showed positive ds-DNA (titer 221) and rising inflammatory markers with ESR 68 mm/h and CRP 149.3 mg/dl. According to the EULAR/ACR-2019 classification criteria, positive ANA with scores more or equal to 10 are indicative of classified SLE. The patient met this criteria with a total score of 12 points, based on positive ANA, plus joint involvement (+ 6 points) for the clinical domains, as well as the presence of positive ds-DNA (+ 6 points) in the immunological domains. The presence of immune mediated rash did not provide any points as it was not clear if it was consistent with acute cutaneous lupus erythematous given rash was reported but not evidenced on physical exam. Further, the patient had active disease given SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score more than 4 points. Her SLEDAI was 10 points. Points were given for: arthritis (+ 4 points), pyuria (+ 4 points), dsDNA (+ 2 points). There were no other organs affected besides the joints and skin, she did not have lupus nephropathy given no evidence of proteinuria, hematuria, and normal creatinine. She was started on a steroid-sparing agent with azathioprine 50 mg daily for 2 weeks with instructions to increase to 100 mg daily thereafter. Unfortunately, she developed generalized hives when increasing the azathioprine dose for which the medication was stopped. Therefore, the patient was started on methotrexate 20 mg weekly and maintained on prednisone 5 mg daily with improvement of symptoms. The patient elected to forgo the second dose of COVID-19 vaccine. Discussion: The elderly patient that debuted with clinical manifestations suggestive of PMR and had initial marked improvement with moderate dose steroids, was later confirmed to have classified SLE according to the EULAR/ACR-2019 classification criteria. Interestingly, she also was found to have positive p-ANCA/MPO without evidence of vasculitis further supporting her unusual presentation and autoantibody profile. Given that the constellation of symptoms presented within days after receiving the Pfizer-BioNTech COVID-19 vaccine, this could suggest but not prove a possible etiologic association between the vaccine administration and the development of SLE. Conclusion: Autoantibody formation and autoimmune disease have been observed following SARS-CoV-2 infection as a result of a robust immune response and molecular mimicry. Likewise, the SARS-CoV-2 spike protein shares a significant portion of peptides with human proteins and could incite autoimmune disease or trigger pre-existing autoimmune conditions. Given the strong temporal association between COVID-19 vaccine administration and the development of SLE in the patient, the authors hypothesize that the mRNA vaccine could have caused hyperstimulation of the patient's immune system. Her aberrant immune response required that she be closely monitored for evolution of her autoimmune disease. The authors reported this case to increase awareness for the possibility of autoimmunity, specifically SLE, following mRNA vaccination against SARS-CoV-2 virus.; Sender's Comments: Based on the current available limited information in the case provided, the causal association between the event Systemic lupus erythematosus and the use of suspect product BNT162B2 cannot be fully excluded.  The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to RAs, Ethics Committees, and Investigators, as appropriate.