Polymyalgia rheumatica and giant cell arteritis with intracranial involvement postvaccination anti-COVID-19

Dear Editor:

Giant cell arteritis (GCA), the most common type of systemic vasculitis in patients over the age of 50, affects medium- and large-caliber arteries, in which it causes parietal infiltration by multinucleated cells, disruption of the internal elastic membrane, thickening of the tunica intima, and partial or total luminal obstruction. Polymyalgia rheumatica (PMR) causes articular and periarticular inflammation that manifests with rigidity and pain in the neck, shoulders, pelvic girdle, and hips. Approximately 40%–50% of patients manifest almost simultaneous symptoms of both entities, and in 10% of cases PMR progresses to CGA.¹ In this paper we describe a case of concomitant PMR and GCA, developed after the patient received a vaccine against the 2019 coronavirus disease (COVID-19), which presented with epileptic seizures and focal neurologic signs secondary to cerebrovascular disease.

The patient was a 71-year-old woman who received a first dose of the anti-COVID-19 (Ad26.COV2-Janssen) vaccine in mid-May 2021. She reported a history of Graves' disease and endometrial carcinoma. Four days after receiving the vaccine, she began experiencing head, neck, shoulder, and hip pain, and, both eight and ten days later, she experienced episodes of dysarthria, numbness and weakness in her right arm, and a generalized tonic-clonic seizure. The most remarkable findings of the ancillary studies performed were an erythrocyte sedimentation rate (ESR) of 95 mm/1st hour (normal range [N] < 30); d-dimer levels of 1496 ng/mL (N < 500); C-reactive protein levels of 5.89 mg/dl (N < 0.5); negative serological and protein chain reaction (PCR) tests for several bacteria and viruses (including the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); mirrored oligoclonal bands in a cerebrospinal fluid (CSF) analysis; a negative immunological panel (including anti-rheumatoid factor antibodies, anti-nuclear antibodies, and anti-neutrophil cytoplasmic antibodies); a normal thrombophilia study (negativity for anti-phospholipid antibodies and lupus anticoagulant, absence of mutations in factor V Leiden and the prothrombin gene, and normal C and S proteins); a brain magnetic resonance imaging (MRI) scan revealing multiple, small cortical-subcortical lesions with evident restriction in the diffusion-weighted sequences (Figs. 1A–1D); an 18F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸FDG-PET/CT) scan showing uptake foci in the aorta, supraaortic trunks, shoulders, and hips (Figs. 1E and 1F), as well as an absence of a neoplastic disease; and a histopathology study of a temporal artery biopsy sample describing characteristic findings of GCA. Five weeks later, coinciding with the implementation of a reduction in her dose of glucocorticosteroids, she experienced a new episode of dysarthria and weakness in her right hemibody, owing two which she was treated with methylprednisolone (1 g/day intravenously [i.v.] for 3 days) and subsequent prednisone (60 mg/day orally). She is currently taking 30 mg/day of prednisone and remains asymptomatic, with all altered laboratory parameters having returned to normal ranges.

Fig. 1.

A and B) Diffusion-weighted MRI scan showing numerous dot-like lesions in the cortical and subcortical regions of both cerebral hemispheres. C) Temporal artery biopsy: disruption of the internal elastic membrane (arrow) and multinucleated giant cell to the right (triangle). D and E) PET/CT scan: ¹⁸FDG uptake in the supraaortic trunks and hips (arrows).

The case of concomitant PMR and GCA (confirmed by a biopsy) described in this paper has several peculiarities: onset of symptoms postanti-COVID-19 vaccination, intracranial involvement in the small-caliber vessel territory (detected in an MRI scan), and extracranial great-vessel and articular involvement (detected in a PET/CT scan). The diagnosis is unquestionable¹ and the relationship with the vaccination is deemed probable (score of 6 in Naranjo's causality scale evaluating adverse drug reactions). As for the intracranial lesions, these could have been the result of two mechanisms: arteriole obstruction secondary to endothelial inflammation or microembolisms caused by the inflammation of the large-caliber arteries, as this type of endothelial dysfunction and thrombi generation is also seen in cases of COVID-19.²

The primary acute neurological complications of a SARS-CoV-2 infection are anosmia, dysgeusia, meningitis, acute disseminated encephalitis, acute necrotizing and hemorrhagic encephalopathy, stroke, brainstem encephalitis, Guillain-Barre syndrome, and myositis, most of which are a result of autoimmune mechanisms and some of which, in rare cases, appear after the administration of an anti-SARS-CoV-2 vaccine. A prospective German study carried out on 232,603 vaccinated subjects reported 21 cases of autoimmune neurological complications (17 new events and four flares of previous conditions) detected within six weeks after the vaccination, including the following: cerebral venous thrombosis (three cases, two associated with thrombotic thrombocytopenia mediated by anti-platelet factor 4 antibodies), cerebral demyelinating disease (eight cases), inflammatory neuropathies (four cases), myositis (three cases), myasthenia gravis (one case), limbic encephalitis (one case), and GCA (one case).³ A survey study conducted in New York (United States) analyzed flares in 2000 patients with a previously diagnosed rheumatic disease who were vaccinated against COVID-19, revealing that 14.9% of all patients experienced a flare, with arthralgia, arthritis, myalgia, and fatigue being the most common symptoms.⁴ A multicenter study recorded 27 cases of immune-mediated disease following the administration of an anti-SARS-CoV-2 vaccine, 21 of which corresponded to patients with a prior history of autoimmune disease and one to a flare of PMR after being in a state of remission for the past 15 years.⁵

Both PMR and GCA are considered clinical entities of the same disease that can manifest either separately or concomitantly, with less than a dozen cases having been reported to date in relation to anti-COVID-19 vaccination, this being the first reported case in Spain. Cases of PMR triggered by the administration of the flu and other vaccines are more common. It has been postulated that adjuvants could play a role in the onset of these conditions (autoimmune syndrome induced by adjuvants [ASIA]). The onset of inflammatory-autoimmune conditions following anti-COVID-19 vaccination is very rare; therefore, this small potential risk should be assumed in view of the benefit of the vaccination.

Acknowledgments

We would like to thank Dr. José R. Antúnez of the Pathology Service of the Hospital Clínico de Santiago for providing the histopathology image.