key: cord-0686688-t6on8tib
authors: Sy, Michael Yu; Fromm, Erin; Doan, Linda; Rojek, Nathan; Brandt, Alexander Ulrich
title: Nicolau Syndrome After Glatiramer Acetate Injection in Close Proximity to Administration of SARS-CoV-2 mRNA Vaccine
date: 2021-11-10
journal: Neurol Neuroimmunol Neuroinflamm
DOI: 10.1212/nxi.0000000000001112
sha: 0022048c8496461e1b3cce3ee5e9e0e053731625
doc_id: 686688
cord_uid: t6on8tib

nan

A 62-year-old man with a history of hyperlipidemia, obesity (body mass index of 30.1 kg/m 2 ), and MS received the first dose of the BNT162b2 vaccine in late March 2021. 2 The patient had been stable on GA 40 mg three times a week (Glatopa) for the past 5 years without new MRI lesions or relapses and no serious injection reactions. An injection of GA given in the lateral abdomen 17 days after the first vaccine dose resulted in retiform purpura surrounding the injection site (Figure, A) . The purpura appeared 1 day before the second dose of the BNT162b2 vaccine and subsequently continued to spread (Figure, 

A 59-year-old woman with a history of hypertension and MS received the first dose of the mRNA-1273 vaccine in early March 2021. 3 The patient had been stable on GA 40 mg three times a week (Copaxone) for more than 10 years without new MRI lesions or relapses. One week after the first vaccine dose, a large welt developed at the site of a GA injection near her right hip. Over the next few weeks, retiform purpura developed around the injection site. A central necrotic eschar developed when she received the second dose of the mRNA-1273 vaccine 4 weeks later, which enlarged over the next 7 days (Figure, E and F). She developed severe burning pain at the site of the wound, and the wound was debrided. Her local dermatologist diagnosed her with Nicolau syndrome but did not perform a biopsy. GA injections continued at other sites throughout the development of this purpuric skin lesion without further reactions. Roughly 10 years ago, she had experienced 1 skin reaction after GA injection that did not develop into the large ischemic lesion observed in the current case.

The COVID-19 pandemic has placed enormous health and economic burden on the worldwide community. The mRNA vaccines from Pfizer (BNT162b2) and Moderna (mRNA-1273) are notable achievements, highly effective in preventing severe COVID-19 syndromes. 2,3 Our second patient reported typical side effects including fever, fatigue, headache, chills, and muscle pain, whereas the first patient had no side effects. Complications related to drug interactions in specific populations have not been reported.

Nicolau syndrome is an exceedingly rare, adverse event in GAtreated patients with MS. 1, 4 Occurrence of Nicolau syndrome in 2 patients with MS at our MS center in close proximity to SARS-CoV2 vaccination with mRNA vaccines raises the possibility of an association between the 2. No other reports of similar skin lesions were observed in our vaccine program at UC Irvine. Our MS center currently has 224 patients on GA, with an estimated 70%-80% having received a SARS-CoV2 vaccine. Of interest, the joint targets of both interventions are professional antigen-presenting dendritic cells (DCs): mRNA vaccines work via mRNA delivery to DCs at the injection site, which then produce and present mRNA-encoded viral antigen to initiate an immune response. 5 Although the mechanisms of GA on the immune system are broad, DCs act as the initial target for drug uptake and presentation. 6 Both patients have been stable on GA, and both tested positive for antibodies against SARS-CoV2 4 months after vaccination.

We report these cases to make MS centers aware of this potential complication. Although our 2 observations are by no means a proof of causation, they suggest that providers and patients should carefully monitor GA injections in close proximity to SARS-CoV2 vaccinations with mRNA vaccine. A timely response coordinated with dermatology has been reported to prevent necrosis and scar formation, but it is unclear whether this approach may also be successful under these new circumstances. 7 Of note, our observation may also be of relevance for other injectables, as Nicolau syndrome has also been observed with other substances, and may be attributed to mechanical affection of the tissue rather than to drug-related effects.

No targeted funding reported.

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NN for full disclosures. 

Case report: two cases of Nicolau syndrome associated with glatiramer acetate

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

Necrotising cutaneous lesions as a side effect of glatiramer acetate

mRNA vaccines-a new era in vaccinology

The evolving mechanisms of action of glatiramer acetate

Embolias cutis medicamentosa of the foot after sclerotherapy