10.5826/dpc.1302a95
text/xml
2160-9381
2698
en
Carlo Mazzatenta
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
COVID-19
Eosinophilic Annular Erythema Due to Certolizumab Pegol Therapy for Rheumatoid Arthritis Post-COVID-19 Vaccine 
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2023-04-29
2022-07-11
2023-04-29
2023-06-05
e2023095
Dermatol Pract Concept
Carlo Mazzatenta
2023/04/29
10.5826/dpc.1302a95
e2023095
Division of Dermatology, Azienda USL Toscana Nord Ovest, Lucca, Italy
2160-9381
COVID-19
en
e2023095
Bassi A, Scarfi F, Galeone M, et al. Generalized granuloma annulare and non-Hodgkin’s lymphoma. Acta Derm Venereol. 2013;93(4):484-485. DOI: 10.2340/00015555-1510. PMID: 23250047.
Eosinophilic Annular Erythema Due to Certolizumab Pegol Therapy for Rheumatoid Arthritis Post-COVID-19 Vaccine 
https://dpcj.org/index.php/dpc/article/download/2698/2110
Eosinophilic Annular Erythema due to Certolizumab
      Pegol Therapy for Rheumatoid Arthritis
              Post-COVID-19 Vaccine
  Andrea Bassi1, Vincenzo Piccolo2, Alessandro Ginori3, Grazia Galippi3, Carlo Mazzatenta1


1 Division of Dermatology, Azienda USL Toscana Nord Ovest, Lucca, Italy
2 Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
3 Pathology Unit, “Monterosso Polyspecialistic Center”, Azienda USL Toscana Nord Ovest, Lucca, Italy



Key words: Eosinophilic annular erythema, certolizumab pegol, adverse drug reaction, COVID-19
Citation: Bassi A, Piccolo V, Ginori A, Galippi G, Mazzatenta C. Eosinophilic Annular Erythema Due to Certolizumab Pegol Therapy for
Rheumatoid Arthritis Post-COVID-19 Vaccine. Dermatol Pract Concept. 2023;13(2):e2023095. DOI: https://doi.org/10.5826/dpc.1302a95
Accepted: October 7, 2022; Published: April 2023
Copyright: ©2023 Bassi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Andrea Bassi, MD, Division of Dermatology, Azienda Toscana Nord Ovest, Lucca, Italy. Tel: +393389340371
Email: bassiderma@gmail.com




Introduction                                                             developed persistent joint pain on the hands and knees for
                                                                         which she had a diagnosis of vaccine induced reactive ar-
Certolizumab pegol (CP) is a PEGylated, humanized                        thritis and started therapy with courses of NSAIDs. In April,
antibody which binds to and neutralizes TNF-α, a key                     due to worsening of the arthritis, hydroxychloroquine and
pro-inflammatory cytokine that plays a central role in in-               prednisone were added. In July, on the basis of the clinical
flammatory processes in immune-mediated inflammatory                     features and serologic tests, she received a conclusive diag-
diseases. It is usually well-tolerated and rarely reported as a          nosis of rheumatoid arthritis. Hence treatment with CP 200
cause of skin reactions, except for the paradoxical worsening            mg/eow was added to therapy. Three weeks after, ie after the
of psoriasis during treatment [1,2];                                     second dose of CP, the patient noticed the appearance of iso-
    Here we report a unique case of possible drug-induced                lated, mildly itchy annular lesions on the upper arms and on
diffuse eosinophilic annular erythema.                                   the back, which were initially diagnosed as annular granu-
                                                                         loma (Figure 1A) and treated with topical steroids.

Case Presentation                                                             At the end of October, the patient was referred to our
                                                                         department for the rapid worsening of the cutaneous lesions
A 22-year-old girl presented to our dermatologic department              which spread on the trunk, arms and legs in association
with a diffuse itchy dermatitis involving the trunk, arms and            with increasing itch. On clinical examination we observed
legs. Medical history revealed that after the first dose of              diffuse erythematous lesions with annular conformation,
BNT162b2 mRNA Covid-19 vaccine in January 2021 she                       most of them with a polycyclic figurate aspect. The edge of



Research Letter | Dermatol Pract Concept. 2023;13(2):e2023095                                                                       1
    Figure 1. Clinical evolution of the skin lesions from September (A) to the end of October (B).



the lesions appeared slightly infiltrated with sparse vesicles          or mildly pruritic, annular papules and plaques on the trunk
and crusts (Figure 1B). The histologic skin sections showed             and extremities. Annular papules often coalesce into palpable
spongiosis of the epidermis and intraepidermal vesicles. In             erythematous arches or rings. During resolution, transient
the superficial and deep dermis, mostly in perivascular areas,          pigment changes may be observed, but no atrophy or scarring
there was a dense inflammatory infiltrate constituted by lym-           occurs. It has a variable response to systemic steroids, anti-
phocytes and eosinophils, with intraepidermal eosinophilic              malarial agents, or, as recently reported, to dupilumab [4].
exocytosis. There were no mucin deposits in the dermis and              Clinical differential diagnosis is with other figurate ­erythema
the PAS stain to detect fungi was negative. A diagnosis of              such as: Wells syndrome, erythema chronicum migrans,
acute spongiotic dermatitis was made, suggesting a possible             ­erythema annulare centrifugum, erythema gyratum repens,
drugs etiology due to the clinical findings (Figure 2). Direct          annular granuloma, subacute cutaneous lupus erythema-
immunofluorescence was negative. Blood tests including In-              tosus and dermatosis of the pemphigoid group [5,6]. His-
direct Immunofluorescence and antitransglutaminase were                 tologically, EAE is characterized by superficial and deep
negative. Based on clinical pathological correlations, accord-          perivascular lymphocytic infiltrate with a prominent eosino-
ing to Naranjo algorithm [3] we posed a diagnosis of a “pos-            philic component.
sible” drug-induced eosinophilic annular erythema (EAE).
Our diagnosis was supported by the improvement of the
                                                                        Conclusions
cutaneous rash and itchy sensation about three weeks after
the discontinuation of certolizumab pegol while continuing              In our case the strict temporal association between drug ad-
therapy with hydroxychloroquine and prednisone.                         ministration and appearance/disappearance of EAE indicate
    EAE is a chronic, recurrent skin disease of an unknown              that this reaction should be added to the list of rare adverse
etiology. It presents as erythematous, usually asymptomatic             events related to certolizumab pegol.




2                                                                            Research Letter | Dermatol Pract Concept. 2023;13(2):e2023095
  Figure 2. Cutaneous histology showed an inflammatory infiltrate in the superficial and deep dermis, mostly in perivascular areas (A),
  (40x, H&E stain); there was also spongiosis of the epidermis and the infiltrate was constituted by lymphocytes and eosinophils with
  eosinophilic exocytosis (B, 200x, H&E stain; C, 400x, H&E stain).




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Research Letter | Dermatol Pract Concept. 2023;13(2):e2023095                                                                             3
