key: cord-0706464-tj51q0m9 authors: Aoki, A.; Yamane, M.; Aoyama, Y. title: A rare case of reactive granulomatous dermatitis during COVID‐19: a possible role of cephalosporine and potential mechanisms date: 2022-04-20 journal: J Eur Acad Dermatol Venereol DOI: 10.1111/jdv.18119 sha: 0c5d881aa71e9113c76098944aed335cf84f89e2 doc_id: 706464 cord_uid: tj51q0m9 nan CD163 (Fig. 2c , d and f). The majority of the infiltrates were CD3 + T cells admixed with abundant CD163 + epithelioid histiocytes. Multinucleate giant cells were not present in most specimens. Bone marrow biopsy showed multiple non-necrotizing granulomas composed of CD163 + epithelioid cells (Fig. 2e ). After cessation of ceftriaxone, cefepime, and G-CSF, 4 the skin lesions rapidly and completely resolved over the following 2 weeks. Lymphocyte transformation test showed positive reactions to both ceftriaxone (Stimulation Index, 7.32) and cefepime (2.82). There was no recurrence during the 3-month follow-up period. Our patient's clinical course was noteworthy. First, his granulomatous lesions resolved rapidly over 2 weeks after drug cessation. Second, our patient's history of SARS-CoV-2 infection was likely a predisposing factor for the development of granulomatous lesions. No previous studies have detailed the unique constellation of clinical features observed in our patient. Given the atypical clinical presentations, it is appropriate to use the unifying umbrella term, RGD. 3 An association between RGD and COVID-19 has not been previously reported, but it is not surprising, considering the involvement of CD14 + 16 + proinflammatory monocytes producing IL-6 in COVID-19. The detrimental role of CD14 + 16 + proinflammatory monocytes in the pathogenesis of COVID-19 is only beginning to be understood: the temporal population shift from CD14 + 16classical monocytes to CD14 + 16 + intermediate or proinflammatory monocytes expressing CD163 in COVID-19 patients are associated with progression to severe disease. [5] [6] [7] This shift may share numerous features with monocyte responses in severe drug eruptions characterized by sequential reactivations of herpesviruses, that is drug-induced hypersensitivity syndrome (DiHS) 8 /drug reactions with eosinophilia and systemic symptoms (DRESS). Granulomatous inflammation has also been reported to occur as a manifestation of DiHS. 9 However, some distinction between RGD and DiHS could be made: RGD differs from DiHS due to its rare association of viral reactivation and its complete resolution after cessation of offending drugs, which support our diagnosis of RGD and elevated transamidase levels and multiple drug hypersensitivity 10 are also consistent with DiHS, but not with RGD. Thus, it can be speculated that RGD develops as an indirect consequence of SARS-CoV-2 infection via exaggerated monocyte activation. Although in our case granulomatous infiltrates resolved rapidly and did not progress to organ damage, long-term monitoring of patients with both diseases is needed. The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries Granuloma annulare triggered by SARS-CoV-2 infection: immunohistochemical staining Reactive granulomatous dermatitis a review of palisaded neutrophilic and granulomatous dermatitis, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, and a proposed reclassification Garc ıa-D ıez A. Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF Frontline Science: COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice Monocytes and macrophages, targets of severe acute respiratory syndrome coronavirus 2: The clue for coronavirus disease 2019 immunoparalysis Monocytes are involved in the balance between regulatory T cells and Th17 cells in severe drug eruptions Drug-induced hypersensitivity syndrome with superficial granulomatous dermatitis-a novel finding COVID-19-related cutaneous manifestations associated with multiple drug sensitization as shown by lymphocyte transformation test The patients in this manuscript have given written informed consent to the publication of their case details. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.