Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report

Abstract

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed “drug-induced PG.” In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.

From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid

“…Liu et al studied the impact of TNF-α on eosinophils and described that they can release both Th1 and Th2 chemokines depending on the surrounding microenvironment, particularly influenced by the presence of interferon (INF)-γ or IL-4 [152]. Consequently, it has been proposed that anti-TNF-α agents may have a dual role, as they can either treat or induce Th2-mediated diseases like BP according to the underlying immune profile [147].…”

IL-12/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum

“…The etiology and molecular pathogenetic events of this disease are yet unknown. Despite this unclear etiology, dysregulation of both innate and adaptive immunity has been implicated in PG, as supported by evidence of Th1/Th17 skewed inflammation and enhanced inflammasome activation associated with overexpression of neutrophils-derived cytokines (6)(7)(8)(9)(10). Appropriately targeting any of these associated pathways can regulate inflammatory milieu and may exhibit a therapeutic effect but recurrences are not uncommon (11)(12)(13)(14).…”