Erythema Nodosum: A Practical Approach and Diagnostic Algorithm

Daniela Michelle Pérez-Garza; Sonia Chavez-Alvarez; Jorge Ocampo-Candiani; Minerva Gomez-Flores

Disclosures

Am J Clin Dermatol. 2021;22(3):367-378. 

In This Article

Pathogenesis

Erythema nodosum is considered a hypersensitivity response to a variety of antigenic stimuli. It has been proposed that EN may be the result of the formation of immune complexes and their deposition in the venules of the septae of the subcutaneous fat.[10] Evidence of circulating immune complexes in early lesions supports the suggestion that the antigen, antibody, and complement play a significant role in the pathogenesis and circulating immune complexes may contribute to tissue injury.[11,12] However, some authors have reported a lack of circulating immune complexes in uncomplicated EN, and a type IV delayed hypersensitivity reaction has been proposed.[13] Several adhesion molecules and inflammatory mediators are involved in the development of the lesions. Expression of adhesion molecules, such as E-selectin, P-selectin, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1, on endothelial cells in patients with EN has been observed.[14] Early lesions are characterized by a neutrophilic inflammatory infiltrate in which activated neutrophils might cause oxidative tissue damage and inflammation owing to the production of reactive oxygen intermediates.[10,15] High levels of cytokines and growth factors, mainly involved in neutrophil recruitment and activation, have been reported both in the skin (mainly interleukin [IL]-6, IL-8, IL-12, interferon-γ, granulocyte colony-stimulating factor and monocyte chemoattractant protein-1) and serum (mainly IL-6, IL-8, IL-12, tumor necrosis factor-α, interferon-γ, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1) of patients with EN.[16] Increased acute-phase reactants have been detected in patients with EN.[12]

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