Multiple lesions of cutaneous focal mucinosis in a patient receiving treatment with tocilizumab: Coincidence or causality?

New and emerging conditions of acquired cutaneous mucinoses in adults

“…The lesions tended to improve and slowly regress after L‐tryptophan was discontinued. Recently, the development of cutaneous mucinosis has been related to the therapy with biologics including anti–TNF‐ α drugs, anti–IL‐12/23 (ustekinumab), and anti–IL‐6 (tocilizumab) 20–24 or to a new class of immuno‐modulatory drugs, anti–colony‐stimulating factor 1 receptor (CSF1R) that have been investigated in clinical trials for different malignant neoplasms 25 . Mucinous skin lesions could also be triggered by subcutaneous injections of interferons both as a localized skin reaction at the injection site and as diffuse papular eruption with the characteristics of lichen myxedematosus 26–30 …”

“…As for ustekinumab, this biologic drug decreasing IL‐23 and T‐helper 17 cell‐induced TNF‐ α levels could also stimulate mucin production by fibroblasts through a paradoxical increase of IFN‐ α 23 . The appearance of cutaneous focal mucinosis after the administration of tocilizumab is a paradoxical phenomenon as the drug is made by a monoclonal antibody that blocks the interleukin 6 (IL‐6) receptors, and one of IL‐6 functions is to stimulate fibroblasts for mucin synthesis 24 . A pathogenetic hypothesis is that IL‐6 could accumulate in the extracellular interstitium and perform its function on new synthesized receptors as an upregulation mechanism or on already existing receptors when the drug concentration decreases in the body 24 …”

“…23 The appearance of cutaneous focal mucinosis after the administration of tocilizumab is a paradoxical phenomenon as the drug is made by a monoclonal antibody that blocks the interleukin 6 (IL-6) receptors, and one of IL-6 functions is to stimulate fibroblasts for mucin synthesis. 24 A pathogenetic hypothesis is that IL-6 could accumulate in the extracellular interstitium and perform its function on new synthesized receptors as an upregulation mechanism or on already existing receptors when the drug concentration decreases in the body 24 As for the reaction triggered by type I interferons, these cytokines can increase the inflammatory potential of dermal fibroblasts stimulating the production of mucin. 31 A reduced degradation of the components of the extracellular matrix by macrophages secondary to CSF1R pathway inhibition has been suggested.…”