Nodular lichen myxoedematous: a new adverse event associated with ustekinumab

Abstract

Nodular lichen myxoedematosus is a localised form of lichen myxoedematosus, a chronic idiopathic cutaneous mucinosis of known aetiology. Ustekinumab is a human interleukin-12/23 monoclonal antibody that could directly or indirectly increase mucin production. Herein, we report for the first time a case of nodular lichen myxoedematosus associated with ustekinumab.

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 …”

“…In fact, this block allows skin dendritic cells to produce elevated amounts of IFN‐α, which likely activates lymphocytes, thereby stimulating fibroblasts to increase mucin secretion 20‐21 . 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 .…”

“…[20][21] As for ustekinumab, this biologic drug decreasing IL-23 and T-helper 17 cell-induced TNF-a levels could also stimulate mucin production by fibroblasts through a paradoxical increase of IFN-a. 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.…”

Nodular-Type Lichen Myxedematosus: A Rare Variant With Exclusive Involvement of the Hands—Report of Two Cases With a Comprehensive Review of the Literature

“…Among adult patients, the average age at onset was 33 years (range, 18-48 years), with a male predominance (4:1). 4,5 In 1 patient presenting with Crohn disease, nodular-type LM was possibly induced by ustekinumab, with clinical improvement after leaving treatment. 5 The upper extremities were the most affected site, followed by the lower extremities and trunk.…”

Pediatric Lichen Myxedematosus: A Diagnostic and Management Challenge

“…Distinguishing SHJCM from NLM based on histopathologic features is rarely feasible. Dermal mucin deposition has failed to show a consistent pattern in either subtype [ 12 , 14 , 15 ]. Nodular lesions of SHJCM may exhibit proliferative fasciitis-like features or lobular panniculitis with increased mucin deposition [ 9 ], so biopsy of a deep or large lesion is advantageous.…”