Exaggerated Imiquimod Application Site Reactions in the Context of Systemic Tumor Necrosis Factor-Alpha Inhibition: More Than a Coincidental Occurrence?

Abstract

Topical imiquimod and tumor necrosis factor (TNF)-α inhibitors have gained wide acceptance as safe and effective treatments for non-melanoma skin cancer (NMSC) and moderate to severe psoriasis, respectively. While mild to moderate application site reactions (ASRs) are a well-known and common phenomenon associated with imiquimod, the potential of TNF-α blockers to elicit cutaneous inflammatory reactions has only recently been recognized. We present two cases of severe, atypical ASRs which occurred during NMSC treatment with imiquimod in the context of infliximab administration for psoriasis, and consider the grounds supporting a non-fortuitous association. To date, no relation has ever been suggested between TNF-α inhibitors and increased susceptibility to developing exaggerated ASRs with imiquimod. We believe that this subject deserves further analysis; meanwhile, increased attention should be drawn to the possibility of this adverse interaction, as simultaneous treatment with TNF-α blockers and imiquimod is becoming increasingly frequent in daily practice.

Evidence for mast cells activation in the lung of propionic acid-induced autism-like rat model (histological and immunohistochemical study)

“…A high level of IL-6 gene was reported in the brain of autistic patients [60] . Besides, other authors established that numerous cytokines including IL-6 and IL-8 are raised in the plasma of young children with ASD and these rises are connected with more impaired communication and abnormal performances [61,62,63] .…”

Imiquimod-induced Psoriatic Erythroderma Treated with Infliximab

“…Imiquimod-induced psoriasis has sometimes been described in adult patients with a prior history of psoriasis (1,8). Moreover, there have been a few reports in children (2).…”

“…In most previous studies, the symptoms were resolved by only application of topical calcipotriol or topical steroids and/or ultraviolet B treatment (1, 2). There have been 2 reports of treatment with infliximab, a chimeric monoclonal antibody against TNF-α, in the course of imiquimod-induced psoriasis, because of a flare of the patient's skin condition and complication of arthritis (8). However, the patients had pre-existing psoriasis, and new lesions developed at the site of imiquimod administration.…”

Impact of Immunity in Autism Spectrum Disorders

“…Other authors reported that increased proinflammatory cytokine levels in the brain (TNF-a, IFN-y, IL-l~and IL-8); and NF-kappaB, may also contribute to autism spectrum disorders (24)(25)(26)(27). In addition, other authors confirmed that several cytokines and chemokines, including IL-l~, IL-6, IL-8 and IL-12p40, are elevated in the ASD plasma of very young children (ages 2-5 years old), and that these increases are associated with more impaired communication and aberrant behaviors (28)(29)(30)(31).…”