Recall-Dermatitis

The recall phenomenon was first described in 1959 by the physician Dr. R. D'Angio et al. as radiation recall and originally described the occurrence of a local dermatitic reaction in a previously irradiated skin area after taking chemotherapeutic agents (e.g. after actinomycin, docetaxel, methotrexate, doxorubicin, gemcitabine, tamoxifen or bleomycin). Later, radiation recall was also described after taking antibiotics (e.g. ceftriaxone: RRD 6 months after radiotherapy and a single intramuscular dose of ceftriaxone -Patel NV et al. 2020; nitrofurantoin:RDD 8 years after radiotherapy- Garrahy I et al. 2019), tyrosine kinase inhibitors or aromatase inhibitors (Sweren E et al. 2021).

The disease can occur within a few days, weeks or years after radiotherapy. Intervals of a few minutes to 14 days have been described for intravenously administered drugs. Docetaxel and gemcitabine were the two drugs most frequently associated with a radiation recall phenomenon (Bhangoo RS et al. 2022). Radiation recall phenomenon can also occur as recall myositis or recall pneumonitis.

Recall dermatitis is defined as a drug-induced dermatitis that occurs exclusively in areas that have previously been exposed to radiation of varying intensity. It occurs in X-ray irradiation fields(radiation recall dermatitis) but also in areas of skin previously exposed to UV or laser radiation(UV recall dermatitis; laser recall dermatitis). Triggering drugs are mainly systemically administered chemotherapeutic agents or antibiotics. Recall dermatitis can occur within days or even months after the skin has been irradiated.

Recall dermatitis initiated by local immunotherapy (imiquimod therapy) was triggered by a subsequent mRNA SARS-COV2 vaccination after topical treatment of actinic keratoses with an imiquimod cream(Zyclara 3.75%) (Roshardt Prieto NM et al. 2023).

The mechanisms underlying recall dermatitis are still unknown. An acquired (e.g. UV radiation), increased reactivity of the epithelial cells or the cells of the innate immune system can be assumed. This phenomenon is referred to as "trained immunity" or "acquired immune memory".

Trained immunity (TI) was first discovered in cells of the innate immune system, e.g. in monocytes, macrophages and natural killer cells. However, TI has also been found in cells with a long lifespan, such as stem cells and fibroblasts (Naik, S et al. 2017).

It has been shown that epithelial stem cells (EpSCs) can develop a long-lasting memory for previous inflammatory stimuli, e.g. topical imiquimod treatment, enabling the skin to respond in a localized manner to subsequent damaging stimuli.

After the initial stimulus, EpSCs apparently retain chromosomal accessibility of several "critical genes" for the inflammatory response, allowing, for example, rapid transcription of AIM2 and its downstream effector genes(caspase-1 and interleukin-1beta) upon a secondary stimulus (Naik, S et al. 2017). The Aim2 gene can thus be described as a local memory. It codes for an activator of the inflammasome.

The absence of the AIM2 protein or its downstream effectors abolishes the memory function of epithelial stem cells for inflammatory impulses (Naik, S et al. 2017).

Furthermore, Trm cells (Trm stands for: T cell resident memory cells) play an important role. Trms are long-lived lymphocytes that colonize tissues and develop after triggering a T cell-mediated immune response. Both ^CD4+ and ^CD8+ Trm cells have been described in skin and other tissues. They exhibit specializations for their resident tissue. Mouse models show that Trm cells function as sentinel alert cells that secrete cytokines and chemokines upon encounter with their cognate antigen. Compared to Trm cells in other tissues, skin Trm remain in loco for years and express skin-specific homing antigens such as the cutaneous lymphocyte antigen (CLA) or the chemokine CCR8. In addition, certain skin retention markers, including CD103 and CD69, are upregulated. The survival of TRM in the skin depends on IL-15 and fatty acid metabolism Ryan GE et al. 2021).

See also under Isotopic response.

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