Despite advances in managing plaque psoriasis, chronic inflammatory dermatosis tends to recur when treatment is discontinued. This reoccurrence often appears in the same spot it had festered in prior to pharmacological intervention. This so-called molecular scarring suggests that the dermis retains a local memory of the disease that will trigger a return once treatment is stopped.
Studies have shown that tissue resident memory T cells (TRM), a subset of noncirculating TRM, are primarily responsible for this phenomenon. Other forces, however, may be involved including regulatory T lymphocytes (Tregs), dendritic cells (DC), and Langerhans cells (LC) (Figure).
“Local Memory” Still Observed Within Dermis and Epidermis
To further examine the occurrence of molecular scarring in patients with psoriasis and plaque psoriasis, Marta Kasprowicz-Furmańczyk, MD, and colleagues developed a literature review to delve into the various effects that interventional therapies have had on immune memory. As reported in this review by Dr. Kasprowicz-Furmańczyk and colleagues in Advances in Dermatology and Allergology, “Despite the clinical resolution of the lesions, within the dermis and epidermis, differences in the populations of cells of the immune system and at the molecular level, constituting local memory, are still observed.”
Phototherapy has an immunosuppressive effect as it induces apoptosis of keratinocytes. UVB-phototherapy has a disruptive effect on the same transmission paths as current anti-psoriasis therapies. Furthermore, early application of this type of treatment may be correlated with a reduction in the relapse of psoriasis patients.
The effectiveness of biologic therapies has been confirmed by many studies; however, each form of this treatment option remains susceptible to relapse after discontinuing treatment. Gene products that resist normalization were observed in patients successfully treated with TNF-α inhibitors. One study showed that even though only 7% of T-cell clones remained in cured psoriatic skin lesions, after a triggering factor, these cells were prone to proliferate interlukin (IL)- 17A again.
IL-23 Antagonists Produce a Comparatively Longer Remission
Inhibiting the IL-17 pathway through anti- IL-17 biologics can have a rapid therapeutic effect, as well as a long-term rate of remission. However, even though no DCs are identifiable in the cured skin, LCs capable of producing IL-23 remain. Anti-IL-12/ IL-23 therapies were found to have a less pronounced molecular scar, which would explain the greater likelihood of longer clinical remission of psoriasis.
The researchers noted that although anti-IL-17 treatments provide a fast clinical response, IL- 23 antagonists produce a comparatively longer remission from the disease. Early intervention with IL-23 antagonism may diminish the formation of TRM, which later becomes molecular scarring. Conventional therapies were also examined by the research team, including methotrexate. It was found that TRM continued to exist in plaques deemed resolved months after successful treatment with methotrexate was completed. Systemic drugs can produce positive results in eradicating T lymphocytes in the patient’s circulation and dermis; however, TRM may be left behind in the epidermis.
Dr. Kasprowicz-Furmańczyk and colleagues concluded, “It seems that several factors influence the proper control of the disease and reduction of TRM, including early initiation of treatment, the type of therapy used, as well as its duration.” They went on to add, “It seems that the use of combined therapies—general and topical treatment—may work more effectively on the number of TRM in the skin of patients with psoriasis, giving longer and more durable remissions of the disease.”
