Disease Modification and Implications in Dermatology

Disease modification is a concept suggesting that early therapeutic intervention alters the natural disease course in immune-mediated inflammatory conditions. The concepts of disease modification have been established in neurodegenerative disorders (including Alzheimer's disease, Parkinson's disease, and epilepsy and rheumatologic disorders (including rheumatoid arthritis, osteoarthritis, and systemic sclerosis. These diseases are characterized by irreversible tissue damage, causing the symptoms. Hence, the concepts and definitions of disease modification aim to reduce or even halt the progression of the disease. Disease-modifying therapies are showing promise in chronic inflammatory disorders such as rheumatoid arthritis and Crohn's disease, with the method and timing of initial treatment impacting long-term disease outcomes. A growing body of evidence suggests that early therapeutic intervention changes the natural disease course in immune-mediated inflammatory conditions, including Crohn's disease and RA. 

One example of this success in dermatology is the use of isotretinoin for the treatment of severe nodulocystic acne. Isotretinoin, which exhibits anti-inflammatory properties, inhibits comedogenesis, sebum production, and proliferation of Propionibacterium acnes, is notable for its efficacy in clearing acne and for inducing disease remission after treatment completion. The use of isotretinoin to halt the progression of severe acne exemplifies how therapies can alter ongoing pathophysiology and prove effective in disease modification. Disease modification from isotretinoin is believed to be mediated by permanent atrophy of sebaceous glands and was FDA-approved in 1982

Disease modification is continuing to make its way in the dermatologic spaces with possible implications for the two most common inflammatory skin diseases: atopic dermatitis (AD) and psoriasis (PSO). 

Thus far, medications used to treat AD and PSO have primarily focused on understanding the mechanisms leading to inflammatory reactions in various tissues, resulting in the development of numerous, mostly safe and effective drugs to combat AD and PSO. Studies in psoriasis are examples of altering comorbidity risk, another form of disease modification. Some early studies suggest that aggressive (ie systemic or biologic medications) early intervention has been hypothesized to reduce the development of psoriatic comorbidities the hypothesis of the impact of aggressive early intervention has not been thoroughly tested, early experience with this clinic has been promising, particularly in its ability to deliver timely care to patients at high risk of psoriatic comorbidity development (ie psoriatic arthritis or other cardio vascular risks). Current studies are underway to examine the influence of aggressive early intervention and its implications in AD and related comorbid conditions (ie, the atopic march). The outlook continues to be hopeful for those patients suffering from chronic inflammatory skin conditions, and we look forward to future studies.

References

M.E. Jacobson et al. J Eur Acad Dermatol Venereol 2024;38:665–672. https://doi.org/10.1111/jdv.19699

Bieber, T. Disease modification in inflammatory skin disorders: opportunities and challenges. Nat Rev Drug Discov 22, 662–680 (2023). https://doi.org/10.1038/s41573-023-00735-0

Justin Love, MPAS, PA-C, resides in the blue zone of Loma Linda, CA. He works for the Loma Linda University Department of Dermatology. In his spare time, he enjoys any ocean-related activities and spending time with his family.