Tretinoin versus Acne
Background Information
Acne refers to a chronic skin condition that result from the clogging of oil and sebaceous material in the hair follicles. The outstanding manifestation of this condition is the eruption of pimples and whiteheads, especially on the facial region. The pathophysiology of the disease is not clearly understood as scholars have put forth many theories explaining the etiology. The relevance of the pathophysiology is to inform the pharmacological approach towards its treatment. One of the possible etiologies is related to the hyperproliferation of the follicular hair tissue. In this theory, the hyperproliferation plugs the follicle and consequently stimulates the production of the sebaceous material. Studies do indicate that the two processes are interlinked by the action of various mediators, including cytokines such as Intracellular Cell Adhesion Molecule-1 (ICAM-1) and interleukin-1. Another theory submits that acne is multifactorial in etiology. It postulates that the onset of acne commences with keratinocyte desquamation. This event coincides with the increased production of androgens, which stimulates increased sebum production. Various pharmacological agents have been used to treat the condition, given the lack of clarity on its etiology and pathology (Cong et al., 2019).
Previous studies have shown varied information regarding the pharmacological agents that should be used to treat acne. In addition, the data has demonstrated various efficacy levels of the pharmacological agents. The researchers who argue in favor of the cell-mediated pathophysiology advocate for anti-inflammatory agents such as topical corticosteroid agents. On the other hand, other scholars say that acne is problematic when it becomes complicated by other factors such as bacterial agents. They, therefore, consider that such complications are the ones that merit pharmacological interventions with agents such as antibiotics. In another argument, some scholars postulate that acne is composed of pimples and cysts hence argue for targeted rather than empirical therapy. Although there is contention on the choice of a pharmacological agent, the scholars agree that it is currently the mainstay of treating acne. Tretinoin is one of the Retinoid agents that is also used as an antineoplastic therapy. Its pharmacological mode of action is that it disrupts the desquamation process of acne development (Xu & Li, 2019a).
Additionally, it disrupts the blockage of the sebum outlet, therefore, preventing its build-up in the follicles. It also has anti-inflammatory properties as it impairs the production of cytokines. However, researchers have conducted studies on its use in acne treatment with varied results (Xu & Li, 2019b). Considered herein, this paper is a review of previous researches on the use of Tretinoin to treat acne.
A study conducted by Guy et al. (2008) considered using 0.05% Tretinoin Gel in treating acne. The authors carried out a Randomized Controlled Clinical study in their study. The researchers recruited participants in a randomized version and distributed the drugs in a controlled performance. They also administered Tretinoin Gel microsphere and vehicle as control of the study. The scholars held their clinical research by doing a manual count of the papules of the participants to ensure that they were standardized. Additionally, individuals with pre-existing medical conditions that would interfere with the study were excluded from the trial. Also, the analysts excluded individuals who were taking anti-inflammatory medications because of the synergistic role such therapy would pose to the Tretinoin. They subsequently carried out a two-step analysis; to evaluate whether Tretinoin was superior to the vehicle and whether it was inferior to the microsphere regarding acne treatment. They based their study on the absolute count. The test, therefore, adopted a pretest and posttest, lesion count. The results indicated that the tretinoin gel was more potent as compared to the vehicle and microsphere. As shown in the figure below, the number of lesions post-treatment reduced significantly with Tretinoin’s use compared to the vehicle in one week.
Figure 1: Number of post treatment lesions in vehicle and tretinoin-treated patients. Extracted from Guy et al. (2008). (Accessed date 01.05.2021).
In another study, Schmidt, Nicholas, and Eugene (2011) sought to review the anti-inflammatory features of Tretinoin when used in treating acne. The authors’ literature review revealed that the drug had been traditionally accepted in treating acne based on its comedolytic effects. The authors carried out a meta-analysis study of data on Tretinoin to establish whether it had additional immunomodulation and anti-inflammatory effects. The scholars, therefore, anchored their research on the role of mediators as an explanation for the pathophysiology of acne. In particular, the scholars indicated that the inflammatory phase of acne took the better part of the disease course and was associated with more symptoms. They identified mediators such as interleukin-1, tumor necrosis factor-alpha, and interferon-gamma as responsible for the disease’s inflammatory stage.
The authors’ study indicated that Tretinoin has an effect of inhibiting the release of the proinflammatory mediators. Notably, the drug blocks the production of interleukin-5 by the T helper cells. The Th2 cells are specific T lymphocytes that play a central role in coordinating the inflammatory response. The researchers also identified that Tretinoin had been shown to modulate the function of macrophages. In immunochemistry, macrophages are responsible for the release of interleukin-6, which is a proinflammatory mediator that recruits other inflammatory cells to the site. As shown in the figure below, the study indicated that Tretinoin also affected other immune factors such as interferon-Y, prostaglandin synthesis, leukotrienes, and proteolytic enzyme activity.
Figure 2: Effect of Tretinoin on pro-inflammatory mediators. Extracted from Schmidt, Nicholas, and Eugene (2011). (Accessed date 01.05.2021).
What are the associated risk factors, and what are the possible mitigation measures? Many previous studies had focused on the beneficial effects of retinoid derivatives. The critics of the use of retinoids in acne treatment argued that it is a potent cytotoxic drug that should only be used to treat neoplastic diseases. Indeed Tretinoin is used in the treatment of Acute Promyelocytic Leukemia (APL). In the backdrop of this opposition, Yoham and Casadesus (2020) conducted a study to show the adverse outcomes of using Tretinoin in acne treatment and the mitigation measures.
The authors conducted a data record review in their study. They identified the most common adverse effects: cardiovascular disorders, arrhythmias, pancreatitis, genital ulcers, hypertension, renal tubular necrosis, headache, bone pain, and diarrhea. They indicated that retinoid toxicity is associated with visual disturbances, fever, and bone pains. They, therefore, proposed serial monitoring tests, including complete blood count and liver function tests (LFTs), and outlawing the use of the drug among women of child-bearing age.
The last article reviewed herein is an update on the current use of retinoids by Bosswell (2016). The author conducted a review of the pathophysiology of acne to identify the most potent agent that ought to be used for treatment purposes. According to him, the two paths leading to acne (extrinsic and intrinsic photoaging) ultimately converge on increased sebum production and its clogging on the hair follicles. He, therefore, postulates that the most appropriate way to arrest the development of acne is by stopping the photodamage stage by the use of vitamin A analogs, Tretinoin being one of them.
