INTRODUCTION

Seborrheic dermatitis (SD) is a frequent skin condition observed in patients of all age groups. Its hallmark symptoms, such as scaling, erythema, and itching, are most commonly found on the scalp, face, chest, back, axilla, and groin areas [1]. The clinical diagnosis of SD is determined by the location and appearance of the lesions. Nonetheless, its multifactorial pathogenesis remains unclear, and its management causes difficulties. It is regarded that the skin lesions in SD result from Malassezia yeast overgrowth, excess lipid secretion by sebaceous glands, dysregulated immune system response, and altered skin barrier function.

However, the latest studies suggest that patients with SD have higher levels of insulin and other metabolic markers compared to healthy controls [2], which may provide us with a better understanding of the pathophysiology of the condition. Now, it moves us towards the idea of routinely assessing the metabolic health of SD patients, at least those with recurrent or severe states, as insulin resistance (IR) may contribute to the severity or duration of seborrheic dermatitis [2]. This review aims to present the current knowledge about the impact of insulin resistance on seborrheic dermatitis, as the insight on these mechanisms may further facilitate the development of targeted therapies and help us achieve better clinical outcomes.

SEBORRHEIC DERMATITIS

Seborrheic dermatitis is most frequently observed in infants during the first three months of life, although it remains present in adolescents and young adults, showing a rising incidence in people over the age of 50. The phrase ‘dermatitis of sebaceous areas’ is used to describe this condition [3], as SD occurs in areas dense in sebaceous glands [4]. The appearance, however, may vary depending on skin type, with potential hyperpigmentation or hypopigmentation, and may occur with or without erythema, and with or without scaling. Treatment so far involved reducing the proliferation of Malassezia spp. and managing the associated inflammatory response. Topical therapies, such as antifungal agents and low-potency corticosteroids, remain the cornerstone of management. However, their effectiveness remains limited also due to potential side effects [5]. As for the newest methods, some case reports indicate that the off-label use of the topical PDE-4 inhibitors crisaborole and roflumilast or the oral PDE-4 inhibitor apremilast may be more effective [6–8].

INSULIN RESISTANCE

Insulin resistance refers to a condition where the body’s tissues become less responsive to insulin, impairing glucose uptake and utilization. IR may be caused by genetic or environmental factors [9], yet its onset is often the result of a dynamic interaction between them, shaped by diet, physical activity, and other external conditions that affect metabolic regulation. Although one of the primary etiological factors in the development of IR is obesity [10], patients with a normal BMI may also experience this condition (“normal weight obesity”) [11].

IR is a condition leading to metabolic syndrome and a risk factor for impaired glucose tolerance, type II diabetes, and cardiovascular and endocrine diseases among others [12,13]. Other risk factors for IR contain chronic inflammation [14], mitochondrial dysfunction or hypertriglyceridemia [15]. Finally, insulin resistance is also suspected to contribute significantly to various dermatological conditions, including seborrheic dermatitis. Insulin and insulin-like growth factor 1 (IGF-1) stimulate sebaceous gland activity and, thus, hypersecretion of sebum, potentially leading to heightened inflammation in patients with SD [16]. Recent studies show clearly that patients with SD have elevated scores of HOMA-IR (homeostasis model assessment of insulin resistance) [17], which poses a new challenge for us, requiring a holistic approach for the dermatology patient.

PATHOPHYSIOLOGY

The sebaceous gland is a major appendage of the skin responsible for producing sebum, which is a lipid-rich substance that plays a crucial role in maintaining skin barrier function and homeostasis. Insulin and insulin-like growth factor 1 are known to influence the sebaceous gland’s activity, primarily through the activation of signaling pathways such as phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) [16]. These pathways regulate sebocyte proliferation, differentiation, and lipid synthesis, which are essential not only for normal sebum production but also its composition. The activation of the mTOR pathway by insulin leads to the upregulation of sterol regulatory element-binding protein-1 (SREBP-1), a significant transcription factor that regulates lipid synthesis in sebocytes. Then, increased SREBP-1 activity results in enhanced production of triglycerides and free fatty acids, which the are main components of sebum [17].

Chronic inflammation is considered a hallmark of both these conditions, insulin resistance and seborrheic dermatitis. Increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukin-6 (IL-6), are observed in insulin-resistant states and are associated with the inflammatory response in SD. These cytokines may further inhibit insulin signaling, creating a vicious cycle of inflammation and metabolic dysregulation. The inflammatory processes and excessive sebum production associated with seborrheic dermatitis are, however, claimed to be potentially driven by elevated androgen levels, which stimulate sebocyte activity [18]. Hyperinsulinemia is known to decrease levels of sex hormone-binding globulin, resulting in increased levels of unbound androgens. The sebaceous gland responds to insulin-mediated signals, either directly or through the IGF-1 axis. Insulin binding to its receptor on sebocytes activates downstream signaling pathways that promote cell growth and lipid synthesis. In a state of insulin resistance, the signaling cascade may become altered, resulting in increased sebum production and inflammation (Fig. 1).

Figure 1: Pathophysiology of the influence of insulin resistance on seborrheic dermatitis.

CLINICAL IMPLICATIONS

Elevated insulin levels may exacerbate skin conditions by increasing sebum production and inflammation, which may worsen SD symptoms [16]. Patients with poor metabolic control are at a heightened risk for flare-ups and more aggressive forms of seborrheic dermatitis [2]. We may surely expect chronic inflammation in patients with type II diabetes or obesity, which would amplify the severity of SD and lead to more frequent and severe flare-ups. The prevalence of type II diabetes and hypertension is significantly higher in patients with SD, indicating a systemic inflammatory response that could play a role in metabolic dysfunction [2,19]. Research shows that patients with SD have significantly elevated not only insulin levels, yet also their BMI and waist circumference [19]. Recognizing insulin resistance in SD patients could lead to tailored treatment strategies, including lifestyle modifications and potential pharmacological interventions aimed at managing both skin and metabolic conditions [20,21].

When it comes to the ways one would handle insulin resistance in seborrheic dermatitis, it was shown that implementing a low-glycemic diet and reducing the intake of insulinotropic foods, such as dairy products, may help improve insulin sensitivity and reduce sebum production [22]. There are some nutritional indicators correlated with SD, and these are increased copper, manganese, iron, calcium, and magnesium and significantly lower serum zinc and vitamin D and E concentrations, meaning that the diet may really affect the course of the condition [23]. From pharmacological solutions, targeting inflammatory pathways through the use of corticosteroids, topical retinoids, or other anti-inflammatory agents may alleviate the inflammatory response associated with SD, too. For sure, investigating insulin-sensitizing agents and anti-inflammatory therapies could offer new strategies for effectively managing this skin condition. As for now, classical methods of treatment with topical antifungals such as ketoconazole or low-potency topical corticosteroids remain in use. They can reduce Malassezia yeast, alleviate inflammation and itching, but they do not always prove to be successful in patients with metabolic dysregulations [24].

COMORBIDITIES

Obesity is a major contributor to systemic metabolic disruptions, including glucose and lipid metabolism disorders, as well as heightened oxidative stress and inflammation [25]. It is reported that even 70–80% of patients with obesity and almost each patient with type II diabetes have insulin resistance [22]. There are studies directly suggesting that SD is more frequent in individuals with obesity [26].

The adipose tissue in obese patients produces an excess of proinflammatory cytokines, and as a result, such patients may experience more severe symptoms and a higher frequency of flare-ups [18]. The increased sebum production associated with insulin resistance may further lead to a more favorable environment for the proliferation of Malassezia yeasts. Obesity was observed to be associated with impaired skin barrier function, dryness, and itching [27], and all these factors do not improve the situation of such individuals in terms of their SD condition.

Similarly, patients with type II diabetes may have a higher incidence of SD [18], and clinicians treating them should recognize the potential for more aggressive disease manifestations in patients with poorly controlled conditions. The inflammatory processes activated by hyperglycemia may worsen the condition of the skin, leading to the increased severity and frequency of SD flare-ups.

CONCLUSION

The relation between seborrheic dermatitis and insulin resistance is increasingly identified, with a slowly evolving paradigm suggesting that dermatologists should consider screening for insulin resistance in patients with severe or recurrent SD. As the sebaceous gland’s function may be influenced by IR, which aggravates the inflammatory response, understanding the role of inflammation and metabolic components of SD in its pathogenesis could pave the way for more effective management strategies for patients. Identifying patients with insulin resistance could allow physicians to better suit treatment for their patients, which would improve overall outcomes.

As for now, it becomes clear that managing seborrheic dermatitis should take into account the interplay between metabolic health, inflammation, and skin disease. To manage the effects of insulin resistance on SD successfully, clinicians should consider evaluating insulin levels and be aware of the potential impact of metabolic factors on the development and exacerbation of seborrheic dermatitis. A holistic approach to the patient’s dermatological health and recognizing and correcting metabolic imbalances occurring with other diseases is extremely relevant.

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