From Mystery to Management: The Ongoing Story of Seborrheic Dermatitis

Introduction - First identified in 1887, seborrheic dermatitis (SD) still remains an enigma. [1]It is a common skin condition frequently linked to overgrowth of Malassezia spp., causing itchiness and flaking. While environmental factors play a role, the exact cause remains unclear. There are several (11) potential gene mutations or protein deficiencies linked to SD, mostly affecting the immune response. [2] How impaired immunity or barrier function leads to SD at the molecular level can help identify new targets for developing treatments and preventing recurrence of SD.

Epidemiology/Prevalence - Seborrheic Dermatitis a widespread concern

Seborrheic dermatitis is a chronic condition characterized by a scaly rash, affecting 3 to 10 out of 100 individuals, more commonly men. Onset typically occurs in young adulthood or after 50 years of age.[3] Dermatitis, though generally benign, can cause distress due to visible scaly patches, and accompanying hair loss. It presents as a frequently recurring, noncontagious condition. Creams and shampoos can alleviate symptoms, however very few provide a long-term relief. It has chronic course, often requiring ongoing maintenance treatment due to its relapsing nature. Patients should be cautioned about factors that can trigger or exacerbate SD, such as certain medications, nutritional deficiencies, immunosuppression, and comorbidities. Treatment of seborrheic dermatitis varies based on factors like age and severity. General skincare practices, including soap substitutes and moisturizing, are essential. Topical antifungals are recommended as first-line treatment, with corticosteroids for significant symptoms or flare-ups. [4] Treatment rotation may be effective with fewer adverse reactions. Oral treatment may be considered for severe or refractory cases, with medications like ketoconazole or itraconazole.

Managing Seborrheic Dermatitis: Current Treatment Approaches

Topical creams, ointments, lotions, shampoos, and oral medications are commonly used to treat SD. Topical treatments include combinations of compounds with one or more of the 3 actions, namely anti-fungal, keratolytic and immunosuppression. Various combinations like 2% salicylic acid with 2% sulfur, 2% ketoconazole cream, 1% clotrimazole with 1% hydrocortisone cream, 10% sulfacetamide with 5% sulfur lotion, betamethasone dipropionate 0.05% lotion, and 0.03% and 0.1% tacrolimus ointment are available. [5,6] Shampoos comprise various active ingredients such as 1% zinc pyrithione, 1% to 2.5% selenium sulfide, 2% ketoconazole, 1% ciclopirox, 5% coal tar with 2% salicylic acid, and 0.1% and 0.03% tacrolimus. Oral medications include itraconazole, fluconazole, and terbinafine. [7]

The pathophysiology of SD is not fully understood, but three key factors are recognized: abnormal lipid secretion by sebaceous glands, colonization by Malassezia spp., and immunologic dysregulation predisposing individuals to SD. [8] The role of Malassezia spp. in SD is complex, involving dsRNA mycoviruses that can alter fungal function and stimulate immune responses. Skin bacterial microbiota, particularly Staphylococcus aureus, may also contribute to SD. [12] Genetic factors, though not well studied, involve mutations related to epidermal differentiation and immune function. Treatment aims to reduce Malassezia spp. proliferation and associated symptoms like pruritus and scaling while minimizing inflammation. Topical antifungal agents are first-line, with low-potency corticosteroids considered for short-term use due to potential side effects. [13,14]

Treatment Challenges

Extended usage of corticosteroid formulations can lead to adverse effects such as skin atrophy or the development of telangiectasia. Antifungal treatment diminishes the yeast population on the skin, resulting in amelioration of seborrheic dermatitis. However, prolonged, irrational use of azoles has led to a widespread problem of development of azole resistant fungal spp. Additionally, patients should be cautioned and counseled to regarding over the counter antidandruff shampoos containing ketoconazole because of its potential to cause dryness and damage to the hair and scalp. [15,16]

Advances in Treatment/ Novel Therapies Selenium Sulfide exhibits antifungal, cytostatic and keratolytic properties and is considered as a first-line agent. The application of a 2.5% Selenium Sulfide shampoo alleviates dandruff, folliculitis, discomfort, and scalp dryness. [9] It is believed that selenium sulfide controls dandruff via its anti-Malassezia effect rather than by its antiproliferative effect. [17] Certain studies suggest that selenium sulfide could be superior to zinc pyrithione in the treatment of seborrheic dermatitis. The reports of fungal resistance to selenium sulfide are rare, if any. Its multifaceted action makes it a good candidate especially in conditions where a fungal infection is not apparent or where azole resistance is suspected due to its prolonged use. [18]

Synergistic Approaches: Selenium Sulfide and Salicylic Acid

Salicylic Acid - another potent keratolytic agent, decreases cell-to-cell adhesion between corneocytes and is available as a combination with various anti-fungal agents. [10] There is ongoing development of newer formulations that blend molecules aimed at different complementing pathways. These formulations include combinations of topical treatments such as anti-fungal/anti-inflammatory, anti-fungal/keratolytic, and keratolytic/immuno-modulatory agents, which are being employed with differing degrees of success. Salicylic Acid, known for its strong keratolytic properties and favorable safety profile, is often paired with various anti-fungal agents. Research has shown similar effectiveness between combinations like ketoconazole-salicylic acid and selenium sulfide-salicylic acid. [11] They offer improved tolerance and effectiveness in treating seborrheic dermatitis in a gentle yet efficient manner.

Lastly, sustained benefits of the available therapies are not achieved due to low patient compliance to the prolonged therapy required in SD. Patient adherence to treatments may be closely linked to how products smell, feel, and look. Products with pleasant scents, smoother textures, and moisturizing properties from conditioners help prevent excessive dryness of the hair and scalp, enhance patient adherence and potentially improve treatment outcomes. [19]

Key takeaways:

• Use of anti-fungal medicines only in cases where a fungal infection is apparent
• Explore non-conventional anti-fungal compounds like Selenium sulfide with a lower fungal resistance
• Synergistic molecules may be combined targeting various mechanisms of action thereby providing complementing action
• Improved product characteristics like smell, texture and visual appearance to improve patient compliance
• Use topical formulations that cause lesser side-effects like dryness of hair and scalp

Conclusion: Navigating towards Effective Solutions

Effectively managing seborrheic dermatitis always requires targeting its infectious etiology. However, addressing multiple contributing factors simultaneously with shampoos that offer a multipronged action is essential. Due to the chronic and persistent nature of seborrheic dermatitis, its complex causes, and challenges with conventional treatments like topical corticosteroids and antifungals which can have harmful side-effects and lead to anti-fungal resistance, safer alternatives like selenium sulfide and salicylic acid may be reconsidered. Additionally, efforts should be made to enhance patient adherence to treatment regimen.

References:

1. History of Seborrheic Dermatitis: Conceptual and Clinico-Pathologic Evolution - PubMed n.d. https://pubmed.ncbi.nlm.nih.gov/28705278/ (accessed May 15, 2024).

2. Karakadze MA, Hirt PA, Wikramanayake TC. The genetic basis of seborrhoeic dermatitis: a review. J Eur Acad Dermatol Venereol 2018;32:529–36. https://doi.org/10.1111/JDV.14704.

3. Overview: Seborrheic dermatitis - InformedHealth.org - NCBI Bookshelf n.d. https://www.ncbi.nlm.nih.gov/books/NBK532846/# (accessed May 15, 2024).

4. Gupta AK, Richardson M, Paquet M. Systematic review of oral treatments for seborrheic dermatitis. J Eur Acad Dermatol Venereol 2014;28:16–26. https://doi.org/10.1111/JDV.12197.

5. Cheong WK, Yeung CK, Torsekar RG, Suh DH, Ungpakorn R, Widaty S, et al. Treatment of Seborrhoeic Dermatitis in Asia: A Consensus Guide. Skin Appendage Disord 2016;1:187. https://doi.org/10.1159/000444682.

6. Tucker D, Masood S. Seborrheic Dermatitis. StatPearls 2023.

7. Gupta AK, Nicol K, Batra R. Role of antifungal agents in the treatment of seborrheic dermatitis. Am J Clin Dermatol 2004;5:417–22. https://doi.org/10.2165/00128071-200405060-00006.

8. Seborrheic Dermatitis and Dandruff: A Comprehensive Review - PMC n.d. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852869/ (accessed May 15, 2024).

9. Godse G, Godse K. Safety, Efficacy and Attributes of 2.5% Selenium Sulfide Shampoo in the Treatment of Dandruff: A Single-Center Study. Cureus 2024;16. https://doi.org/10.7759/CUREUS.57148.

10. Emollients, moisturizers, and keratolytic agents in psoriasis - ScienceDirect n.d. https://www.sciencedirect.com/science/article/abs/pii/S0738081X08000163?via%3Dihub (accessed May 15, 2024).

11. Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al. Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing. ACS Omega 2021;6:8210–25. https://doi.org/10.1021/ACSOMEGA.0C06242/SUPPL_FILE/AO0C06242_SI_001.PDF

⁠12. Jackson JM, Alexis A, Zirwas M, Taylor S. Unmet needs for patients with seborrheic dermatitis. J Am Acad Dermatol [Internet]. 2024;90(3):597–604. Available from: http://dx.doi.org/10.1016/j.jaad.2022.12.017

13.⁠ ⁠Kashyap A, Sharma KN. Seborrheic dermatitis demystified: Doctor’s secret guide. Virtued Press; 2023.

14.⁠ ⁠Vest BE, Krauland K. Malassezia Furfur. 2024 [cited 2024 May 21]; Available from: https://pubmed.ncbi.nlm.nih.gov/31971731/

15.⁠ ⁠Sinawe H, Casadesus D. Ketoconazole. StatPearls Publishing; 2023.

16.⁠ ⁠Choi FD, Juhasz MLW, Atanaskova Mesinkovska N. Topical ketoconazole: a systematic review of current dermatological applications and future developments. J Dermatolog Treat [Internet]. 2019;30(8):760–71. Available from: http://dx.doi.org/10.1080/09546634.2019.1573309

17.⁠ ⁠Ranganathan S, Mukhopadhyay T. Dandruff: The most commercially exploited skin disease. Indian J Dermatol [Internet]. 2010 [cited 2024 May 21];55(2):130. Available from: http://dx.doi.org/10.4103/0019-5154.62734

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19.⁠ ⁠Godse G, Godse K. Safety, efficacy, and attributes of 2.5% selenium sulfide shampoo in the treatment of dandruff: A single-center study. Cureus [Internet]. 2024 [cited 2024 May 21];16(3). Available from: https://pubmed.ncbi.nlm.nih.gov/38681430/

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