Topical steroid withdrawal and atopic dermatitis

Abstract

It is widely accepted and rigorously evidenced that topical corticosteroids (TCS) are effective treatments for atopic dermatitis (AD). Whilst TCS are known to have various adverse effects including skin atrophy, telangiectasia and perioral dermatitis, clear instructions from prescribers on how and where to apply, when to taper or stop use can mitigate these risks, as well as close monitoring by the prescribing clinician before refilling prescriptions. An emphasis on the basics of AD management, such as liberal emollient use, can reduce the requirement for TCS.(1) One of the most divisive and debated adverse effects of TCS is Topical Steroid Withdrawal (TSW). First described in 1969, the last 15 years have seen a sharp rise in publications in the medical literature. There has also been a trend in coverage and discussion of the condition across social media alongside the topic of steroid phobia.(2-4) Topical Steroid Withdrawal is also termed Topical Steroid Addiction or Red Skin Syndrome. Signs and symptoms are described either after cessation of TCS, or when increased use or dosage of TCS are required to prevent these symptoms reoccurring, suggesting dependence.(3-6) Diagnosing TSW is challenging due to the lack of agreed criteria and significant overlap of its clinical features with other adverse effects of TCS, rosacea and a flare of AD itself. There is also a wide variation in its presentation. These combined factors have led to some colleagues questioning its very existence.(3, 4) See Table 1.Table 1Features of Topical Steroid Withdrawal (TSW).Clinical features that overlap with other dermatoses(3-5)Erythema, burning, stinging, itching, vesiculation/papules, oedema/swelling, exudation, pustules, telangiectasia, skin atrophy, rosacea appearance, desquamation, skin shedding, friable/cracked skin, thickened skin, reduced skin elasticity, lymphadenopathy,‘Headlight sign’: eruption over the face, sparing of the nose and the upper lipSigns specific to TSW(3, 4)Clinical features being symptomatically and morphologically different to patient's primary dermatosis‘Red sleeve sign’: erythema of upper or lower limb ending abruptly at the dorsal and palmar border, sparing palms and solesDistribution(5)Face and genitals most commonly affected sitesSkin affected can extend beyond area affected by primary dermatosisHistopathology(3)No agreed pathognomonic histologyPrevalence (5)UnknownRisk Factors(3, 4, 5)Use of TCS >6 months, usually >12 monthsInappropriate use of moderately or highly potent TCS, particularly on face or genital areaReported more commonly in womenOnset(3)Variable, ranging from days to months after cessation of TCSPrognosis(5)Variable, ranging from several months to several years in some patient reportsManagement(4)No agreed management pathway and no prospective randomized studies.Most papers discuss or suggest cessation of TCS either abruptly or via tapering.Other management strategies such as topical calcineurin inhibitors have also been reported.TCS: Topical corticosteroids Open table in a new tab TCS: Topical corticosteroids To date, two systematic reviews of TSW have been published in 2015 and 2022 describing a total of 1479 cases. Both papers reported TSW to be a distinct clinical entity, but also acknowledged their limitations being a reliance on low quality studies.(3, 5) The absence of prospective randomised controlled trials that have identified TSW means its prevalence remains unknown. This lack of comprehensive data not only hinders our ability to predict the likelihood of encountering TSW cases in practice but also poses challenges when reassuring patients that are concerned about TCS use, further discussed below.(7) TSW is linked to the “excessive” or “inappropriate” use of potent or moderately potent TCS, though quantities and frequency of application are not consistently described in the literature. The condition has also been observed in 39 patients using low potency TCS. Most of these reports lack detail but many involved at least daily facial use for several years.(3, 5) It is not clear if women are more likely to suffer from TSW (80% cases) or because the majority of studies report it in the context of cosmetic TCS use on the face, as postulated by Tan and colleagues.(3-5) In studies focusing on inflammatory skin conditions there is equal sex distribution. TSW is uncommon in children under the age of three, comprising only 0.3% cases.(5) Areas of the body most commonly affected are the face and genitals, possibly due to the increased permeability of the stratum corneum.(4, 8) Various mechanisms of TSW have been put forward: tachyphylaxis, dysregulation of glucocorticoid receptor, rebound vasodilation and rebound cytokine cascade secondary to TCS-induced barrier impairment. However, all have insufficient evidence to support them.(4, 5) Additionally, the condition has no pathognomonic histopathological features to provide diagnostic certainty. Without a laboratory investigation to support clinical findings, there are many variables open to interpretation. Whilst discussion continues in the medical literature about if, how, and when to diagnose TSW, patients are becoming increasingly untrusting of TCS. Steroid phobia is the fear of TCS and is widespread, with 21% - 84% patients with AD describing these feelings.(7) Many patients seek information from the unregulated realm of the internet, and social media has spotlighted TSW. A 2022 analysis by Bowe et al. of the user-generated content relating to TSWS found a 274% increase in mentions of #topicalsteroidwithdrawal in 2020 compared with 2016 on platforms including Instagram, Twitter and Facebook.(2) This poses a significant risk of misinformation. Fearful patients or their carers may be misled to believe an AD flare is due to TSW and not the underlying condition. This could result in undertreatment and suffering due to the morbidities of AD: extreme itch, sleep deprivation and infections which can be life-threatening. This is especially problematic in young children in whom there are fewer effective alternative therapies, even though in this patient group the risk does appear to be minimal.(5) It seems that the patient voice in TSW is now as loud as the medical community's. As a result of patient enquiries, in 2021 the UK's Medicines and Healthcare products Regulatory Agency (MHRA), the UK government's regulatory body for medicines, published a review of the evidence on TSW.(8) It concluded that that there was a growing body of evidence of TSW, though reactions occur “very infrequently”. Consequently, TSW is now mentioned in all patient information leaflets provided with TCS in the UK. The MHRA also require that TSW is now considered in any UK study protocols using TCS, as has been the case in the SEAL study (Stopping Eczema and ALlergy; NCT03742414). International Topical Steroid Awareness Network (ITSAN) is a large patient advocacy group whose aim is to raise awareness of TSW.(9) In 2010, with Allergy & Asthma Network they funded, recruited for and published a survey of 2160 patients. In this, 79% adults and 43% caregivers of children that had used any corticosteroids reported symptoms consistent with TSWS, albeit not physician-diagnosed cases. Whilst there is bias in this data, which was acknowledged by the authors, we should view this study's conception and results as loud patient demand for further research into TSW. Until we have a better understanding of prevalence, risk factors and consensus diagnostic criteria we must concentrate on listening to our patients’ concerns, prioritizing shared decision making. Physicians that fail to acknowledge patient beliefs and opinions about TCS are at risk of fracturing the patient-doctor relationship, as patients feel unheard and dismissed.(7) That being said, with AD as common as it is, and TCS remaining the bedrock of management for this and many other dermatoses, it is imperative that more research is done so as to define, understand and mitigate TSW. Large scale longitudinal trials could offer more reliable and translatable data to help inform our clinic practices as we understand what to look for and in whom. In order to protect patients from misdiagnosis, it is imperative that basic research finds a validated diagnostic test. We also require pathognomonic clinical and histological features to be defined. Research in to alternative treatment options for AD will offer more choice to both patients and physicians. These advances will strengthen our understanding of and approach to TSW, as well as support the vital patient-doctor relationship. 1.Wollenberg A, Kinberger M, Arents B, Aszodi N, Avila Valle G, Barbarot S, et al. European guideline (EuroGuiDerm) on atopic eczema – part II: non-systemic treatments and treatment recommendations for special AE patient populations. Journal of the European Academy of Dermatology and Venereology. 2022;36(11):1904-26.2.Bowe S, Masterson S, Murray G, Haugh I. Topical steroid withdrawal through the lens of social media. Clin Exp Dermatol. 2022;47(8):1554-7.3.Hwang J, Lio PA. Topical corticosteroid withdrawal ('steroid addiction'): an update of a systematic review. J Dermatolog Treat. 2022;33(3):1293-8.4.Tan SY, Chandran NS, Choi EC-E. Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal. Clinical Drug Investigation. 2021;41(10):835-42.5.Hajar T, Leshem YA, Hanifin JM, Nedorost ST, Lio PA, Paller AS, et al. A systematic review of topical corticosteroid withdrawal ("steroid addiction") in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol. 2015;72(3):541-9.e2.6.Sidbury R, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Drucker AM, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. Journal of the American Academy of Dermatology. 2023;89(1):e1-e20.7.Tan S, Phan P, Law JY, Choi E, Chandran NS. Qualitative analysis of topical corticosteroid concerns, topical steroid addiction and withdrawal in dermatological patients. BMJ Open. 2022;12(3):e060867.8.MHRA. Topical steroid withdrawal reactions: a review of the evidence. MHRA Public Assessment Report September 2021. Medicines & Healthcare products Regulatory Agency; 2021.9.Barta K, Fonacier LS, Hart M, Lio P, Tullos K, Sheary B, et al. Corticosteroid exposure and cumulative effects in patients with eczema: Results from a patient survey. Annals of Allergy, Asthma & Immunology. 2023;130(1):93-9.e10.

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