Breaking the cycle: a comprehensive exploration of topical steroid addiction and withdrawal

Abstract

Topical steroid withdrawal (TSW) is a skin condition characterized by red burning, itchy, painful skin lesions, often accompanied by peeling, and cracking. Patients experience sleep disturbances due to intense itching, significantly impacting their quality of life. A majority of affected individuals develop secondary bacterial infection, marked by heavy colonization of Staphylococcus aureus (S. aureus) and alterations in the skin microbiome. TSW is described as a rebound effect following discontinuation of prolonged use of mid-to-high-potency topical corticosteroids. There exist no definitive diagnostic criteria for this entity, and it is often misdiagnosed as a flare-up of an underlying condition or a contact allergy. Despite numerous personal reports and experiences shared on online platforms, studies on TSW remain scarce in scientific literature. Recognizing and effectively managing this condition is critical for healthcare providers seeking to develop comprehensive management plans. These plans typically include supportive therapy for both physical and psychological symptoms, as well as the gradual tapering of corticosteroid use before complete discontinuation. This review aims to consolidate the existing knowledge on TSW, providing a comprehensive resource for its identification, management, and treatment. By enhancing understanding of TSW, this review seeks to support healthcare providers in implementing optimal management strategies and improving patient outcomes.

Keywords: atopic dermatitis; corticosteroids; topical steroid addiction; topical steroid withdrawal; treatment and management.

Figure 1

(A) Erythematoedematous subtype of steroid withdrawal characterized by severe oozing, crust, redness and excoriation. (B) Papulopustular subtype of steroid withdrawal with erythema, papules and pustules. Permission obtained to reuse figure from (14).

Figure 2

Pathophysiology of topical steroid addiction (TSA) and withdrawal (TSW). Exogenous application of topical corticosteroids (TCS) suppresses intrinsic cortisol production by keratinocytes (A) through negative feedback mechanisms involving the downregulation of enzymes like CYP11A1, CYP17A1, 3βHSD1, CYP21, and CYP11B1. Upon TCS withdrawal, the elimination of exogenous cortisol and reduced enzymatic activity leads to a temporary reduction in cortisol production, worsening inflammation in TSW. TCS also inhibits the proliferation and extracellular matrix protein synthesis of keratinocytes and fibroblasts (B), reducing steroidogenesis of epidermal lipids such as ceramides, cholesterol, and fatty acids, resulting in a thinned stratum corneum and increased transepidermal water loss (I). Skin atrophy arises from TCS-induced reduction in collagen synthesis (C), caused by decreased prolyl hydroxylase activity and collagen mRNA degradation. Chronic TCS use also inhibits endothelial nitric oxide (NO) production, leading to vasoconstriction, which reverses upon TCS withdrawal, causing excess NO release and subsequent vasodilation (D). The vasodilation is associated with adverse effects such as erythema, itching and burning. Reapplication of TCS is often sought to reverse these adverse effects, resulting in a cycle of vasoconstriction and vasodilation (D), termed the “trampoline effect” or “neon sign,” and excess NO accumulation (E), leading to hyperdilation of blood vessels beyond their pre-steroid state (F). This excess NO and prolonged hyperdilation are thought to contribute significantly to the erythema characteristic of TSA/TSW. Prolonged TCS use induces immunosuppression as well, making the skin more susceptible to the overgrowth of microorganisms. When TCS are withdrawn, these microorganisms can act as superantigens, inducing cytokine release and subsequent inflammation (G). Papulopustular and acneiform lesions, characteristic of the papulopustular subtype of TSW, are thought to result from TCS degradation of the follicular epithelium and subsequent extrusion of follicular contents (H). These interconnected processes illustrate the impact of TCS on keratinocyte and fibroblast function, endothelial response, immune function, and follicular epithelium and skin barrier integrity, ultimately driving the pathological changes observed in TSA and TSW (Created with BioRender).

Figure 3

Signs and symptoms of TSW. (A) Widespread redness in the arm. (B) Serious redness in the ear. (C) Elephant wrinkles. Permission obtained to reuse figure from (14).

Figure 4

Phases of TCS withdrawal. Before TCS withdrawal patients’ skin appears normal. Phase I is characterized by acute red skin which spreads gradually. It lasts for a few days to weeks. Phase II is marked by dry, itchy, thickened skin. Some patients show signs of depression due to lack of treatment and continuous worsening of skin lesion. Phase III is the recovery phase where patients show gradual improvement of skin lesion with occasional aggravated skin flares. Phase IV is the recovered phase where patients skin normalizes and regains its original appearance. This phase may take weeks to years.

Figure 5

TCM therapy showed marked improved skin lesion. (A) 12 days after the last course of prednisone, with MSSA Staphylococcus aureus infection and poor response to steroid injection. (B) Improvement of skin lesions by 1 Week of TCM use including internal tea, external herbal bath and creams. (C) 1 month of TCM use, (D) 3 months of TCM use, (E) By 6 months, skin remained to be well controlled. No steroids or antibiotics were used during the course of TCM therapy. (F) Skin reveals no apparent recurrence 3 months after TCM discontinuation. Figure permitted to use from (45).

Figure 6

Damping moderate to severe AD with corticosteroid. Topical corticosteroid use should be limited to 2–4 weeks for appropriate response. Tapering steroid dose, followed by site-specific corticosteroids may help dampen AD severity by reducing the need for corticosteroids and limiting adverse effects like TSW.