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An Overview of TSW: Exploring corticosteroid addiction and withdrawal from a medical and patient perspective by Dr Heba Khaled

What is TSW?

Topical Steroid Withdrawal (TSW) is a debilitating skin condition which can occur after the termination of topical steroid (TS) use, after a period of frequent and/or prolonged use.

The condition is considered to be rare, and although it usually follows frequent TS application of at least a year, it has also been reported after much shorter periods of use.

Whilst TS are still being applied, the condition is referred to as Topical Steroid Addiction (TSA), the withdrawal period begins once the use of TS has been discontinued.

What are the symptoms?

During TSW, the skin typically cycles between phases of being red or hyper pigmented, inflamed and burning, to extremely dry and flaky. This is often accompanied by an unbearable ‘bone-deep’ itch, raw and weeping skin, loss of body temperature control, weight loss, enlarged lymph nodes and hair loss.

Anxiety and depression are common during TSW due to the severity and persistence of the symptoms.

The symptoms and length of withdrawal vary between individuals, but the withdrawal period usually lasts between 3 months and 2 years. After the withdrawal process, healthy skin usually returns completely, although in some cases, with the initial skin problem (e.g. eczema). 

The inflammation that occurs with TSW can cause hyperpigmentation in darker skin.

Who is at risk?

A recent meta-analysis summarised observations of TSW patients from 34 studies dating from 1969-2013 (Hajar, 2015). The combined figures suggest that TSW is significantly more common in females (81% of 1085 patients) over the age of 18 (92.8% of 1085 patients). Whether this gender unbalance is attributed to females being more susceptible to TS addiction or having a greater tendency for applying TS in the first instance, remains unclear. The addiction is likely more common in adults due to their prolonged exposure to TS. 

The study highlights other common characteristics amongst TSW patients: 97% used TS on their face, 98.6% used high- or mid-potency TS, and 85.2% used TS for more than 12 months.

The most common indication for TS use was atopic dermatitis (33.3%), followed closely by cosmetic use, pigmentary disorders, facial rash and other indications.

These findings lay out a clear demographic of those most at risk of TSW, and specific risk factors which should be considered by the doctor and discussed with the patient upon prescription of TS.

What are topical steroids?

Topical steroids (also known as topical corticosteroids) are creams prescribed to manage a range of skin conditions, including eczema, psoriasis, dermatitis, rashes, rosacea and other inflamed, itchy or red skin complaints. They are intended for use on particular areas of skin, not for the whole body or for prolonged periods of time. TS are available in four potencies (strengths): mild, moderate, potent and very potent. The strength of TS required is recommended by the doctor, although patients are often started on mild TS, then progress up the ‘TS potency ladder’ if the strength is not sufficient, or if symptoms worsen. Mild TS can be purchased at pharmacies without a prescription; however, a prescription is required for stronger potencies. Potent TS are rarely given on repeat prescription, as their prolonged use is discouraged. 

Corticosteroids are available in forms other than topical creams; oral steroids, steroid inhalers and steroid injections are also used to control some conditions. The side effects of non-topical steroids are more well-documented than those of TS, hence their long-term use is usually more closely monitored by doctors. The NHS website lists side effects of all types of steroids (www.nhs.uk/conditions/steroids/) however does not yet feature TSA/TSW.

Although both can be referred to as ‘steroids’, corticosteroids should not be confused with anabolic steroids, which are an entirely different drug. Anabolic steroids mimic the effects of testosterone, so are sometimes misused to increase muscle mass and improve athletic performance. 

How do topical steroids work?

TS are a man-made source of steroid hormone, which have important roles naturally in the body. Natural corticosteroids are synthesised and released from the adrenal cortex, a part of the adrenal glands which sit just above both kidneys. There are two classes of corticosteroid- glucocorticoids and mineralocorticoids. Glucocorticoids are the type that we are interested in, as they are used in TS. Mineralocorticoids, on the other hand, are involved in water regulation in the kidneys. The main types of glucocorticoids are cortisol (or hydrocortisone), corticosterone and cortisone, which were first isolated from the body in 1948 (Kendall, 1948). In 1952, it was observed that topically applied hydrocortisone improved some skin conditions (Sulzberger and Witten, 1952), and so the development of TS began. 

When TS are applied, the active steroid ingredient binds glucocorticoid receptors on cells, which then exerts an effect on the cell internally. Once a glucocorticoid-receptor complex is formed, this can then regulate gene transcription in the cell (Lu NZ 2006, Rhen 2005), i.e. change the types and amounts of molecules that the cell is making, which affects the cell’s behaviour.

  • A reduction in inflammation, generated by reducing the production of inflammatory signals by the cell. Also, blood vessels are narrowed (vasoconstriction), which slows blood flow and also the number of inflammatory molecules being delivered to the site (Ahluwalia, 1998). This explains the reduction in redness caused by TS.
  • A reduction in cell production, which is particularly beneficial in cases of psoriasis, where the rate of cell proliferation is elevated (Uva, 2012).
  • Immune system suppression, which is again elicited by the change in signals produced by the cell. These signals inhibit the actions of white blood cells by stopping their attraction to the site, and their multiplication (Uva, 2012). White blood cells contribute to inflammation, so calming them helps control symptoms of swelling, redness, and itching. 

This combination of properties allows TS to control the symptoms of many inflammatory skin conditions. The improvement caused by TS is often fast and impressive, so users can be tempted to apply the creams more often or in higher doses than recommended. There are well-recognised side effects of TS use, which include thinning of the skin, stretch marks, folliculitis, discolouration, acne and rosacea (NHS website). It is for these reasons that physicians recommend sparing use of TS, on small areas and for short periods of time. 

How do topicals steroids cause TSA/TSW?

There remains little to no research on how and why some users become ‘addicted’ to TS. The prevailing theory is that although historically is was believed that our only source of cortisol was the adrenal glands, in recent years is has been shown that our keratinocytes (90% of the cells on our outermost skin layer) also produce cortisol (Cirillo, 2011). The overexposure of these cells to cortisol can alter their characteristics, which in turn can alter the surrounding immune environment, causing atopic skin. Encountering too much cortisol can also alter the glucocorticoid receptors on the keratinocytes, probably in an attempt to limit cortisol uptake from their surroundings (Juhasz, 2017). TS exert their vasoconstrictive effects by suppressing nitric oxide (NO) release, which usually is released in inflammation to widen blood vessels. The ‘red skin syndrome’ seen in TSW is the result of NO release from cells as there are no longer steroids present to instruct them to hold it back (Rapaport, 2006).   

Many thanks to Alice Burleigh for writing this section.

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