Use of Topical Corticosteroids in Dermatology: An Evidence-based Approach.

Topical corticosteroids (TCs) are the pillars of dermatotherapeutics. These drugs are the "magic molecules," provided they are used judiciously and appropriately, following a rational prescription. On exhaustive literature search in multiple databases, we found a significant evidence favoring the use of TCs in atopic eczema, localized vitiligo, psoriasis, chronic hand eczema, and localized bullous pemphigoid. However, contrary to conventional wisdom, we did not find any high-level scientific evidence in support of prescribing TCs in cutaneous lichen planus, sarcoidosis, and seborrhoeic dermatitis. Besides, evidence clearly advocates judicious use of mild-to-moderate corticosteroids (if required) in pregnancy and lactation and there is no risk of any fetal abnormality.

What was known?

Topical corticosteroids are the most commonly prescribed drugs by dermatologists in an outpatient setting

TCs are being used since ages, in eczema, vitiligo, psoriasis, lichen planus, hand eczema, etc

Topical steroid addiction or red burning skin syndrome is increasingly being recognized, due to illegitimate prescriptions by physicians.

Introduction

Since the introduction in early 1950s, topical corticosteroids (TCs) have become the most commonly prescribed drugs by dermatologists in an outpatient setting. These agents form the mainstay of treatment for many skin conditions. If used appropriately, they are safe and effective, and side effects are rare. Not only dermatologistsbut also steroids have been rampantly prescribed by quacks, general physicians, pediatricians, gynecologists, and specialists of innumerable disciplines.

Unfortunately, TCs are increasingly being abused by doctors and patients. Topical steroid addiction and red burning skin syndrome are legitimate clinical entities which are well recognized these days. Sometimes, these terms are used synonymously.[1] As a result, the problem of steroid phobia is being increasingly recognized by physicians worldwide which, sometimes, is associated with simple fear, due to ignorance of the patient. In addition, current advice to patients to apply TC preparations “sparingly” or “thinly” contributes to steroid phobia, increasing the risk of poor clinical response, and treatment failure. Such cautionary advice also overlooks the fact that the vast majority of patients are prescribed TCs of mild potency for which the evidence suggests that the risk of harm is minimal. In the patient's mind, the current advice groups all steroids together regardless of their potential for adverse effects. The advice also tends to reinforce an erroneous concern that the risks from TCs may be similar to those from systemic corticosteroids.[2]

In this article, we have reviewed the various indications of TCs in dermatology with an overview of the evidence available in support of using these drugs in various dermatoses. Wherever possible, we have tried our best to corroborate the evidence, and analyze them in such a manner that both the opposing concerns may be addressed, and we may come up with a balanced view on TC use in clinical dermatology. At the outset, we would like to summarise the levels of evidence. Level I suggests evidence from a systematic review of randomized controlled trials. Level II corroborates with evidence obtained from at least one well-designed Randomized Controlled Trial. Level III takes into consideration, evidences obtained from well-designed controlled trials without randomization. However, Level IV relates to well-designed case-control and cohort studies. Level V considers evidence from systematic reviews of descriptive and qualitative studies. Level VI and VII are poor quality evidences. Level VI considers evidence from a single descriptive or qualitative study and Level VII takes into account, opinion of authorities and/or reports of expert committees.

Discussion and Evidence

Eczema

Eczema is a noninfective, chronic, inflammatory dermatological entity manifesting as inflamed, pruritic, erythematous, and/or asteatotic skin.[3] Numerous therapeutic modalities are available to combat this notorious dermatosis, TCs being the most commonly prescribed ones. However, most of the patients show excellent response to emollients.[45] According to the traditional school of thought, it is advisable to use TCs during acute episode and withdraw them, once the symptoms have been controlled. However, recent authors are of the opinion that proactive approach is better than the more commonly followed reactive approach.[6] As per recent guidelines, it is favorable to use high-dose corticosteroids during the acute flares and continue with low-dose corticosteroids when the episode is under control.

Besides, step-up and step-down approach can be followed which refers to increasing the potency of the steroid in acute flares and lowering the potency in the periods of remission.[7] Overall, a systematic review of the best strategies for using TCs in the treatment of established eczema is, therefore, required.[8]

Here is a brief overview of some of the major randomized controlled trials (RCTs) comparing the use of different TCs in eczema [Table 1].

Table 1

Evidence in favor of using topical corticosteroids in eczema

These studies showed significant improvement in 13%–100% of patients after 1–12 weeks of treatment. Most of the studies found significant improvement with TC in comparison with placebo. However, three studies could not demonstrate a significant difference between placebo and TC. Few RCTs showed that intermittent treatment with a potent TC could reduce the number of flare-ups. Three RCTs and two small randomized within-patient comparison studies have examined the use of wet-wrap bandaging applied over TC. To summarize, we are not in a position to recommend the “best” TC, as till now, not a single RCT has compared all the available preparations of TC of similar potency. Besides, there is no clear RCT evidence supporting the use of twice-daily over once-daily TC administration. However, it is now clear that application of twice-weekly potent TC to stable eczema can reduce the number of flare-ups in adults as well as children although the long-term safety profile of such intermittent or pulse therapy in infants, is absent.[34]

In a systematic review of treatments for atopic eczema, RCTs of TCs collected data on thinning of the skin and suppression of pituitary – adrenal axis. These RCTs could not show any evidence of harm – although the studies were short-term.[35] There is no RCT evidence that skin thinning is a problem with the correct use of TC although the fact that most RCTs are of short duration is a limitation in basing the conclusions solely on RCT-generated evidence in this regard, and other non-RCT evidence should be used to issue firm recommendations.

Vitiligo

Vitiligo is an acquired pigmentary disorder, attributed to the destruction of melanocytes. Therapeutic modalities which are present include topical and systemic corticosteroids, topical calcineurin inhibitors, photo (chemo) therapy, vitiligo surgery, and depigmentation of normally pigmented skin. Immunosuppressive therapy with highly potent TCs (clobetasol) gives excellent results in cases of localized stable vitiligo.[363738]

Herein, we have tabulated the evidence available in favor of using TCs in vitiligo [Table 2].

Table 2

Evidence in favor of using topical corticosteroids in vitiligo

A meta-analysis, an additional systematic review, and several RCTs showed that Class III TCs are effective in comparison with placebo, either alone or in combination with narrowband – ultraviolet B (UVB), or psoralen plus UVA light (using sunlight or artificial light sources), in treating generalized and localized vitiligo. There is some RCT evidence that topical clobetasol propionate is of equivalent effectiveness with tacrolimus in treating this condition. All studies examining the effect of TCs reported adverse effects, with the more frequent being atrophy, telangiectasia, hypertrichosis, and acneiform papules.[55]

Psoriasis

Topical steroids have been used since ages to manage mild-to-moderate plaque psoriasis (scalp and nonscalp). These are available in different potencies and formulations, but their use relies mostly on the basis of individual experience. Here is a brief summary of evidence in favor of using topical steroids in psoriasis [Table 3].[5657]

Table 3

Evidence in favor of using topical corticosteroids in psoriasis (nonscalp)

To summarize, both Class III and Class IV TCs are effective in inducing remission in psoriasis; however, Class IV appears superior. It remains unclear whether once- or twice-daily dosing should be recommended, but frequency, as well as duration, should be tapered down in a maintenance phase because of concerns with cutaneous and systemic adverse effects of TCs. Skin atrophy is the most common complication, but it is less of an issue in psoriatics than atopics. However, the continuous use of very potent or ultrapotent TCs may cause irreversible skin atrophy and striae, may cause psoriasis to become unstable, and may have systemic effects when used over a large surface area.[82] The ointment formulations appear to be the most effective, but there are many alternative galenicals to increase feasibility and treatment adherence without losing too much effectiveness of the drugs.

Scalp psoriasis, though, responds to a wide array of topical therapies but TCs form the first line of management, and the response is excellent.[5657] The evidence in favor of steroids has been tabulated [Table 4].

Table 4

Evidence in favor of using topical corticosteroids in psoriasis (scalp)

The results in scalp psoriasis are similar to that seen in chronic plaque psoriasis elsewhere in the body.

Lichen planus

Lichen planus (LP) is a common chronic inflammatory dermatosis associated with disrupted cell-mediated immunity. Cutaneous lesions are often extremely pruritic and require rigorous intervention. Symptomatic oral LP is painful, and complete healing is uncommon, which necessitates active intervention. TCs are conventionally used as first-line therapy in cutaneous LP, but high-level scientific evidence is conspicuous by its absence. However, TCs show good results in oral LP, and the evidence has been summarized below [Table 5].[96979899]

Table 5

Evidence in favor of using topical corticosteroids in lichen planus

There is no evidence in favor of prescribing TCs in cutaneous LP although it is widely accepted as the first-line treatment for the same.[110] This an indicator of the fact that, like several other more uncommon inflammatory dermatoses, in LP too, the use of TCs is fairly undocumented, but not necessarily unwarranted, as the advent of TC as a group of agents happened in the age of empiricism when the use of medicines was dictated by hypothetical reasoning rather than being guided by evidence generated from RCTs.

Only limited evidence exists for the efficacy of TCs in oral LP. In addition, there is no evidence that topical calcineurin inhibitors are more effective than TCs in oral LP.[111]

Mycosis fungoides

The most common form of cutaneous T-cell lymphoma is mycosis fungoides (MF), which accounts for approximately 60% of cases. Several reviews and guidelines on the management of MF have been published. TCs have been used in the treatment of mild, patch stage MF with good results,[112] but unfortunately, evidence in favor of using them, is lacking.[113] The current evidence-based recommendation is: TCs, especially Class I (potent) compounds, are effective at temporarily clearing patches and plaques in some patients with early-stage IA/IB MF.

Bullous pemphigoid

Bullous pemphigoid (BP) is an acquired common autoimmune blistering dermatosis characterized by the development of autoantibodies against the components of the basement membrane zone of the skin. Interestingly, superpotent topical steroids have emerged as a first-line therapy for limited disease.[114] Two randomized clinical trials have been published in favor of topical steroids, and the summary has been tabulated as under [Table 6].

Table 6

Evidence in favor of using topical corticosteroids in bullous pemphigoid

The two RCTs suggest the use of TCs as the first line for the treatment for both localized and mild disease. Relatively, few and mild side effects are associated with TC use in BP; however, their use in extensive disease may be limited by more side effects and practical factors.

Cutaneous sarcoidosis

Sarcoidosis is a granulomatous disease with multisystem involvement. Topical high potency fluorinated corticosteroids (with or without occlusive dressing) have been successfully used in localized cutaneous sarcoidosis, but high-level scientific evidence is lacking.[117118]

Hand eczema

Chronic hand eczema is an extremely common and notorious entity encountered by general physicians and dermatologists. Currently, evidence-based guidelines for the management of this condition is lacking. However, there a few randomized clinical trials favoring the use of TCs [Table 7].

Table 7

Evidence in favor of using topical corticosteroids in hand eczema

There is insufficient data on which to base a choice between short bursts of potent TCs compared with continuous application of mild TCs. There is little evidence of steroid-sparing effect of emollients. There is an insufficient evidence of an additive effect of topical antibacterial agents. In addition, there is a lack of data supporting the superiority of topical calcineurin inhibitors to TCs.[122]

Infantile hemangiomas

Superficial infantile cutaneous hemangiomas are difficult to manage. Two small case series using ultrapotent TCs for periocular hemangiomas have been reported. However, evidence in favor of using this therapy for other sites is lacking. Garzon et al. assessed the cessation of growth, shrinkage or flattening of the lesion, and lightening of the surface color. Seventy-four percent of the cases demonstrated either good or partial response to ultrapotent TCs.[123] In another study by Pandey et al., mometasone was applied twice daily and compared with intralesional triamcinolone acetonide injections at monthly intervals at 1–2 mg/kg. Topical steroids were found to be a good alternative to intralesional steroids for treating superficial hemangiomas.[124]

Miscellaneous Conditions

Alopecia areata

One RCT demonstrated that potent TCs are marginally more effective than placebo when used continuously for a minimum of 3 months. In observational case series, children between the ages of 3 and 10 years appear most likely to respond.[125]

Anogenital pruritus

In idiopathic cases, TCs may be helpful, but they may mask malignancy and other underlying disease.[126]

Cutaneous lupus erythematosus

All the controlled trials of TC were of short duration, but the evidence supports the use of potent TCs in DLE (Discoid lupus erythematosus). Although TC use may be associated with skin atrophy, it is probably not important in DLE, which produces severe scarring and atrophy in itself.[127]

Melasma

There have been one systematic review[128] and one trial of 17 participants followed for 3 months.[129] Although the study reports that betamethasone was effective as a depigmenting agent (P < 0.05), the numbers were very small, and seven of 16 women in the study found no therapeutic difference between treatment and placebo. There is controversy over the balance between benefits and harms of using TCs in the treatment of melasma, especially since long-term use on the face can cause skin thinning and telangiectasia.

Perioral dermatitis

There is insufficient evidence (level of evidence: D) on the effects of nonfluorinated steroids in patients with perioral dermatitis. A split-face RCT of hydrocortisone butyrate versus 1% hydrocortisone alcohol cream is available.[130] Two patients with perioral dermatitis showed a moderate rebound of the eruption after withdrawal of topical treatment, in each case on the hydroxybutyrate-treated side of the face. In view of the study design and the small number of patients, it is difficult to draw conclusions.

Seborrheic dermatitis

Even though, TCs are considered to be the first line therapy for the management of seborrheic dermatitis, but, there is absence of high-level evidence supporting the use of TCs. Studies have shown that steroids are superior to placebo in the treatment of mild to moderate seborrheic dermatitis. Besides, there were no statistically significant differences between steroids and calcineurin inhibitors in terms of the assessed outcomes in a few studies. In addition, no statistically significant differences were found between steroids and azoles in their effectiveness in producing total clearance of lesions of seborrheic dermatitis.[131]

Pregnancy and Lactation

Women with skin conditions often need TCs during pregnancy. However, the knowledge about the effects of TCs on the fetus is scarce. The current best evidence supports the use of mild-to-moderate TCs in comparison to potent/superpotent alternatives in pregnancy because of the associated risk of fetal growth restriction with the latter. There is no significantly increased risk of orofacial clefts, preterm delivery, growth retardation, and fetal death when mild-to-moderate TCs are used in pregnancy. However, it must be noted that potent or superpotent TCs should be used as second-line therapy only for the shortest possible duration. Whenever high potency corticosteroids are used, meticulous obstetric care is mandatory because they increase the likelihood of low birth weight baby. Depending on the severity of the dermatoses, women should use TCs of the least potency required, and the duration and amount of application of the drug must be monitored judiciously. The risk of adverse events is increased when areas with high absorption (genitals, eyelids, skin folds, armpits, and vulva) are treated with topical steroids. There is lack of evidence regarding the safety profile of newer lipophilic TCs (mometasone furoate, fluticasone propionate, and methylprednisolone aceponate) with a good therapeutic index. On theoretical grounds, these should be associated a lesser risk of low birth weight, but high-level scientific evidence is lacking, and it is not possible to comment on the adverse effect profile of these newer congeners.[132133134135]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Twice-weekly application of potent topical corticosteroids (TCs) in stable eczema significantly reduces the number of flares. Moreover, skin thinning and suppression of the pituitary – adrenal axis are not seen if TCs are used judiciously and appropriately

Class III TCs are highly effective in the management of generalized or localized stable vitiligo. Long-term use must be avoided because of the risks of steroid-induced adverse effects

Both Class III and Class IV TCs are effective in inducing remission in psoriasis (both scalp and nonscalp)

TCs are widely used as first-line therapy in cutaneous lichen planus (LP), but high-level scientific evidence is categorically absent. There is not a single-randomized controlled trial (RCT) supporting the use of TCs in cutaneous LP. However, there are evidence in favor of prescribing TCs in oral LP

Interestingly, TCs have emerged as the first-line treatment for both localized and mild bullous pemphigoid

In chronic hand eczema, TCs have been found to be beneficial, but the choice between short bursts of potent TCs versus continuous application of mild TCs, is difficult, due to lack of evidence

Evidence in favor of using TCs in mycosis fungoides, cutaneous sarcoidosis, infantile hemangiomas, seborrhoeic dermatitis is lacking

In pregnancy and lactation, mild-to-moderate TCs can be safely prescribed, without the fear of associated risk of preterm labor and fetal growth restriction, provided TCs are not applied for a long duration and over areas with high absorption rates. Potent or superpotent TCs should be used only as second-line therapy because of risk of developing low birth weight baby.