Topical Management of Recalcitrant Psoriasis and Eczema

Richard M. Haber, MD, FRCPC

Division of Dermatology, University of Calgary, Calgary, AB, Canada
Reprinted from Skin Therapy Letter FP 6(3):1-4 (December 2010) due to content update

Introduction

Psoriasis and eczema, especially atopic eczema, are two of the most common cutaneous conditions seen by family physicians and dermatologists. Although the etiology of both conditions is unknown, immunologic abnormalities with an increase in immune mediators are thought to play major roles. These skin disorders are not curable, but can be controlled with proper topical therapy. However, psoriasis and eczema can at times be recalcitrant to conservative topical treatment. As such, it may be helpful for family physicians to be aware of more aggressive or innovative topical options for recalcitrant cases. Patients unresponsive to aggressive topical therapy may require systemic treatment or phototherapy, which carry a greater potential for adverse effects. Such cases are best managed by dermatologists with more experience in using these therapies.

Overview of Topical Corticosteroids

Due to their anti-inflammatory, immunosuppressive, and antiproliferative properties, corticosteroids are effective for treating a variety of inflammatory dermatoses, including psoriasis and atopic eczema.

Potency

• • • • The potency rating of a topical corticosteroid describes the intensity of the agent’s clinical effect

¹

• • • .

Seven groups of topical steroid potencies have been developed, these are ranked from superpotent (Group 1) to low potency (Group 7). Table 1 lists the topical corticosteroid potencies and gives available examples in Canada.

Vehicle Considerations

• Ointments are water-in-oil emulsions and are more hydrating to the stratum corneum. They provide an occlusive barrier, and because of an increased depot effect, drug penetration is enhanced, leading to greater potency.
  • For example, Table 1 shows the same chemical compound, triamcinolone acetonide 0.1%, can be Class 4 potency as an ointment, but only Class 5 as a cream. Therefore, an ointment can be useful in treating refractory dermatoses, especially for thick, fissured, and lichenified skin lesions.

Administration and Dosing

• Localized recalcitrant conditions may benefit from using a corticosteroid ointment under occlusion (e.g., plastic wraps and hydrocolloid dressings), which can increase the drug permeability up to 10 times.²
• Topical corticosteroids are usually applied once or twice daily. The duration of daily use of ultra-potent formulations should not exceed 3 weeks.³ Medium and high strength topical corticosteroids can be used up to 3 months.³ It can be difficult to adhere to these guidelines, as psoriasis and atopic eczema are chronic, requiring long-term therapy.
• In general, it is best to treat active disease more aggressively and then taper to the lowest strength that can maintain disease control.
• Use of superpotent topical corticosteroids should not exceed 50 grams per week in order to avoid excessive absorption and adrenal suppression.

Adverse Effects from Overuse or Prolonged Use

• Risks from long-term topical corticosteroid use include tachyphylaxis – a diminished pharmacologic response after repeated drug administration.¹
• There is a potential for rebound – a severe exacerbation of the dermatosis after abrupt discontinuation.4
• Systemic complications include suppression of the hypothalamic-pituitary axis, hyperglycemia, Cushing’s syndrome, and avascular necrosis.⁴
• Local adverse effects associated with prolonged use of potent topical corticosteroids include skin atrophy, striae, purpura, telangiectasia, acneiform eruptions (steroid-induced acne, perioral dermatitis, and rosacea), hypopigmentation, and hypertrichosis.⁴

Topical Treatments for Psoriasis

Psoriasis vulgaris is a common, chronic, inflammatory skin disease affecting 2% of the population.⁵ Most psoriatic patients have limited disease (>5% body surface area) and can be successfully treated with topical agents.⁵ Plaque psoriasis (PPs) and psoriasis involving the scalp, palms or soles can be particularly refractory to topical therapy.

Topical agents used to treat psoriasis include corticosteroids, vitamin D analogue (calcipotriol), retinoids (tazarotene), tar, anthralin,⁶ salicylic acid, and topical calcineurin inhibitors (TCIs). Also, combination therapies are available and may be useful because of their increased potency, decreased side-effects, and increased adherence due to less frequent dosing. A systematic review of topical treatments for chronic PPs included 131 randomized controlled trials with 21,448 participants concluded:⁷

• Vitamin D analogue (calcipotriol) was significantly more effective than placebo.
• Potent (betamethasone dipropionate) and very potent (clobetasol propionate) topical corticosteroids were better than placebo, with very potent preparations working better than weaker ones.
• Dithranol (anthralin) and tazarotene worked better than placebo.
• Combination therapies with a vitamin D analogue (calcipotriol) and a potent corticosteroid were more effective than either product alone.
• Potent topical corticosteroids were less likely than calcipotriol to cause local adverse events.

Recalcitrant Plaque Psoriasis

For recalcitrant PPs, a well-tolerated first-line regime would normally be a combination of a vitamin D analogue (calcipotriol) and potent steroid (betamethasone dipropionate 0.05%) applied daily at bedtime.

• Resistant patients can also be treated with a potent corticosteroid, such as clobetasol propionate 0.05% cream or ointment, twice daily for 2-3 weeks.
  • Use of a potent corticosteroid as “intermittent pulse dosing” may be helpful as a maintenance regimen.⁸
  • In this regimen, after clearing the patient with the potent steroid, remission is maintained with continued use of the potent steroid, using it for 3 consecutive doses at 12-hour intervals once weekly.
  • A study using betamethasone dipropionate glycol 0.05% with this regimen extended remission to 6 months in 60% of patients.⁹ No serious local or systemic side-effects were observed.
• A new treatment that may be effective for recalcitrant PPs of the body is clobetasol propionate 0.05% spray.
  • In a randomized double-blinded vehicle-controlled study of moderate to severe psoriasis, 75% of patients were reported to be clear or almost clear at 4 weeks following twice daily use of the spray.¹⁰
  • There were no reports of hypothalamic-pituitary-adrenal suppression and patients showed reductions in scaling, erythema, and plaque elevation.
• Calcipotriol + betamethasone dipropionate ointment, clobetasol propionate ointment, followed by pulsed therapy, or clobetasol propionate 0.05% spray could be tried for recalcitrant psoriasis on the palms and soles.
  • Very potent steroids can be used on the palms with little risk of atrophy. Superpotent steroids have been used under occlusion on palms and soles with good results.¹¹
• Tazarotene cream or gel can be used as monotherapy, but this retinoid is often used in combination with a topical steroid, such as mometasone furoate 0.1% cream, to reduce skin irritation, which is the major side-effect of tazarotene.
  • Tazarotene 0.1% gel once daily in combination with mometasone furoate 0.1% cream once daily has been shown to be more effective than calcipotriol ointment twice daily or mometasone furoate 0.1% cream twice daily.¹²

Scalp Psoriasis

For recalcitrant scalp psoriasis, the following treatments could be considered:

• Salicylic acid 3% + betamethasone dipropionate 0.05% lotion may be helpful as the salicylic acid has been shown to increase penetration of the topical steroid.¹³
• A new gel formulation containing calcipotriol + betamethasone dipropionate 0.05 % can be very helpful for moderate to severe scalp psoriasis.¹⁴
• A clobetasol propionate 0.05% shampoo applied to the scalp for 15 minutes and then lathered and shampooed out can be effective for difficult scalp psoriasis.¹⁵
• Another option is fluocinolone 0.01% in a peanut oil base that is applied to the scalp under a shower cap at bedtime and washed out the next morning.

Topical Treatment Suggestions for Recalcitrant Psoriasis

Plaque Psoriasis (excluding face and body folds)

• Calcipotriol + betamethasone dipropionate ointment (e.g., Dovobet™)
• Pulsed superpotent topical corticosteroids, such as clobetasol propionate or halobetasol propionate 0.05% (e.g., Ultravate®) ointment/cream used twice daily Saturday and Sunday
• Clobetasol propionate spray (e.g., Clobex™)

Palms and Soles

• All treatments suggested for plaque psoriasis (above) can be tried
• Superpotent topical corticosteroid with saran wrap or hydrocolloid occlusion overnight
• Topical tazarotene 0.1% cream/gel once daily +/– topical mometasone furoate 0.1% cream once daily

Scalp Psoriasis

• Betamethasone dipropionate + salicylic acid lotion (e.g., Diprosalic™)
• Calcipotriol + betamethasone dipropionate (e.g., Xamiol™ gel)
• Clobetasol propionate shampoo (e.g., Clobex™)
• Fluocinolone acetonide topical oil 0.01% (e.g., Derma- Smoothe/FS®)

Dosing Strategies for Protracted Remission

• Typically, Class 1 topical steroids are prescribed for rapid clearing in acute flares. Following initial control of psoriasis with a superpotent topical steroid, weekend-only therapy has been demonstrated to be extremely beneficial in maintaining long-term remission.^16-19
• With the aim of prolonging the initial therapeutic response while limiting the risks associated with extended corticosteroid use, a recent randomized, double-blind, placebo-controlled study of mild to moderate psoriasis assessed the safety and efficacy of a combination regimen of initial short course superpotent corticosteroid (halobetasol ointment 0.05%) followed by long-term weekend-only use to previously affected sites of psoriasis.¹⁶ Twice daily adjunctive therapy with a moisturizer (ammonium lactate lotion 12%) was added to enhance the steroidal component of treatment and minimize potential localized skin reactions.
  • Findings showed that the combination of twice daily halobetasol with the moisturizer for 2 weeks had excellent clinical efficacy with an absence of adverse effects.
  • Subsequent reduction in the dosing frequency of halobetasol ointment to weekend-only use (known as weekend or pulse therapy) while continuing twice daily emollient therapy maintained initial clinical efficacy for a longer duration when assessed at 12 weeks.
• The use of a second agent, such as calcipotriol ointment, applied on weekdays in combination with a weekend-only regimen of halobetasol ointment has also been shown to increase the duration of remission versus weekend-only halobetasol alone when assessed at 6 months.¹⁹

Topical Treatment of Eczema

Atopic Eczema (AE)

AE is a chronic, pruritic, relapsing inflammatory skin disease.²⁰ The lifetime prevalence is estimated to be between 10-20% in children and 1-3% in adults.²¹

• The topical treatment approach includes reducing inflammation with topical corticosteroids or TCIs (i.e., tacrolimus or pimecrolimus).
• AE patients have a skin barrier abnormality,²² as such, regular daily use of moisturizers to decrease transepidermal water loss is important. Recently, barrier repair creams²³ have become available for improving the skin barrier function. In an investigator-blinded, randomized trial of moderate to severe AE, a barrier cream reduced clinical disease and pruritus at 28 days of treatment comparably to fluticasone propionate 0.05% cream, a Class 5 corticosteroid.
• Avoidance of external irritants (e.g., harsh soaps, strong laundry detergents, and wool clothing) is beneficial.

Topical corticosteroids are the treatment of choice for AE; selection depends on disease severity and treatment site.

• For milder AE of the face and body folds, mild to moderate steroids (Class 6 or 7) are commonly used.
• For more severe AE and eczema on the trunk and extremities, more potent corticosteroids may be necessary (Class 4 or 5), but are best used only for a few weeks, then tapered to a milder preparation for maintenance. Generally, ointments work better than creams.
• Once the pruritus and thickness are controlled, switching to a TCI, such as tacrolimus ointment (0.03% for ages 2-15, 0.1% for >15 years), is very useful and helps to minimize side-effects from corticosteroids.
• If potent topical steroids are needed for long duration, consider pulse application at 1-2 times weekly dosing.

Chronic Hand Eczema (CHE)

CHE is a common condition and irritant dermatitis is more prevalent than allergic dermatitis. Early-onset hand eczema may be associated with atopy.

• A recent consensus statement on the management of CHE²⁴ suggested that topical therapy should include corticosteroids and TCIs.
• There is evidence of efficacy for long-term intermittent monotherapy with mometasone furoate cream.²⁵
• For very refractory hand eczema, especially on the palms, superpotent topical corticosteroids can be helpful and sideeffects, such as atrophy, are unusual when used on thick palmar skin.
• Möller²⁶ found the risk of recurrence of CHE was reduced by the very potent corticosteroid, clobetasol propionate, when used on an intermittent schedule of 2 applications a week, compared with a moderately potent corticosteroid cream.

Lichen Simplex Chronicus (LSC)

LSC is characterized by lichenification of the skin as a result of primary excessive scratching or rubbing.²⁷

• When treated topically, often potent corticosteroid creams or ointments, such as betamethasone dipropionate, are necessary to control the pruritus and inflammation and to break the “itch-scratch” cycle.
• The use of potent topical corticosteroids under occlusion may be needed for successful treatment.
• Topical tacrolimus has been reported to be effective.²⁸

Topical Treatment Suggestions for Recalcitrant Eczema

Atopic Eczema (excluding face and body folds)

• Potent topical corticosteroids for 2-3 weeks followed by tapering to a milder topical corticosteroid or TCI (i.e., Protopic™ ointment or Elidel® cream)
• Pulsed potent topical corticosteroid (i.e., fluocinonide 0.05% ointment/cream used twice daily Saturday and Sunday (use with caution in young children and if treating for longer than 2-3 weeks)
• Barrier repair creams (e.g., CeraVe®, EpiCeram®) can be tried in conjunction with topical corticosteroids or TCIs

Chronic Hand Eczema

• Superpotent topical corticosteroid for 2-3 weeks followed by tapering to a milder corticosteroid or TCI
• Superpotent topical corticosteroid with saran wrap or hydrocolloid occlusion overnight

Lichen Simplex Chronicus

• Superpotent topical corticosteroid for 2-3 weeks followed by tapering to a milder corticosteroid or TCI
• Superpotent topical corticosteroid with saran wrap or hydrocolloid occlusion overnight

References

1. Warner MR, Camisa C. Topical corticosteroids. In: Wolverton SE (ed). Comprehensive dermatologic drug therapy. 2nd ed. Philadelphia: Elsevier- Saunders, p595-624 (2007).
2. Feldmann RJ, et al. Penetration of 14c hydrocortisone through normal skin: the effect of stripping and occlusion. Arch Dermatol 91:661-6 (1965 Jun).
3. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for the use of topical glucocorticosteroids. American Academy of Dermatology. J Am Acad Dermatol 35(4):615-9 (1996 Oct).
4. Lee NP, Arriola ER. Topical corticosteroids: back to basics. West J Med 171 (5-6):351-3 (1999 Nov-Dec).
5. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 60(4):643-59 (2009 Apr).
6. Lebwohl M, Ting PT, Koo JY. Psoriasis treatment: traditional therapy. Ann Rheum Dis 64(Suppl 2):ii83-6 (2005 Mar).
7. Mason AR, Mason J, Cork M, et al. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev (2):CD005028 (2009).
8. Mikhail M, Scheinfeld. Evidence-based review of topical treatment for psoriasis. Adv Stud Med 4(8):420-29 (2004).
9. Katz HI, Prawer SE, Medansky RS, et al. Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica 183(4):269-74 (1991).
10. Jarratt MT, Clark SD, Savin RC, et al. Evaluation of the efficacy and safety of clobetasol propionate spray in the treatment of plaque-type psoriasis. Cutis 78(5):348-54 (2006 Nov).
11. Volden G. Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Derm Venereol 72(1):69-71 (1992).
12. Guenther LC. Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging. Skin Therapy Lett 7(3):1-4 (2002 Mar).
13. Lebwohl M. The role of salicylic acid in the treatment of psoriasis. Int J Dermatol 38(1):16-24 (1999 Jan).
14. van de Kerkhof PC, Hoffmann V, Anstey A, et al. A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Br J Dermatol 160(1):170-6 (2009 Jan).
15. Andres P, Poncet M, Farzaneh S, et al. Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis. J Drugs Dermatol 5(4):328-32 (2006 Apr).
16. Emer JJ, Frankel A, Sohn A, et al. A randomized, double-blind, placebocontrolled study to evaluate the safety and efficacy of ammonium lactate lotion 12% and halobetasol propionate ointment 0.05% in the treatment and maintenance of psoriasis. J Clin Aesthet Dermatol 4(2):28-39 (2011 Feb).
17. Katz HI, Hien NT, Prawer SE, et al. Betamethasone dipropionate in optimized vehicle. Intermittent pulse dosing for extended maintenance treatment of psoriasis. Arch Dermatol 123(10):1308-11 (1987 Oct).
18. Katz HI, Prawer SE, Medansky RS, et al. Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica 183(4):269-74 (1991).
19. Lebwohl M, Yoles A, Lombardi K, et al. Calcipotriene ointment and halobetasol ointment in the long-term treatment of psoriasis: effects on the duration of improvement. J Am Acad Dermatol 39(3):447-50 (1998 Sep).
20. Simpson EL. Atopic dermatitis: a review of topical treatment options. Curr Med Res Opin 26(3):633-40 (Mar 2010).
21. Leung DY, Bieber T. Atopic dermatitis. Lancet 361(9352):151-60 (2003 Jan 11).
22. McGrath JA. Filaggrin and the great epidermal barrier grief. Australas J Dermatol 49(2):67-73 (2008 May).
23. Sugarman JL, Parish LC. Efficacy of a lipid-based barrier repair formulation in moderate-to-severe pediatric atopic dermatitis. J Drugs Dermatol 8(12):1106-11 (2009 Dec).
24. English J, Aldridge R, Gawkrodger DJ, et al. Consensus statement on the management of chronic hand eczema. Clin Exp Dermatol 34(7):761-9 (2009 Oct).
25. Veien NK, Olholm Larsen P, Thestrup-Pedersen K, et al. Long-term, intermittent treatment of chronic hand eczema with mometasone furoate. Br J Dermatol 140(5):882-6 (1999 May).
26. Moller H, Svartholm H, Dahl G. Intermittent maintenance therapy in chronic hand eczema with clobetasol propionate and flupredniden acetate. Curr Med Res Opin 8(9):640-4 (1983).
27. Lotti T, Buggiani G, Prignano F. Prurigo nodularis and lichen simplex chronicus. Dermatol Ther 21(1):42-6 (2008 Jan-Feb).
28. Aschoff R, Wozel G. Topical tacrolimus for the treatment of lichen simplex chronicus. J Dermatolog Treat 18(2):115-7 (2007).