Steroids represent a mainstay in dermatologic therapy. For decades, multiple steroids have been used in various manners to treat a range of diseases and inflammatory disorders. While they are generally beneficial to patients, clinicians and researchers have learned of potential adverse effects of corticosteroid use that are important to consider when prescribing these agents. Furthermore, effective alternative and adjunct therapies have emerged. At the 2010 Winter Clinical Dermatology Conference in Hawaii, several experts shared insights on use and application of steroids and the overall management of patients with steroidresponsive dermatoses. This article compiles a number of clinical pearls from the conference.
Maintenance Therapy with TCIs
Topical calcineuron inhibitors (TCIs) as an alternative to topical corticosteroids are still a treatment of interest. Interestingly, data show that use of tacrolimus 0.1% ointment (Protopic, Astellas) as an intermittent maintenance therapy reduced exacerbations and was cost-effective, compared to vehicle.1 As noted by Amy Paller, MD, the study found over a 12-month period a significant reduction in the incidence of AD flares among adults who applied tacrolimus two times per week compared to those who applied the ointment vehicle only. Utilization costs were lower in the active maintenance group.
An additional clinical benefit of TCIs, Dr. Paller noted, is that they serve as an alternative to corticosteroids that may improve compliance (and subsequently response) among patients who express safety concerns about topical corticosteroids.
Barrier Care and Repair
Barrier function has been a topic of significant interest in recent years in dermatology, particularly in relation to topical steroids. Dr. Paller observed that topical corticosteroids compromise barrier function within two to three days of use. They decrease epidermal proliferation and differentiation, decrease synthesis of lipids and lipid lamellae, and increase kallikrein expression. Dr. Paller also observed that, while the concomitant steroid-induced suppression of inflammation leads to improvement of dermatoses, patients usually rebound if corticosteroid therapy is stopped.
Enter barrier care agents. Importantly, barrier care agents are classified as medical devices rather than drugs, noted Linda Stein Gold, MD. She observed that barrier enhancing agents do not achieve their intended used through chemical reaction. Instead, according to FDA designation, they are classified among devices intended for diagnosis, cure, mitigation, or prevention of disease by affecting the structure or any function of the body. Therefore, clinical trials may not always be required for a barrier agent to be on the market.
James Q. Del Rosso, DO noted that there are two elements of barrier care: barrier repair (the treatment of skin disease) and barrier protection (preventing skin disease). Barrier repair constitutes the replenishment of the intercellular lipid membrane. According to Dr. Del Rosso, barrier repair creams are typically ceramide-based topical emulsions that maintain hydration of the stratum corneum and reduce TEWL.
Barrier Repair. Barrier repair creams are ceramide-rich formulations that restore the skin barrier by replacing lipids. According to Dr. Stein Gold, Mimyx (Stiefel) has been shown to reduce AD flares when used along with steroids, to prolong remission, and to reduce steroid use by 62 percent.2,3 Other barrier repair creams include Atopiclair (Graceway), which has been shown to improved EASI scores and decrease the need for rescue steroids,4 Eletone (Ferndale), and EpiCeram (Promius), which has been shown to confer similar efficacy to fluticasone propionate cream.5 In a 28-day study, patients applied either EpiCeram to body and face twice-daily or fluticasone propionate 0.05% cream to body and hydrocortisone 2.5% cream to face twice daily. By day 28, patients receiving EpiCeram experienced a 56 percent SCORAD reduction, as compared to fluticasone-treated patients who experienced a 67 percent reduction reduction. In addition, EpiCeram-treated patients had a 59 percent reduction in pruritus at 28 days, while fluticasone- treated patients saw a 66 percent reduction in pruritus. Finally, 74 percent of the EpiCeram group had reduced sleep disturbance, as compared to 88 percent of fluticasone-treated patients.
Barrier Protection. According to Dr. Del Rosso, barrier protection agents reduce contact allergy and irritation by blocking exposure. Barrier protection agents reduce positive patch tests in patients with known sensitivity, he noted, and are known for having very low irritancy potential and not exacerbating dermatitis, he said.6
Tetrix (Coria) is an aluminum-magnesium hydroxide stearate-based barrier protection cream indicated to manage and relieve burning associated with eczematoses, according to Dr. Del Rosso. In a 21-day cumulative irritation study,6,7 Tetrix received a mild rating under semi-occlusion and rated lower than negative control. It also protected against common allergens and improved contact dermatitis. Moreover, the study showed that substantivity is established just 15 minutes after handwashing.
Corticosteroids in Psoriasis
Cutaneous Atrophy Risks. Potent corticosteroids are associated with adverse events, such as cutaneous atrophy in the treatment of psoriasis.9 Mark Lebwohl, MD observed that tazarotene (Tazorac, Allergan) has been shown to reduce the effects of steroid-induced epidermal atrophy.
Intertriginous Psoriasis. To treat psoriasis of the face and intertriginous areas low-potency fluticasone propionate ointment 0.005% may be a reasonable option, according to Dr. Lebwohl. In one study, he said, patients experienced significant results with fluticasone treatment at two weeks, and recurrence rates were lower on face and intertriginous areas.
Corticosteroid Compatibility with Vitamin D Therapies. Given the recent interest in topical vitamin D analogues, compatibility with other topical medications, such as corticosteroids, still linger. The effects of pH and temperature influence the stability of calcipotriene (Dovonex, Leo Pharma), Dr. Lebwohl said, and he noted that the agent is not compatible with many corticosteroids (hydrocortisone valerate ointment is an example).10 However, data indicate that using calcipotriene with a potent steroid often yields more significant results than does either agent alone.11 Calcipotriene ointment and halobetasol ointment in combination have also been shown to offer significant improvement in long-term psoriasis.12
Clobetasol Spray (Clobex, Galderma) combined with calcitriol (Vectical, Galderma) was found to clear or almost clear psoriasis in 80 percent of patients at week 2 and in 94 percent of patients at week 4.13 Dr. Lebwohl also noted that a study presented at the 2007 AAD meeting regarding the chemical stability of topical psoriasis medications indicated that calcitriol and Clobetasol are compatible.14
Dealing with Non-compliance
A major factor in the success of all topical therapeutic regimens, particularly topical treatments, is compliance. Dr. Paller therefore recommended that physicians review use of medications with patients at each visit rather than assume that the patient is or is not taking the medication. Reviewing medications frequently also allows repetition that may affect patient's willingness to take the medications. Also helpful, according to Dr. Paller, is to ask the patient to bring the medication to each visit. Finally, Dr. Paller suggested the possibility of employing “patient logs,” so that the patient becomes used to administering medication consistently.
Importantly, explore reasons for treatment failure when patients are not compliant with therapy, Dr. Paller urged. There are many reasons for non-compliance, from insufficient parent involvement, avoidance of conflict, and the nature of the medication itself. That's why she suggested that physicians should maintain a more positive approach and empower patients and families to be more pro-active about taking medications and maintaining health.
Corticosteroids are a mainstay in themanagement of various dermatoses, but adjunctive and alternativetherapies are important. For maintenance therapy in AD, TCIs may be costeffectiveand provide good long-term results. In psoriasis, agents such astazarotene can reverse steroid-induced atrophy, while additional of topicalvitamin D analogues can provide enhanced efficacy. The notion of BarrierCare (Barrier Repair and/or Barrier Protection) continues to gain prominence,with data showing that a topical hand protectant can reduce the incidenceof contact dermatitis. Patient/family education, patience, and frequentregimen review may be key to long-term therapeutic compliance.
Glucocorticoids and Hemangiomas
There is rising interest in glucocorticoids as a potential therapy for conditionsvarying from alopecia to hemangiomas. June K. Robinson, MD presented data onthe low risk of adrenal insufficiency following systemic glucocorticoid therapy ininfants with hemangiomas.8 In an 18-month study of 16 infants treated with systemicglucocorticoids for hemangioma matched with 10 healthy controls, treatedpatients received prednisone at a starting dose of 2-3mg/kgd for four weeks, followedby a tapering period. The mean duration of GC treatment was 7.2 months.Results showed that just one out of the 16 patients had adrenal insufficiency bycorticotropin testing.
Case Report: Using a Skin Barrier Treatment asFirst Line Monotherapy for Severe Atopic Dermatitis
By Ellen Frankel, MD and Amylynne Frankel, MD
Atopic dermatitis is a chronic, cyclical, inflammatory skin conditionidentified by pruritus, typical lesion morphology and distribution,family history, and relapsing course.1 Prevalence of atopicdermatitis is estimated between 16 to 23 percent of school childrenand three percent of the total population of the UnitedStates.2 In practice, topical corticosteroids are the standard ofcare in managing the inflammation of atopic dermatitis, but problemswith their usage, such as cutaneous complications, HPA axissuppression, and tachyphylaxis, limit the long-term use of theseagents.3 Additionally, emollients are the standard of care in maintenanceand prevention therapy and have been proven steroidsparing.3 However, there is a lack of evidence evaluating theeffectiveness of emollients as first line monotherapy in inflammatoryconditions.3
Recent research indicates that atopic patients have a geneticpredisposition for epidermal barrier dysfunction that allows easypenetration of irritants/allergens and excessive transepidermalwater loss (TEWL); inevitably leading to pruritus and inflammation.4Clinically, many patients describe their acute flares as a period ofsevere pruritus followed by atopic manifestations (i.e., rashes),thus supporting the aforementioned hypothesis. For this populationof atopic patients, it may be appropriate to focus treatment effortson restoring epidermal barrier function, relieving itch, and replenishinghydration to the stratum corneum.
In recent corneometry and TEWL analysis, three commerciallyavailable, prescription-strength barrier therapies were evaluated: ahyaluronic acid based emollient foam (Onset Therapeutics), aceramide-rich emulsion (Promius Pharmaceuticals), and a PEA-containingcream (Stiefel Laboratories). All three products were similarlyeffective in reducing transepidermal water loss, but their abilityto deliver rapid and sustained hydration was distinctive (Figure 1).6This article describes the first case report using a prescription strength emollient as a first linemonotherapy treatment for a patientwith severe atopic dermatitis.
An eight-year, two-month oldCaucasian male presented with severeatopic dermatitis. The patient's parentreported the child's tumultuous historyof atopic dermatitis since an early ageof two months. Most recently, thepatient's severe pruritus was ineffectivelytreated with hydroxyzine hydrochloride (antihistamine) andaluminum acetate (astringent solution) by his pediatrician. Thepatient's mother expressed frustration with the failure of previoustreatments and was alarmed by the level of severe excoriation andlichenification that had resulted from incessant scratching over thepast several weeks. Despite reporting a moderate level of pain, therewas no mention of sleep disruption. Given the history of failure withmultiple topical therapy regimens, including topical steroids andtopical immunomodulators, a decisionwas made to try a different topicalbasedapproach.
On physical examination, thepatient had a body surface areainvolvement of 18 percent, with severeoozing, crust, and excoriation.Furthermore, the patient suffered frommoderate papulation, lichenification,and dryness, resulting in a SCORAD of55.4 and investigator global assessmentof “severe” (5 out of 6). Thepatient's guardian was instructed to discontinue all previous treatmentsand was prescribed a new regimen. A nonsteroidal, pH-neutral,hyaluronic acid-based emollient foam (Onset Therapeutics),was prescribed for twice daily (or as needed) use. (Figure 2)
After two weeks of therapy there, was marked improvement inalmost every clinical sign of atopy (papulation, oozing/crust, excoriation,and lichenification), a 2-point improvement in investigatorglobal assessment to “mild” (3 out of 6), and a 48 percent reduction in SCORAD. This improvement continuedwith a 79.1 percent reduction in SCORADafter four weeks of treatment, advancingrecovery to an IGA score of “almostclear” (2 out of 6) with only one percentof the total body surface area affected.(Figure 3) The treatment was effective inreducing most clinical signs of atopy,however erythema was only marginallyaffected.
After two weeks, the patient's motherreported a 79.3 percent reduction in hisitch, using a visual analogue scale.Furthermore, the guardian noted that thetwo-week improvement was “excellent”as the new regimen achieved “good control”of her son's eczema while eradicatingthe previously reported pain. Herenthusiasm for the regimen continuedafter four weeks of treatment with highsatisfaction ratings and a 93.1 percentreduction in itch VAS. (Figure 4)
Atopic dermatitis is a common, chronicrelapsing inflammatory condition thatoften affects children. Topical corticosteroidsare the gold standard in managingthe inflammatory lesions of atopy,but there are several reasons an alternativeapproach may be necessary.There are risks associated with corticosteroiduse over long periods, forlarge body surfaces and intertriginous regions. Furthermore, arecent study reveals that during an active atopic flare, corticosteroidshave a positive affect on improving barrier function, but duringan atopic remission, corticosteroids can be detrimental to epidermalbarrier function as they can promote barrier breakdown.5 Ifcontemporary opinion indicating that epidermal barrier dysfunctionis the fundamental precursor to the pruritus and inflammation ofatopic dermatitis holds true, then there is a need for clinicallyproven therapeutic alternatives.
Recently, barrier therapy has emerged as an effective adjuncttreatment for patients with active atopic dermatitis. An effectivebarrier therapy should establish a superficial barrier that protects against potential irritants/allergens,normalizes transepidermal water loss,restores stratum corneum hydration,and supports the skin's natural recoveryfrom barrier dysfunction.
This article reports the first case ofusing a new, hyaluronic acid-based,pH-neutral, nonsteroidal emollientfoam as a first line monotherapy forsevere atopic dermatitis. The patientpresented with widespread, severeatopic dermatitis. Following four weeksof treatment, the patient was almostclear of all signs of atopy. While thepatient's mild erythema was unaffectedby the treatment, the severe pruritus(excoriation) and moderate lichenification,papulation, oozing/crust, and drynesswhere significantly improved.
Although more clinical work is needed,the positive therapeutic outcome inthis patient suggests that barrier treatmentsmay be a safe and effectivealternative for first line, monotherapytreatment of atopic patients with milderythema and severe clinical manifestationsof pruritus.
Dr. Ellen Frankel has received honorariafrom Medicis, Candela, Amgen,Wyeth, and Onset. Dr. AmylynneFrankel has no financial interests toreport.