Overcoming Persistent Barriers to Effective Management of Atopic Dermatitis Jack B. Cohen, DO Clinical Professor Department of Dermatology UT Southwestern Medical Center Dallas, TX
Atopic Dermatitis I have no conflicts of interest to disclose. Off-label uses of medications will be discussed. I retain the rights to the clinical images. This CME presentation was supported by an educational grant from Sanofi-Genzyme Pharmaceuticals through UNT Health Science Center in conjunction with John Fling, M.D., Professor of Pediatrics.
Atopic Dermatitis Please DO NOT take pictures of the slides! It is distracting and they do not come out well anyway. A PDF handout is available online when you claim your CME credit.
Pre- Test Question 1 Atopic dermatitis: A. is often associated with allergic rhinitis and asthma. B. is caused primarily by food allergies. C. can be controlled by an elimination food diet. D. is caused by elevated IgE. E. is only seen in infants and children.
Pre- Test Question 2 Antihistamine use in atopic dermatitis: A. is essential to controlling the itch. B. as limited value in controlling itch. C. is the key to controlling histamine, the primary mediator of itch in atopic dermatitis. D. is best treated with the non-sedating antihistamines. E. is more frequently used in atopic dermatitis by specialists, compared to primary care physicians.
Pre- Test Question 3 The key to controlling atopic dermatitis is: A. Prescribing proper topical corticosteroids. B. Prescribing topical calcineurin inhibitors. C. Prescribing topical phosphodiesterase-4 inhibitors. D. Prescribing moisturizers. E. Education of the chronic nature of the condition and proper skin care.
Pre- Test Question 4 The most common reason for treatment failure in atopic dermatitis is: A. The topical corticosteroid is not potent enough. B. Topical corticosteroid phobia. C. Not bathing enough. D. Non-adherence to treatment. E. Adverse reactions to topical medications.
Pre- Test Question 5 Which of the following is true about systemic corticosteroid use in atopic dermatitis is true: A. Systemic corticosteroids are safe for long term use. B. Low doses of systemic corticosteroids can control atopic dermatitis. C. Rebound flares often occur after use. D. Systemic corticosteroids have a slow onset of action in atopic dermatitis. E. Intramuscular corticosteroids have a superior safety profile compared to oral corticosteroids.
Learning Objectives: Atopic Dermatitis To correctly diagnose atopic dermatitis and the differential diagnosis. To enact a treatment plan. To educate the patient and parents to the chronicity of the condition and need for consistent long term preventative factors and treatment. To identify and overcome barriers to successful control of atopic dermatitis.
Atopic Dermatitis Atopic dermatitis is common, affecting up to 20% of children and 3% of adults worldwide. There is wide variation in the incidence among countries and ethnic background. The incidence increased in the last few decades in developed countries, but stabilized recently. Adult-onset AD is not uncommon affecting between 11% and 13% of adults in some countries. Mei-Yen Yong A, Tay YK. Atopic Dermatitis: Racial and Ethnic Differences. Dermatol Clin. 2017;35:395-402.
Atopic Dermatitis **First barrier Get the diagnosis right!
Atopic Dermatitis Diagnosis: Atopic dermatitis is diagnosed on clinical signs and symptoms based on criteria outlined by Hanifin and Rajka. Major Features: Recurrent pruritus Early age of onset (60 %< 1 yr., 25%, 1 5 years old) Typical morphology and distribution Adults flexural lichenification and linearity Infancy and childhood facial and extensor involvement Chronic or chronically relapsing dermatitis Personal or family history of asthma, allergic rhinoconjunctivitis, atopic dermatitis. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis, Acta Derm Venereol Suppl (Stockh) 1980; 92:44-47
Atopic Dermatitis
Atopic Dermatitis
Atopic Dermatitis
Atopic Dermatitis Adult atopic dermatitis can be varied and subtle manifesting as hand dermatitis or lichen simplex chronicus.
Atopic dermatitis Familial atopic dermatitis 60% have 1 parent with AD. 80 % have both parents with AD. 50% have familial and personal tendencies toward allergic rhinitis. 25% have familial and personal tendencies toward asthma. Hanifin JM. Atopic dermatitis. J Amer Acad Dermatol. 1982;6:1-13.
Cutaneous minor features: Atopic dermatitis Skin signs of dryness xerosis, hyperlinear palms, keratosis pilaris, ichthyosis vulgaris Mid facial pallor Pityriasis alba Nipple eczema Chronic hand dermatitis Tendency for skin infections (S. aureus, HSV, molluscum) White dermatographism Allergic shiners Eyelid pleats (Morgan-Dennie folds) Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis, Acta Derm Venereol Suppl (Stockh) 1980; 92:44-47.
Xerosis and Ichthyosis Vulgaris
Hyperlinear Palms and Keratosis Pilaris
Atopic Dermatitis Morgan-Dennie folds Pityriasis alba Allergic shiners
Atopic Dermatitis Staph. aureus Infection **Mostly MSSA, not MRSA
Atopic Dermatitis with Molluscum
Atopic Dermatitis with HSV
Atopic dermatitis Extra-cutaneous minor features: Recurrent conjunctivitis Cataracts Keratoconus Other features that provoke itching: Wool intolerance Sweating causes pruritus Food intolerance Course influenced by emotional or environmental factors Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis, Acta Derm Venereol Suppl (Stockh) 1980; 92:44-47.
Atopic Dermatitis A common question: Is it something the child is eating? Is it an allergy to something in my diet? **Second Barrier: Overcoming the parent and patient tendency to blame food allergy!
Atopic Dermatitis Among 248 one-year-old children, the incidence of food allergy (hives, anaphylaxis) was 4% in children without AD and 13% in children with AD. During this period, the parents intentionally avoided giving at least one food to 23% of the children, yet more than 80% of these restrictions can be regarded as unnecessary. Yrjänä JMS, Bloigu R, Kulama P. Parental confusion may result when primary health care professionals show heterogeneity in their knowledge, attitudes, and perceptions regarding infant nutrition, food allergy, and atopic dermatitis. Allergol Immunopathol. 2018;17:Epub ahead of print.
Atopic Dermatitis 1186 double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies were performed in AD children. Positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food. Exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic. Roerdink EM, Flokstra-de Blok BM. Association of food allergy and atopic dermatitis exacerbations. Ann Allergy Asthma Immunol. 2016:116:334-8.
Atopic Dermatitis Retrospective study showed 2.8% (81) of the 2851 patients with food allergy (hives and anaphylaxis) developed AD, compared to only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD. Yu HS, Tu HP, Hong CH, Lee CH. Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy. Int J Mol Sci 2017;18:1-10.
Atopic Dermatitis Excessive restriction of suspected food allergies can lead to nutrition deficiency. Milk - lower Ca, Zn, and vitamin B2. Eggs - lower intake of vitamin A, B1, B2, niacin, and cholesterol. wheat and soybean - lower intake of Ca, P, Fe, K, Zn, vitamin B2, vitamin B6, and niacin. Beef, pork, and chicken - lower intake of Fe and higher intake of K, vitamin A, and B2. Kim J, Kwon J, Noh G, Lee SS. The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract. 2013;7:488-94.
Atopic Dermatitis My most useful criteria: Flexural dermatitis Recurrent itching and rash Family history Dry skin Personal history of asthma Wool or label intolerance
Atopic Dermatitis Differential Diagnosis: Infants: Seborrheic dermatitis, psoriasis, candidiasis, scabies, Wiscott-Aldrich synd., non-bullous congenital ichthyosis, ichthyosis vulgaris, congenital syphilis, histiocytosis X, biotin or zinc deficiencies. Adults: Seborrheic dermatitis, psoriasis, contact dermatitis, asteotic dermatitis, nummular dermatitis, tinea infection, drug eruptions, lichen planus, necrolytic migratory erythema, scabies, and mycosis fungoides.
Histology- non-specific. Atopic Dermatitis sub-acute spongiotic dermatitis to psoriasiform dermatitis (lichen simplex chronicus) depending on the chronicity of the rash. Eosinophils may be prominent. Most helpful to exclude mycosis fungoides* and psoriasis. *Repeat biopsies, gene re-arrangement study, and flow cytometry help.
Atopic Dermatitis Lab - Elevated serum IgE - 80%. Culture pustules and bullae. Tzanck smears and HSV cultures from umbilicated vesicles and punched out erosions. KOH any patch with an advancing edge of scale. Scrape burrows for scabies mites and ova.
Atopic Dermatitis Therapy The majority of patients with atopic dermatitis are able to be adequately controlled with combinations of : 1. Emollients 2. Topical corticosteroids (still mainstay of treatment) 3. Topical tacrolimus (Protopic) or pimecrolimus (Elidel) 4. Topical crisaborole (Eucrisa) 5. Oral antihistamines have limited value sedative effects. 6. Oral antibiotics for infections.
Potency does not equal efficacy! Selection of the topical steroid based on: 1. Intactness of the epidermal barrier 2. Sites 3. Extent 4. Age of the patient
Area of skin Steroid Potency Vehicle Dry, exposed areas Hands, Feet, or other thickened skin Intermediate to High Intermediate to Ultrapotent Ointment, Cream, or Foam Ointment, Emollient Cream, or Foam Scalp Intermediate to High Gel, Solution, or Foam Axilla Low Lotion or cream Face Low Cream Groin Low Cream Eyelids Low Cream or Ointment, May use an ophthalmic product
Topical Corticosteroid Side Effects Side effects correlate with the potency of the topical steroid and the length of time applied. Lotrisone x 1 year = atrophy, telangiectasia, and erythema.
Fluocinonide cream x 12 years for Atopic Dermatitis
After Discontinuing Fluocinonide cream X 10 years
Topical Corticosteroid Phobia Topical corticosteroid (TCS) phobia refers to the negative feelings and beliefs related to TCSs experienced by patients and patients' caregivers. Patients were receiving information about corticosteroids included physicians, friends and relatives, broadcast media, print media, and the internet. TCS phobia are commonly reported by patients across cultures and may be associated with a higher rate of non-adherence. Li AW, Yin ES, Antaya RJ. Topical corticosteroid phobia in atopic dermatitis: a systematic review. JAMA Dermatol. 2017 ;153:1036-1042.
Topical Calcineurin Inhibitors Tacrolimus (Protopic) ointment 0.1% or 0.003% and pimecrolimus (Elidel) cream 0.1% are approved non-steroid topical therapy to atopic dermatitis for age 2 and up. These bind to calcineurin and block its function as a transcription factor for numerous cytokines from T cells, including TNFα and interleukins 2, 3, and 4. Side effects: Burning at the application site is more with tacrolimus 0.1% (58%) than with 0.03% (29%) or pimecrolimus (11%).
Topical Calcineurin Inhibitor Phobia There were 990,000 annual visits for AD from 2003-2012 (3.2 visits/1000 people/year). TCS were the most frequently used medication (59% of visits). Topical calcineurin inhibitors (TCI) were the second most prescribed medication for AD among dermatologists (23% of visits), while antihistamines were second among all other physicians (16-44% of visits). Unlike other medications, use of TCIs decreased over time. He A, Feldman SR, Fleischer AB. Trends in atopic dermatitis management: comparison of 1990-1997 to 2003-2012. J Drugs Dermatol. 2018;17:135-140.
Phosphodiesterase 4 inhibitors The crisaborole (Eucrisa) treated group achieved ISGA scores of clear or almost clear with 2- grade improvement than in the vehicle-treated group at 29 days (Trial 1-32.8% vs. 25.4%, P = 0.38, Trial 2-31.4% vs. 18.0%, P < 0 001). Greater % of clear and almost clear scores were observed in the treatment groups (Trial 1-51.7% vs. 40.6%, P = 0.005; Trial 2-48 5% vs. 29 7%; P < 0 001). There was earlier success in ISGA score and improvement in pruritus (P 0 001). Ahmed A, Solman L, Williams HC. Magnitude of benefit for cisaborole in treatment of atopic dermatitis in children and adults does not look promising: a critical appraisal. Br J Dermatol. 2017 Dec 3. [Epub ahead of print]
Phosphodiesterase 4 inhibitors Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application seen in 4% (1% in placebo) of patients, as the only related adverse event. Zebda R, Paller AS. Phosphodiesterase 4 inhbitors. J Am Acad Dermatol. 2018 Mar;78(3S1):S43-S52 10 Epub 2017 Dec 15.
Atopic Dermatitis **Third Barrier - Education of the patient and their family members to control environmental factors such as local humidity, avoidance of sweating, avoidance of irritants and allergens, proper bathing and skin hydration, and stress reduction techniques.
Atopic Dermatitis Education methods: Pamphlets Physician time Nurse education Rady Children s Hospital Eczema Center website has a virtual curriculum for therapy education.
Atopic Dermatitis Therapy Educate the patient and/or parents: A. The condition is controllable but has a chronic, usually intermittent course. B. Atopic dermatitis is not infectious nor contagious, but secondary infections can occur. C. The condition is generally not diet related. D. The condition is not due to being unclean. Frequent washings with soap and water worsen the condition. E. The condition has a genetic disposition and often runs in families.
Atopic Dermatitis Therapy To bathe or not to bathe? Rehydration helps improve the epidermal barrier in AD, whereas evaporation worsens the skin damage. **Fourth Barrier Getting patients to bathe in only warm water!
Atopic Dermatitis Therapy Educate the patient and/or parents: 2. NO hot showers or bubble baths!! 3. Avoid soaps that dry the skin. 4. Switch to soap-free cleansers: Oil of Olay, Dove for Sensitive Skin, Cetaphil cleansing lotion or bar, Aveeno bar, or Cerave Cleansing lotion. 5. Limit time in bath to 5-15 minutes to hydrate skin in warm water. 6. Moisturize Moisturize Moisturize especially right after the bath while skin is still moist.
Atopic Dermatitis **Fifth Barrier Getting patients and their parents to apply emollients and/or medications immediately after showers or baths, while the skin is damp..consistently.
Atopic Dermatitis Therapy Cost savings with adequate moisturization is staggering. This is an often underappreciated aspect to management, relative to the high cost of prescription medication with much less potential side effects. Vaseline was the most cost effective of 7 moisturizers tested for prevention of AD development in high risk infants. Xu S, Immaneni S, Hazen GB, Silverberg JI, Paller AS, Lio PA. Cost-effectiveness of Prophylactic Moisturization for Atopic Dermatitis. JAMA Pediatr. 2017.6;171: Epub 2017 Feb 6.
Atopic Dermatitis Therapy Even moderate to severe atopic dermatitis responds to soak and smear therapy. Kohn, L.L., Kang, Y., and Antaya, R.J. A randomized, controlled trial comparing topical steroid application to wet versus dry skin in children with atopic dermatitis (AD). J Am Acad Dermatol. 2016; 75: 306 311. Soak and smear technique: Hydration in tap water for 20 minutes before bedtime. Apply mid potency to high potency topical steroid to WET skin. Wear pajamas. Cotton gloves for hands. Treat nightly x 4 days to 2 weeks. Gutman AB, Kligman AM, Sciacca J, James WD. Soak and smear: A standard technique revisited. Arch Dermatol. 2005;141:1556-9.
Atopic Dermatitis Therapy Adjunct treatment - Bleach baths reduce recurrent Staph. aureus infections. Randomized investigator blinded placebo controlled study of 31 severe childhood AD measured at 1 and 3 months. Chronic use of dilute bleach baths 2 X/week combined with intranasal mupirocin decreased the EASI scores in AD with secondary Staph. aureus compared to plain water baths(placebo) and intranasal mupirocin. Effects were seen only in the submerged body sites. Nasal colonization was not decreased. Huang JT, Abrams, Thiougan B, Pallor AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009;123:808-14.
Atopic Dermatitis **Sixth barrier: Treatment of widespread or localized recalcitrant to topical therapy (moderate to severe) atopic dermatitis. Significantly impacts the quality of life of patients and their families (loss of sleep, time applying medication, and cost.) Significantly impacts you and your office staff - educating the patient about their disease, discussing treatment options, and monitoring the patient and their labs for adverse reactions.
Atopic Dermatitis If patients are not getting better always re-think* the diagnosis, and possible triggering factors. Contact dermatitis to moisturizers and even topical corticosteriods need patch testing. Scabies Tinea Mycosis fungoides Non-adherence **Seventh Barrier: Non-adherence to systemic and topical medications is the most frequent cause of failure to improve!
Adherence in Atopic Dermatitis 37 children with atopic dermatitis were given triamcinolone ointment 0.1% and counseled to use it twice a day for 4 weeks, return in 4 weeks, and continue treatment for another 4 weeks. Electronic monitors in the cap measured adherence. Patients were not informed of monitoring. 26 patients completed the 8 weeks. Mean adherence from baseline only 32%. Adherence was higher on or near office visit days and decreased rapidly. Krejci-Manwaring J, Tusa MJ Feldman, SR. Stealth monitoring of adherence to topical medication: adherence is very poor in children with atopic dermatitis. J Amer Acad Dermatol. 2007;56:211-6.
Moderate to Severe Atopic Dermatitis Therapy Therapeutic options: Phototherapy (UVB, UVA1, or PUVA) Systemic immunosuppressive therapies Systemic corticosteroids Steroid sparing immunosuppressive medications methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil will be briefly discussed. Biologic therapy - dupilumab
Systemic Corticosteroids Systemic corticosteroids (IM and oral). Most common immunosuppressive used to control the moderate to severe flares of AD. *The most commonly mismanaged therapy. Rapid improvement, but rebound flares are common. Long-term use is generally not recommended because moderate doses are required for control and side effects result. Combine with steroid-sparing immunosuppressive medication to decrease dose and toxicity. Yu SH, Drucker AM, Lebwohl M,Silverberg JI. A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitis. J Amer Acad Dermatol. 2018;78:733-40.
Systemic Corticosteroids Limitations 1. Rebound flares are common, often with more widespread area involvement. 2. Important side effects - Short term - GI upset, headache, insomnia, increased appetite, weight gain, mood changes and even psychosis. Long term hypertension, diabetes, edema, osteopenia, osteoporosis, Cushingoid features, myopathy, increased risk of infections, reactivation of TB, cataracts, peptic ulcers, glaucoma, hypokalemia, avascular necrosis of the hip, acne, depression, adrenal suppression, and growth retardation in children.
Systemic Corticosteroids Several therapeutic options are available to try to minimized drug dosages, flares and side effects. 1. Prednisone 60 80 mg (1 mg/kg) q am or in divided doses X 1 week and then rapidly tapered, while instituting topical medications and/or phototherapy to maintain remission. 2. Intramuscular triamcinolone acetonide suspension 40 80 mg or other injectable depot corticosteroids are preferred by some physicians, but the absorption is variable over 2 4 weeks. When used long term the same side effects occur as oral steroids.
Medication Response onset Long term use Side effects Drug interactions Cost/month *HealthWarehous e.com Systemic Corticosteroids Rapid, relapses common Try to minimize Too many to fit in this chart Few 20 mg/d $13 Methotrexate 2-4 weeks Yes Nausea, HA, fatigue, liver toxicity, anemia Sulfa medication 15 mg/week $149 Azathioprine Slow, 4-6 weeks, peak 3 or > mos. Maybe Hematologic, LFT elevations, infections, GI upset,? CA Allopurinol 100 mg/d-$64 150 mg/d-$94 Cyclosporine Rapid, 2 weeks No Nephrotoxic, Hypertension Many, interferes with CP450 200 mg/d-$297 300 mg/d-$439 Mycophenolate mofetil 2-4 weeks Maybe GI upset, serious infections,? CA Aluminum and Calcium antacids, cholestyramine 2 g/d-$235 3 g/d-$352 Generic: $125-200
Dupilumab Dupilumab (Dupixent) is an interleukin-4 alpha antagonist indicated for the treatment of adults with moderate to severe atopic dermatitis not adequately controlled with topical medications. Initial dose 600 mg (two 300 mg) SQ injections followed by 300 mg SQ every 2 weeks. 38% clear or almost clear at 16 weeks vs. placebo 10% and 36% sustained improvement at 52 weeks 51% get 75% improvement in EASI scores at 16 weeks vs placebo 15%.
Dupilumab Adverse reactions: Injection site reactions 10% vs. placebo 5%. Conjunctivitis (mostly allergic) 10% vs. placebo 2%. Herpes simplex 4% vs. placebo 2%. Hypersensitivity reactions < 1%. Warning: Avoid live vaccines.
Atopic Dermatitis **Eighth barrier: Medication cost, formulary coverage, and Step Therapy restrictions. This is becoming an increasing barrier. Generic topical corticosteroids are now expensive and some not covered at all. TCIs -pimicrolimus and tacrolimus are very expensive. Crisaborole (Eucrisa) is very expensive.
Atopic Dermatitis Therapy We re not sure which interventions will be most effective, but what we do know now is that patients and families can t be taught how to manage eczema in a five minute office visit, and that education must be intensive and ongoing to be effective. Lawrence Eichenfeld, MD Rady Children s Hospital at UC-San Diego Skin and Aging June 2009