Atopic Dermatitis Adam Goldstein MD Associate Professor UNC

Atopic Dermatitis Adam Goldstein, MD Associate Professor UNC Department of Family Medicine Chapel Hill, NC aog@med. unc. edu

Objectives Improve ability to accurately diagnose and manage 90% of cases of atopic dermatitis n Recognize differences in infant, childhood and adult presentations of atopic dermatitis n Improve ability to diagnose and manage conditions associated with and sometimes confused with atopic dermatitis n

Atopic Dermatitis: Definition n n Atopic dermatitis = eczema = itchy skin Greek- meaning u (ec-) over u (-ze) out u (-ma) boiling Infants & small children (affects 1 in 7) Atopic dermatitis of childhood may reappear at different site later in life.

Atopic Dermatitis: Cause n The exact cause is unknown.

Atopic Dermatitis: Cause (Charlesworth, Am J Med, 2002)

Atopic Dermatitis: Cause n n ? Inborn skin defect that tends to run in families, e. g. asthma or hay fever 85% with high serum Ig. E and + skin tests food & inhalant (Jones, Clin Rev Allergy, 1993)

Morphology

Distribution In infants, the face is often affected first, then the hands and feet; dry red patches may appear all over the body. n In older children, the skin folds are most often affected, especially the elbow creases and behind the knees. n In adults, the face and hands are more likely to be involved. n

Distribution

Hand Eczema

Foot Eczema

Atopic Derm Adults

Atopic Derm Adults

Atopic Dermatitis: Associated features n n n The skin is usually dry, itchy & easily irritated by: u soap u detergents u wool clothing May worsen in hot weather & emotional stress. May worsen with exposure to dust & cats.

Associated Findings n Pityriasis alba

Associated Findings n Xerosis

Associated Findings n Keratosis Pilaris

Associated Findings n Ichthyosis

Hyperlinear Palmar Creases

Diagnosis n n Major characteristics u Pruritus with or without excoriation u Typical morphology and distribution u Chronic relapsing dermatitis u Personal or family history of atopy (asthma, allergy, atopic derm, contact urticaria) Other characteristics u Xerosis/Ichthyosis/palmar hyper/kerat. pilaris u Early age of onset u Cutaneous colonization and/or overt infections u Hand/foot/nipple/contact dermatitis, cheilitis, conjunctivitis, Erythroderma, subcapsular cataracts (Drake, JAAD, 1992)

Differential Diagnosis n Seborrheic dermatitis

Differential Diagnosis Seborrheic dermatitis n Scabies n

Differential Diagnosis Seborrheic dermatitis n Scabies n Drugs n

Differential Diagnosis Seborrheic dermatitis n Scabies n Drugs n Psoriasis n

Differential Diagnosis Seborrheic dermatitis n Scabies n Drugs n Psoriasis n Allergic contact dermatitis n

Differential Diagnosis n n n Seborrheic dermatitis Scabies Drugs Psoriasis Allergic contact dermatitis Cutaneous T-cell lymphoma

Atopic Dermatitis: Treatment 1. Reduce contact with irritants (soap substitutes) 2. Reduce exposure to allergens 3. Emollients 4. Topical Steroids 5. Antihistamines 6. Antibiotics 7. Steroid sparing 8. Other (herbals, soaps)

1. Reduce contact with irritants n n n Avoid overheating: lukewarm baths, 100% cotton clothes, & keep bedding to minimum Avoid direct skin contact with rough fibers, particularly wool, & limit/eliminate detergents Avoid dusty conditions & low humidity Avoid cosmetics (make-ups, perfumes) as all can irritate Avoid soap- use soap substitute Use gloves to handle chemicals and detergents

Soap Substitutes n n Cetaphil- soap substitute- far less drying and irritating than soap Cleansing & moisturizing formulations, all OTC Lotion, bar, ‘soap’, cream, sunscreen Costs about $8 -9 for 16 oz.

2. Reduce exposure to allergens n n Keep home, especially bedroom, free of dust. Allergic reactions include house dust mite, molds, grass pollens & animal dander. Special diets will not help most individuals b/c little evidence that food is major culprit. If food allergies exists, most likely d/t dairy products, eggs, wheat, nuts, shellfish, certain fruits or food additives.

3. Emollients n n n Emollients soften the skin soft and reduce itching. Moisture Trapping effectiveness u Best: Oils (e. g. Petroleum Jelly) u Moderate: Creams u Least: Lotions Apply emollients after bathing and times when the skin is unusually dry (e. g. winter months).

Emollients (cont’d) n n Large variety (e. g. Vanicream, Eucerin, Lubriderm, Moisturel, Curel, Neutrogena) Inexpensive emollients include vegetable shortening (Snowdrift by Martha White) and petroleum jelly (Vaseline) Urea creams Oils

Emollients: Alpha-Hydroxy acid n n u u u n Creams are excellent for relieving dryness, but can sting & sometimes aggravate eczema Useful for maintenance when no longer inflamed Forces epidermal cells to produce keratin that is softer, more flexible and less likely to crack Preparations Glycolic Acid (8%) Lactic Acid or Lac-Hydrin (5 -12%) Urea (3 -6%) Use 1 X/ day

Emollients: Oils n n Consider using bath oil or mineral oil-based lotions in lukewarm bath water Add to tub 15 minutes into bath Bath oil preparations: u Alpha-Keri u Aveeno bath u Jeri-Bath Colloidal oatmeal (Aveeno) reduces itching

4. Corticosteroids Topical steroids very effective n Ointments for dry or lichenified skin n Creams for weeping skin or body folds n Lotions or scalp applications for hair-areas. n

Corticosteroids n n n Hydrocortisone 1 -2. 5% applied to all skin. Quite safe used even for months Use intermittently thin areas- (eg-face & genitals) Stronger potency topical steroids for nonfacial/genital regions. Avoid potent/ultrapotent topical steroid preparations on face, armpits, groins & bottom.

Corticosteroids n n n Once under control, intermittent use of topical corticosteroid may prevent relapse Systemic steroids may bring under rapid control, but may precipitate rebound Once daily probably most cost effective (Green, Br J Dermatol, 2005)

Steroids and Young Children Fluticasone proprionate cream 0. 05% n Moderate- severe atopic derm > 3 months n Applied bid 3 -4 weeks- mean 64% BSA n No HPA suppression n (Friedlander, J Am Acad Dermatol, 2002)

Corticosteroids: Pearls n n n Different preparations prescribed for different parts of body or for different situations Educate on u potencies & proper usage u write down directions Bring all topicals each appointment to clarify use

5. Antibiotics Atopic eczema frequently secondarily colonized with a bacteria (up to 30%). n Use oral antibiotics in recalcitrant or widespread cases. n

Keep it simple

6. Antihistamines n n n Oral antihistamines can reduce urticaria & itch Non-sedating antihistamines less side effects but more expensive Sedative effect of hydroxyzine & diphenhydramine helpful

7. Steroid Sparing n Topical calcineurin inhibitors u n n Tacrolimus ointment & pimecrolimus cream Oral Cyclosporine Ultraviolet light therapy (phototherapy) with PUVA (psoralens plus ultraviolet A radiation) or combinations of UVA & UVB (Jekler, J Am Acad Dermatol, 1990)

Tacrolimus ointment (0. 03%, 0. 1% [Protopic]) Mild to moderate eczema n Steroid dependent or signs of atrophy n Non-steroid responsive n BID x 2 -4 weeks to evaluate response n Transient stinging possible n Longer disease-free intervals n Cost similar to high potency steroids n (30 gm/$60) (Ruzicka, N Engl J Med, 1997)

Pimecrolimus cream 1% (15, 30, 100 gm [Elidel]) n Approved Dec. 2001 n Blocks production/release cytokines T-cells Moderate eczema n Steroid sparing n Transient stinging 8% children, 26% adults n Cost similar to high potency steroids n (30 gm/$60) (Ruzicka, N Engl J Med, 1997) (Eichenfield, J Am Acad Dermatol, 2002)

Tacrolimus ointment & pimecrolimus cream n n Licensed for patients > 2 years old mild-moderate eczema Safety? In controlled trials appear safe in adults and children u In 2005, FDA issued warnings about a possible link between the topical calcineurin inhibitors and cancer (? increased risk of lymphoma and skin cancers with topical exposure) u However, no definite causal relationship established FDA recommends that these agents are used only as second-line therapy in patients unresponsive to or intolerant of other treatments u Avoid in children younger than two years of age u Use for short periods of time and minimum amount necessary u Avoid continuous use u Avoid in patients with compromised immune systems u n

Ointments (Tacrolimus) better than cream (Pimecrolimus)

Oral Cyclosporine and PUVA

Self Monitoring The patientoriented eczema measure (Charman, Arch Dermatol, 2004)

Other Psychological support n Alternative treatments u Chinese herbal tea t Variably effective-not very palatable t Liver toxicity possible n

Other n Evening Primrose Oil / Star Flower Oil u Contains gamma linolenic acid, fatty acid (deficient some atopic subjects)

Alternative medications some patients may use for eczema Licorice n Calendula n Echinacea n Golden Seal n Nettle n Oats n

Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial. n Lactobacillus u prenatally to mothers – (FH eczema, AR, asthma) u postnatally for 6 months to infants n Endpoint: Chronic recurring eczema n Eczema in probiotic 50% < than placebo (23% vs 46%) n Number needed to treat = 4. 5 (95% CI 2. 6 -15. 6). (Kalliomaki, Lancet 2001)

Other Laughter May Be Best Medicine. . . For Allergies NEW YORK, NY - Although few would consider allergies to be funny, results of a new study suggest that laughing them off might actually work. Dr. Hajime Kimata, of Unitika Central Hospital in Japan, induced allergic responses on the skin of 26 people with allergic dermatitis by exposing them to house dust mites, cedar pollen and cat hair, and then had them watch ``Modern Times'', featuring Charlie Chaplin. The participants exhibited a significant reduction in their allergic responses after watching the classic comedy, according to the report in the February 14 th issue of The Journal of the American Medical Association. The effect lasted for 4 hours after the viewing

Other n Coal tar or less messy preps (liquid carbonis detergent 5 -10%) in Eucerin or Aquaphor u Chronic lichenified eczema patches u Coal tar smells & stains clothes so apply qhs using old clothes and old linens u Coal tar can provoke a folliculitis.

Soaps n Mild or Hypoallergenic u u u u Dove (unscented): Contains lotion Keri Oil of Olay Basis Purpose Cetaphil Skin Cleanser (non-soap) Neutrogena bar Pure Ivory soap is very drying/irritating

Antibacterial Soaps Dial and Lever 2000 n Cetaphil antibacterial cleansing bar n

Evidenced-based review 2002 n n (BMJ Clinical Evidence) Positive evidence that: u topical corticosteroids relieve symptoms and are safe u emollients & steroids better than steroids alone u excellent control of house dust mite reduces symptoms if positive mite RAST scores & children t bedding covers most effective Little to no evidence that: u dietary change reduces symptoms u breast feeding or mother's diet prevents infant eczema

Systematic review 2000 n Positive evidence: u Topical steroids u Oral cyclosporine u UV light u Psychological approaches n Insufficient evidence u Ag avoidance pregnancy u Antihistamines u Dietary restriction u Dust mite avoidance u Hypnotherapy u Emollients u Massage u Evening primrose oil u Topical coal tar u Topical doxepin u Chinese herbs (Hoare, Health Technol Assess, 2000)

Systematic review n Not beneficial: u Cotton clothing u Biofeedback u Bid vs qd topical steroids u Bath additives u Topical antibiotic/steroids vs steroids alone (Hoare, Health Technol Assess, 2000)

Final Pearls Educate parents that the goal is CONTROL not CURE n Atopics exposed to herpes virus or smallpox vaccination may get severe infection with widespread involvement d/t altered skin barrier. n

Severe herpes infections in children with eczema

Atopic Derm and Smallpox Vaccine (Ann Intern Med 2003; 139)

Costs H/C 1% Bid-tid 30 gm $3. 00 TAC 0. 1% Bid 30 gm $8. 00 Fluticasone propionate 0. 05% Qd-bid 30 gm $42. 00 Mometasone furoate 0. 1% Qd 30 gm $45. 00 Betamethasone dipropionate 0. 05% Bid 30 gm $20. 00 Clobetasol propionate 0. 05% Bid 30 gm $15. 00 Halobetasol propionate 0. 05% Qd-bid 30 gm $72. 00 Pimecrolimus 1% Bid 30 gm $56. 00 Tacrolimus 0. 1% Bid 30 gm $60. 00 Drugstore. com 2004

CASE 1 n n 3 year old female with h/o eczema since 4 months old. Had done well on hydrocortisone 2. 5% ointment when flared last winter. Parents ran out of the ointment and have been using vaseline and OTC hydrocortisone 0. 5% without improvement. Child is now waking at night and constantly scratching. What do you want to do?

Case Treatment strategy: Review mild skin care regimen t Confirm use of • mild cleanser • daily moisturizers & • mild laundry detergent t Prescribe sufficient potency & quantity of topical corticosteroids t Which steroid class(es) would you px? t

Case- topical steroid choices TAC 0. 1% oint. bid worse areas x 7 -14 days n Switch to H/C 2. 5% ointment BID n Taper over 4 weeks to emollients if possible n Confirm parents understand dangers of prolonged steroid use and not to use potent steroids on face n

F/U 2 weeks later: n Only slightly improved- now what?

Now. . . n n n Add oral antistaphylococcal agent for 7 -14 days. REVIEW mild skin care regimen Follow-up in 2 weeks and SUCCESS!

CASE 2 34 yo female with h/o hand eczema diagnosed by former MD for 6 years. Seems to get worse in winter, but never goes away entirely. A friend told her it could be a fungus. She was given fluocinonide (lidex) 0. 05% cream and it helps some. She wants a refill.

CASE 2 n n Not likely fungus given chronicity May have secondary staph infection May need more potent Class I steroid initially, e. g. clobetasol propionate (temovate) ointment Class II Fluocinonide (lidex) 0. 05% cream ok less severe

Case 3 n n n 75 YO male with chronic itchy spots. Using hydrocortisone cream 2. 5% bid to ankle- minimal improvement Using Class II Fluocinonide (lidex) 0. 05% ointment under occlusion to hip area- “only thing that works”

Case 3 n n n 2. 5% H/C too weak Fluocinonide (lidex) 0. 05% ointment under occlusion causing atrophy Good case for topical tacrolimus

Patient Education n National Eczema Association u www. eczema-assn. org

Thank you.

References n n n Drake LA, et al. Guidelines of Care For Atopic Dermatitis. J Am Acad Dermatol 1992; 26: 485 -8. Atopic eczema. In Clinical Evidence British Medical Journal 2001. Available online at www. clinicalevidence. org Correale CE, Walker C, Murphy L, Craig TJ. Atopic Dermatitis: A Review of Diagnosis and Treatment. J Fam Pract 1999; available at http: //www. aafp. org/afp/990915 ap/1191. html Ruzicka T, Bieber T, Schopf E, et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997; 337(12): 816 -21. Eichenfield LF, Lucky. AW, Boguniewicz M, et al. Safety and efficacy of pimecrolimus cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J A Acad Dermatol 2002; 46; 495 -504.

References n n n Charlesworth EN. Pruritic dermatoses: overview of etiology and therapy. Am J Med 2002; 113 S, 9 A: 25 S-33 S. Wahn U, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics 2002; 110 (1 Pt 1): e 2. Friedlander SF, et al. Safety of fluticasone proprionate cream 0. 05% for the treatment of severe and extensive atopic dermatitis in children as young as 3 months. J Am Acad Dermatol 2002; 46: 387 -394. Hoare C, et al. Systematic review of treatments for atopic eczema. Health Technol Assess 2000; 2: 1 -191. Green C, Colquitt JL, Kirby J, Davidson P. Topical corticosteroids for atopic eczema: clinical and cost effectiveness of once-daily vs. more frequent use. Br J Dermatol 2005; 152: 130 -41. Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Arch Dermatol 2004; 140: 1513 -9.