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1. Atopic Dermatitis Doctor Anne ISVY UVSQ

2. General information • Atopic Dermatitis = atopic eczema • Chronic inflammatory pruritic skin disorder • Periods of remission marked by acute inflammatory relapses: “flares” • Role of allergic reactions still a matter of debate

3. General information • Most common skin disease in infants and children • Can appear at any age: • Typically before the age of 5 years • Clears by adolescence • Can persist into adulthood • Associated with asthma and allergic rhinitis

4. Epidemiology • Prevalence in industrialised countries has increased in recent decades, • 10-20% in childhood according to various studies, country dependent: • lifetime occurrence: 20% in boys and 19% in girls in 1 104 children aged 3-11 years in Birmingham, UK Kay J et al, J Am Acad Dermatol, 1994 • lifetime occurrence: 17% in 6 755 Turkish children aged 10-11 years Civelek E et al, J Investig Clin Immunol, 2011 • Increasing prevalence with improving lifestyle, nutrition, environmental factors, standard of living

5. PathophysiologyCongenital skin barrierdefects ALLERGENPENETRATION Cutaneous hyper-reactivity to environmental stimuli Xerosis of the skin Reduction of hydrolipidic film Abnormal cohesion of stratum corneum cells

6. PathophysiologyAllergenpenetration • Langerhans cells: antigen-presenting cells • Process antigenic material in the stratum spinosum of the epidermis and present it on their surface • Migrate to lymphoid tissue and interact with naïve-T cells • Induction of activation by specific IgE on the surface • Production of inflammatory cytokines (IL-1, IL-6, IL-8 et TNF-a) • Recruitment of inflammatory cells

7. PathophysiologyAllergenpenetration

8. PathophysiologySensitisation ECZEMA DAMAGE • New contact with allergen: • Specific T-cell activation • Production of inflammatory cytokines IL-4 and IL-5 • Specific IgE production • Recruitment of eosinophils

9. ClinicalpresentationAtopic background Allergic rhinoconjunctivitis Allergic conjunctivitis Asthma Family history of atopy in 60% of cases

10. ClinicalpresentationElementarylesions Eczematiform patches: poorly definederythematous or squamous papules or vesicles (fluid-filled bumps) Weeping, crusted lesions, fissures Xerosis and pruriginous Scratches and excoriations Lichenification: thickened, scaly, red or grey skin

11. Scratches and excoriations Erythematous papules or vesicles

12. Lichenification Diffuse thickening of the epidermis, with resulting accentuation of skin lines Represents chronic disease

13. ClinicalpresentationSites • Infant: exudative lesions • Face: eyes, infra-orbital folds, cheilitis, cheeks, forehead • Scalp • Limbs: extensor surfaces • Bottom • Children from 2 years to puberty: lichenified lesions • Limbs: flexor surfaces: elbow flexure, popliteal spaces • Neck • Back of hands and feet, wrists, ankles

14. Infant

15. Typical facial rash in infant

16. Child

17. Child

18. ClinicalpresentationSites • Adult phase • Begins at puberty and frequently continues into adulthood • Dry, scaling, erythematous papules and plaques • Large lichenified plaques from chronic lesions • Sites • Flexural folds • Face • Neck • Upper arms and back • Dorsa of the hands, feet, fingers and toes • Nails

19. Adult

20. Adult

21. Cheilitis Nail lesions

22. Diagnosis • Based on the findings of: • The history • The physical examination

23. DiagnosisHanfin and Rajka diagnostic criteria • Main features: • Pruritus • Eczema (acute, sub-acute, chronic) • Chronic or relapsing history • Frequently associated features: • Onset at a young age • Atopy (personal or family history, IgE reactivity) • Xerosis • Other features: • Atypical vascular responses (facial pallor, white dermographism or delayed blanch) • Keratosis pilaris, palmar hyperlinearity and ichthyoses • Ocular or periorbital changes • Perioral changes or periauricular lesions • Perifollicular accentuation, lichenification, prurigo

24. Keratosis pilaris White dermographism

25. Diagnosis • No specific laboratory findings • Elevated IgE levels found in > 80% of affected patients • IgE levels are also elevated in patients with other atopic diseases

26. Diagnosis • In case of ineffective treatment • Allergy skin tests (patch-test): if suspicion of contact dermatitis • Skin biopsy: to eliminate differential diagnosis • Acute phase: spongiosis (intercellular oedema between the epidermal keratinocytes leading to micro-or macrovesicles), infiltration of leukocytes, mostly lymphocytes, into the epidermis and upper dermis • Chronic phase: inflammation and spongiosis mild or completely absent, thickening of the epidermis, acanthosis (thickening of the stratum spinosum), hyperkeratosis (thickening of the stratumcorneum) and parakeratosis (dysfunction of the keratinisation)

27. DiagnosisHistopathology Spongiosis Lymphocytes in the epidermis Lymphocytes surrounding dermal vessels

28. Differentialdiagnosis • Scabies • Seborrhoeic dermatitis • Psoriasis • Neurodermatitis • Systemic illnesses (malignancy, thyroid disorders and hepatic or renal failure) can cause pruritus and excoriations • Adults with new-onset pruritus: thorough history and complete physical examination to exclude systemic disease • Contact dermatitis: • history reveals exacerbation of the rash after contact with a particular substance • standard therapy unsuccessful patch testing to identify cause of allergic contact dermatitis

29. Seborrhoeic dermatitis Scabies

30. Complications • Infection • Lesions at any stage can develop secondary infections • Cause of exacerbation of eczema • Impetigo (staphylococcal and streptococcal infections) with crusting and weeping lesions • Risk of widespread herpes simplex virus infection (Kaposi's varicelliform eruption): • painful vesicles on an erythematous base in areas of dermatitis or on normal-appearing skin • constitutional symptoms can also develop

31. Impetigo Highly contagious gram-positive bacterial infection of the superficial layers of the epidermis

32. Kaposi's varicelliform eruption

33. Complications • When the lesions resolve, areas of hyperpigmentation or hypopigmentation can persist

34. Impact School absenteeism Emotional stress Sleep disturbance Relationship problems children-parent Irritability Social stigma of a visible skin disorder Mental depression in adults

35. Treatment • Education of patients and parents • Chronic disorder • Course of disease by flares • No risk of underdevelopment • Repeated treatment • Reassure apprehension over topical corticosteroid use • Fight against • Infection • Inflammation • Dryness

36. TreatmentNon-medicated management Maintenance of an effective skin barrier • Avoid hot (> 33°C) and long (> 5 minutes) baths • Use soft and superfatted soaps • Avoid wool clothes, prefer cotton long sleeved underwear • Avoid close contact with herpes infected individuals (Kaposi's varicelliform eruption) • Respect normal immunisation schedule • No systematic food avoidance +++

37. Treatment Emollients • Mainstay of general management • Should by applied continuously, even if no inflammatory skin lesions • Once or twice daily • Vaseline • Other ointments and creams • Polidocanol reduces pruritic symptoms • Preparation with urea: intensive hydration

38. TreatmentTopicalglucocorticosteroids • First-line therapy in acute flare-ups • Control of moderate to very severe disease • Potency determined by a vasoconstriction assay utilising a numerical scale ranging from class 4 (weakest), to class 1 (superpotent) • Potential local side-effects: • Striae, petechiae, telangiectasia, atrophy, acne or rosacea (incidence correlates with length of use and potency of product) • Systemic side-effects remain debatable: • Possible suppression of the hypothalamic-pituitary-adrenal (HPA) axis • In rare and extreme instances, growth retardation in children • Systemic absorption is determined by the extent and severity of disease, drug formulation and drug potency Callen J et al. Br J Dermatol, 2007

39. Topical glucocorticosteroids

40. TreatmentTopicalglucocorticosteroids • Higher strength for brief periods (1 to 2 weeks) to gain quick control of disease flares • Choice of topical corticosteroid depends on: • Age of patient • Severity of disease • Area of body • Class 3 recommended for infants with mild disease • Class 2 possible for moderate-to-severe flares (except on the face and bottom of infant) • Class 1 should not be used in children under 12 years of age and are limited to a 1- to 2-week course in patients with severe flares

41. TreatmentTopicalglucocorticosteroids • Acute flare-ups: • Apply once a day (better in the evening) • In combination with emollient skin care • Count the number of tubes used between 2 consultations • Initial therapy: high potent steroid • Secondary: time-dependant dose reduction or change to lower potency • Applied on unaffected skin twice weekly prevents future flare-ups

42. TreatmentTopicalcalcineurininhibitor • Topical anti-inflammatory therapy as second-line • Tacrolimus ointment (0.03%) and pimecrolimus cream (1%) approved in children > 2 years • Tacrolimus (0.1%) ointment: only for use in adults • Useful alternative for sensitive skin areas (face, intertriginous areas) • Side-effects : • Transient burning sensation of the skin • Viral infections (eczema herpeticum, eczema molluscatum) • No evidence of a causal link with cancer

43. TreatmentNew nonsteroidalbarriercreams • Approved as “medical devices” by the FDA • For mild-to-moderate atopic dermatitis in both paediatric and adult patients • Example: Atopiclair® • Hyaluronic acid which acts as a moisturising agent • Glycyrrhetinic acid, which is believed to have anti-inflammatory effects • Other factors thought to have anti-oxidant properties and to restore the barrier function of the skin

44. TreatmentPhototherapy Standard second-line treatment for adults PUVA, broad-band UVB, narrow-band UVB, UVA Combination with corticosteroids in acute flare phases UV therapy is restricted to adolescent > 12 years

45. TreatmentSystemic • No systemic steroid (risk of relapse after discontinuation, side effects) • Antihistamines • Sedative properties • Useful as a short-term adjuvant to topical treatment during relapses with severe pruritus • Hyposensitisation (immunotherapy): • Not established for the treatment of AD • Well-controlled studies needed

46. TreatmentSystemic • Cyclosporin A: • Reduces levels of proininflammatory cytokines • Severe refractory disease • Side effects: renal toxicity, blood pressure • 3-5mg/kg/d 2 months and dose reduction during 6 months to avoid relapse after stopping • Monitoring of blood pressure and renal function

47. TreatmentSystemic • Azathioprine • Non licensed indication • Evidence of efficacy in severe recalcitrant disease • Side effects: myelosuppression, hepatotoxicity, gastrointestinal disturbances, increased susceptibility for infections, skin cancer?

48. TreatmentFuture Perspectives • Increasing knowledge of the cellular and molecular aspects of atopy • Inhibiting components of the allergic inflammatory response • Cytokine modulation (TNF inhibitor) • …

49. Complications of treatment • Kaposi's varicelliform eruption • Emergency admittance • Treatment with acyclovir (Zovirax, 500 mg/m2 x3 per day; slow perfusion: 20 mg/kg/8 hours) • Impetigo (< 5 lesions) • Daily bath • Topical antiseptic (chlorhexidine) • Topical antibiotic: fusidic acid or mupirocin (x2/day, 5 days) • Widespread impetigo (> 5 lesions, fever): • +/- avoid school, family circle examination • systemic antibiotic 7-10 days: • Macrolides: erythromycin, josamycin • Penicillins: cloxacillin, amoxicillin + clavulanic acid • Synergistin: pristinamycin • Oral fusidic acid

50. Conclusion • Most common skin disease in children • Prevalence still increasing • Complex disease, many features still not understood • Treatment : • Partner with doctor • Education++ • Emollients and topical corticosteroids