Management of atopic dermatitis


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Management of atopic dermatitis 2011

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  • worldwide
  • AD14
  • As a result of genetically determined epidermal-barrier dysfunction and the effect of environmental factors, nonatopic dermatitis is the first manifestation of atopic dermatitis. Subsequently, because of their genetic predisposition for IgE-mediated sensitization, patients become sensitized. This phenomenon is favored by Staphylococcus aureus enterotoxin products. Finally, scratching leads to tissue damage and the release of structural proteins, triggering an IgE response in patients with atopic dermatitis. This sensitization to self-proteins can be due to the homology of allergen-derived epitopes and human proteins in the context of molecular mimicry.
  • AD25
  • maternal age, maternal education, family income, family history of atopy, maternal smoking and drinking alcohol during pregnancy, maternal diet and supplements such as multivitamins or fish oils during pregnancy, duration of breast feeding and consumption of infant formula, age of introduction of solid foods or highly allergenic foods, infant history of allergy, acute bronchiolitis, number of siblings, pet raising, cockroaches and carpets at home, environmental tobacco smoke, fungi on the walls of the house, frequent use of microwave oven or magnetic oven, moving into a new house, new paintings Vasoactive intestinal peptide, substance P, nerve growth factor toward Th2
  • AD8
  • difference between active and placebo covers at 6 months was highly significant (p=002). severity of eczema decreased in both groups, but active group showed significantly greater improvements in severity score (difference between mean final scores 4.3 units, p=0.006)
  • AD9
  • AD10
  • AD18
  • The four test products were Cetaphil Daily Advance ultra hydrating lotion (CDA lotion; Galderma); Epidrat ultra hydrating lotion (E lotion; Quimica Farmaceutica Ltda); Physiogel lotion (P lotion; Stiefel Laboratories); and Physiogel AI cream (PAI cream; Stiefel Laboratories)
  • micronized desonide AD11
  • consumption of high-potency corticosteroids ( fig. 2 a) was significantly lower in the emollient group compared to the control group from D0 to D21 [8.87 8 1.37 g vs. 4.86 8 0.97 g (–45.2%), p = 0.019] and from D0 to D42 [14.7 8 2.08 g vs. 8.56 8 1.74 g (–41.8%), p = 0.025]. consumption of moderate-potency topical corticosteroids from D0 to D21 and D42 in the 2 study groups is shown in figure 2 b. From D0 to D21 and from D0 to D42, the emollient group consumed slightly less moderate- potency topical corticosteroid than the control group (4.66 8 0.65 g vs. 4.91 8 0.75 g and 7.43 8 1.13 g vs. 8.03 8 1.23 g, respectively), but this difference of consumption was not significant either at D21 (–5.1%, p = 0.8043) or D42 (–7.5%, p = 0.722).
  • Prolonged duration can alter barrier function
  • AD13
  • AD26
  • AD29
  • AD21
  • AD23
  • AD28
  • AD17
  • Management of atopic dermatitis

    1. 1. Management of Atopic dermatitis Sasikarn Suesirisawad, M.D.
    2. 2. <ul><li>AD is a chronic relapsing inflammatory skin disease </li></ul><ul><li>AD associated with local infiltration of Th 2 that secrete IL-4, IL-5, IL-13, IL-31 </li></ul><ul><li>More than 50% develop asthma </li></ul><ul><li>75% develop AR </li></ul><ul><li>Complex interrelationship of genetic, environmental, immunologic, and epidermal factor </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    3. 3. Epidemiology <ul><li>Affects 15-30% of children, 2-10% of adult </li></ul><ul><li>60% begin during the first yr </li></ul><ul><li>45% begin within the first 6 mo </li></ul><ul><li>85% begin before 5 yrs </li></ul><ul><li>Up to 70%: spontaneous remission before adolescence </li></ul><ul><li>Predisposed to developing AR/asthma later in childhood .. “Atopic march” </li></ul>NJEM 2008;358:1483-94
    4. 4. Epidemiology <ul><li>E merges in 1 st month of life, while its prevalence decreases by age . </li></ul><ul><li>G irls more often suffer from AD than boys ... but until age of 6 , both sexes are affected equally. </li></ul><ul><li>Increase exposure to allergen & decline in BF were reason for increasing of AD. </li></ul><ul><li>Williams H.C.:  Is the prevalence of atopic dermatitis increasing?.   Clin Exp Dermatol   1992; 17:385-391 </li></ul><ul><li>Childhood eczema found correlation with increased socioeconomic class </li></ul><ul><li>Williams H.C., Strachan D.P., Hay R.J.:  Childhood eczema: disease of the advantaged?.   Br Med J   1994; 308:1132-1135 </li></ul>Pediatr Allergy Immunol 2010:21:1028 - 1035
    5. 5. Risk factor in development of AD <ul><li>Genetic host factors </li></ul><ul><li>Gene encoding epidermal or other epithelial </li></ul><ul><li>structural proteins </li></ul><ul><li>Loss of function mutations of </li></ul><ul><li>epidermal barrier protein filaggrin (FLG) </li></ul><ul><li>Transepidermal water loss (hallmark) </li></ul><ul><li>& penetration of environmental allergens </li></ul>N Engl J Med 2008;358:1483-94
    6. 6. Risk factor in development of AD <ul><li>Genetic host factors </li></ul><ul><li>Gene encoding major elements of immune system: </li></ul><ul><li>3q21, 1q21, 16q, 17q25, 20p, 3p26 regulation of IgE synthesis </li></ul><ul><li>- Exaggerated T cell responses: imbalance between Th1 & Th2 </li></ul><ul><li>- Reduced skin innate immune response: </li></ul><ul><ul><li>human B defensins, cathelicidin, dermcidin (antimicrobial peptide) </li></ul></ul>N Engl J Med 2008;358:1483-94
    7. 7. Risk factor in development of AD <ul><li>Environmental factors </li></ul><ul><li>Food allergens (egg, milk, wheat, soy) </li></ul><ul><ul><li>Associate to infantile AD </li></ul></ul><ul><ul><li>Related to disease severity </li></ul></ul><ul><li>Aeroallergens (pets, mites, pollen) </li></ul><ul><ul><li>Exacerbation AD in older children </li></ul></ul>N Engl J Med 2008;358:1483-94
    8. 8. Risk factor in development of AD <ul><li>Other factors </li></ul><ul><li>Weather conditions or humidity </li></ul><ul><li>Skin irritants : soap, detergent </li></ul><ul><li>Infections : S. aureus, M. furfur, HSV </li></ul><ul><li>Emotional stress </li></ul>Persistent or worsening disease
    9. 9. N Engl J Med 2008;358:1483-94.
    10. 11. Acute AD <ul><li>Intensely pruritic, erythematous papule associated with excoriations , vesiculation, and serous exudate </li></ul>Thomas Bieber . NEJM 2008; 358:1483-94 Histology: Spongiotic area within the epidermis
    11. 12. Chronic AD <ul><li>May have all skin type, Dry skin </li></ul><ul><li>Lichenification … Thickening of skin with accentuated surface markings and fibrotic papules </li></ul>Thomas Bieber . NEJM 2008; 358:1483-94 Hyperplastic of epidermis with hyperkeratosis
    12. 13. Color Textbook of Pediatric Dermatology, 4th Edition. Infantile type Childhood type Adult type Face, scalp, trunk, extensor surfaces of extremities Flexural folds of ext (antecubital, popliteal fossa) neck, ankles Upper arms, back, wrists, hands, fingers, feet, toes
    13. 15. Conventional Therapies <ul><li>Identification and elimination of exacerbating factors (irritants, proven allergens) </li></ul><ul><li>Addressing psychological aspects </li></ul><ul><li>Education </li></ul><ul><li>Hydration </li></ul><ul><li>Moisturizers </li></ul><ul><li>Topical corticosteroids </li></ul><ul><li>Topical calcineurin inhibitors </li></ul><ul><li>Anti-infective therapy </li></ul><ul><li>Anti-pruritic therapy </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999 <ul><li>Goal </li></ul><ul><li>Efficient short-term control of acute symptoms </li></ul><ul><li>Flare prevention </li></ul><ul><li>Avoidance side effects </li></ul>
    14. 16. Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    15. 17. <ul><li>Irritative substances </li></ul><ul><li>Allergens ( food and inhalant) </li></ul><ul><li>Infectious microorganisms </li></ul><ul><ul><li>Staphylococcus aureus </li></ul></ul><ul><ul><li>Malassezia furfur </li></ul></ul>
    16. 18. Exacerbating factor in AD
    17. 19. Irritants <ul><li>A lowered threshold of irritant responsiveness. </li></ul><ul><li>Detergents, soaps, chemicals, pollutants, abrasive materials, extreme of temperature and humidity </li></ul><ul><li>Cleansers with minimal defatting activity and neural pH. </li></ul><ul><li>New clothing should be laundered before it is worn to reduce formaldehyde and chemicals. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    18. 20. Irritants <ul><li>Changing detergent to a milder one, liquid are more </li></ul><ul><li>preferred than a powder one, extra rinse cycle </li></ul><ul><li>Occlusive clothing should be avoided, cotton should be used. </li></ul><ul><li>Temperature should be temperate to minimize sweating. </li></ul><ul><li>Swimming is well tolerated, shower and use mild soap to remove chlorine. </li></ul><ul><li>Non-sensitizing sunscreen should be used to avoid sunburn. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    19. 21. Fabienne Rance. Ped AI 200 8;19:279 -84
    20. 22. Environmental risk factors for early infantile atopic dermatitis <ul><li>Purpose: To evaluate influence of various environmental risk factors for early infantile AD. </li></ul><ul><li>Population: 2048 mother–child pairs from Taiwan in 2003. </li></ul><ul><li>Method : Information on environmental risk factors for infant gathered by questionnaire were available from 1760 infants at 6 months of age. </li></ul><ul><li>Result: 118 of 1760 (6.7%) were AD. After adjusting for confounding factor, fungi on walls [OR 2.14 (95% CI 1.41–3.22)] and frequent use of microwave oven at home [aOR 1.71 (95% CI 1.13–2.58)] increased risk of early infantile AD. </li></ul><ul><li>Conclude : Fungi are especially important in humid climate as in Taiwan and The hazards of microwave use should be paid more attention. </li></ul>Pediatr Allergy Immunol 2007: 18: 441–447
    21. 23. Pediatr Allergy Immunol 2007: 18: 441–447
    22. 24. Aeroallergens <ul><li>HDM, animal danders, pollens </li></ul><ul><li>In 1940s, Tuft et al. demonstrated that AD patient who underwent bronchoprovocation of HDM extract developed cutaneous lesions after inhalation to dust mites </li></ul><ul><li>Study with patch testing have shown that direct contact with inhalant allergens can also result in eczematous lesions </li></ul><ul><li>Respiratory and direct contact may be important in the induction and exacerbation of AD </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    23. 25. Double-blind controlled trial of effect of HDM allergen avoidance on AD Tan et al. Lancet 1996; 347: 15-18 Patient 48 patients (24 adults; mean age 30, 24 children mean age 10) Positive skin test (>= 2mm than NSS) to aeroallergens Intervention Goretex bedcovers, benzyltannate spray for carpets and a high-filtration vacuum cleaner (6 month) Compare Cotton bedcovers, water spray, conventional domestic vacuum cleaner Outcome <ul><li>Der p1 concentration (ng/m2) </li></ul><ul><li>Eczema severity score </li></ul><ul><li>Surface area score </li></ul>
    24. 26. Tan et al. Lancet 1996; 347: 15-18 p= 0.002 ** 12.6 4.2 p= 0.006
    25. 27. Psychosocial factors <ul><li>Relaxation, behavioural modification, biofeedback may all be benefit </li></ul><ul><li>Massage therapy can be adjunct treatment for AD </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    26. 28. Hydration <ul><li>Atopic dry skin and decreased ceramide level enhanced transepidermal water loss and reduced water binding capacity </li></ul><ul><li>Soak affected area or bath for 10 minutes in warm water and apply occlusive agent to retain absorbed water </li></ul><ul><li>Bleach bath with dilute sodium hypochlorite recommended to reduce skin infection </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition Imokawa al: J Invest Dermatol   1991; 96:523-526
    27. 29. Hydration <ul><li>Hand and foot dermatitis treated by soaking limb in basin. </li></ul><ul><li>It is essential to use occlusive preparation within few minute after hydration skin to prevent evaporation. </li></ul><ul><li>Bathing may remove allergens from skin and reduce colonization by S. aureus. </li></ul><ul><li>Balneotherapy in acidic hot spring shown to help refractory AD </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition Kubota al:  Acta Derm Venereol   1997; 77:452-454.
    28. 30. “ Soak and seal” Method <ul><li>Soak the affected area for approximately 10 minutes in warm water </li></ul><ul><li>Seal an occlusive agent to retain the absorbed water within a few minutes (for prevent evaporation which is damage to the epidermis) </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    29. 31. An. Bras. Dermatol. vol.82 no.1 Rio de Janeiro Jan./Feb. 2007 Breaking the cycle: how I manage difficult AD
    30. 32. Wet wrap Pediatrics 2008;122;812-824
    31. 33. Wet dressing <ul><li>Wet-wrap dressings reduce pruritus and inflammation by cooling skin, act as barrier to trauma associated with scratching, improve penetration of steroid. </li></ul><ul><li>Severe AD showed significant improvement after 1 week of treatment using tubular bandages applied over diluted topical steroid. </li></ul>Wolkerstorfer A.:  De Waard van der Spek FB, et al. Efficacy and safety of wet-wrap dressings in children with severe atopic dermatitis: influence of corticosteroid dilution.   Br J Dermatol   2000; 143:999-1004. Boguniewicz M:  Conventional therapy.   Immunol Allergy Clinics North Am   2002; 22:107-124.
    32. 34. Moisturizers and occlusives <ul><li>Use of effective emollient combine with hydration help to preserve stratum corneum barrier and decrease need for topical steroid. </li></ul><ul><li>Lotion contain more water than cream and may be more drying because of evaporation effect. </li></ul><ul><li>Vaseline is effective occlusive when use to seal in water after bathing. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    33. 35. Process of moisturizers <ul><li>Repairing skin barrier </li></ul><ul><li>Transiently increase water in stratum corneum </li></ul><ul><li>Decrease transepidermal water loss </li></ul><ul><li>Restoring lipid barriers’ ability to attract, hold and redistribute water </li></ul>Lynde CW. Skin Therapy Lett 2001;6:3-6 Kraft JN, et al Skin Therapy Lett 2005;10:1-8
    34. 36. Effect of a new moisturizing lotion on immediate and cumulative skin hydration: Two randomized, intra-individual, vehicle and comparator-controlled studies <ul><li>Patient: Female ≥ 18 yr with very dry skin on legs. </li></ul><ul><li>Intervention : Cetaphil Daily Advance (CDA lotion), Epidrat ultra hydrating lotion (E lotion), Physiogel lotion (P lotion), Physiogel AI cream (PAI cream) </li></ul><ul><li>Compare: Non-treated control </li></ul><ul><li>Outcome : CDA lotion induced significantly greater hydration than nontreated control (p < 0.001), induced skin hydration up to 3 days treatment cessation and improvement in skin dryness score up to 7 days after treatment cessation (p < 0.05) </li></ul>Journal of Dermatological Treatment. 2011; 22: 221–225
    35. 38. The Steroid-Sparing Effect of an Emollient Therapy in Infants with Atopic Dermatitis Grimalt et al. Dermatology 2007;214: 61–7 Patient 173 infants, moderate to severe AD, SCORAD Index 20-70 Intervention Exomega lotion (containing water, petrolatum, Shea butter, Evening primrose oil, glycerin, paraffin oil, niacinamide, butylene glycol, benzoic acid, carbomer oat extracts) Compare Placebo Outcome Primary Outcome: Amounts of use of high potency (0.1% Locatop) and moderate potency topical steroids cream (Locapred) Secondary Outcome: SCORAD index
    36. 39. Grimalt et al. Dermatology 2007;214: 61–7 P<0.05 P=0.722 * P<0.0005 **P<0.0001
    37. 40. Corticosteroid <ul><li>Reduce inflammation and pruritus are effective both acute and chronic AD. </li></ul><ul><li>Side effect are thinning of skin, telangiectasia, bruising, hypopigmentation, acne, striae, secondary infection. </li></ul><ul><li>Perioral dermatitis can occur with use of topical steroid on face. </li></ul><ul><li>High-potency topical steroid may lead to atrophic changes and systemic side effect. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    38. 41. Stepwise management of patients with AD. Akdis et al. J ALLERGY CLIN IMMUNOL JULY 2006
    39. 42. Current Medical Research & Opinion Vol. 26, No. 3, 2010, 633–640
    40. 43. Factors affecting systemic absorption of Topical Steroids <ul><li>Patient-related </li></ul><ul><li>Age </li></ul><ul><li>Individual response to drug </li></ul><ul><li>Presence or absence of skin inflammation </li></ul>David PariserAmerican Journal of Therapeutics 2009; 16 : 264–73 <ul><li>Drug-related </li></ul><ul><li>Concentration </li></ul><ul><li>Potency </li></ul><ul><li>Extent of BSA involved </li></ul><ul><li>Duration </li></ul><ul><li>Location / skin thickness </li></ul><ul><li>Vehicle </li></ul><ul><li>Use of occlusive dressings </li></ul>
    41. 44. Pediatric patients: aware of age-appropriate indications Hengge et al. J Am Acad Dermatol 2006; 54:1-15 Brodkin et al. Cutis 1997; 60: 279-80
    42. 45. Corticosteroid <ul><li>Ointments are most occlusive and better delivery of medication while preventing evaporative losses </li></ul><ul><li>In humid environment, cream may better tolerated than ointments. </li></ul><ul><li>Cream and lotions are less effective and lead to skin dryness and irritation. </li></ul><ul><li>Solution used on scalp and hirsute area </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    43. 46. Vehicle: Sequence of potency <ul><li>Ointment </li></ul><ul><li>Cream </li></ul><ul><li>Lotion </li></ul><ul><li>Gel </li></ul><ul><li>Spray </li></ul><ul><li>Foam </li></ul>Maximum Minimum
    44. 47. Corticosteroid <ul><li>Finger tip unit (FTU) proposed as applying topical steroid </li></ul><ul><li>Amount of topical medication that extend from tip to the first joint of index finger </li></ul><ul><li>1 FTU to cover hand and groin </li></ul><ul><li>2 FTUs for face or foot </li></ul><ul><li>3 FTUs for arm </li></ul><ul><li>6 FTUs for leg </li></ul><ul><li>14 FTUs for trunk </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    45. 48. Corticosteroid <ul><li>Step care approach with mid range or high potency preparation, followed by low potency preparation. </li></ul><ul><li>Once daily treatment may help adherence to regimen, fluticasone propionate and mometasone. </li></ul><ul><li>Fluticasone , once control of AD with once daily regimen was achieved, long term control could be maintained with twice-weekly, resulted in fewer relapses and less need for topical steroid. </li></ul>Wolkerstorfer A. et al:  Fluticasone propionate 0.05% cream once daily versus clobetasone butyrate 0.05% cream twice daily in children with atopic dermatitis.   J Am Acad Dermatol   1998; 39:226-231. Lebwohl M.:  A comparison of once-daily application of mometasone furoate 0.1% cream compared with twice-daily hydrocortisone valerate 0.2% cream in pediatric atopic dermatitis patients who failed to respond to hydrocortisone: Mometasone Furoate Study Group.   Int J Dermatol   1999; 38:604-606.
    46. 49. V ariation in T opical S teroid P rescribing H abits <ul><li>Step-care approach </li></ul><ul><ul><li>Mid-range or high potency to induce remission followed by quick tapering down to low-potency preparations </li></ul></ul><ul><li>Short-burst treatment </li></ul><ul><ul><li>use short bursts of a potent preparation followed by a steroid-free “holiday period” of emollient use only until relapse occurs </li></ul></ul><ul><li>Maintenance therapy </li></ul><ul><ul><li>When once daily achieved, shifted to twice-weekly applications to areas that had previously been involved but now appeared normal </li></ul></ul>Krakowski et al. Pediatrics 2008; 122 : 812-24 Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    47. 50. Corticosteroid <ul><li>Topical steroid can decrease S. aureus colonization </li></ul><ul><li>Allergen-induce immune activation can alter T cell response to glucocorticoid receptor binding affinity. </li></ul><ul><li>Systemic steroid should be avoided in AD. </li></ul><ul><li>Dramatic improvement with systemic steroid associated with flaring of AD after discontinuation. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    48. 51. Tacrolimus and Pimecrolimus are structurally similar Pimecrolimus 810.48 Da C 43 H 68 CINO 11 Tacrolimus 822.05 Da C 44 H 69 NO 12 ·H 2 O HO H 3 CO CH 3 OH O CH 3 · H 2 O CH 3 H 3 CO OCH 3 N O O O O H 3 C H 3 C O OH H H CI H 3 CO CH 3 OH O CH 3 CH 3 H 3 CO OCH 3 N O O O O H 3 C H 3 C O OH H H CH 3
    49. 52. Topical Calcineurin Inhibitors <ul><li>Pimecrolimus cream 1% (≥ 2 yr) (Elidel) </li></ul><ul><ul><li>mild to moderate AD. </li></ul></ul><ul><li>Tacrolimus ointment 0.1% (adult) </li></ul><ul><li>0.03% (≥ 2 yr) (Protopic) </li></ul><ul><ul><li>moderate to severe AD . </li></ul></ul>
    50. 53.    Topical calcineurin inhibitors complexing with macrophilin-12 and calcium-calmodulin to block dephosphorylation of NF-AT by calcineurin, preventing translocation of NF-AT to the nucleus. CaN, Calcineurin; MP-12, macrophilin-12;NF-ATc, nuclear factor of activated T cells in the cytoplasm;NF-ATn, NF-AT in the nucleus; NF-κB,nuclear factor-kappa B; TCI, topical calcineurin inhibitor. Journal of the American Academy of Dermatology V olume 53, Issue 1 Suppl (July 2005)
    51. 54. Topical calcineurin inhibitors(TCIs) <ul><li>Useful for treatment face and intertriginous area. </li></ul><ul><li>Inhibitory effect on cytokine production </li></ul><ul><li>Application site : Stinging, burning, redness in 10-30% of patient esp in extensive excoriation but mostly transient < 1wk </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    52. 55. <ul><li>6-week RCT </li></ul><ul><li>Compared twice daily Tx with pimecrolimus 1% with tacrolimus  0.03% ointment </li></ul><ul><li>141 children ( 2 – 17 yr ) with moderate AD </li></ul><ul><li>Pimecrolimus had better local tolerability. </li></ul><ul><li>No difference in efficacy Tx, after 6 wks </li></ul><ul><li>Pimecrolimus cream 1% had better formulation attributes and local tolerability than tacrolimus ointment 0.03% while providing similar efficacy and overall safety in pediatric patients with moderate AD. </li></ul>A randomized investigator-blinded study comparing pimecrolimus cream 1% with tacrolimus ointment 0.03% in the treatment of pediatric patients with moderate atopic dermatitis Kempers et a.lJ AM ACAD DERMATOL OCTOBER 2004
    53. 57. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: Results from 3 randomized, comparative studies <ul><li>6-week RCT in 1065 patients </li></ul><ul><li>Compared twice daily Tx with pimecrolimus  1% cream with tacrolimus ointment 0.03% in 426 children with mild AD; 0.1% in 226 children with moderate to severe AD and in 413 adults with mild to very severe AD. </li></ul><ul><li>Significantly more patients treated with tacrolimus had almost or completely cleared AD (43 vs 31 %) </li></ul><ul><li>Tacrolimus ointment is more effective and has a faster onset of action than pimecrolimus cream; their safety profiles are similar. </li></ul>Paller et alJ AM ACAD DERMATOL MAY 2005.
    54. 58. Paller et alJ AM ACAD DERMATOL MAY 2005.
    55. 59. <ul><li>Patient: Adult and pediatric (n = 347) with AD </li></ul><ul><li>Intervention: Tacrolimus ointment 0.03% </li></ul><ul><li>Compare: Pimecrolimus cream 1%; </li></ul><ul><li>Control: - </li></ul><ul><li>Outcome: EASI at the end of study, tacrolimus ointment was significantly more effective than pimecrolimus cream ( p = 0.0002). Frequency of adverse events was comparable between treatment groups (24.0% for tacrolimus ointment vs. 25.6% for pimecrolimus cream) </li></ul>Safety and Efficacy of Tacrolimus Ointment Versus Pimecrolimus Cream in the Treatment of Patients with AD Previously Treated with Corticosteroids Robert al. Acta Derm Venereol 2010; 90: 58–64
    56. 60. Robert al. Acta Derm Venereol 2010; 90: 58–64
    57. 61. In a Public Health Advisory issued March 10, 2005, FDA recommended physicians to consider: <ul><li>Use TCIs only as second-line therapy in unresponsive to or intolerant of other Tx </li></ul><ul><li>Avoid use of TCIs in < 2 yrs ; found higher rates of URI in < 2 yrs treated with pimecrolimus </li></ul><ul><li>Use TCIs only for short periods of time and use minimum amount necessary to control symptoms; avoid continuous use </li></ul><ul><li>Avoid use TCIs in compromised immune systems </li></ul>
    58. 62. FDA issued warnings about possible link between TCIs and cancer 2006 placed &quot;black box&quot; <ul><li>Animal studies in mice, rats, monkeys have increased risk of lymphoma and skin cancers with TCIs </li></ul><ul><li>2004, FDA received 29 reports of cancers in adults and children treated with TCIs; half were lymphomas and other half were cutaneous tumors </li></ul>
    59. 63. Current Medical Research & Opinion Vol. 26, No. 3, 2010, 633–640
    60. 64. Tar preparations <ul><li>Tar inhibit influx of proinflammatory cells and in expression od adhesion molecules in response to epicutaneous allergen challenge. </li></ul><ul><li>Tar preparation used with topical steroid in chronic AD may reduce need for more potent steroid preparation. </li></ul><ul><li>Tar shampoos are often beneficial for scalp involvement. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    61. 65. Paghdal KV - J Am Acad Dermatol - 01-AUG-2009; 61(2): 294-302
    62. 66. Adverse effects of Tar Preparations. <ul><li>Avoid using Tar in inflamed skin because it may result in skin irritation. </li></ul><ul><li>photosensitivity reactions </li></ul><ul><li>pustular folliculitis. </li></ul>Rare
    63. 67. Microbial agent <ul><li>Lipophilic yeast M. sympodialis and superficial dermatophyte T. rebrum associated with elevated with specific IgE levels in AD, clinical improvement after antifungal therapy </li></ul><ul><li>Boguniewicz M., SchmiGrendelmeier P., Leung D.Y.M.:  Atopic dermatitis.   J Allergy Clin Immunol   2006; 118:40-43. </li></ul><ul><li>S. aureus are superantigen result in persistent inflammation or exacerbation of AD </li></ul><ul><li>Leung:  Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis: evidence for a new group of allergens.   J Clin Invest   1993; 92:1374 </li></ul><ul><li>More than half of AD had S. aureus culture from skin. </li></ul>
    64. 68. Antiinfective therapy <ul><li>Systemic ATB may necessary to treat AD when secondary infection with S. aureus is present. </li></ul><ul><li>Penicillin or first or second generation cephalosporins for 7-10 days are usually effective. </li></ul><ul><li>Maintenance ATB therapy should be avoided, because it may result in colonization by methicillin-resistant organisms. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    65. 69. Antiinfective therapy <ul><li>Topical ATB mupirocin (Bactroban) may be effective for treating localized involvement. </li></ul><ul><li>Twice-daily treatment for 5 days with nasal preparation of mupirocin may reduce nasal carriage of S. aureus. </li></ul><ul><li>Daily bathing with antimicrobial soap 1.5% triclocarban reduces in S. aureus colonization and greater improvement than placebo soap. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition
    66. 70. Bleach baths   <ul><li>Sodium hypochlorite 6% solution (liquid chlorine bleach) has activity against S. aureus including MRSA. </li></ul><ul><li>Lukewarm water, soak in the bath for 5 to 10 min. </li></ul><ul><li>Rinse with fresh water, pat themselves dry </li></ul><ul><li>Immediately apply an emollient and/or prescribed medications. </li></ul><ul><li>The baths are taken two times per week. </li></ul>Krakowski AC et al. Management of atopic dermatitis in the pediatric population. Pediatrics 2008; 122:812 .
    67. 71. Mechanism of Pruritus <ul><li>Neuropeptides, proteases, kinins, cytokines induce itching. </li></ul><ul><li>IL-31 (produced by T cells) : </li></ul><ul><li>- strongly pruritogen </li></ul><ul><li>- up-regulated by exposure to </li></ul><ul><li>staphylococcal exotoxins in vitro. </li></ul>N Engl J Med 2008;358:1483-94.
    68. 72. Antipruritic agents <ul><li>Systemic antihistamine and anxiolytics may be most useful through their tranquilizing and sedative effects </li></ul><ul><li>TCA doxeptin: both H1 and H2 receptor binding affinity as well as long half life. </li></ul><ul><li>Second-generation antihistamine: effective in treating pruritus, modest clinical benefit </li></ul><ul><li>Cyclosporin A: decrease transcription of proinflammatory cytokines </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    69. 73. Treatment of pruritus with topically appliedopiate receptor antagonist <ul><li>open pilot study on 18 patients with different chronic pruritic disorders </li></ul><ul><li>using a topical formulation of 1% naltrexone for 2 weeks. </li></ul><ul><li>A punch biopsy was performed in 11patients before and after application of naltrexone cream </li></ul><ul><li>randomized, placebo-controlled, crossover trial was performed with the same </li></ul><ul><li>We included in this trial 40 patients with localized and generalized atopic dermatitis with </li></ul><ul><li>severe pruritus. </li></ul><ul><li>Results: In the open study more than 70% of the patients using the 1% naltrexone cream experienced </li></ul><ul><li>a significant reduction of pruritus. More interestingly, the topical treatment with naltrexone caused an </li></ul><ul><li>increase of epidermal MOR staining. The regulation of the epidermal opioid receptor correlated with the </li></ul><ul><li>clinical assessment. The placebo-controlled, crossover trial demonstrated clearly that the cream containing </li></ul><ul><li>naltrexone had an overall 29.4% better effect compared with placebo. The formulation containing </li></ul><ul><li>naltrexone required a median of 46 minutes to reduce the itch symptoms to 50%; the placebo, 74 minutes </li></ul>J AM ACAD DERMATOL.JUNE 2007
    70. 74. Hospitalization <ul><li>Erythroderma </li></ul><ul><li>Toxic </li></ul><ul><li>Remove Pts from environmental allergen or stressor </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    71. 75. Systemic immunomodulatory therapies <ul><li>Cyclosporine </li></ul><ul><li>Recombinant human Interferon-gamma </li></ul><ul><li>Azathioprine </li></ul><ul><li>Mycophenolate mofetil </li></ul><ul><li>Phototherapy </li></ul>
    72. 76. Cyclosporin A <ul><li>Cyclosprin A (5MKD) using either intermittent or continuous treatment show no significant differences between two approaches. </li></ul><ul><li>Severe AD treated with cyclosporin A, 5MKD for 6 wks, monitored until relapse and treated with second 6 wks course. Subset of Pts get clinical benefit. </li></ul>Harper al:  Br J Dermatol   2000; 142:52-58.
    73. 77. Phototherapy and photochemotherapy <ul><li>UV light : modality for chronic AD. </li></ul><ul><li>High dose UVA1: decrease dermal IgE-binding cells, down regulating proinflammatory cytokines or inducing apoptosis in skin-infiltrating CD4+ T cells. </li></ul><ul><li>Photochemotherapy with oral methoxypsoralen therapy followed by UVA may be indicated in severe AD. </li></ul>Hanifin J.M., Cooper K.D., Ho V.C., et al:  J Am Acad Dermatol   2004; 50:391-404.
    74. 78. Clinical Efficacy of Blue Light Full Body Irradiation as Treatment Option for Severe Atopic Dermatitis <ul><li>Patient : 36 pts with severe, chronic AD resisting long term disease control with local corticosteroids </li></ul><ul><li>Intervention : 1 cycle of 5 consecutive blue light-irradiations (28.9 J/cm2).Patients were instructed to ask for treatment upon disease exacerbation despite interval therapy with topical corticosteroids </li></ul><ul><li>Compare: - </li></ul><ul><li>Outcome: The majority of pts noted first improvements after 2–3 cycles. EASI score was improved by 41% and 54% after 3 and 6 months </li></ul>. Becker.D et al . Plos One.2011;6(6):e20566. Epub 2011 Jun 8.
    75. 79. *=p≤0.05 ***=p≤0.02 **p≤0.005 ***p≤0.002
    76. 80. Recombinant human IFN-ɣ <ul><li>IFN-ɣ suppresses IgE synthesis and inhibit Th2 cell function. </li></ul><ul><li>rhIFN-ɣ reduced severity and decrease total circulating eosinophil in AD. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    77. 81. Azathioprine <ul><li>Affect purine nucleotide synthesis and metabolism. </li></ul><ul><li>Side effect : myelosuppression, hepatotoxicity, GI disturbance, susceptible for infection, skin cancer. </li></ul><ul><li>Onset of action is slow, benefit may not be apparent for several month after treatment. </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999
    78. 82. <ul><li>Allergen desensitization </li></ul><ul><li>Intravenous gammaglobulin </li></ul><ul><li>Omalizumab </li></ul><ul><li>Antifungal therapy </li></ul><ul><li>Traditional Chinese herbal therapy </li></ul><ul><li>Probiotics </li></ul><ul><li>Essential fatty acids </li></ul><ul><li>Leukotriene receptor antagonists </li></ul>
    79. 83. <ul><li>Prevention </li></ul><ul><ul><li>Delayed solid food introduction </li></ul></ul><ul><ul><ul><li>No protective effect was seen by delaying the introduction of solid food after 4 month. </li></ul></ul></ul><ul><ul><ul><li>Avoidance of soybean, nuts, and cocoa in first 6 months , did have protective effect in the nonintervention cohort. </li></ul></ul></ul><ul><ul><ul><li>AAP recommend for delayed beyond 4 month of life </li></ul></ul></ul><ul><ul><li>Probiotics </li></ul></ul><ul><ul><ul><li>The evidence for the use of probiotics for treatment of AD is lacking, however, there does appear to be benefit to the use of prenatal probiotics for prevention of AD. </li></ul></ul></ul>
    80. 84. <ul><li>Environmental and behavioral modification </li></ul><ul><ul><li>U nfavorable indoor climate, HDM exposure </li></ul></ul><ul><ul><li>Zinc : decrease plasma level found in AD </li></ul></ul><ul><ul><li>Vitamin D : induces expression of protective antimicrobial peptides </li></ul></ul><ul><ul><li>C ontact allergies </li></ul></ul><ul><ul><li>Food – induced eczema </li></ul></ul><ul><ul><li>Education </li></ul></ul><ul><ul><li>Skin care and emollient </li></ul></ul>
    81. 85. Conventional Therapies <ul><li>Identification and elimination of exacerbating factors (irritants, proven allergens) </li></ul><ul><li>Addressing psychological aspects </li></ul><ul><li>Education </li></ul><ul><li>Hydration </li></ul><ul><li>Moisturizers </li></ul><ul><li>Topical corticosteroids </li></ul><ul><li>Topical calcineurin inhibitors </li></ul><ul><li>Anti-infective therapy </li></ul><ul><li>Anti-pruritic therapy </li></ul>Mark Boguniewicz, Donald Leung.Middleton’s Allergy 7’th edition 1 893-1999