Atopic dermatitis

Anchalee Senavonge MD.
Allergy and Immunology division
Pediatric department
King Chulalongkorn Memorial Hospital

Outline
• Definition and epidemiology
• Pathophysiology
• Clinical manifestation
• Adult vs Children onset
• complication
• Natural course
• Diagnosis
• Treatment

.
Definition
• Non-contagious chronic relapsing inflammatory skin disease
• Often associated with other atopic disorders (50% asthma, 75% AR)
• The hallmarks of atopic dermatitis
1.) Chronic, relapsing form of skin inflammation
2.) A disturbance of epidermal-barrier function  Dry skin
3.) IgE-mediated sensitization to food and environmental allergens
Middleton's Ed.8
Bieber T. N Engl J Med 2008;358:1483-94
Weidinger S, Novak N. Lancet 2016;387: 1109-22

Epidemiology
• Prevalence has doubled/tripled during past 3 decades
-15 to 30% of children
- 2 to 10% of adults
• Frequently starts early onset
- 45% within the first 6 months of life
- 60% during the first year of life
- 85% before 5 years of age
• Up to 70% of children have a spontaneous remission before adolescence
Middleton's Ed.8
Bieber T. N Engl J Med 2008;358:1483-94
Weidinger S, Novak N. Lancet 2016;387: 1109-22

Age group 6 to 7 years
• 385,853 participants from 143 centers in 60 countries
• Ranged from 0.9% in India to 22.5% in Ecuador
Age group 13 to 14 years
• 663,256 participants from 230 centers in 96 countries
• Ranged from 0.2% in China to 24.6% in Columbia
Lower in boys than girls in both groups
Odhiambo JA. J Allergy Clin Immunol 2009;124:1251-8
ISAAC

11-16% in 6-7 year-old
7-10% in 13-14 year-old

1. Genetic and role of epidermal barrier
2. Role of allergens
3. Immune dysregulation
Middleton's Ed.8
Boguniewicz and Leung. Immunol Rev. 2011 July ; 242(1): 233–246.

• Most patients with AD have a genetic predisposition to develop an IgE response to
common environmental allergens
• Suggesting atopic dermatitis–specific genes
- Atopic dermatitis is higher among monozygotic twins (77%) than among dizygotic
twins (15%)
- History of atopic families had a significantly higher risk in AD
1. Genetic and role of epidermal barrier
Middleton's Ed.8
Bieber T. N Engl J Med 2008;358:1483-94.

Middleton's Ed.8
Genes that have been proposed as
playing a key role
1.) Skin barrier/epidermal
differentiation genes
2.) Immune response/host
defense genes

Filaggrin gene
• Loss-of-function variants in the FLG gene is the strong association
• Chromosome 1q21
• FLG mutations are found in 10-50% of AD but also in 9% in non-AD population
• Reduction in FLG expression are in nearly almost patients AD
Gene encoding the
epidermal barrier protein
W. H. Irwin McLean. The scientist, December 1, 2010.
Alan D. Irvine. N Engl J Med 2011;365:1315-27.
Leung and Guttman-Yassky. J Allergy Clin Immunol. 2014 October ; 134(4): 769–779.

Filaggrin = filament aggregating protein

Leung and Guttman-Yassky . J Allergy Clin Immunol 2014;134:769-79

Other gene
• Gene complex comprising over 50 genes encoding proteins
• Located within chromosome 1q21
• Involved in the terminal differentiation and cornification of keratocytes (primary cell
types of epidermis)
Int Immunol 2015;27;269-80
Epidermal differentiation complex

2. Role of allergens
Elevated serum IgE levels can be demonstrated in
80% to 85% of patients with AD
Allergen
- Foods
- Aeroallergen
- Microbial agents
-Autoantigens
Non-allergen
- Stress
- Irritant: soap, detergent, fabric, cosmetic
- Temperature change: hot, sweat, humidity
Itch scratch cycle
Middleton's Ed.8

Food
~ 1/3 of children with severe atopic eczema suffer from FA
• Most common : cow's milk or hen's egg
• Dysfunctions in the epidermal barrier seem to be vitally important in the
development of food allergies in patients with atopic eczema by facilitating
sensitization after epicutaneous allergen exposure
• Maybe associated with genetic that increased risk of food allergy
• Food-specific T cells have been cloned from lesion and blood of patients with AD
Middleton's Ed.8
Ebisawa M,et al. Chem Immunol Allergy. Basel, Karger, 2015, vol 101, pp 181–190.

Aeroallergen
House-dust mites, animal danders, and pollens
• Severity of AD; correlated with the degree of sensitization to aeroallergens
• Aeroallergens intranasally exacerbate AD
• Direct contact with inhalant allergens eczematous skin eruptions
• Reducing dust mite allergen clinical improvement in AD patients
Middleton's Ed.8

Infection
•Yeast: Malassezia sympodials
•Dermatophyte: Trichophyton rubrum
•Bacteria: S. aureus exotoxin superantigen
•>90% cultured from their skin
•~50% had sIgE antibodies directed against the staphylococcal toxins on their skin
• May also be associated with colonization of the nares
•correlate between the presence of IgE against superantigens and severity of AD
Middleton's Ed.8

SEB (superAg Staphylococcal Enterotoxin B binds to HLA and Vβ3+ on TCR

Autoantigens
• Several groups have suggested a role for autoantigens in chronic AD
• Release intracellular antigen from damaged skin by infectious organisms or
scratching could trigger IgE or T cell–mediated responses
• Hom s 1: IgE-reactive autoantigens, a 55-kD cytoplasmic protein in
keratinocytes
• DFS70 (dense fine speckles 70 kD)
• MnSOD (human manganese superoxide dismutase) by molecular mimicky
leading to cross-reactivity -skin-colonizing yeast M. sympodialis
Middleton's Ed.8

Middleton's Ed.8
CCL11-Eotaxin-1
CCL13- MCP-4
CCL26: Eotaxin-3
CCL11,13,26- CCR3 Eos, CCR2 MCTARC (CCL17)- CCR4 Th2
CTAK(CCL27)-CCR10 T cells
CCL18-CCR10 T cells enter
epidermis
CCL1, 22- CCR4,8 Th2

Acute phase: Inflammation
Th2 mainly
Th17,Th22
Middleton's Ed.8
W. Peng and N. Novak. Clinical & Experimental Allergy, 2015 (45), 566–574.

Chronic phase: lichenification
Mixed response
Th1,Th2,Th17,Th22
W. Peng and N. Novak. Clinical & Experimental Allergy, 2015 (45), 566–574.

Leung and Guttman-Yassky. J Allergy Clin Immunol. 2014 October ; 134(4): 769–779.
Summary acute & chronic phase
Spongiosis
Th2 , Th 17,22
Lichenification
Th1, Th2, Th17, Th22
CXCL9(MIG)
CXCL10(IP-10)
CXCL11(ITAC)
-CXCR3 on Th1

AD: Immune dysregulation
Middleton’s allergy: Principles and practice 8th ed
↑IgE, sIgE
↑FceRII (CD23)
↑FceRI
↑CTACK (CCL27), TARC (CCL17)
↑Th2 cytokine
↓Th1 cytokine
↓Treg
↓AMP
↑cAMP ↑ IL-10 ↑PGE2

• Principal features
- Severe pruritus
- Chronic relapsing course
- Typical morphology and
distribution of the skin lesions
- History of atopic disease
Clinical manifestation
Middleton's Ed.8
Practice parameter 2013
J Allergy Clin Immunol 2014;134:769-79

Morphology and distribution
Infantile type
 Generally acute
 Lesions mainly on face and the extensor surfaces of the
limbs
 Trunk might be affected, but the napkin area is typically
spared
Childhood type
 From age 1-2 years onwards
 Polymorphous manifestations with different type of skin
lesions
 Lesions particularly in the flexural folds
Adolescents and adult type
 Often present lichenified and excoriated plaques
 At flexures, wrists, ankles, and eyelids
 Head and neck : involved the upper trunk, shoulders, and scalp
 Might have only hand eczema or present with prurigo-like
Weidinger S. et al,Lancet;387:1109-22

Adult-onset AD
• AD in adults is characterized by marked clinical heterogeneity, with
numerous clinical profiles that do not always coincide with those
observed in children
• The course is generally intermittent, with phases of latency and
exacerbation
Silvestre Salvador JF, et al. J Investig Allergol Clin Immunol 2017; Vol. 27(2): 78-88

Adult-onset AD: clinical patterns
1. Chronic, persistent form
• had AD since childhood, (20%-30% of childhood cases persist into adulthood)
2. Relapsing course
• 12.2% childhood AD
• AD resolves before or during adolescence and then recurs in adulthood
3. Adult-onset AD
• 18.5% of all cases of AD first appear in adulthood
• usually in 20 to 40 years
• clinical presentations that are rare in children eg, nummular eczema, prurigo, and
head-and-neck dermatitis

Nummular eczema: round, inflamed sores ,
located most often on the lower limbs . They
tend to be refractory to treatment
Prurigo: usually appears at 40-50 years of age, consists of
highly pruriginous papules and lumps, generally on the
shoulder girdle and arms

In the most chronic cases, hyperpig
mented and lichenified areas are
visible on the neck; this phenomenon is
known as ‘dirty neck’ due to its unclean
appearance
“portrait” type
extends to seborrheic areas (upper ch
est, back)
-morphology similar to folliculitis
-Pityrosporum ovale as trigger
Typical distribution.
On the face, both eyelid and lips tend
to be involved. Chronic atopic cheilitis
is also common in young women

Dyshidrotic eczame: recurrent flare-
ups of blistering on palm, sides of the fingers Inflammatory pattern are “red” in
appearance associated with
superinfection Presence of alopecia areata
indicates a high severity
lichenification, excoriations, crusts, and xerosis
Severe case: achromic lesions (eg, vitiligo) in
the most lichenified flexural areas

Infection: Herpes Simplex
Herpes simplex : Eczema herpeticum
- Pathophysiologically, possibly less active of plasmacytoid dendritic cell activity may be
involve [pDCs are important mediators of antiviral immunity through their ability to
produce large amounts of type I interferons (IFNs) on viral infection]
- reduced interferon-γ (IFN-γ) production are significantly associated with AD and EH
and may contribute to an impaired immune response to HSV
- reduce human cathelicidin
-
Middleton's Ed.8

Infection: Eczema herpeticum
Skin: Often present with herpetic vesicles: small, monomorphic, dome-shaped
papulovesicles that rupture to form tiny punched-out ulcers overlying an erythematous
base over face, neck, and upper trunk.
• May have secondary staphylococcal infection
• Often accompanied by fever and lymphadenopathy
• Investigation:
• Tzanck test: multinucleated giant cells and acantholysis (cell separation)
• Viral culture
• Direct fluorescent antibody stain
• PCR (Polymerase Chain Reaction) sequencing
• Treatmant: oral/IV acyclovir
Middleton's Ed.8

Infection: Eczema herpeticum
• A disseminated, distinctly monomorphic eruption of dome-shaped
vesicles, accompanied by fever, malaise and lymphadenopathy
Wollenberg et al. Journal European Academy of Dermatology and Venereology 2016, 30, 729–747

Infection: Eczema Vaccinatum
Severe adverse reaction to smallpox vaccination
- serious local or disseminated, umbilicated, vesicular, crusting skin rashes
- widespread infection of the skin in people with previous diagnosed skin conditions
such as eczema or atopic dermatitis
Smallpox vaccine is contraindication in AD patients
Canadian Family Physician. 2012;58(12):1358-1361.
Middleton's Ed.8

Infection: Malassezia sympodialis
• Predominantly of the head and neck
• Lipophilic yeast, formerly Pityrosporum ovale
•common in seborrheic area and scalp
• Clinical significance because patients improve after antifungal therapy (Tx head-neck-
shoulder dermatitis with topical ciclopirox olamine)
• Dx: KOH (difficult to c/s)
Middleton's Ed.8
Practice parameter 2012

Infection: Molluscum contagiosum
•Viral infection
•Autoinoculation and spread of lesions can occur from scratching
•Lesions: translucent flesh-colored papules with an umbilicated core
•If diagnosis is in question, biopsy will show papillomatosis with central umbilication and
viral inclusion bodies known as Henderson-Patterson bodies (Molluscum bodies)
• Resolve spontaneously, treatment speeds healing and prevents spreading by auto- and
heteroinoculation
Middleton's Ed.8
Barrett & Luu et al. Imm Aller Clin N Am 37(2017) 11-34
Lobular hyperplasia -characteristic cup-shaped
invaginations, eosinophilic inclusion

Stephan Weidinger, Natalija Novak. The Lancet, Volume 387, Issue 10023, 2016, pp. 1109-1122
Staphylococcus
Eczema
herpeticum
Molluscum
contagiosum

Diagnosis
• No objective test for the diagnosis of AD
• Diagnosis is based on a constellation of clinical features
• Pruritus and chronic or relapsing eczematous lesions with typical
morphology and distribution, and a history of atopic disease
• The presence of pruritus is critical to the diagnosis of AD
Middleton's Ed.8
Practice parameter 2013.

J. TADA. JMAJ 45(11): 460–465, 2002.

Barrett & Luu et al. Imm Aller Clin N Am 37(2017) 11-34

• Attempts to standardize severity scoring
• Used primarily in clinical research trials
Middleton's Ed.8
Carel K.Ann Allergy Asthma Immunol. 2008;101:500–507.
Severity

SCORAD
Disease severity
- mild <25
- moderate 25-50
- severe> 50

Complication: Ocular problems
• Atopic keratoconjunctivitis : bilateral, and symptoms include itching, burning,
tearing, and copious mucoid d/c
• Eyelid dermatitis
• Chronic blepharitis : visual impairment from corneal scarring
• Keratoconus : result from persistent rubbing
• Increased numbers of IgE-bearing Langerhans cells are found in the conjunctival
epithelium of patients with AD
Middleton's Ed.8

Middleton's Ed.8
Differential
diagnosis

Natural course
•Early onset of AD increase risk for respiratory allergy: Asthma, ARC
• Highest incidence of asthma: onset of AD < 3 months, in those with severe AD and a
family history of asthma
• Respiratory allergy
• Onset of AD < 3 months + ≥2 atopic family members 50%
• Onset of AD≥3 months + no atopic family members 12%
• Children with AD have more severe asthma than asthmatic children without AD

Natural course
•60% manifests during the 1year of life, 90% before 5 years
•Eczematous lesions usually do not occur before 2nd month of life
•The earliest clinical signs: skin dryness and roughness
•80% mild disease
•Continuous for long periods or relapsing–remitting nature with repeated flare-ups
•Up to 70%, greatly improves or resolves until late childhood
• Risk factors for a long course: early and severe onset, family history of AD, and
early allergen sensitizations.
Weidinger S., Novak N., Lancet 2016; 387: 1109–22.

Natural course
Thai CPG
17% มีผื่นกําเริบเป็นช่วงๆ ถึงอายุ 7 ปี
20% มีอาการเรื้อรังถึงผู้ใหญ่
2/3 อาการหายไปภายในอายุ 5 ปี
Predictive factors of a poor prognosis
1. Widespread AD in childhood
2. Concomitant AR and asthma
3. FH of AD in parents or siblings
4. Early age at onset of AD
5. Very high serum IgE levels
6. Filaggrin gene null mutations
Nelson textbook of Pediatric 20th edition

Natural course
•205 children mild AD(61.0%), moderate (29.3%) severe (9.7%)
•Early AD= in first two years of life : 64.4%.
•AD completely disappeared in 102 cases (49.8%) by the
median age of 3.5 (1.5-7.8) years.
•Early onset and severity of AD were major determinant of
prognosis.
•AR and asthma was 36.6%, and 9.3%
•Conclusions: Half of AD had completely disappeared at
preschool age. Good prognosis was mostly determined by early
onset AD and mild severity. Late onset, FH of atopy , ↑serum
IgE level are associated with respiratory allergy
Asian Pac J Allergy Immunol 2015;33:161-8
Chula

Natural course Siriraj
Somanunt S, et al. Asian Pac J Allergy Immunol. 2016 Dec 12. doi: 10.12932/AP0825
Remission rate
Duration
<2 y
≥2 y

Natural course
102 AD patients (60.8% female) were followed for 10.2±4.7 years. Median age at diagnosis= 1.5 (0.1-12.0) years
-44% complete remission at median age of 6.3 (2.0-15.0) years
-Remission rate of AD was higher in early AD than later onset AD
-47% of early AD (onset <2 years) had concomitant food allergy which egg and cow’s milk were leading causes.
-Most common allergen sensitization=DP, DF
-AR 61.8% and asthma 29.4,median age of 4.6 and 3.8 years
-Early AD and food allergies significantly associated with early asthma (onset <3years) (OR=10.80,OR=8.70)
Conclusions: Almost half of AD children had complete remission at school age with a better prognosis in early AD. At
preschool age, 2/3 developed AR and 1/3 asthma. Early AD and food allergy were risk factors of early asthma.
Siriraj

All food allergies were more frequently found in early AD
(<2 years old)
Natural course Siriraj

Investigation
Diagnosis of AD is based on clinical “No specific laboratory tests”
• Serum IgE and eosinophil counts are elevated
• SPT, Patch test can identify the allergens
• Skin biopsies
- Not essential for the diagnosis
- Exclude other diagnoses
- more severe
- unclear diagnosis
- unsatifactory response to therapy

N. Visitsunthorn et al. Ann Allergy Asthma Immunol 117 (2016) 668-673
Patch test in AD Siriraj
•Prospective, self-controlled study 56 AD  SPT APT , OFC
•moderate AD (49.1%) mild (20%) severe (13.2%)
•Food allergen (lyophilized CM, EW, EY, wheat, soy, shrimp)
•APT+ve49% (sen 40%, spec90.2%, PPV 65.2%, NPV 76.6%)
•SPT+ve54.7%(sen40%, spec 93.9%, PPV 75%, NPV 77.3%)
•Aeroallergen (to DP,DF,AC)
•APT positive 33.9%, 35.8%,21.8% (1/3)
•SPT positive 28.3%, 24.5%, 9.4% (1/4)

N. Visitsunthorn et al. Ann Allergy Asthma Immunol 117 (2016) 668-673
Patch test in AD Siriraj
•Conclusion: APTs with locally prepared lyophilized allergen extracts were safe and high
speciﬁcity, median PPV, and low sensitivity for evaluation of suspected food allergy in
children with AD
•When APT and SPT both negative, OFC negative 74-90%
•When APT and SPT both positive, OFC positive 100%

Management of AD
• Irritants and allergens avoidance
• Topical treatment
• Moisturizer, bath, wet wrap
• Topical corticosteroids
• Topical calcineurin inhibitors
• Topical antiseptic
• Other
• Systemic treatment
• Antihistamines
• Prednisolone and immunosuppressive drugs
• Antibiotics
• Tar preparation
• Phototherapy
• Immunotherapy
• Prevention

1. Thai CPG2013
2. Practice parameter 2012
3. American Academy of Dermatology 2014
4. European Task Force on Atopic Dermatitis; position paper 2015
5. Middleton 8th edition textbook
1. แนวทางการดูแลรักษาโรคผื่นภูมิแพ้ผิวหนัง 2556
2. Schneider et al. JACI.2013.12.672
3. Eichenfield et al. J Am Acad Dermatol. 2014 July ; 71(1): 116–132.
4. Wollenberg et al. Journal European Academy of Dermatology and Venereology 2016, 30, 729–747
5. Middleton’s allergy: Principles and practice 8th edition

Skin hydration
Lotion <cream< oil< gel< ointment
Thai Practice parameter AAD European task force Middleton
-เด็ก250 g/week,
ผู้ใหญ่ 500 g/week
≥2 ครั้ง/วัน และบ่อยๆได้ตาม
ต้องการ
-ชนิดขึ้นกับดุยพินิจ
-ทาก่อนหรือหลังยา ยกเว้น
ointment ทายาก่อน
-Amount N/A
-not clear that more
expensive ‘‘barrier
creams” are more
effective than
traditional such as
petrolatum
-2-3 times/day
-Lipids mimic
endogenous
(palmitoylethanolami
de, glycyrrhetinic
acid), ceramides
-Head-to-head trial-
no one superior to
others
-30 g/day or 1
kg/month in adult
-At least 2 times/day
Amount N/A
-Alpha-hydroxy acids
-Ceramide deficiency
due to highly express
sphingomyelinase
deacylase

Moisturizers types
1. Occlusive: best= petrolatum, mineral oil
• Hydrocarbon: parafin
• fatty acid: lanolin acid
• fatty alcohol: lanolin
• Phospholipid: Lecithin
• Polyhydric alcohols: Propylene glycol
• Ceremide
2. Humectant
• Glycerin, urea, propylene glycol, pyrrolidone carboxylic acid, hyaluronic acid,
panthenol (vit B5), sorbitol, gelatin, honey
• natural humectant WI dermis is glycosaminoglycans eg. Hyaluronic acid
3. Emollient: ceramide, stearic, linoleic, demethicone
4. Barrier
Czarnowicki et al. J Allergy Clin Immunol 2017;139:1723-34.

Anti-inflammatory agents in moisturizer
• Aloe vera (Salicylic acid, manesium lactate and gel polysaccharudes) -Zermix
• Bisabolol (extract from German chamomile)- Atopiclair
• Shea butter (Butyrospermum parkii)
• Niacinamide (Vitamin B3)- La Roche-Posay, Cetaphil
• Palmitoylethanolamide (PEA) –Physiogel AI
• Licochacone A/Glycyrrhiza inﬂata (extract from licorice root) -Eucerin
• Glycyrrhetinic acid/Glycyrrhiza glabra (extract from licorice root)
• Stimutex-AS (Spent grain wax+shea butter+Argania spinosa kernel oil) -Ezerra
• Grape seed (Vitis vinifera) –Eucerin, Atopalm
• Panthenol (vitamine B5): Cetaphil, La Roche-Posay
• Chamomile (Matricaria chamomilla)
• Coconut oil

Bathing
-< 5-10 นาที
-นํ้าไม่ร้อนจัด (อุ่นหรือ
อุณหภูมิห้อง)
-Avoid antiseptic สบู่
ไม่ระคายเคือง
-ทาemollient ทันที
-At least 10 min
-Warm
-Apply occlusive
moisturizer
-5-10 min
-lukewarm
-Non-soap cleaner,
neutral to low pH,
fragrance free
-Soak and smear
technique
-5 min
-Warm
-Bath oil (last 2 min),
non-irritant, w/o
antiseptiic
-10 min
-Warm (not lukewarm)
-Apply emollient

Bleach bath
N/A -Consider to reduce
severity of AD
-In 1 RCT: ½ cup of bleach
in 40 gallons of water twice
weekly plus intranasal
mupirocin 5 days/month
-may be helpful in
moderate to severe
AD with frequent
bacterial infections
-Topical antiseptics –lack good
evidence
-Sodium hypochlorite (100 mL
of 5% household
Bleach/100 L, full tub)
-reduce skin
infection but may
lead to irritation, use
with caution
-Diluted bleach bath
(1/4-1/2 cup/tub)
1 cup=250 ml

Wet wrap therapy
ในรายกําเริบรุนแรงหรือดื้อ
ยา ในเด็ก>6 เดือน
-duration 2-14 วัน (ไม่
เกิน 7 วัน)
-In refractory AD
-Combine with TCS’
currently not
recommended with
TCI
-In significant flares or
recalcitrant disease
-Several hr to 24 hr for
several days
-Use with diluted TCS
in acute, oozing ,
erosive lesions
-Up to 14 days
(usually 3 days)
-In acute
exacerbation,
resistant AD
-not with TCI

Wet wrap therapy (WWT)
• Reduce pruritus and inflammation
• ↑penetration of TCS
• ↓water loss
• physical barrier against scratching
• Overuse: chilling, maceration of the skin, infrequently secondary
infection
แนวทางการดูแลรักษาโรคผื่นภูมิแพ้ผิวหนัง 2556
Schneider et al. JACI.2013.12.672

Thai CPG WWT
• เริ่มจากการทาสารให้ ความชุ่มชื้น หรือยาทาสเตียรอยด์ หลังการอาบนํ้า
1. สารเพิ่มความชุ่มชื้นผิวหนัง
2. ยาทาสเตียรอยด์ ความแรงปานกลาง ได้แก่ mometasone fluorate หรือ fluticasone proprionate
ทาให้เจือจางให้เป็น ร้อยละ 10 ของความเข้มข้นเดิม
3. ทั้งสารเพิ่มความชุ่มชื้นผิวหนังและยาทาสเตียรอยด์
• ความถี่ในการทาผลิตภัณฑ์ที่ใช้ทาผิว:1-3 ครั้งต่อวันแต่ควรทายาสเตียรอยด์เพียงวันละ 1 ครั้ง
• พันผิวหนังด้วยผ้าที่นุ่มและทาให้ชุ่มด้วยนํ้าหรือนํ้าเกลือในชั้นแรก ทับด้วยผ้าแห้ง
• ผ้าที่ใช้: เสื้อผ้าที่ทาจากผ้าฝ้ าย ผ้ากอส หรือ cotton tubular bandage
• ทาให้ผ้าชั้นแรกชุ่มด้วยนํ้าหรือนํ้าเกลือเป็นระยะ ทุก 1, 2, หรือ 3 ชั่วโมง ควรหยุดทาในเวลากลางคืน
• ระยะเวลาในการพันผ้ารอบผิวหนัง: 3, 6, 8, 12, หรือ 24 ชั่วโมง
• ตําแหน่ง: บริเวณแขน ขา ใบหน้า หรือทั่วร่างกาย
• ระยะเวลา: 2 – 14 วัน (แนะนําไม่เกิน 7 วัน)

David A. Norris et al. J Am Acad Dermatol 2005;53:S17-25
Topical
corticosteroid
(TCS)

Topical
calcineurin
inhibitors
(TCI)
macrophilin-12
(previously known as
FK506-binding proteins)

Combined
therapy

Thai Practice parameter AAD European task
force
Middleton
Amo
unt
FTU=0.5 g N/A 1 FTU=0.5 g=2 palms
area
rule of 9's
15 g in infants
30 g in children
up to 60–90 g in
adolescents
1 FTU: hand or groin
2 FTUs face or foot
3 FTUs arm
6 FTUs leg
14 FTUs trunk
Total adult body 30 g
Dura
tion
ฤทธิ์อ่อนหรือปานกลางวัน
ละ 2 ครั้ง เมื่อควบคุม
อาการ ได้ควรลด ใช้ยาทา
เป็นช่วงๆ และใช้ยาที่มีฤทธิ์
อ่อนที่สุด ที่สามารถควบคุม
โรคได้
- Ultrahigh potency
1-2 weeks (not on
facial or skinfold)
- high-potency up to
3 weeks
stopped on
improvement
- -
TCS

Steroid side effect of TCS
• Local
• atrophic change, thinning of the skin with telangiectasias, bruising
• hypopigmentation, striae, hypertrichosis
• steroid acne, rosacea, perioral dermatitis
• secondary infections
• face, eyelids, intertriginous areas especially sensitive
• Systemic
• suppression of HPA axis
• eyes: glaucoma, cataracts
• iatrogenic Cushing's syndrome
• growth suppression
• “Steroid addiction”: primarily of the face of adult women treated with TCS,
who complain of a burning sensation
Middleton 8th edition
Thai guideline แนวทางการดูแลรักษาโรคผื่นภูมิแพ้ผิวหนัง

Topical calcineurin inhibitors
Second-line therapy (approved from 2 years of age)
• steroid sparing, delicate areas: eyelid, perioral, genital, axilla, inguinal fold
• twice daily once daily stop
• proactive: twice weekly
Property
• inhibit proinflammatory cytokine production from T cells
• Anti-inflammatory potency of 0.1% tacrolimus ointment similar to
intermediate TCS
• anti-pruritic effects: inhibition of mast cell degranulation
Middleton’s allergy: Principles and practice 8th edition

• Transient localized burning and itching during first week of topical
Tacrolimus
• Not cause skin atrophy
• Generalized viral infection such as eczema herpeticum or molluscum
has been observed
• Not increase risk of malignancy up to 12 months follow up
• Avoid in immunodeficiency, pregnancy
TCI adverse effects

Pimecrolimus cream (Elidel)
• 1% (≥ 2 yr)
• mild to moderate AD
• Lipophilicity: preferentially
distribute to the skin > systemic
circulation
Tacrolimus ointment (Protopic)
• 0.1% (>16 yr),
• 0.03% (≥ 2 yr)
• moderate to severe AD

Petite study
• Open-label, randomized, parallel group
• 3-12 months, AD affecting >5% total body surface area, IGA 2-3 (mild to
moderate)
• randomized 1:1 to
1. PIM 1% cream (n = 1205)
2. TCS (n = 1213)
Duration 5 years
• Primary objective : to compare safety over the first 5 to 6 years of life
• Secondary objective: long-term efficacy
Sigurgeirsson et al. Pediatrics 2015. Vol 135. Number 4

Safety: similar
• PIM: more bronchitis, infected
eczema, impetigo,
nasopharyngitis, 2-4%, not
considered clinically significant
Steroid sparing effect
• PIM required substantially fewer
steroid days than TCS group (7 vs
178)
• 36% of children not requiring any
TCSs
Sigurgeirsson et al. Pediatrics 2015. Vol 135. Number 4
Treatment success %

Proactive therapy
• long-term, low-dose (twice weekly), previously affected areas of skin
• ↓relapse, ↓need for TCS
• Mid-potent steroids (methylprednisolone aceponate, fluticasone propionate
and mometasone fuorate cream)1
• Tacrolimus ointment (0.03% children, 0.1% adult)1,2,3
• combination emollients on the entire body
• as young as 2 years of age for 12 months2,3
• การรักษาแบบ proactive therapy โดยการทายา topical immunomodulators
สัปดาห์ละ 2 ครั้ง จะช่วยลดการกําเริบของโรคได้ (evidence 1b, recommendation A) 4
1. Eichenfield et al. J Am Acad Dermatol. 2014 July ; 71(1): 116–132.
2. Middleton’s allergy: Principles and practice 8th edition
3. Schneider et al. JACI.2013.12.672 (JTF)
4. . แนวทางการดูแลรักษาโรคผื่นภูมิแพ้ผิวหนัง 2556

Systemic immunomodulating agents
• Systemic CS (evidence 4, recommend D)
• Cyclosporin A (Adult: evidence 1b, recommend A) (children: evidence 2b, recommend B)
• Azathioprine (evidence 1b, recommend A)
• Methotrexate (evidence 4, recommend C)
• Mycophenolate mofetil (evidence 4, recommend D)
• IFN-γ

Cyclosporin A
Thai Practice parameter AAD European task
force
Middleton
(1a,A)
-สามารถใช้ในผู้ใหญ่ที่
อาการรุนแรงเรื้อรัง
-อาจนํามาใช้ในเด็กที่
มีอาการรุนแรงและ
เรื้อรัง
-severe AD in
children and adults
benefit from CPA 5
mg/kg/day
N/A 3-5 Mkday tapered
after 6 weeks to
2.5-3 Mkday
duration 3 months
to 1 year
Benefit in adult, 5
Mkday
-in pediatric either
intermittent or
continuous
showed no
difference

Systemic corticosteroid
• Oral prednisone
• Acute exacerbation of AD (short course 0.5-1 MKD for ≤1 weeks)
• Avoided in chronic, relapsing disorder AD
• However, the dramatic improvement associated with an equally
dramatic flaring of AD after discontinuation
• Intensified topical skin care with TCS during tapering to suppress
rebound flaring of AD

Antimicrobial drugs
Secondary bacterial infection
• Oozing, pustules and fissure
• Semisynthetic penicillin or 1st or 2nd generation Cephalosporin 7-10 days
• Maintenance antibiotic should be avoided risk MRSA
• Topical anti-staphylococcal 3/day to affected areas 7-10 days, may be
effective for treating localized areas of involvement
• Disseminated eczema herpeticum(Kaposi varicelliform) systemic
acyclovir
• Superficial dermatophytosis and M. sympodialis topical antifungal

Antihistamine (ATH)
• Systemic antihistamines and anxiolytics: may be most useful1,2,
particularly concomittant urticaria or AR2
• Although, reportedly ineffective in treating the pruritus associated with AD,
2nd -generation ATH showed modest clinical benefit1
• Pruritus often worse at night sedative ATH at bedtime2
• No effects on AD score
• Topical antihistamines and anesthetics should be avoided because of
potential sensitization1,2
1.Middleton’s allergy: Principles and practice 8th edition
2 Schneider et al. JACI.2013.12.672

Biologic treatment
1. Dupilumab: FDA approved in March 2016 IL4/13 receptor
2. Nemolizumab  IL-31
3. Omalizumab
4. Rituximab

Namita A. Gandhi et al. Nature review. Jan 16 vol 15
IL-4 and IL-13 have
Common receptor
moiety: IL4Rα
Dupilumab

Dupilumab
RRs of dupilumab 300 mg every week to every 2 weeks
vs placebo: 3.3 (95% CI 2.9-3.6) I. Snast et al. Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and
Meta-Analysis. Am J Clin Dermatol Nov 2017

Thaci et al. LANCET 2016
• dbRCT 380 patients
• ≥18 years, EASI score ≥16
• 1:1:1:1:1:1 ratio
1. SC Dupilumab 300 mg weekly
2. SC Dupilumab 300 mg every 2 weeks
6. SC Placebo
For 16 weeks
• Primary endpoint: EASI reduction
• Result: EASI reduce
1. −74%
2. -68%
3. −64%
4. −45%
5. −65%
6. Placebo -18%
• Conclusion: improve clinical response
in dose-dependent manner
Thaçi et al. Lancet 2016; 387: 40–52

SOLO 1 and 2 study
• 2 independent, dbRCT (SOLO 1, SOLO2)
• SOLO1- 671, SOLO2- 708 patients
• ≥18 years, EASI ≥16, IGA ≥3
• 1:1:1 ratio for 16 weeks
1. SC dupilumab 300 mg weekly
2. SC dupilumab 300 mg every other week
3. Placebo
• Primary endpoint: proportion of IGA 0/1 or
2 point improve
• SOLO 1
1. weekly: 83/223 (37%)
2. every other week: 85/224 (38%)
3. Placebo: 23/224 (10%)
• SOLO 2
1. weekly 87/239 (36%)
2. every other week: 84/233 (36%)
3. Placebo: 20/236 (8%)
• Conjunctivitis more, skin infection less than
placebo
• Conclusion: confirm and expand on results of
previous early-phase trials, not address long term
efficacy
Simpson EL et al. N Engl J Med 2016; 375:2335-48.

LIBERTY AD CHRONOS study
• dbRCT 740 patients
• ≥18 years, EASI ≥16, IGA ≥3
• 3:1:3 ratio, for 52 weeks concomitant with TCS
(±TCI)
1. SC dupilumab 300 mg weekly
2. SC dupilumab 300 mg every 2 week
3. Placebo
• Coprimary endpoint: % IGA 0/1 or 2 point
improve and EASI improve 75% at week 16
and 52
• Result: week 16 similar to week 52
1. IGA 125/319 (39%), EASI 64%
2. IGA 41/106 (39%), EASI 69%
3. IGA 39/315 (12%), EASI 23%
• Side effect: conjunctivitis -mild, 2 severe (1 in
active, 1 in placebo)
• Conclusion: Dupilumab add on to TCS for 1
year improve AD with acceptable safety
Blauvelt et al. LANCET 2016; 389: 2287-303

Nemolizumab; NEJM 2017
• Phase 2, dbRCT, 212 patients
• 18-65 years, EASI ≥ 10, pruritus score ≥50 (0-
100), IGA ≥ 3
• 1:1:1:1, for 12 weeks
1. SC Nemolizumab 0.1 mg/kg q 4 weeks
4. SC placebo q 4 weeks
• Primary endpoint : % pruritus visual-
analogue scale improve at week 12
• Secondary : EASI
• Results: pruritus VAS reduce
1. 43.7%
2. 59.8%
3. 63.1%
4. 20.9%
• EASI -23, -42, -40, -26
• Conclusion: improvement in primary
outcome of pruritus for all groups received
nemolizumab every 4 weeks
Ruzicka T et al. N Engl J Med, March 2017; 533 376:826-35.

Immunothreapy
• considered for selected patients with house dust mite, birch or grass pollen
sensitization, who have severe AD and a positive corresponding atopy
patch test
• Summary Statement 8: There are some data indicating that
immunotherapy can be effective for atopic dermatitis when this condition
is associated with aeroallergen sensitivity.
• อาจมีประโยชน์ในผู้ป่วยที่มีปฏิกิริยาการแพ้อย่างชัดเจนจากการ ตรวจเลือด specific IgE หรือ skin prick
test โดยเฉพาะผปู้่ วยที่มีการแพ้ไรฝุ่น พบว่าลดความรุนแรงของโรคทั้งบริเวณและความรุนแรง รวมถึงลดการใช้ยา
ทาสเตียรอยด์ลงได้

Prevention
• Primary prevention
การให้นมแม่ มีข้อมูลจาก meta-analysis ว่าการให้นมแม่เพียงอย่างเดียวอย่าง น้อยจนถึง 6 เดือนแรกของชีวิต
สามารถลดอุบัติการณ์ของโรคผื่นภูมิแพ้ผิวหนังได้
การใช้ hydrolyzed cow's milk formula ชนิด eHF-C หรือ pHF-W formula ในทารกกลุ่มที่มี
ความเสี่ยงสูง (high risk) เช่น มีประวัติบิดา มารดา หรือพี่น้อง เป็นโรคภูมิแพ้ สามารถลดการเกิดโรคผื่นภูมิแพ้
ผิวหนังได้
การป้ องกันอื่น ๆ เช่น การให้จุลินทรีย์สุขภาพ (probiotic) มีการศึกษาถึงการให้ Lactobacillus GG แก่
มารดาขณะตั้งครรภ์และทารกแรกคลอด ช่วยป้ องกันการเกิดผื่นภูมิแพ้ผิวหนัง ได้
การหลีกเลี่ยงอาหารที่ก่อให้เกิดอาการแพ้ในมารดาที่มีความเสี่ยงสูง (high risk) ขณะตั้งครรภ์ไม่มีผลต่ออุบัติการณ์
ของโรคผื่นภูมิแพ้ผิวหนังในบุตร และอาจส่งผลต่อภาวะทาง โภชนาการของมารดาและทารกได้
• Secondary preventionให้หลีกเลี่ยงสารก่อภูมิแพ้และตัวกระตุ้นให้โรคกําเริบ

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