ATOPIC DERMATITIS

Presented by : Dr Jeebanjyoti Mishra, Senior Resident

Department of Dermatology ,SCB Medical college ,
Cuttack
INTRODUCTION

 Chronic ,recurrent ,inflammatory itchy cutaneous disease that

often starts at early childhood [1]
 Atopy : personal or familial tendency to produce IgE in
response to low doses of allergens, usually proteins, and to
develop typical symptoms of asthma, rhinoconjunctivitis or
eczema/dermatitis’ [1]
EPIDEMIOLOGY [1]

 One-fifth of all individuals during their lifetime [2]

 Developed world : Allergic epidemic
 Developing countries prevalence is on rise
 India : Rising trend in last four decade

Prevalence Developed world ( %) World (% )

children 10-30 2-16

Adults 2-10 7.1

NATURAL HISTORY [1]

 50% - Onset in first year of life

 95% < five years of age
 Childhood onset : spontaneous remission before
adolescence (75%)
 Remaining 25% continue recurrent relapsing course
  Associated with other atopic disorders
 Asthma, allergic rhinoconjunctivitis
 Food allergies, and eosinophilic esophagitis
 ATOPIC MARCH [11]

• Development of AD in
infancy and subsequent
allergic rhinitis and asthma
in later childhood: atopic
march [8]
• Percutaneous sensitization
[1]

• Systemic Th2 immunity

• Predisposes patients to nasal
and airway hyper reactivity
(Incidence 30-50 %)
• Food allergy in about 35%
( IgE mediated )
GENETICS
 Familial transmission with strong maternal influence

 Concordance rate of atopic dermatitis

 Monozygotic twins 75% , Dizygotic twins 30%

 Loss of function mutations in the FLG gene (chr 1q21)

 SPINK 5 gene mutation: ( LEKTI Protein production defect )

 Other skin barrier genes : LAMA3, TMEM79, Late Cornified

Envelope-like Proline-rich 1 (LELP1), and claudin-1

(CLDN1)
RISK FACTORS [9] [10]

Life style factor Others

Environmental factor • Obesity • Rural << Urban
Detergents • Mechanical damage • Increased income and
TemperatuAllergens/Irritants (repetitive scratching) education
House dust mite • Adherance to • Increased use of
re treatments antibiotics
Sweating, wool fiber • Infection
Lower humidity,UV • Food allergens
Airborne pollution,
use of hard water
 PATHOGENESIS [1]

Defective skin
barrier

Hyper-
Defective innate
immunological
immune system response
DEFECTIVE SKIN BARRIER [1]

 Down regulation of cornified envelope genes

 ( Filaggrin , Loricrin )
 Exogenous proteases
 (House dust mite, S.Aureus)
 Altered lipid composition
 Ceramide,Long chain FFA
 Cholesterol
 Proteolytic enzymes
 Lack of endogenous proteases inhibitors (LEKTI)
ROLE OF FILAGGRIN PROTEIN [7]

 Filaggrin gene is found in the epidermal differentiation

complex (EDC) [10]
◦ Expressed during terminal differentiation
◦ Involucrin, loricrin, and S100 calcium binding proteins
 Filaggrin degradation products: Natural moisturiser factor
 Filaggrin deficiency
 Disruption of keratinocyte differentiation
 Impaired corneocyte cohesion
 Impaired tight-junction formation
 Decreased water retention
 Altered lipid formation
 Cutaneous infection
 SKIN BARRIER DEFECTS
Decreased barrier function
Allergens
Increased allergen absorption and
microbial colonisation
Sensitization to allergens
Allergens
Increased allergic immune response
• ‘outside-in’ hypothesis:
“ Functional disruption of
the epidermal barrier
facilitates recognition of
environmental
allergens, irritants and
microbes, and initiates
an inflammatory
cascade “ [7]
ROLE OF SKIN MICROBIOME [7]

 Disease flares : fall in skin microbiota diversity, increase in S.

aureus/epidermidis
◦ Peptides and superantigens : eczematous inflammation
◦ Delta toxin : mast cell degranulation
◦ Alpha toxin: keratinocyte apoptosis
◦ Enterotoxins: T cell stimulation

 Bleach baths appears to improve AD severity ** [10]

(Dilute sodium hypochlorite baths )
IMMUNE DYSREGULATION [1]
IMMUNE DYSREGULATION [6]
 BASIS OF PRURITUS
Exposure to allergens , change in
• Non histaminergic
humidity, excessive sweating signalling more relevant
• Over expression of
Cutaneous hyperactivity and receptors of IL-31in
scratching epidermis and macrophages
• Stress induced
Induce proinflammatory cytokines neuropeptides
and chemokines release
• Eosinophil derived proteins
• Proteases act on proteases
activated receptors
Vicious itch scratch cycle
• Eicosanoids
CLASSIFICATION

Onset Morphology
• AD of infancy • Acute
• AD of childhood • Sub acute
• AD of adolescence and • Chronic
adulthood
CLINICAL PRESENTATION
 Cardinal features: Itch with chronic fluctuating rash with range
of features [1]
 Itching,macular erythema,papules and vesicles,eczematous area with
crusting,lichenification and excoriation,hyper and
hypopigmentation,dryness of skin,secondary infection
 Major features :
Pruritus
 Rash on face and/or extensors in infants and young children
 Lichenification in flexural areas in older children
 Chronic relapsing dermatitis
 Personal / family history of atopy
AGE WISE DISTRIBUTION [10]
 Infantile phase Childhood phase Adult phase

Age group Infants 18-24 months Late onset :after

< 1 Years onwards puberty
Senile onset : after
60 years
Distributions Face , anywhere, Elbow and knee Flexures ,
Spares napkin flexures,neck, hands ,feet ,face ,n
areas atopic dirty ipple,vermilion
Extensor area neck,wrist, border lips
(crawling ) ankles
Morphology Erythema,oedemat Erythema,crusting, Papules ,vesicles,
ous excoriation,hyper/ excoriation,
papules ,vesicles , hypopigmentation , lichenification
crusting lichenification less
common
Important Usually start with Flexural Flexural predominant
Rule out
OTHER FEATURES

Dennie Morgan fold Facial erythema/pallor

Recurrent conjunctivitis Pityriasis alba
Keratoconus Chelitis
Orbital darkening Nipple eczema
Anterior subcapsular cataract Xerosis, Icthyosis
ATOPIC
DERMATITIS
Perifollicular accentuation Early age of onset
Itch when sweat White dermographism
Hyperlinear palms/Soles Intolerance to wool and lipid
Keratosis pilaris Non specific hand feet dermatitis
Food hypersensitivity Tendency for cutaneous infection
REGIONAL VARIANTS [11]

• Juvenile plantar
• Atopic hand • Eyelid eczema dermatosis
dermatitis • Nipple eczema • Head and neck
• Chelitis sicca • dermatitis
Prurigo form AD
• Lip licker‘s eczema • Frictional lichenoid
• Discoid eczema dermatosis
• Ear eczema
REGIONAL VARIANTS OF AD
 Atopic dermatitis of hand
◦ Affects ~60% of adults with AD
◦ Risk factor : Exposure to water/irritants
◦ Volar wrists and dorsum of the hands
◦ Patchy vesicular/ lichenified eczema
◦ Nails : coarse pitting and ridging
◦ Feet << Hands
 REGIONAL VARIANTS OF AD
• Cheilitis sicca 
– Eczematous changes,
dryness of the vermilion
lips
– Peeling and fissuring
– Angular chelitis
– Common in winter
•  Lip-licker's eczema :
– Patients try to moisten
their lips
– Licking causes irritation
 REGIONAL VARIANTS OF AD [11]

• Ear eczema :
– Erythema, scaling, and
fissures
– Bacterial superinfection *
• Eyelid eczema
– Can represent the only
manifestation of AD
– Common in adults
– Characterized by
lichenification of the
periorbital skin
 REGOINAL VARIANTS [11]

• Nipple eczema 
 Can devlop in Adults
and children
• Prurigo form of AD 
 Favors the extensor
aspects of the
extremities
 Firm, dome-shaped
papules and nodules
with central scale-
crust
REGIONAL VARIANTS –OTHERS [11]

 Head and neck dermatitis

◦ After puberty, Malassezia yeasts: Aggravating factor
◦ Face, scalp, and neck.
 Juvenile plantar dermatosis
◦ Presents with “glazed” erythema, scale, and fissuring
◦ Balls of the feet and plantar aspect of the toes
 Frictional lichenoid eruption 
◦ Children , Site :elbows , knees and dorsal hands
◦ Presentation : Multiple small, flat-topped, pink to skin-colored
papules on the
 Nummular (discoid) lesions
◦ Coin-shaped eczematous plaques, oozing and crusting
COMPLICATIONS [1]

 Psycho-social aspects
 Growth delay
 Exfoliative dermatitis
 Infections
 Occular complications
 Others :
 Lymphoma, asthma , allergic-rhinitis , dry skin
Diagnosis
 History & clinical examination
a) Pruritus
b) Course of disease
c) Morphology & distribution
Diagnostic criteria : Four
a) Hanifin & Rajka criteria (1980)
b) UK working party criteria( 1994)
c) AAD criteria (2003)
d) JDA criteria (2008)
Hanifin & Rajka criteria (1980)
 Major criteria:
 Pruritus
 Typical morphology & distribution
a) Flexural involvement in adults
b) Face, extensors in infants & children
 Chronic relapsing-remitting course
 Personal /family h/o atopy ( asthma, allergic
rhinitis)
Minor criteria
 Xerosis,
 Ichthyosis
 Palmar hyper linearity
 Keratosis pilaris
 Immediate skin test reactivity
 Raised serum IgE
 Nipple eczema
 Anterior neck folds
 Cheilitis
 Recurrent conjunctivitis
 S. Aureus colonization
Cont.………
 Dennie-morgan fold
 Orbital darkening
 Perifollicular accentuation
 Keratoconus
 Anterior subcapsular cataract
 P. alba
 itch when sweat
 Intolerance to wool
 White dermographism
Severity index

 Mild : Mild erythema, dry skin, or desquamation

irrespective of BSA
 Moderate: Eruption with severe inflammation in < 10% of
the BSA
 Severe: Eruption with severe inflammation 10% to <30% of
the BSA.
 Most severe: Eruption with severe inflammation in >/30% of
the BSA

 SCORAD- Both objective and subjective.

 EASI- Only objective.

[Ikeda M, Ohya Y, Katoh N et.al. Japanese guidelines for atopic dermatitis 2020. Allergology
International 69 (2020) 356-369]
Histopathology
 Acute atopic eczema-
a) Spongiosis,
b) Perivascular infiltrates
c) Parakeratosis.
 Chronic eczema-

a) Hyperkeratosis, hypergranulosis
b) Acanthosis
c) Sparse infiltrates.
Routine skin biopsy - NOT recommended
Treatment

 Two modes :
a)Non- pharmacological
b) Pharmacological
1) First line therapy
2) Second line therapy
3) Third line therapy
[Michael J, Tidman, Catherine HS. Atopic Eczema. In: Griffiths MD, editor. Rook’s
Textbook of Dermatology, 9th ed. New Delhi: Wiley publisher; 2016]
Non-pharmacological methods
 Patient & parents education
 Avoidance of triggering factors
 Bathing, wearing
 Appropriate cleanser use
 Selection of Occupation
 Avoidance of cosmetics
 Contact with pets
 Psychological intervention

[Michael J, Tidman, Catherine HS. Atopic Eczema. In: Griffiths MD, editor.
Rook’s Textbook of Dermatology, 9th ed. New Delhi: Wiley publisher; 2016]
Pharmacological methods
 Divided into therapy ( Moisturizer therapy
a) First line – Moisturiser , topical steroid

b) Second line therapy

1) TCI
2) Wet-wrap therapy
3) Phototherapy

c) Third line- Immunosuppressants

Wet wrap therapy
 Indication: Severe AE in younger children
 Method: Two layers of tubular bandage
a)Inner - wet layer
b)Outer- Dry layer
 Low-medium potent topical steroid with
emollient before dressing
 Changed every 12 hrs
 Duration- 3 days
Third line therapy

 Cyclosporine

 Azathioprine

 Methotrexate

 Mycophenolate mofetil

 Alitretinoin
Cyclosporine in AE

 Indication: Severe, chronic, refractory AE

 Both children & adults
 Start dose- 2.5-3.5 mg/kg/d
Maximal dose- 5mg/kg/d ( tapering- 0.5-1mg/kg/d
every 2 wks)
 Improvement- 55% after 6-8wks of use
 Limitation: Rapid recurrence on discontinuation
 Maintainance: may be upto 1 yr with close monitoring
Biological therapy

 Dupilumab Approved
 Rituximab
 Omalizumab
 Mepolizumab Off-label use
 Ustekinumab
 Lebrikizumab
 Nemolizumab
 Tralokinumab

 Tezepelumab Up coming
 Upadasatinib,Tofacitinib
 Apremilast, Crisaborole
 28/ 09/2022

Thank
you
REFERRENCES
 1. Michael J, Flohr C, Holden CA. Atopic Eczema. In: Griffiths MD, editor. Rook’s
Textbook of Dermatology, 9th ed. New Delhi: Wiley publisher; 2016
 2.M. I. Asher, S. Montefort, B. Bj¨orkst´en et al., “Worldwide time trends in the
prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in
childhood: ISAAC Phases One and Three repeat multicountry cross-sectional
surveys,”The Lancet, vol. 368, no. 9537, pp. 733–743, 2006.
 5. Japanese guidelines for allergic diseases 2020 , Allergology International, 2020
 6. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical
implications. Allergy Asthma Proc. 2019;40(2):84-92.
doi:10.2500/aap.2019.40.4202
 REFERRENCES
 7. Tsakok T, Woolf R, Smith CH, Weidinger S, Flohr C. Atopic dermatitis:
the skin barrier and beyond. Br J Dermatol 2019;180:464-74
 8.Zheng T, Yu J, Oh MH, Zhu Z. The atopic march: progression from
atopic dermatitis to allergic rhinitis and asthma. Allergy, asthma &
immunology research. 2011 Apr 1;3(2):67-73.
 9.Schram  ME, Tedja  AM, Spijker  R,  et al. Is there a rural/urban
gradient in the prevalence of eczema? A systematic review. Br J
Dermatol. 2010;162(5):964–973.
 10.Kang S,Amalgai AL,Bruckner AH et al Atopic dermatitis.Fitzpatricks
dermatology ,9th ed .McGraw-Hill Publisher;
 11. Maeve A. McAleer, Grainne M. O'Regan and Alan D. Irvine
Dermatology, 12, 208-227
SYNDROMES ASSOCIATED WITH AD
 HIES – Hyper IgE Syndrome
 wiskott Aldrich syndrome
COMPLICATION :PSYCHOSOCIAL
 Itch-scratch : sleep disturbances
 Impairment of quality of life
 Neuro - cognitive impairment
 Social exclusion
 Mental health :
 Emotional stress , Exhaustion , Depression , anxiety ,
conduct disorder
COMPLICATIONS….short it
 Non-specific, irritant hand
dermatitis
 Aggravated by repeated
wetting and by washing
with soaps, detergents, and
disinfectants
 Cause of occupational
disability
 Generalized redness,
scaling, erosion,
crusting,lymphadenopathy,
and fever
 Dermatological emergency
 Superadded infections

HAND DERMATITIS
EXFOLIATIVE DERMATITIS
COMPLICATIONS
 Herpes simplex  Eyelid dermatitis, chronic
 Kaposi varicelliform eruption
 Supericial fungal infections blepharitis
◦ Dermatophyte and P.Versicolor  Corneal scarring
 Bacterial infection
◦ 90 % cases of AD skin lesions  Keratoconjuctivitis
have S. Aureus  Keratoconus
◦ Complicates erythroderma
◦  Cataract
Folliculitis,Pyoderma,Impetigo
 Retinal detachment

Infections Occular symptoms

IMMUNE DYSREGULATION [5]
IMMUNE DYSREGULATION
SEVERITY ASSESSMENT

 SCORAD Index (Scoring Atopic Dermatitis )

 EASI (Eczema Area and Severity Index)

 POEM (Patient Oriented Eczema Measure )

ACUTE ECZEMA [7]
Epithelial damage leads to innate immune activation

Release of pro-inflammatory cytokines and chemokines by

Keratinocytes

skin becomes infiltrated with more TH2 cells and additional

CD4+ subsets, including TH22 and TH17 cells

TH2 inflammation leads to recruitment of additional immune cell

subsets including eosinophils and mast cells ( Histamine
release )
CHRONIC AD [7]

TH1 lymphocytes mixed with TH1, TH2 and TH22

infiltration

Activated lymphocytes adopt a tissue-resident

memory T cell phenotype

Rapid recall responses when re-exposed to

antigens/cross-reactive to autoantigens or
antigens
EPIDEMIOLOGY INDIA

Indian population Current Severe eczema Lifetime

symptoms [4] prevalence

Children 2.7 % 0.3 % 4.4 %

Adolescents 3.6 % 0.4 % 8.9 %