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1. ATOPIC DERMATITIS
PRESENTER- DR.RASHI GUPTA
MODERATOR- DR AMIT TIWARI SIR

2. HISTORICAL ASPECT
Atopy comes from a greek word “ atopos” ,given by Coca & Cooke in 1923
which means “without place,”
The term atopic dermatitis first given in 1933 by Sulzberger and Wise.
 Besnier in 1892 described the association of hay fever and asthma with
atopic dermatitis( then called Prurigo diathésique)
 Hebra in 1844 noted its flexural localization.

3. DEFINITION
• Aka Atopic eczema
• an itchy, chronic or chronically relapsing inflammatory skin condition
that often starts in early childhood (usually before 2 years of age)
• The European Academy of Allergy and Clinical Immunology proposed
a definition of: ’Atopy is a personal or familial tendency to produce IgE
antibodies in response to low doses of allergens, usually proteins, and
to develop typical symptoms of asthma, rhinoconjunctivitis or
eczema/dermatitis

4. • Incidence & prevalence is highly variable
• Increasing in developing countries
• Symptom starts appearing during infancy in 50-60%
• 90% by age 5
• Population‐based surveys show significant AE prevalence differences not
only between but also within countries,
↓
environmental rather than genetic factors as the main drivers of
changes in disease burden

5. DIAGNOSTIC CRITERIAS
HANIFIN & RAJKA CRITERIA

6. UK working Group’s diagnostic criteria- 1994
MAJOR CRITERION
• itchy skin condition (parental report of scratching or itching in a child)
MINOR CRITERIA
• H/o skin crease involvement
• Visible flexural dermatitis (dermatitis of cheeks/forehead and outer limbs
in children under 4 yrs)
• H/o generalised dry skin
• Personal history of other atopic disease (h/o any atopic disease in a first
degree relative in children under 4 yrs)
• Onset of rash before age of 2 yrs

7. PATHOPHYSIOLOGY
caused by complex interactions among genetic, immune, and environmental risk factors
A defective epidermal permeability barrier represents a consistent feature of AD and is evident in the nonlesional as
well as lesional skin

8. GENETICS
• Filaggrin
genetics &
epidermal
barrier
dysfunction
• lipids
ENVIRONMENTAL
FACTORS
• Climate
• Urban & rural living
• Diet
• Breast feeding &
delayed weaning
• Obesity & physical
exercise
• THE HYGIENE
HYPOTHESIS
• Day care
• Farm & animals
• Pets
• Endotoxin exposure
• Helminth & parasites
• Childhood inf &
vaccinations
• Microbiome of gut &
skin
• antibiotics
IMMUNE
DYSREGULATION
• Regulatory T cell
• Innate immune
cells
• igE,atopy,allery
OTHERS
Food allergy
Infection
Allergic contact
dermatitis
Pruritus
Sweating
Endocrine &
physcological factors

9. • Genetic Factors
• Genes that encode proteins important to the epidermal barrier and immunologic
functions have been implicated
• 6 genome screens identified numerous susceptibility loci on chromosomes 1q21, 1q24,
3p24, 3q14, 3q21, 4p, 4q22, 5q13, 11p14, 13q14, 15q14‐15, 15q21, 17q21, 17q25, 18q
and 20p
• Genome‐wide association studies (GWAS): association between AE and FLG gene
• Candidate genes associated with AE were found to dominantly cluster into the antigen
presentation and immune response pathway or the cell signalling/movement pathway

10. • Filaggrin genetics and the epidermal barrier in atopic eczema
• Filaggrin is encoded within the epidermal differentiation complex (EDC) on 1q21, which
comprises a large number of diverse proteins including loricrin, involucrin, S100
proteins and others
• Environmental influences on skin barrier integrity, such as frequent use of detergents
and water hardness  increases AE risk, through skin barrier impairment by:
- reduction in natural moisturizing factor
- increase in skin pH
- upregulation in protease activity
• loss‐of‐function variants of FLG (1q21) in ~ 50% of severe AE

11. Profilaggrin (filaggrin monomers) in keratohyalin granules
During terminal differentiation of keratinocytes , dephosphorylation of profilaggrin
f/b cleavage with matriptase and other proteases
Frees filaggrin monomers  bind, aggregate keratin bundles and intermediate
filaments to form cellular scaffold
Metabolism of filaggrin monomers, in stratum corneum, releases amino acids
Epidermal water retention through their hygroscopic properties (‘natural
moisturizing factor’)
FLG mutation
(nonsense
mutation)
inhibition of LEKTI

12. • Other atopic diseases such as asthma and allergies have also shown an
association with FLG
• Reduction of the histidine‐ rich protein to trans‐urocanic acid and
pyrrolidone‐5‐carboxylic acid (PCA) is important in maintaining the
epidermal pH gradient
• filaggrin mutation associated clinical features may include ichythosis vulgaris,
keratosis pilaris and hyperlinear palms

13. • Lipids
• Reduced extracellular lipids and impaired ceramide production are
characteristic of epidermal barrier defects[ increased activity of serine
proteases enzymatic activity in the epidermis]

14. • Environmental factors
• Climate
• Symptoms increase with latitude
• UV radiation- facilitates conversion of trans‐urocanic acid[filaggrin
background product] into immunosuppressive cis‐urocanic acid isoform 
effective therapy for AE
• Lower outdoor temperatures- disease worsening, indoor climate is less
important

15. Urban versus rural living
• Higher eczema burden in cities compared to countryside[less affluent
settings] possibly due to differences in hygiene‐related exposures (parasitic,
bacterial and viral infections, vaccination, antibiotics and farm
environment), environmental pollution, including smoking, allergen
exposure and sensitization, diet and infant feeding practices
Diet
• Fresh fruits,vegetable,protein from cereals, nuts & fishes : protective effect
• Fast food: triggers
• High fish intake (n‐3 PUFA) during pregnancy lowers AE risk in offspring up
to 5 years of age by 25–43%

16. Breastfeeding and delayed weaning
• WHO recommends exclusive breastfeeding for 6 months for allergy
prevention
• Although datas from various studies failed to show any statistically
significant benefit with exclusive breast feeding
Obesity and physical exercise
• Obesity and TV [>5hr] viewing- positive association with AE ( RF or
causal association ???]

17. • Hygiene hypothesis
Microbial exposure might influence the development of disease
Risk is inversely related to sibship size
Basic hygiene
• Frequency of washing and use of household cleaners and wet wipes-
associated with increased risk of AE between 2.5-3.5 years(weak
association)
Day care
• Associated with increased microbial exposure, in particular respiratory
tract infections,
• Some studies report reduction in risk & others mention it as a risk factor

18. Farm environment and animals
• Consumption of unpasteurized farm milk during the first 2 years of life:
independent protective factor
• Once raw cow’s milk is boiled, the protective effect is lost.
• Reduction in risk if mother had direct contact with farm animals during
pregnancy & becomes more significant if exposure is both prenatal &
postnatal
• Suggests importance of perinatal priming of the immune system
Pets
• Potentially protective against AE
• Dog exposure in early life is protective

19. Endotoxin exposure
• Up to 50% reduction in AE risk when exposed to high endotoxin
exposure
• Endotoxins are known to be inducers of IL10 & IFN-gamma
Helminth parasites
• Protective effect
• Depends on the type and burden of the parasite
• Timing of infection (especially in early life or during pregnancy)

20. Childhood infections and vaccinations
• Chickenpox, mumps, whooping cough and measles: either positive or no
associations
• Although a US case–control study: a 50% risk reduction with chickenpox
infection in 0-8 years of age
• Antibiotics
• 41% increase in risk if atleast one course of antibiotic taken in early life
• 7% increase in risk with each additional course of broad spectrum
antibiotics

21. Microbiome of the gut and skin
• Early gut microflora of children who develop AE has more
Staphylococcus aureus and coliforms & less lactobacilli and
bifidobacteria
• Low diversity of infant gut microbiota in early life- increase in AE risk
• Mode of delivery, feeding practices and exposure to antibiotics
influence the host microbiota in the immediate postnatal period

22. • IMMUNE DYSREGULATION
• Two different hypotheses:
• Immunological aberrations are thought to be a primary event in the initial
development of atopic dermatitis (AD) followed by barrier defects ,
according to the so called “inside-to-outside hypothesis”.
• When the skin barrier is impaired, allergens or many irritant stimuli that can
easily penetrate the epidermal barrier, and induce a secondary
immunologic reaction “outside-to-inside hypothesis

23. • T cells infiltrate early in the disease process
• CD4+ : CD8+ ratio 7 : 1
• CLA+ (skin‐homing receptor) and predominantly CD45RO+
• Eosinophils also present
• Allergens evoke th2 responses in lymphocytes in in atopics but not in
healthy controls
• Allergen‐specific Th2 cells are critical in AE pathogenesis  IL‐4, IL‐5 and
IL‐13  down‐regulate filaggrin expression in keratinocytes thereby
inducing further epidermal barrier disruption
• IL‐4 down‐regulates expression of cutaneous defensins & increase
expression of bact. Adhesion molecules Staph. colonization

24. • In chronic AE lesions,IL‐5, granulocyte– macrophage colony‐stimulating factor
(GM‐CSF), IL‐12 and IFN‐γ predominate
• IL12-polarization of IFN gamma producing th1 cellkeratinocyte apoptosis
& epidermal spongiosis
• IL22high levels in chronic AE  keratinocyte proliferation , reduced
expression of antimicrobial proteins & downregulate filaggrin expression
• Keratinocyte derived IL‐7‐like cytokine thymic stromal lymphopoietin (TSLP)
is central to AE pathogenesis by direct neuronal triggering of itch
• IL‐31- directly signals to neurones mediating pruritus
• High levels of Th17  downregulate filaggrin expression

26. REGULATORY T CELLS
• T‐reg inhibits spontaneous dermatitis, hyper‐IgE, food allergy,
aeroallergen sensitivity, cow’s milk allergy and ACD
• Glucocoticosreoids increase Treg cell population
• Staph. aureus superantigens stimulate th2 cells & reverse T‐reg
function, leading to enhanced inflammation
• Parasites induce regulatory T cells- protection against allergic
responses

27. Innate immune cells
• Type 1 cytokine secreting NK and γδ T cells in AE patients undergo
selective apoptosis  type 2 cytokine skewing
• Nuocytes; innate lymphoid cells (ILCs) secrete type 2 cytokines

28. • Ige atopic march & allergy
• ‘Atopic march’ : progression within an individual from AE to other atopic diseases like
allergic rhinitis, food allergy and asthma.
Filaggrin is not expressed in the airway or gut
• ? Progression is causal or reflects co‐manifestation
• Possibility that sensitization through the skin is critical for asthma pathogenesis and
so, impaired skin barrier in AE is to be blamed.

29. IgE
• Th2 cells  induce B‐cell class switching of ab production to IgE.
• IgE by plasma cells in lung and skin  bind high affinity receptor (Fc epsilon
RI) on mast cells, basophils, LCs and eosinophils  internalization and cellular
activation  immediate release of preformed or newly synthetized
inflammatory mediators
• Histamine: vasodilation (classical weal and flare), itch  urticaria
• Total IgE, specific IgE and no. of IgE‐mediated allergic reactivities a/w AE
severity

30. • Histamine concentrations during itch have no difference between AE and
controls (nonsedating antihistamines are not very effective in the t/t of AE)
• Omalizumab, anti‐IgE, therapy is effective in the treatment of asthma but no
reduction in severity of AE (not effective t/t)
• Although skin inflammation in AE is mainly mediated by T cells, IgE is
important in antigen presentation to T cells as well as weal and flare
exacerbations. (prevention of T‐cell mediated inflammation by allergen
avoidance is an important part of AE management)
Thus, allergic sensitization: secondary phenomenon in AE: acts as important
trigger for disease flares and disease chronicity, but is not the primary defect.

31. FOOD ALLERGY
Prevalence of associated food allergy in AE : 30–40% ,
• But prevalence of food allergy induced AE is rare
• Food allergen avoidance is beneficial, not ‘curative’
• Allergic responses to milk, egg, wheat, soy, peanut and fish account for 85% of
reactions
• No evidence that weal size or specific IgE level predict immediate or delayed
hypersensitivity severity. Many individuals with a positive test for IgE lack clinical
reactivity

32. INFECTIONS
• >90% have S. aureus identifiable on skin swabs, often at very high density,
more in lesional skin
• Superantigen expression correlates with disease severity
• Eczematous response is induced by concomitant exposure of skin to
staphylococcal superantigen and house‐dust mite allergen in humans
(synergistic enhancement)
• Herpes simplex virus (HSV): ’Kaposi varicelliform eruption’ or eczema
herpeticum
• Others- HPV‐induced warts, fungal infections and viruses (such as HSV‐1
and ‐2, vaccinia, coxsackie A and poxvirus of molluscum)
• Disease flares in AE a/w Staph aureus & S. epidermidis

33. • AUTOIMMUNITY
• Variety of autoantigens and autoreactive T cells and IgE against
autoallergens correlate with disease activity
• Scratching may release membranous and intracellular antigens from
keratinocytes  Th2 responses and IgE targeting self proteins

34. PRURITUS
• Role of NFAT signaling in keratinocytes expression of TSLP (Thymic
stromal lymphopoietin) - itch mediator
• Histamine  pruritogen
• Cold temperatures (25C) increase itch intensity
• PAR2, its receptor & PAR4  overexpressed in AD & trigger itch by
mast cells tryptase, trypsin and thrombin
• Capsaicin reduces pruritus
• Raised Ach induces pruritus (vasodilatation & sweating)
• IL-31 corelates disease severity

35. SWEATING
• Induces itching and aggravates AE
• Sweating responses to neurogenic stimuli are altered in AE sufferers:
Directly induced sweat production normal, whereas axon
reflex‐induced sweating is of lower volume with a longer latency
• On adrenaline stimulation at higher concentrations sweating in
nonatopic increases, whereas in AE decreases
• IgE‐mediated allergic reactivity to components of sweat

36. ENDOCRINE & PSYCHOLOGICAL FACTORS
• When subjected to formal stress tests (public speaking and
performance of mental arithmetic) endocrinological changes occur:
adrenaline, ACTH, corticotrophin‐releasing factor (CRF) and cortisol,
growth hormone, prolactin and progesterone exacerbation
• Premenstrual flare
• Pregnancy exacerbated eczema in 52% of women

37. CLINICAL FEATURES

38. • INFANTILE PHASE (<2 yrs
-predominantly head and
neck, most commonly face
-acute papulovesicular
lesions with serous
exudates and crusting
-extensor aspect of knees
and elbows
-napkin area generally
spared

39. Childhood phase (2 years to puberty)
• Lichenified papules and plaques in a scaly background
• involvement of flexures of wrist, antecubital and popliteal fossae
predominantly
• Dirty neck is a striking feature[ATOPIC DIRTY NECK]
• true eczematous lesions with vesiculation may occur, often in discoid
patches
• Hands may be affected in >50% of patients with active AE & the prevalence
increases with age
• A patchy, vesicular and lichenified eczema is a common manifestation

41. ADULT PHASE
Lichenification, especially of the flexures and hands
• Can occur on the nipples, especially in adolescent and young women.
• Involvement of the vermilion of the lips and the adjacent skin
• A distribution on the face, upper arms and back correlates with areas of
maximal thermal sweating
• Malassezia sensitivity
• Photosensitivity

44. SIGNS IN ATOPIC DERMATITIS
• Reverse sign (lichenified eczema around unaffected folds of elbows and
knees)
• Allergic salute (exaggerated linear crease from repeated rubbing of nasal
tip)
• Allergic shiners (violaceous/greyish discoloration and swelling around eyes)
• Hertoghe’s sign
• Atopic red face
• Dirty neck
• Atopic pleats (Dennis Morgan folds)
• Headlight sign (sparing of nose and medial cheek that is perinasal and
perioral areas even with extensive facial involvement)

45. NAIL CHANGES
• Beau’s lines
• nail pitting
• koilonychia
• trachyonychia
• leukonychia
• brachyonychia
• melanonychia
• onychomadesis
• onychoschizia
• onychlysis

46. HISTOPATHOLOGY
• Acute, exudative eczema is characterized by marked spongiosis, with
intraepidermal fluid collection leading to the formation of vesicles (micro
and macro) or even bullae. Some dermal edema may also be present,
together with perivascular lymphocytes that extend into the epidermis and a
variable number of eosinophils
• . In subacute lesions, vesiculation is absent whereas acanthosis,
hyperkeratosis and parakeratosis become evident
• In chronic, lichenified AD, epidermal thickening is more pronounced in a
pattern that may be either irregular or regular (psoriasiform). Changes in the
granular layer vary from thickening secondary to rubbing, as seen in lichen
simplex chronicus, to thinning when there is a psoriasiform pattern, seen in
some nummular lesions. Spongiosis and inflammation are less seen

48. COMPLICATIONS & COMORBIDITIES
• Psychosocial aspects- itching, distress at bath time and difficulty going to
sleep, emotional stress, neurocognitive impairment, anxiety, stress
vulnerability
• Growth delay
• Bacterial infections- staphylococci or streptococci sec inf
• Viral infections- acute generalized infections with herpes simplex virus
(eczema herpeticum), to produce clinical picture of Kaposi varicelliform
eruption.
• High incidence of common warts and molluscum contagiosum. HIV
infection may aggravate AE (‘recall’)
• Systemic and cutaneous lymphomas
• Asthma and allergic rhinitis

49. Ocular abnormalities
• Dennie–Morgan fold is often
present as a fold of skin under
the lower eyelids.
• Conjunctival irritation
• Keratoconus
• Cataract- posterior and anterior
subcapsular
• Retinal detachment

50. INVESTIGATIONS
• Total and specific serum IgE levels: 70-80% pts
• Prick test
• Atopy patch test
• Total eosinophilic count
• Bacteriology and virology swabs
• Potassium hydroxide mount(to rule out cut. Fungal inf.)
• Mineral oil examination(for scabies)
• Laboratory investigations to r/o primary immunodeficiency disorders
• Zinc and serum albumin levels
• Imaging studies
- absent thymus in SCID

51. SCORING SYSTEMS IN ATOPIC DERMATITIS
1.SCORAD(SCORing atopic dermatitis)
2. EASI(eczema area & severity score)
3. POEMS(patient oriented eczema measure)
4. SASSAD(six area,six sign atopic dermatitis)
5. DLQI

53. MANAGEMENT
• Successful treatment of AD requires a systematic, multipronged approach that
incorporates
• General skin care measures:
• Education
• Appropriate skin hydration and use of emollients or skin barrier repair
measures
• Avoidance of irritants
• Identification and avoidance of proven allergens
• Antiinflammatory therapy topical steroids, topical calcineurin inhibitors,
topical PDE4 inhibitor
• Antipruritic interventions (sedating antihistamines, behavioral modification)
• Identification and treatment of complicating bacterial, viral, or fungal
infections
• Treatment of psychosocial aspects of disease

54. Education
Explain/demonstrate how to apply emollients
Various topical medications should be used with intervals
In children > 12 months, use shampoos recommended in AD
When talking to the patient (guardian), make sure the recommendations are understood and followed
Revision of recommendations at least once a year
Emollient therapy Application
min. 2-3 times a day!
Glycerol is better tolerated than urea or sodium chloride
Propylene glycol can easily cause irritation in young children < 2 years of age and should not be used in
these patients
In children < 2 years of age it is recommended to use emollients without protein allergens and haptens
Do not use emollients containing peanut extracts which increase the risk of sensitization and allergies!
Emollients are poorly tolerated in inflammation sites – use the appropriate doses of emollients (250-500
g/week

55. 1. Control of triggers
• Use of non-irritant
cotton clothes
• Avoidance of
exposure to hot and
humid conditions
• Avoid housedust,
mites and pollens
• Identify allergy to
specific food
• Education and stress
management

56. Bathing and emollients
• Foaming detergents and soaps should be avoided
• A soap substitute emollient for cleansing
• Adding 1/2 cup of sodium hypochlorite to the bath eliminates itching
• Dispersible bath oils
• Regular use of emollients softens the skin and reduces itch
• A generous quantity (150–250 g/week for children to 500 g/week for adults) should be prescribed to encourage
their frequent use
• ’Designer emollients’ contain ingredients such as ceramide
• ointment (highest moisturising ability, more occlusive, less stinging)- on lichenified skin

57. • TOPICAL CORTICOSTEROIDS
• Predominant treatment for the inflammation of AE
• Strength and mode of application depends on severity of the
dermatitis, the sites to be treated and the age of the patient
• Once daily treatment in evening, with morning application of
emollients
• Corticosteroid‐resistant or infected or crusted dermatitis:
steroid/antibiotic or steroid/antiseptic combinations.
• Educate patients about the quantities to apply, for example the
fingertip unit (child- 10 g/week)

58. TOPICAL CALCINEURIN INHIBITOR
• tacrolimus- 0.1% adults, 0.03% children
• 1% pimecrolimus
• >= 2 years of age
• Second line agents
• recalcitrant patches not responding to TCS
• sensitive sites: face, anogenital areas, skin folds

59. PDE 4 INHIBITOR
CRISABOROLE
• inhibition of breakdown of cAMP, reduced TNF-alpha, IL-12, IL-23
• FDA approved in 2016
• mild to moderate AD
• 2% ointment, twice daily, 4 weeks
• >= 2 yrs of age
• S/E- site pain (burning/stinging), pruritis, flare
• safer and effective
• maintenance/ sequential therapy

60. TANNINS
• astringent, anti-inflammatory, antipruritic, antibacterial, and
desiccant effects
• Lotion, cream, and bath and wrap solutions are available
• Tannins and an emollient cream base work together to provide
effective treatment for skin dryness
• Zinc oxide and talc are added to the lotion form of tannins to provide
hygroscopic qualities, making it suitable for use as a monotherapy or
supplementary therapy for skin lesions accompanied by exudate and
located in close proximity to intertriginous areas

61. • Itch and antihistaminics
• controlling inflammation is the most effective treatment
• The use of anti‐inflammatory preparations, emollients and reduction of
trigger factors remains the initial approach
• H1‐receptor antagonists used for their sedative effect.
•
• Eg-hydroxyzine, promethazine or trimeprazine given 1 h before bed

62. • Antibiotics & infection
• In recurrent flares of AE associated with infection,
prolonged antibiotic treatment, topical antiseptics,
topical steroid/antibiotic combination creams
• Measures to reduce staph colonization of nose and
perineum
• Herpes simplex infection treated with oral
anti‐herpetics
• If the patient is febrile or toxic- intravenous therapy
• Dilute bleach baths
• Potassium Permanganate soaks

63. IMMUNOMODULATORY AGENTS
Systemic glucocorticoids
• Short course of oral glucocorticoids may be appropriate for acute
exacerbation
• Dose 0.5mg/kg
• Should be tapered over several weeks to avoid severe rebound flare
after discontinuation
• Special consideration should be made with pediatric patients because
of concerns with delayed or reduced bone growth

64. • Phototherapy
• Broadband UVB, broadband UVA, narrowband UVB (311nm), UVA-1 (340 to
400nm), & combined UVAB phototherapy are useful in chronic cases
• Limit use to once per annum
Ciclosporin
• Highly effective treatment in both adults and children. An initial dose of 2.5–3.5
mg/kg/day is recommended with a maximal daily dose of 5 mg/kg/day
• Rapid response with reduction in severity by 55% at 6-8 wks
• Regular monitoring of renal function and blood pressure
Azathioprine
• Patients with absent TPMT (thiopurine methyl transferase) activity should not
receive azathioprine; those with normal or high TPMT activity should receive a dose
of 1–3 mg/kg/day, and those with low TPMT activity should receive a dose of 0.5–1
mg/kg/day
• Regular blood monitoring for neutropenia

65. Methotrexate
• In adults, this would typically involve starting at 10 mg per week (following a
5 mg test dose) and increasing by 2.5 mg weekly to a maximum 25 mg per
week or until response is achieved
• Max response seen at 10 weeks & continue several months after
discontinuation
Mycophenolate mofetil
• Who fail to respond to or are intolerant of azathioprine and/or methotrexate,
mycophenolate may be considered as a fourth line agent, with dosage up to
2 g/day
• Side effects include gastrointestinal disturbance, leukopenia lymphopenia
and anaemia
Alitretinoin (9‐cis retinoic acid)
for chronic hand eczema

66. Allergy management
• Foods- in absence of immediate hypersensitivity, IgE radioallergosorbent
tests are unhelpful and a 3–4‐week trial of a modified elimination diet
may be considered.
• Commonly, dairy produce, beef, eggs, chicken, fish, wheat, citrus and
berry fruits, food additives, chocolate and nuts may be excluded.
• Aeroallergens.- intensive eradication of mite allergens from the house
• Desensitization- Allergen‐specific immunotherapy might reduce need
for topical CS and development of tolerance with high level exposure to
allergen
• Contact allergy- avoidance of the responsible foods and medicaments is
advised

67. • Maintainance therapy
• Continue to reduce exposure to trigger factors, as far as is practical
• continuous use of emollients with the addition of very intermittent use of
topical corticosteroids will suffice in mild cases
• addition of twice weekly application of potent topical steroids to the healed
areas (the ’weekender approach’) can safely and significantly reduce relapses
of AE
• If relapse occurs again, topical corticosteroids should be used daily again for a
week and then stepped down to the weekender approach once more
• mid‐week use of tacrolimus ointment to the topical corticosteroid weekender
approach has been used to improve control of severe AE [43]

69. • Wet wrap technique-
• for the control of severe AE
especially in younger
children(SCORAD >50)
• Two layers of absorbent tubular
bandage are applied to the skin.
• The inner layer is presoaked in
warm water and the outer layer is
dry. A generous quantity of a
low‐potency topical corticosteroid(
(0.05 percent fluticasone
propionate or mometasone furoate
diluted 1: 3 for the body or 1: 9 for
the face)is applied to the skin
before the dressings
• Kept overnight or changed every
12hrs

70. Biological therapies
• Omalizumab- a monoclonal antibody against IgE for asthma
• Patients with a FLG wild‐type status showed a significantly greater clinical
response
• Rituximab- two infusions of 1000 mg 2 weeks apart showed
improvement in some
• Dupilumab a fully human monoclonal antibody to the shared α‐subunit
of the IL‐4 receptors that blocks IL‐4 and IL‐13 signalling showed clinical
efficacy
Under trials:
• Lebrikizumab, a monoclonal antibody that specifically targets IL‐13
• Topical phosphodiesterase (PDE) inhibitors and apremilast, an oral small
molecular inhibitor of PDE 4

72. Newer topical & systemic in treatment of AD
IMMUNE AXIS TARGET DRUG ROUTE
Th2 IL-4/13
IL-13
IL-13
IL-31
TSLP
TSLPR
OX40
IL-33
DUPILUMAB
TRALOKIUMAB
LEBRIKIZUMAB
NEMOLIZUMAB
TEZEPELUMAB
MR-8226
GBR-830
ETOKIMAB
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION
SUBCUTANEOUS INJECTION

73. IMMUNE AXIS TARGETS DRUGS ROUTE
JAK-signal transducer and
activator of transcription
JAK 1 & 3
JAK 1& 2
JAK 1
JAK 1
JAK1,2,3 & TYK3
JAK 1 & 2
TOFACITINIB
BARICITINIB
UPADACITINIB
ABROCITINIB
DELGOCITINIB
RUXOLITINIB
ORAL or TOPICAL
ORAL
ORAL
ORAL
TOPICAL
TOPICAL
PDE4 inhibitor CRISABOROLE
APREMILAST
TOPICAL
ORAL
ARYL HYDROCARBON
RECEPTOR AGONISTs
TAPINAROF TOPICAL
HISTAMINE 4 receptor
antihistamines
ZPL-3893797 ORAL

74. • UPADACITINIB (Rinvoq), ABROCITINIB (Cibinqo) (JAK1 INHIBITOR)
- FDA approved in age >=12 yrs, Jan 2022
- moderate to severe AD
- quick onset of action.
-well tolerated
- S/Es acne, nasopharyngitis, URTI, oral herpes, increase creatine
phosphokinase, headache

75. • RUXOLITINIB
• FDA approved in march 2021
• a topical selective Janus kinase (JAK)1/JAK2 inhibitor,
• treatment of mild to moderate atopic dermatitis (AD) in non-
immunocompromised patients 12 years and older whose disease is
not adequately controlled with topical prescription therapies, or

76. DUPILUMAB
• IL- 4/13 inhibitors, key Th2 cytokines
• FDA approved age >6yrs in march 2017
• Now FDA approved for 6 months – 5yrs in June,2022
• In moderate- severe AD
• subcutaneously, 300 mg every 2 weeks upto 1 year
• favorable safety profile
• S/Es nasopharyngitis, URTI, headache, conjunctivitis, injection site
reaction

77. • TRALOKINUMAB
• IL13 antagonist
• For moderate to severe AD > 18yrs
• FDA approved in dec,20221
• Subcutaneous injections
• initial dose of 600 mg (four 150 mg injections), followed by 300 mg (two
150 mg injections) administered every other week.
• After 16 weeks of treatment, for patients with body weight below 100 kg
who achieve clear or almost clear skin, a dosage of 300 mg every 4 weeks
may be considered.

78. Thank you