Clinical Diagnosis


  • Classic distribution:
    • Children <2 years old: facial and extensor surfaces
    • Children >2 or adults: flexor surfaces
  • Minor features include white dermatographism, delayed blanch response, pityriasis alba

Differential Diagnosis

  • Usually presents <5 years old in 90% of patients
  • 70% of children with AD have spontaneous remission before adolescence
  • In adults with new onset dermatitis, especially without a history of childhood eczema, asthma or allergic rhinitis, other diseases need to be considered (especially malignancy)
    • AD affects 2-15% of adults
  • ~1/3rd of children with AD develop asthma, 50% develop AR, and 1/3rd with moderate-severe AD may have a food allergy
Congenital disorders
  • Comel-Netherton syndrome - rare autosomal recessive SPINK5 mutation resulting in generalized erythrodermic eczematous dermatitis with flaking/exfoliation at birth or within first weeks of birth, sparse fragile hair that is bamboo-like on microscopy (trichorrhexis invaginata) by 6 months of age, failure to thrive, atopic predisposition (particularly food allergy), and pathognomonic ichthyosis linearis circumflexa after 2 years old
    • Diagnosis with microscopic examination of hair (bamboo stalk appearance), absent LEKTI staining on immunohistology, SPINK5 gene mutation screening
  • Hartnup syndrome - autosomal recessive mutation of an amino acid transporter (SLC6A19) causing lack of amino acid uptake from gut and kidneys with resultant amino acid deficiency (particularly tryptophan). May present with amino aciduria, episodic pellagra-like rash, and cerebellar ataxia.
Chronic dermatoses
  • Seborrheic dermatitis
  • Contact dermatitis (irritant or allergic) - may occur to drugs or other compounds in topical medications
  • Nummular eczema
  • Lichen simplex chronicus - not a primary process, the patient senses pruritus in an area of skin (with or without underlying pathology) and scratches/rubs repetitively causing trauma to the point of lichenification (thickening of the skin with variable scaling). May be caused by AD.
  • Pityriasis rubra pilaris
  • Psoriasiform dermatitis - most often with raised red plaques with silvery scales
  • Asteototic eczema - xerosis leading to pruritus, lichen simplex chronicus
  • Pityriasis rosea
  • Keratosis pilaris - papular rash “chicken skin” on face and outer aspects of the upper arms and thighs
  • Perioral dermatitis - small red papules around mouth > nose > eyes, exacerbated with chronic inhaled/topical steroid use, often worsens with steroids
    • Treatment options include metronidazole gel +/- erythromycin PO, TCI, doxycycline if >8 years old, and may take 3-6 weeks to clear
Infections and infestations
  • Scabies - more acute onset and, in contrast to AD, are localized in the axillae, groin and genital area with sparing of the face (>1 year old), intensely pruritic, often more family members are affected
    • Scaling papules on penis is scabies until proven otherwise
  • HIV-associated dermatitis
  • Infective dermatitis with HTLV-1 - occurs in Caribbean/Japanese origin, appears with Staph/Strep superinfection resistant to treatment; evaluate with HTLV-1 antibodies, PCR
  • Cutaneous T cell lymphoma (mycosis fungoides/Sezary syndrome) - epidermal malignancy of CD4+ T cells, often requires multiple and/or serial biopsy for diagnosis; most often misdiagnosed as chronic contact dermatitis, AD, or psoriasis
  • Langerhans cell histiocytosis
  • Gluconoma/glucogonoma (islet cell tumor)
  • Letterer-Siwe disease - infants, young children with seborrheic rash, lymphadenopathy, hepatosplenomegaly, diagnosis via biopsy
  • Wiskott-Aldrich syndrome - male; infections, petechiae, epistaxis, bloody diarrhea or history of bleeding
    • Diagnosis supported by thrombocytopenia with low mean platelet volume, WASP gene mutation
  • SCID, especially Omenn syndrome - recurrent or persistent chest infection, diarrhea, candidiasis, failure to thrive, erythroderma
    • Diagnosis supported by ALC <2.8 109/L in infants <3 mo, lymphocyte subsets, gene mutation screening
  • Ataxia-telengectasia
  • Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
  • Hyper-IgE syndromes
  • Agammaglobulinemia
Metabolic disorders
  • Zinc deficiency (acrodermatitis enteropathica) - infants with periorifacial (around mouth/anus, relative sparing of upper lip known as the U sign) and acral (extremities) dermatitis (crusted plaques with a heaped up border), alopecia, failure to thrive
    • Diagnosis by plasma zinc concentration, SLC39A4 gene mutation screening; low alkaline phosphatase may be low
  • Pyridoxine (vitamin B6) and niacin deficiency
  • Multiple carboxylase deficiency
  • Phenylketonuria
  • Kwashiorkor - "flaking paint" dermatitis and edema caused by diet deficient in protein but not calories, often due to unnecessarily restrictive food allergy diets in the US
  • Dermatitis herpetiformis- may present atypically, with erythema, urticarial plaques, or papules with severe pruritus, burning/stinging, sometimes preceding the eruption by 8-12 hours (simulating scabies)
    • Usually occurs 20-40 yo, but children with recalcitrant eczema, pruritic impetigo and papular urticaria should be suspected of having DH
    • Biopsy demonstrates neutrophilic microabscesses in dermal papillae and granular IgA
  • Histamine intolerance - reported that a subset of adult patients with AD improve on histamine-free diet, worsen with histamine challenge

AD vs. Hyper IgE syndromes

History and Physical

  • POEM - Patient-oriented eczema measure


  • Relevant allergy testing
    • 50-80% have elevated total IgE level and IgE sensitization to foods/environmental allergens, about 20-50% do not
    • Foods - about a third of infants and young children with AD will show clinically relevant reactivity to a common food allergen
      • Reaction patterns:
        • Immediate, non-eczematous IgE-mediated reactions, with some children developing a transient morbilliform rash 6-10 h after the initial immediate reaction (disappearing within a few hours) and considered to be a “late- phase” IgE-mediated response
        • Isolated eczematous delayed-type reactions, occur 6-48 hours after ingestion with flares of eczema on common AD sites, suggestive for a non IgE-mediated pattern
        • A combination of immediate-type reaction followed by an eczematous delayed-type reaction has been described in ~40% of children with positive OFC
      • NIAID guideline: test children <5 yo with moderate-severe AD for milk, egg, peanut, wheat, soy if AD is refractory to optimal treatment or if there is a recurrent history of immediate exacerbation after ingestion of a specific food
      • In older children and adults, Birch pollen-related foods have been described as potential triggers of AD (even when cooked)
    • Aeroallergens - AD may flare with topical contact with environmental allergens
    • Atopy patch testing not recommended for AD (NIAID guideline)
    • Elimination diet x 4 weeks, directed by allergy testing (as described in algorithm below) vs. empiric elimination of egg and milk, as some patients may have eczema that flares with foods despite negative testing

FA eczema algorithm.png

  • Total IgE level - often >1000 IU/mL, but noted to be as high as 10,000-100,000 IU/mL
  • Evaluate infection
    • Bacterial culture for MRSA - consider skin and nasal cultures from child and caretaker
    • Fungal culture, KOH prep - consider if rash scaly or if there are nail changes
      • Malassezia sympodialis fungal infection is a particular problem in young adults with refractory head and neck eczema and can be diagnosed clinically, with KOH prep, and/or sIgE to Malassezia
  • Specialized testing
    • Specific IgE to Malassezia sympodialis (previously termed Pityrosporum ovale), T. rubrum, C. albicans
    • Specific IgE to S. aureus enterotoxin A and B - may correlate with disease severity
    • Anti-IgE IgG level
    • Specific IgE to manganese superoxide dismutase - antibodies produced against fungal enzyme manganese superoxide dismutase may cross-react with a similar human enzyme found in skin, and could result in an autoimmune inflammatory response
    • Filaggrin genotype test - mutation in filaggrin may result in dysfunctional epidermal barrier and is implicated in pathogenesis of AD
      • Null mutations found in 14-56% of patients with AD, ~13% of eczema may be due to filaggrin mutations on a population scale; note that a substantial number of patients with severe AD do not have filaggrin mutations and 40% of normal individuals with filaggrin mutations have no skin disease
      • May also increase risk of developing food allergy, asthma, allergic rhinitis (however it is actually not expressed in the airway), and eczema herpeticum
      • Available tests:
        • IBT test looks for six prevalent mutations (R501X, 1249insG, R2447X, 2282Δ4, E2422X, S2554X)
        • National Jewish PCR looks for 5 most frequent mutations in European (Caucasian) populations (R501X, 2282del4, R2447X, S3247 and 3702delG)
        • Physical exam: hand eczema and palmar hyperlinearity are strong clinical markers of mutations


Avoid irritants and allergens
  • Environmental allergen control measures- may result in clinical improvement of AD
    • Both respiratory and skin contact with these allergens may be important in induction/exacerbation of AD
    • Avoid playing on grass, carpets
  • Laundry
    • New clothing should be laundered before it is worn to reduce the content of formaldehyde and other chemicals.
    • Residual laundry detergent in clothing may be irritating, and, although changing to a milder detergent can be helpful, using a liquid rather than a powder detergent and adding an extra rinse cycle are more beneficial.
    • Avoid fabric softener and dryer sheets.
  • Occlusive clothing should be avoided, and cotton or cotton blends should be used (avoid wool, synthetics)
  • Minimize sweating (adjust climate)
  • Avoid scratching, keep fingernails short, wear mittens at night, keep hands busy
  • Summer
    • Swimming is usually well tolerated; however, because swimming pools are treated with chlorine or bromine, patients should shower and use a mild cleanser immediately afterward and then apply moisturizers or occlusives.
    • Sunlight may be beneficial to some patients with AD, non-sensitizing sunscreens should be used to avoid sunburn (e.g. Vanicream sunscreen)
    • Avoid prolonged sun exposure which can cause irritating dryness, overheating, and sweating.
Skin cleansing
  • Use cleansers with minimal defatting activity and a neutral pH (e.g. Dove sensitive skin, Cetaphil, Vaniderm, Basis, Aveeno, Purpose, and Neutrogena)
  • Bathe at least daily in tub
    • Schneider: "Soak and seal method" bathe 1-2 times daily, soak 10-15 min in lukewarm water, submerge as much surface area as possible (cover exposed areas with wet towels), use gentle moisturizing cleansers only where needed (Olay Moisturinse, Aveeno Advanced Care Wash), then pat dry and apply topicals immediately
    • Fonacier: Soak for 20 min (with or without oatmeal or baking soda) then quickly clean with mild soap, or do a quick 5 min bath. Drip dry and apply occlusive emollient (like petroleum jelly) immediately.
Moisturizers and skin care
  • Aqua-phor, Hydrolatum (petroleum jelly with water), Vaseline (petroleum jelly), CeraVe (contains ceramides), Vanicream applied multiple times daily
    • Components: occlusives (e.g. petrolatum) retard evaporation but needs to be applied on damp/wet skin, humectants (e.g. glycerol) attract and hold water in the skin the skin, and emollients (e.g. lanolin) lubricate the stratum corneum
    • Vehicles: ointments best for lichenified skin and have less preservatives but are aesthetically undesirable, creams preferred for moist intertrigenous areas but requires preservatives that may be sensitizing and irritating, and solutions, gels, sprays are preferred for scalp but can contain alcohol and proylene glycol that burn and irritate
  • Ammonium lactate 5 or 12% (AmLactin, HydroLac, LacHydrin) BID, available OTC
  • Ceramide moisturizers
    • CeraVe cream 450 gram jar, available OTC
    • Osmotics TriCeram ointment 3.4 oz tube, available OTC
    • Nouriva repair cream (ceramides, cholesterol, free fatty acids), 30g tube, available OTC
    • Epiceram emulsion (3:1:1 ratio of ceramides, cholesterol, free fatty acids), 90 g tube, Rx
    • Hylatopic Plus cream or foam (hyaluronic acid, ceramides, fatty acids)
  • Barrier moisturizer devices
    • Atopiclair cream, 100g tube, BID-TID
    • Mimyx cream, 70, 140g tube, TID
    • Tetrix cream, 2 x 2 oz tube kit, BID-TID
  • Wet wrap dressings - caution when using with potent topical steroids due to increased absorption
  • Unna (zinc oxide) boot dressings - cotton bandage dressing impregnated with Zn oxide which soothes irritation and keeps skin moist (some unna boots also contain calamine, glycerin, acacia, castor oil, and/or white petrolatum)
    • Keep dressing in place with socks, bandages, co-flex (etc.) and keep on overnight
    • Long term use may lead to skin maceration, folliculitis, and secondary infections or rarely adrenal suppression (with moderate-to-potent corticosteroids)
  • Topical corticosteroids- 1st line treatment for acute exacerbation
    • Schneider: For acute flare, apply BID x 7-14 days then wean to daily, every other day, to none. Duration should not be limited to 5-7 days, use "touch rule" (apply steroids to rough skin until smooth)
      • Face: use class VI-VII e.g. aclometasone dip. 0.05% ointment, desonide 0.05% ointment, hydrocortisone 1-2.5% ointment
      • Body: use class II or lower, e.g. mometasone furoate 0.1% ointment (II), triamcinolone acetonide 0.1% ointment (III), mometasone furoate 0.1% cream (IV), hydrocortisone valerate 0.2% ointment (IV)
      • Scalp: use mid-low potency oil, lotion, foam, or gel
    • For preventative treatment of previously involved but now normal-appearing skin: apply steroid used for treatment 2 consecutive nights weekly
    • Clinical pearl - for AD patients with immediate rebound after stopping steroid or if steroid has to be used every day, the steroid potency is probably too low (provided that all other aspects of eczema care are maximized)
  • Oral corticosteroids - effective but associated with rebound flare-up, requires tapering, reserved for crisis management
Topical calcineurin inhibitors
  • Especially useful in areas prone to atrophy: eyelid, perioral, genital, axilla, inguinal
  • Protopic (tacrolimus) 0.1% ointment has the strength of a mid-potency topical corticosteroid and should be considered first-line therapy for facial eczema where treatment with corticosteroids is limited because of safety concerns
  • Protopic is approved for use in Europe as twice-weekly maintenance/proactive therapy to areas typically with AD in patients as young as 2 years of age for up to 12 months
  • Adverse reactions
    • A local burning sensation is the only common adverse event, with a reduction of this sensation within 3 days of initiating therapy
    • FDA black box warning regarding increased risk of malignancy discourages prolonged use (see below)
    • TCIs may increase risk for topical viral infections (eczema herpeticum, molluscum) of treated skin and patients should be monitored for this complication
    • A small percentage of patients can experience facial flushing after an alcoholic beverage
    • Use with caution in children <2 years old (due to high body surface/weight ratio), and patients with abnormal epidermis (e.g. Netherton’s syndrome) because significant percutaneous absorption of TCIs could occur, which may result in systemic serum concentrations known to cause immunosuppression
Anti-pruritic strategies
  • Oral - most effective for sedation
    • Children: Hydroxyzine 2 mg/kg PO QHS
    • Older patients:
      • Doxepin - up to 1 mg/kg PO QHS
      • Paroxetine (Paxil) - 10 mg PO QHS
      • Mirtazapine - 7.5-45 mg PO QHS
    • Schneider: cetirizine QAM and hydroxyzine or diphenhydramine 1 mg/kg PO QHS
  • Topical
    • Pramoxine (Prax lotion, Sarna)
    • Ice pack PRN
Antibiotics for superinfection
  • Bleach baths - usually 1/4-1/2 cup of regular (unscented unconcentrated) liquid bleach per 40 gallon bathtub 3-5 times/week (for small baby bathtubs, 10 mL per gallon) = 0.005 % final concentration or ~0.5 cup of 6% bleach in a full bathtub
    • Unclear whether effectiveness can be explained by S. aureus reduction or astringent effect
    • Lio: daily when flaring, 2-3 times/week for maintenance, soak for 10 min
    • Burning sensation can occur with open lesions
    • Rinse off with clean water if there are concerns about skin irritation
  • Antifungal
    • Topical
    • Malassezia infection - consider itraconazole 100 mg PO QD x 2 months then 100 mg Qweek (Lio)
  • Anti-Staph - MSSA usually more important than MRSA; refractory cases suggest MRSA
    • Oral
      • Cephalexin 50 mg/kg/day div PO TID x 7-14 days (adults 1-4 g/day div BID-QID), dicloxacillin if able to swallow tablets
      • MRSA: Clindamycin, TMP-SMX, doxycycline/minocycline; 7-10 days often sufficient
    • Topical - for localized impetiginized lesions and treatment of nasal MRSA carriage
      • Bactroban (mupirocin 2%) topical ointment, TID up to 12 days for impetigo, 15, 22, 30g
      • Bactroban nasal (mupirocin calcium 2%) ointment indicated for treatment of nasal MRSA carriers, 0.5 g intranasal BID x 5 days, supplied as 10-pack of 1 g tubes
      • Altabax (retapamulin 1%) topical ointment, BID x 5 days for impetigo, 5, 10, 15g
  • Antiseptic cleansers - may be used for patients with frequent bacterial infections on the whole body or critical areas only, however some concern for systemic absorption limits these antiseptics to patients with weepy-type AD, mothers with AD that have small babies, patients with elevated risk for systemic infection (e.g. catheters, chronic wounds, immunodeficiency)
    • Triclosan 1-2% soaps include pHisoderm, Dial liquid, Softsoap liquid hand soap
    • Chlorhexidine gluconate 0.5-1% include Hibiclens and Hex-A-Clens
  • Vitamin D deficiency may play a role in decreased antimicrobial peptide production
  • Other antibacterial measures:
    • “Spring cleaning” the patient’s bedroom, washing and replacing the linen, and wiping down surfaces and toys may help to reduce re-infection from fomites
    • Tubs and tubes of moisturizers and ointments may need replacing if there is a risk of bacterial contamination
Coal tar
  • Tar preparations - Fonacier: "Help control itching, redness and scaling when all else fails"
    • Coal tar bar soap, T-gel shampoo, Triton Mg 217 medicated tar ointment 3.8 oz
    • Compound formula with 10% liquid coal tar distillate, 5% salicylic acid, 3% lactic acid in aquaphor ointment base
  • Antipruritic and anti-inflammatory effects similar to class 7 steroid, should only be used in chronic lesions, can be used as monotherapy or in combination with topical steroids. Shampoo good for AD involving scalp.
  • Adverse effects include photosensitivity, folliculitis, odor/dark color stains clothes and decreases compliance
  • Some data indicate that immunotherapy can be effective for AD when it is associated with aeroallergen (particularly dust mite) sensitivity
Vitamin D
  • Practice parameter 2012: patients with AD may benefit from supplementation with vitamin D, particularly if they have a documented low level or low vitamin D intake
Written treatment plan


Treatments for Recalcitrant Disease

Usage Notes
  • Flohr: Initially 2.5 mg/kg/d, increase to maximum of 5 mg/kg/d in exceptional circumstances
  • Fonacier
    • Dose: 3-5 mg/kg/d for 6 weeks (children as young as 22 mo responded to 2.5 mg/kg/d), then decrease 1 mg/kg/d every 2 weeks until at 1 mg/kg/d, then increase dose interval by 1 day every 2 weeks with goal of discontinuing after 3-6 months
  • PeDRA (Pediatric Dermatology Research Alliance)
    • Dose: 5 mg/kg/day (300 mg/d max), maintain x 3 mo then taper (max 1 year)
  • AD Working Group (2012): 5 mg/kg/d div BID, weaned by 1 mg/kg/d per month, discontinued completely after 6 months
  • Rapid 2-3 week response, most with good response (93%), but rebound in 50%, 10% with sustained remission >6 months, risk of renal toxicity requiring lab monitoring
  • May be most effective for AD driven by secondary bacterial skin infections rather than allergens
  • Limit to 1 year
  • Flohr: CBC/diff, CMP, BP at baseline, then q2 weeks x 2 mo then q3 mo
  • Fonacier: BP, CBC/diff, CMP q2 weeks x 3 mo then monthly, Cr x 3 prior to start, glucose, HgbA1C, Mg, CsA level
  • PeDRA: BP Qweek x 4 then Qmo; CBC, LFTs, BUN/Cr, CMP, uric acid, lipids Qmo x 3 then Q2 mo
  • PeDRA: check patient's baseline thiopurine methyltrasferase (TPMT) activity, if normal 2.5-3.5 mg/kg/day, if intermediate, use 1 mg/kg/day. Maintain x 3 months then taper (max 2 years)
  • Flohr: Initially 1 mg/kg/d, increase to maximum of 3 mg/kg/d, taking account of TPMT result; TPMT <3 nmol/h/mL – contraindicated, TPMT 3-8 nmol/h/ mL – low dose 0.5-1 mg/kg/day, TPMT 8-14.5 nmol/h/mL 1-3 mg/kg/day, TPMT >14.5 nmol/h/mL consider >3 mg/kg/day if no response
  • Onset slow (4-8 weeks) therefore can use concurrent prednisone for 1 month
  • Potential adverse effects include myelotoxicity, headache, GI upset, hepatotoxicity
  • There are concerns about risk of lymphoma and progressive multifocal leukoencephalopathy; unclear if these would occur in patients treated for AD
  • Limit to 2 years
  • PeDRA: CBC, LFTs, BUN/Cr, at 2, 4, 8, 12 weeks then q8 weeks
  • Flohr:
    • CBC/diff, CMP, and TPMT levels at baseline, then q1 week for first month, then q3 mo
    • Increases in dose should be accompanied by weekly blood tests
    • Repeat blood count if severe throat infection or other signs of potential marrow suppression
  • Initially 200 mg/kg once weekly increased to a maximum of 400 mg/kg once weekly, depending on response. Test dose is usually given at start of therapy, followed by blood a week later.
  • Folic acid is given at least once weekly in conjunction with MTX (5 mg weekly on a different day). However, folic acid regimens vary, and evidence is not conclusive as to which is most efficacious.
  • Onset of action is slow (4-8 weeks)
  • GI symptoms (nausea), LFT abnormalities, and bone marrow suppression are potential side effects, but MTX is generally well tolerated and considered safe in the long-term (based on rheumatologic experience in children and adults)
  • The SC route can be used if PO ineffective or nausea is severe
  • Lio:
    • Consider adding Silybum marianum (milk thistle 250 mg PO BID) to protect liver
    • For nausea, divide dose to BID, ginger root/snaps
  • CBC/diff, CMP, CXR, procollagen III (only in adults because unreliable in growing children) at baseline then q2 weeks x 1st mo and at this frequency after each dose change
  • Lio: baseline CBC, CMP, hepatitis panel, recheck at 1 week then q4-6 weeks
Mycophenolate mofetil
  • 40-60 mg/kg/d (3 grams/d maximum)
  • Onset 1‐2 months
  • Can use concurrent prednisone or cyclosporine x 1 month
  • Limit to 2 years
  • CBC, CMP at 1 month then qMo
  • LFTs 3Mo

  • Interferon-gamma - may be useful as a treatment for moderate-to-severe atopic dermatitis patients who have a history of recurrent skin infections with HSV, molluscum contagiosum, or HPV
  • Phototherapy and photochemotherapy
    • Dermatology referral, helpful in 60% of refractory cases, narrow band UVB (311 nm) safe
    • Natural sunlight is beneficial but avoid sunburn and excessive sweating
    • Adverse effects include an increased risk of developing skin cancer, itch, acute burns
    • Lio: narrow band UVB 3 times/week can be an incredibly powerful treatment for those who are not responding adequately to aggressive topical management, and can stave off more powerful immunosuppressant medications in some

Baseline pretreatment screening for systemic AD tx.png

Experimental or Unproven Treatments

  • IVIG
  • Omalizumab
  • Thiazolidinediones - peroxisome proliferator-activated receptor gamma (PPAR-g) agonists, e.g. rosiglitazone (Avandia), increases insulin response and decreases proinflammatory cytokines
  • Traditional Chinese herbal therapy
  • Probiotics
  • Essential fatty acids
  • LTRA
  • Histamine-free diet

Adverse Effects of Therapy

Malignancy Risks

  • AD itself as well as long-term use of potent topical corticosteroids have been associated with a 2-fold risk of lymphoma
  • A nested case-control study of almost 300,000 patients with AD found no increase in risk of lymphoma in patients treated with TCIs

Topical Steroids (Schneider)

  • Steroid side effects are rare and reversible
    • Reversible: telangiectasia, atrophy, acne, rosacea, increased hair growth
    • Non-reversible: striae
    • Low-mid potency steroids will not cause clinically significant adrenal suppression
  • Arkwright: Contrary to common belief, there is little objective evidence that long-term use of topical corticosteroids causes chronic skin atrophy, adrenal suppression, growth retardation, or reduced bone mineral density




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