Atopic dermatitis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Differentiating Atopic Dermatitis from other Diseases

Category	Diseases	Etiology	Inherited	Acquired	Clinical manifestations													Para-clinical findings									Gold standard	Additional findings
					Demography	History and risk factors	Symptoms						Physical examination
																		Lab Findings							Imaging	Histopathology
							Appearance				Itching	Bleeding	Fever	BP	Tenderness	Nail pitting	Other	CBC			ESR/CRP	Electrolytes	BUN/Cr	LFT
							Single/ Multiple	Rash	Involved areas	Pustule								WBC	Hb	Plt
Skin disorders	Atopic dermatitis																											Hayfever Asthma
	Allergic contact dermatitis	Delayed-type hypersensitivity response Skin inflammation mediated by hapten-specific T cells	–	+	Any	Contact with allergens in the past 1-2 days Positive family history	May be multiple after 1-2 days of exposure	Erythematous well-demarcated papules	Surrounding the area in contact with the offending agent	–	+	–	–	Nl	+	–	Stinging and burning Localized swelling Lichenified pruritic plaques	Nl to ↑ (Eosinophilia)	Nl	Nl	Nl	Nl	Nl	Nl	NA	NA	Clinical manifestation + patch test	Prevention by avoidance
	Irritant contact dermatitis	Activation of the innate immune system by the pro-inflammatory properties of chemicals	–	+	Any, more occupational exposure	Cumulative exposure to irritants	Usually single immediately after the exposure	Well-demarcated red patch with a glazed surface	Any area in contact with the irritant	–	+	–	–	Nl	+	–	Swelling, blistering and scaling of the damaged area Dryness Thicker skin	Nl	Nl	Nl	Nl	Nl	Nl	Nl	NA	Spongiosis Intraepidermal vesicles or bullae Necrosis of keratinocytes	Clinical manifestation + patch test	Negative hypersensitivity tests
	Seborrheic dermatitis	Unknown	–	+	Any, onset during the 1st days or weeks of life	Stress Cold, dry weather		Greasy scaling on a yellow-red base	Scalp, axilla, and diaper area		–
	Psoriasis	Keratinocyte hyperproliferation Dysregulation of the immune system	+	+	Any, 2 peaks of onset 30-39 years and 50-59 years	Smoking Skin trauma Alcohol abuse Stress Cold weather Vitamin D deficiency Drugs	Multiple	Well-circumscribed, pink papules and symmetrically distributed cutaneous plaques with silvery scales	Scalp Trunk Gluteal cleft Extensor surface of elbows and knees	+	+	+ Auspitz sign (pinpoint bleeding)	_	Nl	+	+
	Lichen simplex chronicus	Lichenified plaques and excoriations of lichen simplex chronicus develop secondary to extensive pruritus due to other conditions such as atopic dermatitis, neuropathic pruritus, etc	–	+	Any, peak at 30-50 years of age	Emotional stress Sleep disturbances Dry weather Sweating Excessive dryness	Multiple	Lichenified and erythematous, pruritic exudative plaque, and excoriations	Scalp, head, neck, hands, arms, and genitals areas	–	+	–	–	Nl	–	–	Color of plaque varies fro, yellow to reddish brown Plaque size can vary between 3X6 cm 6X10 cm areas.	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Markedly hyperplastic epidermis Irregular hyperkeratosis and parakeratosis Thick granular zone Acanthosis	Clinical manifestation	Sexual dysfunction Sleep disturbances Depression Dissociative disturbances
	Ichthyosis vulgaris	Loss of function mutations in the filaggrin gene (FLG) Autosomal dominant inheritance with incomplete penetrance	+	+	Usually in infancy	Dry and cold weather Increased risk of atopic diseases including asthma, alllergic rhinitis and atopic dermatitis	Multiple	Xerosis and gray scaling Palmar hyperlinearity Keratosis pilaris	Extensor surfaces of the extremities Scalp Trunk	–	–	–	–	Nl	–	–	Scales can vary from mild scaling to large, plate (armor)-like scales and thickening of the skin.	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Reduced keratohyalin granules Perinuclear keratin retractions in granular cells Thick stratum corneum Basket-weave pattern of stratum corneum	Clinical manifestation	Increased risk for atopy, including asthma, allergies, and atopic dermatitis
	Nummular dermatitis (discoid eczema)	Unknown	–	+	Any, two peaks, 6th-7th decade of life in males and 2nd-3rd decade of life in females	Temperature changes (particularly winter) Emotional stress Dry skin Environmental irritants Recent surgery Medications like topical antibiotic creams and isotretinoin	Multiple	Nl	Upper extremities Lower extremities Lower trunk	–	+	–	–	Nl	–	–	Chronically lesions result into central clearing leading to annular lesions.	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Spongiosis Perivascular lymphocytic infiltrates, with eosinophils and occasional neutrophils	Clinical manifestation	Superinfection with staphylococcus aureus
	Netherton's syndrome	Autosomal recessive mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5), encoding LEKTI, a serine protease inhibitor	+	–	Affects neonates	Atopic diseases including food allergy and strong family history of asthma, atopic dermatitis and allergic rhinitis	Multiple	Classic triad Congenital ichthyosiform erythroderma Trichorrhexis invaginata Allergic diseases with elevated serum levels of immunoglobulin Ichthyosis linearis circumflexa (ILC) - serpiginous migratory pink-red plaques with double-edged scale at the margins	Diffuse pattern Axillae, Hair Inguinal folds Gluteal cleft Groin Lower legs	+	+	–	–	Nl	–	–	Trichorrhexis invaginata (hair involvement): Sparse, short, spike and brittle "Bamboo hair" or "ball and socket deformity" of hair and eyebrows Nodes along the hair shaft	↑ serum immunoglobulin E (IgE) levels ↑ Eosinophilia	Nl	Nl	Nl	Nl	Nl	Nl	Nl	psoriasiform hyperplasia Reduced granular layer Dyskeratosis, Dermal inflammatory infiltrate including neutrophils and eosinophils	Clinical manifestation	Systemic and skin superinfections Failure to thrive Electrolyte imbalances, including hypernatremic dehydration Atopic diseases
	Diseases	Etiology	Inherited	Acquired	Demography	History and risk factors	Single/ Multiple	Rash	Involved areas	Pustule	Itching	Bleeding	Fever	BP	Tenderness	Nail pitting	Other	WBC	Hb	Plt	ESR/CRP	Electrolytes	BUN/Cr	LFT	Imaging	Histopathology	Gold standard	Additional findings
Infection	Dermatophytes
	Candida
	Herpes simplex
	Staphylococcus aureus
	Molluscum contagiosum	Molluscum contagiosum virus inoculation through direct skin contact	–	+	Any, peak among children >5 years of age and young adults	Often asymptomatic Tender or pruritic skin lesions Self resolve within 2 months Immunocompetent patients present with extensive and severe infections	Multiple	Flesh-colored, dome-shaped papules with a central umbilication Lesions are 2-5mm in diameter	Face, trunk, antecubital, popliteal fossae and groin	–	+	–	–	Nl	–	–	If molluscum contagiosum is acquired as sexually transmitted disease, it involves, groin and genital region.	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Keratinocytes containing eosinophilic inclusion bodies (Henderson-Paterson bodies) H&E stain - inwards indentation of the epidermis	Clinical manifestation	mMlluscum contagiosum lesions on the eyelid may lead to follicular or papillary conjunctivitis .
	Scabies					Positive family history	Multiple	Erythematous papular lesions	Flexor wrists, finger webs and genitalia		+++
	Diseases	Etiology	Inherited	Acquired	Demography	History and risk factors	Single/ Multiple	Rash	Involved areas	Pustule	Itching	Bleeding	Fever	BP	Tenderness	Nail pitting	Other	WBC	Hb	Plt	ESR/CRP	Electrolytes	BUN/Cr	LFT	Imaging	Histopathology	Gold standard	Additional findings
Immunologic disorders	Dermatitis herpetiformis	Autoimmune disorder as a result of gluten sensitivity leading to the formation of IgA antibodies	–	+	Any, mean age of disease onset is 2nd-4th decade	Intermittent pruritic papules and vesicles Associated small intestine celiac disease with villous atrophy and crypt hyperplasia	Multiple	Excoriated papules or plaques and vesicles arranged in a clustered fashion Symmetrical Erosions and excoriations	Extensor surfaces including arms, knees, and buttocks.	–	+	–	–	Nl	–	–	Oral manifestation such as vesicles and erosion may be present	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Papillary micro-abscesses Sub-epidermal blisters containing neutrophils, eosinophils, and fibrin Sub-epidermal vacuolization	Direct immunofluorescence microscopy (DIF) - presence of granular deposits of IgA within the dermal papillae	Abdominal bloating, pain, diarrhea, or constipation
Immune deficiency	Wiskott-Aldrich syndrome	Mutation in the gene encoding for Wiskott-Aldrich syndrome protein (WASp) on the short arm of the X chromosome X-linked disorder	+	–	Seen almost exclusively in males in infancy	Blleeding: severe thrombocytopenia, Eczema - similar to atopic dermatitis Recurrent sino-pulmonary infections Opportunistic infections. Autoimmune diseases Malignancies	Multiple	Rash is clinically similar to atopic dermatitis Erythematous and pruritic lesions Lesions can bleed due to thrombocytopenia Cutaneous manifestations includes petechiae and ecchymosis	Rash can involve lesions located at the same areas of classical atopic dermatitis: extensor surfaces of extremities and cheeks or scalp	–	+	+	–	Nl	–	–	Infants can present with petechiae, prolonged bleeding from umbilicus or circumcision, purpura, hematemesis, melena, epistaxis, hematuria or unusal bruising	↑ Eosinophilia	Nl	Thrombocytopenia and small platelets	Nl	Nl	Nl	Nl	Nl	Hyperkeratosis Psoriasiform hyperplasia Dyskeratosis Epidermal psoriasiform hyperplasia Marked intercellular edema with spongiotic vesiculation	Clinical manifestation	↑ serum immunoglobulin A (IgA) levels ↑ serum immunoglobulin E (IgE) levels
	Hyper-IgE syndrome	Defects in the JAK-STAT signaling pathway leading to dysfunctional T helper cell type 17 (Th17) differentiation	+	–	Rare, begin in infancy	Cold abscesses Pruritic eczema Allergic diseases Noneruption of permanent teeth Multiple bone fractures and scoliosisis Peripheral T-cell lymphoma Coronary artery aneurysms	Multiple	Papulopustular Severely pruritic eczematous rash Pustular and may impetiginized Lichenification may occur	Face and scalp Upper trunk and shoulders Buttocks Area behind the ears and around the hairline	+	+	–	–	Nl	–	–	Characteristic coarse facies Increased alar width and broad nasal bridge High-arched oral palate Hyperextensible joints	↑ Eosinophilia	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Eosinophil-rich infiltration around the hair follicles	Clinical and laboratory findings	↑ serum immunoglobulin E (IgE) levels
Category	Diseases	Etiology	Inherited	Acquired	Demography	History	Single/ Multiple	Rash	Involved areas	Pustule	Itching	Bleeding	Fever	BP	Tenderness	Nail pitting	Other	WBC	Hb	Plt	ESR/CRP	Electrolytes	BUN/Cr	LFT	Imaging	Histopathology	Gold standard	Additional findings

References

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