Table 1.

Differential for Refractory Atopic Dermatitis

Diagnostic considerations	Diagnostic assessment
Primary immunodeficiencies
Transient hypogammaglobulinemia of infancy	Low serum IgG, normal vaccine responses
Autosomal dominant hyper IgE syndrome (AD-HIES)	STAT3 mutation
Autosomal recessive HIES	DOCK8 mutation, TYK2 mutation
Wiskott-Aldrich syndrome	WASp gene mutation
IPEX syndrome	FoxP3 gene mutation
Severe combined immunodeficiency	Low lymphocyte count, poor immune function, various gene mutations including ADA, common gamma chain, PNP, others
Skin infection
Bacterial (eg, S aureus)	Skin culture
Viral (EV, EH, EC)	Viral PCR, culture
Fungal (Malassezia, Candida)	Fungal culture, skin scraping for fungal hyphae
Exposures
Irritants (eg, scratching, fragrances, wool)	History, patch testing
Food allergies	History, PST, IgE to food
Environmental allergies	History, PST
Other conditions
Netherton syndrome	Bamboo hair, SPINK5 gene mutations
Acrodermatitis enterohepatica	Plasma Zinc levels, SLC39A4 gene mutations
Filaggrin mutation	FLG null mutations
Contact dermatitis	Patch testing, improvement after allergen removal
Scabies	Skin scraping
Psoriasis	Clinical diagnosis
Erythroderma of other causes, including oral steroid withdrawal	Clinical diagnosis
Malignancies (eg, cutaneous T cell lymphoma)	Skin biopsy

Abbreviations: AD-HIES, autosomal-dominant hyper-IgE syndrome; DOCK8, dedicator of cytokinesis 8; EC, eczema coxsacki; EH, eczema herpeticum; EV, eczema vaccinatum; HIES, hyper-IgE syndrome; Ig, immunoglobulin; IPEX, immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; PCR, polymerase chain reaction; PNP, purine nucleoside phosphorylase deficiency; PST, prick skin test; TYK2, tyrosine kinase 2.