Palmar plantar erythrodysesthesia differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mandana Chitsazan, M.D. [2]

Overview

Palmar plantar erythrodysesthesia (PPE) must be differentiated from other skin disorders that involve palms and/or soles, such as Graft-versus-host disease, contact dermatitis, palmoplantar plaque psoriasis, dyshidrotic eczema, and palmoplantar pustulosis.

Differentiating Palmar Plantar Erythrodysesthesia from other Diseases

Palmar plantar erythrodysesthesia (PPE) must be differentiated from other skin disorders that involve palms and/or soles, such as Graft-versus-host disease, contact dermatitis, palmoplantar plaque psoriasis, dyshidrotic eczema, and palmoplantar pustulosis.

Disease	Clinical manifestation	Histopathology	Additional diagnostic clues
Palmar plantar erythrodysesthesia	Areas of well-defined intense erythema and edema	A variable degree of epidermal (keratinocytes) necrosis Vacuolar degeneration of the basal cell layer of epidermis Spongiosis Hyperkeratosis Lymphohistiocytic infiltrates Superficial perivascular infiltration of dermis by lymphocytes and eosinophils Papillary dermal edema Neutrophilic eccrine hidradenitis Eccrine squamous syringometaplasia, in severe PPE (WHO grades 3 and 4)	History of chemotherapeutic agent use
Graft-versus-host disease (GVHD)	A diffuse macular erythema which may form papules	Histologic features of Graft-versus-host disease and palmar plantar erythrodysesthesia are identical in early stages and serial biopsies may be needed to distinguish between these two entities. Features suggestive of Graft-versus-host disease: Degenerate keratinocytes at all levels of the epidermis Adjacent lymphocytes (satellite cell necrosis)	Extracutaneous manifestations of Acute GVHD, including: Gastrointestinal symptoms, such as diarrhea and abdominal pain Elevated liver enzymes
Allergic contact dermatitis	Well-demarcated, eczematous eruptions localized to the area of skin that in contact with the culprit allergen Acute eruption: Vesicular Chronic eruption: Lichenified and scaly plaques	Eosinophilic spongiosis Exocytosis of eosinophils and lymphocytes	History of allergen exposure Pruritic lesions Patch testing may help to identify allergens
Palmoplantar plaque psoriasis	Sharply defined erythematous, scaly plaques on the palms and/or soles Fissures	Acanthosis Hyperkeratosis Parakeratosis Neutrophilic infiltration in the epidermis and stratum corneum (Kogoj pustules and Munro's microabscesses) Abundant mononuclear cells (mainly myeloid cells and T cells) in the dermis	Pruritus is common Positive Koebner phenomenon
Dyshidrotic eczema	Deep-seated clear vesicles; later, scaling, fissures and lichenification occur Deep-seated vesicles or blisters on the tips and lateral sides of the fingers, palms, and soles with subsequent scaling, fissures and lichenification	Acute: Intraepidermal spongiotic vesicles or bullae that do not involve the intraepidermal portion of the eccrine sweat duct (acrosyringium) A sparse, superficial perivascular infiltrate of lymphocytes Chronic: Predominance of parakeratosis and acanthosis with minimal or no spongiosis and a dermal lymphocytic infiltrate	Intensely pruritic History of recurrence
Palmoplantar pustulosis	Multiple pustules on the palms and/or soles, with surrounding erythema and hyperkeratosis Fissures Nail changes Brown macules at the site of resolving pustules	Parakeratosis Loss of granular layer Psoriasiform epidermal hyperplasia Spongiosis Pustules filled with neutrophils and eosinophils in the upper epidermis Mast cell and eosinophil infiltration in the upper dermis Mixed perivascular and diffuse infiltrate in the dermis (lymphocytes, neutrophils, eosinophils, and mast cells)	Non-pustular psoriasis-like eruptions may be seen in other areas Nail changes may be seen Arthralgia or unspecified arthritis may be seen in some patients