CAE category | Cutaneous eruption | Time to onset | Clinical findings | Histopathology |
Inflammatory | Maculopapular (morbilliform) | 3 to 6 weeks | Erythematous macules and flat papules on trunk and dorsal aspect of extremities | Superficial, perivascular, lymphohistiocytic infiltrate +/– eosinophils. |
Eczematous | 0 to 3 weeks | Pruritic, erythematous papules coalescing into plaques predominantly on trunk and extremities | Spongiotic dermatitis with superficial, perivascular, lymphohistiocytic infiltrate +/– eosinophils. | |
Psoriasiform | 0 to 3 weeks | Well-demarcated, erythematous papules or plaques with adherent scale of the trunk and extremities (most common); palmoplantar, pustular, inverse, or guttate variations | Regular acanthosis with hypogranulosis; confluent parakeratosis; and superficial, perivascular dermatitis with lymphocytes, histiocytes, and neutrophils. | |
Lichenoid | 6 to 12 weeks | Flat-topped, violaceous papules with adherent scale | Lichenoid and vacuolar dermatitis with lymphocytes and histiocytes, hyperorthokeratosis, wedge-shaped hypergranulosis, and saw-tooth rete ridges. | |
Granulomatous | 3 weeks or later | Red-brown papules or nodules on the head, trunk, or extremities | Nodular, histiocytic dermatitis with minimal surrounding lymphocytes or other inflammatory cells, negative special stains for organisms. | |
Vitiligo | 7 to 16 weeks or later | Depigmented macules and patches | Decreased or absent melanocytes at the dermal-epidermal junction. | |
Neoplastic | Cutaneous squamous cell carcinoma/keratoacanthoma | 12 to 18 weeks or later | Hyperkeratotic papules and nodules | Full-thickness epidermal atypia with a crateriform architecture in the case of keratoacanthoma. |
Severe cutaneous reactions | SJS/TEN | 1 to 4 weeks (may be shorter on re-exposure) | Dusky red, coalescent, macular eruption, with atypical target lesions with central vesiculation and mucosal involvement | Full-thickness epidermal necrosis with a sparse, superficial, perivascular, lymphohistiocytic infiltrate and possible vacuolar degeneration. |
DRESS | 2 to 8 weeks | Erythematous macules and papules (nonspecific cutaneous findings) Facial edema and lymphadenopathy | Interface dermatitis with basal vacuolization; spongiosis; perivascular, lymphocytic infiltrate; vascular damage. | |
AGEP | <1 week | Widespread erythema with numerous tiny, pinpoint pustules | Spongiotic psoriasiform dermatitis with subcorneal pustules and numerous dermal eosinophils. | |
Connective tissue disease | Dermatomyositis | >12 weeks | Erythematous or violaceous papules in photodistribution "heliotrope eruption" (pink-violaceous erythema and edema of the eyelids) | Sparse interface dermatitis with focal dyskeratosis and increased dermal mucin. |
Lupus erythematosus | ≥6 weeks | Features of acute lupus erythematosus (eg, malar rash), subacute lupus erythematosus (erythematous papules and plaques; annular, polycyclic plaques on upper trunk, neck, and arms), or discoid lupus erythematosus (papulosquamous, photodistributed eruption) | Superficial and deep, perivascular and periadnexal dermatitis with overlying interface dermatitis and increased dermal mucin. | |
Antibody mediated | Bullous pemphigoid | 13 to 16 weeks or later | Prodromal pruritus followed by formation of tense vesicles | Subepidermal, vesicular dermatitis with superficial, perivascular, and intravesicular eosinophils. Direct immunofluorescence positive for IgG and C3 at the dermal-epidermal junction. |
Hair | Alopecia areata | 13 to 16 weeks or later | Round, alopecic patches on the scalp without scale or erythema | Nonscarring alopecia with lymphocytic infiltrate at the base of the hair follicles. |
Rare, including possible exacerbation of pre-existing disease | Acneiform | 1 to 8 weeks or later | Erythematous, follicular papules and pustules | Acute neutrophilic folliculitis with disturbance of the follicular epithelium. |
Sweet syndrome | ≥4 weeks | Erythematous, edematous, and tender plaques and nodules on face, upper extremities, and trunk | Papillary dermal edema with minimal epidermal change and underlying, neutrophilic dermatitis without vasculitis. | |
Pyoderma gangrenosum | 16 weeks(?) | Inflammatory papule, pustule, or nodule that subsequently enlarges and ulcerates with undermined, violaceous borders | Diffuse, neutrophilic, dermal infiltrate often with fibrosis, granulation tissue, and negative tissue cultures and/or special stains for organisms. |
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