Differentials
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Systemic lupus erythematosus (SLE) usually occurs in young women; drug-induced lupus can occur in anyone.
SLE commonly involves the kidneys, drug-induced lupus rarely.
INVESTIGATIONS
CBC: anemia, leukopenia, thrombocytopenia; rarely pancytopenia. (Drugs and infections should be excluded as a cause.)
Serum complement: often low.
SLE is associated with antibodies to double-stranded DNA; drug-induced lupus is associated with antibodies to single-stranded DNA.
Autoimmune blistering disorders
SIGNS / SYMPTOMS
Pemphigus vulgaris and linear IgA disease may both cause mucosal and cutaneous blistering and can be very difficult to distinguish clinically from Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN).
INVESTIGATIONS
Skin histology and direct immunofluorescence studies are critical.
Staphylococcal scalded skin syndrome
SIGNS / SYMPTOMS
Staphylococcal scalded skin syndrome (SSSS) typically arises in children, whereas toxic epidermal necrolysis (TEN) is more common in adults. Both cause blistering/peeling of the skin. However, the level of split is much higher in the epidermis than with TEN. SSSS is not associated with prominent mucosal involvement and often has a perioral focus.
INVESTIGATIONS
Skin histology shows full-thickness necrosis in TEN.
Infection
SIGNS / SYMPTOMS
Infections can cause a variety of exanthems, often with fever, which can be difficult to distinguish from hypersensitivity reactions.
INVESTIGATIONS
Microbiological culture (bacteria), PCR (viruses).
Infections will often worsen on withdrawal of antimicrobial treatment and may improve with introduction of treatment.
Psoriasis
SIGNS / SYMPTOMS
Typically presents as erythematous, circumscribed, scaly papules and plaques on elbows, knees, extensor surfaces of limbs, and the scalp.
INVESTIGATIONS
Skin biopsy shows psoriasiform lesions caused by practolol are accompanied by fibrosis, which is not normally a feature of psoriasis.
Lichen planus
SIGNS / SYMPTOMS
Cutaneous lichen planus typically presents with intensely pruritic lesions on flexor wrists, ankles, trunk, and extremities.
INVESTIGATIONS
Biopsy of lesional skin for histopathology shows lymphohistiocytic infiltrate and necrotic keratinocytes with hyperorthokeratosis and hypergranulosis in nondrug-induced lichen planus.
In lichen planus, parakeratosis, spongiosis, and patchy inflammatory changes suggest a drug-induced cause.
Other nondrug-related rashes
SIGNS / SYMPTOMS
Differential diagnosis of any drug-related rash is the nondrug-related form of the condition that it looks like; in a few cases, such as SLE, psoriasis, and lichen planus, features help to distinguish drug-related from nondrug-related rashes.
INVESTIGATIONS
Peripheral blood eosinophilia and an eosinophilic cellular infiltrate in any lesion suggest a drug-related effect.
Exanthematous reactions are often due to infections; a specific diagnosis may be possible if the causative organism can be identified.
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