Cutaneous adverse drug reactions (CADRs) include a wide range of clinical symptoms from moderate and self-limiting cutaneous eruptions such as maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs).

CADRs are delayed-type hypersensitivity reactions. Usually the inflammation starts within 12 - 24 hr or sometimes after many days of antibiotic exposure. Though these reactions are usually mild and can be treated by discontinuing the antibiotic or by simple treatments, patients with SCARs need hospitalization.

SCARs can manifest in a variety of ways. The most common SCAR is Stevens-Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) followed by drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP)). Antibiotics are the most commonly implicated medications of SCARs, followed by antiepileptic drugs, allopurinol, and non-steroidal anti-inflammatory drugs (NSAIDs).

CADRs affect 1 - 3% of people in developed nations. SCARs are rare reactions, yet they have a significant mortality rate. SCARs have a frequency of 0.4 - 1.2 cases/ million/year with a 14 - 70% mortality.

Stevens-Johnson Syndrome(SJS) and Toxic Epidermal Necrolysis (TEN)

SJS and TEN form a spectrum of the same disease differentiated by the extent of epidermal necrosis and detachment. In SJS there is < 10% of epidermal detachment and in TEN there is >30%. SJS/TEN overlap lies between the two extremes. SJS/TEN is often preceded by a prodrome of upper respiratory type of symptoms - fever, general malaise, nonproductive cough, stinging eyes and a sore mouth. They rapidly progress to an exanthem of macules and targetoid lesions, epidermal detachment and erosive mucositis of at least 2 surfaces, usually within 3 days. Early painful erythema of the palms and soles is a major feature of SJS/TEN.

TEN has a mortality of > 30%.

Risk factors for SJS/TEN:

• HIV infection
• Certain HLA alleles
• Renal failure
• Radiotherapy

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

DRESS is another severe form of SCAR. The eruption is most commonly urticaria-like plaques or an exanthem. However, vesicles, pustules,cheilitis, purpura, targetoid lesions and erythroderma have been reported. Fever, edema ( particularly facial and acral), lymphadenopathy, leukocytosis, eosinophilia, and/or atypical lymphocytosis, hepatitis, and non-erosive mucositis have been reported with variable frequency. Long standing severe lesions are characterized by extensive scaling referred to as exfoliative dermatitis. Involvement of >50% of the body surface area (BSA), severe edema, infiltrated skin lesions, scaly erythema and purpura differentiate DRESS from drug exanthems.

DRESS mortality is approximately 10%. Risk factors for DRESS:

• Renal failure
• Advanced age

Acute Generalized Exanthematous Pustulosis

AGEP manifests as a fever with rapidly spreading multiple pin-head sized, sterile, non-follicular pustules on an erythematous and edematous base, particularly in the intertriginous zones of the neck, submammary, inguinal, axillary area, trunk, and upper extremities. Palms and soles are rarely affected.

Systemic features of AGEP may include fever, leukocytosis, neutrophilia, eosinophilia, and hypocalcemia.

Organ involvement is not common. Skin symptoms usually resolve without treatment in 1 - 2 weeks after discontinuation of the offending antibiotic. The reported mortality is less than 5%.

Serum Sickness-Like Reactions (SSLR)

SSLR clinically resembles Serum Sickness (SS). SS is the prototype immune-complex mediated hypersensitivity reaction. In SSLR there are no circulating immune complexes, normal serum complement levels, and no evidence of internal organ involvement such as nephritis or hepatitis.

Clinical features include pruritic urticarial or serpiginous plaques, fever, malaise, and polyarthralgia or polyarthritis typically 5 - 10 days after exposure to the offending drug/antibiotic. The disease is self-limiting and resolves spontaneously on discontinuation of the offending drug.