Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) are a group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose, mouth, and lips. In more severe cases, SCARs also involves serious damage to internal organs.

SCARs includes five syndromes:

1. Drug reaction with eosinophilia and systemic symptoms (i.e. DRESS syndrome), also termed drug-induced hypersensitivity syndrome (DIHS);
2. Stevens–Johnson syndrome (SJS);
3. Toxic epidermal necrolysis (TEN);
4. Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN); and
5. Acute generalized exanthematous pustulosis (AGEP).

The five disorders have similar pathophysiologies, i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop the SCARs-inducing effects of specific drugs and thereby avoid treatment with them.^[1] Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares a similar pathophysiology with SCARs and is caused by some of the same drugs which cause SCARs.^[2]

Adverse drug reactions are major therapeutic problems estimated to afflict up to 20% of inpatients and 25% of outpatients. About 90% of these adverse reactions take the form of benign morbilliform rash hypersensitivity drug reactions such as MPR. However, they also include more serious reactions:

1. Pseudo-allergic reactions in which a drug directly stimulates mast cells, basophils, and/or eosinophils to release pro-allergic mediators (e.g. histamine);
2. Type I, Type II, and Type III hypersensitivity reactions of the adaptive immune system mediated by IgE, IgG, and/or IgM antibodies; and
3. SCARs and MPR which are Type IV hypersensitivity reactions of the innate immune system initiated by lymphocytes of the T cell type and mediated by various types of leukocytes and cytokines.^[3]

Type IV hypersensitivity reactions are off-target drug reactions, i.e. reactions in which a drug causes toxicity by impacting a biological target other than the one(s) for which it is intended. They are T cell-initiated delayed hypersensitivity reactions occurring selectively in individuals who may be predisposed to do so because of the genetically-based types of human leukocyte antigens (i.e. HLA) or T-cell receptors they express; the efficiency with which they absorb, distribute to tissues, metabolize, and eliminate a drug or drug metabolite; or less well-defined idiosyncrasies.^[1][4][5]

Categorizing SCARs as a group focuses on the similarities and differences in their pathophysiologies, clinical presentations, instigating drugs, and recommendations for drug avoidance.