Drug-induced Exanthem: Causes

Pathogenesis (disease development)

The pathogenesis of hypersensitivity syndrome is not fully understood. It is probably multifactorial, partly toxic, partly immunogenic. The immunological reaction is caused by binding of reactive substances to endogenous receptors such as MHC molecules (Major Histocompatibility Complex; group of genes encoding proteins important for immune recognition, tissue compatibility in transplantation and immunological individuality). Triggers of an allergic reaction can be both the active drug substance and additives (additives, adjuvants). Different pathophysiological mechanisms underlie the allergy, which have been classified into four types according to Coombs and Gell. The type I to type III reactions are mediated by antibodies, while the type IV reaction is triggered by T cells. In a narrower sense, allergy is now often understood to mean only type I allergy: type I allergy (synonyms: immediate type, type I allergy, type I immune reaction, immediate allergic reaction) is characterized by a rapid response of the immune system (within seconds or minutes) upon second contact with the allergen. The initial contact, which is usually asymptomatic, is called sensitization. In this case, T and B lymphocytes independently recognize the antigen in question. The secondary reaction is IgE-mediated. Here, the allergen binds to the IgE present on the mast cells (part of the immune system) and histamine is released. Furthermore, inflammatory mediators such as prostaglandins and leukotrienes are released. The following symptoms may occur: Urticaria (hives) (anaphylactic reaction: 15-20 min; IgE- mediated: 6-8 h), rhinitis (inflammation of the nasal mucous membranes), angioedema (sudden swelling of the skin or mucous membranes), bronchospasm (cramping of the muscles surrounding the airways), and even anaphlactic shock (the most severe allergic reaction, which can be fatal). Type II allergy (cytotoxic type) is divided into type IIa and type IIb. Type IIa is characterized by the formation of IgG or IgM antibodies against body cell-bound antigens (autoantibodies). This is followed by binding of the antibodies to the antigens with subsequent destruction of the affected cells by complement, macrophages and NK cells (natural killer cells). Type IIb is characterized by antibody-antigen interaction as in type IIa. However, cell destruction here is not by binding but by receptor binding (reaction with hormone receptors). The following symptoms may occur: no skin reactions, but hemolytic anemia, thrombocytopenia (lack of platelets), etc. Type III allergy (synonyms: type III allergy, immune complex type allergy, type III hypersensitivity reaction, immune complex type, Arthus type) is characterized by the formation of immune complexes (allergen + antibodies), which can be cellular or float (“swim”) freely in the blood. The immune complexes form within hours after allergen contact. The allergic immune complex reaction is mediated by antibodies (IgG, IgA, IgM). The immune complexes activate the complement system and initiate phagocytosis (“eating the cell”) of the complexes by leukocytes (white blood cells), which in turn releases cytotoxic enzymes. The following symptoms may occur: Urticaria (hives), vasculitis (inflammation of blood vessels), nephritis (inflammation of kidneys), arthritis (inflammation of joints), etc. Type IV allergy (synonym: late-type allergic reaction) is an allergy that is cellularly mediated by sensitized T lymphocytes. It is triggered by the active drug substance or by contact with additives (contact allergy) in drug production. The following symptoms may occur: Contact dermatitis (inflammatory reaction of the skin triggered by direct contact of the skin with allergens), drug exanthema (multiforme-like, lichchenoid (lichen-like); reaction time: 24-72 h).

Type I, IIa, III and IV allergies play a role in allergic reactions to a drug or its additives. In addition to allergic reactions, pseudoallergic reactions (pathological reaction to a noxious substance (pollutant) acting on the body, which resembles an allergy but is not based on an antigen-antibody reaction) can also occur.This is a direct IgE-independent release of histamine from mast cells with, for example, antibiotics, muscle relaxants, and opioids.

Etiology (Causes)

Biographic causes

  • Genetic burden from parents, grandparents, unspecified.

Behavioral causes

Disease-related causes

  • Autoimmune diseases, unspecified
  • Limitation of liver function, unspecified
  • Limitation of renal function, unspecified
  • Lymphoroliferative disorders, unspecified
  • Viral infections such as HIV or EBV

Medications

1 Type I allergy (immediate type) 2 Type III allergy (Arthus phenomenon) 3 Type IV allergy (allergic late-type reaction)/allergic contact dermatitis 4 Type IV allergy (allergic late-type reaction)/Lichen ruber-like or psoriasiform DMD 5 Type IV allergy (allergic late-type reaction)/blistering DMD.

6 Fixed drug exanthema (exanthema that reappears at the same skin site after re-administration of the drug).

The list of drugs represents only the most common triggers. There is no claim to completeness.