Hives (Urticaria): Causes

Pathogenesis (development of disease)

Urticaria is characterized by edema (water retention) of the dermis (skin), which is an expression of an increase in vascular permeability (vascular permeability). The mediators (messengers) are released mainly from mast cells (cells of the body’s defense system that have stored certain messengers, including histamine and heparin). One can distinguish an immunological from the non-immunological pathomechanism. The immunological pathomechanism of urticaria is usually characterized by type I allergy (immediate type). Within seconds to a few minutes, cellular IgE antibodies mediate the release of various mediators. Histamine, prostaglandins and leukotrienes are released from mast cells and basophilic granulocytes (belong to the group of white blood cells). The first contact with the allergen is asymptomatic. Second contact causes the allergen to bind to the IgE present on the mast cells, histamine is released and the immediate reaction occurs. Serum sickness or urticarial vasculitis (see below) is characterized by type III allergy (synonyms: type III allergy, immune complex type allergy, type III hypersensitivity reaction, immune complex type, Arthus type). This is characterized by the formation of immune complexes (allergen + antibodies), which can be both cellular and free floating (“swimming“) 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.

Etiology (causes)

Acute and chronic courses of urticaria and their causes:

  • The acute form of progression is more common.
    • Acute spontaneous urticaria (ASU; symptom duration of < 6 weeks): triggering factors are infections, food, allergies, often idiopathic (disease occurring without a tangible cause), and drugs.
  • The chronic course (symptom duration of ≥ 6 weeks) is subdivided as follows.
    • Chronic inducible urticaria (CINDU): causes are:
      • Approximately 15-20% induced by physical stimuli (= physical urticaria; e.g., cold urticaria, pressure urticaria/contact urticaria, light urticaria).
      • Approximately 5-10% by allergic reactions (eg, food allergies);
      • Aquagenic urticaria (triggered by contact with water);
      • In more than half of cases, the cause is idiopathic
    • Chronic spontaneous urticaria (CSU); causes are:
      • Intolerance of endogenous substances (= autoreactive urticaria).
      • Reaction to a focus of infection or inflammation (= infectious urticaria).
      • Hypersensitivity to food components (= intolerance urticaria).
      • In about one third of cases, the cause is idiopathic

Biographical causes

  • Spring-born (possibly due toearly contact with inhaled allergens (especially pollen)).
  • Occupation – work exposed to vibrations (e.g. jackhammer).

Behavioral causes

  • Nutrition
    • Food/additives, e.g., milk, eggs, fish (food allergens).
    • Spicy food
    • Food preservatives and / or food coloring.
  • Physical activity
    • Heavy exertion
  • Mechanical irritation/pressure

Disease-related causes

Skin and subcutaneous (L00-L99)

  • Acute urticaria
  • Allergic urticaria
  • Aquagenic urticaria – hives after water contact.
  • Cholinergic urticaria – hives caused by sweating or heavy exertion.
  • Chronic urticaria – for example, based on allergic contact dermatitis when using acrylate or methacrylate-based nail cosmetics.
  • Idiopathic urticaria – hives, the cause of which is unclear.
  • Contact urticaria
  • Periodic/recurrent urticaria
  • Urticaria due to cold/heat
  • Urticaria bullosa – hives associated with blistering.
  • Urticaria circinata – polycyclic limited foci.
  • Urticaria cum pigmentatione – hives, after which subsides hyperpigmentation occurs.
  • Urticaria e calore (heat urticaria).
  • Urticaria factitia – hives due to mechanical irritation.
  • Urticaria gigantea
  • Urticaria haemorrhagica – associated with hemorrhages.
  • Urticaria mechanica (pressure urticaria)
  • Urticaria pigmentosa – benign generalized proliferation of tissue mast cells.
  • Urticaria porcellanea – whitish edematous wheals.
  • Urticaria profunda – associated with deep edema formation.
  • Urticaria rubra – bright red discoloration of the wheals.
  • Urticaria solaris – urticaria triggered by solar radiation.
  • Urticaria vasculitis – systemic form of hives associated with vascular inflammation.

Infectious and parasitic diseases (A00-B99).

  • Hepatitis B infection
  • Hepatitis C infection
  • Infections, unspecified:
    • Bacteria (including Helicobacter pylori or, less commonly, Yersinia colonization).
    • Parasites (including Anisakis simplex (nematodes, predominantly found in fish); Toxocara canis (canine roundworm)). → chronic spontaneous urticaria
    • Protozoa (including Leishmania, Plasmodia, Toxoplasma and Trypanosoma) → chronic spontaneous urticaria.
    • Viruses

Musculoskeletal system and connective tissue (M00-M99).

  • Systemic lupus erythematosus (SLE) – autoimmune disease with formation of autoantibodies mainly against antigens of the cell nuclei (so-called antinuclear antibodies, ANA), in some circumstances also against blood cells and other body tissues.

Injuries, poisonings, and other consequences of external causes (S00-T98).

  • Angioedema – transient swelling of the subcutaneous tissue of the lip/lid region.
  • IgE-mediated wheat allergy with the clinical picture of chronic urticaria – keeping a symptom and food diary if necessary.
  • Insect bites [type I allergy (immediate type)]
  • Intolerance reactions to preservatives and / or dyes (pseudoallergies).
  • Food allergies [type I allergy (immediate type)] – if necessary, keeping a symptom and food diary.
  • Oral allergy syndrome (OAS) – contact urticaria of the oropharyngeal mucosa (Os = mouth, pharynx = throat) – in older children and adolescents, the most common clinical manifestation of food allergy; clinical picture: itching or burning of lips, palate, tongue, pharynx and possibly ears; onset: immediately after contact with the triggering allergen (latency up to 2 h after ingestion of the food possible).
  • Serum sickness – type III hypersensitivity reaction of the immune system (immune complex disease) to a foreign, non-human protein, which is applied, for example, in vaccine sera or serum therapy. In addition, various drugs, such as sulfonamides and penicillins and other antigens can cause serum sickness

Drugs

Environmental pollution – intoxications (poisonings).

  • Solar radiation
  • Strong cold / heat