Quincke’s Edema: Causes

Pathogenesis (development of disease)

The common pathway for the development of quincke’s edema (angioedema) is activation of the bradykinin pathway. This peptide is a potent vasodilator that leads to rapidly developing edema in the interstitium: According to the cause, the following forms of Quincke’s edema (angioedema) are distinguished:

  • Histamine-mediated angioedema.
    • Allergic angioedema; occurs in half of cases in association with urticaria (hives); most common form
    • Allergy-like angioedema – in the context of infections, intolerances (intolerance reactions; usually triggered by drugs such as acetylsalicylic acid (ASA) or autoimmune reactions (pathological (pathological) reaction of the immune system against the body’s own tissue).
    • Physical-conditional: e.g., pressure, cold, light, etc.
    • Idiopathic angioedema – without apparent cause (rare).
  • Bradykinin-mediated angioedema (bradykinin is a peptide and tissue hormone that is, among other things, vasoactive (blood vessel altering) and involved in pain production).
    • Hereditary angioedema (HAE) – due to C1 esterase inhibitor (C1-INH) deficiency (blood protein deficiency); approximately 6% of cases:
      • Type 1 (85% of cases) – decreased activity and concentration of C1 inhibitor; autosomal dominant inheritance (new mutations about 25% of cases).
      • Type II (15% of cases) – decreased activity with normal or increased concentration of C1 inhibitor.

      De novo mutations account for approximately 10-20% of cases.

    • RAAS inhibitor-induced angioedema (RAE) – caused by cardiovascular medications: ACE inhibitors (ACE inhibitor (ACEi); common) or AT1 antagonists (angiotensin II receptor subtype 1 antagonists, AT1 receptor antagonists, AT1 blockers, angiotensin receptor blockers, “sartans“) (rare).
    • Acquired angioedema:
      • Especially in malignant lymphoma (colloquially lymph node cancer) (type 1) or
      • C1 inhibitor antibodies (type 2).
  • Other angioedema – the development cannot be explained by histamine alone, nor by bradykinin alone; other endogenous substances play a role here.

Etiology (causes)

Biographical causes

  • Genetic burden
    • By parents, grandparents
    • C1 inhibitor gene mutations (HAE-C1-INH/hereditary angioedema (HAE) with C1 inhibitor mutation).
    • Bradykinin-induced angioedema/HAE-C1-INH (type 1/type 2).

      • Bradykinin-induced angioedema: factor XII mutations (HAE-FXII), plasminogen mutation (HAE-PLG).
      • Other/unclear etiologies: Angiopoietin-1 mutation (HAE-ANGPT1), unknown mutations (HAE-UNK).
  • Spring-born (possibly due toearly contact with inhaled allergens (especially pollen)).

Behavioral causes

  • Physical activity
    • Physical exertion [trigger of acute HAE attacks].
  • Psycho-social situation
    • Stress [trigger of acute HAE attacks]

Disease-related causes (including triggers for HAE attacks).

Endocrine, nutritional, and metabolic diseases (E00-E90).

  • C1 esterase deficiency – glycoprotein from the serine protease inhibitor group, which has a regulatory effect in the complement system (defense system).

Infectious and parasitic diseases (A00-B99).

  • Infectious diseases, unspecified

Neoplasms – tumor diseases (C00-D48).

  • Malignant lymphoma – malignant neoplasm of the lymphatic system.

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

  • Allergic reactions, unspecified
  • Taumata [trigger of acute HAE attacks]

Medication

  • ACE inhibitors (antihypertensives) [>50% of cases with severe angioedema; trigger of acute HAE attacks]
  • Acetylsalicylic acid (ASA).
  • Angiotensin receptor neprilysin antagonists (ARNI) – dual drug combination: sacubitril/valsartan.
  • AT1 antagonists (angiotensin II receptor subtype 1 antagonists, AT1 receptor antagonists, AT1 blockers, angiotensin receptor blockers, “sartans”) (rare)
  • Hormone replacement therapy (HRT)
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Estrogen-containing contraceptives – these can cause attacks to cluster [trigger acute HAE attacks].
  • X-ray contrast media (as an immediate response).

Operations

  • Surgeries including dental procedures [triggers of acute HAE attacks].

Other causes

  • Menstruation (menstrual period) [trigger of acute HAE attacks]; ovulation (ovulation).
  • Physical – pressure, cold, light, etc.
  • Psychological stress situations
  • Pregnancy