Angioedema

Angioedema is the swelling of skin, subcutaneous, or submucosal tissue due to acquired or genetic causes.

This disease is associated with auto-immune processes.

Presentation

In hereditary angioedema, the patients present with swelling that develops 2 to 5 hours after any stimulus such as a minor trauma or infection. The swelling can involve any part of body and is often associated with rashes. The patients frequently experience abdominal symptoms such as nausea, vomiting, abdominal pain and diarrhea. The patients usually have one episode of attack per month. Some patient may have a higher frequency of attacks Attacks usually last from 12 to 48 hours.

In acquired angioedema, the predominant feature of angioedema is swelling of the face, mucous membranes and hands. Swelling may be itchy and associated with skin rash. Sensations of the skin can be decreased due to extravasation of fluid that causes compression of the nerves. If the swelling of the mucus membranes of the upper respiratory tract is severe, respiratory distress along with cough and wheezing may occur [9][10]. The patient is unable to breathe which leads to rapid decrease in the oxygen concentration in the arterial blood. If this is not treated promptly, permanent brain damage may occur.

Workup

The diagnosis of angioedema can often be made on clinical grounds. Certain investigations are helpful in confirming the diagnosis and etiology of this disease. Mast cell tryptase levels are raised in the patients suffering from angioedema. However, unlike other allergic conditions, there is no response to therapy with antihistaminic and steroidal drugs.

In hereditary angioedema, there is often a typical family history. In addition, the deficiency of C2 and C4 component of the complement system is present. In patients with F12 gene mutation, the diagnosis is done by excluding other types of angioedema.

Treatment

The treatment of angioedema depends upon the etiology.

Hereditary angioedema:

  • The patient should avoid specific stimuli.
  • C1-INH concentrated blood should be transfused.
  • Fresh frozen plasma containing C1-INH may be used.
  • Androgens such as danazol which can increase aminopeptidase-P are given. Aminopeptidases-P inhibits bradykinin.

ACE-inhibitors angioedema:

  • The use of the ACE inhibitor drug should be discontinued.
  • Alternative drugs such as Angiotensin Receptor Blockers (ARBs) are given.

Allergic angioedema:

  • Exposure to the allergen should be avoided. If possible, desensitization should be done.
  • High dose cetirizine in given in acute attacks.
  • Steroids may be used.
  • Adrenaline may be used if respiratory distress occurs.

Acquired angioedema:

  • Antifibrinolytics such as tranexamic acid or ε-aminocaproic acid are used in this case.
  • Cinnarizine can also be used.

Burn angioedema:

  • Endotracheal tube should be passed prophylactically as soon as the patient is received as inhalation burns can lead to swelling obstruction of the airway. If obstruction has developed, endotracheal tube can not be passed.
  • If angioedema develops and endotracheal tube has not yet been passed, emergency cricothyriodectomy or mini-tracheostomy is necessary.

Prognosis

Early recognition of angioedema and aggressive treatment results in a very good prognosis. Early intubation with endotracheal tube lead also improves the prognosis by limiting the respiratory distress. If the treatment is delayed, it may even prove fatal for the patient.

Etiology

Hereditary angioedema: Occurs due to an autosomal dominant gene mutation. The genes include the SERPING1 gene and F12 gene. Both of these genes lead to pathological activation of complement pathway.

Acquired angioedema: Acquired angioedema can result from the following causes:

  • Immunological
  • Allergy to certain allergens such as peanuts and food colors [1]
  • Reaction to medications such as ACE inhibitors
  • Burn
  • Idiopathic

Epidemiology

  • Allergic angioedema is most common in the United States.
  • Drug-induced angioedema is more common in African-American.
  • Annually 80000 to 112000 patients suffering from angioedema visit emergency department.

Sex distribution
Age distribution

Pathophysiology

Angioedema is the swelling of subcutaneous tissues and mucosa due to accumulation of fluid [2] [3]. It results from various stimuli that cause the release of bradykinin [4] [5]. In addition to being a potent vasodilator, bradykinin also facilitates the extravasation of fluid from the blood vessels. Intravascular fluid therefore starts accumulating extravascularly leading to the swelling. The skin around the eyes is the loosest skin of the body; therefore, the fluid accumulate there first and later other area of the face also succumb to swelling.

Angiotensin converting enzyme (ACE) normally causes the breakdown of bradykinin in the body. However, when ACE inhibitors are used, bradykinin breakdown is suppressed and angioedema can develop.

In hereditary angioedema, there is a decreased production of C1-INH which leads to the activation of the complement system [6] [7]. This unopposed activation of complement system results in the continuous production of bradykinin. In autoimmune angioedema, antibodies are formed against C1-INH and bradykinin is similarly increased.

In addition, some agents such as alcohol and some drugs (such as ibuprofen and aspirin) can increase the incidence of angioedema [8].

Prevention

  • Susceptible individuals should avoid drugs such as alcohol, aspirin and ACE Inhibitors.
  • Exposure to known allergens should be avoided.
  • Burns should be prevented.

Summary

Angioedema is swelling of skin, subcutaneous and submucosal tissues and can be acquired or genetic. In genetic angioedema, SERPING1 and F12 genes are involved. Acquired angioedema can be due to drugs, allergy or burns. The main mechanism of swelling in angioedema is the activation of bradykinin which is a potent vasodilator. The patients usually present with swelling of face and hands. In severe cases, respiratory distress can occur.

Patient Information

Angioedema means the swelling of the skin and underlying tissue because of the collection of fluid. It can result from genetic causes or from acquired causes. The patients usually develop swelling of the face, arms and hands. Sometimes, swelling may involve the upper respiratory tract which leads to breathing difficulties. Emergency management may be indicated in such cases. The treatment depends upon the cause but the overall prognosis is good.

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References

  1. Frigas E, Nzeako UC. Angioedema. Pathogenesis, differential diagnosis, and treatment. Clinical reviews in allergy & immunology. Oct 2002;23(2):217-231.
  2. Scheirey CD, Scholz FJ, Shortsleeve MJ, Katz DS. Angiotensin-converting enzyme inhibitor-induced small-bowel angioedema: clinical and imaging findings in 20 patients. AJR. American journal of roentgenology. Aug 2011;197(2):393-398.
  3. Wakisaka M, Shuto M, Abe H, et al. Computed tomography of the gastrointestinal manifestation of hereditary angioedema. Radiation medicine. Dec 2008;26(10):618-621.
  4. Kaplan AP. Mediators of urticaria and angioedema. The Journal of allergy and clinical immunology. Nov 1977;60(5):324-332.
  5. Oschatz C, Maas C, Lecher B, et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity. Feb 25 2011;34(2):258-268.
  6. Kalmar L, Hegedus T, Farkas H, Nagy M, Tordai A. HAEdb: a novel interactive, locus-specific mutation database for the C1 inhibitor gene. Human mutation. Jan 2005;25(1):1-5.
  7. Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends in molecular medicine. Feb 2009;15(2):69-78.
  8. Asero R, Bavbek S, Blanca M, et al. Clinical management of patients with a history of urticaria/angioedema induced by multiple NSAIDs: an expert panel review. International archives of allergy and immunology. 2013;160(2):126-133.
  9. Rye Rasmussen EH, Bindslev-Jensen C, Bygum A. Angioedema--assessment and treatment. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke. Nov 12 2012;132(21):2391-2395.
  10. Kaplan AP. Angioedema. The World Allergy Organization journal. Jun 2008;1(6):103-113.

  • Allergic reactions associated with airborne fish particles in IgE‐mediated fish hypersensitive patients - JF Crespo, C Pascual, C Dominguez, I Ojeda - Allergy, 1995 - Wiley Online Library
  • Angioedema acute hypersensitivity reaction to injectable hyaluronic acid - JM Leonhardt, N Lawrence, RS Narins - Dermatologic surgery, 2005 - Wiley Online Library
  • A survey on the management of pollen-food allergy syndrome in allergy practices - S Ma, SH Sicherer, A Nowak-Wegrzyn - Journal of allergy and clinical , 2003 - Elsevier
  • Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter review and an algorithm for airway management. - AG Chiu, KA Newkirk, BJ Davidson - The Annals of otology, , 2001 - ukpmc.ac.uk
  • Bibliography Current World Literature - RL Carrau, A Khidr, KF Gold - Head and Neck Surgery, 2006 - journals.lww.com
  • Adverse reactions to benzoates and parabens. - DW Jacobsen, DD Metcalfe, HA Sampson - Food allergy: adverse , 1996 - cabdirect.org
  • Acute Angioedema and Urticaria Associated with Herpes Simplex Infection - P Youngnak-Piboonratanakit, Y Takahashi - Acta stomatologica , 2008 - hrcak.srce.hr
  • Angioneurotic edema attributed to the use of losartan - EW van Rijnsoever, WJM Kwee-Zuiderwijk - Archives of internal , 1998 - Am Med Assoc
  • THE CHARACTERISTICS OF ACUTE KIDNEY INJURY COMPLICATED IN ACUTE HEPATITIS AETIOLOGY AND OUTCOME OF ACUTE RENAL FAILURE RELATED - V Luyckx, M Obeidat, A Zadovni, S Jackson - NDT , 2009 - ckj.oxfordjournals.org
  • A vote for inhaled adrenaline in the treatment of severe upper airway obstruction caused by piercing of the tongue in hereditary angioedema - D Trachsel, J Hammer - Intensive care medicine, 1999 - Springer
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