Clinical Notes : Dermatology

173. Angiodema

 

What is angiodema

Angioedema is a skin reaction similar to urticaria.

It is most often characterised by an abrupt and short-lived swelling of the skin and mucous membranes.

All parts of the body may be affected but swelling most often occurs around the eyes and lips.

In severe cases, the internal lining of the upper respiratory tract and intestines may also be affected.

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Angiodema

 

What's the difference between angioedema and urticaria?

Angioedema and urticaria are very similar in many ways and can co-exist and overlap.

Urticaria occurs more commonly and is less severe than angioedema as it only affects the skin layers whereas angioedema affects the tissues beneath the skin (subcutaneous tissue).

The main differences between urticaria and angioedema are shown in the following table.

 

Whatever the cause of angioedema, the actual mechanism behind the swelling is the same in all cases.

Small blood vessels in the subcutaneous and/or submucosal tissues leak watery liquid through their walls and cause swelling.

This same mechanism occurs in urticaria but just closer to the skin surface.

What are the clinical features of angioedema?

Symptoms and signs of angioedema may vary slightly between the different types of angioedema but in general, some or all of the following occur.

  • Marked swelling, usually around the eyes and mouth

  • Throat, tongue, hands, feet and/or genitals may be affected too

  • The skin may appear normal, i.e. no hives or another rash

  • Swellings may or may not be itchy

  • Swellings may be painful, tender or burning

  • In severe angioedema swelling of the throat and/or tongue may make it difficult to breath

  • Swelling of the lining of the intestinal tracts may cause gastrointestinal pain and cramps

 

Some features specific to the different types of angioedema are listed below.

 
 

How is the diagnosis of angioedema made?

A detailed medical history is invaluable in diagnosing angioedema.

  • Diary of exposure to possible irritants

  • Medications used, including over-the-counter (OTC) drugs and herbal remedies (even if taking them irregularly)

  • Family history of skin rash, allergies

 

Skin prick testing may be performed to try and identify any allergens.

If hereditary angioedema is suspected, blood tests to check for levels and function of specific complement blood proteins may be done.

What is the treatment for angioedema?

Treatment of angioedema depends on the severity of the condition.

In cases where the respiratory tract is involved the first priority is to secure the airway.

Patients may need emergency hospital care and require intubation.

 

 

Angioedema associated with urticaria

Patients with mild acute angioedema can usually be treated in the same way as acute urticaria.

In many cases, the swelling is self-limiting and resolves spontaneously after a few hours or days.

 

In more severe cases where there is persistent swelling, itchiness or pain the following medications may be used.

 

Chronic angioedema with chronic autoimmune or chronic idiopathic urticaria is often difficult to treat and response to medication variable.

 

The following treatment steps are recommended.

Each step is added to the previous one if an inadequate response is obtained.

 
 
 
 

Omalizumab, an anti-IgE monoclonal antibody, has been reported to be effective in some refractory cases of angioedema.

The goal of treatment for chronic angioedema is to reduce itch, swelling, tenderness and pain to a tolerable level to maintain function (eg, at work, school, and during sleep).

Hereditary angioedema

Acute episodes of hereditary angioedema do not respond to adrenaline, antihistamine and corticosteroids.

Most acute episodes of Type I and II hereditary angioedema are not life-threatening.

  • The mainstay of emergency medical treatment is intravenous C1 inhibitor concentrate (a blood product).

  • If this is unavailable, fresh frozen plasma can be infused, but this occasionally exacerbates the angioedema.

  • Icatibant, a synthetic peptidomimetic drug and bradykinin B2 receptor antagonist, can be used in emergencies for the symptomatic treatment of acute attacks of hereditary angioedema in adults with C1-esterase-inhibitor deficiency. It was approved by the FDA in 2011. 

  • Ecallantide is a potent and selective human plasma kallikrein inhibitor that is also indicated for the symptomatic treatment of hereditary angioedema, approved for use by the FDA in 2009. It is a protease that is responsible for iberating bradykinin from its precursor kininogen. Ecallantide has been reported to cause anaphylaxis in 4% of cases and thus has a black box warning in the USA.

 

The chance of an attack can be reduced with the following medications:

  • C1 inhibitor concentrate infused an hour before a surgical procedure

  • Anabolic steroids (stanazolol, oxandrolone and danazol) to increase circulating levels of normal functional C1 inhibitor. These have 'male-like' hormonal activity, so may cause weight gain, menstrual irregularities and virilism.

  • Tranexamic acid has been used in pre-pubertal children and may be effective in Type III hereditary angioedema.

  • A monoclonal antibody, lanadelumab, which inhibits active plasma kallikrein, has been approved in the USA for the prevention of hereditary angioedema attacks.

 
 

Angiodema

DermNetNZ  (CCPL)

Access

Cetrizine is available in Ireland as Cetrine, Cetriz, Histek, Zirpine, Zirtek, Zirtene.

Diphenhydramine is not available in Ireland as a separate tablet or injectable.

Updates

Management (1) :

With airway involvement

  • FIRST LINE : adrenaline (epinephrine) + airway protection

    • adrenaline (epinephrine) : 0.3 mg (1:1000) intramuscularly every 1-2 hours when required

      • Episodes of urticaria with angio-oedema affecting the head and neck, which could potentially compromise the airway, should be treated promptly with adrenaline.

      • The status of the airway should be assessed and closely monitored in all patients with angio-oedema, and all necessary steps must be taken to ensure the airway is always secured. In severe cases, consultation with an anaesthetist may be necessary.

      • Beta-blockers can interfere with the action of adrenaline, and discontinuing this drug in patients with urticaria and angio-oedema should be considered if comorbid conditions allow.

      • For patients with a history of urticaria associated with angio-oedema, 2 self-injectable adrenaline pens should be prescribed. Patients must be instructed how to use them, and if adrenaline is required to treat an episode, the patient should be instructed to promptly seek medical care.

  • PLUS :  H1-receptor antagonists (antihistamines)

    • diphenhydramine 25-50 mg orally every 4-6 hours when required, maximum 300 mg/day; 10-50 mg intravenously every 4-6 hours when required, maximum 400 mg/day

 

  • PLUS : intravenous systemic corticosteroids

    • methylprednisolone sodium succinate :

      • children: 0.5 to 1.7 mg/kg/day intravenously given in divided doses every 6-12 hours;

      • adults: 10-40 mg by intravenous infusion initially, followed by 40-120 mg once daily thereafter

    • If urticaria is particularly severe, a short course of systemic corticosteroids may be indicated.

      • Although there have been no controlled studies, systemic corticosteroids have undeniable and often prompt effects in urticaria, but their use is limited by their extensive side-effect profile.

      • Consequently, it is imperative that all efforts are made to treat patients with steroid-sparing agents before utilising corticosteroids.

      • Topical corticosteroids have no role in the management of urticaria.

 

  • PLUS : trigger identification and avoidance

    • Acute urticaria is generally self-limiting.

    • Triggers can often be identified and need to be strictly avoided if possible. This can involve dietary modifications, the discontinuation or substitution of medicines, and the removal of physical stimuli.

Without airway involvement

  • FIRST LINE :  trigger identification and avoidance

    • Acute urticaria is generally self-limiting.

    • Triggers can often be identified and need to be strictly avoided if possible. This can involve dietary modifications, the discontinuation or substitution of medicines, and the removal of physical stimuli.

 

  • PLUS : H1-receptor antagonists (antihistamines)

    • loratadine : 10 mg orally once daily

    • desloratadine : 5 mg orally once daily

    • cetirizine : 10 mg orally once daily

    • levocetirizine : 5 mg orally once daily

    • fexofenadine 180 mg orally once daily

      • It should be stressed to patients that antihistamines have their greatest efficacy if taken prophylactically rather than reactively after lesions develop.

      • Antihistamines are the mainstay of therapy in acute urticaria

      • Second-generation antihistamines are generally the primary option as they are very well tolerated, with few if any adverse effects as only tiny amounts cross the blood-brain barrier.

        • Choice of agent should be based on individual responses in both efficacy and side-effect profile.

        • Although all second-generation antihistamines have a favourable side-effect profile, cetirizine has been reported to cause a slightly greater rate of sedation as compared with the others.

      • First-generation antihistamines are often a secondary option due to their side effects, particularly sedation.

        • Many patients are unable to tolerate these drugs, even in low doses given at night.

        • Furthermore, their pharmacokinetics often necessitates 3 or 4 times-daily dosing, which is inconvenient and makes compliance more difficult.

        • If used, physicians should start at a low dose and titrate as tolerated to a clinically effective dose.

      • Tricyclic antidepressants also have potent H1 blockade and have also been used in the treatment of urticaria.

        • Doxepin provides the additional benefit of a longer half-life and is therefore suitable for once-nightly dosing.

        • Therapy must be dictated by individual variations in response in both efficacy and side-effect profile.

 

  • PLUS : systemic corticosteroids

    • prednisolone : 0.5 to 1 mg/kg/day orally given in 1-2 divided doses for 5-7 days

      • If urticaria is particularly severe, a short course of systemic corticosteroids may be indicated.

      • Although there have been no controlled studies, systemic corticosteroids have undeniable and often prompt effects in urticaria, but their use is limited by their extensive side-effect profile. Consequently, it is imperative that all efforts are made to treat patients with steroid-sparing agents before utilising corticosteroids.

      • Topical corticosteroids have no role in the management of urticaria.

 

  • ADJUNCT :  adrenaline (epinephrine)

    • adrenaline (epinephrine) 0.3 mg (1:1000) intramuscularly every 1-2 hours when required

      • If there is extensive angio-oedema of the torso or limbs, adrenaline may be indicated to bring it under control.

      • Beta-blockers can interfere with the action of adrenaline, and discontinuing this drug in patients with urticaria and angio-oedema should be considered if comorbid conditions allow.

      • All patients with a history of urticaria associated with angio-oedema should be prescribed 2 self-injectable adrenaline pens and instructed on their use. 

        • If adrenaline is required to treat an episode, the patient should be instructed to promptly seek medical care.

 

1. Urticaria and angio-oedema

BMJ Best Practice

Last reviewed: June 2019

Last updated: March  2018

Access

The following meds are available in Ireland :

Cetrizine (Cetrine, Cetriz, Histek, Zirpine, Zirtek, Zirtene)

Loratadine (Histaclar, Lorat)

Fexofenadine (Fexofanadine HCL, Telfast)

Desloratadine (Dasselta, Destor, Neoclarityn)

Levocetrizine (Levocetrizine Glenmark, Levocetrizine Teva, Levocetrizine KRKA, Rynozal, Xyzal)

 

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