Symptoms and diagnosis management

Identifying hereditary angioedema symptoms

Hereditary angioedema (HAE) can produce episodes of nonpitting, nonerythematous swelling in the abdomen, face, and throat. Berinert, a safe and effective on-demand therapy, can help treat acute abdominal, facial, and laryngeal attacks. The safety and efficacy of Berinert for prophylactic therapy have not been established. Berinert is approved for patient self-administration after proper training by a healthcare professional.

Attacks often begin in childhood, becoming more severe over time. The number of episodes an individual may experience is unpredictable. Some people experience weekly attacks, while others may go years without one.10

The swelling associated with an attack often gets worse over a period of 12 to 24 hours, and resolves within 72 hours. However, symptoms can last for up to five days.10,11 Unlike allergic reactions, there is no itching or redness with HAE.3 In addition, patients with abdominal swelling often experience severe abdominal pain and nausea, which can be accompanied by dizziness, vomiting, and diarrhea.8,12

HAE episodes are usually asymmetrical and localized to a single area of the body, but simultaneous or closely spaced attacks can also occur.3,10 Attacks can also be migratory, starting in one location and then spreading to another before resolving. Migratory attacks tend to be erratic. They can begin abruptly and move from site to site within hours, or they can spread slowly, taking days to move from one site to the next.11,13

Sometimes, early HAE symptoms appear anywhere from minutes to one to two days before the onset of an episode. These prodromal symptoms may include sudden mood changes, irritability, aggressiveness, anxiety, extreme fatigue, or a tingling sensation of the skin where the swelling will begin.8,10

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Why does swelling occur?

The swelling associated with hereditary angioedema occurs because of locally increased vascular permeability and the extravasation of plasma from capillaries or postcapillary venules into the deeper cutaneous and/or mucosal layers. The exact mechanism by which C1-INH deficiency causes HAE symptoms has not been documented. But it seems to result from faulty, uninhibited activation of the kallikrein-kinin system (KKS).3,14

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Diagnosing hereditary angioedema

A hereditary angioedema diagnosis is commonly delayed. This is partly due to the fact that the condition is fairly rare and not often seen in practice.8 In addition, HAE symptoms may resemble other conditions, including allergic reaction, acute appendicitis, gallbladder attack, submucosal abdominal tumor, diverticulitis, and irritable bowel syndrome.3,4,6

Hereditary angioedema can be confirmed only by a series of blood tests. Here are the steps involved in testing for HAE:

  1. All patients who are suspected of having a C1-INH deficiency should have their serum C4 levels measured
  2. If C4 is low, then the C1-INH protein level and function should be measured
  3. A low C1-INH level indicates type I HAE. If C1-INH levels appear normal or raised (and C4 is low), a C1-INH function test is done. If no function is detected, type II HAE is probable
  4. If C1-INH function and/or level are low, along with a low C4 level, the tests should be repeated to confirm the findings8,10

Patients suspected of having HAE are often referred to an allergist or clinical immunologist. If you need help locating an HAE specialist, you may want to contact the US Hereditary Angioedema Association. The organization maintains a robust list of doctors across the country who treat patients with hereditary angioedema.

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Starting your patient on Berinert

When starting a patient on Berinert, there are several precautions you may want to discuss:

  • Before patients self-administer Berinert, it is important that they undergo training from a healthcare professional. Self-administration should be considered for all patients. Click here for training and instructional materials in support of Berinert intravenous infusion.
  • It is recommended that patients receiving blood products, such as Berinert, receive vaccination for hepatitis B (may be in combination with hepatitis A vaccine)11
  • Some medications may trigger or worsen HAE attacks, including angiotensin-converting enzyme inhibitors and estrogen contraceptives11

Also, according to consensus guidelines, it is advisable to register HAE patients in national and international database registries to help researchers make progress in finding a cure for the disease. The US Hereditary Angioedema Association maintains a scientific registry.11 Learn more about the registry.

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Important Safety Information

Berinert®, C1 Esterase Inhibitor (Human), is a plasma-derived concentrate of C1 Esterase Inhibitor (Human), indicated for the treatment of acute abdominal, facial or laryngeal attacks of hereditary angioedema (HAE) in adult and adolescent patients. The safety and efficacy of Berinert for prophylactic therapy have not been established.

Berinert is contraindicated in individuals with a history of life-threatening systemic reactions to C1 esterase inhibitor preparations (including anaphylaxis).

Monitor patients for early signs of allergic or hypersensitivity reactions (including hives, generalized urticaria, chest tightness, wheezing, hypotension, and anaphylaxis). If hypersensitivity is suspected, immediately discontinue administration of Berinert and initiate appropriate treatment. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reactions.

Thrombotic events have been reported in patients receiving C1 esterase inhibitor products, including Berinert, at the recommended dose as well as when used off-label or at higher-than-labeled doses. Closely monitor patients with risk factors for thrombotic events.

Patients able to recognize signs and symptoms of HAE attack and comprehend necessary training can self-administer Berinert. Patients should not attempt to self-administer unless they have been trained and determined to be capable by healthcare provider. Advise patients to immediately seek medical attention following self-administration for laryngeal attacks, and to seek medical attention if progress of any attack makes them unable to properly prepare or administer dose of Berinert.

Berinert is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

The most serious adverse reaction reported in subjects who received Berinert in clinical studies was an increase in the severity of pain associated with HAE. Dysgeusia was the most common adverse reaction reported in over 4% of subjects and more frequently than in the placebo group.

Berinert has not been evaluated in pregnant women or nursing mothers, and should be used only if clearly needed. The safety and efficacy of Berinert have not been established in children (ages 0 through 12) or in the geriatric population. In clinical trials, the half-life of Berinert was shorter and clearance was faster in children than in adults; the clinical implication is not known.

Please see full Prescribing Information.