Acute allergies are characterised by the sudden onset of symptoms, i.e. they occur within seconds to minutes. In angioedema, the allergic reaction is limited to the deep layers of the skin and the underlying tissue. If acute allergic symptoms occur in organ systems that were not in direct contact with the triggering allergen, this is called a general allergic reaction. Such reactions are called anaphylaxis. Symptoms of anaphylaxis often occur in different organs. In addition to angioedema, anaphylaxis can also manifest with skin redness, urticaria (hives), conjunctivitis, rhinitis, asthma, abdominal pain and diarrhoea, as well as a drop in blood pressure and shock. Urticaria, rhinitis, rhino-conjunctivitis and asthma are also acute allergies, but are covered elsewhere in this guide.
WHAT IS ANGIOEDEMA?
Angioedema is usually localized but poorly demarcated swelling caused by oedema of the deep layers of the skin and underlying fatty tissue. The oedema is caused by an increase in the permeability of the small blood vessels and leakage of blood fluid into the surrounding tissue. Angioedema usually develops within minutes.
• Allergic angioedema: often the patient finds the triggering factor (the allergen) themselves, as the reaction occurs minutes after contact with an allergen. Food allergies are probably the most common cause of allergic angioedema. Insect stings, especially from bees or wasps, can provoke angioedema-type skin reactions. Contact with latex (for example, rubber gloves, condoms) can trigger angioedema and other acute allergic symptoms. In most cases, allergy-related angioedema does not appear in isolation, but often together with skin redness, urticaria, an asthma attack, rhino-conjunctivitis, or diarrhea. Sometimes even anaphylactic shock can be triggered. The most common food allergens include peanuts, celery, soy, and crustaceans such as shrimps.
• Angioedema caused by medication can be a complication of taking medication. The first occurrence of angioedema may be days, even years, after starting treatment. The drug class most commonly responsible for isolated angioedema (without urticaria or other manifestations) is that of ACE inhibitors. Non-steroidal anti-inflammatory drugs such as aspirin and many other drugs (Brufen®’ Ponstan®, Voltaren® etc.) taken for pain can cause angioedema, urticaria, asthma and/or even anaphylactic shock. These reactions are not due to an allergy mechanism but to intolerance. Many other drugs can be responsible for angioedema and other acute allergic and non-acute reactions.
• Vibration-induced angioedema is a rare condition. If the skin is in contact with a vibrating object, people sensitive to it develop local angioedema at the site of contact. The typical example is the construction worker who gets swollen hands after using a jackhammer.
• Angioedema caused by deficiency of a C1 inhibitor is rare but, because of its localization at the larynx, can endanger the patient’s life and should be known to doctors. This disease can be hereditary (inherited) or acquired. The hereditary form is the result of a gene mutation and can be transmitted to offspring. The relapses often begin in childhood or adolescence. They are often caused by trauma or surgery, especially to the teeth, and often affect the face, extremities, and genital area. Infestation of the upper respiratory tract (larynx) can be life-threatening (suffocation).
The intestine can be affected. Oedema of the intestinal wall causes severe abdominal pain with diarrhea and can feign intestinal obstruction. Other triggering factors in women are changes in hormonal balance, such as puberty, the start of oral contraceptives, and pregnancy. However, the first manifestations can also occur in adulthood. The acquired form occurs as a manifestation of a certain type of cancer of the white blood cells (B lymphocytes) or an autoimmune disease such as systemic lupus erythematosus.
Unfortunately, in most cases of chronic or recurrent angioedema, no aetiology (cause) is found. This is called idiopathic angioedema (no known cause). This type of angioedema is often associated with urticaria.
How is angioedema treated?
• Allergic angioedema: Consult a specialist (allergist, dermatologist) for treatment, identification of an allergen, and prevention of new episodes. Avoiding the allergen helps to prevent relapses.
• Drug-induced angioedema: the specialist must identify the drug that causes it and recommend permitted agents. Every patient with angioedema, with or without other allergic manifestations, must be questioned about their medication use so that the medication in question can be identified and avoided.
• Angioedema caused by deficiency of a C1 inhibitor: precaution of a possible emergency situation. Possibly long-term use of a drug (danazol, tranexamic acid). Angioedema caused by C1 inhibitor deficiency: Long-term use of a drug (danazol, tranexamic acid) or only in relapses (C1 esterase inhibitor, Icatibant). Affected patients need to know their disease, be able to distinguish the severity of relapses and be able to correctly inform medical staff of their diagnosis.
• Treatment of idiopathic, allergy-related, and drug-induced angioedema is purely symptomatic, i.e. it aims to treat the symptoms but not the underlying causes. Primarily, antihistamines are used, as in urticaria and angioedema sometimes treatment with a corticosteroid is added for a short time. Adrenaline is used if there is a risk of choking after the angioedema is localized in the throat. Several other medications are used to treat asthma attacks.
WHAT IS ANAPHYLAXIA?
Allergy of the immediate type can be expressed by a spectrum of systemic symptoms. The application, ingestion or inhalation of an allergen may cause symptoms not only at the site of contact (e.g. contact urticaria when the allergen touches the skin, lip oedema and jukking in the mouth when an allergen is ingested, asthma attack after inhalation of an allergen) but may also cause manifestations in other organs. The whole spectrum of systemic reactions of the immediate type is classified under the term anaphylaxis. In its worst manifestation, anaphylaxis can end in anaphylactic shock. Severe asthma and the shock associated with anaphylaxis can lead to death. For these reasons, anaphylaxis should be classified as a medical emergency.
The symptoms of anaphylaxis vary widely. Before the cardiovascular symptoms (drop in blood pressure, loss of consciousness: the shock in the sense of the word) appears, there are usually but not always skin symptoms (redness, urticaria…), symptoms of the eyes (redness of the conjunctiva), symptoms of the respiratory tract (nasal flow, whistling breathing, shortness of breath, swelling in the throat) and gastrointestinal symptoms (nausea, vomiting, diarrhea, defecation). Fortunately, most of the anaphylactic symptoms remain confined to one or more organs without ending in shock.
What allergens can cause anaphylaxis?
• Redness, urticaria
• Redness of the conjunctiva
• Nasal flow, shortness of breath
• nausea, vomiting, Diarrhea, defecation.
•Food allergens such as peanuts, walnuts and other nuts, celery, soy and crustaceans such as shrimps are among the most common food allergens
•Stings from hymenoptera (wasps and bees) can cause all stages of anaphylaxis, while reactions to stings from other insects rarely go beyond stage II.
• Anaphylactic reactions can also occur when allergens are injected as part of desensitization (pollen, dust mites, animals…).
• Latex (rubber gloves, balloons…) can trigger anaphylactic reactions leading to shock.
• Another important group of substances that can trigger anaphylaxis is that of drugs. Non-steroidal anti-inflammatory drugs such as aspirin and many other drugs (Brufen®, Ponstan®, Voltaren®…) can cause anaphylactoid manifestations (reactions similar to anaphylaxis, but their mechanism is not allergic). The allergist must identify the painkiller responsible and make recommendations for alternative treatments. The other drugs commonly responsible for anaphylaxis of allergic origin are penicillins and other antibiotics and general anesthetics, but there are many other drugs that can cause anaphylaxis. It is the allergist’s job to make the diagnosis (possibly with the help of skin or laboratory tests) and suggest alternatives.
• Anaphylaxis can also manifest after physical exercise. In these cases, a food cofactor is often to blame. The peculiarity of this form of food allergy is that it only manifests when ingestion of the allergen is followed by physical exertion. This entity is called exercise-induced food anaphylaxis.
It is not possible to provide here a complete list of all allergens that can cause anaphylactic reactions, as the content of this list is constantly increasing.
CLASSIFICATION OF STAGES BY SEVERITY OF ANAPHYLAXIA
Different degrees of severity must be distinguished in anaphylaxis. The classification was originally used in reactions to bee or wasp venom, but it is useful for all anaphylactic reactions.
• Stage I: generalised urticaria, malaise, anxiety.
• Stage II: One or more symptoms of stage I plus at least two of the following: Angioedema, chest tightness, abdominal pain, nausea, diarrhea, dizziness.
• Stage III: One or more symptoms of stage II plus at least one of the following: Dyspnoea (difficulty breathing), dysphagia (difficulty swallowing), dysphonia (voice disorder), confusion, fear of death.
• Stage IV: One or more symptoms of stage III plus at least one of the following symptoms: Cyanosis (bluish skin colour, especially visible on the face and extremities), hypotension (drop in blood pressure), collapse (circulatory collapse), syncope (collapse and fainting).
HOW IS ANAPHYLAXIS TREATED?
When treating a patient with anaphylaxis, a distinction can be made between emergency treatment and follow-up treatment.
• Any anaphylactic reaction must be cause for consultation with a doctor, immediately if possible, because if there is a relapse, the reaction may be worse.
• Stages III and IV are emergencies that require immediate medical treatment by a specialized team (transport in an ambulance) and hospitalization in a hospital with an emergency ward (resuscitation). In the cities, there are emergency services that visit patients at home or hospitals with intensive care and resuscitation units. In rural areas, one doctor is usually responsible for the emergency service. All doctors have been trained in the recognition and initial treatment of anaphylaxis.
• In the case of a sting by a hymenoptera, the stinger of the bee with its venom gland, which remains in the skin after the sting, must be removed as quickly as possible. Similarly, the ingestion of suspected food or the administration of suspected medication must be stopped immediately. The patient’s body must be placed in a horizontal position, the legs elevated and the airways kept clear.
• After any anaphylaxis, a consultation with an allergist is necessary. This specialist must confirm the diagnosis and look for an unknown allergen or confirm or rule out the role of a suspected allergen. To do this, the specialist has various tests such as skin tests to find IgE-dependent causes of the allergy.
Once an allergen is identified, the specialist will give advice on how to avoid re-exposure to the causative allergen. An allergy passport, which lists the type of allergen and reaction, as well as the diagnostic modalities, must be given to the patient. This passport is important for any other doctor the patient sees. In an emergency, it enables the diagnosis of anaphylaxis to be made more quickly in certain cases and the allergen causing the anaphylaxis to be identified. In the case of occupational anaphylactic reactions, the specialist can take occupational health measures. If necessary, he will report to the insurance company (e.g. SUVA).
• The specialist will prescribe an emergency kit for patients with severe anaphylactic reactions, containing drawn-up adrenaline injections and other anti-allergic medication such as antihistamine and corticosteroid tablets. The specialist will also look at preventive measures if re-exposure to the allergen is unavoidable. He will also deal with other allergic symptoms such as asthma that may accompany anaphylaxis.
• The allergist will also make sure that the patient is not taking any medication that could aggravate the anaphylaxis, complicate its treatment or render the adrenaline ineffective (especially beta-blockers, drugs for hypertension, and glaucoma).
• Finally, induction of tolerance or desensitization may be carried out in the case of certain allergens that have caused anaphylaxis, such as wasp or bee venom or certain medications. This intervention aims to induce tolerance and consists of administering the allergen in increasing doses, under medical supervision. This is also part of the allergist’s remit.
Dr. Philip Taramarcaz
Terrassière Allergy and Asthma Center, Geneva