Table of Contents
1. What is Urticaria
Urticaria (also known as hives) is a disease characterized by the sudden development of itchy pale red bumps (wheals, hives) on the skin. Wheals may present in variable sizes and shapes and have a fleeting nature, with the skin returning to its normal appearance in around 24 hours. These wheals may appear in certain parts of the body, or they may be generalized.
Hives are often accompanied by swelling known as angioedema. A few patients have only angioedema without hives.
Angioedema is a swelling in the deeper skin layers. The borders of the swellings are therefore less visible, and their color is often not evidently different from the normal skin. Angioedema frequently occurs on the face, lips, hands, and feet. Itching is not frequent, and patients may complain of pain. Its duration is around 48 to 72 hours.
The name “urticaria” originates from the Latin name “Urtica dioica” due to its similarity to the effect produced by this European nettle coming in contact with the skin.
Urticaria is a common disease that affects around 1 in 5 people at some point in their lives. Urticaria may be acute or chronic. In acute urticaria, skin lesions resolve completely within a few days, while in chronic urticaria, lesions persist for more than six weeks. Chronic urticaria is further classified as chronic spontaneous urticaria (CSU) when triggers are not identified and chronic inducible urticaria (CIndU) when it is triggered by physical factors such as heat, cold, pressure, or vibration.
Acute urticaria (AU) is more common in children, while chronic urticaria (CU) mainly affects women between 25 and 35 years.
Urticaria can affect the patient’s quality of life. It is disfiguring, unpredictable and intensely itchy, which can interfere with sleep and activity. Urticaria can become unbearable, causing emotional distress and possibly leading to depression.
Hippocrates (460-377 BC) described elevated itchy lesions caused by nettles and mosquitoes, which he called “knidosis”, after the Greek word for nettle (knido). In the 10th century, Ali Ibu Al-Abbas called it “essera”, which in the Persian language means elevation. The word “urticaria” was first introduced in 1769 by William Cullen in his book “Synopsia Nosalogiae Methodica”.
Jean Astruc (1684-1766), the founder of modern dermatology and histology, showed that the weal (or wheal) was due to local obstruction of oedema. Dale and Laidlow showed that the tissue contained an amine that affected smooth muscles and vessels and called it histamine. In the last few decades, great advances in the diagnosis and treatment of urticaria have occurred.
2. Course of Urticaria
2.1. How Does Urticaria Develop?
Urticaria develops when specific immune cells in the body, called mast cells, become activated. This results in the release of chemicals such as histamine, causing itching, redness, and swelling. Hives appear suddenly and disappear within several hours, usually within less than 24 hours and may appear once again in other areas of the body.
Urticaria develops either after an allergic trigger (usually recognized by the patient) such as food, medication, insect stings and/or physical contact with allergens or after exposure to physical factors such as heat, cold, vibration, and pressure. This is why it is called inducible urticaria or spontaneously with no identified trigger. Non-allergic triggers may occur after viral illnesses. However, most chronic spontaneous urticaria appears suddenly without any identified trigger.
What Is The Prognosis?
In acute urticaria, it is crucial first to identify the allergic triggers such as food or drugs to avoid further exposure, as acute hives may be part of a severe allergic reaction (called anaphylaxis) that may be life-threatening if untreated. Furthermore, avoidance of the trigger is the most crucial step to avoid recurrence in the future.
In chronic spontaneous urticaria (CSU), the trigger is unknown and usually non-allergic. It can be frustrating, as it affects how an individual looks and is unpredictable. In many cases, affected people avoid many foods unnecessarily, without benefit. The good news is that CSU is a benign condition as it is not life-threatening, not contagious, and is easily treatable in most people. They are rarely permanent; almost 50% of affected people are hive-free within 1 year.
Inducible urticaria tends to be long lasting for years but eventually disappears.
Can Urticaria Become Dangerous?
Most cases of acute and chronic urticaria are non-allergic and, although bothersome, are not dangerous. The exception is acute urticaria due to allergy, as it may progress to anaphylaxis and may be life-threatening if left untreated.
3. Diagnosis of Urticaria
3.1. Medical History
Urticaria is commonly known as hives. It is usually diagnosed based on the appearance, history, and associated factors and confirmed upon examination by a physician. Taking a photo of the affected skin during the attack is helpful to guide the physician as to whether this is urticaria or not.
Hives are usually reddish raised areas on the skin which are itchy. On darker skin, the redness may not be very visible.
Hives often disappear, and new hives may appear in other areas; however, an individual spot does not last more than 24 hours, and the skin appears normal upon resolution. Changes in the skin like bruising, blood-like spots, or brown discoloration are usually not seen in urticaria.
Hives on the skin may sometimes occur along with swelling and itching of loose skin tissue like the lips, eyelids, tongue, or the tissues inside the mouth; this is called angioedema. In some conditions, angioedema can occur alone, without associated urticaria.
Your doctor will ask you questions regarding any other intercurrent illness, medication use, or exposures that may trigger urticaria and about other symptoms that indicate systemic involvement like fever, joint pain, weight loss, or malaise.
Hives may come and go for days at a time. Hives that last more than six weeks are referred to as “chronic urticaria.”
Three key elements are essential for the diagnostic approach to urticaria. The first element is to confirm the correct diagnosis (acute versus chronic, exclude other differential diagnoses and reach the correct classification of either Chronic Spontaneous Urticaria (CSU) (previously called idiopathic) or Chronic Induced Urticaria (CIndU). The second is to determine the culprit or triggers. The third is to assess the burden of urticaria on the patient (urticaria activity scoring, degree of urticaria control, and impact on life).
Your doctor will also ask you about smoking habits; type of work; hobbies; symptom occurrence in relation to weekends, holidays, and foreign travel; surgical implantations; relationship to the menstrual cycle; response to therapy; stress. He may ask about your family members who may have similar symptoms or other allergies.
Additionally, these symptoms will be revisited while on a different regimen of treatments until disease control is achieved.
3.2. Clinical Examination And Identifying The Cause
Urticaria is not a disease in itself; it is only a symptom. Urticaria can be associated with various conditions and triggers; see the section on “triggers” below
Depending on the pattern of presentation and history, your doctor may be able to identify the cause.
Usually, no specific cause or trigger despite examination and testing is identified in most patients. In these cases, “idiopathic” (a medical term indicating no real cause) is used.
Various things can trigger urticaria, including infections, certain medications, allergy to food or food additives, insect bites or certain plants, and physical factors.
Some patients have urticaria triggered by physical factors such as pressure, scratching, heat, cold, vibration, water, and sunlight.
– Viral, bacterial, and parasitic infections are among the causes of hives
– Food allergies can cause hives. In addition, a patient with a food allergy may also present with angioedema, vomiting, diarrhea, dizziness, and collapse if the reaction is very severe (in this case, the skin hives are part of another disease called anaphylaxis).
– Food additives such as preservatives, coloring agents, etc.
– Allergy to a new medicine
– Allergy to insect stings
– Allergy to latex- which is contained in rubber gloves, balloons, condoms, etc.
– Tobacco use is known to induce urticaria
– In female patients, the state resulted in hormonal changes like pregnancy and menstrual cycles that may induce urticaria.
– Stress is a very well-known immunologically provoking factor.
Your doctor may do a general and comprehensive bedside examination. Usually, your clinical examination is expected to be normal. Your doctor may perform specific provocation testing if he suspects CIndU (ice cube, heat stimulus, photo-light test, or stroking the skin with a blunt, firm object)
3.3. Laboratory Testing
Usually, testing is not required to diagnose spontaneous urticaria that is acute or lasting less than 6 weeks (hives occurring with no identified trigger). If it lasts longer than six weeks, your doctor may consider doing some tests.
Some blood tests may be requested in chronic hives to check if your hives are a part of any other disease.
If your hives are clearly triggered by food or medicines, your doctor may recommend allergy testing by skin prick testing or blood tests.
In rare cases a skin biopsy (taking a small sample of skin) may be required, especially if there are some unusual features or you do not respond to the usual treatment.
It is always helpful to have photos of your hives since they change over the course of hours. It is particularly important to check your skin for any persistence, sequelae, or pigmentations after 24 hours of lesions and to take photos in order to help reach a proper diagnosis and exclude other differentials.
If no cause is identified, it may be helpful to keep a diary of symptoms and note down all the associated events; this may help identify the trigger.
4. Types of Urticaria
4.1. Triggers and Types of Urticaria
Urticaria can have a wide spectrum of presentations and subtypes. Urticaria is differentiated based upon its duration, with acute urticaria lasting for less than 6 weeks and chronic urticaria lasting for a longer time. Acute urticaria is more frequent, affecting about 20% of all people during their lifetime. Chronic urticaria can be further classified into spontaneous (where wheals appear out of the blue without the need for an external trigger) and inducible forms. Other factors like stress, medications, infections, and others can worsen symptoms; however, they are not necessary for symptoms to appear.
On the other hand, patients with chronic inducible urticaria only have wheals when exposed to a specific trigger. Chronic Inducible urticaria is divided into physical urticaria and non- physical urticaria. Physical urticaria constitutes the largest group of chronic inducible urticaria. It is induced by a physical stimulus on the skin such as pressure, cold, heat, light and vibration. The distribution of wheals is localized to the site exposed to the trigger. The areas not exposed to the trigger are free of symptoms. The most common forms of inducible urticaria include symptomatic dermographism and cold urticaria. Cholinergic urticaria, contact urticaria and aquagenic urticaria are non-physical forms of chronic inducible urticaria. Cholinergic urticaria develops when wheals are brought about due to a rise in body temperature like a hot bath, exercise etc.
Chronic spontaneous urticaria constitutes the bulk of patients with chronic urticaria, while chronic inducible urticaria is less frequent. Patients with chronic spontaneous urticaria can also have associated inducible urticaria and vice versa.
4.2. Classification of Urticaria
5. Acute Urticaria
Acute urticaria is characterized by the sudden onset of wheals or angioedema, or both, with symptoms lasting for less than 6 weeks. The wheals are associated with itching or a burning sensation. The symptoms can be bothersome; however, in most cases resolve within a few days to weeks. The cause is not always clear; infections, medications, food can trigger symptoms. It is imperative to recognize the presence of associated symptoms like shortness of breath, difficulty swallowing, dizziness and seek emergency medical advice if present. If a specific trigger is identified, it is important to avoid the same.
TRIGGERS AND CAUSES
Acute urticaria can be triggered by infections like flu, medications like pain killers (Aspirin, Ibuprofen, Diclofenac), antibiotics. If an individual is allergic to a specific food, this can also trigger urticaria. If food or medication is suspected to be triggering urticaria, it is important to make a clear association between consumption of the culprit and the start of urticaria symptoms (usually within a few hours). Sometimes, no clear cause can be identified.
In most cases, the cause can be identified by taking medical history itself, like in the case of urticaria triggered by infection or medications and requires no further testing. Further testing may be warranted if an allergic reaction to a culprit food is suspected to confirm the association.
Acute urticaria usually resolves within a few days to weeks. Symptomatic treatment with antihistamines (allergy medications) helps control the appearance of wheals, itchiness, and angioedema. Higher doses of antihistamines and short courses of steroids may be indicated in some cases. Emergency medical advice should be sought in the presence of associated symptoms like shortness of breath, difficulty swallowing, dizziness. If a specific trigger is identified, it is essential to avoid the same in the future.
6. Chronic Spontaneous Urticaria (CSU)
Chronic spontaneous urticaria is characterized by spontaneous (out of the blue) occurrence of itchy wheals, angioedema, or both, daily or for most of the days of the week for more than 6 weeks. This type of urticaria can take months or several years to resolve. Chronic urticaria can be a nuisance with a significant effect on the quality of life; however, it is not life-threatening.
TRIGGERS AND CAUSES
Urticaria or hives occur secondary to the activation of certain cells in the body’s immune system known as mast cells. Mast cells are commonly present in the skin, gastrointestinal and respiratory tract. In chronic urticaria, mast cell activation in the skin is triggered by the production of antibodies against the body’s own substances. Chemicals present in the mast cells like histamines are released into the skin, which can cause irritation of nerve endings resulting in localized itching. In addition, blood vessels expand and leak fluid, leading to redness and swelling. Chronic spontaneous urticaria is almost never allergic in origin. Various factors can trigger or worsen symptoms but are not the cause of urticaria itself. These include infections, medications like pain killers (aspirin, diclofenac, ibuprofen), stress, food like histamine rich foods, food additives like preservatives, color etc. Food induced worsening of symptoms are due to intolerance, and food allergy is rarely a cause of chronic urticaria. In most cases, no underlying cause can be determined.
The diagnosis of chronic urticaria is based on symptoms, and further testing is not usually warranted. Basic tests may be done to determine the nature of the disease, especially in the presence of associated systemic symptoms, to rule out severe allergic reactions/anaphylaxis. Allergy testing for food is not indicated in patients with chronic spontaneous urticaria unless history suggests the immediate onset and recurrence of symptoms after a particular food.
There is no cure for chronic urticaria at the current time, but symptoms can be controlled in most patients. The main aim of treatment is complete control over symptoms. The main treatment for chronic urticaria are antihistamines which are anti-allergy medicines. Non- sedating antihistamines (2nd generation antihistamines) are recommended, and dosage can be increased up to a maximum of 4 times the dose if symptoms are not controlled on single dosing. Biologic agents like omalizumab or immunosuppressive medications are added if antihistamines do not relieve symptoms. Although corticosteroids may be used for a short time during severe flares, steroids should not be used for long. If specific triggers like medications or food are identified, these should be avoided.
7. Types of Inducible Urticaria
7.1. Symptomatic Dermographism (Dermographic Urticaria or Urticaria Factitia)
Symptomatic dermographism is the most common type of physical urticaria characterized by the development of itching or burning sensation, wheals which are brought about by applying a sheer force on the skin like rubbing, firm stroking, scratching or scrubbing. It manifests as though someone has been writing of the skin. Itchy wheals appear within 5 minutes following the trigger and can last for 30 minutes or more. Symptoms can become worse at night and with friction. It is important to note that the skin manifestations never occur spontaneously and appear only at the sites where the stimulus is applied. Symptomatic dermographism should be differentiated from simple dermographism, where wheals without itching appear after firm stroking of the skin.
TRIGGERS AND CAUSES
The cause for symptomatic dermographism is not known. Symptoms are triggered by physical stimuli on the skin like rubbing, scratching, pressure etc.
Symptomatic dermographism can be identified through a detailed medical history and reviewing photos of wheals. Patients report the appearance of striped wheals following scratching, rubbing or pressure. The diagnosis can be confirmed by provocation testing using a wooden spatula or specialized instruments like dermographometers (Fric test). Firm pressure is applied to the skin in a stroking motion. The appearance of pruritic wheals within 10 minutes after provocation is considered positive for symptomatic dermographism. A wheal response without itching indicates simple dermographism.
The management of symptomatic dermographism involves the avoidance of trigger stimuli as far as possible, including the avoidance of tight clothing, removal of tags etc. Symptoms can be controlled by the regular use of certain medications. The most recommended medications are the daily administration of a single dose of non-sedating antihistamines (anti-allergy medicines). If symptoms are not controlled on the daily administration, the dose can be increased up to four times the regular dose. Other drugs like omalizumab may be added if sufficient relief is not obtained.
Your doctor can give you more information on the available options.
7.2. Cold Urticaria or Cold Contact Urticaria
Cold urticaria is characterized by the appearance of itchy wheals, angioedema or both on skin contact with cold objects, liquids, or air. Cold urticaria is the second most common type of physical urticaria. Wheals and angioedema occur within minutes of exposure and is limited to the exposed areas of the skin; however, prolonged, extensive cold exposure (e.g., swimming in cold water) can trigger severe systemic reactions/anaphylaxis (Shortness of breath, drop in blood pressure, loss of consciousness, choking sensation etc.). Each patient has a temperature level (threshold) below which the symptoms are triggered. Temperature above this level does not trigger the onset of wheals. The higher the temperature threshold, the more frequent will the occurrence of wheals on cold exposure.
TRIGGERS AND CAUSES
The cause for the development of cold urticaria has not been determined. Symptoms are triggered by exposure to cold objects, liquids, or air.
The diagnosis of cold urticaria is suggested by a typical history and confirmed by provocation testing. Provocation testing involves the application of a cold object on the skin. The ice cube test involves the application of a plastic bag containing an ice cube in a small amount of water against the skin for 5 minutes. The development of wheal within 10 minutes after removal is considered positive. Electronic testing devices like the Temptest available in some centers can be used for provocation testing to identify the temperature level (threshold) at which the symptoms occur and how long from exposure to cold the wheals appear.
Management of cold urticaria includes avoiding cold exposure, wearing warm clothing, gloves, caps, scarves in cold temperatures. High-risk situations like exposure to cold baths, swimming, cold foods, beverages etc., should be avoided. Complete avoidance of cold exposure may be difficult. Medications can help to raise the tolerance level of cold exposure. A single daily dose of non-sedating antihistamines is recommended in patients who have frequent symptoms. Up-dosing to four times, the regular dose can be considered if the symptoms are not controlled. Other drugs like omalizumab may be added if sufficient relief is not obtained. In patients who develop severe systemic reactions/ anaphylaxis (Shortness of breath, drop in blood pressure, loss of consciousness, choking sensation etc.) following cold exposure, carrying an adrenaline auto-injector (Epipen) for emergency use may be warranted.
Your doctor can give you more information on the available optionsU
7.3. Solar Urticaria / Light Urticaria
Solar urticaria is a rare type of physical urticaria. In solar urticaria, itchy wheals appear within a few minutes after exposure to direct sunlight. Parts of the skin not exposed are usually unaffected. Exposure of areas of skin to sunlight through light clothes and glass can also trigger wheals as these do not completely obstruct UV rays and visible light. The severity of symptoms can increase with the intensity of sun exposure.
TRIGGERS AND CAUSES
The cause for the development of solar urticaria is not clearly understood. Symptoms are triggered by exposure to direct sunlight.
Diagnosis of solar urticaria is made based on patient history and provocation testing. A simple test is the exposure of a small area of the skin to direct sunlight. A more formal evaluation is done by exposing different skin areas to different wavelengths of light (UV-A and UV-B) by phototesting. Sunscreens and photoactive medications should be avoided before photo testing. The test is considered positive if a wheal appears at the site of exposure within 10 minutes. Wheals usually subside within 1-2 hours.
Patients with solar urticaria should avoid exposure to direct sunlight, wear protective clothing and use high protection sunscreens. Treatment with non-sedating antihistamines can help to control the symptoms. If symptoms are not controlled on the maximum dose of antihistamines, other drugs like omalizumab may be added.
Your doctor can give you more information on the available options.
7.4. Delayed Pressure Urticaria
Delayed pressure urticaria is a subtype of physical urticaria characterized by recurrent redness and painful swelling that appears after pressure stimulus to the skin. Symptoms usually appear 4 to 6 hours after the stimulus but may occur within 30 minutes. A prominent swelling can last up to 72 hrs. Delayed pressure urticaria is generally uncommon, but it ranks third in frequency among the physical urticarias.
It can co-exist with chronic spontaneous urticaria or other types of physical urticarias. It should be differentiated from symptomatic dermographism, where the wheals appear within minutes of exposure to the pressure stimulus.
TRIGGERS AND CAUSES
The activities that typically trigger symptoms include wearing tight clothes or shoes (affecting constricted areas), sitting on a hard surface, riding a bicycle, or standing for prolonged periods, strenuous walking (affecting the soles and feet), carrying heavy bags (affecting the palms, hands, shoulders), compression against a pillow (affecting the face).
Patient history alone can provide adequate clues for diagnosis. Provocation testing is performed by applying sustained pressure to the skin; a common method is a sandbag test which is performed by hanging a weight from the shoulder, thigh, or forearm for 15 minutes and then observing for symptoms over the next 24hrs. The delayed appearance (approximately 6 hours) of redness and swelling at the site is considered a positive result. This is usually not associated with itching but rather a painful or burning sensation.
The treatment of delayed pressure urticaria is a challenge. Initial management includes the avoidance of triggers like tight-fitting clothes, shoes, or modification of triggers (e.g., broadening the straps of bags). Although antihistamines are a first-line treatment with higher than standard doses if needed, the disease is usually resistant to antihistamines.
Your doctor can give you more information on the available options.
7.5. Heat Urticaria
Heat urticaria is an uncommon form of urticaria characterized by the development of wheals, itchiness within minutes after local heat exposure to the skin (hot water or hot air). Heat urticaria should be differentiated from solar urticaria, especially when symptoms appear in the summer. In solar urticaria, only areas of the skin exposed to sunlight are involved whereas in the case of heat, urticaria skin under clothing may also be involved. Diagnosis of heat urticaria can be made by applying a test tube of hot water on the skin for 4 to 5 minutes. The test is considered positive if a wheal develops at the site after removal within 10 minutes. Temptests available in some centers can also be used for provocation testing. Non-sedating antihistamines may help to control symptoms.
7.6. Exercise-induced Urticaria
Exercise may trigger urticaria, which may also be an early manifestation of exercise-induced anaphylaxis. There are also other triggers, such as food. In exercise-induced anaphylaxis, exercise is the only trigger, and it may not be induced by passively raising the core body temperature, such as in cholinergic urticaria.
7.7. Vibratory Urticaria
Vibratory urticaria or angioedema is a rare type of physical urticaria. It is characterized by redness, swelling without wheals, itching within a few minutes at the site of skin exposure to vibration. Examples of common triggers include cutting grass, working with machinery, riding a motorcycle, horseback riding, mountain biking etc. Symptoms increase in severity in 4 to 6hrs and usually resolve within 24hrs. Diagnosis can be made by putting the arm on a vortex mixer for 10 minutes. The test is considered positive if redness, itching, and swelling develop around the arm at the application site. Treatment involves the avoidance of vibratory stimuli. Non-sedating antihistamines are effective, with room for increasing the dose up to fourfold if needed.
7.8. Cholinergic Urticaria
Cholinergic urticaria manifests with the appearance of characteristic itchy wheals triggered by an active or passive rise in body temperature following body heating, exercise, sweating, hot baths, strong emotions etc. These patients typically develop tiny wheals surrounded by a large area of redness, frequently involving the trunk and extremities. Symptoms usually last for 15-60 minutes. Rarely patients can also have associated angioedema (swelling of the deeper skin) or systemic symptoms (Shortness of breath, drop in blood pressure, loss of consciousness, choking sensation etc.)
TRIGGERS AND CAUSES
Symptoms of cholinergic urticaria are triggered by heating, exertion, sweating, hot baths, strong emotions (excitement or fear) or eating spicy foods, unlike chronic spontaneous urticaria, where wheals appear out of the blue.
A diagnosis of cholinergic urticaria is based on clinical presentation. Provocation testing is done to confirm the diagnosis. Moderate exercise is carried out using a stationary bike or treadmill. The test is positive if wheals appear within 10 minutes of the exercise challenge.
Another option is a passive heat challenge which can also help to differentiate cholinergic urticaria from exercise-induced anaphylaxis. This involves non-exertional elevation of the patient’s core body temperature by placing one or both arms in a hot water bath (44°C) until a rise in body temperature of at least 0.7°C is achieved. The appearance of generalized urticaria indicates cholinergic urticaria.
Identification and avoidance of the triggers are crucial for managing cholinergic urticaria but may not always be possible. Non-sedating antihistamines with up-dosing in patients not responding to standard dose is effective in some patients. Other drugs like omalizumab may be added if sufficient relief is not obtained with the maximum dose of antihistamines. In patients who develop severe systemic reactions/anaphylaxis (Shortness of breath, drop in blood pressure, loss of consciousness, choking sensation etc.), carryingan adrenaline auto-injector (Epipen) for emergency use may be warranted.
Your doctor can give you more information on the available options.
7.9. Contact Urticaria
Contact urticaria is a rare type of inducible urticaria, characterized by the development of wheals at the contact site of an external agent (like plants, food, additives, chemicals, cosmetic agents etc.) and the skin. Avoidance of the contact trigger is advised. Antihistamines can help to control symptoms.
7.10. Aquagenic Urticaria
Aquagenic urticaria is another rare type of inducible urticaria in which wheals appear on skin contact with any source of water regardless of temperature. Similar to cholinergic urticaria, patients develop tiny wheals. It is diagnosed by applying a wet compress at normal temperature (35-37°C) to the upper body for 30 minutes. The appearance of localized wheals within 10 minutes indicates a positive test and helps differentiate it from cold urticaria (triggered by cold liquids), cholinergic urticaria (triggered by sweating). The treatment primarily includes non-sedating antihistamines.
8. Patient-Related Outcome Measures (PROMS)
TOOLS TO MEASURE AND ASSESS URTICARIA
Questionnaires may be useful to document urticaria activity and patient’s symptom control and quality of life at initial presentation and changes in response to treatment.
8.1. Disease Activity – Urticaria Activity Score (UAS) & Angioedema Activity Score (AAS)
There are two tools to measure urticaria activity: (1) Urticaria Activity Score (UAS), used to assess the number of wheals (ranging from 0: none to 3: >50 wheals) and intensity of itch (ranging from 0: none to 3: severe); (2) Angioedema Activity Score (AAS), used to assess and monitor disease activity in adult patients with predominant angioedema (with or without wheals).
Due to the unpredictability of wheals and itching, it is recommended that UAS should be done for 7 consecutive days to compensate for fluctuations that commonly occur in disease activity. This score is summed over 7 days before the medical visit, giving the UAS7 score (0–42 points).
AAS is a five-question tool with four answer options for each of the 5 items ranging from 0 (none) to 3 (severe); the range for cumulative daily AAS score is 0–15, the weekly AAS (AAS7) is 0–105, and monthly AAS (AAS28) is 0–420, where a higher value indicates a higher level of angioedema activity/severity. The main question is whether the angioedema has occurred in the last 24 hours. If the answer is yes, five additional questions are asked about “severity of physical discomfort caused by angioedema”, “ability to perform daily activities during the presence of angioedema”, “cosmetic disfigurement caused by angioedema” and” global assessment of impairment, and severity caused by angioedema”, which refer to the 8-hour period after the onset of angioedema.
8.2. Symptoms Control – Urticaria Control Test (UCT) & Angioedema Control Test (AECT)
Both Urticaria Control Test (UCT) & Angioedema Control Test (AECT) were developed specifically to assess the control status and therapeutic response.
UCT aims to determine the level of disease control in all forms of chronic urticaria (CU): CSU (with or without angioedema), CIndU, and combinations of both subtypes. It is a 4-item self-report retrospective questionnaire with a recall period of four weeks. Five answer options for each of the 4 items that are scored from 0 to 4 points; the range of summary score is 0–16, where a higher value indicates a higher level of urticaria control, a cut off of 12 is used to identify patients with “well-controlled,” and “poorly controlled” (< 12 points) urticaria.
AECT aims to measure the level of disease control from the perspective of patients with predominant angioedema (with or without wheals). It is a 4-item self-report retrospective questionnaire with a recall period of 4 weeks (AECT-4 weeks) or 3 months (AECT-3 months). Five answer options for each of the 4 items that are scored from 0 to 4 points; the range of summary score is 0–16, where a higher value indicates a higher level of angioedema control, a cut off of 10 is used to identify patients with “well-controlled,” and “poorly controlled” (< 10 points) angioedema.
8.3. Quality of Life – Chronic Urticaria Quality of Life Questionnaire (CUQ2oL) & Angioedema Quality of Life Questionnaire (AEQoL)
The CU-Q2oL was explicitly developed to assess the impact of CU on the quality of life in patients. It is a 23-item self-administered questionnaire covering the previous 2 weeks. The items are divided into six domains: Pruritus (2 items), edema (2 items), impact on daily activities (6 items), impact on sleep (5 items), limitations (3 items), and physical appearance (5 items), according to the validation study of the original version. A five-point Likert scale is used to assess the intensity of each item separately (ranging from 0: “nothing” to 5: “very much”). For each of the six dimensions, a score is calculated, and then a total index for all dimensions. The minimum total score is 23. Higher values reflect greater impairment of the symptom-specific health-related QoL.
The AEQoL is an instrument for the assessment of QoL impairment in patients with predominant angioedema (with or without wheals): The instrument includes 17 items that cover 4 domains related to the impact of angioedema on functioning, fatigue/mood, fear/shame, and food. Each item has 5 answer options. The total score is transformed into a linear scale from 0 to 100, with higher values reflecting greater impairment of the symptom-specific health-related QoL