6 - 41 - URTICARIA AND ANGIOEDEMA

Question 1

Autoantibodies against what Ig and receptot that activate mast cells and basophils and induce histamine release may be detected in up to half of patients with chronic spontaneous or idiopathic urticaria (type II autoimmunity)?

Answer 1

Immunoglobulin (Ig) E or the high-affinity IgE receptor (FcεRI)

Question 2

A certain population of patients may develop angioedema mediated by ______________ rather than histamine.

Answer 2

bradykinin

Question 3

local and transient skin or mucosal edema that develops in deep tissues mostly without itching but may accompany pain or burning sensations

Answer 3

Angioedema

Question 4

what subtype sof urticaria present with wheals that are usually small (<5 mm) and disseminated in the provoked area of the skin

Answer 4

cholinergic, adrenergic, and aquagenic urticaria

Question 5

“a serious, lifethreatening generalized or systemic hypersensitivity reaction” and “a serious allergic reaction that is rapid in onset and might cause death.

Answer 5

Anaphylaxis

Question 6

classification divides urticaria into acute and chronic at how many weeks from the onset?

Answer 6

6 weeks

Question 7

Question 8

urticaria that occurs spontaneously almost every day without any apparent cause or trigger

Answer 8

Spontaneous urticaria

Question 9

most common subtype among the physical urticarias

Answer 9

Symptomatic dermographism, also called as urticaria factitia, dermographic urticaria, mechanical urticaria, or simply dermographism

Question 10

itching or burning skin sensations and the development of pruritic wheals and flare in areas exposed to shearing forces on the skin

Answer 10

Symptomatic dermographism, also called as urticaria factitia, dermographic urticaria, mechanical urticaria, or simply dermographism

Question 11

physical urticaria being characterized by the appearance of wheals and flare in response to cold

Answer 11

Cold urticaria

• The cutaneous appearance of wheals and flare is typically flat and widely spread but may also be punctate.
• Itching and wheals of the skin occur within minutes and persist up to 1 hour.
• In severe cases, the mouth and pharynx may swell after drinking cold liquid.

Question 11

erythematous edematous and deep swelling may appear 9 to 18 hours after cold challenge

Answer 11

delayed cold urticaria

Question 12

widespread wheals and flare develop in response to cooling of the core body temperature, not by the local exposure to cold

Answer 12

systemic cold urticaria

Question 13

In rare and severe cases of symptomatic dermographism, erythematous lines may accompany punctate wheals characteristic of cholinergic urticaria

Answer 13

cholinergic dermographism

Question 14

In certain cases of DPU, wheals of symptomatic dermographism may return in the same site or newly develop 3 to 6 hours after stimulation and persist for up to 48 hours

Answer 14

delayed dermographism

Question 15

In some rare cases, wheals may be markedly augmented when the skin is chilled

Answer 15

cold-dependent dermographism

Question 16

rare subtype of physical urticaria characterized by wheals and flare that develop within minutes after local heat exposure to the skin and disappear within a few hours at the longest

Answer 16

Heat urticaria

• In contrast to cholinergic urticaria that involves small punctate eruptions in response to conditions that elicit sweating, patients with heat urticaria develop wheals and flare that spread in the area of skin exposed to heat, regardless of the core body temperature or sweating

Question 17

rare subtype of physical urticaria characterized by wheals and flare that develop within minutes after local exposure of the skin to certain wavelengths of light

Answer 17

Solar urticaria

• The urticarial lesions usually resolve within hours but may accompany headache, syncope, dizziness, wheezing, and nausea.
• The shape of skin eruptions in solar urticaria is consistent with the area exposed to the light of an eliciting wavelength.

Question 18

deep dermal wheals that appear in a continuously compressed region with a latency of 30 minutes or several hours after the release of the compression

Answer 18

Delayed pressure urticaria

• The wheals last for several hours or up to 3 days and may be accompanied by a** burning sensation or pain** rather than the itching often seen with CSU

Question 19

rare subtype of physical urticaria characterized by cutaneous swelling developing immediately at the site of contact with vibratory stimuli, such as jogging, vigorous toweling, or using lawnmowers

Answer 19

Vibratory urticaria and angioedema

• Recently, the missense mutation of ADGRE2 has been reported to be associated with familial vibratory urticaria with autosomal dominant inheritance

Question 20

rare subtype of urticaria induced by local skin exposure to water

Answer 20

Aquagenic urticaria

• The eruptions are i**nduced regardless of the temperature of the water. **
• This characteristic of aquagenic urticaria helps differentiate it from cold urticaria and heat urticaria, which may also be induced by skin exposure to water at certain temperatures.
• Aquagenic urticaria is characterized by small wheals, resembling eruptions of cholinergic urticaria, but wheals in this urticaria subtype are** generally fewer in number **as compared with eruptions of cholinergic urticaria.

Question 21

distinct subtype of urticaria induced by stimuli that cause sweating and distinctive for its small urticarial eruptions

Answer 21

Cholinergic urticaria

• more common in children, adolescents, and young adults
• Stimuli can be physical exercise, a hot temperature environment, or emotional or gustatory excitation
• punctate 1- to 4-mm wheals or red spots with or without surrounding flare

Question 22

major antigen in sweat

Answer 22

MGL_1304

protein produced and released by Malassezia globosa on human skin

Question 23

subtype of inducible urticaria characterized by immediate development of a wheal and flare reaction at the site of contact with specific substances

Answer 23

Contact urticaria

• It may be either immunologic (IgE mediated) or nonimmunologic.
• wheal and flare usually appears within 30 minutes and completely disappears within a few hours and may also develop into generalized urticaria and even anaphylaxis

Question 24

Cases in which oral edema and discomfort are the main symptoms, induced by contact of the oral mucosa with certain foods

Answer 24

oral allergy syndrome (OAS)

Question 25

recurrent urticarial lesions that last for more than 24 hours, leaving pigmentation and demonstrating histopathologic evidence of leukocytoclastic vasculitis

Answer 25

Urticarial vasculitis ## Footnote * Shapes of wheals and flare observed in urticarial vasculitis are similar to those observed in spontaneous urticaria and may be indistinguishable from those of CSU with long-lasting wheals

Question 26

most frequent sign observed in anaphylaxis

Answer 26

Wheal and flare

Question 27

wheal and flare reaction induced by scratching a lesion of mastocytosis

Answer 27

Darier Sign

Question 28

Recently, a missense mutation in _________ has been identified in patients with autosomal dominant vibratory urticaria and revealed to make mast cells sensitive to vibration in an IgE-independent manner

Answer 28

ADGRE2

Question 29

Many studies have suggested chronic persistent infection by what bacteria as an important cause of CSU

Answer 29

Helicobacter pylori ## Footnote but its significance is disputed

Question 30

Several days to a few weeks after the administration of the offending agent, which could be not only heterologous serum, but also be certain drugs, urticaria may develop with fever, lymphadenopathy, myalgia, arthralgia, and arthritis.

Answer 30

SERUM SICKNESS

Question 31

Question 32

Biomarkers reflecting disease severity in CSU

Answer 32

* FDP, * D-dimer, * F1+2, * CRP, * interleukin-6 (IL-6), * MPV

Question 33

how do you do utologous serum skin test (ASST)?

Answer 33

In ASST, 0.05 mL of autologous serum is intradermally injected on the volar forearm skin along with normal saline and 10 µg/mL of histamine as the negative and positive controls, respectively

Question 34

Question 35

Provocation test for symptomatic dermographism

Answer 35

* The **forearm** is more suitable for this test than the abdomen, back, or pretibial areas. * The result is considered positive if the patient shows a wheal and reports itching at the site of provocation at **36 g/mm2 or less**. * A **wheal** response **without itching** on provocation at **60 g/mm2 or higher** indicates the** less clinically significant simple dermographism. ** * Reactions of this subtype of urticaria and other inducible urticarias, except for DPU, should be evaluated **5 to 10 minutes after testing**

Question 36

Provocation of heat contact urticaria

Answer 36

* Provocation of heat contact urticaria is performed by applying **hot metal, water, or a glass cylinder** filled with **hot water at 45°C to the skin of the volar forearm** * The TempTest used for cold contact urticaria may also be used for this type of urticaria

Question 36

provocation test for solar urticaria

Answer 36

* A provocation test for solar urticaria should be done on the **buttock** skin, but parts of the trunk that are usually covered by clothes can also be tested. * The light source may be **sunlight** or a **slide projector** from a distance of **10 cm with or without filters or a monochromator** (ultraviolet [UV] A or B, or visible light)

Question 36

Cold provocation procedure

Answer 36

* Cold provocation is performed by applying a **wrapped ice cube or cold water for 5 minutes**. * In this way, the threshold duration of cold application can be determined. * The use of a **thermoelectric element (TempTest) ** can be used to determine the threshold by temperature * These tests induce wheal formation in cold contact urticaria but not for systemic cold urticaria, in which patients develop widespread wheals in response to cooling of the core body temperature or to cold wind

Question 37

Provocation test for delayed pressure urticaria

Answer 37

* Provocation may be performed by suspending a **7-kg weight on a 3-cm shoulder strap for 15 minutes** or applying rods supported in a frame to the back, thighs, or forearm. * Unlike the other inducible urticarias, the skin reaction should occur after a latent period, typically **2 to 4 hours after the pressure **has been applied.

Question 37

Provocation test for vibratory urticaria and angioedema

Answer 37

* The forearms are held on a flat plate placed on a **vortex mixer** that runs at between **780 and 1380 rpm for 10 minutes**. * The site of application should be assessed for **swelling 10 minutes after testing**

Question 38

Provocation test for aquagenic urticaria

Answer 38

* Provocation is performed by attaching **wet clothes at body temperature for 20 minutes**. * Wiping the test area with an **organic solvent and challenging with saline** instead of tap water may increase the reactivity.

Question 39

Provocation testing for cholinergic urticaria

Answer 39

* Skin testing with **intradermal injection of 0.1 mL of acetylcholine at 100 µg/mL **may reinforce the diagnosis of cholinergic urticaria. * The test result should be considered positive if the** test site shows satellite wheals around the injection site**. * The specificity of this test seems to be high, but the sensitivity is approximately 30% to 50%

Question 40

contact urticaria provocation testing

Answer 40

* suspected substance is applied in its original form or as an extract on a normal looking area of the **volar forearm or the upper back for 15 to 20 minutes.** * If this test result is negative, **occlusive application is applied **followed by a **prick test. ** * For patients with a history of severe symptoms, tests should be started with sufficiently diluted suspected substances.

Question 41

subtype of hereditary angioedema characterized by **lack C1-INH protein**

Answer 41

Type I

Question 42

subtype of hereditary angioedema characterized by **lack of activity of C1-INH **because of genetic point mutations

Answer 42

Type II

Question 42

subtype of hereditary angioedema characterized by **normal** C1-INH

Answer 42

Type III ## Footnote * rare subtype * develops mostly in females, and a gain-offunction mutation of factor XII may be identified in some patient

Question 43

Autoinflammatory diseases known to include urticaria-like symptoms

Answer 43

Schnitzler syndrome and cryopyrinassociated periodical syndrome (CAPS)

Question 44

urticaria-like eruptions and monoclonal IgM or possibly IgG gammopathy accompanied by systemic symptoms such as fever and bone and muscle pain

Answer 44

Schnitzler syndrome

Question 45

The common and crucial cause of Cryopyrin Associated Periodical Syndrome

Answer 45

gain-of-function mutations in **NLRP3 (CIASI)**, resulting in **overproduction of IL-1β**

Question 46

four factors appear to be associated with prolonged prognosis of urticaria

Answer 46

(1) initial disease severity, (2) presence of angioedema, (3) combination of CSU and physical urticaria(s), and (4) autoreactivity (positive ASST result)

Question 47

mainstay of treatment for all kinds of mast cell–mediated urticaria

Answer 47

second-generation nonsedating antihistamines ## Footnote Generally, first-generation sedating antihistamines are no longer recommended

Question 48

For intractable cases resistant to standard doses of antihistamines, increased dosing of antihistamines up to how many fold is recommended in EAACI guideline?

Answer 48

fourfold

Question 49

For cases in which high-dose antihistamines fail to achieve enough improvement, several additional therapies are recommended. The guideline published by the British Society for Allergy and Clinical Immunology (BSACI) and the American consensus document recommend adding what medication?

Answer 49

antileukotrienes

Question 50

A recent meta-analysis of randomized controlled studies showed that what dosage of omalizumab is recommended for intractable CSU regardless of the levels of serum total IgE?

Answer 50

300 mg/month ## Footnote In theory, omalizumab inhibits circulating IgE and consequently decreases the number of FcεRI on mast cells and basophils.

Question 51

Question 52

The same treatment principles and algorithm are suggested for both pregnant and lactating women with urticaria. Among antihistamines, what is often chosen based on its long availability and safety record?

Answer 52

chlorphenamine ## Footnote * Current guidelines on urticaria support the use of **cetirizine and loratadine** desirably **after the first trimester of pregnancy** if the benefits of an antihistamine are considered to outweigh any risks of administration for an individual patient