Chapter 6: Urticaria and Angioedema Flashcards
What percentage of the population will have at least one episode of Urticaria?
20%
What length of time defines chronic urticaria?
Six weeks
What is the likelihood of determining the cause of urticaria
high probability for acute urticaria
Only 5 to 20% of the cases of chronic urticaria
what is a hive or wheal
a circumscribed, erythematous or white, non-pitting, edematous, usually pruritic plaque that changes in size and shape by peripheral extension or aggression during the few hours or days that the individual lesion exist.
The eczematous, central area (wheal) can be pale in comparison to the erythematous surrounding area (flare)
what is a major difference between hives and angioedema
angioedema is deeper than hives
angioedema without urticaria may suggest what
may indicate a C1 esterase inhibitor deficiency
what is the most important mediator of urticaria
histamine
what happens when the H1 receptors are stimulated by histamine
an axon reflex, vasodilation, and pruritus
what happens when H2receptors are stimulated
vasodilation occurs
H2receptors are also present on the mast cell membrane surface and, when stimulated, further inhibit the production of histamine.
What is a common cause of acute urticaria?
Histamine release that is induced by allergen (drugs, foods or pollens) and mediated by IgE is a common cause of acute urticaria, and particular attention should be paid to these factors during the initial evaluation.
What plays a key role in infantile urticaria?
Food origin is important. in one series it accounted for 62% of patients, more than drug etiology of 22%.
what type of hypersensitivity is associated with most cases of acute urticaria?
Type I.
What causes the histamine release of the type I hypersensitivity reaction?
Circulating antigens such as foods, drugs or inhalants interact with cell membrane-bound IgE to release histamine.
Food allergies are the most common cause of anaphylaxis.
What is an Arthus reaction?
Type III hypersensitivity reaction
Occurs with deposition of insoluble immune complexes in vessel walls. These complexes Are composed of IgG or IgM with an antigen such as a drug.
Complement-mediated acute urticaria can be precipitated by administration of whole blood, plasma, immunoglobulins, and drugs or by insect stings.
What causes the urticaria in a type III hypersensitivity reaction.
Urticaria occurs when the trapped complexes activate complement to cleave anaphylotoxins C5a and C3a from C5 and C3. C5a and C3a are potent releasers of histamine from mast cells.
What are some non-immunologic mediators that cause the release of histamine
pharmacologic mediators, such as acetylcholine, opiates, polymyxin B, and strawberries, react directly with the cell membrane bound mediators to release histamine.
What is the pathogenesis of chronic urticaria?
Cutaneous mast cell release of histamine.
True or false:
over 30% of chronic urticaria patients have an autoimmune phenomena
true
Positive autologous serum skin test, antibodies to the alpha subunit of the basophil IgE receptor and to IgE, and thyroid autoimmunity.
Be sure to rule out physical urticaria.
what is the differential diagnosis of chronic urticaria
- Cutaneous lupus erythematosus
- Urticarial Vasculitis
- Urticaria pigmentosa
- Sweet’s syndrome
- Fixed drug eruption
- Bullous pemphigoid
- Muckle-Wells Syndrome (urticaria-deafness-amyloidosis syndrome)
- Chronic infantile neurologic cutaneous articular syndrome (neonatal onset multisystemic inflammatory disease)
- Schnitzler’s syndrome
should a biopsy taken of the urticarial plaque?
Yes. Patients with hives that are characteristic of urticarial vasculitis should have a biopsy taken of the urticarial plaque.
These hives burn rather than hitch and last longer than 24 hours.
what is the first-line treatment of urticaria
Non-sedating H1 antihistamines (Allegra 180 mg daily)
H2 receptor antagonist have few side effects and may be useful as an adjunct to therapy
Patients who have no response to any of these approaches may respond to immunotherapy with 200 to 300 mg of cyclosporine per day
what is the mechanism of action of antihistamines for the treatment of urticaria?
Antihistamines control urticaria by inhibiting vasodilation and vessel fluid loss.
Antihistamines do not block the release of histamine. If histamine has been released before anti-histamine is taken the receptor sites will be occupied in the antihistamine will have no effect
in addition to anti-histamines, what is an adjunct of therapy that can be used to treat urticaria in the anxious or depressed patient?
Doxepin
Initial dose is 10 to 25 mg. Gradually increased does up to75 mg for optimal control
what side effects are associated with antihistamines
antihistamines are structurally similar to atropine; therefore the produce atropinelike peripheral and central anticholinergic effects such as dry mouth, blurred vision, constipation, dizziness
what type of antihistamine receptors are in the skin
85% of histamine receptors in the skin or the H1 subtype
15% are H2 receptors
Studies suggest that the combination of H1 and H2 blockers do not improve treatment
What is the mechanism of action for doxepin
Doxepin is a tricyclic antidepressant
– potent blockers of histamine H1 in H2 receptors
What are second line treatment options for urticaria
- Oral corticosteroids
- Leukotriene modifier.
- Dapsone
- Calcineurin inhibitors
At what dosage should you use oral corticosteroids for treatment of urticaria
- Prednisone 40 Mg Per Morning or 20 Mg Twice per Day
2. Prescribe thirty 20 Mg Tablets. Patient Takes Five Day of 60 Mg, 40 Mg, and 20 Mg Each Morning
For the treatment of urticaria, how long before leukotriene modifier becomes effective
several weeks
Montelukast was demonstrated to be effective for patients with NSAID-exacerbated chronic urticaria
what should be considered before starting Dapsone Therapy
G6PD
- Obtain a G6PD level to avoid more severe hemolytic anemia in G6PD deficient patients
What calcineurin Inhibitor Is Useful for the Treatment of Urticaria
Cyclosporine
Patients with Severe Unremitting Disease to Respond Poorly to Antihistamines May Respond to 4 Mg/KgDaily of Cyclosporine for Four Weeks
What Are Third Line Agents for the Treatment of Urticaria
- IV IG
- Methotrexate
- Topical Measures (Aveeno, Sarna, Itch X)
what is Darier’s sign
when mechanical event elicits whealing in 1 to 3 minutes after con
what is pressure urticaria
a deep, burning, or painful swelling occurring 2 to 6 hours after a pressure stimulus and lasting 8 to 72 hours
what is the treatment for pressure urticaria
systemic steroids given in short duration tapers are the most effective treatment for severe, disabling delayed pressure urticaria
what is cholinergic urticaria
in its milder form, heat bumps. The most common of the physical urticaria
What are the clinical features of cholinergic urticaria?
Round, papular wheals 2 to 4 mm in diameter that are surrounded by slight to extensive red flare.
Typically the hives occur during or shortly after exercise.
Cholinergic urticariamay become confluent and resemble typical hives
How is cholinergic urticaria diagnosed
the most reliable and efficient testing method is to ask the patient to run in place or use the exercise bicycle for 10 to 15 minutes, and then to observe the patient for one hour to check with typical micro papular hives.
What is the treatment for cholinergic urticaria
Zyrtec and twice its recommended dose of 20 mg is very effective.
What is exercise-induced anaphylaxis
Exercise acts as a physical stimulus that, through an unknown mechanism, provokes mast cell granulation and elevated serum histamine levels.
What is thought to provoke (EIA) exercise-induced anaphylaxis or exercise-accentuated anaphylaxis
may occur only after ingestion of certain foods such as celery, shellfish, wheat, fruit, milk and fish
Attacks occur when the patient exercises within 30 minutes after ingestion of the food; eating the food without exercising (and vice versa) causes no symptoms.
What is the treatment for exercise-induced anaphylaxis?
H1 antihistamines were recommended as pretreatment and acute therapy.
What is cold urticaria?
A group of disorders characterized by urticaria, angioedema, or anaphylaxis that develop after cold exposure.
What finding in a patient’s history is common with primary cold urticaria
recent history of a virus infection (Mycoplasma pneumoniae)
what age group is typically affected by primary acquired cold urticaria?
Children and young adults
what is the most common cause of severe reactions with primary acquiredcold urticaria?
swimming in cold water is the most common cause of severe reactions and can result in massive transudation of fluid into the skin, leading to hypotension, fainting, shock, and possibly death.
What is secondary acquired cold urticaria
only 5% of patients with cold urticaria.
Additional Labs should be order: CBC, ESR, ANA, mononucleosis spot test, RPR, rheumatoid factor, total complement, cryoglobulins, cryofibrinogens, cold agglutinins, and cold hemolysins.
what is solar urticaria
hives that occur in Sun-exposed area minutes after exposure to the sun and disappear in less than one hour
what is Aquagenic pruritus
severe, prickling skin discomfort without skin lesions occurs within 1 to 15 minutes after contact with water at a temperature and last for 10 to 120 minutes
what role does histamine play with Aquagenic pruritus
histamine does not play a role in the pathogenesis
what is angioedema?
hive-like swelling caused by increased vascular permeability in the subcutaneous tissue of the skin and mucosa and the submucosal layers of the respiratory and GI tracks.
What are three types of hereditary angioedema?
Type I: deficiency of C1 INH protein
type II: dysfunctional C1 INH protein
type III: coagulation factor VII gene mutation
What are two types of acquired angioedema
Type I: associated with lymphoproliferative diseases
type II: Autoimmune (anti-C1 INH antibody)
What induces most cases of angioedema?
Most cases of angioedema or idiopathic
What are the general types of angioedema?
– Hereditary angioedema – acquired C1 inhibitor deficiency – inherited angioedema with normal C1 inhibitor levels – ACE I – associated angioedema – idiopathic angioedema – allergic angioedema – NSAID associated angioedema – angioedema with the urticarial vasculitis
What is the time of onset for ACE – I associated angioedema?
The onset usually occurs within hours to one week after starting therapy.
Type I acquired angioedema is associated with what?
Type I is associated with lymphoproliferative diseases, including monoclonal gammopathy of unknown significance and high-grade lymphomas
Type II acquired angioedema is caused by what process?
Thought to because to by an auto antibody to the C1 INH protein.
Angioedema may be the first symptom of an internal disease, and proceed by how much time?
Angioedema can precede internal disease by up to seven years
What is the treatment of acquired angioedema type I?
Treatment of underlying lymphoproliferative disease is often curative.
What is the most common type of hereditary angioedema?
There are two types: type I being the most common at 85% of cases, type II with 15% of cases.
What defines type I hereditary angioedema?
Characterized by an insufficient production of C1 inhibitor.
What defines type II hereditary angioedema?
Have normal to elevated concentrations of C1 inhibitor, but the protein is functionally deficient.
Spontaneous occurrences are seen in up to 25% of patients.
Most cases begin in late childhood or early adolescence
Hereditary angioedema presents by what age?
Usually experience attacks by the second decade of life
Angioedema occurs at what three sites?
- Subcutaneous tissue
- Abdominal organs
- Upper airway
What is the most common type of contact urticaria?
The non-immunologic type is the most common and most benign. This form does not require prior sensitization
Anaphylaxis may occur after application of bacitracin ointment.
What is contact urticaria?
Characterized by a wheal and flair that occur within 30 to 60 minutes after cutaneous exposure to certain agents. Direct contact of the skin with these agents may cause a wheals and flare response restricted to the area of contact, generalized urticaria, urticaria and asthma, or urticaria combined with and anaphylactoid reaction.
How is the diagnosis of contact urticaria confirmed?
An open patch test may be performed by applying a drop of the suspected substance to the ventral form and observing the site for the wheal 30 to 60 minutes later.
What is pruritic urticarial papules and plaques of pregnancy
(PUPPP) also known as polymorphic eruption of pregnancy
Affects between 1 and 130 and 1 and 300 pregnancies.
Most frequently in primagravitas and begins late in the third trimester of pregnancy (mean onset, 35 weeks) or occasionally in the early postpartum.
The initial lesions may be confined to the striae.
What is the mean duration of the PUPPP
Six weeks, but the rash is usually not severe for more than one week.
Clearing in most cases before or within one week after delivery.
Recurrence with future pregnancies is unusual.
What is thought to to play a role in the development of PUPPP
It was postulated that abdominal distention or reaction to it may play a role in the development of PUPPP
What is urticarial vasculitis?
A subset of vasculitis characterized clinically by urticarial skin lesions and histologically by necrotizing vasculitis.
Immune complexes are thought to lodge in small blood vessels with activation of complement, mast cell degranulation, infiltration by acute inflammatory cells, fibrin deposition, and blood vessel damage.
One of the two subgroups of urticarial vasculitis?
- Hypocomplementemia
2. Normal complement levels
What is the most common cause of normal complement UV?
Idiopathic
What is the most common cause of hypocomplementemia UV
May proceed a syndrome that includes obstructive pulmonary disease and uveitus, systemic lupus erythematosus, Sjogren’s syndrome or cryoglubulinemia.
What is serum sickness?
It is a disease produced by exposure to drugs, monoclonal antibody therapy, blood products, or animal derived vaccines.
Circulating antibodies react with the newly introduced antigen to form precipitating antigen-antibody complexes.
When do symptoms appear for serum sickness?
Symptoms appear 8 to 13 days after exposure to the drug or antisera and last for 4 or more days.
What are the symptoms for serum sickness?
Fever malaise skin eruptions arthralgia nausea and vomiting occult blood in stool lymphadenopathy
White blood cell count may be as high as 25,000
What are the most common cause of serum sickness?
Drugs are the most common cause of serum sickness.
Penicillin
sulfa drugs
thiouracil
etc.
What is mastocytosis
A group of rare diseases characterized by abnormal growth of mast cells in skin, bone marrow, liver, spleen, and lymph nodes.
Histamine is release by scratching the lesions or ingesting certain agents.
What happens with mast cell degranulation occurs?
Cause episodic flushing, dyspepsia, diarrhea, abdominal pain, musculoskeletal pain, or hypotension
What is the most common form of mastocytosis?
Cutaneous mastocytosis
What is the most common cause of pediatric mastocytosis?
Sporadic and appeared during the first two years of life, especially on the trunk
Urticaria pigmentosa is the most frequent variant
For the classifications of cutaneous mastocytosis according to the World Health Organization?
- Urticaria pigmentosa (UP)
- Diffuse cutaneous mastocytosis (DCM)
- Mastocytoma of the skin
What should be considered in patients that develop cutaneous mastocytosis after the age of two?
Often accompany by systemic disease
What is a solitary mastocytoma?
A larger solitary collection of mast cells
Their reddish-brown nodules are plaques that can be several centimeters in diameter. Stroking induces whealing (“Darier’s sign”)
Rare in adults, most common at birth or in first week of life.
Most occur on the extremities but not in the palms are soles
What is urticaria pigmentosa
Second most frequent manifestation of mastocytosis in children
Maybe present at birth, may appear in infancy and childhood, is presence in 80% of affected individuals within six months.
Discuss adult onset urticaria pigmentosa
If UP develops after age 10 is more likely associated with systemic disease. Mean age of onset is 26.5 years
Lesions are well demarcated, red-brown, slightly elevated plaques averaging 0.5 to 1.5 cm in diameter
The palms and soles are spared
What is Telangiectasia macularis eruptiva perstans (TMEP)
TMEP is the rarest cutaneous form of mastocytosis.
Limited to adults and consist of telangectasias
What is the most aggressive form of mastocytosis?
Mast cell leukemia
Occurs in fewer than 2% of patients
What symptoms should make make you suspect mastocytosis
Mastocytosis should be suspected in patients with recurrent anaphylaxis who present with syncopal or near syncopal episodes without associate hives or angioedema
What is the treatment for urticaria pigmentosa?
Patients may benefit from a combination of H1 and H2 histamine antagonists.
Application of 0.05% betamethasone under plastic film occlusion for eight hours daily for six weeks leads to control pruritus and Darier’s sign
