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1)Peripheral swelling: skin and urogenital area (e.g., eyelids or lips, tongue, hands,
feet, scrotum, etc.)
2)Abdomen: Abdominal pain (sometimes it can be the only presenting symptom of
angioedema)
3)Larynx: Throat tightness, voice changes, and breathing trouble (indicators of
possible airway involvement), potentially life-threatening.
.
Diagnosis
Examination in patients with suspected angioedema includes the following:
1)Dermatologic Areas of swelling with or without erythematous skin, often with illdefined margins; the face, extremities, and genitalia are most commonly affected
[3]
2)GI No specific findings may be present, even in severe cases of angioedema, or
there may be abdominal distention and signs consistent with bowel obstruction;
changes in bowel sounds and diffuse or localized tenderness may be present; the
clinical picture may resemble that of an acute abdomen
Testing
Most mild cases of angioedema do not require laboratory testing. Suspected
allergies to food, stinging insects, latex, and antibiotics can be screened and
diagnosed. The value of aeroallergen screening for patients with angioedema is
limited, except with regard to establishing atopic status.
1)C4 level
2)C1 esterase inhibitor (C1-INH) quantitative and functional measurements
3)C1q level
Screening laboratory studies have limited value in most cases. For chronic or
recurrent angioedema without a clear trigger, clinicians may consider the following
tests:
7)CH50 level
8)Thyroid studies, including levels of thyroid stimulating hormone, free T4, and
thyroid autoantibodies (antimicrosomal and antithyroglobulin), particularly in
women or in patients with a family history of thyroid disease or other autoimmune
diseases
If the history and physical examination findings suggest specific problems, other
tests that may be helpful include the following:
Most angioedema patients do not need any imaging studies. However, when
internal organ involvement is suspected, during acute attacks, the following studies
can be performed:
Management
The primary goal of medical treatment for angioedema is to reduce and prevent
swelling, as well as to reduce discomfort and complication.
Most medications used in treating urticaria and anaphylaxis are also used
in the management of many types of angioedema. Epinephrine should be
used when laryngeal angioedema is suspected. In addition, supportive care should
be provided, regardless of the etiology.
Pharmacotherapy
Surgical option
Background
Angioedema, first described in 1586,[6] is usually defined by pronounced swelling of
the deep dermis, subcutaneous or submucosal tissue, or mucous membranes as a
result of vascular leakage.[3] Other terms, such as giant urticaria,[7] Quincke
edema,[8] and angioneurotic edema,[9] have also been used in the past to describe
this condition. Clinically, angioedema is usually nonpitting and nonpruritic. Involved
skin often shows no change in color or may be slightly erythematous (see the image
below).
Swelling that involves the tongue and upper airways is cause for greater
concern than swelling involving other areas, owing to the potential of
airway compromise.[11, 12] Laryngeal swelling is life-threatening and
should be treated as a medical emergency.
with urticaria. When both angioedema and urticaria are evident during clinical
presentation, the episode is primarily mast cellmediated.[13] Affected patients
describe subjective pruritus, sometimes associated with hypersensitivity to an
offending agent (eg, a food or drug). However, the underlying triggers are often
unidentifiable.
There are also a significant number of angioedema cases that present with
angioedema alone. In such cases, the clinical presentation, trigger, cause, and
response to treatment may be quite different from those in cases that present with
both angioedema and urticaria; therefore, some experts believe that these patients
may (at least in part) have different pathophysiologic mechanisms.[11] Many such
cases do not respond to antihistamines. Vasoactive mediators other than
histamine (eg, bradykinin) may be involved in the swelling.[11] (See
Pathophysiology.)
Pathophysiology
Angioedema is a result of the fast onset of an increase in local vascular
permeability in subcutaneous or submucosal tissue. Histamine and bradykinin
are the most recognized vasoactive mediators known to be critical in the
pathologic process of angioedema; most cases of angioedema are primarily
mediated by 1 of these 2 mediators, though some investigators indicate the
possibility that both may be involved in certain cases.[17] (See Classification and
Subtypes of Angioedema.)
Mast cells can also be activated by other nonIgE-mediated processes, such as the
binding of IgG antibodies to IgE receptors on mast cells or basophils, leading to
spontaneous mast cell activation and histamine release. Another example of non
IgE-mediated mast-cell activation is the reaction induced by intravenous (IV)
contrast material.
Plasma and tissue factors, such as bradykinin, and certain components in the
contact system or the fibrinolytic system are also found to play an important role in
certain forms of angioedema.[20, 21] For angioedema without evidence of
histamine involvement, bradykinin is likely the most important mediator.[11]
Other mediators
Besides mast cells, many other cellular components (eg, macrophages, dendritic
cells, lymphocytes, monocytes, eosinophils, and endothelial cells) are
involved in the pathogenesis of angioedema.[3, 23] These contribute to the
generation, maturation, and activation of mast cells and basophils and thereby
exert an influence on histamine release.[24] Release of vasoactive substances
causes vasodilatation of endothelial cells, as well as smooth muscle bowel
contraction,[25] ultimately manifesting in the common clinical presentation of the
disease.
Autoantibodies against the mast cell IgE receptor or mast cellbound IgE (or
basophils) are another common cause of histamine release. Additionally, proteases
may activate the complement cascade associated with C3a, C4a, and C5a, which
are considered anaphylactoids, and result in increased capillary permeability and
extravasation of fluid.[25]
Type III Normal C1-INH concentration and function with C1-esterase dysfunction
[31] ; often seen in women with factor XII gene mutations. [20, 32, 33]
There are no reliable diagnostic tests to establish the diagnosis of type III HAE;
rather the patients family history and clinical presentation are key diagnostic
components. Originally described as affecting women only, type III HAE was
subsequently reported in a few men as well.[34] Orofacial involvement seems to be
the most common presentation for type III HAE, but abdominal attacks are seen less
frequently in this variant. The new classification has proposed to combine HAE Type
I and II and name it as C1-IHN HAE, whereas HAE Type III is to be differentiated into
FXII-HAE and U-HAE.[16]
Type II AAE is associated with autoantibodies (IgG, and less often, IgM) directed
against the C1-INH molecule.[25] Depletion of C1-INH results in the production of
large amounts of bradykinin and other vasoactive substances, which causes the
signs and symptoms of angioedema.
Etiology
More than 40% of chronic angioedema is idiopathic. Trauma, surgical procedures,
and stress are common nonspecific triggers for angioedema attacks.
Angioedema has also been associated with certain conditions or syndromes, such as
the following:
Hypersensitivity angioedema
Hypersensitivity (allergic) angioedema is often associated with urticaria. It is
typically observed within 30 minutes to 2 hours after exposure to the allergen. Mast
cellmediated angioedema or urticaria may be triggered by food, drugs, animal
bites, stings (eg, from Hymenoptera), preservatives, or food coloring.[13] Food
coloring and preservatives may cause angioedema with or without urticaria.[25]
Pseudoallergic angioedema
Pseudoallergic angioedema (PAE) is not mediated by IgE; that is, the angioedema
is caused by a nonallergic or nonimmunologic reaction. However, its clinical course
and presentation are very similar to those of allergic angioedema. Typical examples
are angioedema induced by NSAIDs and that induced by intravenous (IV) contrast
material; aspirin (ASA) is the most common culprit.
Nonallergic angioedema
Nonallergic angioedema does not involve IgE or histamine and is generally not
associated with urticaria. The 5 types of nonallergic angioedema are as follows[20] :
HAE
AAE
Renin-angiotensin-aldosterone system (RAAS)-blocker-induced angioedema (RAE)
PAE
IAE
Hereditary angioedema
Acquired angioedema
ACE inhibitors can precipitate attacks of angioedema by directly interfering with the
degradation of bradykinin, thereby potentiating its vasoactive effect. ACE inhibitor
induced angioedema (AIIA or ACEI-AAE) is bradykinin-mediated, as in cases of HAE
and AAE. ACEI-AAE occurs when ACE inhibitors interfere with the degradation of
bradykinin, a potent vasoactive nonapeptide.
The most common sites of ACEI-AAE are the face, lip, and tongue, but abdominal
involvement has been reported as well.[3] Abdominal computed tomography (CT)
can be informative in cases with GI involvement.[2]
Genetic screening for ACE polymorphism may help identify the population at risk for
ACEI-AAE. In 0-9.2% of cases, patients with ACEI-AAE may develop angioedema
when switching to an angiotensin II receptor blocker (ARB).[30]
Idiopathic angioedema
The causes of IAE are, by definition, not identifiable. Furthermore, the exact
mechanisms are unclear, though nonspecific mast cell activation and degranulation
are suspected.[43, 26] On the basis of responses to medication, some cases are
thought to be mediated by mast cell activation, albeit independent of IgE. Some
cases may be associated with urticaria. Common triggers include heat, cold,
emotional stress, and exercise.
Other causes
The link between infection and angioedema is vague at best. Helicobacter pylori
infection has been found to be associated with HAE exacerbation, and treatment of
H pylori infection has led to clinical improvement of chronic urticaria and
angioedema.[28] Systemic viral, bacterial, or parasitic infection may stimulate the
immune system and cause improper activation or inflammatory changes.
Patients with Gleich syndrome exhibit elevated eosinophil levels with angioedema.
Gleich syndrome, which responds well to corticosteroids, is thought to be related to
hypereosinophilic syndrome.[46] In addition to the elevated eosinophil count,
immunoglobulin G (IgG) autoantibody against endothelial cells has been identified.
individuals, autoantibody (IgG) has been found to crosslink FceRI on mast cells,
resulting in mast cell activation and release of histamine, cytokines, and other
proinflammatory mediators. Immunomodulatory drugs may be beneficial for this
type of angioedema.[47]