Kembara Xtra - Medicine - Angioedema

​Medicine - Angioedema 
BASIC DESCRIPTION
 Antihistamines, corticosteroids, and, if necessary, epinephrine should be administered to all patients who present with angioedema (AE).
If it is believed that AE is caused by allergen exposure, it is necessary to try to pinpoint the culprit and educate the patient on how to minimize exposure in order to prevent a recurrence.

Recurrent AE that is not caused by allergen exposure has to be sent to a professional to confirm the diagnosis and find out if there are any other therapeutic options.

DESCRIPTION Acute extravasation of fluid (AE) is an acute, localized swelling of the skin, mucosa, and submucosa.

AE frequently appears as a component of the urticaria presentation, but when it does not include wheals, it should be identified as a separate illness.
AE can be life-threatening if the upper airway is affected. It starts between minutes to hours and resolves within hours to days.
There are two main categories for AE, each with distinctive subtypes:
All cases that are not regarded as hereditary AE (HAE) fall under the category of acquired AE (AAE).
Idiopathic Histaminergic AAE (IH-AAE): response to antihistamine therapy, no known etiology
Idiopathic nonhistaminergic AAE (InH-AAE): No cause has been found, and antihistamine therapy has not been effective.
ACEI-AAE, also known as angiotensin-converting enzyme inhibitor-related AAE
C1-INHAAE, or C1-inhibitor (C1-INH) deficiency-related AAE
- HAE: Bradykinin-mediated AE, which is caused by mutations in the genes that control the complement cascade.
Caused by a lack of C1-INH, C1-INH HAE
Patients with FXII-HAE have an FXII mutation but a normal C1-inhibitor.
Patients with U-HAE have normal C1-inhibitors; the etiology is unknown.

Synonym(s): Quincke edema; angioneurotic edema

IH-AAE, InH-AAE, ACEI-AAE: any age; C1-INH-AAE: >40 years; HAE: infancy to the second decade of life; Predominant gender: male = female, with the exception of FXII-HAE, which primarily affects females.
Prevalence
When compared to whites, the frequency of AE related to ACEI use is up to four times higher. AAE: - IH-AAE: most prevalent kind of AE - ACEI-AAE: 0.1-2.2% of patients using ACEI.
Note that self-identified race should not affect judgments concerning the beginning of ACEI because race is now understood to be a social construct rather than a biological one.
C1-INH-HAE: 1:10,000 to 100,000 - C1-INH-AAE: 1:500,000 HAE

IH-AAE: caused by the release of vasoactive substances; ACEI-AAE: believed to be caused by increased plasma levels of bradykinin; C1-INH-AAE: nongenetic changes to C1-INH function; may be caused by autoantibodies
HAE: - Attacks are brought on by sustained mechanical pressure, cold, heat, trauma, emotional stress, menses, sickness, and inflammation. It has been linked to other lymphoproliferative disorders such systemic lupus erythematosus.
C1-INH-HAE: Type I: Decreased production of C1-INH; Type II: Normal or high levels of C1-INH, but dysfunctional; FXII-HAE: Normal C1-INH with presence of coagulation factor XII gene mutation; Formerly type III HAE: Symptoms frequently estrogen dependent, induced by estrogen administration (hormone replacement therapy or oral contraceptives) or pregnancy; U-HAE: Normal C1-INH

Genetically speaking, HAE types I and II are X-linked dominant, but HAE with normal C1-INH is autosomal dominant.
25% of HAE cases are caused by spontaneous genetic alterations.

RISK FACTORS Include taking drugs and consuming foods that can trigger allergic responses; having a prior diagnosis of HAE or AAE; and having a favorable family history.

DURATIONAL PREVENTION
Do not use ACE inhibitors in type I or II HAE. Avoid recognized triggers.

CONDITIONS OFTEN Associated with

 Urticaria Quincke illness (AE of the uvula)


DIAGNOSIS
AAE: - No known positive AE family history
- Examine for: - Exposure to common allergens such as food (shellfish, nuts, eggs, milk, wheat, soy), latex, insect bites/stings, and medicine (antibiotics, aspirin, opioids, NSAIDs, and OCPs). - A positive skin prick test can be used to confirm an allergy.
 Contact with ACE
If ACEI, allergies, or other reasons have been ruled out, exposure to physical stimuli (cold or vibration) is then considered idiopathic (IH-AAE).
If AE returns after using preventative antihistamines, it is considered InH-AAE.
HAE: Positive family history of AE in a second-degree relative; laboratory confirmation is required for C1-INH-HAE, FXII-HAE, and U-HAE.

HISTORY Acute, usually asymmetrical swelling with onset in minutes to hours Unlike urticaria, AE does not appear with wheals and is often nonpruritic, yet it has the potential to be excruciatingly painful and burning.
Recent contact with medicines or food allergens
Recognize potential triggers, such as traumatic experiences or environmental exposure.
Family background Angioedema Recent infection, autoimmune disease history, or cancer

PHYSICAL EXAMINATION Vitals: Signs of systemic involvement and increased severity include tachypnea, tachycardia, and hypotension.
Tense, nonpitting skin swelling that is skin-colored or slightly erythematous; commonly affects the larynx, lips, periorbital area, and tongue; can affect any portion of the body; evaluated for oropharynx involvement or symptoms such stridor.
GI tract involvement, which more frequently occurs in some kinds of HAE, might present as sporadic, unexplained stomach pain.

ALERT

Select history and physical findings, such as involvement of the anterior tongue, base of the tongue, or larynx, stridor within 4 hours of the onset of symptoms, and drooling, increase the risk of early intubation and tracheostomy.
Despite the fact that these complications can happen with any subtype, patients with HAE are more likely to require an intubation, tracheostomy, or even pass away.


DISTINCTIVE DIAGNOSIS

Anaphylaxis, erysipelas, urticaria, contact dermatitis, food and drug allergies, dermatomyositis, lymphedema, insect bite reactions, and diffuse subcutaneous infiltrative process are all connective tissue diseases. 

DETECTION & INTERPRETATION OF DIAGNOSIS
Initial examinations (lab, imaging)
The history and clinical examination alone should serve as the basis for the first diagnosis.

CBC, ESR, complement testing (C4, C1-INH, C1-INH function), allergy testing, and paraproteinemia screening (SPEP, UPEP) are only a few of the laboratory tests available. Complement testing helps to discriminate between different AE types; this evaluation should be carried out in cooperation with an allergy specialist:
A sensitive but non-specific screening test for inherited and acquired C1-INH deficiency is low serum C4.
- If C4 is normal, find out the level and function of C1-INH and check C4 again when having an acute episode.
– Consider other causes and/or require genetic testing (e.g., FXII gene) if C4 level and C1-INH level and function are still normal.
C4 level, C1-INH level, and C1-INH function all suggest type I C1-INH-HAE if they are low.
poor C4 and poor C1-INH function are the hallmarks of C1-INH-HAE, type II, however C1-INH levels might be normal or increased.
Complement levels should be measured in addition to allergy tests to identify potential triggers in cases with recurrent AE with urticaria.
GI AE or ileus can be shown on abdominal radiographs and CT scans.
It's possible for C1-INH deficiency to coexist with internal cancer. Rarely, AE may develop into a paraneoplastic condition. Patients with AAE would have imaging (CT scan, radiography, etc.) as part of a neoplastic workup.

Tests in the Future & Special Considerations
Neoplastic and autoimmune workups are necessary if C4 and C1q antigen levels are low (as they are in AAE). To rule out hematologic malignancies or cancer, many tests such a CBC, a peripheral smear, protein electrophoresis, immunophenotyping of lymphocytes, and imaging examinations are frequently used.

Treatment and general precautions
Eliminate a potential trigger by intubating if the airway is endangered.
For patients who are unable to respond to initial therapy or who are unstable, volume replacement is crucial.

First Line: MEDICATION
 If an allergic reaction (AE) manifests as hypotension or respiratory impairment, provide epinephrine (1:1,000); 0.1 mg/kg (0.3 mg for children and 0.5 mg for adults).
Use first-line therapy if the reason of the AE is unknown: intramuscularly every 5 to 15 minutes
If there is airway involvement, epinephrine
- H1 antagonist (maximum dose of 50 mg of diphenhydramine administered intravenously to children and adults). Delirium, urine retention, constipation, and elevated ocular pressure are a few of the possible side effects in older persons.
- H2 antagonists (IV ranitidine, adult dosage is 50 mg; pediatric dosage is 1 mg/kg with a 50 mg maximum).
- Corticosteroids (IV methylprednisolone, adult: 50 to 100 mg, child: 1 mg/kg, maximum 50 mg; or IV hydrocortisone, adult: 200 mg, child: 100 mg) IH-AAE - Acute treatment: first-line therapy, as previously mentioned 
Before considering treatment failure or an alternate diagnosis, such as InHAAE or InH-AAE, second-generation antihistamines (cetirizine, fexofenadine, loratadine, etc.) should be taken daily. For acute treatment, antihistamines are ineffective; corticosteroids and epinephrine should be used if upper airway involvement is present.
- Prevention: Take tranexamic acid, up to 3 grams per day for adults, or seek a specialist's referral for immunosuppressive medications. 
ACEI-AAE - Acute treatment: Remove the causal agent. First-line therapy, as above, may not be effective.
Off-label medications include icatibant, a bradykinin receptor antagonist, Berinert, a C1-INH substitute, and ecallantide, a kallikrein inhibitor.
- Prevention: Eliminate the responsible party; angiotensin receptor blockers (ARBs) are a suitable replacement due to their low incidence of cross-reactivity.
Treatment options for C1-INH-AAE include kallikrein inhibitor (ecallantide), bradykinin receptor antagonist (icatibant), and C1-INH replacement (Berinert, Ruconest). H1/H2 antagonists, corticosteroids, and epinephrine are ineffective and not advised.
 Improvement brought on by treating the underlying condition - Remission from the underlying condition may be achieved as a preventative measure.
Patients with U-HAE/HXII-HAE do not respond to corticosteroids and antihistamines, according to the FXII-HAE/U-HAE. A specialist in allergy and immunology should choose the best course of treatment, which may include C1-INH drugs, icatibant, ecallantide, progesterone, danazol, and tranexamic acid.
- Prevention: In women, hormone therapy or pregnancy may exacerbate symptoms. Avoiding these circumstances may stop clinical assaults.
Second-line acute HAE therapy: In the absence of first-line treatments, FFP can be explored, but caution is advised because it may make an attack worse.

QUESTIONS FOR REFERENCE
The care of an allergy/immunology expert will be beneficial for patients who present with their first episode of AE, recurrent AE, or both, and who have a positive family history. This management will include diagnosis, therapy selection, education, and the creation of emergency and procedural action plans.

SURGICAL AND OTHER PROCEDURE
if increasing laryngeal edema prohibits endotracheal intubation, a tracheostomy

CONSIDERATIONS FOR ADMISSION, THE INPATIENT, AND NURSING
The degree of airway involvement determines whether admission is necessary. Risk stratification can be done using Ishoo criteria. All patients in need of airway assistance or experiencing respiratory distress will benefit from therapy in an intensive care unit.

PERSONAL CARE AFTERCARE RECOMMENDATIONS
Patient monitoring; diagnostic testing if symptoms are severe, chronic, or recurrent; and specialised management for people with recurrent AE.
DIET Steer clear of known food allergies.

EDUCATION OF PATIENTS

Inform them about how to avoid known triggers, various forms of treatment, when to seek emergency care, and how to wear a medical alert bracelet.

PROGNOSIS: AE symptoms frequently go away in a matter of hours to 2 to 4 days. A compromised airway makes AE potentially fatal.
Patients with HAE experience 20 attacks on average each year, with each one possibly lasting 3 to 5 days. The frequency of occurrences and the amount of missed days from work or school can be reduced by prophylaxis.

COMPLICATIONS
Anaphylaxis