Child and Chest Health Care Delhi NCR

Hereditary angioedema is a potential life threatening condition.

It requires earliest possible diagnosis and immediate treatment to save the life in certain cases.

It is caused by either deficiency of C1  inhibitor(Type 1) or dysfunction (Type 2).

It is an autosomal dominant disorder.

In a randomised control trial ,published in JAMA,Lanadelumab,a monoclonal human antibody against Kallikrein was proved to be very effective in reducing the frequency of attacks as well as reducing the severity of individual attack.The level of evidence is level 1,means excellent.

The study was conducted at 41 places in Canada,Jordan,Europe and United states. All the subjects included were previously diagnosed cases of Hereditary angioedema and all were more than 12 years of age.

84 patients were given Lanadelumab and 41 were given placebo.There was a run in period of 4 weeks preceded by 2 weeks of wash out period for any prophylactic treatment being used by patients knowingly or unknowingly. Patients were followed up for a period of 26 weeks for occurence of any episode of angioedema its severity, or any adverse effect of interventional medication.Patients were randomised 2:1 to receive Lanadelumab and placebo. The Lanadelumab receiving patients were divided into 3 groups, and the treatment period was of 26 weeks. The first group received Lanadelumab suncutaneously 150 mg every 4 weeks,second group received 300mg every 4 weeks and the third group 300mg every 2 weeks. The number of episode of angioedema and its severity was observed through a study period of 26 weeks. Adverse events were also observed.

In the group receiving 150mg Lanadelumab subcutaneously every 4 weeks,mean number of attack was 0.48(CI₉₅ 0.31-0.73) in comparision to mean number of attack 1.97 in the placebo group(CI₉₅ 1.64-2.36) ).In the group receiving 300mg of Lanadelumab every 4 weeks .the mean number of attack was 0.5((CI₉₅ 0.36-0.77) ) and for those receiving 300mg of Lanadelumab every 2 weeks the mean number of attack was 0.26(CI₉₅ 0.14-0.46) )

Patients receiving Lanadelumab had improved quality of life with reduced number of attacks(p<0.001),less use of anti C1 inhibitor medications( an20.2% vs 65.9%; p < 0.001) and less episode of moderate to severe attacks(p<0.001)

Adverse effects were seen in 98.5% cases and they were mild to moderate, including headace(7.1%),pain at the site of injection(41.7%),erythma at the site of injection(9.5%) and bruising at the site of injection(6%)

REFERENCES:

Pulmonology Advisor > Trial Tracker > Lanadelumab may be an effective prophylactic treatment for hereditary angioedema

Angioedema is characterised by sudden onset of swelling of eyelids,lips,tounge,genitals,dorsum of the hands and feet,which are visible on clinical examination and not clinically visible swelling of the gastrointestinal tract

Swelling of gastrointestinal tract present as pain abdomen of varying severity .Sometimes, acute severe pain like acute abdomen leading to unnecessary surgery.

Swelling involves the deeper subcutaneous layers.

There may be pain and itching but occasionally only pain is there.

It may take upto 72 hours for the resolution of sewlling.

It may be histamine related or non histamine related.

In histamine related angioedema,urticaria (wheals) will be present along with swelling

There may be a prodrome in the form of tightness or tingling of the area before swelling.

The most serious complication of angioedema is involvement of larynx in the form of laryngeal edema.

When the swelling involves the throat and uvula,it can readily be seen on clinical examination

It  may cause complete obstruction of airway needing intubation and sometimes tracheostomy to save the life.

Fortunately,life threatening episodes are rare.

Dental procedures,with injection of procaine into gum is a common precipitant but laryngeal edema may be spontaneous.

There is no response to epinephrine,antihistamine and corticosteroids on the swelling.

 

If there is only swelling without urticaria,it is not associated with histamine and it may of two types-HEREDITARY AND ACQUIRED ANGIOEDEMA.

HEREDITARY ANGIOEDEMA can be of three types;Type 1-reduced production of C1 inhibitor

Type 2-sufficient production but decreased function of C 1 inhibitor

Type 3-Estrogen dependent,due to mutation in factor xii seen mostly in women

ACQUIRED ANGIOEDEMA can also be of three types;Type 1-associated with reduced C 1esterase inhibitor

Type 2-Drug induced,most common offending drug is ACE inhibitor

Type 3-Histamine dependent regarded as urticaria without wheals

HEREDITARY ANGIOEDEMA is an autosomal dominant disease.

ACQUIRED ANGIOEDEMA may be seen in association with neoplasia,lymphoproliferative disorders and rarely infections.

In case of suspicion of hereditary angioedema type 1 and type 2, decreased levels of serum C 4,C 1inhibitor and decreased function of C 1 inhibitor should be assessed.

TREATMENT

Acute therapy is required during life threatening episodes,which is fortunately rare.

Specific treatment is concentrate of human C1 inhibitor ,the availability of which is limited

The approved drug is BERINERT,used as an intravenous formulation in the dose of 20 unit/kg

In case of non availability of this specific reatment,FFP(fresh frozen plasma) may be used which is least specific but widely available.

Bradykinin type 2 receptor antagonist ICATIBANT is approved for the age of 18 years and older

All treatmens are most effective when they are given early after onset of signs and symptoms

It may take 1-4 hours for the start of action after giving the drug.

Icatibant can be given in ACE inhibitor induced angioedema

Icatibant can be stored on room temperatue and can be given subcutaneously

Icatibant is licensed for home treatment in Europe.

CINRYZE-Purified C1-INH is approved for prophylaxix after acute attack in adolescents and older children

It is given in the dose of 1000 units intravenously twice a week

Danazol is another drug being used as short term prophylaxix ,but it is not given in children,

due to the side effects of premature closure of epiphysis

Danozol increases the production of C1 inhibitor in liver,

For histamine related angioedema, non sedating antihistamine is the drug of choice

In case of no response to usual  dose of nonsedating antihistamine ,the dose may be increased to 4 times

REFERENCES:

• Borzova E and Gratton C ,Angioedema.In Zuberbier Tet al.Urticaria and AngioedemaBerlin:Springer Verlag 2010.122.
• Bindslev-JensenC,CanonicaGV,Church mk,GimenzArnou AM et al. eaaci/ga2lan/edf/wao Guideline .Treatment of Urticaria .Allergy2010;64:1417-1426
• Nelson Textbook of Pediatrics 20 e