Anaphylaxis
Anaphylaxisis a potentially life-threatening, systemic allergic reaction caused by the release of histamine and other vasoactive mediators from mast cells.
The risk of death is increased in patients with pre-existing asthma, particularly if this is poorly controlled, and in individuals in whom treatment with adrenaline (epinephrine) is delayed.
Anaphylaxis: IgE-mediated mast cell degranulation:
Foods:• Peanuts • Tree nuts
• Fish and shellfish • Milk
• Eggs • Soy products
Insect stings:
• Bee venom • Wasp venom
Chemicals, drugs and other foreign proteins:
• Intravenous anaesthetic agents, e.g. suxamethonium, propofol
• Penicillin and other antibiotics
• Latex
Anaphylactoid: non-IgE-mediated mast cell degranulation:
Drugs:
• Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs)
• Opiates
• Radiocontrast media
Physical:
• Exercise • Cold
Idiopathic:
• No cause is identified in 20% of patients with anaphylaxis
Management:
Prevent further contact with allergen: e.g. Removal of bee sting
Ensure airway patency
Administer intramuscular adrenaline (epinephrine) promptly
• Adult dose: 0.3–1.0 mL 1:1000 solution
• Repeat at 5–10 min intervals if initial response is inadequate
Administer antihistamines:
• e.g. Chlorphenamine 10 mg i.m. or slow i.v. injection
• Directly opposes effects of mast cell activation
Administer corticosteroids
• e.g. Hydrocortisone 200 mg i.v.• Prevents rebound symptoms in severely affected patients
Provide supportive treatments
• e.g. Nebulised β2-agonists to decrease bronchoconstriction
• I.v. fluids to restore or maintain blood pressure
• Oxygen
Angioedema
Angioedema is the episodic, localised, non-pitting swelling of submucous or subcutaneous tissues. This most frequently affects the face, extremities and genitalia.Involvement of the larynx or tongue may cause life-threatening respiratory tract obstruction, and oedema of the intestine may cause abdominal pain and distension.
In most cases, the underlying mechanism is degranulation of mast cells. However, angioedema may occasionally be mediated by increased local bradykinin concentration. Differentiating the mechanism of angioedema is important in determining appropriate investigations and treatment.
Hereditary angioedema (HAE):
HAE, also known as inherited C1 esterase inhibitor deficiency, is an autosomal dominant disorder caused by decreased production or activity of C1 inhibitor protein.
This complement regulatory protein inhibits spontaneous activation of the classical complement pathway. C1 inhibitor is also a regulatory protein for the kinin cascade, activation of which increases local bradykinin levels and gives rise to local pain and swelling.
angioedema may be spontaneous or triggered by local trauma or infection. Multiple parts of the body may be involved, especially the face, extremities, upper airway and gastrointestinal tract.
Episodes of angioedema are self-limiting and usually resolve within 48 hours. Patients with HAE generally present in adolescence, but may go undiagnosed for many years. A family history can be identified in 80% of cases. HAE is not associated with allergic diseases and is specifically not associated with urticaria.
Acute episodes are always accompanied by low C4 levels and the diagnosis can be confirmed by C1 inhibitor measurement.
Prevention is with modified androgens (e.g. danazol), which increase endogenous production of complement proteins. Severe acute attacks should be treated with infusion of purified C1 inhibitor or fresh frozen plasma.
Acquired C1 inhibitor deficiency:
This rare disorder is clinically indistinguishable from HAE but presents in late adulthood. It is associated with autoimmune and lymphoproliferative diseases.Treatment of the underlying disorder may induce remission of angioedema
ACE-inhibitor associated Angioedema:
It occur in 0.1–0.2% of patients treated with ACE inhibitors, it is due to Inhibition of breakdown of Bradykinin , Usually affects the head and neck, and may cause life-threatening respiratory tract obstruction . Can occur years after the start of treatment, there is no specific investigations and it require discontinuation of ACE inhibiter and avoidance of angiotensin II receptor blockers.Transplantation and Graft Rejection
Transplant rejection:Solid organ transplantation inevitably stimulates an aggressive immune response by the recipient, unless the transplant is between monozygotic twins.
The type and severity of the rejection response is determined by the genetic disparity between the donor and recipient, the immune status of the host and the nature of the tissue transplanted. The most important genetic determinant is the difference between donor and recipient HLA proteins.
The extensive polymorphism of these proteins means that donor HLA antigens are almost invariably recognised as foreign by the recipient immune system, unless an active attempt has been made to minimise incompatibility.
Classification of transplant rejection:
Hyperacute rejection results in rapid and irreversible destruction of the graft. It is mediated by preexisting recipient antibodies against donor HLA antigens, which arise as a result of previous exposure through transplantation, blood transfusion or pregnancy. It is very rarely seen in clinical practice as the use of screening for anti-HLA antibodies and pre-transplant cross-matching ensures the prior identification of recipients with antibodies against a potential donor.
Acute cellular rejection is the most common form of graft rejection. It is mediated by activated T lymphocytes and results in deterioration in graft function. If allowed to progress, it may cause fever, pain and tenderness over the graft. It is usually amenable to increased immunosuppressive therapy.
Acute vascular rejection is mediated by antibody formed de novo after transplantation. It is more curtailed than the hyperacute response because of the use of intercurrent immunosuppression, but it is also associated with reduced graft survival.
Aggressive immunosuppressive therapy is indicated, and physical removal of antibody through plasmapheresis may be effective.
Chronic allograft failure, also known as chronic rejection, is a major cause of graft loss. It is associated with proliferation of transplant vascular smooth muscle, interstitial fibrosis and scarring. The pathogenesis is poorly understood but contributing factors include immunological damage caused by subacute rejection, hypertension, hyperlipidaemia and chronic drug toxicity.