A0002154 32154 No.ofPages:6 SEETHARAMAK Complement:Deficiency Diseases meningococcal meningitis.emphasizing the importance of The gastrointestinal tract can also be affected by hae the alternative pathway in host defence against meningo In fact,gastrointestinal involvement is especially common cocc in children with HAE.Symptomsar ）compared de anorex tiant he ment components.SLE and discoid lupus have also been Abdominal symptoms can occur in the absence of described in isolated patients. concurrent cutaneous or pharyngeal involvement ofsymptoms referable to HAEoccurs in more the ado C1 esterase inhibitor deficiency though trauma,anxiety and stress are frequently cited as events that initiate attacks,more than half of patients annot e ns annd cut may follow inherited in an autosomal dominant fashion.There are at least two forms of CI INH deficiency.In the most commor of HAE is divided into prophylaxis f attacks and treatn Long INH P otein (5-30%of r erm prev ho ha the less common form(type )which accounts for the suffered frequent and debilitating att acks.Antifibrinolytic vated protein is con Pof CI INH re activity leads to the angic oedema characteristic of the have been found to be useful in long-term prophylaxis of disorder are still incompletely understood Neither the HAE. These agents have not been used extensively in the ema nor the androgen ne ider oth the ally int ment system and the kinin system in the pathogenesis ofthe may need short-term prophylactic therapy (e.g.before oral oedema surgery).In these circumstances,dana therapy may be he chinical symptoms of HAE are the result of initiated one week before surgery or EACA the day before h ed by A number of drug have bee sed in an attem t to venule dilation. The three mos interrupt an attack of HAE once it has begun.Adrenaline, hal trac nt. ous thr re encouraging e impeded androgens to prevent such episodes.pharyngeal e in nearly two-thir f the Further Reading ay ini a'tightnes Colten HR and Rosen FS (1992)Complement deficiencies.Annual accompanied by hoarseness and stridor, ated with progresses to respiratory obstruction an represents a threatening nd IA and A P1976 emergency. cks usually progress for days and ma:the yndrome and its nent.Annals of Interna Attacks involving the skin may involve an extremity,the Kolble Kand Reid KBM(1993)Genetic deficiencies ofthe omplement face or genitalia.The oedema may vary in size from a few of I 10g6 nent of a whole extremity.The her thanre Tuanc Lokki MLad Colte 5)Genetic deficiencies of complement e rat and are HR045 tightness in the skin caused by Ros and Densen P()Complement deficiency states an neous fluid.but there is no pain. and other infections in an immune deficiency.:243-273. ENCYCLOPEDIA OF LIFE SCIENCES/e2001 Nameningococcal meningitis, emphasizing the importance of the alternative pathway in host defence against meningo￾cocci. These patients appear to have a particularly high mortality rate (75%) compared to complement-sufficient patients or patients with deficiencies of terminal comple￾ment components. SLE and discoid lupus have also been described in isolated patients. C1 esterase inhibitor deficiency A genetically determined deficiency of C1 esterase in￾hibitor (C1 INH) is responsible for the clinical disorder hereditary angio-oedema (HAE). C1 inhibitor deficiency is inherited in an autosomal dominant fashion. There are at least two forms of C1 INH deficiency. In the most common form (type I), which accounts for about 85% of patients, the serum of affected individuals is deficient in both C1 INH protein (5–30% of normal) and C1 INH activity. In the less common form (type II), which accounts for the remaining 15% of patients, a dysfunctional protein is present in normal or elevated concentrations, but its functional activity is markedly reduced. The pathophysio￾logical mechanisms by which the absence of C1 INH activity leads to the angio-oedema characteristic of the disorder are still incompletely understood. Neither the mediators responsible for producing the oedema nor the mechanisms initiating their production have been clearly identified, although evidence implicates both the comple￾ment system and the kinin system in the pathogenesis of the oedema. The clinical symptoms of HAE are the result of submucosal or subcutaneous oedema. The lesions are characterized by noninflammatory oedema associated with capillary and venule dilation. The three most prominent areas of involvement are the respiratory tract, skin and gastrointestinal tract. Attacks involving the upper respiratory tract represent a serious threat to the patient with HAE. Before the use of impeded androgens to prevent such episodes, pharyngeal oedema occurred at least once in nearly two-thirds of the patients. The patients may initially experience a ‘tightness’ in the throat and swelling of the tongue, buccal mucosa and oropharynx follow. In some instances, laryngeal oedema, accompanied by hoarseness and stridor, progresses to respiratory obstruction and represents a life-threatening emergency. Attacks usually progress for 1–2 days and resolve over an additional 2–3 days. Attacks involving the skin may involve an extremity, the face or genitalia. The oedema may vary in size from a few centimetres to involvement of a whole extremity. The lesions are pale rather than red, usually not warm, and are characteristically nonpruritic. There may be a feeling of tightness in the skin caused by accumulation of subcuta￾neous fluid, but there is no pain. The gastrointestinal tract can also be affected by HAE. In fact, gastrointestinal involvement is especially common in children with HAE. Symptoms are secondary to oedema of the bowel wall and may include anorexia, dull aching of the abdomen, vomiting and crampy abdominal pain. Abdominal symptoms can occur in the absence of concurrent cutaneous or pharyngeal involvement. The onset of symptoms referable to HAE occurs in more than half the patients before adolescence, but in some patients, symptoms do not occur until adulthood. Even though trauma, anxiety and stress are frequently cited as events that initiate attacks, more than half of patients cannot clearly identify an event that initiated an attack. Dental extractions and tonsillectomy can initiate oedema of the upper airway, and cutaneous oedema may follow trauma to an extremity. Therapy of HAE is divided into two categories: prophylaxis of attacks and treatment of attacks. Long￾term prevention of attacks may be indicated in those patients who have had laryngeal obstruction or have suffered frequent and debilitating attacks. Antifibrinolytic agents such as e-amnocaproic acid (EACA) have been used with some success in the long-term prevention of attacks. More recently, impeded androgens such as danazol and stanozolol, which have attenuated androgenic potential, have been found to be useful in long-term prophylaxis of HAE. These agents have not been used extensively in children, however, because of their androgenic effects. They act by stimulating the synthesis of functionally intact C1 INH by the normal gene. In some instances, patients may need short-term prophylactic therapy (e.g. before oral surgery). In these circumstances, danazol therapy may be initiated one week before surgery or EACA the day before surgery. A number of drugs have been used in an attempt to interrupt an attack of HAE once it has begun. Adrenaline, antihistamines and corticosteroids are of no proven benefit. However, recent trials with partially purified C1 INH are encouraging. Further Reading Colten HR and Rosen FS (1992) Complement deficiencies. Annual Review of Immunology 10: 809–834. Figueroa JE and Densen P (1991) Infectious diseases associated with complement deficiencies. Clinical Microbiological Reviews 4: 359–395. Frank MM, Gelfand JA and Atkinson JP (1976) Hereditary angioede￾ma: the clinical syndrome and its management. Annals of Internal Medicine 84: 580. Kolble K and Reid KBM(1993) Genetic deficiencies of the complement system associated with disease – early components. International Reviews of Immunology 10: 17–36. Lokki ML and Colten HR (1995) Genetic deficiencies of complement. Annals of Medicine 27: 451–459. Ross SC and Densen P (1984) Complement deficiency states and infections: epidemiology, pathogenesis, and consequences of neisserial and other infections in an immune deficiency. Medicine 63: 243–273. a2154 No. of Pages: 6 SEETHARAMAK Complement: Deficiency Diseases A0002154 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net 5