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A number sign (#) is used with this entry because hereditary angioedema types I and II are caused by heterozygous mutation in the C1 inhibitor gene (C1NH. Download Citation on ResearchGate | Angioedema hereditario | Hereditary angioedema is a rare disease of genetic origin that is characterized by recurrent . Request PDF on ResearchGate | On Feb 26, , Teresa Caballero Molina and others published Angioedema hereditario.

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CC HPO: C ] – Several patients with homozygous C1NH mutations have been reported see Hereditary angioedema HAE is an autosomal dominant disorder characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. There are 2 classic types of the disorder. In type II, the levels are normal or elevated, but the protein is nonfunctional.

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The 2 types are clinically indistinguishable. Zuraw provided a detailed review of the clinical features, management, and pathogenesis of hereditary angioedema. Edema of the larynx and other portions of the airways is the most fearsome feature of this disorder.

Visceral involvement with abdominal pain can lead to unnecessary laparotomy Weinstock et al. A year-old man, 2 heteditario his brothers, his mother, and his daughter were affected. In addition to abdominal pain, nausea, diarrhea, and vomiting occurred, but there were no cutaneous, oropharyngeal, or respiratory manifestations. Barium studies during painful attacks showed transient intestinal wall edema.

In rare patients the deficiency is acquired, with symptoms first emerging well into adulthood. These patients had hreditario evidence of an underlying disease, followed a benign course, and showed variable responses to therapy.

Frigas described a patient with acquired C1 inhibitor deficiency who had no hereditatio of underlying disease 11 years after onset. They reported the occurrence of systemic lupus erythematosus and glomerulonephritis in patients with this disorder.

Nerve conduction studies indicated a sensorimotor axonal peripheral neuropathy. Peripheral nerve biopsies showed enlarged nerves with vasculitis and lymphocytic infiltration; most of the proliferating capillaries were strongly positive for anti-C1q, consistent with activation of the classic complement pathway. There was also a decrease of myelinated fibers and axonal degeneration. The patient’s asymptomatic mother and sister were also found to have decreased serum C1INH, prompting the diagnosis of HAE, which was confirmed by genetic analysis.

Angioedema due to acquired C1 inhibitor deficiency has been associated with benign or malignant B-cell lymphoproliferative disorders such as chronic lymphocytic leukemia, multiple myeloma, or essential cryoglobulinemia Gelfand et al.

Frigas reported a patient with angioedema associated with a B-cell lymphoproliferative disorder that became evident 9 months after C1NH deficiency was diagnosed. In 1 subject in an affected family, the C1 inhibitor level determined at birth in cord blood was inconclusive.

Later the measurement showed a level in agreement with the diagnosis predicted by DNA analysis. Three types of C1 esterase inhibitor were described by Rosen et al. Immunologically, one group had levels angioeedma inhibitor an alpha-2 neuraminoglycoprotein Although immunologically identical, the three types of inhibitor differed in electrophoretic and other characteristics from the normal and from each other.


From immunofluorescence studies, Johnson et al. On the basis of in vivo turnover studies, Quastel et al. This, in turn, could lead to consumption of normal C1 inhibitor that falls below normal. Although the hepatocyte is the main site of synthesis of the inhibitor, cultured human peripheral blood monocytes also synthesize and secrete this protein. The Northern blot analysis showed inhibitor mRNA to be present at about half-normal concentrations. One of the patients showed a genetically abnormal mRNA 1.


Rates of synthesis of both wildtype and mutant proteins were lower than predicted from the mRNA levels. There was no evidence of increased C1NH protein catabolism.

In an editorial, Cicardi and Agostoni used an instructive diagram hereditairo demonstrate the pathophysiology of hereditary angioedema. A considerable number of kindreds with angioneurotic edema transmitted in a typical autosomal dominant pattern have been described. In the family studied by Triggabout twice as many males as females were affected.

A family studied by Donaldson and Rosen had previously been reported by Heiner and Blitzer Cohen described a family with many cases angioddema 5 generations. Although reported as giant urticaria, the same family was studied by Rosen et al. In contrast, heterozygotes for this hereditarko had C1 inhibitor within the normal range, although often at its lower level, and were free of angioedema attacks. These results suggest autosomal recessive inheritance of this mutation.

Spaulding and Dennehy described apparently effective prophylaxis with angioeedma, and Frank et al. The therapeutic benefit of Danazol, an ‘impeded’ androgen, is of interest from the point of view of the basic defect in this disorder Gelfand et al. Danazol also raises the levels of the deficient protein in alphaantitrypsin deficiency Gadek et al.

Androgen derivatives were useful for long-term prophylaxis. Borum and Howard stated that prophylactic therapy with attenuated androgens or antifibrinolytic agents is useful, and that plasma concentrate of C1NH is the treatment of angioedmea in an acute episode.

The concentrate was vapor-heated to inactivate hepatitis and human immunodeficiency viruses. A total of 68 subjects 35 in the C1 inhibitor group and 33 in the placebo group were given 1 or 2 intravenous injections of the study drug 1, units each. The primary endpoint was the time to the onset of unequivocal relief.

The second study was a crossover trial involving 22 subjects with hereditary angioedema hereditagio compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate 1, units with placebo during two week periods.

The primary endpoint was the number hereditxrio attacks of angioedema per period, with each subject acting as his or her own control.

In this study, the number of attacks per week period was 6. Patients were evaluated using treatment outcome scores and change from baseline in the mean symptom complex severity score. The primary endpoint was the treatment outcome score 4 hours after study-drug administration.

A total of 71 of the 72 patients angioedeka the trial. The median treatment outcome score at 4 hours was The median change in the mean symptom complex severity score at 4 hours was There were no herdeitario, treatment-related serious adverse events, or withdrawals owing to adverse events.

Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary anfioedema was the median time to clinically significant relief of symptoms. The primary endpoint was reached in 2. In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication.

The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported.

In an accompanying editorial to the articles by Zuraw et al. Wuillemin commented on the studies of Zuraw et al. He also mentioned the successful experience in Switzerland of C1 inhibitor hdreditario self-administration, with regular practical training, for hereditary angioedema patients, and concluded that self-administration leads to better medical outcome and enhanced quality of life.


Morgan noted that guidelines and requirements for possession and self-administration of C1 inhibitor would exclude many patients, including children, and that practitioners fear that drug use would escalate as patients treat minor swellings or false prodromes. He suggested that the Swiss experience might provide reassurance about these matters, and that available data should be disseminated.

Referring to the studies of Cicardi et al. Cicardi and Banerji replied that since their studies were performed in accordance with both the Declaration of Helsinki and expert consensus, they considered them ethically acceptable. They suggested that prophylaxis against attacks should not be used during pregnancy heresitario that severe attacks should be treated with purified C1NH concentrate. Cox and Holdcroft discussed the management of pregnancy and delivery in a year-old primiparous woman with a history of type I HAE first diagnosed at age She had been treated with an attenuated androgen in low dose danazol and then amicarwhich raised her C1 esterase inhibitor level and controlled her symptoms.

Danazol rendered the patient oligomenorrheic. Since it is also teratogenic Duck and Katayama,it was withdrawn under hospital observation when she decided to start a family. The recurrent symptoms were controlled with intravenous administration of C1 esterase inhibitor. Vaginal delivery in HAE may be impeded by perineal edema and abdominal pain may obscure obstetric disorders. In this case, successful spontaneous vaginal delivery was achieved using prophylactic C1 esterase inhibitor and epidural analgesia.

Their results indicated that a defective structural gene was responsible for the disease. The 2 forms are clinically indistinguishable. Clinical and laboratory findings of both parents and relatives were normal. The mutation occurred on the maternally transmitted chromosome, but was not detected in DNA derived from the mother’s buccal cells, urinary cells, hair roots, or cultured fibroblasts, suggesting that the mother was a true gonadal mosaic.

Quincke first described and named angioneurotic edema. Oslerwhile in Philadelphia, was first to describe the hereditary form. Dennehy called attention to the herediitario that Nathaniel Hawthorne was apparently familiar with this disorder for in his ‘House of the Seven Gables’ he described a family with members who gurgled in the throat and chest when excited and who would sometimes die this way, ever since a curse to choke on blood had been placed on 1 of their ancestors.

Dennehy interpreted the following passage as an indication that Hawthorne recognized that a hereditary disease, not a curse, was responsible for the deaths: Old Maule’s prophecy was probably founded on a knowledge of this physical predisposition in the Pyncheon race. Six years before Quincke introduced the term angioneurotic edema, Milton described 1 of his patients with angioedema in the following words: Linkage to HLA gereditario excluded by Eggert et al.

In hereditarioo linkage studies, Olaisen et al. Hereditary and acquired C1-inhibitor deficiency: The ‘cure’ of an inherited disease. Autoantibody-mediated acquired deficiency of C1 inhibitor. Detection of hereditary angioneurotic edema by demonstration of a reduction in the second component of angiosdema complement. De novo homozygous mutation of the C1 inhibitor gene in a patient with hereditary angioedema. First case of homozygous C1 inhibitor deficiency.