Medical Literature - 1979

Sheffer AL, Fearon DT, Austen KF. 10/1979 Journal of Allergy & Clinical Immunology

Oct;64(4):275-280

Daily therapy and alternate-day therapy with the attenuated androgen oxymetholone were compared in patients with hereditary angioedema (HAE). Fifteen of 16 patients who experienced at least monthly attacks of HAE without treatment were asymptomatic on administration of 5 mg oxymetholene daily. When 13 of the patients who had been maintained asymptomatically on 5 mg oxymetholone daily were advanced to a treatment schedule of 5 mg every other day, seven attacks occurred during a cummulative 50 mo of therapy. The adverse effects that occurred with daily oxymetholone therapy largely subsided when the patients received alternate-day therapy, while a significant mean rise in C4 protein and function occurred only on daily therapy. Statistically significant mean increases in serum levels of C1INH occurred with daily therapy and were maintained with alternate-day therapy. Clinical benefit can be obtained with a treatment program that does not produce a statistically significant rise in C4 protein or function and does not raise C1INH to the lower limit of normal. The finding that alternate-day therapy diminished the side effects of the drug while affording a substantial reduction in the incidence and severity of attacks indicates the feasibility of this therapeutic approach.

Available online at: jacionline.org/article/0091-6749(79)90144-1/

Atkinson JP 6/1979 Annals of Allergy, Asthma & Immunology

In summary, HAE is a dominantly inherited form of angioedema which is manifested by nonpainful, nonerythematous, nonpruritic and nonpitting swelling of the extremities, face, gastrointestinal and respiratory tracts unaccompanied by urticaria. These patients have deficient activity of the C1 INH and the laboratory diagnosis can be easily made by finding low C4 and C1 inh levels during an attack. Effective and specific therapy is now available that prevents the clinical syndrome and corrects the serologic hallmarks of the disease. [References: 21].

42(6):348-352

Not available online.

Frank MM. 11/1979 Arthritis & Rheumatism

Nov;22(11):1295-1299.

Available online at: onlinelibrary.wiley.com/doi/10.1002/art.1780221118/abstract (small fee)

Donaldson VH. 11/1979 Disease-A-Month

Nov;26(2):1-37.

Available online at: diseaseamonth.com/article/S0011-5029%2879%2980015-2/pdf (small fee)

Gadek JE, Hosea SW, Gelfand JA, Frank MM. 7/1979 The Journal of Clinical Investigation

Jul;64(1):280-286

Hereditary angioedema (HAE), an auto-somal dominant disorder characterized by attacks of episodic edema is associated with decreased functional levels of the C1 esterase inhibitor. Approximately 85% of patients have lowered antigen levels of a normal inhibitor protein. 15% of patients have normal or elevated antigenic levels of functionless protein. We have examined the response to danazol therapy of patients with the variant HAE phenotypes possessing the abnormal protein in an effort to determine if these patients possess a normal structural C1 inhibitor allele. Four patients with a variant HAE phenotype were treated successfully with danazol. In two patients, distinguished by the presence of a functionless, albumin-bound, C1 inhibitor (phenotype 2), phenotypic analysis of the danazol response by bidirectional immunoelectrophoresis revealed the appearance of the normal C1 inhibitor gene product during danazol therapy. This relatively cathodal C1 inhibitor peak appears in conjunction with the development of nearly normal functional activity. All of the functional C1 inhibitory activity which appeared in the phenotype 2 treatment serum was associated with the electrophoretically normal inhibitor. This normal protein could be separated from the functionless inhibitor protein by immunoadsorption and molecular sieve chromatography. Danazol therapy of the two patients with an electrophoretically normal, functionless C1 inhibitor (phenotype 3) also resulted in a clinical remission associated with development of a significant increment in functional serum C1 inhibitory activity and C1 inhibitor protein. These findings demonstrate that these two HAE phenotypic variants are heterozygous for the normal serum C1 inhibitor, a finding which was not apparent before phenotypic analysis of this serum during danazol therapy. These data provide strong evidence for a basic similarity between the common form of HAE and its phenotypic variants. They also suggest that a structural gene lesion may result in the abnormalities of serum C1 inhibitor function and disease expression in all three of these HAE phenotypes.

Available online at: ncbi.nlm.nih.gov/pmc/articles/PMC372115/

Warin AP, Gatecliff M, Greaves MW, Warin RP, Williamson DM. 7/1979 British Journal of Dermatology

Jul;101(Suppl 17):18-19.

Not available online.