New Instrument for the Evaluation of Prodromes and Attacks of Hereditary Angioedema (HAE-EPA).

A disease-specific, patient-reported outcome instrument suitable for evaluation of prodromes and attacks of hereditary angioedema (HAE) is a clinical unmet need. We constructed such instrument and examined its validity, acceptability, and discriminative ability. Sixty-six patients participated in a survey addressing their demographics, social, and medical status. Discriminant content validity involved: (1) construct definition by in-depth cognitive debriefing interviews, (2) item selection identifying relevant categories, and (3) judgment of the format whereby questionnaires were tested on experienced patients and its content/reliability was validated. Prodromes and attacks affecting certain body systems (domains) were organized in "clusters". Internal consistency, content, and convergent validities were analyzed. Analyses of variance and regression models were used to evaluate the discriminative ability of the instrument to differentiate between attacks and prodromes. The study demonstrates very high internal consistency (Cronbach's α: attacks 0.88-0.98, prodromes 0.78-0.98). Analysis of variance confirmed significant differences between all dimensions and in pre-defined clusters (F (4, 61) = 45.74, p < 0.001, Eta2 = 0.77). Significant correlations were found between dimensions of prodromes and attacks. Prodromes are associated but differentiated from attacks. Correlations in severity were high for all domains. Interactions were found between prodromes and patients' experience in illness. In conclusion, the new Prodrome-Attack Evaluation questionnaire (HAE-EPA) is capable of distinguishing attacks and prodromes of HAE, as well as determining associations between the two interrelated phenomena. The new instrument achieves the required discriminative ability, acceptability, and content validity/reliability and therefore can be used as a reliable tool for the investigation of prodromes, attacks, and their relationships.

The Enigma of Prodromes in Hereditary Angioedema (HAE).

A prodrome is a premonitory set of signs and symptoms indicating the onset of a disease. Prodromes are frequently reported by hereditary angioedema (HAE) patients, antedating attacks by a few hours or even longer. In some studies, high incidence of prodromes was reported by patients, with considerable number being able to predict oncoming attacks. Regrettably, prodromes have never received a consensual definition and have not been properly investigated in a systematic fashion. Therefore, their nature remains elusive and their contribution to the diagnosis and treatment of disorders is uncertain. The term "prodrome," as used in various pathologies, denotes different meanings, timing, and duration, so it may not be equally suitable for all clinical situations. Perception of a prodrome is unique for each individual patient depending on self-experience. As modern drugs delegate the administration decision to the patients, early detection of a developing attack may help mitigate its severity and allow deployment of appropriate therapy. New diagnostic instruments were recently developed that can assist in defining the attributes of prodromes and their association with attacks. We will review the prodrome phenomenon as exhibited in certain clinical situations, with an emphasis on prodromes of HAE.