Signs and symptoms preceding acute attacks of hereditary angioedema: results of three recent surveys.

In patients with hereditary angioedema (HAE), premonitory symptoms ("prodromes") may appear hours to days before attack onset. It remains to be determined if prodromes could be useful indicators for early treatment initiation. Most published reports of prodromes have been limited to case reports or small case series. The common objective of several recent survey-based studies was to collect information relevant to prodromal patterns in patients with HAE. Three separate surveys solicited prodromal data from HAE patients. Although differences in survey methodologies permit only descriptive analysis of data, responses to the surveys provide the largest compilation of observational data on this topic to date. Prodromes were reported by 82.5-95.7% of patients surveyed. In one survey, about two-thirds of subjects reported experiencing prodromes before all or most acute HAE attacks, and only 6% of subjects noted the appearance of prodromes in <10% of all attacks. The most common types of prodromal symptoms were related to skin/soft tissue and gastrointestinal tract. Most prodromes were experienced hours to days before the onset of angioedema. A large percentage of surveyed subjects indicated being able to predict an impending HAE attack all or most of the time; <10% reported being rarely or never able to predict an attack. Although insufficient to establish the clinical role of prodromal symptoms, results of these surveys provide additional data on the scope of prodromes and could stimulate further research into the potential efficacy and cost-effectiveness of HAE attack prediction and prodrome-triggered interventions.

Per-attack reporting of prodromal symptoms concurrent with C1-inhibitor treatment of hereditary angioedema attacks.

INTRODUCTION: Prodromal symptoms commonly precede hereditary angioedema (HAE) attacks. There is continuing interest in evaluating prodromes as treatment indicators, but a paucity of relevant data. This study was designed to prospectively identify prodomal characteristics in patients voluntarily reporting such information around the time of seeking treatment for an acute HAE attack. METHODS: Twenty-eight patients with HAE were enrolled in this survey, which was conducted in the context of an open-label study of treatment of HAE attacks with plasma-derived C1-inhibitor concentrate. At the time of treatment, patients were encouraged to answer survey questions about prodromal symptoms preceding that particular HAE attack. RESULTS: Twenty-one patients provided prodromal information for 253 treated HAE attacks. Seventy-one percent of patients (15/21) reported prodromes. Three patients accounted for approximately 80% of the attacks and 89% of the reported prodromal symptoms. Prodromes were experienced before 67.6% (171/253) of attacks, with a mean of 1.4 prodromes per attack. Fatigue was the most frequent prodrome (42% of attacks), followed by nausea (26%), and flu-like symptoms (22%). The median duration of a prodrome before an attack was 12 h (range, 0.33-24 h). CONCLUSIONS: Despite many limitations in the study design, these findings confirm that prodromes are frequently associated with HAE attacks in many patients and occur sufficiently early to allow time for treatment initiation. The frequency of "false positive" prodromal symptoms remains undetermined, and the authors captured data only on attacks severe enough to warrant treatment. Additional well-designed prospective studies are clearly needed to continue investigating the potential clinical relevance of prodromes.

Frequency, timing, and type of prodromal symptoms associated with hereditary angioedema attacks.

Hereditary angioedema (HAE) types I and II are autosomal dominant conditions characterized by recurrent attacks of edema formation in the subcutaneous tissue of the body or walls of the upper respiratory or gastrointestinal tract. Frequently, prodromal symptoms occur before an HAE attack. If certain prodromal symptoms were determined to be both sensitive and specific in predicting an acute HAE attack, treatment at the time of the prodrome could prevent development of an attack and decrease morbidity and mortality associated with HAE. The goal is to determine the frequency and timing of prodromal symptoms occurring before HAE attacks. After Institutional Review Board approval, a four-page survey was produced, using a focus group of patients with HAE and was assessed by HAE patients and physicians with expertise in HAE for cognitive reliability. Once devised, the questionnaire was sent to 158 HAE patients. The survey focused on questions related to prodromal symptoms that patients developed before their last HAE attack. Forty-six patients returned the survey and 40 (87.0%) reported the presence of prodromal symptoms before their last HAE attack. Forty-four of 46 (95.7%) reported having had prodromal symptoms before HAE attacks in the past. The most commonly reported prodromal symptoms included unusual fatigue, rash, and muscle aches. Prodromes occur frequently before HAE attacks. This high frequency suggests that prodromal symptoms could be a reliable indication to begin treatment to prevent an acute HAE attack, thus decreasing the anxiety associated with having an HAE attack.

Treatment of hereditary angioedema with plasma-derived C1 inhibitor.

BACKGROUND: Plasma-derived C1 inhibitor (C1-INH) concentrate is a treatment option for acute hereditary angioedema (HAE) attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efficacy as required by the FDA. OBJECTIVE: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks. METHODS: THE FOLLOWING KEYWORDS WERE SEARCHED IN PUBMED AND OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efficacy and the safety of C1-INH concentrate. RESULTS: The English-language literature search revealed several studies showing significantly improved relief of HAE symptoms with the administration of C1-INH concentrate - many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years. CONCLUSION: C1-INH concentrate appears to be a very safe and effective treatment option for HAE.