Michael J. Prematta

Fresh frozen plasma for the treatment of hereditary angioedema.

BACKGROUND Fresh frozen plasma (FFP) has been used as a treatment option for patients with hereditary angioedema (HAE) because it contains Cl esterase inhibitor, and alternate therapies are not yet available in the United States. However, because FFP also contains other substrates, it has been hypothesized to have the potential to worsen or precipitate an acute attack of HAE. OBJECTIVE To research patient records and the medical literature to determine whether FFP can exacerbate symptoms or precipitate an attack of HAE. METHODS The following keywords were searched in PubMed and OVID: hereditary angioedema, angioedema and fresh frozen plasma, angioedema and FFP, and hereditary angioneurotic edema. English-language articles were searched from 1966 to the present. Also, after institutional review board approval, the medical records of patients with HAE at our institution who have received FFP since 1990 were reviewed to determine if there was evidence that FFP exacerbated the symptoms of HAE. RESULTS The English-language literature review and our patient medical record review failed to identify instances when FFP exacerbated symptoms of HAE or precipitated an attack. Several reports and our experience suggest that FFP is an effective prophylactic agent before surgery and for treatment of acute HAE attacks without evidence of exacerbation or initiation of symptoms. CONCLUSIONS FFP seems to be safe and effective in preventing exacerbations of HAE before surgery and for acute exacerbations of HAE without evidence of it initiating an attack or worsening a preexisting attack.

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.

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

IntroductionProdromal 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.MethodsTwenty-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.ResultsTwenty-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).ConclusionsDespite 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.

A sixty-five-year-old man with rash, fever, and generalized weakness.

Diffuse erythematous rash accompanied by high-grade fever, eosinophilia, and facial edema can be caused by a variety of infective, allergic, or systemic etiologies. We present a case of 65-year-old man with septic arthritis, who had a vancomycin antibiotic spacer placed in his infected knee and was also started on intravenous (i.v.) vancomycin. After 2 weeks he presented with sudden onset of fever and generalized weakness. Physical examination was significant for tachycardia and hypotension, facial edema, diffuse erythematous rash, and bilateral wheezing. Laboratory values indicated acute renal insufficiency associated with eosinophiluria and significant peripheral eosinophilia. Septic shock was highly suspected and he was treated with i.v. fluids and broad-spectrum antibiotics. Despite aggressive management his condition rapidly deteriorated with persistent of shock state, increase in facial edema, and rash. Other suspected etiologies included hypersensitivity reactions to i.v. antibiotics (piperacillin/tazobactam) or vancomycin, systemic vasculitis, or idiosyncratic reactions to medications such as Stevens-Johnson syndrome. The patient was started on high-dose i.v. steroids, which led to improvement of his clinical condition. Clinical presentation of adverse drug reactions is highly variable and may present as potentially life-threatening multiorgan failure. Early recognition of the etiology and removing the offending agent is important to improve the outcome.