INTRODUCTION:

Angiotensin-converting enzyme (ACE) inhibitors cause angioedema due to diminished degradation of bradykinin. Angiotensin receptor blockers may occasionally cause angioedema but the mechanism is unknown, and are generally considered safe, even in those who have reacted to ACE inhibitors. We determined whether aliskiren, a renin inhibitor, has an effect on the rate of bradykinin degradation.

METHODS:

The ability of renin to metabolize bradykinin was studied and the rate of bradykinin degradation compared in the presence or absence of aliskiren. Enalapril, a known ACE inhibitor that causes angioedema served as positive control.

RESULTS:

Renin was unable to digest bradykinin, indicating that a renin inhibitor is unlikely to affect the rate of bradykinin degradation. In a plasma system, aliskiren had no effect on the rate of bradykinin degradation while enalapril inhibited it appreciably. An inhibitory effect of aliskiren on the rate of bradykinin degradation by human pulmonary endothelial cells was observed, estimated to be about 5% of that of enalapril.

CONCLUSION:

Aliskiren has no effect upon the rate of bradykinin degradation in plasma and a minimal effect employing vascular endothelial cells. The latter suggests inhibition of a non-renin enzyme that is a minor contributor to bradykinin degradation.

IMPORTANCE Isotretinoin is frequently prescribed for the treatment of acne vulgaris. Among the numerous documented adverse effects, most common are xerostomia and cheilitis. Lip abscesses as a consequence of cheilitis present dramatically and may pose a diagnostic challenge. OBSERVATIONS We present a case of a 15-year-old boy with a severe lip abscess requiring incision and drainage and hospital admission for intravenous antibiotic treatment of methicillin-resistant Staphylococcus aureus. We discuss the pathophysiologic characteristics of isotretinoin therapy and the likely causative role that the medication played in the development of the lip abscess.

CONCLUSIONS

AND RELEVANCE Although rare, lip abscesses related to isotretinoin therapy present with substantial morbidity and should be promptly recognized. Misdiagnosis of mucositis and angioedema may delay appropriate therapy.

GOALS:: The objective of this study was to better understand the presenting signs and symptoms of angiotensin converting enzyme (ACE) inhibitor-induced gastrointestinal angioedema, review the medical literature related to this condition, and bring this diagnosis to the attention of clinicians.

BACKGROUND::

Angioedema occurs in 0.1% to 0.7% of patients treated with ACE inhibitors and ACE inhibitors account for 20% to 30% of all angioedema cases presenting to emergency departments. However, only recently have ACE inhibitors been recognized as a cause of angioedema of the gastrointestinal tract. Patients with this disease present with one or more episodes of abdominal pain associated with nausea, vomiting, and/or diarrhea. STUDY:: We present four cases of ACE inhibitor-induced gastrointestinal angioedema seen at a single institution and review the literature of other case reports.

RESULTS::

Review of the medical literature identified 27 case reports of ACE inhibitor-induced angioedema of the gastrointestinal tract. Multiple ACE inhibitors were implicated in these case reports suggesting that this disease is a class effect of ACE inhibitors. In cases where the race of the patient was stated, 50% were identified as being African American. Ascities was described as a radiographic finding in 16 of 27 cases. There were no reported cases of paracentesis or ascitic fluid analysis described in any of the identified case reports.

CONCLUSIONS::

This series highlights ascites as a key feature that distinguishes ACE inhibitor-induced gastrointestinal angioedema from infectious enteritis. This series also confirms the increased incidence of this condition among African American women, an unpredictable interval between medication initiation and the development of symptoms, and the heightened probability of symptom recurrence if ACE inhibitors are not discontinued. ACE inhibitor-induced gastrointestinal angioedema is a rare cause of acute abdominal complaints, but is likely underdiagnosed and should be considered in the differential diagnosis of all individuals taking ACE inhibitors with such symptoms. Early recognition of ACE inhibitor-induced gastrointestinal angioedema may avoid recurrent episodes or costly, invasive evaluations.

Objective:

The purpose of this review was to evaluate blood pressure (BP) reductions and adverse events between patients younger than 65 and older than 65 years of age receiving a combination of an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin receptor blocker (ARB).

Design:

A retrospective cohort study comparing the effectiveness of ACE-I and ARB combination in patients < 65 (younger) and ≥ 65 years of age (elderly).

Setting:

This study was conducted at the VA Western New York Healthcare System.

Participants:

A total of 176 patients: 54 patients in the younger group and 122 in the elderly cohort.

Interventions:

No specific interventions were performed.Main Outcome Measures: The purpose was to evaluate differences in BP reductions and incidence of adverse events in younger and elderly patients receiving a combination of an ACE-I and an ARB.

Results:

In the elderly group (mean age 76), the mean reduction in standing blood pressure (SBP) was 14.2 ± 15.6 mmHg (95% confidence interval [CI] 11.2-17.3; P < 0.0001). Similar results were obtained in the younger group (mean age 59), with a mean SBP reduction of 10 ± 14.9 (95% CI 5.6-14.5; P < 0.0001). The mean SBP reduction was not significantly different between the two age cohorts (P = 0.57). The incidence of adverse events was not different between the two age groups (cough P = 0.67, hyperkalemia P = 1.0, angioedema P = 0.31).

Conclusion:

There was no significant difference in effectiveness or safety between the elderly and younger cohorts. The pharmacist monitoring elderly patients on combination therapy should still closely follow these patients; however it is reassuring that elderly patients do not experience adverse reactions at rates higher than do younger patients.

PURPOSE OF REVIEW:

Since angiotensin-converting enzyme inhibitors (ACEIs) were first introduced in the 1980s for treatment of hypertension and congestive heart failure, there has been progressive increase in use due to these and other new indications. This fact has led to a parallel increase in adverse effects induced by ACEIs, mainly angioedema, with different degrees of severity.

RECENT FINDINGS:

Different studies indicate that ACEI-induced angioedema is associated with high levels of bradykinin of different origin and this preferentially occurs in females and in African-American populations. The diagnosis of ACEI-induced angioedema can be difficult, due to its variable latency period from the initiation of treatment. Differential diagnosis of other causes of angioedema must be considered. The management of ACEI-induced angioedema involves the withdrawal of the causative drug and the treatment of the reaction with different drugs depending on its severity. Some studies have shown that angiotensin II receptor blockers (ARBs) may be an alternative, although some patients (<10%) with ACEI-associated angioedema also develop angioedema episodes after ARB intake. Therefore, ARBs may be reserved for patients with high therapeutic need for angiotensin inhibition.

SUMMARY:

The present review will focus on current and relevant aspects of ACEI-induced angioedema. The pathological mechanism, epidemiology and risk factors, differential diagnosis, patient management and treatment will be discussed.

Chronic spontaneous urticaria (CSU) is a common skin disorder with etiology that is not well understood.In this study, we evaluated the prevalence of autologous serum skin test (ASST) and skin prick testing (SPT) to house dust mite (HDM) in 862 CSU cases in China. Clinical features, courses and treatment responses were also recorded.The prevalence of positive ASST was 46.3%, and patients aged 30-39 years had the highest positive rate (52.1%). Positive SPT to HDM was seen in 153 patients (17.7%) with the highest positive rate (34.2%) in patients aged 20 or less. Patients with positive ASST had higher urticaria activity scores (UAS) (4.18±0.65 vs. 3.67±0.53) but lower positive rates of HDM (24.6% vs. 37.6%), as compared with those with negative ASST (odds ratio (OR) 1.84, 95% CI 1.38-2.47). Patients could be categorized into four groups based on the results of ASST and SPT to HDM and patients with positive ASST and positive SPT to HDM had the highest disease activity scores, experienced higher frequencies of angioedema, diseases duration, and required higher dosage of loratadine every month, compared with other subgroups (P<0.0001).Patients with CSU showed varied responses of positive ASST and varied sensitivity to HDM, Patients with positive ASST and/or positive SPT had more disease activity compared with patients with negative ASST and/or negative SPT. Further classification can be made based on the result of SPT and ASST.

Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy for the treatment of hypertension, congestive heart failure, and diabetic nephropathy. ACE inhibitors are associated with adverse side effects such as persistent dry cough (ACE-cough) and, rarely, life-threatening angioedema (ACE-AE). The authors investigated the influence of ACE I/D polymorphism in combination with serum ACE activity, B2 receptor -9/+9 polymorphism, and B2 receptor C-58T single nucleotide polymorphism (SNP) on the development of ACE-AE and ACE-cough. The frequencies of ACE I/D as well as B2 receptor +9/-9 and C-58T polymorphisms were compared in patients with ACE-AE, ACE-cough, and ACE inhibitor-exposed controls, and serum ACE activity was measured. There were 52 cases of ACE-AE, 36 cases of ACE-cough, and 77 controls. The genotyping revealed a significant association between the B2 -9 allele and ACE inhibitor-induced AE (62% vs 38%, P=.008), and ACE inhibitor-induced cough (61% vs 38%, P=.02) when compared with controls. There was no significant association between ACE I/D polymorphism as well as the B2 C-58T SNP with both ACE-induced AE and cough. ACE activity was significantly higher in controls compared with patients with ACE-AE (34.5±1.14 mU/mL vs 17.8±0.86 mU/mL, P=.0001) and ACE-cough (34.5±1.14 mU/mL vs 23.3±1.88 mU/mL, P=.0001). Thus, our data suggest that the B2 -9 allele and reduced ACE activity are associated with both ACE-AE and ACE-cough.

These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. The Joint Task Force on Practice Parameters understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because the cost of a given test or agent is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In some instances the cost benefit of an intervention is considered relevant, and commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The Joint Task Force is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the Workgroup convened to draft the parameter, the Task Force Reviewers, and peer review by members of each sponsoring society. Although the Task Force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the Joint Task Force and the Practice Parameters Workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Workgroup chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias.

Classification is based on GA(2)LEN/EAACI/WAO/EDF guidelines (2009). These guidelines classify urticaria according to clinical manifestations. Urticaria is mediated by mast cells. According to level of mast cell degranulation clinical signs are superficial (Urticaria) or deep swelling (Angioedema).