Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor.

BACKGROUND: Hereditary angioedema (HAE) is often caused by low serum levels or functional deficiency in C1 inhibitor (C1-INH); however, in some cases, C1-INH serum level and function are measured as normal (HAE-nl-C1INH). Management of HAE-nl-C1INH is similar to management of HAE with C1-INH deficiency, including on-demand therapy for angioedema attacks and, potentially, prophylaxis. Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated for treatment of acute HAE attacks. This study assessed the clinical profile and treatment outcomes in an HAE-nl-C1INH population with a history of rhC1-INH treatment. METHODS: Medical records containing patient-reported outcomes from ten US treatment centers were analyzed retrospectively for medical history, angioedema attack characteristics, attack treatments, and clinical outcomes. RESULTS: Twenty-three patients were included, with wide US geographic representation. Most patients (87.0%) were female; median age was 36.0 years (range, 19-67 years). Of 20 patients with available data, 4 had their first angioedema attack during childhood (aged <12 years), 3 during adolescence (aged 12-17 years), and 13 during adulthood (aged 18-29 years, n = 7; aged ≥30 years, n = 6). Median age at HAE-nl-C1INH diagnosis was 31.5 years (range, 9-59 years). Previous failed treatments included high-dose antihistamines (n = 20) and corticosteroids (n = 20). Use of US Food and Drug Administration (FDA)-approved HAE therapy positively impacted patient-reported assessments of angioedema attacks. Most patients were taking rhC1-INH or lanadelumab as prophylaxis and icatibant or rhC1-INH for acute management. Most patients reported improved disease control with these therapies, including reductions in angioedema attack frequency and severity. Although most patients were receiving prophylactic therapy, availability of treatment for breakthrough attacks was important. CONCLUSION: Findings from this retrospective study support use of FDA-approved HAE medications for prophylaxis and acute treatment of HAE attacks in patients with HAE-nl-C1INH. Individualized HAE treatment regimens were needed to optimize therapeutic outcomes.

A case of successful acyclovir desensitization in a bone marrow transplant patient.

INTRODUCTION: The incidence of acyclovir-induced hypersensitivity is rare. To our knowledge, there are four published case reports of oral acyclovir desensitization in adults. Evidence-based guidelines prompt the use of acyclovir for herpes simplex virus (HSV) prophylaxis and treatment. Literature on the cross-reactivity of structurally similar antiviral agents is conflicting, presenting a clinical challenge when choosing an alternative agent. This is a case of successful acyclovir desensitization in an allogeneic stem cell transplant patient. CASE REPORT: A 69-year-old female patient, diagnosed with myelodysplastic/myeloproliferative neoplasm, presented to the hospital for donor mismatch allogeneic bone marrow transplant. The patient reported acyclovir-induced angioedema while receiving treatment for non-complicated herpes zoster (shingles) infection.Management & Outcome: After the acyclovir oral desensitization was conducted in an ICU setting with 1:1 patient-nurse ratio, the patient was successfully started on acyclovir therapy, 800mg by mouth twice daily for HSV prophylaxis with no further complications. Discussion: Oral acyclovir desensitization can provide an option for HSV therapy in patients reporting severe allergy.

Skin prick/puncture testing in North America: a call for standards and consistency.

BACKGROUND: Skin prick/puncture testing (SPT) is widely accepted as a safe, dependable, convenient, and cost-effective procedure to detect allergen-specific IgE sensitivity. It is, however, prone to influence by a variety of factors that may significantly alter test outcomes, affect the accuracy of diagnosis, and the effectiveness of subsequent immunotherapy regimens. Proficiency in SPT administration is a key variable that can be routinely measured and documented to improve the predictive value of allergy skin testing. METHODS: Literature surveys were conducted to determine the adherence to repeated calls for development and implementation of proficiency testing standards in the 1990's, the mid-2000's and the 2008 allergy diagnostics practice parameters. RESULTS: Authors publishing clinical research in peer-reviewed journals and conducting workshops at annual scientific meetings have recommended proficiency testing based primarily on its potential to reduce variability, minimize confounding test results, and promote more effective immunotherapeutic treatments. Very few publications of clinical studies, however, appear to report proficiency testing data for SPT performance. Allergen immunotherapy recommendations are updated periodically by the Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the Joint Council of Allergy, Asthma and Immunology (JCAAI). CONCLUSIONS: Despite consensus that all staff who perform SPT should meet basic quality assurance standards that demonstrate their SPT proficiency, the gap between recommendations and daily practice persists. By embracing standards, the accuracy of SPT and allergy diagnosis can be optimized, ultimately benefiting patients with allergic disease.