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Angioedema urticaria [keywords]
- Hereditary angioedema: what the gastroenterologist needs to know. [REVIEW]
- Clin Exp Gastroenterol 2014.:435-445.
Up to 93% of patients with hereditary angioedema (HAE) experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH) laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist.
- Diagnosis and Treatment of Bradykinin-Mediated Angioedema: Outcomes from an Angioedema Expert Consensus Meeting. [JOURNAL ARTICLE]
- Int Arch Allergy Immunol 2014 Nov 15; 165(2):119-127.
Several types of angioedema exist beyond hereditary angioedema (HAE) types I/II; however, the diagnostic and treatment needs of these conditions are not well understood. Noticeably, there are no licensed treatments available for other forms of angioedema beyond HAE types I/II, and similarly they are unresponsive to conventional antihistamine/glucocorticoid treatment. A group of angioedema experts met in Budapest in May 2013 to discuss such issues, presenting their experience, reviewing available literature and identifying unmet diagnostic and treatment needs in three different angioedema types: HAE with normal C1-inhibitor (C1-INH; previously referred to as type III HAE); nonallergic angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEI-AAE), and acquired angioedema due to C1-INH deficiency (C1-INH-AAE). The group identified unmet diagnostic and treatment needs in HAE-nC1-INH, C1-INH-AAE and ACEI-AAE, explored remedies and made recommendations on how to diagnose and treat these forms of angioedema. The group discussed the difficulties associated with using diagnostic markers, such as the level and function of C1-INH, C1q and C4 to reliably diagnose the angioedema type, and considered the use of genetic testing to identify mutations in FXII or XPNPEP2 that have been associated with HAE-nC1-INH and ACEI-AAE, respectively. Due to the lack of approved treatments for HAE-nC1-INH, ACEI-AAE and C1-INH-AAE, the group presented several case studies in which therapies approved for treatment of HAE types I/II, such as icatibant, ecallantide and pasteurized, nanofiltered C1-INH, were successful. It was uniformly agreed that further studies are needed to improve the diagnosis and treatment of angioedema other than HAE types I/II. © 2014 S. Karger AG, Basel.
- Subtypes of chronic Urticaria in patients attending allergy clinics in Venezuela. [Journal Article]
- Eur Ann Allergy Clin Immunol 2014 Nov; 46(6):210-5.
Chronic urticaria (CU) is one of the most puzzling clinical entities confronted by the medical profession. It is a common motive for consultation, and in a sizable proportion of patients no identifiable cause is evident. Since there are relatively few publications regarding CU in developing countries, we performed a prospective 3-year study on the demographic and clinical features of patients with CU. Four hundred and twenty-three subjects were studied, 52 children and 371 adults, 295 females (69.7%), with a mean age of 38.4 ± 17.8 years. More often, wheals and angioedema (AE) were present on the head, upper and lower limbs and the trunk. AE was present in 162 patients (38.4%). The most frequent subtypes were chronic spontaneous urticaria, aspirin-exacerbated cutaneous disease, dermographic urticaria, and combinations of various subtypes. A better understanding of the characteristics of patients suffering CU is helpful for clinicians dealing with this ailment, and provides guidance for new investigations on its pathogenesis, which will hopefully result in a better management of this vexing condition.
- Burden of Illness in Hereditary Angioedema: A Conceptual Model. [JOURNAL ARTICLE]
- Acta Derm Venereol 2014 Nov 14.
The objective of the Hereditary Angioedema Burden of Illness Study in Europe was to assess the real-world experience of HAE from the patient perspective. Based on open-ended qualitative interviews with 30 patients from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experienced unnecessary medical procedures due to diagnostic delays, anxiety and fear about attacks, and passing HAE to children, reduced work/school productivity, and limited career/educational achievement. Patient caregivers also experienced worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among the wide-ranging short- and long-term HRQoL impacts of HAE. These findings can be used to highlight important issues in clinical management, raise awareness of the patients' experience among policymakers and help guide measurement of HRQoL outcomes in future studies in HAE.
- Contact System Activation on Endothelial Cells. [JOURNAL ARTICLE]
- Semin Thromb Hemost 2014 Nov; 40(8):887-894.
When the contact system assembles and activates on negatively charged surface materials, plasma coagulation rapidly follows. This mechanism is redundant for hemostasis but mediates pathological thrombus formation, as was reported in a multitude of in vivo studies. The epidemiological data are presently scarce to firmly support a role for the contact system in human thrombotic disease, while its physiological function and mode of activation remains mysterious. Besides its role in blood coagulation in vitro, the contact system is responsible for the production of bradykinin. This inflammatory peptide is involved in episodes of pathological tissue swelling in (hereditary) angioedema, but potentially also in the physiological regulation of vascular permeability. A body of evidence indicates that contact system factors are recruited to the surface of activated endothelial cells, where proteins that are locally released can activate them. Furthermore, clinical and biochemical studies indicate that plasmin, the effector enzyme of the fibrinolytic system, can evoke contact system activation. This auxiliary role for plasmin may so far not have been fully appreciated in pathophysiology. To conclude this review, we propose a complementary model for contact system activation on the endothelial cell surface that is initiated by plasmin activity.
- Chemistry and Pharmacology of Angiotensin-Converting Enzyme Inhibitors. [JOURNAL ARTICLE]
- Curr Pharm Des 2014 Nov 12.
The renin-angiotensin system has been established as an attractive target for pharmacological intervention since the discovery of first angiotensin-converting enzyme inhibitors (ACE-Is). In fact, these drugs are primarily used in the management of cardiovascular system-related diseases and renal insufficiency. Their mechanism of action involves the adjustment of balance between vasoconstrictive, hypertrophic and salt/water-retentive angiotensin II and vasodilatory and natriuretic bradykinin by the inhibition of angiotensin II biosynthesis and bradykinin degradation. Currently there are thirteen family members approved for use in humans. They differ in structure, chemistry and pharmacokinetic and pharmacodynamic properties yet they display a similar pharmacologic and toxicologic profile. All of them are effective in the treatment of hypertension as well as in cardiac insufficiency or diabetic nephropathy. Although they are generally well-tolerated several serious side-effects including life-threatening angioedema, renal failure and persistent dry cough could occur during the administration of ACE-Is, which may require the cessation of therapy. Furthermore, to provide maximum safety and efficiency of ACE-Is-based therapy, the knowledge of the related drug interactions and chronokinetics seems to be an absolute requirement. Here we discuss the above-mentioned issues regarding the pharmaceutical and chemical properties of the commercially-used ACE-Is.
- The clinical spectrum and therapeutic management of hypocomplementemic urticarial vasculitis: data from a French nationwide study of 57 patients. [JOURNAL ARTICLE]
- Arthritis Rheumatol 2014 Nov 10.
Background: Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology, rarely described in the literature. Patients and methods: To analyze the clinical spectrum and the therapeutic management of patients with HUV, we conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histological leukocytoclastic vasculitis and hypocomplementemia. Results: Urticarial lesions were typically erythematous papules more pruritic than painful, associated with angioedema in 51%, purpura in 35% and livedo reticularis in 14%. Extra-cutaneous manifestations included constitutional symptoms (56%), musculoskeletal (82%), ocular (56%), pulmonary (19%), gastrointestinal (18%) and kidney involvement (14%). Patients with HUV typically presented with low C1q complement level and normal C1 inhibitor level, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine (HCQ) or colchicine seemed to be as effective as corticosteroids in 1(st) -line therapy. In patients with relapsing and/or refractory disease, cutaneous and immunological response rates seemed to be higher using immunosuppressive agents, in particular azathioprine (AZA), mycophenolate mofetil (MMF) or cyclophosphamide, while rituximab (RTX)-based regimen may have a higher efficacy. Finally, cutaneous response was strongly associated with immunological response after therapy. Conclusion: HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly musculoskeletal and ocular involvement associated with anti-C1q antibodies found in half of patients. The therapeutic strategy has yet to be defined. © 2014 American College of Rheumatology.
- Flurbiprofen-induced unilateral eyelid angioedema. [Journal Article]
- Cutis 2014 Oct; 94(4):E12-3.
- Presence of c1-inhibitor polymers in a subset of patients suffering from hereditary angioedema. [Journal Article]
- PLoS One 2014; 9(11):e112051.
Hereditary angioedema (HAE) is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks. Subjects suffering from HAE have been classified in type I patients with decreased functional and antigenic levels of C1-inh, and type II patients with decreased functional but normal antigenic C1-inh levels. However, a few reports have demonstrated that some mutations cause C1-inh polymerization in vitro, and it is speculated that C1-inh polymers may exist in patient plasma, challenging the current classification of HAE patients. To investigate the presence of C1-inh polymers in patient plasma samples, we developed an immunological method, where monoclonal antibodies produced against polymerized C1-inh were applied in native PAGE western blotting. Using this approach we analyzed genuine plasma samples from 31 Danish HAE families, and found that plasma samples from three genotypically distinct HAE type I families (classified upon C1-inh plasma concentrations) contained C1-inh polymers. Identical C1-inh polymerization phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del),and one mutation affected helix C (p.Thr167Asn). In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients.