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Abstract
Abdominal pain is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of abdominal pain is angioedema of the gastrointestinal tract due to recurrent angioedema without wheals. Abdominal involvement is very common in hereditary angioedema (HAE), but it is also described in acquired angioedema and allergic forms. In patients with HAE, the involvement of gastrointestinal tract with resultant abdominal pain occurs in 43-93% of cases. Attacks can involve the entire gastrointestinal tract, such as the oropharynx, small intestine, colon, liver, or pancreas. Pain is the most common gastrointestinal symptom, and it may occur for many years even without cutaneous or respiratory symptoms. The case report we included in this article emphasizes the importance of accurate evaluation of personal and family history in patients with a long history of acute, severe, and unexplained abdominal pain, and it gives an example of how diagnostic delay may be longer if gastroenterological symptoms are the predominant clinical presentation. Furthermore, sometimes the simultaneous presence of concomitant gastrointestinal disorders and HAE may cause difficulties in differential diagnosis. Gastroenterologists and other physicians should add HAE to their list of potential causes of unexplained abdominal pain. The initiation of appropriate prophylaxis and treatment will prevent needless suffering and useless surgical and medical procedures.
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Barni S, Giovannini M, Liccioli G, Sarti L, Gissi A, Lionetti P, Mori F. Case Report: Refractory Chronic Spontaneous Urticaria Treated With Omalizumab in an Adolescent With Crohn's Disease. Front Immunol 2021; 12:635069. [PMID: 33737936 PMCID: PMC7962273 DOI: 10.3389/fimmu.2021.635069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 01/21/2021] [Indexed: 01/17/2023] Open
Abstract
Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is often associated with autoimmune or autoinflammatory conditions. Omalizumab is recommended in the treatment of refractory CSU in patients over 12 years of age who do not respond to four standard doses of antihistamines. Omalizumab blocks the mast cells’ degranulation, thus interrupting the resulting inflammatory cascade driven by T-helper 2 (Th2) cytokines. The efficacy of omalizumab in controlling CSU and possible associated diseases has been studied in few patients so far. In particular, some case reports describe adults with CSU and concomitant inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) or ulcerative colitis (UC). Although the treatment of CD with anti-tumor necrosis factors-α (TNF-α) seems to be effective in controlling CSU, no cases of the utility of omalizumab in patients with both conditions have been described so far. At the moment, there is no evidence that the pathogenetic mechanisms underlying CD are linked to the same pathways that are inhibited by omalizumab for the treatment of CSU. We present the first pediatric case of refractory CSU and CD in which omalizumab led to CSU remission, even if the follow-up period was limited. In conclusion, our experience shows how CSU could be associated with CD and successfully treated with the monoclonal anti-IgE antibody in a patient on immunosuppressive therapy. However, more data is needed from a larger population.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Giulia Liccioli
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Lucrezia Sarti
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Anna Gissi
- Gastroenterology and Nutrition Unit, Meyer Children's University Hospital, Florence, Italy
| | - Paolo Lionetti
- Gastroenterology and Nutrition Unit, Meyer Children's University Hospital, Florence, Italy
| | - Francesca Mori
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
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Reichhardt MP, Meri S. SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces. Front Immunol 2016; 7:85. [PMID: 27014265 PMCID: PMC4781872 DOI: 10.3389/fimmu.2016.00085] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 02/22/2016] [Indexed: 12/11/2022] Open
Abstract
Complement is present mainly in blood. However, following mechanical damage or inflammation, serous exudates enter the mucosal surfaces. Here, the complement proteins interact with other endogenous molecules to keep microbes from entering the parenteral tissues. One of the mucosal proteins known to interact with the early complement components of both the classical and the lectin pathway is the salivary scavenger and agglutinin (SALSA). SALSA is also known as deleted in malignant brain tumors 1 and gp340. It is found both attached to the epithelium and secreted into the surrounding fluids of most mucosal surfaces. SALSA has been shown to bind directly to C1q, mannose-binding lectin, and the ficolins. Through these interactions SALSA regulates activation of the complement system. In addition, SALSA interacts with surfactant proteins A and D, secretory IgA, and lactoferrin. Ulcerative colitis and Crohn's disease are examples of diseases, where complement activation in mucosal tissues may occur. This review describes the latest advances in our understanding of how the early complement components interact with the SALSA molecule. Furthermore, we discuss how these interactions may affect disease propagation on mucosal surfaces in immunological and inflammatory diseases.
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Affiliation(s)
- Martin Parnov Reichhardt
- Immunobiology Research Program, Research Programs Unit, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki , Helsinki , Finland
| | - Seppo Meri
- Immunobiology Research Program, Research Programs Unit, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki , Helsinki , Finland
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Wang Z, Ding L, Wang Z, Wang J, Zhu N, Diao Y, Demmy TA, Haitsma JM, Lech-Maranda EE, Bangia NN, Czuczman MA, Qian X, Kovacs KL. Circulating CD4+CXCR5+T Cells Exacerbate B Cell Antibody Production in Crohn's Disease Through IL-21 Secretion. Immunol Invest 2015; 44:665-77. [DOI: 10.3109/08820139.2015.1074246] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Abenavoli L, Proietti I, Zaccone V, Gasbarrini G, Addolorato G. Celiac disease: from gluten to skin. Expert Rev Clin Immunol 2014; 5:789-800. [DOI: 10.1586/eci.09.46] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Habal F, Huang V. Angioedema associated with Crohn's disease: Response to biologics. World J Gastroenterol 2012; 18:4787-90. [PMID: 23002350 PMCID: PMC3442219 DOI: 10.3748/wjg.v18.i34.4787] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 05/31/2012] [Accepted: 06/15/2012] [Indexed: 02/06/2023] Open
Abstract
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
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Kessel A, Peri R, Perricone R, Guarino MD, Vadasz Z, Novak R, Haj T, Kivity S, Toubi E. The autoreactivity of B cells in hereditary angioedema due to C1 inhibitor deficiency. Clin Exp Immunol 2012; 167:422-8. [PMID: 22288585 PMCID: PMC3374274 DOI: 10.1111/j.1365-2249.2011.04527.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2011] [Indexed: 01/29/2023] Open
Abstract
Patients with hereditary angioedema (HAE) tend to produce autoantibodies and have a propensity to develop immunoregulatory disorders. We characterize the profile of autoantibodies in a group of HAE patients and investigate their memory B cells' phenotype and activation status. We studied the activity status phenotype, Toll-like receptor (TLR)-9 expression and total phosphotyrosine in B cells isolated from HAE patients. Additionally, the following autoantibodies were assessed in the serum of 61 HAE patients: anti-nuclear, rheumatoid factor, anti-cardiolipin, anti-tissue transglutaminase, anti-endomysial, anti-Saccharomyces cerevisiae, anti-thyroid and anti-neutrophil cytoplasmic antibodies. In 47·5% of HAE patients we detected at least one of the tested autoantibodies. Expression of CD69, CD5 and CD21 was found to be significantly higher on memory B cells from HAE patients compared to healthy controls (4·59 ± 4·41 versus 2·06 ± 1·81, P = 0·04, 8·22 ± 7·17 versus 3·65 ± 3·78, P = 0·05, 2·43 ± 0·54 versus 1·92 ± 0·41, P = 0·01, respectively). Total phosphotyrosine in B cells from HAE patients was significantly higher compared to healthy controls (4·8 ± 1·1 versus 2·7 ± 1·3, P = 0·0003). Memory B cells isolated from the HAE group contained higher amounts of TLR-9 compared to healthy controls (8·17 ± 4·1 versus 4·56 ± 1·6, P = 0·0027). Furthermore, the expression of TLR-9 in memory B cells from HAE patients with autoantibodies was significantly higher than the control group (10 ± 4·7 versus 4·56 ± 1·6, P = 0·0002) and from that in HAE patients without autoantibodies (10 ± 4·7 versus 5·8 ± 0·9, P = 0·036). HAE patients have enhanced production of autoantibodies due most probably to the increased activation of B cells, which was found to be in association with a high expression of TLR-9.
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Affiliation(s)
- A Kessel
- Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel.
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Farkas H, Csuka D, Gács J, Czaller I, Zotter Z, Füst G, Varga L, Gergely P. Lack of increased prevalence of immunoregulatory disorders in hereditary angioedema due to C1-inhibitor deficiency. Clin Immunol 2011; 141:58-66. [PMID: 21636327 DOI: 10.1016/j.clim.2011.05.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 04/18/2011] [Accepted: 05/09/2011] [Indexed: 11/18/2022]
Abstract
Hereditary angioedema due to deficiency of C1-INH (HAE-C1-INH) is associated with enhanced consumption of the early complement components, which may predispose for autoimmune disease. We assessed the prevalence of such disorders among HAE- C1-INH patients and their impact on the natural course of HAE-C1-INH. Clinical data and immunoserological parameters of 130 HAE-C1-INH and 174 non-C1-INH-deficient patients with angioedema were analyzed. In our study, the incidence of immunoregulatory disorders was 11.5% in the population of HAE-C1-INH patients and 5.2% among non-C1-INH-deficient controls with angioedema. Immunoserology screening revealed a greater prevalence of anticardiolipin IgM (p=0.0118) among HAE-C1-INH patients, than in those with non-C1-INH-deficient angioedema. We did not find higher prevalence of immunoregulatory disorders among our HAE-C1-INH patients. However, in patients with confirmed immunoregulatory disorders, the latter influenced both the severity of HAE-C1-INH and the effectiveness of its long-term management. Appropriate management of the immunoregulatory disease thus identified improves the symptoms of HAE-C1-INH.
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Affiliation(s)
- Henriette Farkas
- Semmelweis University, 3rd Department of Internal Medicine, Budapest, Hungary.
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Marks DJB, Seymour CR, Sewell GW, Rahman FZ, Smith AM, McCartney SA, Bloom SL. Inflammatory bowel diseases in patients with adaptive and complement immunodeficiency disorders. Inflamm Bowel Dis 2010; 16:1984-92. [PMID: 20848466 DOI: 10.1002/ibd.21280] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Crohn's disease and ulcerative colitis are idiopathic chronic inflammatory diseases that primarily affect the gastrointestinal tract. The underlying causes remain poorly understood, but there is a growing body of evidence advocating a likely primary pathogenic role for immunodeficiency in the development of Crohn's lesions. Concordantly, a number of congenital immunodeficiencies disrupting the cellular innate immune system strongly predispose to noninfectious, Crohn's-like inflammatory bowel disease. There are case reports and series suggesting that the same may be true for some of the congenital adaptive and complement immunodeficiencies. This review considers and critiques these potential associations.
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Angioedema occurring in pediatric patients with Crohn disease treated with adalimumab. J Pediatr Gastroenterol Nutr 2010; 51:223-5. [PMID: 20410840 DOI: 10.1097/mpg.0b013e3181c615e1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Klemmer N, Vittecoq O, Fremeaux-Bacchi V, Tron F. Association of hereditary angioneurotic edema with spondylarthropathy: Report of a case. Joint Bone Spine 2008; 75:95-6. [DOI: 10.1016/j.jbspin.2007.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2007] [Accepted: 05/28/2007] [Indexed: 11/30/2022]
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Abenavoli L, Proietti I, Leggio L, Ferrulli A, Vonghia L, Capizzi R, Rotoli M, Amerio PL, Gasbarrini G, Addolorato G. Cutaneous manifestations in celiac disease. World J Gastroenterol 2006; 12:843-52. [PMID: 16521210 PMCID: PMC4066147 DOI: 10.3748/wjg.v12.i6.843] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.
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Affiliation(s)
- L Abenavoli
- Institute of Internal Medicine, Catholic University, L.go Gemelli 8, 00168 Rome, Italy
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Koruth JS, Eckardt AJ, Levey JM. Hereditary angioedema involving the colon: endoscopic appearance and review of GI manifestations. Gastrointest Endosc 2005; 61:907-11. [PMID: 15933700 DOI: 10.1016/s0016-5107(05)00334-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Jacob S Koruth
- Department of Medicine, Worcester Medical Center, Massachusetts, USA
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Agostoni A, Aygören-Pürsün E, Binkley KE, Blanch A, Bork K, Bouillet L, Bucher C, Castaldo AJ, Cicardi M, Davis AE, De Carolis C, Drouet C, Duponchel C, Farkas H, Fáy K, Fekete B, Fischer B, Fontana L, Füst G, Giacomelli R, Gröner A, Hack CE, Harmat G, Jakenfelds J, Juers M, Kalmár L, Kaposi PN, Karádi I, Kitzinger A, Kollár T, Kreuz W, Lakatos P, Longhurst HJ, Lopez-Trascasa M, Martinez-Saguer I, Monnier N, Nagy I, Németh E, Nielsen EW, Nuijens JH, O'grady C, Pappalardo E, Penna V, Perricone C, Perricone R, Rauch U, Roche O, Rusicke E, Späth PJ, Szendei G, Takács E, Tordai A, Truedsson L, Varga L, Visy B, Williams K, Zanichelli A, Zingale L. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol 2004; 114:S51-131. [PMID: 15356535 PMCID: PMC7119155 DOI: 10.1016/j.jaci.2004.06.047] [Citation(s) in RCA: 440] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2004] [Revised: 06/24/2004] [Accepted: 06/24/2004] [Indexed: 01/13/2023]
Abstract
Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.
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Key Words
- aae
- acquired angioedema
- angioedema
- c1 esterase inhibitor
- c1-inh
- hae
- hane
- hano
- hereditary angioedema
- hereditary angioneurotic edema
- angioneurotic edema
- chemically induced angioedema
- human serping1 protein
- aae, acquired angioedema
- aaee, (italian) voluntary association for the study, therapy, and fight against hereditary angioedema
- ace, angiotensin-converting enzyme
- app, aminopeptidase p
- at2, angiotensin ii
- b19v, parvovirus b19
- bmd, bone mineral density
- bvdv, bovine viral diarrhea virus
- c1, first component of the complement cascade
- c1-inh, c1 esterase inhibitor
- c1nh, murine c1 esterase inhibitor gene
- c1nh, human c1 esterase inhibitor gene
- c2, second component of the complement cascade
- c3, third component of the complement cascade
- c4, fourth component of the complement cascade
- c5, fifth component of the complement cascade
- ccm, chemical cleavage of mismatches
- ch50, total hemolytic complement, 50% cell lysis
- cmax, maximum concentration
- cpmp, committee for proprietary medicinal products
- cpv, canine parvovirus
- dhplc, denaturing hplc
- ff, (ovarian) follicular fluid
- ffp, fresh frozen plasma
- hae, hereditary angioedema
- hae-i, hereditary angioedema type i
- hae-ii, hereditary angioedema type ii
- haea, us hae association
- hav, hepatitis a virus
- hbsag, hepatitis b surface antigen
- hbv, hepatitis b virus
- hcv, hepatitis c virus
- hk, high molecular weight kininogen
- hrt, hormone replacement therapy
- huvs, hypocomplementemic urticaria-vasculitis syndrome
- lh, luteinizing hormone
- masp, mannose-binding protein associated serine protease
- mbl, mannan-binding lectin
- mfo, multifollicular ovary
- mgus, monoclonal gammopathies of undetermined significance
- mr, molecular mass
- nat, nucleic acid amplification technique
- nep, neutral endopeptidase
- oc, oral contraceptive
- omim, online mendelian inheritance in man (database)
- pco, polycystic ovary
- pct, primary care trust
- prehaeat, novel methods for predicting, preventing, and treating attacks in patients with hereditary angioedema
- prv, pseudorabies virus
- rhc1-inh, recombinant human c1 esterase inhibitor
- rtpa, recombinant tissue-type plasminogen activator
- shbg, sex hormone binding globulin
- ssca, single-stranded conformational analysis
- tpa, tissue-type plasminogen activator
- uk, united kingdom
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Abstract
The Hungarian HAE Center was established in 1994, in Budapest. Assignments of the Center include diagnostic work-up of patients with angioedema; developing national guidelines for the recognition, treatment of patients with HAE; maintaining the registry, patient education, supply patients with info-card and C1-INH concentrate, follow-up of patients, telephone 'hot-line' service, under- and postgraduate education as well as pursues scientific activities. Established in 1996, the Hungarian HAE Patients' Association a foundation to support HAE patients; and a Hungarian HAE website. Hungarian HAE Working Group is the main organizer of the European C1-INH Deficiency Workshops to be held at two-year intervals from 1999.
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Affiliation(s)
- Henriette Farkas
- Allergy and Angiooedema Outpatients Clinic, Kútvölgyi Clinical Center, Semmelweis University, Kútvölgyi út 4, H-1125 Budapest, Hungary.
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Farkas H, Visy B, Fekete B, Karádi I, Kovács JB, Kovács IB, Kalmár L, Tordai A, Varga L. Association of celiac disease and hereditary angioneurotic edema. Am J Gastroenterol 2002; 97:2682-3. [PMID: 12385467 DOI: 10.1111/j.1572-0241.2002.06059.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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