Acquired Angioedema - Occurrence, Clinical Features and Associated Disorders in a Danish Nationwide Patient Cohort

Bygum, Anette; Vestergaard, Hanne

doi:10.1159/000351452

Cited by 45 publications

(53 citation statements)

References 30 publications

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“…In our cohort, the diagnostic delay turned out to be short, probably due to the selection of patients referring directly to an AE reference center; the median was 2 years, which differs slightly from recent data in the literature [51] .…”

contrasting

confidence: 77%

Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

Triggianese

Guarino²,

Pellicano³

et al. 2017

Int Arch Allergy Immunol

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Background: Angioedema (AE) is a potentially life-threatening condition with hereditary (HAE), acquired (AAE), or iatrogenic causes. A careful workup allows for the identification of the etiology of attacks and the appropriate management. In this cohort study, based on a clinical practice setting, we aimed at investigating clinical and laboratory findings concerning different features of patients with recurrent AE who were referred to a single, tertiary-level center for HAE. Methods: Clinical and laboratory data of patients fulfilling the criteria for C1-inhibitor-deficient HAE (C1-INH-HAE), C1-INH-AAE, angiotensin-converting enzyme inhibitor-related AE (ACEI-RA), and idiopathic AAE (I-AAE) were evaluated. Descriptive statistics were analyzed by means of the Mann-Whitney U test. The Fisher exact test was used for group comparisons. Results: Patients were diagnosed with type 1 HAE (n = 14), type 2 HAE (n = 1), C1-INH-AAE (n = 8), ACEI-RA (n = 16), or I-AAE (n = 26). We included only patients with concomitant autoimmune diseases from the I-AAE group (n = 8, aut-I-AAE). Age at disease onset and at diagnosis was younger in type 1 HAE than in all the other groups. The diagnostic delay was longer in type 1 HAE than in ACEI-RA. C4 and C1q levels were lower in C1-INH-AAE than in type 1 HAE, ACEI-RA, and aut-I-AAE. Both HAE and C1-INH-AAE showed lower C1-INH antigen and function compared to the other groups. Peripheral attacks were more frequent in type 1 HAE, while airway, abdominal, and oral attacks were prevalent in C1-INH-AAE. Conclusion: Investigating the clinical and laboratory features of recurrent AE without wheals represents a major topic for facilitating early diagnosis and improving treatment strategies for this heterogeneous and misdiagnosed condition.

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contrasting

confidence: 77%

Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

Triggianese

Guarino²,

Pellicano³

et al. 2017

Int Arch Allergy Immunol

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“…In severe C1-INH-AAE, besides symptomatic therapy treatment of the underlying disease is a sine-qua-non in order to attenuate antibody-production to C1-Inh. Elimination of autoreactive B-cells with anti-CD20 (Rituximab) turned out to be effective (69,70).…”

Section: Treatmentmentioning

confidence: 99%

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

Zeerleder

Levi

2016

Annals of Medicine

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Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. In HAE with normal C1-inhibitor, a significant percentage of patients have an increased activity of factor XIIa due to a FXII mutation (FXII-HAE). Treatment of C1-inhibitordependent angioedema focuses on restoring control of BK generation by inhibition of CP proteases by correcting the balance between CP inhibitors and BK breakdown or by inhibition of BK-mediated effects at the BKR2 on endothelial cells. This review will address the pathophysiology, clinical picture, diagnosis and available treatment in C1-inhibitor-dependent angioedema focusing on BK-release and its regulation. ä KEY MESSAGESInadequate control of bradykinin formation results in the formation of characteristic subcutaneous and submucosal edemas of the skin, upper airways, facial structures, abdomen and extremities as seen in hereditary and acquired C1-inhibitor-dependent angioedema. Diagnosis of hereditary and acquired C1-inhibitor-dependent angioedema may be troublesome as illustrated by the fact that there is a significant delay in diagnosis; a certain grade of suspicion is therefore crucial for quick diagnosis. Submucosal edema formation in hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age. To date effective therapies for acute and prophylactic treatment are available. ARTICLE HISTORY

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“…Most data regarding the acquired form of the disease relies on case reports and case series. A recent Danish nationwide study identified only eight patients with AAE, who constituted less than 10% of the C1INH deficiency cohort [3]. The diagnostic delay was on average 1 year and 8 months.…”

Section: Commentarymentioning

confidence: 99%

“…Similarly, a British study showed an average diagnostic delay of 5 years [4]. Many patients with AAE have an underlying lymphoproliferative disorder, ranging from relatively benign causes such as monoclonal B cell lymphocytosis or monoclonal gamopathy of unknown significance to acute B cell leukemia [3,5,6]. AAE might be the presenting symptom [5].…”

Section: Commentarymentioning

confidence: 99%

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2014

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A 60-year-old woman was admitted for evaluation of a two day history of afebrile watery diarrhea, nausea, vomiting, and diffuse abdominal pain. She had not eaten outside her home, has not traveled recently and has not been exposed to animals. No one in her vicinity had similar symptoms.Although the differential diagnosis for abdominal pain, diarrhea, and vomiting is broad, I would first consider infectious gastroenteritis, the most common cause of acute diarrhea. A targeted medical history for recent travel, antibiotic treatment, similar symptoms in relatives or coworkers and eating out may offer diagnostic clues. Noninfectious causes of acute diarrhea in a 60-year-old patient include medications' side effects, ischemic colitis, and diverticulitis. Conditions causing chronic diarrhea might be confused with acute diarrhea early in their course.The patient's past medical history was significant for untreated stage II chronic lymphocytic leukemia (CLL) known for 3 years, with splenomegaly, stable lymphocytosis, and otherwise normal blood counts. She also had essential hypertension and hypertriglyceridemia. Her medications were ramipril, disothiazide, bezafibrate, and aspirin.Diarrhea in patients with CLL can have many etiologies. Acute diarrhea is commonly infectious and unrelated to CLL, with most pathogens being viruses (e.g., adenovirus, rotavirus, and Norwalk virus) or various bacteria (e.g., Escherichia coli, Clostridium difficile, Campylobacter jejuni, Salmonella, and Shigella spp.). Opportunistic pathogens (e.g., microsporidia and cryptosporidium) are more common after treatment with immunomodulating drugs (e.g., fludarabine). Noninfectious causes include chemotherapy-related diarrhea, which can be life threatening. CLL itself might rarely cause diarrhea through direct bowel involvement.On physical examination, the blood pressure was 90/55 mmHg, pulse 60 beats/min, temperature 35 C and respiratory rate 18. There was diffuse abdominal tenderness but no peritoneal irritation; the liver span was 12 cm in the midclavicular line; the spleen was palpated 4 cm below the rib line.Labs showed a white-cell count of 14,000 mm 23 (68% lymphocytes), hematocrit level at 37.5%, and platelet count at 120 mm 23 . The serum sodium level was 133 mmol/l, potassium 4.3 mmol/l, urea 52 mg/dl, and creatinine 1.68 mg/dl (the patient's baseline creatinine level was 0.87 mg/dl). Arterial blood gas results were normal.The approach to a patient with acute diarrhea depends on its severity and the patient's comorbidities. This patient's hypotension and acute renal failure warrant further workup. Leukocytosis and thrombocytopenia could indicate severe infection, but could also be CLL-related. I would start with intravenous infusion of isotonic saline, order blood and stool cultures and proceed with hemodynamic and laboratory monitoring while rehydrating the patient.The patient received aggressive hydration therapy and was treated empirically with intravenous ciprofloxacin and metronidazole for a presumed intra-abdominal major infection. A...

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Acquired Angioedema - Occurrence, Clinical Features and Associated Disorders in a Danish Nationwide Patient Cohort

Cited by 45 publications

References 30 publications

Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

Recurrent Angioedema: Occurrence, Features, and Concomitant Diseases in an Italian Single-Center Study

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

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