Abdominal Attacks Research Articles

Successful enucleation of radicular cyst after prophylaxis in a hereditary angioedema patient

Hereditary angioedema (HAE) due to C1-INH deficiency (C1-INH-HAE) is an autosomal dominant inherited disease characterized by recurrent skin and mucosa swellings that commonly involve the extremities, intestines, face, genital area and upper airways. Dental procedures are important attack triggers in C1-INH-HAE patients. Attacks following dental procedures are commonly localized to the face and larynx. Laryngeal edema can cause death by asphyxiation.A 48-year-old female patient was admitted to our hospital because of the excessive accumulation of calculus on the teeth which was noticed during routine dental examination. At the oral examination calcified dental plaque, bleeding by gingival probing, and discoloration of the teeth #31-32 were detected. By radiographic and clinical findings radicular cyst pre-diagnosis was made, and it was decided to enucleate the cyst.However, the patient’s medical history revealed that she was diagnosed with C1-INH-HAE at the age of 40. To prevent possible facial and laryngeal edema, 1000 units of C1 inhibitor concentration was given 1 hour before the procedure. Under local anesthesia, the lesion was totally enucleated with its capsule. The risk of having attack after tooth extraction is about 37.5% and nearly 1/3 of these attacks are associated with laryngeal edema in patients with C1-INH-HAE. However, prophylaxis with C1 inhibitor concentration led to a 44.1% reduction in angioedema attacks on a per-patient basis. With this case, we wantedto draw attention to the importance of questioning the patient and his/her family for recurrent nonpruritic skin and mucosa swelling and abdominal pain attacks before surgical interventions to the mouth, neck, and throat area.

The evaluation of ENA-78 and fibrinogen levels for the differential diagnosis of familial Mediterranean fever and acute appendicitis

AbstractBackgroundFamilial Mediterranean fever (FMF) is a disorder mainly present in the Mediterranean region, characterized by abdominal attacks that mimic acute peritonitis. Therefore, FMF might be confused with other conditions presenting with acute abdominal pain, particularly acute appendicitis (AA). We aimed to evaluate whether epithelial-derived neutrophil-activating peptide-78 (ENA-78) and fibrinogen levels and white blood cell (WBC) counts could be used as potential markers in the differential diagnosis of acute FMF attacks and AA.MethodsThe study involved three groups: patients with AA who underwent surgery (group 1, n = 30), patients with FMF attacks (group 2, n = 30), and patients with FMF who were attack-free (n = 30, controls), which included patients who were diagnosed as having FMF previously but had no attacks for a month.ResultsSignificant differences were detected in the ENA-78 and fibrinogen levels between group 1 and group 2. No significant difference was found in the WBC count between group 1 and group 2. It was concluded that the WBC count was more sensitive (66%) for group 1, and fibrinogen showed higher sensitivity (86%) and specificity (96%) for group 2 compared with the other parameters.ConclusionsWe suggest that AA can be distinguished in patients with signs of peritonitis who were diagnosed as having FMF previously with the use of ENA-78 and fibrinogen levels; fibrinogen and ENA-78 might be helpful in discriminating between FMF attacks and AA.

Safety of recombinant human C1 esterase inhibitor for hereditary angioedema attacks during pregnancy

Hereditary angioedema (HAE) is a rare (<1 in 50,000) ge-netic disorder characterized by episodes of cutaneous andmucosal angioedema. HAE is caused by insufficient suppressionof complement and contact-system cascades due to a deficiencyof functional C1 inhibitor (C1-INH). It has been demonstratedthat HAE abdominal attacks are more frequent during preg-nancy, but there is no consensus on which trimester is mostassociated with increased attack rates.Some data suggest thatmore severe attacks and symptoms occur during thefirsttrimester, whereas other data suggest a greater number of attacksin the second and third trimesters. Changes in hormone levelsduring pregnancy may exacerbate HAE attacks, and concernswith administration of certain medications during pregnancy cancomplicate HAE management.

Efficacy and safety of long-term treatment with intravenous colchicine for familial Mediterranean fever (FMF) refractory to oral colchicine.

Colchicine is the mainstay of treatment for familial Mediterranean fever (FMF). Intravenous (IV) colchicine, administered over several months, has been shown to be effective for FMF patients unresponsive to oral colchicine. The objective of this study was to evaluate the efficacy and safety of long-term IV colchicine treatment in oral colchicine-resistant FMF. We analyzed data of 15 patients with frequent FMF attacks, despite a maximal tolerated dose of oral colchicine (2-3mg/day), who were treated with weekly IV injections of 1mg of colchicine for at least 12 months. Treatment efficacy was determined by changes in frequency, duration and severity of FMF attacks. Safety was assessed according to adverse events. The mean duration of IV colchicine treatment was 5.16 ± 2.85years. Decreases were observed from pre-treatment period in the monthly mean rates of abdominal attacks (from 5.6 ± 3.7 to 1.9 ± 3.3, p = 0.0009), joint attacks (from 6.5 ± 5.1 to 1.6 ± 1.6, p = 0.01) and overall attacks (from 22.3 ± 16.2 to 7.4 ± 5.7, p = 0.002) as well as in the mean duration (from 3.8 ± 1.5 to 2.4 ± 1.1days per attack, p = 0.008) and severity of attacks (from 9.9 ± 0.3 to 5.7 ± 2.6, on a scale of 0-10, p < 0.05). The rate of adverse events was low, and they were mainly gastrointestinal. No severe or serious adverse events were recorded. Long-term treatment with IV colchicine in patients unresponsive to oral colchicine therapy is effective and safe.

Severe Abdominal HAE Attacks: An Analysis of 7 Cases

Abdominal angioedema attacks are a frequent and typical symptom of hereditary angioedema (HAE) but very often generate diagnostic problems. The study presents laboratory and clinical findings of 7 patients with HAE 1/2 hospitalized due to severe attacks. In all cases, at admittance severe abdominal pain, flatulence, strong weakness, different grade of nausea/vomiting or diarrhoea and abundant free fluid in peritoneal cavity were present. In the history of all patients, recurrent 2 to 3 day long abdominal attack with ascites, were announced. Laboratory data done before the treatment showed elevated leukocytosis, hematocrit, serum glucose, high D-dimers and decreased value of APTT. All patients had an abdominal ultrasound examination, in 5 patients additional abdominal angio-CT was performed to exclude thromboembolic episode. The infusion of human C1 inhibitor concentrate was administered as causative treatment. Completely withdrawal of symptoms was noted up to72 hrs after infusion. In addition all laboratory parameters normalized as well as the free fluid in abdominal cavity disappeared, however, D-dimers serum level despite a decreasing tendency reached the normal range just after 2 weeks.

Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient?

Çekiç Ş, Özgür T, Karalı Y, Özkan T, Kılıç SŞ. Vedolizumab treatment in a patient with X-linked agammaglobulinemia, is it safe and efficient? Turk J Pediatr 2019; 61: 937-940. The loss of inflammatory regulation resulting from the absence of B-lymphocytes leads to a risk for autoimmune and autoinflammatory complications. There is no data on the use of Vedolizumab in patients with X-linked agammaglobulinemia (XLA) as well as children with another primary immunodeficiency (PID) diseases. A 4-year-old boy was admitted to our clinic with a history of recurrent respiratory tract infections. He was diagnosed with XLA based on extremely low immunoglobulins, very low level of B cells, genetic mutation of BTK gene, and family history. At the age of 8, he suffered from intermittent fever attacks, abdominal pain, weakness, oral aft, and weight loss. His clinical and laboratory features were consistent with inflammatory bowel disease. Histopathological examination of the biopsy material obtained from terminal ileum, colon and cecum showed Crohn`s disease. Initially, he was treated with prednisolone and infliximab. Because of the lack of response, infliximab treatment was switched to adalimumab. Terminal ileum was resected to relieve obstruction complication. Although he had been treated with adalimumab, a significant improvement was not observed. Vedolizumab (Entyvio™), a humanized monoclonal antibody α4β7 integrin-receptor antagonist, was commenced. After treatment with vedolizumab, his fever and abdominal pain attacks reduced, his total daily calorie intake increased and weight gain improved. He began to walk again and continued his school education properly. No side effects were observed in 18 months. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect were seen during the treatment.

Hereditary angioedema: a Chinese perspective.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder of vascular permeability associated with heterogeneous clinical manifestations, with prevalence estimated at 1/50,000. Most disease-causing variants lie within the SERPING1 gene, while FXII12, PLG and ANGPT1 gene variants are also reported to associate with HAE. Research on HAE in China began in the 1980s, and later studies identified some clinical characteristics of Chinese HAE patients that differ from the western population. Type 1 HAE (98.73%) accounts for the majority of Chinese HAE patients while no type 3 HAE patient has been diagnosed in China to date. Compared with other populations, the onset age (21.25 years) of Chinese HAE patients is older and the percentage of abdominal attacks (34.18%) is lower. A spectrum of mutations within SERPING1 has been established and a total of 56 mutations have been reported among Chinese patients. Currently, there is no approved drug for acute attacks on the Chinese market, and the choices for long-term prophylaxis are limited to danazol and tranexamic acid. Danazol has demonstrated good efficacy and is tolerated in most Chinese patients, although it has some side effects, especially at the beginning of the treatment with higher doses. Oedematous attacks are effectively prevented with a dosage of ≤200mg/day in 80% patients. This article provides a brief update of HAE and reviews the research progress in the Chinese population within the past 30 years.

Neonatal onset familial Mediterranean fever

Objectives: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent, self-limited attacks of fever with serositis. Recently, it was shown that FMF patients with early disease onset have more severe disease. The aim of this study was to describe the demographic, clinical and genetic features of FMF patients who had disease onset during the neonatal period.Methods: Medical records of all patients diagnosed as FMF and had been seen in the outpatient clinic of Paediatric Rheumatology department between January 2013 and January 2014 were retrospectively evaluated. Patients with disease onset during the first month of life were included to the study.Results: Among 317 patients; 19 (12 males) were included to the study. Approximately 60% of the patients had family history of FMF. Homozygous p.M694V mutation was detected in 42% of the cases. Thirteen patients present with attacks of fever and remaining had attacks in the form of restlessness, resembling infantile colic starting in the neonatal period. Majority of these patients developed classical abdominal attacks between the ages of 1 and 2.5 years. The diagnosis of FMF was significantly delayed; the median age at onset of therapy was 3.5 years (range 7 months–17 years).Conclusion: Patients with FMF could have complaints even in the neonatal period. Homozygous p.M694V mutation is a prominent mutation in this group of patients. In order to prevent diagnostic delay physicians dealing with these type of patients should be more vigilant.

Mutation in Nav1.7 causes high olfactory sensitivity

Mutations in the sodium-channel Nav 1.7, encoded by the gene SCN9A, are known to cause pain disorders. In particular, gain-of-function missense mutations in Nav 1.7 have been shown to be causal in primary erythromelalgia. We present a patient with erythromelalgia, pain attacks and hyperosmia with a mutation within the sodium-channel gene SCN9A. A 50-year-old woman presented with burning pain in both feet and abdominal pain attacks developed over the course of 10years. Furthermore, this patient experienced a hypersensitivity for odours. Clinical investigation as well as serum/cerebrospinal fluid laboratory findings and electrophysiological testing were unremarkable. Olfactory testing showed high olfactory acuity for all screened modalities and good intranasal sensitivity. Furthermore, quantitative sensory testing within the trigeminal area revealed very low thresholds for thermal, tactile and pain detection. In addition, quantitative sensory testing at the lower legs showed hyperalgesia and, as the disease progresses, thermal sensory function loss. Skin biopsies of the proximal and distal lower limbs revealed reduced epidermal nerve fibre density indicating small fibre neuropathy. Genetic analysis of the SCN9A gene demonstrated a heterozygous mutation in Exon 20 - c.3734A>G (p.N1245S). Treatment with clinically available sodium-channel inhibitors did not result in significant pain relief. Local application of the sodium-channel blocker ambroxol however, reduced pain intensity. Continuous odour exposure stabilised mood and induced a short-term pain relief. This clinical note illustrates the course of middle-age onset erythromelalgia and points to clinical findings related to a likely pathogenic missense mutation affecting the sodium-channel Nav 1.7. SIGNIFICANCE: This case report illustrates the course of middle-age onset erythromelalgia with presumed gain-of-function in olfactory and pain sensation associated with a Nav1.7 channel mutation.

Efficacy of recombinant human C1 esterase inhibitor across anatomic locations in acute hereditary angioedema attacks.

Hereditary angioedema (HAE) may occur at or spread to multiple anatomic locations during an acute attack. Recombinant human C1 esterase inhibitor (rhC1-INH) is approved for treating acute HAE attacks. To examine the time to the beginning of symptom relief with rhC1-INH by attack location. Data for patients ≥12 years of age with an acute HAE attack who received rhC1-INH 50 IU/kg or placebo were pooled from two double-blind clinical trials with open-label extensions. The time to the beginning of symptom relief was defined as the first time point that the visual analog scale severity score at an attack location decreased by ≥20 mm versus baseline, with persistence. Data were reported as median time values (95% confidence interval [CI]). For abdominal attacks, the median time to the beginning of symptom relief was 60.0 minutes (95% CI, 47.0-62.0 minutes; n = 194 attacks) with rhC1-INH versus 240.0 minutes (95% CI, 45.0-720.0 minutes; n = 15 attacks) with placebo. The median time to the beginning of symptom relief for peripheral attacks was 105.0 minutes (95% CI, 90.0-120.0 minutes; n = 169 attacks) with rhC1-INH versus 303.0 minutes (95% CI, 180.0-720.0 minutes; n = 17 attacks) with placebo. For oro-facial-pharyngeal-laryngeal attacks or urogenital attacks, the median time to the beginning of symptom relief with rhC1-INH was 64.5 minutes (95% CI, 60.0-120.0 minutes; n = 36 attacks) and 119.0 minutes (95% CI, 40.0-270.0 minutes; n = 13 attacks), respectively, versus 306.0 minutes (95% CI, 30.0-495.0 minutes; n = 6 attacks) and 320.0 minutes (n = 1 attack) with placebo. In shortening the median time to the beginning of symptom relief of acute HAE attacks, rhC1-INH 50 IU/kg was efficacious, regardless of attack location.

Food as a trigger for abdominal angioedema attacks in patients with hereditary angioedema

BackgroundHereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited disease. In most HAE-affected subjects, defined trigger factors precede angioedema attacks. Mechanisms of how trigger factors stimulate the contact activation pathway with bradykinin generation are not well elucidated. In recent studies, hypersensitivity reactions and food were stated as relevant triggers. We investigated HAE affected people for possible hypersensitivity reactions or intolerances and their relation in triggering angioedema attacks.MethodsA questionnaire was filled in, recording date of birth, gender, and self-reported angioedema attacks associated with the ingestion of foodstuffs, administration of drugs, hymenoptera stings and hypersensitivity reactions against inhalation allergens. All participants performed a skin prick test against inhalation allergens and food. In patients who stated an association of possible hypersensitivity with angioedema, a serological ImmunoCAP test was also performed.ResultsFrom the 27 women and 15 men analyzed, 79% stated trigger factors. From those food was mentioned in 36%. The suspected food included tomato, green salad, fish, citrus fruits, apple, onion, garlic, cheese, chili, kiwi, milk, tree nuts, strawberry, pineapple, shrimps, bread, banana, leek, chicken and alcohol, and were associated with abdominal angioedema. Neither the skin prick test nor the ImmunoCAP-test turned out positive for the tested food allergens.ConclusionFood seems to be a relevant trigger factor, causing angioedema in HAE affected patients. The reason, however, is not IgE-mediated hypersensitivity, but most probably an intolerance reaction to food products.

Hereditary angio-oedema in the Western Cape Province, South Africa.

Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa. To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa. A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described. Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack. A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively. Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000. HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly.

Hereditary angio-oedema in the Western Cape Province, South Africa

Background. Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa. Objectives. To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa. Methods. A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described. Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack. Results. A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively. Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000. Conclusions. HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly.

Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight: findings from the Icatibant Outcome Survey, a cohort observational study

BackgroundIcatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant.MethodsAttack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI.ResultsData from 2697 icatibant-treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9–83.8%) were treated with a single icatibant injection without the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of BMI. Patients with obese BMI used pdC1-INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal).ConclusionOverall, icatibant was comparatively effective in treating attacks in patients across all BMI groups.Trial registration NCT01034969.

A missense mutation in the plasminogen gene, within the plasminogen kringle 3 domain, in hereditary angioedema with normal C1 inhibitor

Hereditary angioedema (HAE) is a genetically heterogeneous disease that is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types, HAE types I and II, are both caused by mutations in the complement C1 inhibitor (SERPING1) gene resulting either in a quantitative or a qualitative deficiency of C1 inhibitor. In so-called HAE type III, in contrast, patients show normal C1 inhibitor measurements in plasma ('HAE with normal C1 inhibitor'). As previously shown by us, one subgroup of 'HAE with normal C1 inhibitor' is caused by mutations of the coagulation factor XII (F12) gene. For the present study, following the exclusion of numerous candidate genes, we screened eight unrelated index patients representing eight 'HAE families with normal C1 inhibitor and no F12 mutation' for mutations in the plasminogen (PLG) gene. A rare non-conservative missense mutation was newly identified in exon 9 of the PLG gene. This mutation (c.1100A > G), encountered in three out of eight patients, predicts a lysine-to-glutamic acid substitution in position 311 of the mature protein (p.Lys311Glu). Using isoelectric focusing of plasma samples followed by an immunoblotting procedure we demonstrated that the presence of the mutation is associated with a dysplasminogenemia, namely the presence of an aberrant plasminogen protein. The predicted structural and functional impact of the mutation, its absence in 139 control individuals, and its co-segregation with the phenotype in three large families provide strong support that it causes disease. Extending a previously proposed gene-based alphabetic nomenclature for the various HAE types one may use the term 'HAE type C′ for the HAE entity described here.

Analgesic Effect of Deqi Induced by Needling at Sanyinjiao (SP 6) Acupoint on Primary Dysmenorrheal Patients with Cold Damp Stagnation Syndrome

To observe the analgesic effect of deqi induced by needling at Sanyinjiao (SP 6) on primary dysmenorrheal (PD) patients with cold damp stagnation syndrome (CDSS). A total of 64 PD patients with CDSS experiencing abdominal pain (≥40 mm in visual analogue scale ，VAS) were randomly assigned into deqi-expectation(DE) group(n＝15) and no-deqi-expectation(NDE) group(n＝49). On the first day of abdominal pain attack, bilateral SP 6 were punctured respectively with thicker needles with deeper insertion for deqi-expectation patients and thin filiform needles with shallow insertion for no-deqi-expectation patients. The needles were removed after 30 minutes, a deqi scale was used to evaluate the deqi condition. According to the results, patients in the DE group were further divided into deqi DE group and no-deqi DE group, patients in the NDE group were also divided into deqi NDE group and no-deqi NDE group. The VAS was used to evaluate the patients' abdominal pain severity before treatment and 0, 10, 20, 30 min after acupuncture needle withdrawal. The rate of deqi in the DE group was higher than that in the NDE group(P<0.05). The VAS scores of abdominal pain in the four groups were decreased at all time-points after needle withdrawal compared with those before treatment (P<0.01), while the VAS score in the deqi DE group were lower than in the no-deqi NDE group 30 min after needle withdrawal (P<0.05). The intervention method of thick needle, deep insertion and some manipulation is easier in inducing deqi than that of thin needle, shallow insertion and no manipulation. The analgesic effect of deqi is better than that of no-deqi for PD patients with CDSS.

Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families

Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare condition with clinical features similar to those of HAE with C1-INH deficiency. Mutations in the F12 gene have been identified in subsets of patients with HAE with normal C1-INH, mostly within families of European descent. Our aim was to describe clinical characteristics observed in Brazilians from 42 families with HAE and F12 gene mutations (FXII-HAE), and to compare these findings with those from other populations. We evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives. Genetic analysis revealed that of the 195 subjects, 134 individuals (77.6% females) carried a pathogenic mutation in F12. The T328K substitution was found in 132 individuals, and the c.971_1018+24del72 deletion was found in 2 patients. The mean age at onset of symptoms in patients with FXII-HAE was 21.1 years. The most common symptoms were subcutaneous edema (85.8% of patients), abdominal pain attacks (69.7%), and upper airway edema (32.3%). Of male individuals carrying F12 mutations, 53.3% (16 of 30) were symptomatic. Compared with reports from Europe, fewer female patients (68.6%) reported an influence of estrogen on symptoms. Our study included a large number of patients with FXII-HAE, and, as the first such study conducted in a South American population, it highlighted significant differences between this and other study populations. The high number of symptomatic males and patients with estrogen-independent FXII-HAE found here suggests that male sex and the absence of a hormonal influence should not discourage clinicians from searching for F12 mutations in cases of HAE with normal C1-INH.

P82: A NATIONAL AUDIT OF HEREDITARY AND AQUIRED ANGIOEDEMA IN NEW ZEALAND

Hereditary Angioedema (HAE) is a rare potentially life threatening genetic condition, but access to effective therapies can reduce mortality and improve quality of life. Patients with this condition in New Zealand remain uncharacterised by number, geographical distribution, severity or treatment experience. New Zealand Immunologists were invited to recruit patients with HAE and AAE to the audit or those identified as having Berinert® for hereditary or acquired angioedema. Participants were consented, their angioedema related health information was collected and they were invited to take part in telephone or face to face interviews about their experience of healthcare. Twenty-one patients with hereditary angioedema were recruited, three of whom had acquired angioedema C1 inhibitor deficiency. Three patients were diagnosed prior to the onset of symptoms due to the diagnosis of a family member with the disease by screening family members. The average diagnostic delay was 12.9 years. Variation in delay between different types of HAE, with the greatest mean delay being in Type 1 HAE at 18.5 years, 13 years in type 2 HAE, and 3.6 years in AAE. Within the cohort of 21 patients there were reports of 4 deaths of family members due to HAE. The majority of patients 19/21 (90%) had a written plan to present to the emergency department. Few (24%) had a Medic Alert® bracelet. In 2015 there were a total of 217 HAE attacks in 16 patients. Five patients (24%) were asymptomatic. Only one patient had angioedema of the upper airway in 2015 but did not require intubation. Six patients had 136 abdominal attacks; some with high frequency (range 1–52). Four patients said HAE had no impact on their life, 10 had minor impact, and 4 moderate and 3 described it as severe. This study characterises a cohort of AAE and HAE patients in New Zealand.

Severe hypertriglyceridemia : Diagnostics and new treatment principles

Severe hypertriglyceridemia is defined at aplasma triglyceride (TG) concentration of >885 mg/dl and may result - in particular when clinical symptoms appear before the age of 40 - from "large variant" mutations in genes which influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary factors have to be excluded and treated before further genetic tests are considered. Typical symptoms in almost all patients are recurrent, sometimes severe abdominal pain attacks, which can result in acute pancreatitis, the most important, sometimes life-threatening complication. To minimize the risk of severe pancreatitis, the aim is to maintain the plasma TG concentration <1000 mg/dl. Other clinical manifestations which can occur and are reversible are eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, dyspnea syndrome, and impaired neurocognitive function. The hyperviscosity syndrome caused by chylomicronemia is seen as the underlying reason for some of the symptoms. Patients with mild-to-moderate hypertriglyceridemia have an increased cardiovascular risk. To lower this is the primary treatment goal here. Treatment mainly consists of alife-long, strict fat- and carbohydrate-restricted diet and the abstention from alcohol. Omega‑3-Fatty acids and fibrates can be used to lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient patients have become available in Germany.

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

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.