Recurrent Episodes Of Swelling Research Articles

Clinical efficiency of the cleaved high-molecular-weight kininogen detection in the diagnosis of hereditary angioedema

Hereditary angioedema (HAE) is an orphan genetically determined disorder with recurrent episodes of swelling in various localization. HAE is divided into two groups: HAE with C1-inhibitor deficiency and without C1-inhibitor deficiency. The main diagnostic tests are: meas urements of levels and function of C1-inhibitor, and levels of C4. These tests are not useful in all cases, for example, in HAE without C1-inhibitor deficiency. The detection of cleaved high-molecular-weight kininogen (cHK), which, even in remission, is expected to be elevated both in patients with HAE due to C1-inhibitor deficiency and in HAE with normal C1-inhibitor is a promising biomarker. The aim of this study was to determine the clinical efficiency of the cHK detection in the diagnosis of HAE. According to the results of the measurements of cHK, the patients were divided into two groups. Group №1 (100% of cHK): 27 patients, of which 19 in the study regions had variants associated with HAE, 8 didn’t have. Group №2 (not 100% of cHK): 13 patients, of which one patient had a variant associated with HAE, 12 didn’t have. The obtained data demonstrate acceptable results of using the measurement of cleaved high- molecular-weight kininogen in laboratory practice in the diagnosis of HAE.

EE529 Characterizing Attack-Related Health Utility in Hereditary Angioedema

Health-state utilities are proxies for patient quality-of-life and are important inputs for health economic models to assess the impact of new medical technologies and guide healthcare decision-making. This study aimed to characterize the health utility of“attacks”associated with hereditary angioedema (HAE), a rare and potentially life-threatening genetic disease characterized by recurrent episodes of swelling.

Recurrent Intra Articular Osteochondroma of Left 4th Finger.

Osteochondromas are common benign bone tumors arising from metaphyseal region of long bones. They are notorious for undergoing malignant transformation. We present a case of a middle aged woman with recurrent episodes of swelling in the middle of left 4th finger post excision. Bone scan was performed to look for any malignant transformation of finger lesion and also to rule out skeletal metastases due to recent onset bone pains. 99m Tc MDP (Technetium methylene diphosphonate) bone scan demonstrated a focal hot spot in middle of left 4th finger along the radial side. There was no evidence of skeletal metastases. Surgery is usually curative (70-90%). Limb sparing wide local excision is treatment of choice.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 μm), increased apical, internal, and external diameter (28 vs 22 μm; 22 vs 20 μm; and 81 vs 65 μm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Hereditary angioedema patients would prefer newer-generation oral prophylaxis

Objective To explore treatment preferences of patients with Hereditary Angioedema (HAE), a debilitating disorder characterized by potentially life-threatening, recurrent episodes of swelling, resulting in significant physical, emotional, and economic burden. With newer oral prophylactic treatments on the horizon, it is important to understand patients’ preferences. Methods An online survey was conducted in 2018 among United States (US) adult patients diagnosed with Type I or II HAE. Respondents were recruited anonymously from online panels and social media. Results Online surveys were completed by 75 patients diagnosed with HAE by a healthcare provider, with a mean of 16.7 years since diagnosis. Most patients (64%) report taking at least one medication for prophylaxis of HAE attacks. While almost all patients surveyed agree it is important to take preventative medication as prescribed, over half (52%) of patients report HAE prophylactic treatment to be burdensome. Despite stating that they like their current medications, 98% of the prophylactic HAE medication users would prefer an oral treatment if available; almost all (96%) prophylaxis users agree that oral preventative medication would fit their life better than an injectable medication, with 67% of users citing convenience as the primary reason to try an oral preventative HAE medication. If a more convenient option were available, nearly all (96%) patients currently not treating their HAE prophylactically would feel encouraged to do so. Conclusions Most patients with HAE would prefer a newer generation oral prophylactic medication that would decrease treatment burden and allow them to live fuller lives.

HEREDITARY ANGIOEDEMA PRECIPITATED BY CONSTIPATION SECONDARY TO STIMULANT MEDICATION USE

Introduction Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent episodes of swelling that commonly affects the skin and gastrointestinal tract (1,8). Various triggers can be the precipitating factors in an acute episode of HAE, however, sometimes the culprit cannot be determined. Case Description We present a patient with a diagnosis of hereditary angioedema, concomitant ADHD, with recurrent gastrointestinal exacerbations. Within 3 years, he had nine presentations to the emergency room, four related to abdominal pain, and the remainder for swelling alone. All presentations with abdominal pain had documentation indicating patient had not had a bowel movement for several days. He had abdominal ultrasounds showing thickened bowel loops and small amount of ascites, indicating likely hereditary angioedema attack with gastrointestinal involvement. HAE attacks became more frequent following initiation of stimulant medication for ADHD. It is hypothesized that these frequent attacks were exacerbated by constipation secondary to stimulant medication use, and upon discontinuation of medication, he has not presented to the ER with further abdominal crisis. Discussion HAE may present as recurrent episodes of swelling in one or more body parts, but should also be suspected when there are recurrent bouts of abdominal pain with or without emesis. Constipation, a common presenting pediatric complaint, can lead to stress on the body and result in an HAE acute attack (3,7). We are presenting this case for health care providers to consider stimulant medication as a cause of constipation in patients with HAE presenting with abdominal crisis. Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent episodes of swelling that commonly affects the skin and gastrointestinal tract (1,8). Various triggers can be the precipitating factors in an acute episode of HAE, however, sometimes the culprit cannot be determined. We present a patient with a diagnosis of hereditary angioedema, concomitant ADHD, with recurrent gastrointestinal exacerbations. Within 3 years, he had nine presentations to the emergency room, four related to abdominal pain, and the remainder for swelling alone. All presentations with abdominal pain had documentation indicating patient had not had a bowel movement for several days. He had abdominal ultrasounds showing thickened bowel loops and small amount of ascites, indicating likely hereditary angioedema attack with gastrointestinal involvement. HAE attacks became more frequent following initiation of stimulant medication for ADHD. It is hypothesized that these frequent attacks were exacerbated by constipation secondary to stimulant medication use, and upon discontinuation of medication, he has not presented to the ER with further abdominal crisis. HAE may present as recurrent episodes of swelling in one or more body parts, but should also be suspected when there are recurrent bouts of abdominal pain with or without emesis. Constipation, a common presenting pediatric complaint, can lead to stress on the body and result in an HAE acute attack (3,7). We are presenting this case for health care providers to consider stimulant medication as a cause of constipation in patients with HAE presenting with abdominal crisis.

Secreted Phospholipases A2 in Hereditary Angioedema With C1-Inhibitor Deficiency.

Hereditary angioedema (HAE) caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) is a disabling, potentially fatal condition characterized by recurrent episodes of swelling. We have recently found that patients with C1-INH-HAE have increased plasma levels of vascular endothelial growth factors and angiopoietins (Angs), which have been associated with vascular permeability in several diseases. Among these and other factors, blood endothelial cells and vascular permeability can be modulated by extracellular or secreted phospholipases A2 (sPLA2s). We sought to investigate the enzymatic activity and biological functions of sPLA2 in patients with C1-INH-HAE. sPLA2s enzymatic activity was evaluated in the plasma from 109 adult patients with C1-INH-HAE and 68 healthy donors in symptom-free period and attacks. Plasma level of group IIA sPLA2 (hGIIA) protein was measured in selected samples. The effect of C1-INH-HAE plasma on endothelial permeability was examined in vitro using a vascular permeability assay. The role of hGIIA was determined using highly specific sPLA2 indole inhibitors. The effect of recombinant hGIIA on C1-INH activity was examined in vitro by functional assay. Plasma sPLA2 activity and hGIIA levels are increased in symptom-free C1-INH-HAE patients compared with controls. sPLA2 activity negatively correlates with C1-INH protein level and function. C1-INH-HAE plasma increases endothelial permeability in vitro, and this effect is partially reverted by a specific hGIIA enzymatic inhibitor. Finally, recombinant hGIIA inhibits C1-INH activity in vitro. sPLA2 enzymatic activity (likely attributable to hGIIA), which is increased in C1-INH-HAE patients, can promote vascular permeability and impairs C1-INH activity. Our results may pave the way for investigating the functions of sPLA2s (in particular, hGIIA) in the pathophysiology of C1-INH-HAE and may inform the development of new therapeutic targets.

Safety, effectiveness, and impact on quality of life of self-administration with plasma-derived nanofiltered C1 inhibitor (Berinert\xae) in patients with hereditary angioedema: the SABHA study

BackgroundHereditary angioedema with C1 inhibitor deficiency is a disabling, potentially fatal condition characterized by recurrent episodes of swelling. Self-treatment is recommended, in order to reduce admissions to the Emergency Room and the time between the onset of the attack and the treatment, resulting in a better treatment outcome and an improved quality of life (QoL). The purpose of this study is to assess the safety, tolerability, and effect on QoL of self-administration of pnf C1-INH for IV use (Berinert®).MethodsAn observational, monocenter, prospective study was designed.Patients referring to a center for angioedema that attended two sessions of self-infusion training course in the period March 2014–July 2015 were enrolled in the study. The primary endpoint was to monitor the safety and feasibility of pnf C1-INH self-infusion. The secondary endpoint was to evaluate the effect of self-infusion on the QoL, by means of the HAE-QoL questionnaire and the need for access to Emergency Room for infusion of Berinert®. Patients’ medical history data were collected upon the first visit and questionnaires were filled after each attack treated with Berinert® (diary and Treatment Satisfaction Questionnaire for Medication) and upon the first visit and the follow-ups (HAE-QoL).ResultsTwenty patients were enrolled (median age = 42, IQR: 39–49; 60% females). Fifteen patients completed the study. A total of 189 attacks were recorded (annual median rate of 4 attacks/patient). Patients waited a median of 2 h (IQR: 1–4) before self-administration, and the resolution of the attack occurred after a median of 6 h (IQR: 4–11). Most attacks were abdominal (39%) and peripheral (22%). 92% of the attacks were treated through self−/caregiver-administration. In most attacks no side effects were reported. The number of attacks with side effects decreased over time, from 37% to 13%. Global satisfaction grew over time during the study period, reaching statistical significance over the first 6 months. The median total HAE-QoL score at baseline was 86 (IQR: 76–103) and improved in a non-significant manner throughout the study period. 8% of the attacks treated with Berinert® required ER admission/healthcare professional help in the study period, compared with 100% in the 3 years before enrollment (p < 0.0001).ConclusionsSelf-administration of pnf C1-INH is safe, and increases patients’ confidence in the treatment, showing also a trend towards an improvement in QoL. It reduces the need for ER admission/healthcare professionals help for the acute attacks, as well as the related costs.

Multicentric Hyaline-Vascular Castleman Disease: A Case Report

Castleman disease is a rare lymphoproliferative disorder. Contrary to its closest differential of lymphoma, the disease tends to run a benign course. However the multicentric variety, which is usually of the plasma cell type, has a more sinister prognosis. It is commonly associated with HIV infection. We report a case of a 65 year old man presenting with recurrent episodes of swelling of the whole body and diarrhoea for 3 years. Physical examination revealed generalized lymphadenopathy with hepato-splenomegaly and ascites. Lymph node biopsy revealed histopathological changes consistent with hyaline-vascular type of Castleman disease (multicentric). He was HIV negative. Patient was treated with high dose corticosteroids and discharged with follow up advice. DOI: http://dx.doi.org/10.3329/jom.v16i1.22402 J MEDICINE 2015; 16 : 48-50

OP0112 Cystic fibrosis related arthritis in adults in south east england

BackgroundAlthough bone and joint manifestations are common in children with cystic fibrosis (CF), they have received little attention in adults. CF-related arthropathy (CFA) is a relatively infrequent complication previously reported...

C1-inhibitor deficiencies (hereditary angioedema): Where are we with therapies?

Hereditary angioedema, an autosomal dominant disorder, presents clinically as recurrent episodes of swelling. It results from either deficient production or function of C1 inhibitor. Acquired angioedema is associated with lymphoproliferative or autoimmune disease. Conventionally attenuated androgens and antifibrinolytics have been used for prophylaxis, both for the long term and presurgically. Fresh frozen plasma and plasma-derived C1 inhibitor concentrate have been used primarily for treatment of acute attacks. All have drawbacks in side effects or potential for infection transmission. New treatments (recombinant C1 inhibitor, icatibant, DX-88, and for acquired angioedema, rituximab) so far show good safety profiles. Early data suggest these may be effective treatment alternatives. The efficacy of current treatment and the potential held by newer agents that target specific elements in complement or kinin pathways are examined. Some agents are likely to have a wider role in treatment of other, more common, forms of angioedema.

Practical Management of C1 Inhibitor Deficiency

C1 inhibitor deficiency is a rare syndrome clinically characterized by recurrent episodes of swelling of subcutaneous tissue or angioedema. It can involve the skin, upper respiratory airways and abdomen. There are two main types: hereditary and acquired. Angioedema can involve practically any part of the cutaneous surface, it can cause lethal laryngeal edema and can present as gastrointestinal obstruction. The attacks can be triggered, in general, by trauma, drugs or infections. Diagnosis is confirmed by decreased serum levels of C4 and absence or marked decrease of the level or function of C1 inhibitor. Commonly employed drugs for prophylaxis and treatment of these patients include anabolic steroids, antifibrinolytic agents, and infusion of C1 inhibitor concentrate. Fresh frozen plasma is an option to be considered for short term prophylaxis or treatment of the acute attack. It is convenient to know this syndrome as it is a potentially life-threatening disease. Diagnosis of this rare syndrome is based on clinical features and characteristic alterations of laboratory tests. The acute attack should be treated as quickly as possible. Prophylactic therapy is indicated in certain circumstances (dental procedures, oral surgery).

Chronic recurrent parotitis in childhood in monozygotic twins. Magnetic resonance sialography

Recurrent parotitis is rare in childhood. Its occurrence is characterized by recurrent episodes of swelling and pain in the parotid gland, which are usually accompanied by fever and malaise. Inflammation usually resolves spontaneously during adolescence. The disorder is a condition of unknown etiology. Sialectasis and stricturing occurs in the distal ducts, whereas inflammation of the gland and duct epithelium is probably caused by a low salivary flow rate. Which one can be considered the primary event or secondary change remains unknown. The main-stay of diagnosis is sialography, which depicts typical intraparotidal duct system lesions as strictures or ectasias and excludes sialolithiasis. We here report two 10-year-old male monovular twins who suffered from recurrent swelling and pain in only their left parotid glands. Symptoms were noted approximately every 6 weeks in both patients strictly. Characteristic sialectasis of the distal ducts was demonstrated by magnetic resonance-sialography. Our findings support the hypothesis that recurrent parotitis is caused by a congenital abnormality of the salivary gland ducts. Diagnostic imaging was performed by magnetic resonance imaging during the acute phase of the disease. This technique helps to make the diagnosis without retrograde application of a contrast agent.

Experience with peritendinous fibrosis of the dorsum of the hand

Fifteen patients with a diagnosis of peritendinous fibrosis of the dorsum of the hand (Secretan's disease) were treated between 1958 and 1980. Thirteen patients had excision of a dorsal fibroma with extensor tendolysis when necessary. Preoperative findings included a hard dorsal mass and limitation of motion. Postoperative courses were characterized by prolonged periods of rehabilitation and recurrent episodes of swelling. Twelve of 15 patients returned to work 3 to 30 months postoperatively. Permanent disability was substantial. None of these patients had significant wound healing problems, and all had improved range of motion. The question of self-inflicted injury was raised in five cases but could not be demonstrated.

Experience with peritendinous fibrosis of the dorsum of the hand

Fifteen patients with a diagnosis of peritendinous fibrosis of the dorsum of the hand (Secretan's disease) were treated between 1958 and 1980. Thirteen patients had excision of a dorsal fibroma with extensor tendolysis when necessary. Preoperative findings included a hard dorsal mass and limitation of motion. Postoperative courses were characterized by prolonged periods of rehabilitation and recurrent episodes of swelling. Twelve of 15 patients returned to work 3 to 30 months postoperatively. Permanent disability was substantial. None of these patients had significant wound healing problems, and all had improved range of motion. The question of self-inflicted injury was raised in five cases but could not be demonstrated.

The syndrome of hyperostosis and hyperphosphatemia

Six children, five girls and one boy, presented with recurrent episodes of swelling, pain, and tenderness of the long bones. On roentgenographic examination all had cortical hyperostosis of the affected areas. Serum phosphate concentration was persistently elevated, and calcium values were normal. Bone biopsy and histologic examination in three patients revealed periosteal new bone formation. The Ellsworth-Howard test was performed on three patients; all had a normal phosphaturic response and an increase in urinary c'AMP to exogenous PTH. The EDTA test, performed on one patient, demonstrated significant phosphaturic response, but a minimal drop in serum phosphate concentration. These findings suggest that the association of cortical hyperostosis and hyperphosphatemia is a distinct clinical entity, and that hyperphosphatemia results from decreased renal excretion of phosphate.