Hereditary angioedema: case report and review of management

For treatment of malaria, the World Health Organization recommends 10 mg of quinine per kg body-weight 3 times a day for at least 7 d. In Guinea-Bissau, as in several other African countries, a 3 d treatment regimen (10 mg/kg twice daily) is currently used. We therefore compared the 3 d treatment period with periods of 5 and 7 d. A total of 145 children with clinical malaria due to monoinfection with Plasmodium falciparum, with > or = 20 parasites per 200 leucocytes, were treated with intramuscular Quinimax 10 mg per kg body-weight twice daily for 3, 5 or 7 d. The children were then examined once weekly for 4 weeks. Following the 3 d treatment regimen, 34 of 43 children (79%) had parasitaemia on day 28 or before; following the 5 d treatment regimen, 36 of 40 children (90%) did so; and following the 7 d treatment regimen, 7 of 62 children (11%) were parasitaemic at that time. This study thus suggests that the currently recommended 3 d Quinimax treatment regimen in Guinea-Bissau for moderate and severe malaria is not effective.     

Hereditary angioedema: modification of clinical manifestations with androgens

HAE is an autosomal dominant trait of decreased levels or function of circulating and tissue C'1 esterase inhibitor. The clinical illness is characterized by disabling episodes of peripheral, oropharyngeal and gut-wall edema. Long-term fluoxymesterone treatment of 5 affected males (393 patient-months) and oxymetholone treatment of 6 affected females (204 patient-months) has significantly decreased the frequency of attacks of edema without substantive side effects.     

Hereditary angioedema. Complex symptoms can make diagnosis difficult

Although rare, hereditary angioedema is a potentially life-threatening disorder that can be difficult to diagnose. It is characterized by a deficiency in C1 esterase inhibitor (C1 INH). Manifestations include gastrointestinal, subcutaneous, and respiratory edema. Factors that trigger episodes vary. Symptoms typically last 48 to 72 hours, but they can last 4 hours to 1 week. Treatment includes prophylactic therapy with attenuated androgens or antifibrinolytic agents. Acute episodes can be medical emergencies, and airway management is a major concern. The treatment of choice in an acute episode is administration of plasma concentrate of C1 INH.     

Hereditary angioedema. A rare cause of acute abdominal pain with ascites

HISTORY AND CLINICAL FINDINGS: Since the age of 16 years a now 25-year-old woman had been known to have C1-inhibitor (C1-INH) deficiency. She presented herself at the emergency department because of acute severe lower abdominal cramps. A urinary infection had been treated with antibiotics for the previous 4 days. There was marked pain on pressure over the lower abdomen, but there were no signs of peritonitis and bowel sound were normal. There had been no nausea or vomiting and the stools had been normal. INVESTIGATIONS: There was a leukocytosis of 10,200/microliter, moderately elevated C-reactive protein (44.8 mg/l), haemoglobin concentration of 17 g/dl and haematocrit of 51%. Radiology revealed oedema of the duodenum and sonography showed free fluid in the abdomen. TREATMENT AND COURSE: After excluding an acute abdomen and in view of the C1-INH deficiency treatment was symptomatic. All symptoms completely disappeared after 2 days. CONCLUSIONS: Exclusively gastrointestinal symptoms and ascites are rare in patients with hereditary angioedema. But knowledge of this manifestation of the disease is important because patients are sometimes operated under the false diagnosis of acute abdomen. In severe cases symptomatic treatment may have to be supplemented by C1-INH administration. Prevention with attenuated androgens should be started or modified, respectively.     

Thrombosis resulting from heparin therapy

Heparin is widely used in current practice for a variety of indications. It is well known that it can cause thrombocytopenia, but not that thrombosis may also develop in thrombocytopenic patients and cause significant morbidity and mortality. A 56-year-old woman developed heparin-induced thrombocytopenia with thrombosis that resulted in the amputation of her leg. It is proposed that the reaction has an immune-mediated mechanism. Several ways of diagnosing the condition are available, specifically the serotonin-release assay and an enzyme-linked immunosorbent assay. The investigational agent danaproid may be effective in the treatment of heparin-induced thrombocytopenia with thrombosis.     

Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven)

Plasma histidine-rich glycoprotein (HRG) was found to be persistently increased in a patient with a history of recurrent arterial thromboembolic events. The mean concentration was 270% of normal pooled plasma. Increased HRG was found in eight of the 17 relatives studied, but none of them has experienced thrombo-embolism yet. Apparently, increased HRG was hereditary with autosomal dominant inheritance. A significant correlation was found between the increased plasma concentration of the protein and the age of the subjects (P < 0.02), whereas no such relation is present in a normal population. The plasma HRG of the proposita and 9 of her family members displayed abnormal binding to heparin, as assessed in a crossed affinity immuno-electrophoresis system: the usual increase in mobility after binding to heparin was absent. The binding of this variant HRG to plasminogen was normal. This case represents the first abnormal HRG variant reported and it is proposed to designate it: HRG Eindhoven.     

Experimental meningococcal septicemia. Effect of heparin therapy

The pathogenesis of experimental meningococcal septicemia and the efficacy of heparin sodium therapy were evaluated by inoculating rabbits intraperitoneally with type B meningococci in mucin. Half the rabbits died, and the respiratory distress and circulatory failure that occurred during the terminal phase of the disease were associated with diffuse pulmonary capillary and venular thrombosis and with renal glomerular fibrin deposition. Platelet and leukocyte counts and plasma fibrinogen levels decreased in all rabbits, and prothrombin and partial thromboplastin times were prolonged. Pretreatment with heparin sodium diminished intravascular fibrin deposition but failed to prevent the pulmonary microthrombi and did not either reduce the mortality or improve the survival time. We conclude that death in meningococcal septicemia is due to widespread thrombosis of the pulmonary microcirculation. The disease is complicated by diffuse intravascular coagulation, which can be controlled with heparin sodium but which is not immediately life-threatening.     

Urticaria and angioedema: pathophysiology, diagnosis, and treatment

BACKGROUND: Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. METHODS: We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had not taken appetite suppressants who were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. RESULTS: There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). CONCLUSIONS: The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.     

Heparin therapy: 1998 (current use of the 80-year-old heparin)

OBJECTIVES: Describe the different features of a common disease: Mycoplasma pneumoniae pneumonia. PATIENTS AND METHODS: The hospital files of 10 consecutive patients with microbiologically proven Mycoplasma pneumoniae pneumonia were reviewed retrospectively. These 10 patients were hospitalized over a 15-month period among 150 patients admitted to the Versailles general hospital for community-acquired pneumonia. We compared our series with data in the literature. RESULTS: Most of the patients with Mycoplasma pneumoniae pneumonia were young apparently healthy adults. A bronchial risk factor (smoking, allergy) was however found in 60% of the patients. The principle symptom was persistent cough (100%), with fever and joint pain, or sometimes headache and signs of ENT involvement. Dyspnea was frequent, related more to associated bronchospasticity than to the severity of the pneumonia. Radiographic findings were quite variable. In one case hemolytic anemia and cold agglutinins suggested the diagnosis. Certain diagnosis was based on positive serology after hospitalization due to the long delay between symptom onset and hospitalization. The prehospital period was characterized by a succession of ineffective empirical antibiotic regimens. In routine practice, macrolides or fluoroquinolones administered for 2 to 3 weeks are the empirical antibiotics of choice. Outcome is generally favorable with rapid clinical and radiological improvement. Antibiotic therapy is not however sufficient alone to achieve improvement in the respiratory impairment: bronchodilators and corticosteroids are necessary to treat the bronchospasticity. CONCLUSION: Despite the benign nature of community-acquired pneumonia due to Mycoplasma pneumoniae, clinical manifestations, particularly bronchial inflammation may have important consequences.