The characteristics of upper airway edema in hereditary and acquired angioedema with C1‐inhibitor deficiency

BackgroundAngioedemas localized in the upper airway are potentially life threatening, and without proper treatment, they may lead to death by suffocation. Upper airway edemas (UAE) in bradykinin‐mediated angioedemas can even be the first symptoms of the disease.MethodsOur survey was performed with a retrospective long‐term follow‐up method from the medical history of 197 hereditary (C1‐INH‐HAE) and 20 acquired C1‐inhibitor deficiency (C1‐INH‐AAE), 3 factor XII and 3 plasminogen gene mutation (FXII‐HAE, PLG‐HAE) patients treated at our center between 1990 and 2020. The UAE group included edemas localized to the mesopharynx, hypopharynx, and larynx, as narrowing of these anatomical regions can lead to suffocation.Results98/197 C1‐INH‐HAE (47 families) and 13/20 C1‐INH‐AAE, 1/3 PLG‐HAE, 1/3 FXII‐HAE patients had experienced UAE at least once according to their medical history. In case of C1‐INH‐HAE patients, in 6/47 families who had undiagnosed ancestors had 13 members who died of suffocation. After the diagnosis, 1‐1 member of two families died of UAE. 44/64 C1‐INH‐HAE patients did not smoke, 20/64 did. The occurrence of UAE was significantly higher in smoker patients. We analyzed 7607 HAE attacks of 56/98 patients. Out of all attacks, the incidence of UAE in the C1‐INH‐HAE group was 4%, and 9.5% in the C1‐INH‐AAE group, respectively.ConclusionEarly diagnosis is key in bradykinin‐mediated angioedemas cases, since the patient must be provided with adequate treatment; and also it is essential to inform patients about the importance of avoiding the trigger factors and the early symptoms of UAE, as these measures could significantly decrease the incidence of lethal UAEs.     

Primary progressive aphasia: a case report

We report a 69-year-old male patient whose motor aphasia started at the age of 61. The language disability remained isolated and progressed over a period of eight years without any additional cognitive deficits. Computed tomography (CT) and magnetic resonance imaging (MRI) showed moderate cortical atrophy with frontal dominance. Single photon emission tomography (SPECT) showed hypoperfusion in the frontotemporoparietal region, positron emission tomography (PET) demonstrated a global cortical reduction of glucose utilization with a lesser decrement in the occipital lobes. The clinical symptoms and the neuropsychological findings fit the diagnosis of primary progressive aphasia.     

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules

Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using ^99mTc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on ^99mTc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of ^99mTc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using ^99mTc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, ^99mTc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules. Received 12 January and in revised form 18 March 1999     

Effect of long-term beta-blockade on aortic root compliance in patients with Marfan syndrome.

BACKGROUND: This study was undertaken to assess the effect of long-term beta-blockade on the aortic root stiffness index and distensibility in patients with Marfan syndrome. METHODS: Aortic root stiffness index and distensibility were calculated according to the formulas of Stefanadis and Hirai, respectively, with 2-dimensional guided M-mode echocardiogram before and after an average of 26 months of atenolol administration. RESULTS: Twenty-three asymptomatic patients were studied (11 men and 12 women, aged 31 +/- 14.2 years). The follow-up was 4 +/- 2.2 years. The dose of atenolol was individualized (mean 43.5 +/- 21.6 mg/d). Heart rate decreased from 79 +/- 9 beats/min to 64 +/- 9 beats/min (P =. 01), and systolic blood pressure decreased from 124 +/- 13 mm Hg to 114 +/- 2 mm Hg (P =.01). Distensibility increased from 1.85 +/- 0. 70 x 10(-6) cm2/dynes-1 to 2.21 +/- 0.76 x 10-6 cm2/dynes-1 (P =.02), and the stiffness index decreased from 9.68 +/- 3.78 to 8.85 +/- 3. 15 ( P =.2). Two groups of responses to treatment were identified. Compared with baseline values 15 (65%) patients who responded to treatment had increased distensibility and decreased stiffness index of the aortic root (P =.05). Eight patients (35%) who did not respond to treatment had no significant change. Body weight >91 kg and baseline end-diastolic aortic root diameter >40 mm were significantly associated with no response (P =.05). Two patients in the nonresponding group had echocardiographic progression of aortic insufficiency. CONCLUSIONS: There was a heterogeneous response in the aortic root elastic properties after long-term treatment with atenolol in asymptomatic patients with Marfan syndrome. Stiffness index and distensibility are more likely to respond when the baseline end-diastolic aortic root diameter is <40 mm.     

Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies

Objective. To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating anti-mitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. Methods. Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. Results. Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. Conclusion. Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies.     

Placental macrophage contact potentiates the complete replicative cycle of human cytomegalovirus in syncytiotrophoblast cells: role of interleukin-8 and transforming growth factor-beta1.

Although syncytiotrophoblast (ST) cells can be infected by human cytomegalovirus (HCMV), in vitro studies have indicated that ST cells do not support the complete viral reproductive cycle, or HCMV replication may occur in less than 3% of ST cells. The present study tested the possibility that placental macrophages might enhance activation of HCMV carried in ST cells and, further, that infected ST cells would be capable of transmitting virus to neighboring macrophages. For this purpose, we studied HCMV replication in ST cells grown alone or cocultured with uninfected placental macrophages. Our results demonstrated that HCMV gene expression in ST cells was markedly upregulated by coculture with macrophages, resulting in release of substantial amounts of infectious virus from HCMV-infected ST cells. After having become permissive for viral replication, ST cells delivered HCMV to the cocultured macrophages, as evidenced by detection of virus-specific antigens in these cells. The stimulatory effect of coculture on HCMV gene expression in ST cells was mediated by marked interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1) release from macrophages, an effect caused by contact between the different placental cells. Our findings indicate an interactive role for the ST layer and placental macrophages in the dissemination of HCMV among placental tissue. Eventually, these interactions may contribute to the transmission of HCMV from mother to the fetus.     

EAACI Guidelines on Allergen Immunotherapy: House dust mite‐driven allergic asthma

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence‐based recommendations for the use of house dust mites (HDM) AIT as add‐on treatment for HDM‐driven allergic asthma. This guideline was developed by a multi‐disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT‐tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add‐on to regular asthma therapy for adults with controlled or partially controlled HDM‐driven allergic asthma (conditional recommendation, moderate‐quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM‐driven allergic asthma as the add‐on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low‐quality evidence).     

Macrophage‐mediated psoriasis can be suppressed by regulatory T lymphocytes

We recently described an inducible human TNF transgenic mouse line (ihTNFtg) that develops psoriasis‐like arthritis after doxycycline stimulation and analysed the pathogenesis of arthritis in detail. Here, we show that the skin phenotype of these mice is characterized by hyperproliferation and aberrant activation of keratinocytes, induction of pro‐inflammatory cytokines, and infiltration with Th1 and Treg lymphocytes, particularly with macrophage infiltration into lesional skin, thus pointing to a psoriasis‐like phenotype. To reveal the contribution of T cells and macrophages to the development of TNF‐mediated psoriasis, ihTNFtg mice were crossbred into RAG1^KO mice lacking mature T and B cells. Surprisingly, the psoriatic phenotype in the double mutants was not reduced; rather, it was enhanced. The skin showed significantly increased inflammation and in particular, increased infiltration by macrophages. Consequently, depletion of macrophages in RAG1^KO or wild‐type mice led to decreased disease severity. On the contrary, depletion of Treg cells in wild‐type mice increased both psoriasis and the number of infiltrating macrophages, while adoptive transfer of Foxp3‐positive cells into RAG1^KO or wild‐type mice decreased both the development of psoriasis and macrophage infiltration. Thus, we conclude that Treg lymphocytes inhibit the pro‐inflammatory activity of macrophages, which are the major immune effector cells in hTNF‐mediated psoriasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.