Mauro Cancian

Inhibitory effect of heparin on skin reactivity to autologous serum in chronic idiopathic urticaria

BACKGROUND Most patients with chronic idiopathic urticaria (CIU) show cutaneous reactivity to intradermal injection of autologous serum. In some cases this reactivity is associated with the presence of autoantibodies directed against IgE or IgE receptors expressed on mast cells, whereas in others no autoimmune mechanisms can be documented. OBJECTIVES The aims of this study were to compare the cutaneous reactivity to serum and plasma samples in a series of patients with active CIU and to address the mechanisms of the inhibitory effect exerted by heparin on the cutaneous responsiveness to the histamine-releasing factors (HRFs) present in CIU serum. METHODS Fourteen patients with CIU were injected intradermally with autologous serum, plasma (anticoagulated by either heparin or EDTA), or serum samples to which heparin had been added. The effects of heparin injection on cutaneous responsiveness to allergens was tested in 5 atopic patients. Moreover, in a set of experiments sera were also adsorbed with Sepharose-conjugated heparin. RESULTS All the patients had positive cutaneous reactions to autologous serum injection. When heparinized plasma was injected, negative reactions were observed in 12 of 14 patients, and a sizable reduction in the wheal-and-flare reactions was recorded in the remaining 2. Compared with results obtained with serum, no substantial change was observed in 6 of 8 patients injected with EDTA-anticoagulated plasma. When heparin was added to serum, abrogation of skin reactivity was seen; nonetheless, no change in the cutaneous response to allergens was associated with locally administered heparin in 5 atopic patients with no history of CIU. Finally, adsorption of CIU sera with solid-phase heparin abrogated the ability to induce cutaneous reactions in 5 of 7 patients, whereas in the remaining 2 a sizable reduction was observed. CONCLUSIONS These data indicate that heparin is able to profoundly inhibit the cutaneous response to HRFs present in the sera of patients with CIU. Although the precise level of action of this heparin-mediated effect is unclear from present data, preliminary evidence seems to indicate that heparin could directly interfere with HRFs present in CIU sera.

Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study.

Hereditary angioedema (HAE) owing to C1 inhibitor deficiency is an autosomal dominant disorder, characterized by recurrent, potentially life‐threatening, localized attacks of tissue swelling. Current treatment involves the infusion of C1 inhibitor protein (C1‐INH) isolated from human plasma.

Guidance for diagnosis and treatment of acute angioedema in the emergency department: consensus statement by a panel of Italian experts

Angioedema attacks, characterized by the transient swelling of the skin and mucosae, are a frequent cause of visits to the emergency department. Swellings of the oral cavity, tongue, or larynx can result in life-threatening airway obstruction, while abdominal attacks can cause severe pain and often lead to unnecessary surgery. The underlying pathophysiologic process resulting in increased vascular permeability and plasma extravasation is mediated by vasoactive molecules, most commonly histamine and bradykinin. Based on the mediator involved, distinct angioedema forms can be recognized, calling for distinct therapeutic approaches. Prompt recognition is challenging for the emergency physician. The low awareness among physicians of the existence of rare forms of angioedema with different aetiologies and pathogenesis, considerably adds to the problem. Also poorly appreciated by emergency personnel may be the recently introduced bradykinin-targeted treatments. The main objective of this consensus statement is to provide guidance for the management of acute angioedema in the emergency department, from presentation to discharge or hospital admission, with a focus on identifying patients in whom new treatments may prevent invasive intervention.

An Uncommon Cause of Acute Pancreatitis

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?

An uncommon cause of acute pancreatitis. Hereditary angioedema-induced acute pancreatitis.

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?

Living with Chronic Spontaneous Urticaria in Italy: A Narrative Medicine Project to Improve the Pathway of Patient Care

Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

Emotional processes and stress in children affected by hereditary angioedema with C1-inhibitor deficiency: a multicenter, prospective study

BackgroundHereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent edema of unpredictable frequency and severity. Stress, anxiety, and low mood are among the triggering factors most frequently reported. Impaired regulation and processing of emotions, also known as alexithymia, may influence outcomes. The aim of this study was to confirm the presence of alexithymia and stress in children with C1-INH-HAE, to determine whether they are also present in children affected by other chronic diseases, and to investigate their relationship with C1-INH-HAE severity. Data from children with C1-INH-HAE (n = 28) from four reference centers in Italy were compared with data from children with type 1 diabetes (T1D; n = 23) and rheumatoid arthritis (RA; n = 25). Alexithymia was assessed using the Alexithymia Questionnaire for Children scale; perceived stress was assessed using the Coddington Life Event Scale for Children (CLES-C).ResultsMean age (standard deviation [SD]) in the C1-INH-HAE, T1D, and RA groups was 11.8 (3.3), 11.7 (2.9), and 11.1 (2.6) years, respectively. Mean C1-INH-HAE severity score was 5.9 (2.1), indicating moderate disease. Alexithymia scores were similar among disease groups and suggestive of difficulties in identifying and describing emotions; CLES-C scores tended to be worse in C1-INH-HAE children. C1-INH-HAE severity was found to correlate significantly and positively with alexithymia (p = 0.046), but not with perceived stress. Alexithymia correlated positively with perceived stress.ConclusionsAlexithymia is common in children with chronic diseases. In C1-INH-HAE, it may result in increased perceived stress and act as a trigger of edema attacks. Comprehensive management of C1-INH-HAE children should consider psychological factors.

A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy.

Introduction: Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA.

Diagnostic and therapeutic management of hereditary angioedema due to C1-inhibitor deficiency: the Italian experience.

PURPOSE OF REVIEW Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disease, with a reported prevalence of about 1 : 50 000. C1-INH-HAE causes disabling symptoms, which may be life-threatening if swelling affects upper airways. Diagnostic procedures are now well established and the role of bradykinin as the main mediator of plasma outflow eliciting angioedema formation has been clearly elucidated. RECENT FINDINGS Increased understanding of the pathogenesis of C1-INH-HAE allowed in recent years the development of new drugs targeted to inhibit bradykinin synthesis (Ecallantide) or activity (Icatibant). At the same time, a recombinant C1-INH concentrate (Ruconest) was produced from the milk of transgenic rabbits and two plasma-derived C1-INHs (Berinert, Cinryze) underwent controlled trials to obtain marketing authorization. In 2012, an Italian network for C1-INH-HAE (ITACA) was established by physicians of 17 HAE reference centres to collect data from Italian patients and to homogenize and improve the diagnostic and therapeutic approach to the disease. SUMMARY Although there is a widespread agreement on therapeutic goals and treatment of C1-INH-HAE acute attacks, different approaches to prophylaxis are still present among HAE experts. The clinical experience of ITACA on a large population of C1-INH-HAE patients followed for several years may help in identifying the most effective strategies for the management of the disease.

Clinical Challenges and Images in GIAn Uncommon Cause of Acute Pancreatitis

Question: A 32-year-old woman presented to the emergency department in acute distress; she had a distended abdomen with marked tenderness and poor peristalsis. Nausea, vomiting, and severe abdominal pain radiating to her back was resistant to analgesic and anti-emetic drugs that had been started 6 hours before admission. Her past clinical history was characterized by recurrent episodes of cutaneous swelling unresponsive to antihistamines, steroids, and other anti-allergy drugs. Laboratory tests revealed hemoconcentration (hematocrit, 48%), leukocytosis (white blood cell count, 11.410 10 9 /L; neutrophils, 9.830 10 9 /L), and hyperamylasemia (470 U/L; reference range, 0‐53), with transaminases and bilirubin in the normal range. Computed tomography was performed and showed an enlarged, edematous pancreas with indistinct edges (Figure A, white arrows) and left pararenal fluid collection (Figure A, black arrow), as well as additional pathologic findings (Figures B and C). What is the diagnosis? How should the patient be managed?