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Introduction: Hereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks. Methods: Retrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). Results: The proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p<0.001 in females); the monthly mean of acute attacks was significantly higher after puberty, and this occurred both in females (median (IQR) = 0.41(2) in the three years before puberty vs 2(2.17) in the three years after, p<0.001) and in males (1(1.92) vs 1.25(1.56) respectively, p<0.001). The increase was greater in females. No significant differences were detected in attack location before and after puberty. Discussion: Overall, our study confirms previous reports on a more severe phenotype in the female gender. Puberty predisposes to increased numbers of angioedema attacks, in particular in female patients.
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INTRODUCTION: Hereditary angioedema due to C1-inhibitor (C1-INH-HAE) is a rare disease characterized by unpredictable swelling attacks that may be life-threatening when affecting the upper airways. Understanding the pathophysiology of HAE and the mechanism of bradykinin-mediated angioedema allowed the development of new therapies for the treatment of HAE: clinical trials are ongoing to expand the number of drugs available for on-demand treatment and prophylaxis. AREAS COVERED: Authors discuss the products that have been used to treat this disease for many years and present the most recently marketed products and those which are under development. EXPERT OPINION: Significant therapeutic progress has been made in HAE. In particular, drugs targeting specific molecules involved in the angioedema formation were developed and studies with new drugs are ongoing. In the coming years, more effective therapies with easier administration route options for on-demand treatment and long-term prophylaxis will be available to treat this disease and the variety of patients. Gene therapy strategies may offer a definitive treatment. High costs of current and new drugs may be a limiting factor for their availability, especially in developing countries.
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Angioedema , Angioedemas Hereditarios , Angioedemas Hereditarios/tratamiento farmacológico , Bradiquinina/uso terapéutico , Humanos , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10 different Italian centers and summarized the most recent literature data. METHODS: A review of patients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG. RESULTS: Thirty-nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lips, and 28.2% suffered from Melkersson-Rosenthal syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG. Oral aphthosis and cervical lymphadenopathy were also described. The mean diagnostic delay was 3.4 years. Histological evaluation was performed in 34/39 patients (87.2%); non-caseating granulomas were found in 73.5% of them. Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%), and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results. Anti-TNF-α and anti-IgE monoclonal antibodies were used in 6 (15.4%) and 1 (2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response. CONCLUSIONS: OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial, management is difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establish registry databases and address challenges of long-term management.
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Granulomatosis Orofacial , Síndrome de Melkersson-Rosenthal , Diagnóstico Tardío , Granulomatosis Orofacial/diagnóstico , Granulomatosis Orofacial/tratamiento farmacológico , Granulomatosis Orofacial/epidemiología , Humanos , Italia/epidemiología , Síndrome de Melkersson-Rosenthal/diagnóstico , Síndrome de Melkersson-Rosenthal/epidemiología , Síndrome de Melkersson-Rosenthal/terapia , Inhibidores del Factor de Necrosis TumoralRESUMEN
Isolated angioedema, which is a localized, non-pitting, and transient swelling of the subcutaneous or submucosal tissue not associated with pruritus, urticaria, or anaphylaxis, may be classified, based on genetic pattern and mediators, respectively, as acquired or hereditary and histamine- or non-histamine-induced. The pediatric population with C1-INH-HAE (Hereditary angioedema due to C1-inhibitor deficiency) is mostly symptomatic. The frequency of symptoms in such a population compared to adults seems to be lower, but we need more prospective data to conclude on this point. The HGR (Hereditary angioedema global registry), which collects symptoms in real time, will probably provide such information. In terms of treatments, pediatric patients are significantly disadvantaged due to the few studies aimed at registering treatment for this population.
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Angioedemas Hereditarios/diagnóstico , Proteína Inhibidora del Complemento C1/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Italia , Masculino , Sistema de Registros , Adulto JovenRESUMEN
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1ß, IL-6, IL-10, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-ß) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects comparing the condition during the crisis respect to the value in the remission phase, in particular type 17 signature cytokines are increased, whereas IL-23 is unmodified and TGF-ß3 is significantly reduced. When comparing healthy and HAE subjects in the remission state, we found a significant difference for IL-17, GM-CSF, IL-21, TGF-ß1 and TGF-ß2 cytokines. These results confirm and extend our previous findings indicating that in HAE there is operating an inflammatory activation process, which involves also T helper 17 (Th17) cytokines and TGF-ß isoforms, associated with localized angioedema attacks and characterized by elevated bradykinin levels.
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Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/inmunología , Regulación de la Expresión Génica/inmunología , Interleucina-17/inmunología , Células Th17/inmunología , Factor de Crecimiento Transformador beta/inmunología , Adolescente , Adulto , Anciano , Angioedemas Hereditarios/genética , Angioedemas Hereditarios/patología , Bradiquinina/genética , Bradiquinina/inmunología , Bronquios/inmunología , Bronquios/patología , Estudios de Casos y Controles , Niño , Proteína Inhibidora del Complemento C1/genética , Proteína Inhibidora del Complemento C1/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Interleucina-17/genética , Interleucina-23/genética , Interleucina-23/inmunología , Interleucinas/genética , Interleucinas/inmunología , Intestinos/inmunología , Intestinos/patología , Masculino , Persona de Mediana Edad , Tejido Subcutáneo/inmunología , Tejido Subcutáneo/patología , Células Th17/patología , Factor de Crecimiento Transformador beta/genética , Interleucina-22RESUMEN
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. METHODS: Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency. RESULTS: 983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5(th) decade and women after the 6(th). Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05. CONCLUSION: This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.
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Angioedemas Hereditarios/epidemiología , Angioedemas Hereditarios/genética , Adolescente , Adulto , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Angioedemas Hereditarios/metabolismo , Citocinas/metabolismo , Interleucina-17/metabolismo , Adolescente , Adulto , Anciano , Angioedemas Hereditarios/patología , Niño , Proteína Inhibidora del Complemento C1/análisis , Proteína Inhibidora del Complemento C1/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Regulación hacia Arriba , Adulto JovenRESUMEN
The background of this article is as follows: Few data are available about the persistence of serum-specific IgG antibodies to L. infantum after acute VL. The objective of this article is to evaluate the persistence of antibodies against L. infantum in patients healed from acute VL, and the kinetic of the same antibodies observed in 2 cases of VL relapse and 2 cases of resistance to therapy. The methods which we used to obtain our objective are the following: 55 apparently immunocompetent, HIV-negative patients were examined for antibodies to L. infantum by IFAT over 14 years period, and we got the following results: Serum-specific IgG antibodies titers decrease slowly, but constantly. In the patients with a diagnosis of VL relapse, the kinetic of antibodies was characterized by an initial reduction, and a subsequent antibody levels rapidly increase, while in the patients with a clinical and parasitological diagnosis of VL not responding to specific therapy, we demonstrated persistent high level of antibodies to L. infantum. Finally, we conclude that specific antibodies to L. infantum might persist for many years, and decrease slowly, but steadily. The persistence of these specific antibodies is not related to poor therapeutic response or prognosis, but an acute increase in their levels might be a sentinel of a VL relapse, while persistence of high antibody levels could suggest a resistance to therapy.
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Anticuerpos Antiprotozoarios/sangre , Leishmania infantum/inmunología , Leishmaniasis Visceral/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina G/sangre , Leishmaniasis Visceral/inmunología , Masculino , Persona de Mediana Edad , Recurrencia , Sicilia , Factores de Tiempo , Adulto JovenRESUMEN
To evaluate seroprevalence of B. henselae infection both in Sicilian children and healthy blood donors. Furthermore, circulation of Bartonella in the natural reservoir was also studied. Two hundred forty-three children, living in Sicily (Palermo), affected by various diseases, without clinical features suggesting B. henselae infection, together with 122 healthy blood donors were serologically investigated for IgG and IgM antibodies by indirect fluorescent antibody test (IFAT). One hundred twenty stray and 62 pet cats were also analyzed only for IgG. Among children 25.1% had IgG antibodies to B. henselae; 18.5% showed a titer 1:64, 2.4% 1:128, 2.4% 1:256, 0.8% 1:512, 0.4% 1:1024, and 0.4% 1:5120. Among healthy blood donors 11.4% had IgG class antibodies to B. henselae; 9.8% showed a titer 1:64 and 1.6% 1:128. All the human serum samples did not show positive results for B. henselae IgM class antibodies. Stray cats (68.3%) and pet cats (35.4%) also had IgG class antibodies to B. henselae. We demonstrated high frequency of serologic evidence of past B. henselae infection, in young Italian children, affected by various diseases, apparently free of any clinical features suggesting B. henselae infection. This observation is supported by high circulation of Bartonella in cats.
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Anticuerpos Antibacterianos/inmunología , Bartonella henselae/inmunología , Donantes de Sangre , Gatos/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/sangre , Antígenos Bacterianos/inmunología , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Lactante , Masculino , Persona de Mediana Edad , Sicilia/epidemiología , Adulto JovenRESUMEN
The aim of the study was to analyze the acute inflammatory response after implantation of a heavyweight mesh of polypropylene (PP) compared with a composite mesh of light PP and polyglactin 910 (PG) in patients undergoing inguinal hernioplasty. A total of 30 male patients with inguinal hernia were included in the study and divided into 2 groups (PP and PP-PG) according to the mesh used. Changes of leukocytes, cytokines, growth factors, and acute phase proteins were evaluated in the sera. Leukocytes and acute phase proteins were significantly increased postoperatively in both groups, and the values were slightly higher in the PP group. Cytokine levels were significantly increased postoperatively in both groups; a slight increase was observed in the PP-PG group, especially for the proinflammatory cytokine. Growth factors decreased significantly in both groups immediately after surgery. The authors found that the use of the mesh is a stimulator of inflammatory response, and the 2 types of mesh induce a similar inflammatory response.
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Materiales Biocompatibles/efectos adversos , Hernia Inguinal/cirugía , Inflamación/inducido químicamente , Poliglactina 910/efectos adversos , Polipropilenos/efectos adversos , Adulto , Anciano , Proteína C-Reactiva/análisis , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Proteína Antagonista del Receptor de Interleucina 1/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Mallas Quirúrgicas/efectos adversos , Factor de Crecimiento Transformador beta/sangre , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
BACKGROUND: The aim of the present study was the detection of asymptomatic coronary re-stenosis after percutaneous coronary intervention (PCI). METHODS: We studied 26 subjects who had been recently implanted with a paclitaxel-eluting coronary stent by both a conventional exercise test and the determination of plasma B-type natriuretic peptide (BNP) levels. RESULTS: At control coronary angiography, nine months after initial PCI, six patients had re-stenosis and 20 were re-stenosis free. We found that re-stenosis was best predicted by the combination of a basal plasma BNP level > or = 50 pg/ml and a positive or uncertain conventional exercise test (positive likelihood ratio of the combination = 10). The best predictor of absence of re-stenosis was a low (< 50 pg/ml) plasma BNP level (negative likelihood ratio = 0.26). CONCLUSIONS: Accordingly, basal BNP level testing can be recommended in the follow-up evaluation of coronary patients after PCI, to improve both the detection and the exclusion of asymptomatic re-stenosis.
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Angioplastia Coronaria con Balón/efectos adversos , Fármacos Cardiovasculares/administración & dosificación , Reestenosis Coronaria/diagnóstico , Estenosis Coronaria/terapia , Stents Liberadores de Fármacos , Péptido Natriurético Encefálico/sangre , Paclitaxel/administración & dosificación , Angioplastia Coronaria con Balón/instrumentación , Biomarcadores/sangre , Angiografía Coronaria , Reestenosis Coronaria/sangre , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Estenosis Coronaria/sangre , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Knowing the dynamics of growth factor and cytokine secretion within the site of a surgical operation is important, as they play a crucial role in the pathophysiology of wound healing and are a target for modifying the repair response. The aim of this study was to evaluate the production of several cytokines and growth factors in the drainage wound fluid from patients undergoing incisional hernia repair: namely, interleukin (IL)-6, IL-10, IL-1alpha, IL-1 ra, interferon-gamma, vascular endothelial growth factors and basic fibroblast growth factor. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases, a closed-suction drain was inserted in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on postoperative days 1-4 and the amount was recorded each time. Growth factors and cytokines production was evaluated as the whole amount produced over a 24-hour period. In all patients, the amount of drain fluid from surgical wounds was more copious the first day after surgery, it decreased significantly afterward. The presence of all cytokines was highest on postoperative day 1, decreasing over the following days. More specifically, the production of IL-1 ra, IL-6, IL-1alpha, and IL-10 on postoperative day 1 fell sharply on postoperative days 3 and 4, whereas, after an initial reduction, interferon-gamma showed an increase from day 2 onward. Vascular endothelial-derived growth factor production increased progressively after the operation reaching statistical significance only on day 4. As for basic fibroblast growth factor, it showed an opposite pattern: it was higher on postoperative day 1 decreasing thereafter. This analysis of cytokine and growth factor production in the drain fluid will lead us to a better evaluation of the events that follow a surgical wound and to a better understanding of the healing process.
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Citocinas/metabolismo , Exudados y Transudados/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Hernia Ventral/cirugía , Succión , Factor A de Crecimiento Endotelial Vascular/metabolismo , Femenino , Hernia Ventral/metabolismo , Humanos , Interferón gamma/metabolismo , Interleucinas/metabolismo , Persona de Mediana Edad , Cuidados PosoperatoriosRESUMEN
The number of old and oldest old patients undergoing surgery of varying severity is increasing. Ageing is a process that changes the performances of most physiological systems and increases susceptibility to diseases and death; accordingly, host responses to surgical stress are altered with ageing and the occurrence of age-related increase in susceptibility to post-operative complications has been claimed. Twenty-four male patients undergoing Lichtenstein (LH) hernioplasty for unilateral inguinal hernia were included in this study and divided in two groups (Young and Old respectively), according to their age. As expression of the acute phase response, we measured changes in concentration of pro-inflammatory cytokines Tumor necrosis factor-alpha and Interleukin-1beta, leukocytes, acute phase proteins C-reactive protein and alpha 1-antitrypsin. Elderly humans showed prolonged and strong inflammatory activity compared to younger subjects in response to surgical stress, indicating that the acute-phase response to surgical stress of elderly humans varies from that of the young, showing initial hyperactivity and a delayed termination of the response. Thus, the acute phase response to surgical stress is higher in old subjects, but the clinical significance of this remains unclear. It is not known whether a causal relationship exists between this stronger acute phase response and the increases in susceptibility to post-operative complications observed in aged patients.
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Proteínas de Fase Aguda/metabolismo , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Estrés Fisiológico/sangre , Anciano , Biomarcadores , Hernia Inguinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Índice de Severidad de la Enfermedad , Estrés Fisiológico/etiologíaRESUMEN
BACKGROUND: Angiogenesis is strongly influenced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), whose production is also regulated by interferon (IFN)-gamma and interleukin (IL)-10. The aim of this study was to evaluate the modifications of serum VEGF, b-FGF, IFN-gamma and IL-10 levels in patients with inguinal hernia undergoing hernioplasty with the Lichtenstein technique (LH) using polypropylene mesh or with Bassini open conventional inguinal hernia repair (BH). MATERIALS AND METHODS: Randomly, 16 patients underwent BH, and 16 were treated with the LH technique using polypropylene mesh. Blood samples were collected 24 h prior to surgery and then 6, 24, 48 and 168 h postoperatively. The serum concentrations of VEGF, b-FGF, IFN-gamma and IL-10 were evaluated. RESULTS: In BH patients, a peak of VEGF synthesis at 6 h with a normalization of this parameter 24 h after surgery has been observed. In the same subjects, b-FGF synthesis increased after surgery reaching significant levels 48 h later. On the contrary, in LH patients, a decrease in the serum VEGF and b-FGF concentrations was detected after surgery and their increase afterwards. IL-10 was increased in both groups 6 h after operation and declined to preoperative levels 24 h afterwards. IFN-gamma enhanced in LH patients 6 h after surgery, whereas no modifications were detected in BH subjects. CONCLUSIONS: This preliminary study shows that VEGF and b-FGF modifications, associated with alterations of cytokine secretion, are detectable in human undergoing hernioplasty, and suggests that they could somehow influence in the wound-healing process.
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Factor 2 de Crecimiento de Fibroblastos/sangre , Hernia Inguinal/sangre , Hernia Inguinal/cirugía , Mallas Quirúrgicas/efectos adversos , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Análisis de Varianza , Ensayo de Inmunoadsorción Enzimática , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
Wound healing is a complex process involving interaction between different cell types, such as growth factors. Among these, vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (b-FGF) are the most important. The aim of this study was to assess the production of VEGF and b-FGF in wound drainage fluid from patients undergoing incisional abdominal hernia repair. Ten female patients with abdominal midline incisional hernia undergoing surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and removed on postoperative day 4. Wound fluid was collected on the I, II, III and IV day and its amount at each time was recorded. VEGF and b-FGF production were evaluated as the quantity produced in 24 hours. In all patients the amount of drainage fluid from the surgical wound was highest on the I day after surgery, after which there was a significant reduction. VEGF production increased progressively after the operation proving significantly higher only on the IV day. The amount of b-FGF, in contrast, was higher on the I day, decreasing thereafter on the following postoperative days. Analysis of the production of growth factors in the drainage fluid has enabled us to better assess the events that occur following surgical wounds and has confirmed the physiology of the healing process and the possible use of these factors in modulating positive healing.