Background
In women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate ...favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with
in utero
exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies.
Methods
C1INH-HAE women who experienced at least 1 pregnancy were included from seven centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). The interview study retrospectively analyzed pregnancies who underwent (group 1) or not (group 2) pdC1INH. The overall goals of the study included immediate and long-term outcomes, in terms of outcomes in the time interval between pregnancy and survey.
Results
A total of 168 pregnancies from 87 included women were analyzed. At term delivery (>37 gestation-week, GW) has been registered in 73.8% of cases, while spontaneous abortion (SA) occurred in 14.2% of cases with a mean GW 7 ± 2. The group 1 including pdC1INH-treated pregnancies comprised a third of the cohort (51/168, time interval 1.5 ± 10.4 yrs), while the group 2 represented 69.6% (117/168, time interval 32.8 ± 14 yrs). The same prevalence of SA occurred when comparing group 1 (11.7%) with group 2 (15.4%) with a similar GW at SA. The group 1 was older at the pregnancy time and younger at the interview than the group 2 (
P
< 0.01 for both); moreover, the group 1 showed a higher prevalence of cesarean delivery (
P
< 0.0001). The overall prevalence of obstetrical syndromes was similar between two groups: however, gestational diabetes was described only in pdC1INH-untreated pregnancies.
In utero
pdC1INH-exposed children (
n
= 45) did not show differences compared with unexposed ones (
n
= 99) in neonatal short-term outcomes.
Conclusion
Through appropriate management and counseling, most of C1INH-HAE women undergo successful pregnancy and delivery. For pregnant C1INH-HAE women being treated with pdC1INH, our findings are reassuring and might lead to an improvement of both the knowledge about treatments and the experience of HAE itself.
Background
The For Angioedema Subcutaneous Treatment (FAST)‐2, a phase III, double‐blind, randomized, multicenter, placebo‐controlled study (ClinicalTrials.gov identifier: NCT00500656), established ...the efficacy and safety of single injections of icatibant, a bradykinin B2 receptor antagonist, in the treatment of hereditary angioedema (HAE) attacks. Here, we evaluate the efficacy and safety of repeated treatment with icatibant in adult patients experiencing HAE attacks during the FAST‐2 open‐label extension (OLE) phase.
Methods
Patients completing the controlled phase were eligible to participate in the OLE phase and receive open‐label icatibant (30 mg subcutaneously) for the treatment of cutaneous, abdominal, and/or laryngeal HAE attack(s) severe enough to warrant treatment. Time to onset of symptom relief was calculated for each attack. Descriptive analyses (median, 95% CIs) were performed for all attacks; post hoc analyses were conducted in patients with at least five icatibant‐treated attacks throughout the FAST‐2 OLE phase. Safety was also monitored.
Results
Fifty‐four patients received icatibant for 374 attacks (176 cutaneous, 168 abdominal, and 30 laryngeal). For cutaneous and/or abdominal attacks (attacks 2–5), the median times to onset of symptom relief ranged between 2.0 and 2.5 h. For all laryngeal attacks, the median times to regression (start of improvement) of symptoms ranged between 0.3 and 4.0 h. Post hoc analyses showed that the overall median time to onset of symptom relief was 2.0 h. Overall, 89.8% of attacks resolved with a single icatibant injection. No drug‐related serious adverse events were reported.
Conclusions
These findings have demonstrated the efficacy and safety of repeated icatibant treatment for HAE attacks.
Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are ...disabling and potentially life-threatening. We evaluated
n
= 17 patients with confirmed HAE diagnosis in basal and crisis state and
n
= 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman’s correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e.,
p
value <0.05) higher values in crisis states rather than in basal states for the three growth factors and cytokine IL-17. When comparing healthy subjects versus HAE patients at basal state, we found out significantly higher values in HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients, there is a connection between IL-17 and growth factors. The low-grade inflammation in absence of attacks is demonstrated by constant higher amount of IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that in this disease there is a level of activation that maintains the system in a “tick-over state,” that can be activate by several stimuli that are able to induce a increase in inflammatory mediators during the acute attack.
SUMMARY
The levels of soluble CD4 (sCD4), sCD8 and β2‐microglobulin (β2‐M) were measured in sera from patients with visceral leishmaniasis during the course of infection. Levels of sCD4. sCD8 and ...β2‐M were raised significantly above levels In normal sera and returned to the normal range after recovery. The decrease in the levels of CDS was related to a reduction of anaemia, leukopenia and thrombocytopenia. In contrast, sCD4 levels fluctuated during the period of infection. β2‐M returned within normal range more rapidly than sCD8 secretion. Our results suggest that T cells are activated during infection, and that it is also possible that the raised levels of these soluble molecules play a role in the impairment of protective immunity.
Immunology of human rickettsial diseases Mansueto, P; Vitale, G; Di Lorenzo, G ...
Journal of biological regulators and homeostatic agents,
04/2008, Letnik:
22, Številka:
2
Journal Article
Recenzirano
Among human rickettsial diseases caused by micro-organisms of the genus Rickettsia (Order Rickettsiales; Family Rickettsiaceae), transmitted to human hosts through arthropod vectors, Mediterranean ...Spotted Fever, or Boutonneuse Fever, and Rocky Mountain Spotted Fever are considered to be important infectious diseases due to continued prevalence in the developed world, and potentially fatal outcome in severe cases. Proliferation of rickettsiae, at the site of the tick bite, results in focal epidermal and dermal necrosis (tache noire). Rickettsiae then spread via lymphatic vessels to the regional lymph nodes, and, via the bloodstream, to skin, brain, lungs, heart, liver, spleen and kidneys. The pathogen invades and proliferates in the endothelial cells of small vessels, target cells of rickettsial infection, destroying them, and spreading the infection to the endothelia of the vascular tree. The damage of the endothelium, and the subsequent endothelia dysfunction, is followed by the activation of acute phase responses, with alteration in the coagulation and in the cytokine network, together with a transient immune dysregulation, characterized by the reduction in peripheral CD4+ T lymphocytes.
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently ...misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.
To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).
The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.
In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 41.7% vs 38 of 58 65.5%, respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).
From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.
ClinicalTrials.gov: NCT01034969.
The potential leishmanicidal activity of interleukin‐15 (IL‐15) was examined while priming with the cytokine phorbol‐myristate‐acetate (PMA)‐activated macrophages and infecting them with Leishmania ...infantum parasites. The activation of macrophage cultures with IL‐15 determined a significant anti‐leishmanial activity, comparable with that induced by interferon‐gamma (IFN‐γ). The killing of Leishmania in macrophages primed with IL‐15, as well as with IFN‐γ, was followed by an increase in the IL‐12 synthesis. The neutralization of IL‐15 or IFN‐γ, by specific monoclonal antibodies (MoAb) caused a significant reduction in leishmanicidal activity. Furthermore, in PMA‐activated macrophages, the neutralization of IL‐12 production by a specific anti‐IL‐12 MoAb reduced leishmanicidal activity induced by IL‐15 and IFN‐γ. Data indicate that IL‐15 could have a role as an activator of leishmanicidal activity, directly or indirectly, by inducing IL‐12 production.
The Icatibant Outcome Survey (IOS) is an observational study monitoring safety and effectiveness of icatibant in the real‐world setting. We analyzed safety data from 3025 icatibant‐treated attacks in ...557 patients (enrolled between July 2009 and February 2015). Icatibant was generally well tolerated. Excluding off‐label use and pregnancy, 438 patients (78.6%) did not report adverse events (AEs). The remaining 119 (21.4%) patients reported 341 AEs, primarily gastrointestinal disorders (19.6%). Of these, 43 AEs in 17 patients (3.1%) were related to icatibant. Serious AEs (SAEs) occurred infrequently. A total of 143 SAEs occurred in 59 (10.6%) patients; only three events (drug inefficacy, gastritis, and reflux esophagitis) in two patients were considered related to icatibant. Notably, no SAEs related to icatibant occurred in patients with cardiovascular disease, nor in those using icatibant at a frequency above label guidelines. Additionally, no major differences were noted in AEs occurring in on‐label vs off‐label icatibant users.
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