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Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

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BACKGROUND: Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered icatibant in patients with HAE type I or II. Secondary objectives included patient convenience and clinical efficacy of self-administration. METHODS: In this phase IIIb, open-label, multicenter study, adult patients were trained to self-administer a single 30-mg icatibant subcutaneous injection to treat their next attack. Icatibant-naïve patients were treated by an HCP prior to self-administration. Evaluations included adverse event (AE) reporting, a validated questionnaire for convenience, and visual analog scale for efficacy. RESULTS: A total of 151 patients were enrolled; 104 had an attack requiring treatment during the study, and 97 patients (19 naïve) were included in the self-administration cohort. Recurrence or worsening of HAE symptoms (22 of 97) was the most commonly reported AE; rescue medications including icatibant (N = 3) and C1-inhibitor concentrate (N = 6) were used in 13 cases. Overall, 89 of 97 patients used a single injection of icatibant. No serious AEs or hospitalizations were reported. Most patients (91.7%) found self-administration preferable to administration in the clinic. The median time to symptom relief (3.8 h) was comparable with results from controlled trials of icatibant. CONCLUSIONS: With appropriate training, patients were successfully able to recognize HAE attacks and decide when to self-administer icatibant. This, coupled with the patient-reported high degree of satisfaction, convenience and ease of use supports the adoption of icatibant self-administration in clinical practice.

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Hereditary angioedema is a rare autosomal dominant disease characterized by recurrent episodes of acute edema affecting the skin and the respiratory and digestive tracts. Acute edema blisters or hydro-static bullae develop after rapid accumulation of interstitial fluid usually associated to cardiac insufficiency. Lesions contain sterile fluid and break up easily resolving without scars. Blisters disappear when fluid accumulation resolves. We describe a patient developing recurrent acute edema blisters as a consequence of cutaneous hereditary angioedema attacks.

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Hereditary angioedema is a rare autosomal dominant disease characterized by recurrent episodes of acute edema affecting the skin and the respiratory and digestive tracts. Acute edema blisters or hydro-static bullae develop after rapid accumulation of interstitial fluid usually associated to cardiac insufficiency. Lesions contain sterile fluid and break up easily resolving without scars. Blisters disappear when fluid accumulation resolves. We describe a patient developing recurrent acute edema blisters as a consequence of cutaneous hereditary angioedema attacks

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BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and safety for moderate to severe CIU treatment. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.

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UNLABELLED: We have analysed the phenotype of T lymphocytes in two X-linked lymphoproliferative disease (XLP) patients with the same SH2D1A mutation differing in initial exposure to Epstein-Barr virus (EBV) and treatment. While memory T lymphocytes (with low CCR7 and CD62L expression) prevailed in both XLP patients, in patient 9, who developed acute infectious mononucleosis (AIM) and received B cell ablative treatment, the predominant phenotype was that of late effector CD8 T cells (CD27-, CD28-, CCR7-, CD62L-, CD45 RA+, perforin+), while in patient 4 (who did not suffer AIM) the prevalent phenotype of CD8 T lymphocytes was similar to that of normal controls (N) or to that of adult individuals who recovered from AIM: CD27+ , CD28+, CCR7-, CD62L-, CD45 RO+ and perforin-. CD57 expression (related to senescence) was also higher in CD8 T cells from patient 9 than in patient 4, AIM or N. Persistently high EBV viral load was observed in patient 9. The results obtained from this limited number of XLP patients suggest that events related to the initial EBV encounter (antigen load, treatment, cytokine environment) may have more weight than lack of SH2D1A in determining the long-term differentiation pattern of CD8 memory T cells.

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Diclofenac (Dc) induces an IgE-independent basophil (Ba) degranulation in susceptible individuals. CD63 Ba expression is utilized as an in vitro test for diagnosis of drug hypersensitivity. We tested the ability of Dc to induce CD63 Ba expression by flow cytometry (BAT) and Ba degranulation using light microscopy (HBDT) in patients sensitive to Dc. We studied 14 patients with diclofenac hypersensitivity, also two patients sensitive to Dermatophagoides pteronyssinus (Dp), and 12 normal controls. HBDT was performed by mononuclear cells toluidine blue staining. BAT determined CD63 expression in antiCD63/anti-IgE/anti-CD45-labelled whole blood. In each case, the percentage of activated Ba post-stimulation with 1 and 10 microg/ml Dc was determined. Positive controls included N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide-induced activation. IgE-mediated Ba activation was induced with a Dp allergenic extract. With Dc 1 microg/ml, mean HBDT in Dc-susceptible individuals was 33.62 +/- 18.35% and 8.49 +/- 4.79% in controls (P = 0.0001). Mean BAT was 2.04 +/- 1.68% and 1.93 +/- 1.40% in controls (P = 0.8). Ba preincubation with Dc did not affect fMLP-induced CD63 expression, neither in Dc-sensitive individuals (P = 0.8) (n = 4) nor in subjects without Dc hypersensitivity (P = 0.25) (n = 4). Ba from the two patients sensitive both to Dc and Dp responded to Dp but not to Dc by BAT: Dc, 1.99 +/- 0.78%; Dp: 60.87 +/- 9.28%; but showed degranulation by HBDT: Dc, 30.53 +/- 1.02%, Dp: 48.78 +/- 22.17%. Dc induces Ba degranulation in sensitive patients in a way that does not induce CD63 expression and is different from IgE-mediated and fMLP-mediated degranulation. Our results suggest that CD63 expression is not a reliable diagnostic method for diclofenac allergy.

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La urticaria crónica es una enfermedad frecuente, caracterizada por la presencia de ronchas y/o angioedema con una duración superior a las 6 semanas. En un número importante de pacientes se comporta como una enfermedad autoinmune asociada frecuentemente con alteraciones en la función tiroidea y com la presencia de anticuerpos antitiroideos. Presentamos una serie de 70 pacientes consecutivos con diagnóstico de urticaria crónica a los cuales les investigamos la función tiroidea y la presencia de anticuerpos antiperoxidasa tiroidea. Siete (10%) tenían diagnóstico de enfermedad tiroidea previa al momento de la consulta. A los 63 pacientes restantes se les estudió los niveles de tirotrofina sérica, 11 de los cuales (17%) presentaron valores anormales, que sumados a los 7 con enfermedad previa llegan a 18 (26%) con función tiroidea alterada. A 61 pacientes se les investigo anticuerpos antiperoxidasa tiroidea, 22 (36%) fueron positivos. De 57 pacientes sin diagnóstico de patología tiroidea previa al momento de la consulta por urticaria, a los que se les estudió tanto los niveles de tirotrofina sérica como la presencia de anticuerpos antiperoxidasa tiroidea, 24 (42%) presentaron alguno de los estudios alterados. El alto porcentaje de alteraciones tiroideas en nuestra serie de pacientes resalta la necesidad de estudiar la función tiroidea y la presencia de anticuerpos antiperoxidasa tiroidea en pacientes con urticaria crónica.

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La urticaria crónica es una enfermedad frecuente, caracterizada por la presencia de ronchas y/o angioedema con una duración superior a las 6 semanas. En un número importante de pacientes se comporta como una enfermedad autoinmune asociada frecuentemente con alteraciones en la función tiroidea y com la presencia de anticuerpos antitiroideos. Presentamos una serie de 70 pacientes consecutivos con diagnóstico de urticaria crónica a los cuales les investigamos la función tiroidea y la presencia de anticuerpos antiperoxidasa tiroidea. Siete (10%) tenían diagnóstico de enfermedad tiroidea previa al momento de la consulta. A los 63 pacientes restantes se les estudió los niveles de tirotrofina sérica, 11 de los cuales (17%) presentaron valores anormales, que sumados a los 7 con enfermedad previa llegan a 18 (26%) con función tiroidea alterada. A 61 pacientes se les investigo anticuerpos antiperoxidasa tiroidea, 22 (36%) fueron positivos. De 57 pacientes sin diagnóstico de patología tiroidea previa al momento de la consulta por urticaria, a los que se les estudió tanto los niveles de tirotrofina sérica como la presencia de anticuerpos antiperoxidasa tiroidea, 24 (42%) presentaron alguno de los estudios alterados. El alto porcentaje de alteraciones tiroideas en nuestra serie de pacientes resalta la necesidad de estudiar la función tiroidea y la presencia de anticuerpos antiperoxidasa tiroidea en pacientes con urticaria crónica. (AU)

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Kikuchi-Fujimoto disease (KFD) is a form of necrotizing lymphadenitis. The disease is a usually benign, self limited cause of lymph node enlargement affecting predominantly young women. Several other clinical manifestations have been described, though the only consistent findings are a macular eruption and a fever. Occasionally, the disease has presented as a fever of unknown origin. Lymph node specimens show areas of necrosis without neutrophilic infiltration. Lymphocyte mediated apoptotic mechanisms are responsible for the necrosis observed. Clinically, it should be differentiated from many different conditions, including infections such as cat scratch disease and rheumatological diseases like Still's disease and Systemic Lupus Erythematosus. Pathologically, it should be differentiated from lymphomas. KFD is widely known in the Far East, but very rare in Latin America. As a matter of fact, we have only detected four reported cases from Argentina, Brazil and Chile. We here describe two additional cases from Argentina. Both occurred in young women. One had a mediastinal compromise and a recurrent course, only observed in 4% of cases. The second one had a classical cervical presentation. The diagnosis in both was made by lymph node biopsy, although, in areas of great prevalence, an aspiration may be sufficient to establish the disease. We anticipate that the real prevalence of this unusual disease is highly underrepresented.

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Kikuchi-Fujimoto disease (KFD) is a form of necrotizing lymphadenitis. The disease is a usually benign, self limited cause of lymph node enlargement affecting predominantly young women. Several other clinical manifestations have been described, though the only consistent findings are a macular eruption and a fever. Occasionally, the disease has presented as a fever of unknown origin. Lymph node specimens show areas of necrosis without neutrophilic infiltration. Lymphocyte mediated apoptotic mechanisms are responsible for the necrosis observed. Clinically, it should be differentiated from many different conditions, including infections such as cat scratch disease and rheumatological diseases like Stills disease and Systemic Lupus Erythematosus. Pathologically, it should be differentiated from lymphomas. KFD is widely known in the Far East, but very rare in Latin America. As a matter of fact, we have only detected four reported cases from Argentina, Brazil and Chile. We here describe two additional cases from Argentina. Both occurred in young women. One had a mediastinal compromise and a recurrent course, only observed in 4

of cases. The second one had a classical cervical presentation. The diagnosis in both was made by lymph node biopsy, although, in areas of great prevalence, an aspiration may be sufficient to establish the disease. We anticipate that the real prevalence of this unusual disease is highly underrepresented.

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As a result of IgG-Fc interaction, sheep erythrocytes sensitized with IgG (E-IgG) are constitutively phagocytosed by resting PMN, although in low numbers. The low efficiency of the system can be improved by opsonization with C3b, since the combination of C3b and IgG makes a powerful opsonic signal. It is accepted that the mechanism of C3b enhancement of IgG mediated phagocytosis is achieved by increasing the adherence of the targets to the phagocyte. Recently, a non-opsonic role for C3b enhancement of IgG mediated phagocytosis has been proposed, in cultured human monocytes. These cells, when adhered on glass surfaces precoated with C3b, showed a marked increase in E-IgG internalization. The effect was dose dependent and it was reproduced utilizing a monoclonal antibody against CR1 (C3b receptor). In the present work we studied the existence of this phenomenon in resting neutrophils and in neutrophils stimulated with two kinds of agents: a phorbol ester (PDBu), which activates the CR1 and fMLP, which increases the expression of this receptor. In previous experiments we determined that the adherence of resting neutrophils on different concentrations of iC3 (which binds CR1 and exerts the same effect that C3b), did not increase the phagocytosis of the E-IgG, using as a control neutrophils adhered on the same concentrations of human serum albumin (HSA) (data not shown).(ABSTRACT TRUNCATED AT 250 WORDS)

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As a result of IgG-Fc interaction, sheep erythrocytes sensitized with IgG (E-IgG) are constitutively phagocytosed by resting PMN, although in low numbers. The low efficiency of the system can be improved by opsonization with C3b, since the combination of C3b and IgG makes a powerful opsonic signal. It is accepted that the mechanism of C3b enhancement of IgG mediated phagocytosis is achieved by increasing the adherence of the targets to the phagocyte. Recently, a non-opsonic role for C3b enhancement of IgG mediated phagocytosis has been proposed, in cultured human monocytes. These cells, when adhered on glass surfaces precoated with C3b, showed a marked increase in E-IgG internalization. The effect was dose dependent and it was reproduced utilizing a monoclonal antibody against CR1 (C3b receptor). In the present work we studied the existence of this phenomenon in resting neutrophils and in neutrophils stimulated with two kinds of agents: a phorbol ester (PDBu), which activates the CR1 and fMLP, which increases the expression of this receptor. In previous experiments we determined that the adherence of resting neutrophils on different concentrations of iC3 (which binds CR1 and exerts the same effect that C3b), did not increase the phagocytosis of the E-IgG, using as a control neutrophils adhered on the same concentrations of human serum albumin (HSA) (data not shown).(ABSTRACT TRUNCATED AT 250 WORDS)