European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real-life clinical assessment.

BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal, web-based survey of 'real-life' respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified. RESULTS: A total of 4316 patients (corresponding to 4363 ongoing courses of AIT) were included. A total of 109 SRs were recorded, and 90 patients (2.1%) presented at least one SR. Most of the SRs occurred in subcutaneous allergen immunotherapy (SCIT) (89%, n = 97). The most frequently reported symptoms were urticaria, rhinitis, dyspnoea and cough. Respiratory symptoms appeared before skin symptoms. Most SRs occurred during the up-dosing phase (75.8%) and were mild in severity (71.6%). Intramuscular adrenaline was administered in 17 SRs, but only 65% of these were subsequently classified as anaphylaxis. Independent risk factors for SRs during SCIT were as follows: the use of natural extracts (odds ratio, OR) [95% confidence interval (CI)] = 2.74 [1.61-4.87], P = 0.001), the absence of symptomatic allergy medications (1.707 [1.008-2.892], P = 0.047), asthma diagnosis (1.74 [1.05-2.88], P = 0.03), sensitization to animal dander (1.93 [1.21-3.09], P = 0.006) or pollen (1.16 [1.03-1.30], P = 0.012) and cluster regimens (vs rush) (4.18 [1.21-14.37], P = 0.023). A previous episode of anaphylaxis increased the risk for anaphylaxis in SCIT (OR [95% CI] = 17.35 [1.91-157.28], P = 0.01). CONCLUSION: AIT for respiratory allergy is safe, with a low number of SRs observed in real-life clinical practice. A personalized analysis of risk factors could be used to minimize SRs.

Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome.

A subgroup of patients with 22q11.2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4(+) T cells. To detect these patients, 20 newborns with 22q11.2 microdeletion and congenital heart disease were followed prospectively for 6 years. Besides detailed clinical assessment, longitudinal monitoring of naive CD4(+) and cytotoxic CD3(+)CD8(+) T cells (CTL) was performed. To monitor thymic activity, we analysed naive platelet endothelial cell adhesion molecule-1 (CD31(+)) expressing CD45RA(+)RO(-)CD4(+) cells containing high numbers of T cell receptor excision circle (T(REC))-bearing lymphocytes and compared them with normal values of healthy children (n = 75). Comparing two age periods, low overall CD4(+) and naive CD4(+) T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA(+)RO(-)CD4(+) T cells. A high-risk (HR) group (n = 11) and a standard-risk (SR) (n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4(+) and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31(+)CD45RA(+)RO(-)CD4(+), naive CD45RA(+)RO(-)CD4(+) T cells as well as T(RECs)/10(6) mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4(+) and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM.

[Air embolism as a rare occurrence of the air leakage complex in premature infants on artificial respiration]. / Die Luftembolie als seltenes Ereignis des Air-Leakage-Komplexes beim beatmeten Frühgeborenen.

A premature baby requiring mechanical respiratory aid because of severe IRDS developed an interstitial pulmonary emphysema and died of massive gas embolism. Air trapped in the pulmonary interstitium because of rupture of overinflated alveoli, penetrated into the pulmonary lymphatics and entered the venous system via the thoracic duct.

[Biomechanical studies on the pathogenesis of ochronotic arthropathy]. / Biomechanische Untersuchungen zur Pathogenese der ochronotischen Arthropathie.

The enzymatic defect leading to alcaptonuria is well known. However, the pathogenesis of the associated arthropathy is poorly understood. From clinical and morphological observations it is assumed that the breakdown of ochronotic cartilage is due to an increased fragility. To test the hypothesis that polymerisation products of homogentisic acid change the biomechanical behaviour of hyalin cartilage, investigations on natural ochronotic cartilage and tissues following in vitro incubation with homogentisic acid were performed. It could be demonstrated that the "ochronotic situation" is associated with an increased hardness and a decreased elasticity of the hyalin cartilage. For the pathogenesis of ochronotic arthropathy it is assumed that these alterations, in association with mechanical stress to the joints, lead to cartilage destruction.

Normal and Friend virus specific cell compartments in Friend leukemia characterized by their sensitivity to actinomycin D in vivo.

DBA/2 mice were infected with the polycythemia inducing Friend Virus (F-MuLV-P) and treated with different doses of Actinomycin D (Act D) when the whole erythroid cell system, as measured by the CFU-E technique with and without addition of erythropoietin (Ep), had been transformed into Ep-independence. During and after this therapy the different stem cell pools CFU-S, CFU-C, BFU-E and CFU-E (with and without Ep) were studied and their sensitivity to Act D in bone marrow and spleen was compared to that of normal mice, recently published by other authors. There seemed to be no difference in the Act D sensitivity between normal erythropoiesis and Ep-independent erythropoiesis caused by F-MuLV-P. Furthermore a cell called ICPC (infectious centers producing cell) was studied. This cell system, detected by spleen colony formation due to high local virus production in an unirradiated host, proved to be Act D sensitive in the spleen but not in the marrow. When the erythroid cell system regenerated after Act D chemotherapy, all erythroid colony growth was Ep-independent. This means that Act D did not induce normal erythropoiesis as seen with hydroxyurea treatment.

[Children of mothers with phenylketonuria (author's transl)]. / Kinder phenylketonurischer Mütter

Microcephaly and considerable motor and mental retardation occurred in two non-phenylketonuric children of an untreated mother with phenylketonuria. The cerebral damage of the children must be considered the consequence of the maternal metabolic disorder. Since the first phenylketonuric children who were treated on strict diet are now reaching the age of marriage and pregnancy, the problem of maternal phenylketonuria is becoming topical. Published reports indicate that of 72 well documented cases with a maternal phenylalanine level above 200 mg/1 (1210 mumol/1) 39 offspring had microcephaly, in 33 intra-uterine growth had been retarded and in 25 there are cerebral palsy and seizures. Almost all had mental retardation. At the same time there have been reports about three normal children whose mothers had kept to a phenylalanine-low diet during their pregnancy.