THE IMPORTANCE OF ENDOTHELIAL DYSFUNCTION FOR THE DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION AND NEW THERAPEUTIC OPTIONS

Background. Pulmonary arterial hypertension may exist as a primary condition or as a secondary condition, most commonly with collagen vascular disease. Patients with pulmonary arterial hypertension usually have bad prognosis as the effectiveness of conventional treatment is poor. New knowledge about importance of endothelial dysfunction in development of pulmonary arterial hypertension has opened a wide field of possible new treatment options.Conclusions. Endothelial dysfunction in pulmonary vascular bed is characterised by an inappropriate release of vasoactive substances from endothelium producing vasoconstriction, remodeling of arterial wall and increased local tendency for thrombosis. Several new drugs have been already tested in clinical case-controlled studies: prostacyclin and its analogues applied intravenously or in inhalations, inhaled nitric oxide and drugs which increase nitric oxide concentration such as sildenafil and l-arginine, endothelin receptors antagonists in tablets and tromboxane antagonist in tablets. Only tromboxane antagonist was shown to be ineffective whereas all other drugs were effective at least in certain subgroups of patients. New clinical trials will give answer not only in respect to the comparative efficacy of the drugs mentioned earlier and their combinations but also to the recognition of factors that determine the success of treatment in individual patient.</p

Mnenje posvetovalnega sestanka revmatologov in pulmologov glede obravnave bolnika s prizadetostjo pljučnega intersticija v sklopu vnetnih revmatičnih bolezni

Vnetne revmatične bolezni so heterogena skupina bolezni, ki lahko prizadenejo tudi pljučni intersticij. Tako kot je pogostnost intersticijske pljučne bolezni (IPB) v okviru vnetnih revmatičnih bolezni variabilna, je tudi klinična slika zelo raznolika: od omejene nenapredujoče prizadetosti pljučnega intersticija do fulminantno potekajoče življenje ogrožajoče bolezni. Podatki za diagnosticiranje in zdravljenje IPB v sklopu vnetnih revmatičnih bolezni so razmeroma skopi. Temeljno zdravljenje praviloma predstavljajo imunomodulacijska zdravila. Nedavno so se jim pri progresivni pljučni fibrozi pridružili še protifibrotiki. Odločitev pri kom, kdaj in kako intenzivno zdraviti IPB pogosto predstavlja izziv. V prispevku podajamo sklepe multidisciplinarnega posvetovalnega sestanka slovenskih revmatologov in pulmologov, ki po mnenju avtorjev glede na dostopne podatke pomenijo dobro prakso pri obravnavi tovrstnih bolnikov. Osredinjamo se na bolnike s sistemskimi vezivnotkivnimi boleznimi in revmatoidnim artritisom

Zgodnji gigantocelični arteritis

Gigantocelični arteritis (GCA) je najpogostejši primarni sistemski vaskulitis pri odraslih po 50. letu starosti v Evropi. Prizadene velike in srednje velike arterije in vnetni proces, ki zožuje ali popolnoma zapre svetlino žile, lahko dovede do hudih/trajnih ishemičnih zapletov kot so oslepitev, možganska kap ali miokardni infarkt. V zadnjem desetletju se je z vključitvijo slikovnih preiskav v diagnostični postopek pomembno skrajšal čas do prepoznave bolezni (t.i. zgodnji GCA). Pospešena obravnava bolnikov (ang. “fast track clinic”) je vodila v zmanjšanje pojavnosti najresnejših ishemičnih zapletov bolezni in znižanje stroškov zdravljenja. Vendar pa bolezen praviloma poteka kronično, s poslabšanji, kar skupaj s kroničnim glukokortikoidnem zdravljenjem vodi v kopičenje okvar organov in tkiv. Prav zato se intenzivno preučuje patogeneza bolezni, z možnostjo implementacije izsledkov kot so sodobne molekularno in celično usmerjene tarčne terapije. Glavni cilji našega preglednega članka so bili: a) analiza raziskav z navedenim časom trajanja od začetka simptomov do postavitve diagnoze, b) raziskava obetavnih molekularnih tarč za zdravljenje GCA in c) prepoznava klinično pomembnih celičnih podtipov. Najbolj obetavne tarčne molekule za tarčno zdravljenje so IL-6, IL-12/IL-23 in citototoksični z limfociti T povezan protein 4, medtem ko terapija z zaviralci TNF-α ni bila uspešna. Kliničnih raziskav z učinkovinami, usmerjenimi proti IL-17, še ni. V prispevku pa smo se dotaknili tudi drugih potencialnih terapevtskih tarč, vključno z molekulami, ki sodelujejujo v signalnih poteh

Autoimmune congenital heart block and primary Sjögren's syndrome:characterisation and outcomes of 49 cases

Objective. To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjogren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB. Methods. The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB. Results. We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/ 44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 ( 64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n= 2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB ( recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB. Conclusion. In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies

Autoimmune congenital heart block and primary Sjögren's syndrome:characterisation and outcomes of 49 cases

OBJECTIVES: To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjögren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB.METHODS: The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB.RESULTS: We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 (64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n=2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB (recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB.CONCLUSIONS: In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies