30 research outputs found
Pediatric rheumatic diseases - per aspera ad astra
DjeÄja reumatologija je relativno mlada i dinamiÄna subspecijalistiÄka struka koja se bavi dijagnostikom i intradisciplinarnim lijeÄenjem sistemskih i miÅ”iÄnokoÅ”tanih bolesti koje nastaju kao posljedica poremeÄaja u regulaciji imunoloÅ”kog sustava, a najÄeÅ”Äe razultiraju razvojem autoimunosti ili autoinflamatorne reakcije te upalom. Postoje brojne razlike izmeÄu djece i odraslih osoba koje boluju od reumatskih bolesti. Novija istraživanja pokazala su da se bolesti poput juvenilnog idiopatskog artritisa mogu ranije i preciznije dijagnosticirati koriÅ”tenjem suvremenih metoda molekularne biologije i efikasnije lijeÄiti ranijom primjenom bioloÅ”ke terapije. S druge strane rano prepoznavanje razliÄitih autoinflamatornih bolesti je kljuÄno za adekvatnu terapiju tih vrlo složenih stanja. Dakle, samo je pitanje vremena kada Äe moderne dijagnostiÄke metode molekularne biologije poput genetskog Äipa radi odreÄivanja āprofilaā i biomarkera bolesnika postati dio rutinske prakse, a rana bioloÅ”ka terapija po modernim principima farmakogenomike, prilagoÄena za svakog bolesnika ponaosob, biti temelj svakodnevne kliniÄke prakse.Progress in the field of pediatric rheumatolgy has been extraordinary; subspecialty is accepted as essential, vital, indispensible and distinct from adult rheumatology. It is clear that arthritis in children is more heterogeneous than RA. Although there are similarities between the inflammatory arthritides occuring in adults and children, RA and JIA appear to be distinct phenotypically with exception for the older child with RF-positive polyarticular arthritis. Progress in molecuĀlar biology has enabled us to diagnose those children earlier, and treat them more efficaciously with variety of drugs and biologic agents. In recent years a new group of hereditary autoinflammatory disorders has emerged. These rare syndromes are charaterized by recurrent episodes of seemingly unprovoked, intermittent inflammation. In the near future we will be able to distinguish various subtypes of autoimune/autoinflammatory diseases earlier in the course, have a better understanding of the biomarkers and other prognostic factors, and most importantly treat them earlier with extended set of various new exciting drugs and biological therapy
The most frequent childhood vasculitides
Vaskulitisi u djeÄjoj dobi predstavljaju izazov za pedijatrijske reumatologe zbog raznolikosti kliniÄke prezentacije i sistemske prirode bolesti. Vaskulitisi nerijetko zahtjevaju multidisciplinski pristup viÅ”e specijalista; reumatologa, dermatologa, kardiologa, nefrologa, neurologa i gastroenterologa. Vaskulitis definiramo prisustvom upale u zidu krvnih žila. Lokalizacija krvnih žila, veliÄina krvnih žila, obim ozljede žilja, te patohistoloÅ”ki nalaz odreÄuju fenotip i težinu bolesti. U radu Äe se raspravljati o klasifikaciji i glavnim obilježjima vaskultisa djeÄje dobi, a detaljnije Äe biti razraÄene dva najÄeÅ”Äa oblika: Henoch-Schƶnleinova purpura i Kawasakijeva bolest.Childhood vasculitis is a challenge for pediatric rheumatologists. It is multisystem in nature and often requires integrated care from multiple subspecialties, including rheumatology, dermatology, cardiology, nephrology, neurology, and gastroenterology. Vasculitis is defined as the presence of inflammation in the blood vessel wall. The site of vessel involvement, size of the affected vessels, extent of vascular injury, and underlying pathology determine the disease phenotype and severity. This article explores the classification and general features of pediatric vasculitides, with detailed analisys of the two most common vasculitides: Henoch-Schƶnlein purpura and Kawasaki disease
The classification of juvenile spondyloarthritides
U radu je prikazana klasifikacija juvenilnih spondiloartropatija.The classification of juvenile spondyloarthritides is presented
Non-invasive imaging of chronic inflammatory myopathies
Cilj svakog uspjeÅ”nog dijagnostiÄkog postupka je postiÄi Å”to pouzdaniji rezultat u Å”to kraÄem vremenu, koristeÄi se pritom Å”to manje invazivnom dijagnostikom. Neinvazivnim slikovnim pretragama možemo u miÅ”iÄu utvrditi edem, kolekcije tekuÄina, infiltracije masnog tkiva, atrofiju, fibrozu i kalcifikate. Najosjetljivija neinvazivna slikovna dijagnostiÄka metoda u danaÅ”njoj suvremenoj dijagnostici upalnih bolesti miÅ”iÄa je MR u T2 slikovnim prikazima sa supresijom masnog tkiva i/ili STIR prikazu. MR je vrlo korisna metoda i pri odreÄivanju preciznog mjesta biopsije miÅ”iÄa. NespecifiÄnost nalaza promjena na miÅ”iÄu, dostupnost, cijena, kao i kontraindikacije za primjenu kod bolesnika s metalnim protezama ili pacemakerima, kao i naÄin izvoÄenja pretrage predstavljaju ozbiljna ograniÄenja te metode. Glavna prednost ultrazvuka miÅ”iÄa, u usporedbi s ostalim slikovnim metodama, je dostupnost i cijena pretrage. PojaÄana vaskularnost miÅ”iÄa utvrÄena pomoÄu PD-a korelira s dužinom trajanja miozitisa, a PD može biti i koristan za utvrÄivanje pojaÄanog signala prokrvljenosti te iskljuÄivanje rupture miÅ”iÄa, bolesti poput cisticerkoze kao i apscesa miÅ”iÄa. Äini se da bi zbog dostupnosti i visoke osjetljivosti kvantitativni ultrazvuk s kontrastom (CEUS), metoda koja omoguÄuje procjenu pojaÄane vaskularnosti miÅ”iÄa u realnom vremenu, uz dodatak elastografije, uskoro mogao zauzeti važniju ulogu u potvrdi kliniÄke sumnje kroniÄne upalne bolesti miÅ”iÄa.In patients with chronic inflammatory myositis noninvasive diagnostic modalities, such as magnetic resonance (MR) imaging, and ultrasonography (US), are able to demonstrate muscular edema, fluid collections, fatty infiltration, atrophy, fibrosis, and calcifications. Because MR imaging is sensitive to the presence of edema and offers better tissue differentiation, current MR imaging with fat suppressed T2-weighted techniques or STIR images appears to be more efficient than US in the diagnosis and management of inflammatory myopathies. MR imaging has also been proposed as a means to guide biopsy in an area of active disease, thereby reducing the problem of sampling error. These changes in signal intensity, however, are not specific for myositis. Although MR imaging is now the imaging modality of choice in this issue, reduced availability, patient discomfort, and exclusion of certain patients with indwelling metal objects, such as pacemakers, are disadvantages. The availability and ease of use of US makes it preferable to MR imaging. Real-time sonoelastography can be used for various musculoskeletal applications, but the clinical utility in diagnosis of myositis is yet to be established. On the other hand, the contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups, and most likely, will soon become preferable, noninvasive imaging method in patients with myositis
JUVENILE SPONDYLOARTHRITIS
Juvenilni spondiloartritis (jSpA) skupina je multifaktorskih bolesti u kojima dolazi do poremeÄenog
meÄudjelovanja imunosnog sustava i Äimbenika okoliÅ”a u ljudi s predisponirajuÄim genotipom, Å”to dovodi do upale i
strukturnih oÅ”teÄenja ciljnog tkiva. Prvi simptomi jSpA rijetko su povezani s kralježnicom, a ÄeÅ”Äe se javljaju nesimetriÄni
oligoartritis zglobova donjih ekstremiteta, daktilitis i periferni entezitis. Postoje brojni kriteriji za klasifi kaciju
jSpA, no veÄina pedijatrijskih reumatologa danas se koristi kriterijima MeÄunarodne lige reumatoloÅ”kih udruženja
(ILAR) prema kojima je najveÄi broj bolesnika s artritisom i entezitisom ili artritisom ili entezitisom uz joÅ” dvije ili viÅ”e
od karakteristika poput bolnosti sakroilijakalnih zglobova na dodir i/ili bolnosti kralježnice zbog upalnog procesa,
HLA-B27-genotipa, bolesti povezane s HLA-B27-genotipom u jednog ili viÅ”e roÄaka u prvom ili drugom koljenu,
uveitisa te muŔkog spola uz viŔe od osam godina života, svrstan u podskupinu juvenilnog idiopatskog artritisa (JIA)
koju nazivamo artritis pridružen entezitisu (ErA). Sukladno tomu, dijagnoza bolesti postavlja se uglavnom na temelju
kliniÄke slike i anamnestiÄkih podataka; od laboratorijskih pretraga potrebno je odrediti antinuklearna antitijela
(ANA), reumatoidni faktor (RF) te HLA-tipizaciju kako bi se utvrdila prisutnost HLA-B27, B7 i/ili DR4-genotipa. S
obzirom na to da velik broj bolesnika ima i supkliniÄku upalu crijeva, preporuÄljivo je provjeriti i fekalni kalprotektin.
Ako postoje simptomi perifernog entezitisa, potreban je pregled muskuloskeletnim ultrazvukom s osnaženim doplerom
(PDUS), a pri znakovima zahvaÄenosti kralježnice radiografsko snimanje te magnetska rezonancija (MR) s kontrastnim
sredstvom. NajveÄi broj djece s jSpA-om lijeÄi se fi zikalnom terapijom i nesteroidnim protuupalnim lijekovima
(NSAIL), dok se refraktorni oblici periferne bolesti mogu lijeÄiti sintetskim lijekovima koji utjeÄu na tijek bolesti
(DMARD), poput sulfasalazina. Kada bolest zahvati i kralježnicu, potrebno je lijeÄenje bioloÅ”kim DMARD-ovima
poput adalimumaba, infl iksimaba i etanercepta. Usprkos mnogimJuvenile spondyloartrhritis is a group of multifactorial diseases in which a disturbed interplay occurs
between the immune system and environmental factors on a predisposing genetic background, which leads to infl ammation
and structural damage of the target tissue. First symptoms of jSpA rarely involve the spine, while asymmetrical
oligoarthritis of lower extremities, dactylitis, and peripheral enthesitis are much more common. Th ere are many classifi
cation criteria for jSpA, but the majority of pediatric rheumatologists currently use the International League Against
Rheumatism (ILAR) criteria according to which most patients with jSpA are classifi ed into the enthesitis-related arthritis
group of juvenile idiopathic arthritis. To meet these criteria, a patient should have arthritis and/or enthesitis,
with two or more symptoms such as sacroiliac joint tenderness and/or infl ammatory back pain, HLAB27 genotype,
HLA B27 genotype-associated disease in a fi rst- or second-degree relative, uveitis, and male sex with eight or more
years of age. Th erefore, diagnosis is most oft en made only based on clinical examination and medical history. Antinuclear antibodies (ANA), rheumatoid factor (RF), and HLA testing with B27, B7, and DR4 alleles are preferred. Since
subclinical gut infl ammation is present in many patients, it is recommended to check fecal calprotectin levels. In patients
with signs of peripheral enthesitis it is warranted to perform power Doppler musculoskeletal ultrasound (PDUS),
and in patients with signs of axial involvement radiographic and contrast-enhanced magnetic resonance imaging.
Most patients are treated with nonsteroidal anti-infl ammatory drugs (NSAIDs) and physical therapy, while in refractory
cases with peripheral disease synthetic disease- modifying antirheumatic drugs (DMARDs), such as sulfasalazine,
are used. In patients with axial involvement, biological DMARDs such as adalimumab, infl iximab, and etanercept are
obligatory. Although a number of studies gave us a good insight into the disease pathogenesis, the response to treatment
and prognosis are still diffi cult to predict
Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis
Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches