DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a rare form of systemic vasculitis of unknown etiology, commonly associated with serum cANCA. Typical manifestations include necrotizing vasculitis and granulomatous inflammation which occur in the upper and lower respiratory tracts and kidneys, however the range of clinical manifestations of GPA can involve almost any organ. Epidemiological studies suggested that prevalence of GPA in Poland is 36/1,000,000 and is slightly lower than in other European countries. A statistically significant decrease in the GPA incidence was found within 2011–2015. Both sexes are affected equally, and a mean age at diagnosis is 40 yrs. Clinical manifestations are heterogeneous and the following presentation of the disease should be taken into consideration: cutaneous (leucocytoclastic vasculitis, purpura, digital infarcts and gangrene), oral (ulcers, granulomatous lesions, gingival hyperplasia with strawberry-like aspect), ocular (episcleritis, scleritis, conjunctivitis, keratitis, uveitis, retinal vasculitis or thrombosis, blindness, proptosis and orbital granulomatous masses), auricular (sensorineural hearing loss and conductive hearing loss), cardiovascular (small vessel vasculitis, occlusive vascular disease, pericarditis, cardiomyopathy, valvular heart disease, ischemic heart disease, heart failure), gastrointestinal (acute abdomen secondary to peritonitis or bowel ischemia), neurological (meningitis, seizures, cerebrovascular accidents, spinal cord lesions, cranial nerve palsies, sensory or motor peripheral neuropathy, mononeuritis multiplex, cerebral mass lesions) as well as musculoskeletal involvements. Therapy should be adjusted to individual patient. Various programs have been proposed for the induction of remission and its maintenance, and management of relapses. Glucocorticoids and cyclophosphamide are the most commonly used medication although rituximab is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide as well as is more effective than cyclophosphamide for treating relapses. Azathioprine is also used for remission maintenance. Plasma exchange is indicated in patients with alveolar hemorrhage

Patologia cardiovasculară la pacienţii cu artrită reumatoidă: epidemiologie, patogeneză şi prevenire

Conferinţa naţională în medicina internă din Republica Moldova cu participare internaţională, 19-20 mai 2011, Chişinău, Republica MoldovaArtrita reumatoidă (AR) este asociată cu un risc sporit de evenimente cardiovasculare (CV). Patologia CV, inclusiv infarctul miocardic şi ictusul reprezintă cauzele majore ale mortalităţii printre pacienţii cu AR. De asemenea, la această populaţie există un risc sporit de infarct miocardic nonfatal şi de insuficienţă cardiacă. S-a estimat că mortalitatea cauzată de CV la pacienţii cu AR este de 2-5 ori mai înaltă decât în populaţia generală. Această creştere este remarcată în primii 8-10 ani de la debutul simptomelor de AR. La fel, ultimele studii au demonstrat că AR este un factor de risc independent pentru patologia CV, la fel de important ca şi diabetul zaharat. Mecanismele care stau la baza acestei incidenţe sporite şi prezic severitatea patologiei CV la pacienţii cu AR nu sunt pe deplin înţelese. Ateroscleroza este o patologie cronică inflamatorie, iar inflamaţia sistemică foarte importantă, asociată cu AR, exercită atât efecte directe asupra endoteliului vascular, cât şi indirect potenţează procesul aterosclerotic. Această stare patologică este cunoscută ca „ateroscleroză potenţată prin inflamaţie cronică”. Se presupune că activarea celulelor endoteliale şi disfuncţia endotelială ulterioară constituie mecanismul de legătură dintre AR timpurie şi ateroscleroză. Profilul citochinic şi interacţiunile proteinelor de adeziune sunt foarte similare în inflamaţia sinovială în caz de AR şi ateroscleroză. S-a demonstrat că câţiva indici ai inflamaţiei corelează cu incidenţa patologiei CV la pacienţii cu AR. Astfel, a fost demonstrat că viteza înaltă de sedimentare a hematiilor este un factor predictiv la aceşti bolnavi. Alte studii au revelat că viteza de sedimentare a hematiilor este un prezicător al mortalităţii CV. Proteina C-reactivă este un factor predictiv recunoscut pentru evenimente CV atât la bărbaţi, cât şi la femei. Această legătură a fost confirmată la pacienţii cu AR. Rolul dereglărilor imune în apariţia unui risc CV sporit a fost sugerat în baza unei mortalităţi semnificativ ridicate printre bolnavii cu AR cu factor reumatoid pozitiv sau anticorpi antinucleari. Din câte se cunoaşte, pacienţii cu test pozitiv la factorul reumatoid sunt expuşi unui risc de maladie mai activă asociată, de regulă, cu o inflamaţie cronică mai severă. Rolul factorilor tradiţionali de risc CV la pacienţii cu AR în dezvoltarea aterosclerozei şi a sechelelor acesteia rămâne neelucidat, iar influenţa lor trebuie analizată în contextul inflamaţiei sistemice. Pentru a preveni patologia CV la pacienţii cu AR sunt necesare măsuri complexe. Controlul optim al factorilor tradiţionali de risc CV este indispensabil, dar crucială este supresiunea inflamaţiei sistemice. S-a demonstrat că tratamentul cu metotrexat reduce riscul de mortalitate CV. Există, la fel, dovezi ale rolului agenţilor anti-TNF-alfa în prevenirea aterosclerozei, iar terapia cu agenţi anti-TNF-alfa inhibă câteva etape de dezvoltare a aterosclerozei. Efectele benefice ale acestei terapii asupra incidenţei evenimentelor CV, precum şi a mortalităţii sunt demonstrate doar de unele studii observaţionale. Sunt necesare deci cercetări privind reducerea riscului CV la utilizarea agenţilor anti-TNF-alfa la pacienţii cu AR

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH GRANULOMATOSIS WITH POLYANGIITIS

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a rare form of systemic vasculitis of unknown etiology, commonly associated with serum cANCA. Typical manifestations include necrotizing vasculitis and granulomatous inflammation which occur in the upper and lower respiratory tracts and kidneys, however the range of clinical manifestations of GPA can involve almost any organ. Epidemiological studies suggested that prevalence of GPA in Poland is 36/1,000,000 and is slightly lower than in other European countries. A statistically significant decrease in the GPA incidence was found within 2011–2015. Both sexes are affected equally, and a mean age at diagnosis is 40 yrs. Clinical manifestations are heterogeneous and the following presentation of the disease should be taken into consideration: cutaneous (leucocytoclastic vasculitis, purpura, digital infarcts and gangrene), oral (ulcers, granulomatous lesions, gingival hyperplasia with strawberry-like aspect), ocular (episcleritis, scleritis, conjunctivitis, keratitis, uveitis, retinal vasculitis or thrombosis, blindness, proptosis and orbital granulomatous masses), auricular (sensorineural hearing loss and conductive hearing loss), cardiovascular (small vessel vasculitis, occlusive vascular disease, pericarditis, cardiomyopathy, valvular heart disease, ischemic heart disease, heart failure), gastrointestinal (acute abdomen secondary to peritonitis or bowel ischemia), neurological (meningitis, seizures, cerebrovascular accidents, spinal cord lesions, cranial nerve palsies, sensory or motor peripheral neuropathy, mononeuritis multiplex, cerebral mass lesions) as well as musculoskeletal involvements. Therapy should be adjusted to individual patient. Various programs have been proposed for the induction of remission and its maintenance, and management of relapses. Glucocorticoids and cyclophosphamide are the most commonly used medication although rituximab is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide as well as is more effective than cyclophosphamide for treating relapses. Azathioprine is also used for remission maintenance. Plasma exchange is indicated in patients with alveolar hemorrhage

Dr Alexander Majkowski: A physician and Kashubian writer and poet

Kashubians known also as Kassubians (in Kashubian language: Kaszëbi) are the Slavonic ethnic group inhabiting the Eastern Pomerania in Poland. They speak the Kashubian language that is classified as the West Slavonic language belonging to the Lekhitic group of languages. Kashubians are the direct descendants of Pomeranians [1]. The Pomeranians came into the northern part of Poland about the 5th century AC. The region they lived is now known as Pomerania. The oldest mention of the region’s name is a seal of prince Barnin the First of Pomerania from the 13th century