Etiology and pathogenesis of spondyloarthritides

Seronegativne spondilartropatije su skupina upalnih reumatskih bolesti koje se zajednički klasificiraju zbog niza zajedničkih i sličnih kliničkih, epidemioloških i genetičkih obilježja. Patogeneza bolesti kod seronegativnih spondiloartropatija najčešće se opisuje kao razvoj kliničkih očitovanja bolesti u genetski predisponiranih osoba uz povoljne okolišne čimbenike. Razvoj seronegativnih spondiloartropatija, a osobito ankilozantnog spondilitisa povezuje se s prisutnošću gena HLA-B27. Dokazano je da osobe s HLA-B27 imaju značajno viši rizik za razvoj SpA. Uloga infekcije u nastanku seronegativnih spondiloartropatija nije posve jasna; njezina je uloga najjasnija u nastanku reaktivnog artritisa, a evidentno je manje očita u ankilozantnom spondilitisu. Povezanost HLA-B27 i infekcije nije sasvim razjašnjena. Teorija o molekularnoj mimikriji temelji se na opažanju sličnosti između molekule HLA-B27 i dijelova mikroba.Seronegative spondyloarthritides are inflammatory rheumatic diseases which are classified together because of numerous common and similar clinical, epidemiologic and genetic characteristics. Pathogenesis of seronegative spondyloarthritides is usually described as development of clinical characteristics of the disease in genetically susceptible person in the presence of favorable environmental factors. Development of seronegative spondyloarthritides, notably ankylosing spondylitis, is strongly connected with presence of the HLA-B27 gene. There are clear evidence that HLA-B27 positive individuals have significantly higher risk for disease development. The role of infection in occurence of seronegative spondyloarthritides is not completely understood - its role is better clarified in the case of reactive arthritis than in ankylosing spondylitis. The relation between HLA-B27 gene and infection is not clarified. Molecular mimicry theory is based on similarities between HLA-B27 molecule and microbial particle

Kidney in inflammatory rheumatic diseases

U radu je prikazano zahvaćanje bubrega u upalnim reumatskim bolestima.Renal lesions in inflammatory rheumatic diseases are presented

Polymyositis/dermatomyositis - clinical picture and treatment

Klinička slika miozitisa varira od bezbolne slabosti mišića do izraženih mialgija sa slabostima mišića i konstitucijskim simptomima. Uz afekciju mišića i kože te konstitucijske simptome bolest se može prezentirati afekcijom pluća, zglobova, srca, gastrointestinalnog sustava. Bitno je napomenuti da se klinička slika sindroma miozitisa može preklapati sa simptomima drugih definiranih bolesti vezivnog tkiva u sindromima preklapanja (SLE, SSCl, RA, SSjö). Najčešće manifestacije bolesti su slabost i zamor muskulature koji su posljedica upale skeletne muskulature (najčešće proksimalne skupine, simetrično i bilateralno). Teški oblici bolesti s afekcijom muskulature ždrijela ili respiratorne muskulature vitalno ugrožavaju bolesnika. Od općih, konstitucijskih simptoma najčešće su izraženi febrilitet, opća slabost i gubitak na težini. Kožne promjene dermatomiozitisa mogu biti lokalizirane ili generalizirane poput vezikobulozne eritrodermije. Patognomonične kožne manifestacije u dermatomiozitisu Gottronove papule i heliotropni eritem. Pluća su najčešće zahvaćen nemišićni organ u polimiozitisu i dermatomiozitisu afekcija kojeg može rezultirati i letalnim ishodom (intersticijska bolest pluća, sekundarna plućna hipertenzija). Srčane manifestacije najčešće su subkliničke, no mogu biti i izražene poput srčanog popuštanja, akutnog koronarnog sindroma ili pak smetnji provođenja. Rjeđa očitovanja bolesti su gastroezofagealni refluks, malapsorpcija, ulceracije sluznice probavnog sustava, kalcifikacije mekih tkiva, Raynaudov sindrom, artralgije/artritis i ostale rjeđe kliničke prezentacije bolesti. Liječenje polimiozitisa/dermatomiozitisa uključuje osnovnu, imunosupresivnu/imunomodulatornu terapiju i simptomatsko potporno liječenje. Temelj liječenja miozitisa predstavljaju glukokortikoidi koji se primjenjuju peroralno u dnevnom režimu u dozama 0,75-1 mg/kg/dan ili u teškim oblicima bolesti parenteralno u pulsnim dozama od 1 g/dan. Imunosupresivi/imunomodulatori dodaju se glukokortikoidima radi bolje kontrole bolesti te smanjenja potrebne doze glukokortikoida. Najčešće se primjenjuje metotreksat u dozi do 25 mg/tjedan. Hidroksiklorokin u dozi ima dobar učinak na kožne manifestacije bolesti. Od ostalih imunosupresiva primjenjuju se azatioprin, ciklosporin (u bolesnika s plućnom afekcijom), mofetil mikofenolat, takrolimus. Intravenski imunoglobulini primjenjeni parenteralno u dozi od 2 g/kg razdjeljeno u više doza pokazuju odličan učinak u bolesnika s afekcijom muskulature jednjaka i ždrijela, u bolesnika s plućnom afekcijom te onih s rezistentnom bolesti. Za sada su iskustva s biološkom terapijom ograničena na mali broj bolesnika. Fizikalna terapija u fazi remisije bolesti nužan je oblik liječenja u oporavku snage zahvaćene muskulature. Pravovremeno suzbijanje infekcija kao i liječenje srčanog popuštanja ponekad su od vitalne važnosti u bolesnika oboljelih od miozitisa. Simptomatsko liječenje boli analgeticima i nesteroidnim antireumaticima umanjuju tegobe, ubrzavaju oporavak i poboljšavaju kvalitetu života u ovih bolesnika.The clinical presentation of myositis ranges from a painless muscle weakness to significant myalgia with muscle weakness and constitutional symptoms. Along with muscle and skin affection and constitutional symptoms, the disease can affect lungs, joints, heart and gastrointestinal system. It is important to note that the clinical presentation of myositis syndrome may overlap with symptoms of other connective tissue disease in overlap syndromes (SLE, SSCL, RA, SSjö). Common manifestations of the disease are weakness and muscle fatigue, which is the result of skeletal muscles inflammation (usually the proximal group of muscles, bilaterally and symmetrical). Severe forms of the disease with affection of the throat and respiratory muscles can vitally endanger patients. Among constitutional (general) symptoms, fever, malaise and weight loss are usually expressed. Skin affection in dermatomyositis can be localized or generalized like vesiculobullous erythroderma. Pathognomonic cutaneous manifestations of dermatomyositis are Gottron’s papules and heliotrope erythema. Lungs are most commonly affected organs (with exception of muscles and skin) in polymyositis and dermatomyositis. The affection of lung can sometimes result in fatal outcome (interstitial lung disease, secondary pulmonary hypertension). Cardiac affection is usually subclinical, but can also be expressed as heart failure, acute coronary syndrome or conduction disturbances. Infrequent manifestations of the disease are gastroesophageal reflux, malabsorption, gastrointestinal mucosal ulceration, soft tissue calcification, Raynaud’s syndrome, arthralgia/arthritis and some other less common clinical manifestations of the disease. Treatment of polymyositis/dermatomyositis includes immunosuppressive/immunomodulatory therapy and supportive, symptomatic treatment. The basis for myositis treatment are glucocorticoids, which are applied orally in a daily dosage regimen of 0.75 to 1 mg/kg/day, and in severe forms of the disease in the i.v. pulse doses of 1 g/day. Immunosuppressants/immunomodulators are added in the therapy along with glucocorticoids for better control of the disease and to reduce the required dose of glucocorticoids (side effects of longterm high doses glucocorticoide use). The most commonly used immunosuppressive drug is methotrexate at a dose of up to 25 mg/week. Hydroxychloroquine has a good effect on the cutaneous manifestations of the disease. Among other immunosuppressants which are used in the treatment of myositis are azathioprine, cyclosporine (in patients with pulmonary affection), mycophenolate mofetil and tacrolimus. Intravenous immunoglobulins applied parenterally in a dose of 2 g/kg divided into multiple doses showed an excellent clinical effect in patients with affection of the esophagus and throat muscles, in patients with pulmonary affection and in patients with resistant disease. The experience with the biologics is limited to a small number of patients. Physiotherapy is a necessary form of treatment for the recovery of muscle strength in the remission phase of the disease. A prompt treatment of infections and heart failure is sometimes life-saving in patients with myositis. Symptomatic treatment of pain with analgesics and NSAIDs reduces pain, speeds up recovery and improves the quality of life in patients with myositis

Classification of vasculitides

Vaskulitisi su heterogena skupina upalnih bolesti kojima je zajedničko obilježje upala u stijenci krvne žile. Postavljanje dijagnoze vaskulitisa vjerojatno je jedan od najvećih izazova u medicini. Klinička slika ovisi o opsegu zahvaćanja pojedinog organa ili organskog sustava te o ukupnom broju zahvaćenih organa. Veliki raspon kliničkih očitovanja vaskulitisa te niska incidencija bolesti otežavaju sustavno kliničko istraživanje vaskulitisa. Svakodnevna praksa te potreba sustavnih kliničkih israživanja nameću potrebu razlikovanja pojednih entiteta. Predlagane su podjele vaskulitičnih sindroma prema etiologiji, patogenezi i tipu imunološke reakcije u stijenci krvne žile, histološkom nalazu u zahvaćenim žilama, zahvaćenosti pojedinih organa i organskih sustava. Niti jedna od predloženih metoda klasifikacije i podjele vaskulitisa nije bila potpuno zadovljavajuća. U tekstu je kratko prikazan povijesni razvoj podjela vaskulitisa. Osobito su naglašene novosti iz recentne podjele i nomenklature vaskulitisa predložene na drugoj konferenciji u Chapel Hillu.Vasculitides are heterogeneous group of inflammatory diseases with one common feature - inflammation in the blood vessel wall. The diagnosis of vasculitides is probably one of the biggest challenges in medicine. Clinical presentation of the disease depends on the extent of affection of single organ or organ systems and the total number of affected organs. A broad spectrum of clinical manifestations and low incidence of the disease makes it difficult to conduct a systematic clinical research of the disease. Everyday practise and a need for systemic clinical research of the disease necessitate the differentiation of individual entities that constitute this heterogeneous group of the inflammatory diseases. In past decades various concepts of the disease classification were proposed - according to the etiology, pathogensis, type of immune response in the blood vessel wall, histological findings in the affected vessels or depending on the involment of particular organs and organ systems. None of the proposed methods of the classification of vasculitides was entirely adequate. This paper briefly presents the historical development of the classification of the vasculitides. The emphasis of this paper was on the novelties from the recent classification and nomenclature of vasculitides that was proposed at the second consensus conference held in Chapel Hill

Prevalence of the American College of Rheumatology classification criteria in a group of 162 systemic lupus erythematosus patients from Croatia

AIM: To identify systemic lupus erythematosus (SLE) patients diagnosed and treated at the outpatient clinic of our Division fulfilling at least four American College of Rheumatology (ACR) classification criteria at the time of the study, to determine the prevalence of each of the criteria at three different time points, and to compare the data with similar studies. ----- METHODS: We performed retrospective and descriptive analysis of medical records of 162 patients fulfilling at least 4 ACR criteria. Classification criteria were counted and the frequency of each criterion was identified at three different time points: disease onset, time of diagnosis, and the time when the study was conducted. ----- RESULTS: At diagnosis and at the time when the study was conducted there were 3.8 and 5.4 fulfilled classification criteria, respectively. The most common criterion at the time of the disease onset was arthritis (52.6%); at the time of diagnosis it was positive antinuclear antibody (ANA) titer (88.0%); and at the time when the study was conducted it was positive ANA titer (95.7%), immunologic disorder (89.5%), arthritis (71.0%), hematologic disorder (70.4%), malar rash (61.7%), and photosensitivity (51.9%). ----- CONCLUSION: The prevalence of ACR criteria in our patients is similar to that in other studies, especially those involving Caucasian patients. Our results confirm the value of the ACR criteria in patients with an already established diagnosis. This is the first study on the prevalence of disease manifestations among Croatian patients with SLE

Povezanost biološke terapije i malignih bolesti u upalnim reumatskim bolestima

Inflammatory rheumatic diseases are chronic, progressive autoimmune diseases which affect the musculoskeletal system and other organ systems. Nowadays, a large number of patients is treated with biological therapy. Although biological drugs selectively affect specific molecules of the immune system, they weaken the overall immune system of the body. Therefore, the patients are more susceptible to infections and other diseases such as lymphomas, breast and skin cancers and melanomas. Chronic inflammation which occurs due to autoimmune disease is also a risk factor for malignant development. So far, studies have not proven direct correlation between biological therapy and solid or haematologic tumours. On the other hand, the increased risk for developing skin cancer in patients on tumour necrosis factor alpha inhibitors has been described. In this review paper we analysed the available medical literature on the risks for malignant disease development in patients with rheumatic diseases who are on biological disease – modifying anti-rheumatic drugs.Sistemske upalne reumatske bolesti jesu kronične, progresivne autoimunosne bolesti koje zahvaćaju lokomotorni sustav i druge organske sustave. Danas je sve više bolesnika liječeno biološkom terapijom. Iako biološki lijekovi selektivno djeluju na specifične molekule imunosnog sustava, oni smanjuju opću obrambenu funkciju organizma, zbog čega su bolesnici podložniji infekcijama, ali i nekim malignim bolestima poput limfoma, karcinoma kože, dojke ili melanoma. Također, sama kronična upala u sklopu autoimunosne bolesti jest rizični čimbenik za razvoj tumorske bolesti. Prema do sada objavljenim studijama, nije dokazana jednoznačna povezanost primjene bioloških lijekova s razvojem solidnih i hematoloških tumora. Suprotno tomu, istraživanja su pokazala povezanost primjene inhibitora tumorske nekroze alfa i razvoja tumora kože. U ovom preglednom radu analizirana je dostupna medicinska literatura o rizicima za razvoj malignih bolesti u bolesnika s reumatološkim bolestima koji su liječeni biološkim antireumatskim lijekovima koji mijenjaju tijek bolesti

Polymyalgia rheumatica

U radu su prikazani etiologija i patogeneza, epidemiologija, klinička slika, dijagnoza, diferencijalna dijagnoza i terapija reumatske polimialgije.The etiology, patogenesis, epidemiology, clinical picture, diagnosis, diferential diagnosis and treatment of polymyalgia reumatica are presented

ETIOLOGY OF ERYTHEMA NODOSUM IN RHEUMATOLOGY OUTPATIENT CLINIC

Nodozni eritem (erythema nodosum, EN) kožna je promjena uzrokovana reaktivnim imunosnim procesom koja se prezentira akutnom pojavom crvenih čvorastih eflorescencija. EN spontano regredira u periodu od 3 do 6 tjedana, ali nerijetko recidivira. Ovaj je rad uključio 98 bolesnika s područja Republike Hrvatske koji su ambulantno liječeni kod istog specijalista internista-reumatologa. Analizirana je prezentacija i definirane razlike između sekundarnog i idiopatskog oblika EN u spomenutoj populaciji. Rezultati pokazuju da je udio EN-a povezanog sa sekundarnom etiologijom bio 47/98. Većinu EN-a sekundarne etiologije činile su infektivne bolesti (23/98), sarkoidoza (18/98) i upalna bolest crijeva (4/98). Usporedbom brojnih kliničkih i laboratorijskih parametara utvrđen je manji broj statistički značajnih razlika (grlobolja, nedavne respiratorne infekcije, promjena titra ASO-a, uzimanje antibiotika). Na temelju rezultata zaključak je da je u pristupu bolesniku s EN-om potrebno uzeti dobru anamnezu s naglaskom na nedavne upale gornjeg dijela respiratornog sustava i pojavu dijareje. Treba učiniti fizikalni pregled, odrediti osnovne hematološke i biokemijske nalaze, odrediti upalne biljege (SE, CRP), napraviti rendgenogram srca i pluća i PPD-test te na taj način odrediti komu je potrebna daljnja obrada. Također, potrebno je napraviti i obrisak ždrijela i/ili odrediti titar ASO-a u dva navrata u razmaku od 2 do 4 tjedna i nastaviti pratiti bolesnika. S obzirom na regionalne razlike u etiologiji EN-a koje su dokazane u literaturi, potrebno je za svaku populaciju utvrditi prevalenciju pojedinih uzroka EN-a i tomu prilagoditi standardiziranu obradu.Erythema nodosum (EN) is a skin lesion presenting with the acute appearance of red nodular eflorescences caused by a reactive immunological process. In most cases EN regresses spontaneously within 3 to 6 weeks and often recurs. This paper is based on a sample of 98 patients from Croatia which were treated in a rheumatologic outpatient clinic by the same internal medicine and rheumatology specialist. Presentation and differences between secondary and idiopathic forms of EN in the Croatian population were analyzed. The results show the final proportion of EN associated with secondary etiology as 47/98. Secondary etiology of EN included mostly infectious diseases (23/98), sarcoidosis (18/98) and IBD (4/98). Comparison of various clinical and laboratory parameters of both idiopathic and secondary EN resulted in a small number of statistically significant differences found (sore throat, recent respiratory infections, ASO titer changes, antibiotics use). The conclusion is that the approach to patients with EN starts by a careful taking of patient history, with an emphasis on recent upper respiratory tract infections and occurrence of diarrhea. A thorough physical examination, basic hematological and biochemical tests, basic inflammatory markers (ESR, CRP), chest X-ray and PPD test are required to determine which patients need further evaluation. A throat swab and/or determination of the titer of ASO on two occasions at intervals of 2–4 weeks should be done. It is important to perform regular patient follow-up. Considering literature substantiated regional differences in the etiology of EN it is recommended that for each population the prevalence of individual causes of EN is determined and the clinical approach accordingly standardized