Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

[Biosimilars in rheumatology and other fields of medicine]. / Rola biosymilarów w reumatologii i innych dziedzinach medycyny.

Biosimilars are follow-up versions of innovative medicines with proved high similarity to the reference product. There may be some minor differences in clinically inactive components of a molecule which can be clinically significant, but they do not substantially affect the high resemblance to the original drug in their safety and potency. Introduction of the biosimilars brings hope to reduce the cost of treatment, so their availability will increase further as the expiration of patents on biotechnologically produced drugs will follow, which is currently taking place. There are new biosimilar drugs being introduced recently; these are monoclonal antibodies. They are much more structurally complicated compared to the first biotech drugs such as insulin, and their production processes are much more complex. Biosimilars as the end products of such sophisticated technology are affected by many variables. It is not possible to create "biogenerics," but only biosimilar drugs. Therefore, despite their similarities to the reference molecules, biosimilars are too different to forego clinical trials. Clinical trials of biosimilars need to be much broader than for generics, but they are limited compared to the reference biologicals' testing. Placebo controlled clinical trials are not required before registering a new biosimilar. Immunogenicity is a major source of concern related to biosimilars, although there may be the same problem with the original drugs.

Intima-media thickness cut-off values depicting "halo sign" and potential confounder analysis for the best diagnosis of large vessel giant cell arteritis by ultrasonography.

Background: Vascular ultrasound enables fast-track diagnosis of giant cell arteritis (GCA), but this method remains subjective. We aimed to determine intima-media thickness (IMT) cut-off values for large vessel GCA (LV-GCA) and identify the clinically relevant factors influencing it. Methods: We included 214 patients referred for ultrasound evaluation within a fast-track clinic due to suspected GCA. IMT was measured in axillary, brachial, subclavian, superficial femoral, and common carotid arteries (CCA), in a place without identifiable atherosclerotic plaques. IMT cut-off values for vasculitis were determined by comparing measurements in arteries classified as vasculitis vs. controls without GCA/polymyalgia rheumatica (PMR). Results: Giant cell arteritis was diagnosed in 81 individuals, including extracranial LV-GCA in 43 individuals. Isolated PMR was diagnosed in 50 subjects. In 83 remaining patients, another diagnosis was confirmed, and they served as controls. The rounded optimal IMT cut-off values for the diagnosis of axillary vasculitis were 0.8 mm, subclavian-0.7 mm, superficial femoral-0.9 mm, CCA-0.7 mm, and brachial-0.5 mm. The IMT cut-off values providing 100% specificity for vasculitis (although with reduced sensitivity) were obtained with axillary IMT 1.06 mm, subclavian-1.35 mm, superficial femoral-1.55 mm, CCA-1.27 mm, and brachial-0.96 mm. Axillary and subclavian arteritis provided the best AUC for the diagnosis of GCA, while carotid and axillary were most commonly involved (24 and 23 patients, respectively). The presence of calcified atherosclerotic plaques was related to an increase of IMT in both patients and controls, while male sex, age ≥ 68, hypertension, and smoking increased IMT in controls but not in patients with GCA. Conclusion: Cut-off values for LV-GCA performed best in axillary and subclavian arteritis but expanding examination to the other arteries may add to the sensitivity of GCA diagnosis (another location, e.g., brachial arteritis) and its specificity (identification of calcified atherosclerotic plaques in other arteries such as CCA, which may suggest applying higher IMT cut-off values). We proposed a more linear approach to cut-off values with two values: one for the most accurate and the other for a highly specific diagnosis and also considering some cardiovascular risk factors.

Familial association of laryngeal, lung, stomach and early-onset breast cancer.

This study analyzes the incidence of different types of cancer among 2839 first-degree relatives of 760 consecutive, unselected laryngeal cancer patients, compared with the general population. A statistically significant excess was seen for other cancers of the larynx (SIR: 400), lung (SIR: 135) and stomach (SIR: 271), and early-onset breast cancer (SIR: 287). Familial laryngeal cancer may not be a single site-specific cancer syndrome.

[Cardiovascular abnormalities in systemic lupus erythematosus patients in echocardiographic assessment]. / Zmiany w ukladzie sercowo-naczyniowym u chorych na toczen rumieniowaty ukladowy w oparciu o badania echokardiograficzne.

UNLABELLED: Cardiovascular system involvement is the third most common reason of death in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the cardiac involvement in the SLE patients with a regard to clinical, serological and environmental risk factors. MATERIAL AND METHODS: 103 patients were included into the study, 91 women and 12 men, aged 16-74 yrs, the control group included 25 subjects. Physical examination, two-dimensional guided M-mode and Doppler echocardiographic recordings were performed. The tests for the presence of ANA, ENA, antiphospholipid antibodies (aCL, LA, anti-beta2GPI and antiprothrombin antibodies), ANCA (anti-neutrophil cytoplasm antibodies), AECA (anti endothelial cell antibodies) were carried out. RESULTS: The following pathologies were significantly more common in the SLE patients: pericardial involvement (58%), organic changes of the mitral valve cusps (54%), organic changes of the aortic valve cusps (36%), widening of the aortal lumen (35%), enlargement of the left atrium (18%), hypokinesis of the left ventricle myocardial muscle (15%). Ultrasound cardiac pathologies were associated with presence of antiphospholipid antibodies, ANCA, anti-hitone antibodies and AECA. High activity of SLE increased risk of pericarditis and ascending aortic wall thickening. Cardiovascular manifestations occurred most frequently in patients with short time duration of SLE. CONCLUSION: Cardiac involvement is a frequent and early systemic complication of SLE and it is the most commonly related to pericardium and valvular apparatus. Cardiovascular manifestations in SLE patients are the most frequently related to the presence of serological risk factors, mainly antiphospholipid antibodies. It suggests their major role in the pathogenesis of the cardiovascular involvement in SLE. Pericarditis are markers of high activity of SLE.

Ovarian cystadenoma as a characteristic feature of families with hereditary ovarian cancers unassociated with BRCA1 and BRCA2 mutations.

The study aimed to determine whether hereditary ovarian cancers that are not caused by BRCA1/BRCA2 constitutional mutations are associated with a predisposition to cystadenoma. The study consisted of two parts. Part one concerned the incidence of ovarian cystadenoma in females from families with hereditary ovarian cancer unassociated with BRCA1 mutations. The study group included 62 female patients from 29 families, without any previously diagnosed malignancy, with no proven constitutional mutation of the BRCA1 gene. The first control group was composed of 62 female patients from 53 families, without any previously diagnosed malignancy, with an identified constitutional mutation of the BRCA1 gene. The second control group comprised 124 female patients for whom the only reason for the examination was a prophylactic check-up. All studied women were subjected to intravaginal ultra- sonographic investigations. In 8 patients with benign and/or borderline ovarian cystadenoma, a complete sequencing of coding fragments of the BRCA2 gene from the peripheral blood DNA was performed. Part two of this study concerned the incidence and pattern of malignant tumors in the families of female patients with ovarian cystadenoma. The final study group included 117 patients who had 726 I0 relatives (359 females and 367 males). We concluded that cystadenoma is likely to be a characteristic feature of the subgroup of families with hereditary ovarian cancers unassociated with BRCA1/BRCA2 constitutional mutations.

Clinical characteristics of hereditary ovarian cancer (HOC) in Poland.

BACKGROUND: Hereditary ovarian cancer (HOC), as any genetic disease, may display clinical characteristics that depends on population. AIM OF THE STUDY: The aim of the study was to describe clinical characteristics of HOC in Polish population basing on analysis of the following features: age at onset, clinical staging, morphological grading and prevalence of serous adenocarcinoma. MATERIAL AND METHOD: The cases were selected basing on analysis of pedigree/clinical features and molecular studies of founder mutations of BRCA1 gene in Poland. RESULTS: The patient's age at diagnosis was ca 49-52 and was similar in all groups. The exception was the subgroup without mutations in group II (breast and ovarian cancers found in families) with mean age at diagnosis ca 46 years (n = 9). In patients with HOC without mutation of BRCA1 gene, lower FIGO stage and lower morphological grade were detected more frequently. The majority of HOC showed histopathological pattern of serous adenocarcinoma. CONCLUSIONS: Clinical features of HOC in Poland and in other countries are similar. 2. Introduction of DNA tests to the clinical and pedigree diagnostic criteria allows detection of subgroups of HOC with different clinical features.

[Characteristics of selected features of hereditary ovarian cancer in carriers of constitutional BRCA1 gene mutation]. / Charakterystyka wybranych cech klinicznych dziedzicznych raków jajnika u nosicielek mutacji konstytucyjnej genu BRCA1.

BACKGROUND: Hereditary ovarian cancer in BRCA1 constitutional mutation carriers shows a characteristic clinical pattern. AIM OF THE STUDY: Evaluation of the type of mutation, age of onset, clinical stage (FIGO) and morphological grade (G) of ovarian cancers in BRCA1 mutation carriers. MATERIAL AND METHOD: We analyzed 16 cases of hereditary ovarian cancers from 14 families. The cases were included into studied group as a result of evaluation of pedigree criteria and molecular-genetic analyses detecting constitutional mutation--5382insC, C61G, 4153delA--founder mutations dominating the Polish population. The following features were compared between studied and control group: C1--age of onset of ovarian cancer in 5-year intervals (below 35, 40, 45, 50 and 55 years of age); C2--clinical staging (FIGO) I/II or III/IV: C3--grading (G1-G3). The data were analyzed statistically. RESULTS: Age of onset < 50, OR--2.52 is highly characteristic for BRCA1 mutation carries. Similarly the staging III/IV is more often observed in studied group--OR 2.71. The most characteristic of studied group is high morphological grading--OR 12.38. CONCLUSIONS: 1. Features of HOC in studied material and in other populations are similar 2. High morphological grading is the most characteristic for HOC in BRCA1 carriers.

Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus.

INTRODUCTION: Antiphosphatidylethanolamine antibodies (aPE) and antiphosphatidylserine antibodies (aPS) belong to a group of antiphospholipid antibodies (aPL) that occur in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). OBJECTIVES: The aim of this study was to examine associations between the elevated serum concentration of aPE/aPS, the clinical manifestations of SLE, and the presence of other autoantibodies. PATIENTS AND METHODS: The study group included 71 patients with SLE. The control group comprised 36 healthy volunteers. In both groups, serum aPS and aPE concentrations were measured with enzyme­linked immunosorbent assays. Clinical data, including clinical manifestations and the laboratory markers of SLE, were obtained from medical records. RESULTS: The study revealed a higher prevalence of aPE in patients with SLE than in controls (54.93% vs. 5.56%). aPS were observed in the study group less frequently compared with aPE (12.68% vs. 54.93%) and were absent in controls. Anticardiolipin antibodies and APS were found to be associated with the presence of aPS. Thrombocytopenia, Raynaud phenomenon, and myocardial infarction were observed more frequently among aPS­positive patients. The presence of aPE was also associated with the occurrence of mucosal ulcers in the mouth cavity. A positive correlation between aPS and erythrocyte sedimentation rate (ESR) was also observed. The serum concentration of aPE inversely correlated with red blood cell count and positively with ESR. CONCLUSIONS: The presence of aPS in patients with SLE is associated with thrombocytopenia, Raynaud phenomenon, and cardiac complications.

[Addison's disease imitating fibromyalgia]. / Choroba addisona imitujaca fibromialgie.

We present the case of a 33-year-old female with generalized pain in the musculoskeletal system, fatigue, and many other symptoms. She was initially diagnosed with fibromyalgia but other tests finally confirmed Addison's disease. Supplementation with adrenal hormones resulted in total remission of pain and of other symptoms. This case serves to illustrate diagnostic pitfalls in patients with a generalized pain syndrome.

[Adverse effects of cyclosporin a observed in rheumatoid arthritis and psoriatic arthritis]. / Dzialania niepozadane w czasie leczenia cyklosporyna a u chorych na reumatoidalne i Luszczycowe zapalenie stawów-obserwacje wlasne.

INTRODUCTION: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) represent diseases which often demand aggressive therapy in order to control the process and inhibit lesion formation in joints and organs. This kind of therapy can be achieved with cyclosporin A (CsA), particularly when combined with methotrexate (MTX). This combination is far more effective than single-drug therapy and is capable of significantly reducing the number of articular lesions. Considering the fact that monotherapy is associated with many adverse effects, it is feared that both drugs in combination may produce cumulative toxicity. The aim of this work was to determine the frequency of adverse effects caused by CsA in patients treated for RA and PA at the Outpatient Rheumatology Clinic of the First Public Hospital in Szczecin. MATERIAL AND METHODS: Our study group consisted of 61 patients, including 47 with RA--35 females, mean age 51 yrs (range: 21-69 yrs), mean disease duration 9.9 yrs (range: 2-23 yrs); 12 males, mean age 51.8 yrs (range: 33-74 yrs), mean disease duration 8 yrs (range: 3-14 yrs) and 14 with PA--6 females, mean age 41.1 yrs (range: 33-55 yrs), mean disease duration 7.8 yrs (range: 2-16 yrs); 8 males, mean age 42.9 yrs (range: 35-50 yrs), mean disease duration 7.0 yrs (range: 0.5-21 yrs). All patients were on MTX. During 11 years of follow-up, CsA was withdrawn due to adverse effects in 20 patients (32.8%). The following adverse effects were observed: arterial hypertension (n=19), hand tremor (n=11), hirsutism (n=7), elevated creatinine (n=17), gingival hypertrophy (n=9), abnormal appetite (n=2), peripheral neuropathy (n=1), lymphocytosis (n=1), skin lesions (n=1), diarrhea (n=2), recurrent infections (n=1), candidiasis (n=1), zoster (n=1), and neoplasm (n=2). Adverse effects responsible for withdrawal of CsA in 14 patients (23%) appeared more frequently during the first 12 months of therapy. Our observations indicate that CsA is well tolerated. The majority of adverse effects subsided after dose reduction or temporary withdrawal of the drug.

[Occurrence and risk factors of musculoskeletal pain and sport injuries in students of physical education in University of Szczecin]. / Wystepowanie i czynniki ryzyka dolegliwosci bólowych ze strony ukladu ruchu oraz urazów sportowych u studentów Instytutu Kultury Fizycznej Uniwersytetu Szczecinskiego.

PURPOSE: The aim of the study was to investigate the occurrence of musculoskeletal pain and sport injuries and also to find their risk factors among students of physical education of the University of Szczecin. MATERIAL AND METHODS: The study was conducted in students of physical education of the University of Szczecin and it was based upon a questionnaire. Of all 525 students, 503 (95.8%) responded the questionnaire, 218 women (43.3%), 285 men (56.7%). The questionnaire involved questions on the musculoskeletal complaints, participation in sports and its character, sport injuries with their localization and associated sport discipline, anthropometric, socio-economic and life style data, psychosocial profile. The univariate stepwise regression analysis, multivariate stepwise regression analysis, U Mann-Whitney test and chi2 test were used for statistical evaluation of the data. The odds ratio was calculated for chosen variables with 95% confidence interval. RESULTS: Almost half of the men and women reported the presence ofmusculoskeletal pain in the previous year. Both women and men claimed the most frequently knee pain, shoulder and ankle pain. Altogether 236 students reported sport injuries, 92 (42.4%) women and 144 (50.5%) men. The students reported the total number of 1065 injuries. Men claimed significantly more injuries then women. The most important risk factors for musculoskeletal pain were sport injuries. The psychosocial factors significantly influenced the occurrence of pain. Participation in certain sports was the main risk factor of injuries in students. Also participation in competitive sport was the risk factor for injuries of knee, ankle, feet and shoulder joints. CONCLUSIONS: 1. Musculoskeletal pain is common in the studied population. 2. Sport injuries are the most important risk factor of musculoskeletal pain in this group. Participation in certain sport disciplines and psychosocial factors are also risk factors ofmusculoskeletal pain. 3. Sport injuries were reported by nearly half of the students, the most common localization of injuries were knee and ankle joints. 4. There are specific injuries related in this group to participation in some sports, and also to participation in competitive sports.

[SAPHO syndrome--clinical features]. / Zespól SAPHO--obraz kliniczny.

OBJECTIVE: Presentation of clinical features of the SAPHO syndrome. MATERIALS AND METHODS: Seventeen patients (15 women and 2 men) with confirmed diagnosis of the SAPHO syndrome was presented. The culture of biopsy of pustulotic skin lesions was performed in 11 patients. ESR, C-reactive protein level and Waaler-Rose test were determined in all patients, and antinuclear antibodies and bone scintigraphy were performed in 16 patients. X-ray of the sterno-clavicular joints was performed in 15 patients. RESULTS: The age of patients was 22-59 yr. (mean: 47.1 yr). The duration of joint symptoms was 0.1-25 yr. (mean: 4.4 years). Pustulosis was presented in 16 patients, only 1 patient had acne. All patients suffered from pain localized on the anterior chest wall. Tenderness of the peripheral joints: wrist (in 7 patients), shoulder (in 7 patients), knee (in 4 patients) was shown. In 6 patients, skin changes preceded joint symptoms, in 2 patients skin changes followed joint symptoms after 5 and 10 yr., respectively. All patients had negative the Waaler-Rose test. Active inflammatory process characterized by an increased ESR and C-reactive protein level was present in 12 patients. Abnormalities in x-ray of the sterno-clavicular joints were present in 4 patients. Characteristic alternations for the SAPHO syndrome in scintigraphic picture of the skeleton were observed in 14 patients. All patients were treated with non-steroidal anti-inflammatory drugs. In 8 patients, treatment with antibiotics, in 11 patients--with sulfasalazine, in 3 patients--with methotrexate and low doses of glucocorticosteroids, in 1 patient--with colchicines was performed. CONCLUSIONS: Association of typical skin changes with pain of the anterior chest wall is the key for diagnosis of the SAPHO syndrome. It seems that this syndrome is more common in Poland than it has been previously estimated.

[Quality of life and activity of disease in patients with rheumatoid arthritis]. / Jakosc izycia i aktywnosc choroby u chorych na reumatoidalne zapalenie stawów.

PURPOSE: The aim of this study was to evaluate the quality of life in patients with rheumatoid arthritis (RA) considering their age, activity of the disease, its duration and radiological stage. MATERIAL AND METHODS: The study group consisted of 151 women (mean age 55.0 years, mean duration of RA 9.4 years) and 45 men (mean age 55.0 years, mean duration of RA 9.4 years). All subjects were treated at the Department of Rheumatology and at the SPSK-1 rheumatology outpatient clinic in Szczecin. Diagnosis of RA was established according to ARA criteria of 1987. The radiological stage of the disease was established according to Steinbrocker's criteria. The patient's quality of life was evaluated with the Health Assessment Questionnaire. The activity of RA was determined with the Disease Activity Score DAS 28. RESULTS: Significant correlation between HAQ score and DAS 28 was found (correlation coefficient--R = 0.38; p < 0.001). Age (R = 0.31, p < 0.001) and radiological stage of RA (R = 0.26, p < 0.001) were also found to affect the quality of life. CONCLUSIONS: The quality of life of patients with rheumatoid arthritis is significantly influenced by their age, activity of the disease, and radiological stage of RA.

[Adult-onset Still's disease]. / Choroba Stilla u doroslych.

INTRODUCTION: The authors present the course and manifestations of adult-onset Still's disease on the basis of five cases diagnosed at the Department of Rheumatology, Pomeranian Medical University in Szczecin. MATERIAL AND METHODS: The usefulness of two most popular sets of diagnostic criteria of adult-onset Still's disease (Yamaguchi and Cush) was analyzed. At onset of the disease, two out of five patients met both sets of the diagnostic criteria, two others met criteria of Yamaguchi and one of Cush. During follow-up, criteria of Yamaguchi were met in all cases. RESULTS: The authors suggest to use the Cushs criteria of adult-onset Still's disease when the patient does not meet the criteria of Yamaguchi and other causes of fever are excluded.

Association between early-onset breast and laryngeal cancers.

Recent studies suggest that there are groups of genes that predispose simultaneously to both early-onset breast and laryngeal cancer. Studies were performed on a large series of unselected patients with laryngeal cancer diagnosed in Szczecin, Poland. Pedigrees of 683 laryngeal cancer patients were analysed for the frequency of early-onset and late-onset breast cancer among first degree relatives. The observed frequencies of breast cancer in these families were compared to those expected. In addition, common mutations/variants in the 3 genes BRCA1, NOD2 and CYP1B1, known to be associated with early-onset breast cancer, were assessed to determine their frequency in 348 unselected laryngeal cancers. The average age at diagnosis of LC among patients, who had relatives affected by BC diagnosed under the age of 50 years was 57.62. In comparison LC patients reporting a first degree relative affected by BC diagnosed above 50 years of age, had an average age of diagnosis of 66.00 years, which was significantly different (p=0.0064). Similarly, the average age of diagnosis of BC among patients with LC diagnosed under age of 50 years was 46.7 years and whereas LC patients with tumors diagnosed above 50 years had relatives diagnosed with breast cancer at an average age of 53.37 years, which was significantly different (p=0.02). From the 348 consecutive ascertained laryngeal cancer patients who had molecular studies undertaken, breast cancers among first degree relatives were found in 18 families including 8 with breast cancers diagnosed less than 50 years of age. A molecular basis was identified (the CYP1B1 355T/T genotype) in only 2 of the 8 early cases suggestive of there being additional, as yet unknown genes that are associated with an early-onset laryngeal-breast cancer phenotype.

[Recurrent polychondritis. Presentation of two cases and a review of the literature]. / Nawracajace zapalenie chrzastek. Opis dwóch przypadków i przeglad pismiennictwa.

Relapsing polychondritis is a rare, chronic disease that can involve all types of cartilage in different sites. The most common symptoms of relapsing polychondritis are features of auricular, nasal and tracheal cartilage inflammation. The authors presented two cases of relapsing polychondritis and related diagnostic and therapeutic difficulties.