Safe and Efficient Use of Tocilizumab in Rheumatoid Arthritis Patient on Maintenance Hemodialysis: A Case Report.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune and inflammatory disease. Conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), Janus kinase inhibitors, and rituximab are used to treat the disease. There are no recommendations or guidelines for the treatment of patients with both inflammatory arthritis and end-stage renal disease (ESRD), despite the safety and efficacy of the mentioned drugs. The anti-interleukin-6 receptor antibody tocilizumab (TCZ) has not been used as a long-term therapy for hemodialysis (HD) patients with RA, except in a few case reports. Case Description: We present the case of a 41-year-old patient with RA and ESRD on maintenance HD due to type 1 diabetes-related complications. Due to high RA disease activity, the patient was not a suitable candidate for a kidney transplant. Because TCZ is used to treat both RA and kidney transplant rejection, therapy with a full dose of TCZ was administered. The patient has achieved sustained clinical remission (for the past four years) with no adverse events reported. Conclusions: Herein, we present the safe and effective use of TCZ in an RA patient on HD who is also a candidate for kidney transplant. Consequently, TCZ could be the treatment of choice for RA patients with ESRD who have not achieved disease control (low activity or remission) with conventional synthetic DMARDs. Clinical studies are required to evaluate the efficacy and safety of biologic DMARDs and Janus kinase inhibitors in patients with both inflammatory arthritis and ESRD.

The risk of developing non-Hodgkin lymphoma and the mortality rate in primary Sjögren's syndrome: a single-centre, retrospective cohort study.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is manifested by the sensation of dry eyes and dry mouth. The higher incidence of non-Hodgkin lymphoma (NHL) among pSS has already been extensively researched. However, there are uncertanties whether the mortality risk in pSS patients and in pSS patients with NHL is increased. The purpose of this study was to describe the prevalence of NHL among pSS patients and to calculate their mortality risk. We retrospectively analysed data on 1367 patients treated in our rheumatology department under the ICD-10 code M35.0. The study finally recruited 155 patients who met the 2016 ACR/EULAR criteria for the diagnosis of pSS. Descriptive statistics was used in data analysis. We applied the indirect standardization by age to compare the incidence rate of NHL in our cohort to general population. Additionally, we compared the mortality in our study to the general population by calculating the standardized mortality ratio (SMR). The overall incidence rate of NHL was 440 per 100,000 patient-years. The SIR compared to the general population was 30.13 (95% CI 12.87-54.63). The overall mortality rate of pSS patients in our cohort was nearly identical to that of the general population (SMR = 0.98 [95% CI (0.47-1.69)]). This study confirms that there are significant differences in lymphoma prevalence, histology, and prognosis across the studied populations. Furthermore, this study found that patients with pSS have similar mortality risk as the general population, and no patient in our cohort died from NHL.

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study).

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.

The frequency and characteristics of ultrasonographic ankle joint involvement in systemic lupus erythematosus: A prospective cross-sectional single-center study.

The involvement of ankles in systemic lupus erythematosus (SLE) has not been widely studied. The aim of our prospective study was to determine the characteristics of the ankle joint and tendon involvement in SLE using ultrasound (US) as an imaging modality. Sixty consecutive patients with SLE underwent a detailed clinical evaluation and US examination. Gray-scale and power Doppler US of the bilateral tibiotalar (TT) joints, subtalar (ST) joints, and ankle tendons were performed using a multiplanar scanning technique. Joint effusion, synovitis, tenosynovitis, enthesitis, and vascularization were assessed according to the OMERACT recommendations. The Total Ankle Ultrasound Score (TAUSS) was calculated as the sum of the grades of joint effusion and synovial hypertrophy for both TT and ST joints bilaterally (ranging from 0-24) and power Doppler activity was assessed separately. Finally, US findings were correlated with physical evaluation, laboratory parameters, and SLE activity scores. US ankle joint involvement was present in 32/60 (53.3%) patients. TT joints were affected in 26 (43.3%) and ST joints in 16 (26.7%) patients. Thirteen (21.7%) patients had US tendons and/or enthesal involvement. TT joint effusion was the most frequent finding, present in 55/240 (22.9%) examined joints, followed by synovial hypertrophy detected in 18/240 (7.5%) joints. The median (interquartile range; range) TAUSS of the US-affected joints was 1 (0-2; range 1-10). There were no significant correlations between US findings and inflammatory parameters or serological parameters of disease activity, but we found a weak positive correlation between TAUSS and the European Consensus Lupus Activity Measurement (r = 0.281, P = .029). This study revealed a high prevalence of pathological US ankle changes in patients with SLE and a positive correlation between ankle US involvement and disease activity score (European Consensus Lupus Activity Measurement).

Successful IL-17A inhibitor cycling in psoriatic arthritis patient: a case report and a literature review.

Psoriatic arthritis is an inflammatory arthritis with heterogeneous disease presentation. The most affected clinical domain of the disease determines the therapeutic approach. We report the case of a 34-year-old man with all six crucial domains of psoriatic arthritis (psoriasis, peripheral arthritis, axial skeletal manifestations, dactylitis, nail changes, and enthesitis) treated unsuccessfully with conventional synthetic DMARDs, NSAID's, and steroids as well as topical treatment and phototherapy. With golimumab as the first line of bDMARD partial remission was achieved. After 24 months the treatment was switched to secukinumab due to secondary inefficacy. The psoriasis and psoriatic arthritis relapsed after 21 months of treatment with secukinumab. The patient was cycled to ixekizumab with an excellent result. IL-17A inhibitor cycling may be a successful treatment option in some difficult to treat psoriatic arthritis patients.

Systemic erythematous lupus after treatment of multiple sclerosis with alemtuzumab.

Alemtuzumab is a humanized monoclonal antibody targeting CD52 protein that has shown great efficacy in the treatment of relapsing remitting multiple sclerosis and is associated with prolonged remission of the disease. Although it is highly effective, alemtuzumab can lead to serious adverse advents among which the most common are secondary autoimmune diseases. We present a patient who was treated with alemtuzumab for relapsing remitting multiple sclerosis. Her disease remained stable in a follow-up period of over ten years. However, during the follow-up period she developed thyroiditis one year, as well as systemic erythematous lupus seven years after the last alemtuzumab infusion, a disease not previously associated with alemtuzumab administration.

Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey.

BACKGROUND: The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. METHODS: Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. RESULTS: 438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. CONCLUSION: This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.

Treatment of refractory adult onset Still's disease with tocilizumab-a single centre experience and literature review.

Adult-onset Still's disease (AOSD) is defined as a systemic inflammatory disorder of unknown aetiology and is classified as a multigene autoinflammatory disease. Treatment of AOSD still remains mostly empirical with nonsteroidal anti-inflammatory drugs, glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs or cyclosporin A. Inhibitors of tumour necrosis factor-alpha and interleukin-1 (IL-1) antagonists have shown efficacy in certain subsets of patients with AOSD. The IL-6 molecule is one of the potential targets in treating AOSD considering that its level is increased in both the systemic and chronic articular forms of the disease. We present a series of eight patients from our centre with refractory AOSD treated with tocilizumab (TCZ). The drug was administered intravenously (6-8 mg/kg every 3-4 weeks) or subcutaneously (162 mg weekly). One patient had a disease relapse during TCZ therapy, and the drug had to be withdrawn in one patient due to a severe infection, while five out of six patients currently treated are in stable remission.Many previous reports have suggested that TCZ is an efficacious option for the treatment of refractory AOSD and the cases presented herein support this finding. A literature search revealed two previous reports of subcutaneous TCZ administration TCZ in AOSD, and our experience supports subcutaneous TCZ as a promising option for treatment of refractory AOSD patients.

Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (ß=-0.5 (95% CI -0.9 to -0.2) and ß=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.

Disease characteristics and causes of early and late death in a group of Croatian patients with systemic lupus erythematosus deceased over a 10-year period.

AIM: To assess the causes of early death (ED) and late death (LD) in patients with systemic lupus erythematosus (SLE) and determine the features of deceased SLE patients followed-up in a single Croatian tertiary hospital center, because little if any data on causes of death (CODs) in SLE patients are available for Croatia. METHOD: We identified SLE patients regularly followed-up at the Division of Clinical Immunology and Rheumatology, University Hospital Center Zagreb, who died from 2002 to 2011. Death was ascertained by matching our institutional records with the Croatian National Death Database. Patients were grouped according to their disease duration to ED and LD and compared by demographic characteristics, classification criteria, organ damage, and CODs. RESULTS: We identified 90 patients (68 women), who died at the age of 58±15 years. The most frequent COD category was cardiovascular diseases (40%), followed by infections (33%), active SLE (29%), and malignancies (17%). No significant difference was found between the frequencies of causes of ED and LD, except for stroke, which caused only LD≥10 years after the diagnosis. SLE was reported in death certificates of only 41 of 90 patients. CONCLUSION: Although stroke occurred both in the early and late disease course, it was primarily associated with LD. Given the low proportion of SLE recorded in death certificates of deceased SLE patients, matching of institutional and vital statistics records may be required to assess the true impact of SLE on mortality.

Opportunities and challenges in rheumatology research in Central Europe.

The Central European Congress of Rheumatology (CECR) has been organized by seven Central European countries: Austria, Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. These countries have lots of similarities, but also differences, with respect to rheumatology research. In this paper, based on questionnaires, we wish to demonstrate achievements and difficulties in rheumatology research performed in our region.

[THE IMPORTANCE OF TRANSITION IN RHEUMATOLOGY].

Rheumatic diseases are among the most common chronic diseases of childhood. Between 30 and 70% of pediatric rheumatology patients reach adulthood with some disease activity, functional limitations, or psychosocial problems. Transition is the purposeful, planned move of chronic pediatric patients from pediatric to adult care. It is a process in which adolescents with chronic conditions prepare for independent care for their health and life in general. Th e establishment of transitional services will ensure better disease control, limit long-term complications, work loss, and unnecessary health care costs, and increase quality of life.

GIANT CELL AORTITIS DIAGNOSED WITH PET/CT - PARANEOPLASTIC SYNDROME?

Vasculitides are heterogenic group of autoimmune connective tissue diseases which often present difficulties in early diagnosing. Giant cell arteritis is vasculitis of large and medium arteries. It predominantly presents with symptoms of affection of the external carotid artery branches. Furthermore, the only symptoms can be constitutional. In clinical practice, vasculitides are sometimes considered as paraneoplastic, but no definite association with malignancies has been established and the mechanisms are still debated. The gold standard for diagnosing giant cell arteritis is a positive temporal artery biopsy, but the results can often be false negative. Additionally, more than half of the patients have aorta and its main branches affected. Considering aforementioned, imaging studies are essential in confirming large-vessel vasculitis, amongst which is highly sensitive PET/CT. We present the case of a 70-year-old female patient with constitutional symptoms and elevated sedimentation rate. After extensive diagnostic tests, she was admitted to our Rheumatology unit. Aortitis of the abdominal aorta has been confirmed by PET/CT and after the introduction of glucocorticoids the disease soon went into clinical and laboratory remission. Shortly after aortitis has been diagnosed, lung carcinoma was revealed of which the patient died. At the time of the comprehensive diagnostics, there was no reasonable doubt for underlying malignoma. To the best of our knowledge, there are no recent publications concerning giant cell arteritis and neoplastic processes in the context of up-to-date non-invasive diagnostic methods (i.e. PET/CT). In the light of previous research results, we underline that the sensitivity of PET/CT is not satisfactory when estimating cancer dissemination in non-enlarged lymph nodes and that its value can at times be overestimated.

[A patient with rheumatoid arthritis and primary biliary cirrhosis successfully treated with adalimumab]. / Uspjesna primjena adalimumaba u bolesnice oboljele od reumatoidnog artritisa i primarne bilijarne ciroze.

Rheumatoid arthritis and primary biliary cirrhosis coexist in up to 6% of cases. Tumor necrosis factor alpha seems to have an important role in the pathogenesis of both diseases. Tumor necrosis factor alpha inhibitors have become an established therapeutic regimen for patients with rheumatoid arthritis. The only approved drug for primary biliary cirrhosis is ursodeoxycholic acid. We describe the case of a female patient with both rheumatoid arthritis and primary biliary cirrhosis in a long term remission of both diseases induced with adalimumab. This case report is an important addendum to a few published similar reports.

[Glucocorticoid induced osteoporosis]. / Glukokortikoidima izazvana osteoporoza.

Secondary osteoporosis most often develops due to glucocorticoid therapy. Glucocorticoids affect all stages of the bone remodeling cycle, its formation and resorption. Osteoblasts are primarily affected, decreasing their activity and enhancing apoptosis. Patients treated with glucocorticoids have lower bone mineral density and increased fracture risk. Glucocorticoid-induced osteoporosis can be prevented by administering the minimal effective dose of glucocorticoids, calcium and vitamin D supplementation or, if possible, by hormone replace- ment therapy. Moreover, appropriate physical activity should be encouraged. Patients who are at higher risk for low-energy fractures (for example post-menopausal women) have to be actively treated, usually with antiresorptive drugs among which bisphosphonates are currently the first line therapy.

Clinical features of the SAPHO syndrome and their role in choosing the therapeutic approach: report of four patients and review of the literature.

Although the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome was defined as a distinct entity more than 20 years ago, its classification within the spectrum of inflammatory rheumatic diseases and the proper therapeutic approach are still a matter of debate. We present four patients diagnosed with the SAPHO syndrome treated and followed-up in our Department, demonstrating the diversity of their clinical courses and their responses to different therapeutic approaches. We also review the clinical, laboratory, and imaging features of the SAPHO syndrome described in the relevant literature. Despite the growing quantity of published data on the clinical features of the syndrome and the recognition of two disease patterns (inflammatory and bone remodeling disease), it is still not clear whether these possible disease subsets require different therapeutic strategies. Tumor necrosis factor-alpha (TNF-α) inhibitors have been suggested to be effective in patients with the inflammatory pattern, whereas bisphosphonates seem to be effective in patients with bone remodeling disease; however, this is still a hypothesis not yet confirmed by adequately designed clinical studies. Further research is needed to assess disease features predicting favorable response to the two therapeutic modalities beyond the first line of therapy - TNF-α inhibitors and bisphosphonates.

Simultaneous presentation of oral and skin anaplastic large T-cell lymphoma.

We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.