Clinical outcomes of tocilizumab therapy in polyarticular and systemic juvenile idiopathic arthritis: a single-center analysis (2018-2022).

This single-center retrospective study aimed to evaluate the safety and efficacy of Tocilizumab (TOC) in children with polyarticular (pJIA) and systemic juvenile idiopathic arthritis (sJIA) who exhibited inadequate responses to disease-modifying antirheumatic drugs (DMARDs) and biological modifiers (bDMARDs). Conducted at the Department of Pediatric Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw, Poland, between 2018 and 2022, the study enrolled 29 patients diagnosed with JIA based on International League of Associations for Rheumatology (ILAR) criteria. The cohort comprised 13 sJIA and 16 pJIA patients, aged 2-18 years, receiving TOC treatment for 24 months. Safety and efficacy assessments included analysis of medical documentation, laboratory tests (CRP, ESR, WBC), and Juvenile Disease Activity Score (JADAS) 71 at baseline, 3, 6, 12, and 24 months post-treatment initiation. Significant reductions in CRP and ESR levels were observed within three months, with sustained improvement in JADAS71 scores over the 24-month treatment period. A substantial majority, 73.07% of patients, achieved inactive disease status or low disease activity, highlighting T0C's effectiveness. Adverse effects were manageable, predominantly involving mild to moderate infections, with no serious adverse events or instances of macrophage activation syndrome (MAS). The study also noted a steroid-sparing effect of TOC, with a reduction in glucocorticoid usage among the cohort. Tocilizumab demonstrates substantial efficacy in reducing disease activity and improving clinical outcomes in patients with pJIA and sJIA, coupled with a favorable safety profile. These findings reinforce the role of TOC as a critical component of the therapeutic arsenal for JIA, offering hope for improved quality of life and disease management in this patient population.

Revising diagnosis of juvenile idiopathic arthritis in adults: a single-center retrospective study.

The study aimed to assess how many adult patients with juvenile idiopathic arthritis (JIA) treated with biologics fulfill classification criteria for adult rheumatic diseases and to evaluate the course of JIA in adulthood. 138 patients with JIA over 18 years old treated with biologics were included in a cross-sectional observative study. Among 138 adult patients with JIA treated with biologics, 81 patients remained with JIA diagnosis. 57 patients were rediagnosed. 31 patients met the criteria for spondyloarthropathy, among them 18 patients for ankylosing spondylitis, 10 patients for psoriatic arthritis, and 3 patients for non-radiographic axial spondyloarthritis. Rheumatoid arthritis was diagnosed in 24 patients and adults' Still disease in 2 patients. 84 patients of all adults with JIA received one biologic agent, 40 received two biologic agents, and 14 received three or more biologic therapies. 10 patients received biologic agents out of recommendations for JIA. Of the adult JIA patients treated with biologics, 41% met the classification criteria for adult inflammatory diseases. Spondyloarthropathy and rheumatoid arthritis were most commonly diagnosed. Nearly 40% of adult JIA patients required at least one modification of biological treatment. Therefore, it is worth considering a revision of JIA to adult-onset inflammatory disease entities, as it broadens the spectrum of disease-modifying drugs.

Primary hypertrophic osteoarthropathy - a rare cause of pain and arthritis in children. Description of 5 cases.

Primary hypertrophic osteoarthropathy (PHOA) is a very rare disease. The typical triad of symptoms, i.e. digital clubbing, periosteal bone formation with bone and joint deformities and skin hypertrophy, may be accompanied by other specific conditions. In the majority of patients, the picture of the disease is incomplete. The dominant clinical symptom may be osteoarticular complaints. Moreover, the final confirmation of the diagnosis of the primary form of hypertrophic osteoarthropathy requires the analysis of much more frequent secondary causes of the disease. Diagnosing primary osteoarthropathy in children is particularly difficult. Some children report joint pain before the onset of the other symptoms of osteoarthropathy, while the physical and imaging examinations show features of arthritis. This can lead to misdiagnoses including the diagnosis of juvenile idiopathic arthritis (JIA) and the unnecessary use of immunosuppressive treatment. The present description of five patients from the Paediatric Rheumatology Department indicates diagnostic difficulties in children with PHOA. All of them were examined due to pain and features of arthritis. We observed an incomplete clinical picture of the disease. One patient required a revision of the previous diagnosis of JIA and discontinuation of ineffective treatment with disease-modifying antirheumatic drugs (DMARDs). PHOA should always be considered in the differential diagnosis of arthritis in children, due to the slow and often atypical development of symptoms, including the presence of pain and arthritis as the predominant symptom of the disease.

The use of radiosynovectomy in patients with juvenile idiopathic arthritis. Assessment of treatment efficacy and safety.

OBJECTIVES: The aim of the study was to evaluate the usefulness of knee joint radiosynovectomy (RS) in patients suffering from juvenile idiopathic arthritis (JIA). MATERIAL AND METHODS: One hundred RS procedures performed in 58 patients with JIA in average age 10.4 years were evaluated. RESULTS: After 6 weeks, a decrease in the number of cases with joint pain from 90.3% to 29%, with joint oedema from 100% to 74.5%, with joint exudate from 100% to 60.6%, with gait disorders from 19.4% to 3.2%, with joint mobility disorders from 51.1% to 26.6% in the RS cases was observed. A reduction of the score in the Colorado scale from 10.9 to 4.66, in the pain visual analogue scale (VAS) from 50 to 10, in the illness VAS assessed by the patient/parent from 69.9 to 32.4, in the illness VAS assessed by the physician from 68.8 to 36.9 was observed. Six months after the RS procedure, a reduction in the number of cases with joint pain from 89.5% prior to the procedure to 29.5%, with oedema from 100% to 58.3%, with exudate from 100% to 46.9%, with gait disorders from 20% to 2.1%, with joint motility disorders from 51.1% to 26.1% was achieved. The score in the Colorado scale was reduced from 10.9 to 4.04, in the pain VAS from 40 to 0, in the illness VAS assessed by the patient/parent from 69.7 to 27.9, in the illness VAS assessed by the physician from 68.8 to 32.4. In ultrasound examinations, the greatest improvement compared to the initial condition was recorded in the 6th month after the RS. Radiosynovectomy was positively evaluated by parents and patients in 34 anonymous surveys. Early and late observations (average 1473 days) did not show lesions at the isotope injection site, and no neoplastic lesions were observed. CONCLUSIONS: Radiosynovectomy is a valuable therapeutic option for local treatment in patients with JIA.

Juvenile systemic sclerosis - observations of one clinical centre.

OBJECTIVES: The systemic form of scleroderma (SSc) in children is a very rare disease; therefore, it is recognized relatively late, which increases the risk of complications. The aim of the study was to assess the clinical symptoms of juvenile systemic sclerosis (JSSc) in our cohort patients. MATERIAL AND METHODS: A group of (N = 22) scleroderma patients aged between 2 and 16 years were observed. Demographic data and all clinical results obtained during 16 years of observation in the clinic of rheumatic diseases of developmental age were collected and analysed. RESULTS: In all observed children the major JSSc criterion was found, i.e. skin thickening proximal to the metacarpal phalangeal and/or metatarsophalangeal joints. Other symptoms are presented as follows: nailfold capillary abnormalities - 100%, Raynaud's phenomenon - 90.9%, sclerodactyly - 27.3%, digital tip ulcers - 27.3%, dysphagia - 18.2%, gastroesophageal reflux - 27.3% (assessed in only 10 children), arrhythmias - 22.7%, heart failure - 9.1%, new-onset arterial hypertension - 9.1%, pulmonary fibrosis - 72.7%, pulmonary arterial hypertension - 9.1%, neuropathy - 13.6%, carpal tunnel syndrome - 4.5%, tendon friction rubs - 4.5%, arthritis - 22.7%, and myositis - 13.6%. There were no cases of renal crisis. Decreased diffusing capacity of oxygen was confirmed in 12 patients (58.3%). The presence of antinuclear antibodies was noticed in 86.7% of patients, and among SSc selective autoantibodies: anticentromere - 31.8%, anti-topoisomerase I - 18.2%, anti-PM-Scl 100 or 75 - 45.5%, anti-RP11, Th/To, PCNA in total in 27.3% were presented. In 4.5% of cases, apart from the presence of anti-PM-Scl autoantibodies, positive lupus band test, reduced concentration of complement, and antiphospholipid antibodies were also found. In 59% of studied children, the body mass index was below the 25th percentile. CONCLUSIONS: The presented retrospective analysis shows that the occurrence of Raynaud's phenomenon with changes in nailfold capillaroscopy is the best screening toll for the assessment of risk of JSSc. All patients of developmental age with Raynaud's phenomenon, especially in the case of the appearance of antinuclear antibodies, should be monitored with capillaroscopy regardless of other laboratory or imaging tests.

Assessment of anti-HBs antibody concentration in children with juvenile idiopathic arthritis treated with biological drugs, vaccinated against viral type B hepatitis in infancy.

OBJECTIVES: The introduction of vaccinations against viral hepatitis B in the years 1994-1996 in Poland significantly improved the epidemiological situation of hepatitis B virus (HBV) infections in our country. According to the report of the National Institute of Public Health - National Institute of Hygiene in 2018, 40 cases of acute hepatitis B were noted while still in the 1980s between 10 and 20 thousand new cases were reported annually. The aim of the study was to determine whether in children treated with biological drugs (adalimumab, etanercept, infliximab) due to juvenile idiopathic arthritis (JIA), vaccinated against hepatitis B in infancy, a protective concentration of anti-HBs antibodies persists. In patients, the value ≥ 10 mIU/ml is regarded as a protective concentration of antibodies, determined at least four weeks after administration of the last vaccine dose. Among healthy individuals, presence of anti-HBs antibodies in any concentration means seroprotection. No booster vaccinations are recommended in basically vaccinated healthy individuals. MATERIAL AND METHODS: The concentrations of anti-HBs antibodies were determined in 56 children with JIA (38 girls - 67.9% and 18 boys - 32.1%) aged from 2 years and 4 months to 17.5 years, treated for at least three months with biological drugs. The diagnosis of JIA was made based on the International League of Associations for Rheumatology (ILAR) criteria. All studied patients were at the stable stage of the disease and received a full course of hepatitis B vaccination during infancy (in accordance with 0,1,6 months injection scheme). RESULTS: In the studied children a protective anti-HBs antibody concentration was found in 34 cases (60.7%), and 22 children (39.3%) had anti-HBs antibody concentration < 10 mIU/ml (in these children no seroprotection was found). CONCLUSIONS: The post-vaccination antibody concentration should be determined in children with JIA, treated with biological drugs and, in case of absence of a protective concentration, revaccination should be started.

Juvenile spondyloarthritis and chronic recurrent multifocal osteomyelitis overlap syndrome in a 16-year-old adolescent. A case report and literature review.

The authors present a very rare case of juvenile spondyloarthritis and chronic recurrent multifocal osteomyelitis overlap syndrome in a 16-year-old girl and discuss diagnostic difficulties associated with this case. Juvenile spondyloarthropathies are a type of rheumatic diseases characterized by non-symmetrical peripheral arthritis and enthesitis as well as by spondylitis. Chronic recurrent multifocal osteomyelitis is a rare, possibly autoimmune disease found primarily in children and adolescents. The disease is characterized by bone marrow inflammation and the presence of lytic and sclerotic lesions. Diagnostic imaging plays a key role in the identification of both diseases. The primary modality is X-ray; however, currently, magnetic resonance imaging and ultrasound are increasingly important. A correct early diagnosis allows one to start appropriate treatment to reduce the consequences of these diseases.The authors present a very rare case of juvenile spondyloarthritis and chronic recurrent multifocal osteomyelitis overlap syndrome in a 16-year-old girl and discuss diagnostic difficulties associated with this case. Juvenile spondyloarthropathies are a type of rheumatic diseases characterized by non-symmetrical peripheral arthritis and enthesitis as well as by spondylitis. Chronic recurrent multifocal osteomyelitis is a rare, possibly autoimmune disease found primarily in children and adolescents. The disease is characterized by bone marrow inflammation and the presence of lytic and sclerotic lesions. Diagnostic imaging plays a key role in the identification of both diseases. The primary modality is X-ray; however, currently, magnetic resonance imaging and ultrasound are increasingly important. A correct early diagnosis allows one to start appropriate treatment to reduce the consequences of these diseases.

Diagnostic and therapeutic difficulties in a patient with chronic recurrent multifocal osteomyelitis coexisting with ulcerative colitis.

Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory bone disease, affecting mainly children. CNO includes a broad clinical spectrum of symptoms and signs, from mild, limited in time, unifocal osteitis to severe, chronic, active or recurrent, multifocal osteomyelitis. In 2014 diagnostic criteria for CNO were proposed, the Bristol Criteria for the Diagnosis of Chronic Non-bacterial Osteitis, taking into account the clinical picture - location and number of inflammatory foci, characteristic changes on radiological examination (X-ray) and magnetic resonance imaging (MRI), C-reactive protein (CRP) concentration, and changes in bone biopsy. The paper presents the case of a four-year-old boy in whom the diagnosis of multifocal osteomyelitis coexisting with ulcerative colitis was established. Attention was paid to the long diagnostic process of the disease, requiring in the first place differentiation with proliferative diseases. The choice of drugs was also a significant problem in the patient described in view of both intolerance of individual preparations and their ineffectiveness.

The Polish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Polish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 154 JIA patients (10.4% systemic, 50.0% oligoarticular, 24.7% RF-negative polyarthritis, 14.9% other categories) and 91 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Polish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Rheumatic fever - new diagnostic criteria.

Rheumatic fever (RF) is an autoimmune disease associated with group A ß-hemolytic streptococcal infection, in the course of which the patient develops carditis, arthritis, chorea, subcutaneous nodules and erythema marginatum. Rheumatic fever diagnosis is based on the Jones criteria, developed in 1944, then revised twice by the American Heart Association (AHA), in 1992 and recently in 2015. The last revision of the Jones criteria consists mainly in the supplementation of the major criteria with echocardiographic examination, the introduction of a concept of subclinical carditis and the isolation of low, medium and high risk populations among the patients. AHA recommends that all the patients with suspected RF undergo Doppler echocardiographic examination after the Jones criteria have been verified, even if no clinical signs of carditis are present.

Self-healing juvenile cutaneous mucinosis.

Girl, aged 4 years old, began the disease with pain of the lower extremities, fever up to 38°C and signs of upper airway infection. Then the patient developed oedema and redness of the whole face, thickened skin, subcutaneous nodular foldings of the frontal, occipital, cervical and axillary regions, extensor areas of the joints; fine, hard whitish nodules in the frontal region and over interphalangeal joints of the hands, pruritus; oedemas of the ankles, knees and joints of the hands, cervical lymphadenopathy and hepatomegaly. Blood tests at the moment of the diagnosis revealed elevation of markers of inflammation as ESR and CRP, leukocytosis, thrombocytosis, hypoalbuminemia, and hyper-alfa-2-globulinemia. Histopathological examination of the skin biopsy specimen and subcutaneous tissue revealed myxoid subcutaneous tissue located under the dermis and a section consisting of myxoid mesenchymal tissue with inflammatory infiltration by histiocytic cells. The presence of acid mucopolysaccharides in fields of the myxoid tissue was also observed. The self-healing juvenile cutaneous mucinosis (SJCM) was diagnosed.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

INTRODUCTION: Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. MATERIAL AND METHODS: There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. RESULTS: FEV1, FEV1/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. CONCLUSIONS: Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression.

OBJECTIVES: Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. MATERIAL AND METHODS: The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases - 37 girls (74%) and 13 boys (26%), aged 1.5-17.5 years - during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children - 28 girls (56%) and 22 boys (44%) aged 2-17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0-1-6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. RESULTS: No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%). CONCLUSIONS: The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B.

Etanercept treatment in juvenile idiopathic arthritis: the Polish registry.

BACKGROUND: To evaluate the long-term safety and efficacy of etanercept treatment in Polish patients with juvenile idiopathic arthritis (JIA). MATERIAL/METHODS: The study involved patients, fulfilling the JIA criteria of the International League of Associations of Rheumatology (ILAR), who were started on etanercept therapy after methotrexate and other synthetic disease-modifying antirheumatic drugs (DMARDs) had proven ineffective. Patient data were collected in an electronic registry. Disease improvement was assessed based on Giannini's criteria. RESULTS: The statistical analysis involved 188 patients. Significant improvement was observed in all clinical and laboratory parameters after the first month of therapy and was maintained in the following months. ACR Pediatric 30, 50, 70, 90, and 100 improvement was observed in 81.4%, 65.9%, 27.5%, 16.2%, and 15%, respectively, of patients after 3 months and in 94.7%, 88.4%, 62.1%, 34.7%, and 26.3%, respectively, after 24 months of treatment. Throughout the 72-month safety observation period, 1162 adverse events were reported; the exposure-adjusted AE rate was 2.96 per patient per year. CONCLUSIONS: In patients with various subtypes of JIA resistant to conventional DMARD treatment, etanercept resulted in significant and long-lasting improvements in disease activity. Combination treatment with etanercept and a DMARD was well tolerated.

[The occurrence of anticardiolipin antibodies bound in circulating immunological complexes in sera of patients suffering from juvenile lupus erythematosus and juvenile idiopathic arthritis]. / Wystepowanie przeciwcial antykardiolipinowych w krazacych kompleksach immunologicznych u dzieci z mlodzienczym toczniem rumieniowatym ukladowym i mlodzieniczym idiopatycznym zapaleniem stawów.

BACKGROUND: The presence of antiphospholipid antibodies (APA), especially anticardiolipin antibodies (ACA), antibodies against beta2-glikoprotein I and lupus anticoagulant leads to thrombotic disorders. The pathogenetic role of APA in children is not exactly explained. The frequency of occurrence of APA and antiphospholipid syndrom in children is 2 to 3 times lower than in adults. OBJECTIVES: The aim of the study was to indicate the presence of ACA in circulating immunological complexes (CIC) from sera of patients suffering from juvenile idiopathic arthritis (JIA) and juvenile systemic lupus erythematosus (JSLE). PATIENTS AND METHODS: 31 sera were investigated, 16 from JIA patients and 15 from JSLE patients. The free ACA IgG class, ACA bound in CIC were estimated by the ELISA method (after dissociation of CIC and y-fraction paecipitation). RESULTS: In CIC isolated from sera of JIA and JSLE patients ACA were discovered. ACA, possessing high avidity, in CIC were more frequently discovered than unbound ACA (38.7% vs. 25.8%). CONCLUSIONS: ACA in CIC were more frequent in sera of JIA patients, unbound ACA were more frequent in sera of JSLE patients.