Early predictors of increased bone resorption in juvenile idiopathic arthritis: OPG/RANKL ratio, as a key regulator of bone metabolism

To explore early changes in the predictors of bone turnover in children with juvenile idiopathic arthritis [JIA]. To identify osteoprotegerin/receptor activator of nuclear factor-kappaB ligand [OPG/RANKL] ratio in the serum of the same patients and its relation to the parameters of joint inflammation and joint destruction. Seventy children with JIA and 30 healthy children individually matched for age, sex, race, and county of residence were included in this study. Serum levels of calcium [Ca], phosphorus [Ph], alkaline phosphatase [ALP], osteocalcin [OC], RANKL and [OPG] were measured. Urinary concentration of deoxypyridinoline [DPD] was also done. All involved joints were assessed by plain radiography. Significant low serum concentrations of ALP and OPG was observed in JIA group, while there was a significant increase in serum level of RANKL and urine level of DPD compared to controls. OPG/RANKL ratio was significantly lower in JIA patients than in controls. OPG/RANKL ratio is correlated with most clinical characteristics, disease activity variables, JIA outcome measures and radiographic findings. DPD, RANKL and OPG/RANKL ratio, respectively, are considered as independent predictors of juxta-articular osteoporosis. OPG/RANKL ratio was the only predictor of bone erosion. The OPG/RANKL ratio could be an early predictor of increased bone resorption and a valuable biomarker for joint inflammation and bone injury in JIA patients

Post-streptococcal reactive arthritis [PSRA]: is it a distinct disease entity?

Reactive arthritis is defined as a sterile inflammatory arthritis occurring in association with primary infection at a distant site. Arthritis following primary throat infection with Group A beta, haemolytic Streptococci [GA beta S] may apply to this definition, Because of the similarity between the diagnostic criteria for acute rheumatic fever [ARF] and post-streptococcal reactive arthritis [PSRA], the diagnosis and treatment of PSRA are not well defined. To clarify whether PSRA is a separate disease entity? and to evaluate the extent of joint affection by using various clinical, laboratory and radiological tools. Twenty-five patients with arthritis secondary to infection with GA beta S who attended the Outpatient Rheumatology Clinics in Assuit University Hospitals were included in this study. Other forms of reactive arthritis [ReA] were excluded. All patients were submitted to complete medical history and clinical examination. Erythrocytic sedimentation rate [ESR], C-reactive protein [CRP], complete blood count, rheumatoid factor [RF], antinuclear antibodies [ANA], throat swab and Antistreptolysin O Titre [ASOT], have been done to all patients. Electrocardiogram [ECG] and Echocardiogram [ECHO] were performed. Plain radiography, ultrasonography [US] and Magnetic Resonance Imaging [MRI] to both knees and ankles were done to all patients. Twenty-five patients with a mean age +/- standard deviation of 22.40 +/- 7.42 years were selected. The arthritis persisted for up to six months with a latent period from 10 days to 2 weeks. ASOT was positive with a range from 200-800 IU. Culture of throat swab was positive for GA beta S in 72% of cases, in addition to other organisms [staphylococci in 24% and pneumococci in 16% of the patients]. All of the patients had non migratory arthritis of lower limbs, Knees and ankles synovitis with minimal effusion was detected in 36% of the patients by using ultrasound and 32% and 40% by using MRI respectively. Synovitis with marked effusion of the knees and ankles was detected in 36% and 44% of patients respectively by ultrasound and 40% by MRI. Post-streptococcal arthritis is a separate disease entity. The extent of joint affection might be evaluated by the use of US and MRI as the findings were concordant in knee joint affection. MRI was preferable in evaluating ankle joint synovitis

calcified intraarticular mass in a man with severe shoulder osteoarthritis: what are the implications?

Rapidly progressive osteoarthritis in the shoulder in the elderly is often associated with chronic rotator cuff calcifications and damage and with apatite crystals identifiable in the joint fluid. The key roles of the crystals and rotator cuff lesions although suspected have been disputed. We describe a 57-year-old man with severe degenerative changes at the right shoulder and other joints. A calcified mass 2-cm in length was found on radiographs medially in relation to the proximal humeral diaphysis. At arthroscopy, the mass was confirmed to be in the joint and due to calcified synovium. Biopsy revealed synovium with apatite like crystal clumps in this mass. Calcium pyrophosphate crystals were also found but in the cartilage only. This case with the apatite crystals only in synovium and with destructive arthritis without a complete rotator cuff tear raise the possibility that synovium as a primary site for apatite deposition might be important in the destructive arthritis. Management of this patient like many with rotator cuff tear arthropathy has been difficult. Rapidly destructive osteoarthritis at the shoulder, much like that in the patient reported here, has been described under a variety of terms that suggest implications for pathogenesis. Neer et al used the term cuff tear arthropathy to describe glenohumeral degenerative arthritis and a rotator cuff tear in twenty-six patients who had required a total shoulder replacement.[1] McCarty et al described 4 elderly women with destructive arthropathy of the shoulder, large effusions, apatite crystals present in the joint effusions and massive tears of the rotator cuffs and coined the term Milwaukee shoulder syndrome.[2],[3],[4]. Dieppe et al suggested the terms apatite-associated destructive arthritis and idiopathic destructive arthritis.[5] Calcifications have been noted in the rotator cuff structures but have not been reported in the joint or synovium.[3] We describe a patient with a similar destructive arthropathy, who had a calcified mass about 2-cm in length in the right shoulder, well visible by X-ray and arthroscopy, that was localized to synovium at arthroscopy. Since this patient did not have prominent rotator cuff disease, our case suggests that intraarticular crystals can be associated with difficult to manage progressive shoulder osteoarthritis without a prominent primary rotator cuff cause

Polarized light microscopy [PLM]: a role in filling the gaps of undiagnosed arthritis

Joint arthritis is a major clinical problem for any rheumatologic clinic. Diagnosis of these types of arthritis usually depends upon certain clinico-investigatory criteria usually settled by international organizations. Even the use of these criteria does not always revealed a solid diagnosis in many occasions. Moreover, there are reported literatures about presence of coexistence between different types of arthritis. Lack of diagnosis may result in poor outcome of management and sometimes worsen the prognosis of the case. This study aimed t. To evaluate synovial fluid analysis in diagnosis of effusion-associated arthritis to reach a final diagnosis in undiagnosed cases and to role out the importance of Polarized Light Microscopy [PLM] in diagnosis of the coexistence of two or more types of arthropathies. The present study is a cross-sectional descriptive hospital-based study, conducted in the department of Rheumatology and Rehabilitation in Assiut University Hospital. Sixty-one patients with established joint effusion [acute or chronic] were included in the study. The patients were grouped according to the type of rheumatological disease into 6 groups each of them represented one of the rheumatological diseases. Twelve cases were diagnosed as RA, 16 as OA, 9 as gout, 1 as pseudogout, 4 as SLE, and 4 as SPA. The final diagnosis could not be reached in 15 of them. The seventh group was the undiagnosed group. All the allocated participants were subjected to synovial fluid [SF] examination, macroscopically using [PLM] and microscopically, for leukocytic count and crystals. Monosodium urate [MSU] and Calcium pyrophosphate dihydrate [CPPD] crystals were identified. Of [SF] analysis were correlated with the preliminary clinical diagnosis which revealed that out of 61 examined cases combined arthritis was diagnosed in 10 cases [16.4%]. These 10 cases were combined OA and CPPD in 5 cases, combined RA and CPPD in 2 cases, and combined RA, MSU and CPPD in one case. Additionally, combined SLE and CPPD was diagnosed in one case and combined SPA and MSU in another one. Consequently, [PLM] examination allowed us to reduce the undiagnosed cases from 24.6% to 16.4%. Examination of SF for MSU and CPPD crystals was worth looking and can change the management strategy. PLM remained the only practical way of identifying these particles in the clinical setting

Von Willebrand factor, thrombomodulin and nitric oxide in Behcet's disease

Twenty-six patients with Behcet's disease [BD] [15 patients with active disease and 11 with inactive disease] and 20 healthy subjects, as a control group, were included in this study. All patients and controls were subjected to measurement of plasma levels of von Willebrand factor [vWF] and thrombomodulin [TM] as well as serum NO, in addition to complete blood picture, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]. The results showed that, means of vWF, TM and NO levels were significantly higher in BD patients than controls. Mean levels of vWF were high in patients with recurrent oral ulcer [ROU] and those with arthritis/arthralgia. Mean values of NO were significantly high in patients with ROU, RGU, patients with arthritis/arthralgia and thrombosis. Mean levels of vWF, TM and NO were significantly higher in active group than inactive group. Positive correlations were found between vWF with ESR2, CRP, TM and NO. Also, positive correlations were found between TM with ESR1 and ESR2. Also, positive correlations were found between NO with ESR1, ESR2 and CRP

Evaluation of bone turnover in seronegative spondyloarthrpathy [SSPA]: relationship to disease activity

Fifty-seven patients with SSPA were enrolled in this study [33 patients with ankylosing spondylitis [AS], 16 patients with psoriatic arthritis [PsA] and 8 patients with reactive arthritis [ReA]]. The healthy volunteers were served as control. Clinical and radiological status was assessed for each patient. Serum calcium, alkaline phosphatase [ALP] and bone-specific alkaline phosphatase [B-ALP], urinary calcium and free D-pyridinoline cross links [f-Dpyr] were assayed for patients and controls. Urinary excretion of f-Dpyr was significantly increased in AS and ReA, and in AS was correlated with inflammatory measures [ESR and CRP]. In PsA, patients with ESR >30 mm/hour had significantly higher levels of f-Dpyr, than those with ESR <30 mm/hour and those with CRP >6 mg/L than those with CRP <6 mg/L. No significant difference in urinary calcium excretion was observed in the patients groups compared with controls. As regard to bone formation in AS, serum calcium was significantly decreased and ALP, but not B-ALP, level was elevated compared with controls, positive correlation was also found between ALP and inflammatory measure [ESR and CRP]. In PsA patients, a significant increase in serum ALP and B- ALP, but not serum calcium was noted compared with controls. No variation was observed in patients with ReA. Finally, f-Dpyr excretion did not correlate with age, disease duration and no clear difference was observed between men and women. In conclusion, the urinary excretion of bone resorption markers [f-Dpyr] was increased in patients with SSpA, uncoupled by bone formation, particularly in AS, leading to bone loss in those patients and disease activity had a role in this bone turnover