Increased clinical symptoms of acromegalic arthropathy in patients with long-term disease control: a prospective follow-up study

Arthropathy is an invalidating complication of acromegaly. This arthropathy deteriorates radiographically despite long-term disease control. However, the clinical course and its relationship to the radiographic course are currently unknown. We aimed to investigate the clinical course of arthropathy during follow-up and its relationship to radiographic progression in long-term controlled acromegaly patients. Prospective follow-up study. We studied 58 patients (mean age 62 years, women 41 %) with controlled acromegaly for a mean of 17.6 years. Clinical progression of joint disease was defined at baseline and after 2.6 years, by the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Australian/Canadian Osteoarthritis Index (AUSCAN) questionnaires for lower limb and hand OA, respectively, and performance tests. Potential risk factors for progression were assessed. The clinical course of arthropathy was related to the radiographic course. On average, hand and lower limb function deteriorated during follow-up, despite large interindividual variations. Joint pain was stable over time. High levels of pain and functional impairment at baseline were related to clinical progression of hand pain and functional limitations. High baseline BMI was a risk factor for functional deterioration in the lower limb. The changes in symptoms and radiographic progression during follow-up were not related. In treated acromegaly patients, joint function deteriorates during prolonged follow-up, despite biochemical disease control, although there was interindividual variation. Clinical and radiographic course of arthropathy were not related. Therefore, in clinical practice, a combination of clinical and radiographic assessment is necessary to evaluate the course of acromegalic arthropathy.     

Viscosupplementation in haemophilic arthropathy: a long-term follow-up study

Haemophilic arthropathy is the most common clinical manifestation of haemophilia, secondary to recurrent haemarthroses and chronic synovitis. Modern bleeding-preventing drugs have limited significantly the incidence of severe arthropathy, and primary approach is usually conservative. Use of intra-articular injections of hyaluronan acid is considered one of the most efficient treatments for early stages of articular degenerative diseases. Assessment of long-term effectiveness of intra-articular administration of hyaluronic acid (HA) in knees, ankles and elbows of patients affected by haemophilic arthropathy was done for 46 patients (10 elbows, 24 knees and 25 ankles) affected by haemophilic arthropathy. They received injections of HA and were evaluated with Visual Analogue Scale, Short Form-36, World Federation of Haemophilia score and Petterson score with a 6-year mean follow-up. Most of the patients showed improvement in pain relief and functional recovery without any complications: only a limited number of patients (8.6%) found poor results, undergoing surgery or other further treatments in the follow-up period for persistent pain or limitation. Viscosupplementation is an effective therapeutic strategy in early stages of haemophilic arthropathy, with no complications and long-term good clinical results.     

Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.     

Progression of valvar aortic stenosis: a long-term retrospective study

Aortic valve stenosis is a potentially serious condition. Progression from mild to severe aortic stenosis is well-recognized but there are few data as to the likely rate of progression. Clinical outcome and cardiac catheterization data were reviewed for 65 patients with valvar aortic stenosis. Each patient had been investigated by cardiac catheterization on at least two occasions, the interval between studies ranging between 1 and 17 years (mean 7 years). In 60 cases the aortic valve gradient had increased, from a median of 10 mmHg (range 0-60) to a median of 52 mmHg (range 15-120). The mean rate of increase of gradient was 6.5 mmHg per year, and was significantly faster in patients in whom there was aortic valve calcification or aortic regurgitation present at the first catheter study (P less than 0.02). This study shows that progression of aortic stenosis may be very rapid, and correlates with valve calcification and regurgitation. If cardiac surgery is proposed for co-existing coronary or mitral valve disease in patients with mild or moderate aortic valve gradients, then aortic valve replacement should be considered at that time.     

Progression of haemophilic arthropathy in children: a Lithuanian – Danish comparative study

Recurrent bleeding into joints initiates a sequence of events leading to a progressive joint damage in people with severe haemophilia. This is a continuous process during childhood and adolescence, therefore joint abnormalities may be minimal on physical examination in very young children – even those receiving on‐demand treatment. The aim of our study was to quantify the burden of arthropathy in Lithuanian patients who had been treated exclusively by on‐demand substitution and compare their physical joint health with age‐matched Danish patients who received prophylaxis from an early age. Boys, aged 4–17 years, with severe haemophilia and no signs of inhibitors were included in the study. Joint outcome based on the Haemophilia Joint Health Score (HJHS) was analysed in two different treatment groups and compared within the matched pairs. In total, 32 (16 in each treatment group) patients were enroled. A total of 192 joints were evaluated. Joint status according to treatment strategy was strikingly different: 27.4 for on‐demand vs. 3.3 for prophylaxis (<0.001) group. Significance of the difference in joint status comparing different treatment strategies was equally strong both in younger (4–9 years) and older (10–17 years) patient groups: 2.2 vs. 12.5 (P = 0.0002) and 3.9 vs. 36.3 (P < 0.0001) respectively. The results further demonstrate the unequivocal effect of prophylaxis on joint status and give an insight into early and late manifestations of joint impairment based on the HJHS in haemophilia patients with treatment on‐demand compared with joint changes that may develop over the time with the preventative treatment.     

Frozen shoulder: a long-term prospective study.

As the natural history of frozen shoulder is poorly documented, a prospective study of 40 patients followed up for 40-48 months (mean 44 months) is described. The range of movement was significantly less than age- and sex-matched controls. Objective restriction was severe in five patients and mild in a further 11. Patients were often unaware that shoulder range was impaired. Dominant arm involvement, manual labour, and mobilisation physiotherapy were associated with a less satisfactory outcome. We conclude that, while objective restriction persists, there is little functional impairment in the late stage of frozen shoulder.     

Progression of mitral regurgitation: a prospective Doppler echocardiographic study.

OBJECTIVES: This study was performed to define the rates and determinants of progression of organic mitral regurgitation (MR). BACKGROUND: Severe MR has major clinical consequences, but the rates and determinants of progression of the degree of regurgitation are unknown. Quantitative Doppler echocardiographic methods allow the quantitation of regurgitant volume (RVol), regurgitant fraction (RF) and effective regurgitant orifice (ERO) to define progression of MR. METHODS: In a prospective study of MR progression, 74 patients had two quantitative Doppler echocardiographic examinations of MR (with at least two methods) 561 +/- 423 days apart without an intervening event. RESULTS: Progression of MR was observed, with increase in RVol (77 +/- 46 ml vs. 65 +/- 40 ml, p < 0.0001), RF (47 +/- 16% vs. 43% +/- 15%, p < 0.0001), and ERO (50 +/- 35 mm2 vs. 41 +/- 28 mm2, p < 0.0001). Annual rates (95% confidence interval) were, respectively, 7.4 ml/year (5.1, 9.7), 2.9%/year (1.9, 3.9) and 5.9 mm2/year (3.9, 7.8). However, wide individual variation was observed, and regression and progression of RVol >8 ml was found in 11% and 51%, respectively. In multivariate analysis, independent predictors of progression of RVol were progression of the lesions, particularly a new flail leaflet (p = 0.0003), and progression of mitral annulus diameter (p = 0.0001). Regression of MR was associated with marked changes in afterload, particularly decreased blood pressure (p = 0.008). No significant effect of treatment was detected. CONCLUSIONS: Organic MR tends to progress over time with increase in volume overload (RVol) due to increase in ERO. Progression of MR is variable and determined by progression of lesions or mitral annulus size. These data should help plan follow up of patients with organic MR and future intervention trials.     

Osteoarthritis, magnetic resonance imaging, and biochemical markers: a one year prospective study

OBJECTIVE: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. METHODS: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months. RESULTS: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004). CONCLUSIONS: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.     

Natural course of acute hepatitis C: a long-term prospective study

BACKGROUND: Acute hepatitis C has a high chronicity rate which appears to be significantly reduced by early antiviral treatment. However, it is unclear if all acutely infected patients should be treated, and when. In this prospective study, patients with a well-documented diagnosis of acute hepatitis C were evaluated to define the natural course, the rate of chronicity, and host and virus-related factors which might predict a self-limiting or chronic evolution requiring early antiviral treatment. METHODS: From 1995 to 2000, 40 consecutive patients with a community-acquired AHC were enrolled. Liver tests, anti-hepatitis C virus antibodies and hepatitis C virus RNA levels were monitored. Median follow-up was 35 months (range 12-68). RESULTS: A total of 24/40 patients had symptomatic disease including 20 with jaundice; 13/40 patients had prompt serum hepatitis C virus RNA clearance and ALT normalisation within 12 weeks; in 12/13 patients this pattern remained unchanged during follow-up. Overall, 27/40 patients remained hepatitis C virus RNA positive with fluctuating ALT levels. Older age and jaundice were predictive of resolution whereas there was no correlation with other host factors, viral genotype or viral load. CONCLUSIONS: Our data demonstrate that spontaneous resolution can occur in about 30% of AHC patients. This favourable outcome rarely occurs in patients with anicteric AHC or in those with jaundice but with persistent viremia for more than 12 weeks from onset; early antiviral treatment for these patients may avoid or reduce chronicity.     

Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study

OBJECTIVE: To assess the evolution of disease subgroups and the frequency of progression of peripheral joint disease in a prospectively studied cohort of patients with psoriatic arthritis (PsA). METHODS: The cohort was identified as the first consecutive 100 patients attending a psoriatic arthritis clinic and who had been the subject of a previously published cross-sectional retrospective study. Nine of the 100 patients had died, three declined follow-up and one could not be traced. The remaining 87 patients (49 females, 38 males) completed the study proforma at a median follow-up interval of 65 months (range 39-90). An analysis of initial plasma viscosity compared with rates of progression of joint score was performed. RESULTS: Eighteen patients changed subgroup; 11 had an increase in the number of joints involved, six a decrease, and one changed from an oligoarticular pattern to predominant spondylitis. Within the polyarticular group 37/51 patients had an increase in the number of joints involved. For the whole population, there were significant increases in the number of joints involved (median 6 vs 11, P < 0.001 Wilcoxon signed rank) and Health Assessment Questionnaire scores (median 0.375 vs 0.5, P < 0.001). The median rate of joint progression was 0.42 peripheral joints per year (range 0-7.2). However, the rate of peripheral joint involvement was highest in the first year of arthritis (median 4.0 joints/yr) as measured in 13 patients who had onset within 12 months of baseline assessment. There were no significant differences in skin and nail scores although nine more patients had developed nail disease. There was a significant correlation between the initial viscosity and rate of progression of joint damage (Spearman correlation, P < 0.011). CONCLUSIONS: Peripheral joint disease is progressive in the majority of patients with PsA and reinforces the need for effective monitoring and treatment.     

Mechanism of action of intradiscal chymopapain in the treatment of sciatica: a clinical, biochemical, and radiological study.

Seventeen patients with intractable sciatica due to prolapse of a lumbar disc, treated by intradiscal injection of chymopapain (chemonucleolysis) were studied. Analysis of serial 24 hour urine collections showed a significant increase in urinary glycosaminoglycan after chemonucleolysis. This was not detected in four patients undergoing routine discography. Enzymic analysis of urinary glycosaminoglycan after chemonucleolysis suggested that the increase in levels was largely due to an increase in the amounts of chondroitin sulphate present, probably resulting from proteoglycan breakdown in the intervertebral disc. Eight of the patients treated by chemonucleolysis underwent serial computed tomography (CT). One month after the injection the only change seen was a loss of definition of the disc prolapse, which could be interpreted as a loss of turgidity in the disc as a result of proteoglycan breakdown by chymopapain. By six months the CT of those patients whose symptoms had improved showed that the degree of disc prolapse was usually less marked and the disc margin more clearly defined, suggesting that by this stage anatomical remodelling had occurred.     

Familial arthropathy in Saudi Arabian children: demographic, clinical, and biochemical features

BACKGROUND: Familial arthropathy comprises a heterogeneous group of arthropathies. It can be either an inflammatory or a noninflammatory condition. The worldwide frequency of these disorders is unknown. OBJECTIVE: To study the demographic, clinical and biochemical features, and survival of a large series of children with familial arthropathies. METHODS: The medical records of children who had an arthropathy and a family history of a similar condition at the Pediatric Rheumatology Clinic at King Faisal Specialist Hospital-Riyadh between 1990 and 2005 were reviewed. These included children with familial juvenile idiopathic arthritis (FJIA), infantile systemic hyalinosis (ISH), the nodulosis-arthropathy-osteolysis (NAO) syndrome, and the camptodactyly-arthropathy-coxa vara (CAC) syndrome. Familial rheumatic diseases including spondyloarthropathies or known syndromes associated with articular manifestations were excluded. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, and provisional and final diagnoses as well as treatment and outcome were reviewed. RESULTS: Sixty-two children with various familial arthropathies were reviewed. Twelve children (9 female/3 male) with FJIA presented with polyarthritis. These children belonged to 4 unrelated families, all of whom were from the same geographical area, with 2 families belonging to the same tribe. The mean age at onset was 2.4 years, and mean age at diagnosis was 3.5 years. All children had high inflammatory markers. Nineteen children (11 male/8 female) with ISH presented in the neonatal period with painful joint contractures and typical mucocutaneous features. The referral diagnosis was inaccurate in 14 patients. Thirteen patients were the product of first-degree cousin marriages, and 5 families had more than 1 affected child. Radiological findings included periosteal reaction and osteolytic lesions. Tissue biopsy was performed in 8 patients and the findings were consistent with the diagnosis in all 8 patients. Despite aggressive management, 16 patients died. The mean age of the remaining 3 surviving children was 20 months. There were 15 children (9 female/6 male) with the NAO syndrome with a mean age at onset of 3.4 years. They were from 7 unrelated families; 5 families had more than 1 affected child. The referral diagnosis was juvenile idiopathic arthritis (JIA). Most children presented with painful deformed hands. Eleven children (70%) had advanced osteolytic changes. All children had normal inflammatory markers. There were 16 children (11 male/5 female) with the CAC syndrome who were diagnosed at a mean age of 3.7 years. Camptodactyly presented at birth or in first months of life, while other features developed in early childhood. JIA was the referral diagnosis. Fourteen children had bilateral coxa vara. Two children exhibited symptoms or signs of pericarditis. Inflammatory markers were normal in all children. CONCLUSIONS: Familial arthropathies are not uncommon conditions which may be easily confused with JIA, causing a delay in diagnosis and management. Careful evaluation of a child presenting with an arthropathy, particularly in a population where consanguinity is common, is required for timely and accurate diagnosis. Overall, the prognosis of these conditions remains guarded despite treatment.     

Assessment of clinical,biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 10⁸ WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1β, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid.Level of evidence: IV.     

Major results of a long-term prospective study of a male population

The results of a prospective study of a Moscow population of males aged 50-59, represented in 4 independent samples (each numbering 500 subjects), are reported. Two examinations were conducted at a 6.5-year interval, and mortality was reviewed in the examined population. High incidence of coronary heart disease (CHD) and its risk factors was established at first screening, and increased further during the next decade. The need for a differential approach to the assessment of CHD risk factors and high mortality rates, and also to the planning of preventive programs with regard to age, presence of CHD and its risk factors, is emphasized.     

Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in acromegalic patients treated with somatostatin analogues: a prospective study

BACKGROUND: Acromegalic patients have increased left ventricular (LV) mass (M) and impaired diastolic function. AIM: Using ultrasonic cardiac tissue characterization, we evaluated the early changes in cardiac fibrosis (IBS) and intrinsic myocardial contractility (CVI) as well as their reversibility after treatment with somatostatin analogues (SMSA) in patients with acromegaly. PATIENTS AND METHODS: Twenty-two acromegalic patients with active untreated disease (Acro(UNTR)) underwent conventional Doppler echocardiography and integrated backscattering; 25 healthy subjects (controls) and eight patients with acromegaly in remission after pituitary adenomectomy (Acro(REM)) served as controls. RESULTS: As expected, Acro(UNTR) at baseline had higher LVM than controls or Acro(REM) (P < 0.001); LVM reduced in acromegalic patients after SMSA (P < 0.005 vs. baseline) while LV ejection fraction did not change. LV diastolic function was reduced in all acromegalic patients, either at baseline or after SMSA therapy (E/A ratio, 0.96 +/- 0.3 and 1.1 +/- 0.3, respectively, P < 0.002 vs. controls, 1.6 +/- 0.3). CVI was reduced in Acro(UNTR) (14.3 +/- 5.8%, P < 0.003 vs. controls, 28.7 +/- 7.5%) and greatly improved after SMSA (22.5 +/- 4.5%, P < 0.003 vs. baseline). Cardiac fibrosis was increased in Acro(UNTR) (IBS(MSI), 53.7 +/- 5.3%P < 0.002 vs. controls) and reduced after SMSA (43.7 +/- 4.2%P < 0.002 vs. baseline) albeit not reaching values observed in controls. More importantly, five of 22 (23%) Acro(UNTR) patients had normal LVM, but increased cardiac fibrosis as revealed by back scattering. IBS values and CVI% were related with serum GH and IGF-1 (P < 0.0001) levels, and the estimated duration of disease (P < 0.005). CONCLUSIONS: The present study demonstrated that active acromegalic patients had early impairment of systolic function and increased cardiac fibrosis; increased fibrosis may precede LV hypertrophy; these changes are related to the activity of disease and might improve during treatment with SMSA.