Anterior sonography of glenohumeral joint in patients with inflammatory joint disease.

Ultrasonography (US) was shown as an effective imaging modality in evaluating the shoulder. The shoulder joint is probably the most accessible joint for sonography in adults. However, inflammatory changes of the shoulder have received too little attention in US studies. Anterior access for US assessment of glenohumeral joint (GHJ) has not been investigated. Another problem of patients with acute synovitis of glenohumeral joint is the difficulty to perform a 90 degrees abduction for the axillary US because of severe pain and active and passive limitation. We offer the anterior access for assessment of glenohumeral joint synovitis (GHS). Sonographic evaluation (Sonosite-Titan) was carried out in 25 patients with acute GHS and 15 healthy controls. The diagnosis of GHS was made after the patients underwent physical examination and the laboratory evidence was obtained. We used the anterior position of transducer applied laterally to coracoid processus along the anterior joint cavity. The problem of anterior joint cavity investigation in neutral position is a poor presentation of the joint and the application of the biceps tendon. The problem is simply resolved after supination of the hand and external rotation of the shoulder. We measured and compared upper, middle, and lower width of the anterior GHJ cavity. Echogenicity of joint cavity was assessed by comparison with adjacent tissues. Homogeneity and regularity of GHJ cavity was designated in both groups as well. We measured labrum-infraspinatus distance on posterior view for assessment of GHJ synovitis. All cases of GHJ synovitis were confirmed by a US Doppler study. US investigation of healthy controls enabled to find normal values of the width of the anterior GHJ cavity that was less than 7.4 mm. The synovitis group showed GHJ cavity expansion: 8.3+/-2.4 (p=0.001) and 10.5+/-3.1 (p<0.001) for the middle and the lower anterior part of the GHJ respectively. The upper part width was not different in synovitis and control groups. Anterior joint cavity extension to 7.4 mm and upper in its lower part was high sensitive (96%) and specific (86%) US sign of synovitis with the test power above 0.9. The posterior labrum-infraspinatus extension had high specificity for synovitis (100%), but only seven of 25 patients (28%) had increased (>2 mm) the value of the labrum-infraspinatus dimension, which was previously proposed as the US sign of synovitis. Echogenicity of the anterior joint cavity in healthy controls was moderately high (far more echogenic than deltoid muscle). Echogenicity of synovitis declined, and mild effusions were found to be common. Those were not to be seen on US of GHJ in neutral position and were revealed only in supination and external rotation of the shoulder. Intra-articular tissue of healthy controls was relatively echo-homogenic compared with nonhomogenic one of the synovitis group. Bone irregularity was found in patients with long-standing GHJ synovitis reflecting erosive process. A certain position of the shoulder and good knowledge of the normal anterior joint cavity parameters enabled us to diagnose synovitis by anterior shoulder sonography, with the patients experiencing minimal pain during movements.

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation.

AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.

Responses to a fourth dose of Haemophilus influenzae type B conjugate vaccine in early life.

OBJECTIVE: To describe the immune response of preterm infants, with a reduced response to primary Haemophilus influenzae type B (Hib) immunisation, to a fourth dose of Hib conjugate vaccine given in early life. DESIGN: Prospective observational study. SETTING: Five Wessex Neonatal Units. PATIENTS: Infants born at < 32 weeks and immunised with three doses of combined acellular pertussis-Hib vaccine, with a Hib IgG geometric mean concentration (GMC) < 1.0 microg/ml after these primary immunisations. INTERVENTIONS: An additional fourth dose of Hib conjugate vaccine given before 1 year of age. Blood taken to assess Hib IgG concentration and avidity after immunisation. MAIN OUTCOME MEASURES: Hib IgG GMC and avidity index. RESULTS: Ninety six infants (mean gestational age at birth 29.1 weeks) received a fourth dose of Hib at a mean age of 7.8 months. Hib IgG GMC after the primary immunisations was 0.17 microg/ml (95% confidence interval (CI) 0.14 to 0.20) rising to 4.68 microg/ml (95% CI 3.36 to 6.57) after the fourth dose (p < 0.0001). The IgG response to the fourth dose correlated positively with the response after the primary immunisations (p < 0.001). Hib IgG geometric mean avidity index (GMAI) after the primary immunisations was 30.87 (95% CI 20.40 to 46.73). This increased to 124.73 (95% CI 109.93 to 141.51) after the fourth dose (p < 0.0001). CONCLUSION: Preterm infants with very low IgG responses to Hib after primary immunisations with a combined acellular pertussis-Hib vaccine mount a good response to a fourth dose of Hib. This study suggests that all infants will benefit from a fourth dose of Hib, regardless of the age at which it is given.

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants.

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.

Alopecia areata and relapsing polychondritis or mosaic autoimmunity? The first experience of co-trimoxazole treatment.

A 13 year old girl presented with auricular chondritis and recurrent episodes of unexplained chest pain, arthritis, bronchitis, conjunctivitis, prolonged steroid resistant alopecia areata, and a history of recurrent tonsillitis. Both the mosaic of autoimmunity and relapsing polychondritis were considered in the differential diagnosis. The patient was successfully treated with co-trimoxazole. The significance of co-trimoxazole, which is an antibiotic and an immunomodulatory drug, in the treatment of autoimmune disease is discussed.

Seasonal distribution of relapse onset in rheumatoid arthritis and spondyloarthropathy: the possible effect of the solar factor.

BACKGROUND AND OBJECTIVE: The seasonal effect on the relapse of rheumatoid arthritis and spondyloarthropathies is still unclear. To assess the seasonal distribution of relapse onset in rheumatoid arthritis (RA) and spondyloarthropathy (SpA) and its association with solar factors. METHODS: The monthly distribution of relapse onsets during the years 1998-2000 was retrospectively chart reviewed in 364 patients. In 1998 a total of 131 patients were studied; 60 with seropositive (sp) RA, 30 with seronegative (sn) RA and 41 with SpA; 113 patients in 1999: 44 with spRA, 38 with snRA and 31 with SpA; 120 patients in 2000: 56 with spRA, 38 with snRA and 26 with SpA. All of them were treated in the Department of Rheumatology, which serves the population of northwestern Israel. Solar activity was analyzed according to the "Solar Terrestrial Activity Report Charts 1998-2000". The Central Israel Bureau of Statistics provided the sun global radiation data. Data was assessed during the summer (April-September) and winter (January-March, October-December). The correlation between the monthly distribution of disease relapses and solar factors was measured (SPSS-10 for WIN). RESULTS: Relapses in spRA patients occurred mostly during the summer months with peak activity during the month of July 2000. Single monthly peaks of spRA relapse onset were noted in January 1998-1999 and April 1998 and for snRA in January 1998 and June 2000, but there were no seasonal differences for spRA, snRA and SpA in 1998-1999 and for snRA and SpA in 2000. Relapses in spRA patients were associated with a summer bias of increased solar activity and global solar radiation in 2000 compared with lower peak solar activity in 1998-1999. Furthermore, in 2000 we found a significant correlation of the spRA monthly relapse count to solar activity (p = 0.005) and global sun radiation (p = 0.048) unlike snRA and SpA. No above-mentioned association and correlation was noted in 1998-1999. We revealed mild negative correlation (p = 0.046) of SpA relapse count only to peak solar flux (PSF) by analysis of data for 1998-2000 as one united group. CONCLUSIONS: Relapses were more frequent during the summer of 2000 (May-June-July) in spRA but not in snRA and SpA. The reasons are still unclear. No seasonal differences were observed in 1998-1999. Enhanced solar activity in summer-2000 compared with 1998-1999 may be inferred to be the proposed cause but coincidence may occur as well. Outbreak in RA and SpA was not registered despite increased peak solar activity in 2000. We observed mild evidence of reciprocal relation between SpA relapsing and solar activity during 1998-2000. Solar and any other possible contributory factors remain still to be elucidated.

Severe transient osteoporosis of the hip during pregnancy. Successful treatment with intravenous biphosphonates.

A young woman with transient osteoporosis of the hip (TOH) during pregnancy, severe pain, physical disability and marked generalized osteoporosis was treated with intravenous biphosphonates with prompt beneficial effects on both clinical symptoms and bone density. The features of this rare and sometimes underdiagnosed condition are reviewed. Intravenous biphosphonates seem to be an effective therapy for TOH.

Silica-related rheumatoid arthritis without lung involvement.

We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis.

Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines.

To determine the immune response of premature infants to meningococcal serogroup C capsular polysaccharide (MCC) and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b (DTaP-Hib) conjugate vaccines, 105 infants born at <32 weeks' gestation had Hib IgG geometric mean concentrations (GMCs) and MCC serum bactericidal antibody (SBA) geometric mean titers (GMTs) measured 1 month after the third immunization. Term infants served as control subjects. Premature infants had Hib GMCs of 0.27 microg/mL, with 21% achieving GMCs >1.0 microg/mL, compared with 0.81 microg/mL and 46% in term infants (P<.001 and P=.003, respectively). The MCC SBA GMT was 398, with 99% achieving an SBA > or =8, compared with 380 and 98% in term infants (P=.84 and P=1.0, respectively). Hib IgG was associated with age at third immunization (P<.001). When combined with the DTaP vaccine used in this study, the Hib GMC of premature infants was extremely low. The SBA GMT to MCC was similar to that of term infants.

Cotrimoxazole treatment for rheumatoid arthritis.

OBJECTIVES: To review the literature on the immunomodulatory and anti-inflammatory properties of cotrimoxazole (CTX)-a combination of sulfamethoxazole and trimethoprim, to summarize the use of this medication in the treatment of autoimmune diseases, to stimulate and renew the interest of both physicians and researchers in this possible therapy for rheumatoid arthritis (RA), and to inspire further investigation in this field. METHODS: A MEDLINE search of the literature from 1966 until 2000 was performed, and information about the pharmacology of CTX and its use in the therapy of rheumatic diseases was critically reviewed. RESULTS: RA treatment is associated with numerous problems such as lack of efficacy, frequent side effects, and high cost. Analysis of the relevant literature revealed that experience with CTX in the treatment of RA is limited. However, the results of several nonrandomized and evidently forgotten clinical trials and laboratory investigations suggested that CTX might serve as an effective and inexpensive therapy for RA. Several lines of evidence suggested that CTX has nonspecific anti-inflammatory and immunomodulatory properties. Although nausea and vomiting were common reasons for CTX withdrawal, they were noted in only some studies, and no major organ toxicity was observed. CONCLUSIONS: Because of its therapeutic qualities, low cost, and relative nontoxicity, CTX seems to warrant a role in the treatment of RA.

Osteoporosis in murine systemic lupus erythematosus--a laboratory model.

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.

Longitudinal study of urinary albumin excretion in young diabetic patients--Wessex Diabetic Nephropathy Project.

AIMS: This study was established to follow changes in albumin/creatinine ratio (ACR) and to determine the prevalence and degree of progression of microalbuminuria (MA) or of clinical proteinuria (CP) in children with Type 1 diabetes. The study has investigated subjects for up to 12 years in establishing the correlation between MA and gender, age, duration of diabetes and glycated haemoglobin (HbA1c). The study has defined clinical cut-offs for MA in daytime clinic urine samples in young diabetic subjects. METHODS: Three hundred and sixty-one patients were involved in the study, with 221 (61.2%) having over six sets of data. Urine samples were collected at routine annual clinic visits and analysed without prior freezing for ACR. Blood samples were taken for HbA1c measurement. Data including sex, age and duration of diabetes were recorded. RESULTS: A random clinic ACR of < 4.5 mg/mmol (males) and 5.2 mg/mmol (females) creatinine was used as the 'clinical cut-off' to define the presence of MA. The presence of MA was independent of HbA1c and duration of diabetes but appeared be associated with the adolescent years (> 10 years). There was little evidence of progression from normoalbuminuria to MA, or from MA to CP. Of patients aged 10-18 years, 30.9% of males and 40.4% of females had one or more episodes of MA. CONCLUSIONS: Persistent MA and random episodes of MA or CP may be associated with the adolescent years but not with duration of diabetes. Further study will reveal if the substantial increases in ACR sometimes seen during adolescence are predictive of diabetic nephropathy. Clinical cut-offs of < 4.5 and < 5.2 mg/mmol creatinine for males and females, respectively, are suggested for the interpretation of changes in ACR in random urine samples in young people with Type 1 diabetes.

Methotrexate-treated arthritis and lymphoproliferative disease--coincidence only?

This paper describes four patients with inflammatory joint diseases treated with methotrexate who developed lymphoma either of unusual type or with bizarre clinical features. The pathogenesis of this unusual condition is discussed and the difficulty in differentiating it from the features of the initial disease is emphasised.

Arthritis related to ileal pouchitis following total proctocolectomy for ulcerative colitis.

OBJECTIVE: To draw attention to arthritis that developed in patients who underwent total proctocolectomy with ileal pouch construction for ulcerative colitis (UC). METHODS: The course of 4 patients who developed arthritis for the first time after ileal-anal pouch anastomosis is described. In addition, the relationship to the chronic inflammation of the pouch-pouchitis-is discussed. RESULTS: The clinical manifestations were very similar to seronegative arthritis affecting mainly the joints of the lower extremities. It was accompanied by enthesopathy (2 patients) and by sacroiliitis (2 patients). All had active pouchitis. The abnormal laboratory test results were nonspecific, indicating chronic inflammation. All 4 patients tested negative for human leukocyte antigen (HLA) B27, and none had other concomitant extraintestinal manifestations. Steroids rapidly improved both the arthritis and pouchitis; however, disease-modifying antirheumatic drugs were required to maintain remission with minimal daily steroids. Flares of the arthritis were always associated with active pouchitis, but the opposite was not necessarily true. CONCLUSIONS: Arthritis related to ileal pouchitis after total colectomy for UC has many similarities to the arthritis associated with inflammatory bowel disease and should be added to the list of enteropathic arthropathies.

Ticlopidine-induced lupus.

Ticlopidine is a widely used drug for prevention of stroke and other serious vascular events with a multitude of possible side effects. An increasing number of drugs are being recognized as the triggering agents of drug-induced lupus. We describe three patients in whom the etiologic connection between ticlopidine and lupus was supported by the appearance of lupus-like features (fever, rash, arthritis, renal involvement, positive antinuclear and antihistone antibodies), shortly after drug initiation, and their gradual resolution after its discontinuation. If suggested by clinical or/and laboratory findings (fever of unknown cause, musculoskeletal involvement, hematologic abnormalities), the possibility of ticlopidine-induced lupus should be taken into consideration and appropriate investigations should be performed. Patients should resolve slowly but completely after withdrawal of ticlopidine.

Successful pamidronate treatment of severe and refractory regional migratory osteoporosis.

We report the case of a middle-aged patient with repeated attacks of regional migratory osteoporosis of the lower limbs, manifesting as severe pain and swelling of both joint and periarticular areas, and marked physical disability during a period of 2 1/2 years. After the therapeutic failure of conservative therapy (physical therapy, rehabilitation therapy, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)) and after the correct diagnosis was reached, pamidronate treatment was instituted. The results were a rapid, complete, and long-lasting remission of the symptoms and the renewal of the patient's previous activities. Intravenous biphosphates are proposed as a safe and promising therapy for regional migratory osteoporosis. To our knowledge, this is the first report of pamidronate treatment for this condition.