Macro-creatine kinase: a neglected cause of elevated creatine kinase.

Macro-creatine kinase (macro-CK) is a neglected cause of raised CK. Over a 10-year period, we observed five cases. Three patients had macro-CK type 1. One patient with fibromyalgia underwent several explorations to find a muscular pathology; another, who had elevated CK-MB (muscle-brain fraction) activity, was referred to a cardiologist, and statin therapy was erroneously discontinued in two patients. Two patients had macro-CK type 2: a man with a neuroendocrine carcinoma and a woman with rheumatoid arthritis. Diagnosis of type 1 obviates the need to carry out pointless and expensive investigations seeking a neuromuscular or cardiac pathology, and also, the unwarranted discontinuation of statin therapy. Type 2 must prompt investigations for a neoplasm.

Differences between women and men with recent-onset axial spondyloarthritis: results from a prospective multicenter French cohort.

OBJECTIVE: To clarify sex differences in early axial spondyloarthritis (SpA). METHODS: In total, 475 patients included in the Devenir des Spondylarthropathies Indifférenciées Récentes (Outcome of Recent Undifferentiated Spondylarthropathies) cohort, a prospective multicenter French cohort of patients with early inflammatory back pain suggestive of SpA, and fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA were studied. The clinical and imaging features were compared between sexes and according to the clinical or imaging arm of the ASAS criteria using univariate and multivariate analysis. RESULTS: Comparisons between the 239 men and 236 women showed that women had higher disease activity when measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Patient Global Score and higher fatigue and functional scores despite having less radiographic sacroiliitis and magnetic resonance imaging (MRI) inflammation of sacroiliac joints and the spine than men. Disease activity measured by the C-reactive protein (CRP)-based Ankylosing Spondylitis Disease Activity Score was not different between men and women. In contrast to patients classified with the clinical arm, disease activity and functional scores did not differ between women and men with sacroiliitis on imaging scans, except for fatigue and the Ankylosing Spondylitis Quality of Life questionnaire. Women with sacroiliitis had more peripheral involvement and more family history, whereas HLA-B27 positivity, elevated CRP, and MRI inflammation of the spine were associated with male sex. CONCLUSION: Women with early axial SpA according to the ASAS criteria had greater disease activity when measured by the BASDAI and worse functioning despite fewer radiologic abnormalities than men. The differences in disease expression may be confounding factors to establish the diagnosis of SpA and to assess disease activity in women, suggesting that the imaging arm is a pivotal measure in the ASAS criteria.

European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: a complete picture of primary Sjögren's syndrome patients.

OBJECTIVE: The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS. METHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sjögren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained. RESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both). CONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. Since these 2 facets weakly overlap, one should identify which of both components is the main target of the treatment to test, when designing clinical trials in primary SS.

[Treatment of gout]. / Traitement de la goutte.

In France, colchicine remains the standard treatment for the acute flare of gout. The lowest dose currently used decreases digestive toxicity. Doses of colchicine should be adapted to renal function and age, and possible drug interactions should be considered. Non steroidal anti-inflammatory drugs are an alternative to colchicine, but their use is frequently limited by comorbidity. When these treatments are contraindicated, corticosteroid injections can be performed after excluding septic arthritis. Systemic corticosteroids could be used in severe polyarticular flares. Anti-IL1 should provide a therapeutic alternative for severe cortico dependant gout with tophus. To prevent acute flares and reduce tophus volume, uric acid serum level should be reduced and maintained below 60mg/L (360µmol/L). To achieve this objective, it is often necessary to increase the daily dose of allopurinol above 300mgs, but the need to adapt the dose to renal function is a frequent cause of therapeutic failure. In the absence of renal stone or renal colic and hyperuraturia, uricosuric drugs are the second-line treatment. Probenecid is effective when creatinine clearance is superior to 50mL/min Benzbromarone, which was withdrawn due to hepatotoxicity, can be obtained on an individualized patient basis in the case of failure of allopurinol and probenecid. Febuxostat, which was recently approved, is a therapeutic alternative. Diuretics should be discontinued if possible. Use of fenofibrate should be discussed in the presence of dyslipidemia and losartan in patient with high blood pressure. Uricolytic drugs (pegloticase), which are currently being investigated, may be useful for the treatment of serious gout with tophus, especially in the presence of renal failure. Education of patient, identification and correction of cardiovascular risk factors should not be forgotten.

[Transversal fractures in spinal ankylosis: a case series of 17 patients]. / Fractures transversales du rachis ankylosé : une série de 17 cas.

PURPOSE: Transverse fractures of the spine are rare. They occur in ankylosed spine and may lead to neurological complications. We report a series of 18 cases observed in 17 patients with ankylosing spondylitis (AS). The objective of this study were to describe the clinical, diagnostic and therapeutic features of our series and to compare our results with those of the literature. METHODS: We conducted a retrospective study from 1975 to 2008 in the neurosurgery and rheumatology departments of the university hospital (CHU) of Clermont-Ferrand. RESULTS: Eighteen transverse spine fractures were documented in 17 patients (one female patient had two fractures of the lumbar vertebrae). The 13 male and four female patients included in this series had a mean age of 57.4 ± 17.2 years and AS for a mean time of 21.3 ± 12 years (5-40). All patients had spinal ankylosis with a "bamboo" spine appearance. The reasons for hospital admission were suspicion of AS flare (n=10) and suspected traumatic fracture (n=8). Trauma, in most cases minor, was noted in 15 patients. Fourteen patients presented with mechanical spinal pain and three had both mechanical and inflammatory pain. Three patients experienced severe pain on mobilization. Two patients had pyramidal syndrome. The mean time to diagnosis of the fracture was 6.8 ± 8.4 weeks (0-22). The fracture was located in cervical spine (n=2), dorsal spine (n=8) and lumbar spine (n=8). It was transdiscal and transcorporeal in nine cases each. Standard radiographs (n=18) identified the fracture in nine cases. The fracture was demonstrated in all CT-scan (n=13). Magnetic resonance imaging (MRI) (n=6) showed the fracture in five cases and epidural hematoma in one. Eleven patients had orthopedic treatment and six underwent surgery. Outcome was favorable in 16 patients. One paraplegic patient died of pulmonary embolism. CONCLUSION: Transverse fractures of the spine are rare and diagnosis should be considered in a patient with AS and ankylosed spine who presented mechanical spine pain following even minor trauma. If standard radiographs are normal, further investigations should be performed using MRI, CT-scan, or both.

Trend towards increased arterial stiffness or intima-media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease.

OBJECTIVES: Increased incidence of cardiovascular disease (CVD) has been observed in AS. The reasons of this increase are not fully understood (greater prevalence of traditional cardiovascular risks, consequences of treatment (NSAID) or biological inflammation). The objectives of this study are to assess intima-media thickness (IMT) and arterial stiffness (i.e augmentation index AIx), markers of sub-clinical atherosclerosis in AS patients and to examine the effects of TNF-alpha inhibitors on arterial stiffness in active AS patients. METHODS: Sixty AS patients were enrolled with 60 healthy controls. Their BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, ESR and CRP levels were recorded. Subclinical atherosclerosis was assessed by measurement of AIx by pulse wave analysis and IMT by carotid echography. RESULTS: We found significantly increased IMT in the AS group compared with healthy controls. After adjustment for confounding factors, an underlying trend towards increased IMT was still present (P = 0.06). No difference was found in arterial stiffness between the two groups. AS patients, treated or not with anti-TNF-alpha at baseline, had significantly increased IMT and AIx or a trend towards increase. IMT was positively correlated with tobacco use, WHR and blood pressure but not correlated with CRP level. Despite improvement in markers of disease activity, arterial stiffness was unchanged after 14 weeks of treatment with TNF antagonists. CONCLUSION: This study shows a trend towards increased subclinical atherosclerosis in AS patients. TNF-alpha blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

[Fractures of the ankylosed spine: MRI features]. / Fractures du rachis ankylosé: intérêt de l'IRM.

The diagnosis of transverse spinal fractures in patients with ankylosing spondylitis and Forestier's disease (DISH) may be difficult. The MRI features of 9 such fractures at the disk, vertebral body, spinal canal and posterior elements are presented. Fractures of the posterior elements (posterior arch fractures and/or rupture of interspinous or supraspinous ligaments and contiguous soft tissue structures) were present in all cases, underscoring the importance of MR signal abnormalities of posterior structures for diagnosis of these fractures. MR is advantageous due to its ability to demonstrate signal abnormalities of the posterior elements, which combined with disk and vertebral body abnormalities, play a major role for accurate diagnosis of this type of fracture.

Septic arthritis as a late complication of carcinoma of the breast.

OBJECTIVES: To see if a past history of radiation therapy is a risk factor for septic arthritis. METHODS: We retrospectively searched our records of 282 patients with septic arthritis and found 10 cases of septic arthritis post-radiotherapy, all in females. We analysed our group, correlating them with the literature. We also compared our patients with a group of septic arthritis patients without radiation therapy. RESULTS: Nine had had radiation therapy for carcinoma of the breast. The shoulder joint was involved in six and the sternoclavicular joint in three. The tenth patient had had brachytherapy and radiation for carcinoma of the cervix and presented with septic arthritis of the hip. The mean age of the patients was 69 yr (49-82 yr). The mean time elapsed since radiation was 16 yr (3-34 yr). Twenty-three cases of shoulder septic arthritis in patients without past radiation therapy were selected for comparison. The five patients with past radiation therapy had fever less often and a longer time lapse before diagnosis. They required longer antibiotherapy. However, this prevented neither bone destruction nor relapse. CONCLUSIONS: In our study, a past history of radiation therapy was observed in 6/50 infections of the shoulder, 3/5 infections of the sternoclavicular joint, 6/23 cases of septic arthritis of the shoulder and all cases of septic arthritis of the sternoclavicular joint for females. Radiation therapy seems to be a risk factor for septic arthritis. Diagnosis would be aided by a greater awareness of the clinical and radiological features of this septic arthritis.

[Fluoroscopy guided L5-S1 transforaminal injection as a treatement for s1 radiculopathy]. / Infiltration foraminale L5-S1 radioguidée dans le traitement de la lombosciatique S1.

OBJECTIVE: To assess the efficacy of fluoroscopy guided L5-S1 transforaminal steroid injections for the treatment of S1 radiculopathy secondary to intervertebral disk disorder. METHOD: 41 patients were included: prospective study (20 patients) and retrospective study (21 patients). All patients suffered from S1 radiculopathy secondary to nerve root compression by intervertebral disk material, as demonstrated by lumbar spine CT. The patients underwent 2 fluoroscopy guided L5-S1 transforaminal injections of steroid (Hydrocotancyl 125 mg), at 8 days interval. RESULTS: 60% of patients showed significant improvement of their painful radiculopathy at day 8 (n:41), 60-67% at day 30 (n:41) and 67% at day 90 (n:18). CONCLUSION: Fluoroscopy guided L5-S1 transforaminal injection showed good efficacy in the treatment of S1 radiculopathy.

No changes in the distribution of organisms responsible for septic arthritis over a 20 year period.

OBJECTIVE: To assess changes in the distribution and resistance of the pathogens responsible for septic arthritis over a 20 year period in patients admitted to the same hospital unit. PATIENTS AND METHODS: Retrospective study of the hospital records of patients admitted between 1979 and 1998 for septic arthritis with positive microbiological diagnosis after blood or joint cultures, or both. RESULTS: 303 cases of septic arthritis were studied, 141 in the period 1979-88 and 162 in the period 1989-98. The incidence between the first and second period did not vary significantly for the staphylococci (67% v. 63%), streptococci (16% v. 20%), and Gram negative bacilli (7% v. 10%). Tuberculous infections decreased from 9% to 4% (p<0.04). No gonococci were isolated in the second 10 year period. Among the staphylococcal species, there was an increase in the number of coagulase negative staphylococci (10 cases v. 21, p<0.05) between the two periods. There was no significant difference in the frequency of occurrence of methicillin resistant pathogens (12.6% v. 16.6%). The number of streptococcal B infections increased (2 v. 10 cases), and beta-lactamine resistant pneumococci emerged. In the second 10 year period, patients were older and were more likely to have co-existing disease, particularly tumoral growth, and less commonly were receiving dialysis. Localisation of joint infection was comparable except for an increase in prosthetic knee infections. CONCLUSION: The distribution and sensitivity of pathogens causing septic arthritis changed little over a 20 year period.

Pamidronate in the treatment of diffuse sclerosing osteomyelitis of the mandible.

Diffuse sclerosing osteomyelitis of the mandible is characterized by bouts of intense pain, sometimes associated with trismus and paresthesia, and leads to progressive deformity. It is of unknown etiopathology, but it is suggested to be one manifestation of the synovitis, acne, pustulosis, hyperostosis, osteomyelitis syndrome, the other features of which may have been overlooked. Treatment results are disappointing, and decortication may be necessary to achieve an acceptable outcome. We report a case restricted to the mandible that responded favorably to treatment with pamidronate. Further trials of pamidronate in patients with diffuse sclerosing osteomyelitis of the mandible, even in those with the aforementioned syndrome, are needed to assess its effectiveness.

Cutaneous lymphoma associated with Epstein-Barr virus infection in 2 patients treated with methotrexate.

Whether patients with rheumatoid arthritis (RA) have an increased risk of developing non-Hodgkin lymphoma is controversial, and opinions differ on the possible role of methotrexate in the occurrence of lymphomas in patients with RA. We report 1 T-cell lymphoma and 1 B-cell lymphoma restricted to the skin associated with Epstein-Barr virus infection that healed completely and spontaneously after discontinuation of methotrexate in a man with RA and a woman with dermatomyositis. Cutaneous infiltrating cells were infected by a replicative form of Epstein-Barr virus. After discontinuation of methotrexate, the cutaneous lesions disappeared completely in 15 days without recurrence. Discontinuation of methotrexate is necessary in patients with RA or dermatomyositis who have a lymphoproliferative disorder, and a follow-up period of several weeks should be observed before specific therapy is initiated.

IL-6 gene amplification and expression in human glioblastomas.

The aggressiveness of human gliomas appears to be correlated with the upregulation of interleukin 6 (IL-6) gene. Using quantitative PCR methods, we detected amplification and expression of the IL-6 gene in 5 of 5 primary glioblastoma samples and in 4 of 5 glioblastoma cell lines. This finding suggests that the amplification of IL-6 gene may be a common feature in glioblastomas and may contribute to the IL-6 over-expression.

[Secondary Gougerot-Sjogren syndrome]. / Syndromes de Gougerot-Sjögren secondaires.

Secondary Sjögren's syndrome is due to another disease. When it develops in connective tissue diseases, their causative role is unchallenged. In AIDS or hepatitis C, exocrine involvement is virus related. Whether or not it qualifies for Sjögren's syndrome is debated. Amyloidosis and sarcoidosis do not produce direct, autoimmune lesions of the glands, hence their exocrine involvements are considered as differential diagnoses. The most common Sjögren's syndrome is found in rheumatoid arthritis. When it appears, the arthritis has been evolving for years, and has reached its typical, seropositive and erosive stage. Accordingly, dryness is not a major concern and should be sought for by proper questioning, specially on eye dryness. When a secondary Sjögren's syndrome is an early complication of rheumatoid arthritis, it could be confused with a primary syndrome with prominent joint involvement. In systemic lupus erythematosus, secondary Sjögren's syndrome develops rarely in the first years of evolution but later in life, when the patient becomes menopausal. In systemic sclerosis, especially in CREST, secondary syndrome can lead to the discovery of the unsuspected connective tissue disease thanks to mouth dryness. It can reveal primary biliary cirrhosis or auto-immune hepatitis. Often precede a true primary Sjögren dysfunctions of the thyroid.

[Catastrophic antiphospholipid syndrome revealed by a cerebrovascular accident: a case report]. / Syndrome catastrophique des anticorps antiphospholipides révélé par un accident vasculaire cérébral: un cas.

We reported the case of a patient with catastrophic antiphospholipid syndrome revealed by an ischemic stroke, and who presented within six weeks several visceral failures, with among others surrenal, cardiac, splenic, cutaneous and hematologic complications.

Increased serum levels of interleukin 10 in Sjögren's syndrome; correlation with increased IgG1.

OBJECTIVE: To determine levels of interleukin 10 (IL-10) and IgG subclasses in serum from 53 patients with primary Sjögren's syndrome (SS). METHODS: Serum levels of IL-10 were measured using specific sandwich ELISA in 25 patients with "definite" SS, 28 with "possible" SS, and 32 healthy controls. Interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were also measured by immunoassays. Immunoglobulin classes, IgG subclasses, and C-reactive protein were measured by nephelometry. RESULTS: Circulating IL-10 was elevated in 25 patients. The increase reached significance in the group with possible SS (p = 0.03) versus controls. In the group with definite SS, IL-10 level was correlated with IgG1 level (p = 0.01, r = 0.67) and with focus score (p = 0.01). IFN-gamma was undetectable in most patients. TGF-beta1 was higher (not significantly) in possible SS than in definite SS. CONCLUSION: IL-10 is increased in SS and may account for the overproduction of IgG1 in the syndrome. High IL-10 in the absence of increased IgG1 in possible SS suggests that IL-10 may be necessary but not sufficient for IgG1 overproduction and that other factors are involved. Whereas the correlation of IL-10 level with focus score was expected, it is intriguing that IL-10 was more frequently increased in the incomplete (possible) form of SS than the complete (definite) form. Elevated IL-10 may characterize the lower stage of eccrine dysfunction and perhaps contributes to limiting its severity.