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.

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.

Polyarticular septic arthritis.

Twenty-five cases of polyarticular septic arthritis (PASA) were observed in our department over a 13-year period. They accounted for 16.6% of all septic arthritis (15% on average in the literature). A male predominance was noted in our patients, as well as in the literature. The knee was the most frequent location followed by the elbow, shoulder, and hip, in varying order depending on the series. An average of 4 joints was involved. The causative microorganism was Staphylococcus aureus in 20/25 of our patients and in about 50% of published cases. Other frequently causative organisms were streptococci and gram-negative bacteria. Blood cultures and joint aspirations were positive in 19/22 and 23/25 of our cases, respectively. Other septic lesions were noted in 10/25 of our cases. Fever and severe leukocytosis were absent at admission in 5/25 (literature, 37%) and 10/25 of our 25 patients, respectively. The underlying disease was rheumatoid arthritis in 13/25, while 9 of the other patients had immunodepression caused by drugs or by concurrent illness. Typically, rheumatoid arthritis was long-standing and erosive, patients having ulcerated calluses on the feet. This skin source was also noted in 23/36 published cases of PASA in rheumatoid arthritis. Systemic lupus erythematosus was an uncommon disease in PASA, but its presence promoted gram-negative infection. Despite effective therapy with 2 antibiotics, 8/25 patients died, a prognosis that is equally severe in cases reported in the literature (30%) and one that has remained surprisingly stable over the last 40 years. For comparison, the death rate was only 4% in our patients with MASA. Factors contributing to a poor prognosis were age greater than 50 years, rheumatoid arthritis as an underlying disease, and disease of staphylococcal origin. Septic polyarthritis should be considered even when the clinical picture is not florid--when patients have low fever and normal white blood cell counts. Nor should the simultaneous involvement of distant joints rule out infection. Indeed, the frequency of underlying rheumatic disease and its treatment may further confuse the clinical presentation. Joints suspected of harboring infection should be aspirated, including those previously affected by the concurrent rheumatism.

POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS Syndrome.

OBJECTIVE: To determine whether there are peculiarities of the POEMS syndrome (a multisystemic disorder associated with polyneuropathy, organomegaly, endocrinopathy of various forms, production of a monoclonal [M] component, and skin changes) in Caucasian patients, especially signs and symptoms absent in other series; and to attempt a reappraisal of the neuropathy and endocrinopathy to find a unifying mechanism. DESIGN: A retrospective, cooperative study compared 25 cases, observed over a 15-year period, with two published series of patients, one of Japanese patients and one of American patients, and with a review of the literature on non-Asian cases. Details were obtained of patients' medical history, physical examination, immunochemical and hormonal testing, roentgenographic examination, computed tomography imaging, and electromyography. RESULTS: The main features of the syndrome found in these patients were those first described in Japan: polyneuropathy, enlargement of the lymph nodes, liver, and spleen, endocrine disturbances, low concentration of the monoclonal component, hyperpigmentation, and hypertrichosis. Three other symptoms were found more frequently than previously reported: skin angiomas, scleroderma changes of the hands, and thrombocytosis. Electromyography and nerve biopsy showed a variety of abnormalities ranging from demyelination to axonal degeneration. Nerve deposits of immunoglobulin were absent. Organomegaly seemed to be heterogeneous. Pathologic findings in the enlarged lymph nodes and spleen were compatible with Castleman's disease. Liver biopsies were usually normal. The endocrine changes were surprisingly diverse, with some observations combining unrelated primary and secondary insufficiencies. No single hypothesis emerged regarding their mechanism. All M components had a lambda-light chain. An IgG M component was found more frequently in solitary lesions. An IgA M component was found more frequently in patients without bone lesions. Sedimentation rate was usually normal. Radiotherapy of solitary plasma-cytomas was followed by dramatic improvement of extramedullary signs and symptoms in all cases. CONCLUSIONS: The symptoms, clinical course, and management of the patients reported here were similar to those observed in the literature. This study confirms the existence of a close link between symptoms and lambda-light-chain production. There are indications that a plasma cell growth factor that does not cross-react with interleukin-6 (IL-6) may be involved.

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.

Cutaneous angiomas in POEMS syndrome. An ultrastructural and immunohistochemical study.

Cutaneous manifestations of POEMS (polyneuropathy, organomegaly, endocrinopathies, M-protein, and skin changes) syndrome in a 51-year-old white man included two types of hemangiomas, ie, cherry-type and subcutaneous hemangiomas. By light microscopy and immunohistochemistry, both types of tumors showed features of capillary hemangiomas. By electron microscopy, a peculiar finding of subcutaneous hemangiomas was the presence of slender abluminal processes of endothelial cells that were frequently anastomosing to form electron-lucent blebs. Although the precise etiopathogenesis of the vascular proliferations remains speculative, these lesions merit study since they constitute an easily recognizable marker of POEMS syndrome.

Discrepancy between 3H-thymidine uptake and cell cycle studies in stimulated lymphocyte cultures treated with methotrexate.

The mode of action of methotrexate (MTX) in rheumatoid arthritis (RA) is unknown. The hypothesis that its cytostatic effect may be involved has been questioned based on the evidence of several negative results, the most intriguing being its lack of effect on the Lymphoblastic Transformation Test (LTT) and other lymphoproliferations in cultures from patients' samples. Our study demonstrates that LTT evaluation by 3H-thymidine uptake, a standard method, is misleading when applied to MTX-treated cells. At in-vitro concentrations similar to those present in the red blood cells of RA patients, MTX produced an early block in the cell cycle without reducing the cellular uptake of 3H-thymidine. While the explanation of this discrepancy is still open to discussion, it is clear that future studies on the immunological status of RA patients on MTX should not use thymidine uptake for the measurement of the lymphocyte response to mitogens and various stimuli, but must rely on other methods for evaluating DNA synthesis.

Pyogenic arthritis in adults.

Septic arthritis has shown no change in incidence, and despite advances in antimicrobial therapy is often responsible for residual functional impairment and for a high mortality rate among debilitated patients. Risk factors include older age, diabetes mellitus, rheumatoid arthritis, immunodeficiency, and a preexisting joint disease (e.g., rheumatoid arthritis) to which the symptoms of septic arthritis are sometimes ascribed. Staphylococcus aureus contributes over two-thirds of identified organisms; a range of streptococci and gram-negative bacilli are next in frequency. The most common site is the knee, followed by the hip and shoulder. Over 10% of patients have polyarticular involvement reflecting bacteremia and diminished resistance to infection; (over 50% of polyarticular forms occur in rheumatoid arthritis patients). Prosthetic joint infection is becoming increasingly common; chronic forms due to intraoperative contamination and resulting in septic loosening should be distinguished from acute hematogenous infection in which emergency treatment can allow to salvage the prosthesis. Demonstration of the organism in the joint is the key to the diagnosis. Joint aspiration should be performed on an emergency basis, if needed after identification of radiographic landmarks or under ultrasonographic guidance. Seeding the fluid on blood culture flasks immediately after aspiration increases the yield. Antibiotics should be started as soon as the microbiological specimens have been collected. When aspiration is difficult (hip) or inadequate, arthroscopic drainage usually makes arthrotomy unnecessary. Early antiinflammatory therapy (nonsteroidal antiinflammatory drugs, systemic or local glucocorticoids, anticytokines, and antiinflammatory cytokines) are being considered as tools for limiting joint damage; their efficacy and safety will first have to be established in animal studies.

Aortic occlusion in a patient with antiphospholipid antibody syndrome in systemic lupus erythematosus.

A 41-year-old woman with systemic lupus erythematosus and lupus anticoagulant developed aortic thrombosis. The patient was receiving low dose aspirin. Aortography showed a complete obliteration of the infrarenal aorta. Computed tomography and magnetic resonance imaging showed no evidence of aortitis. The patient improved with medical treatment. Six other published cases are reviewed.

Comparison of standard one-minute treadmill exercise and strandness test (absolute walking distance) in relation to site of lesion, walking distance, and diastolic blood flow velocity (Doppler curves).

In 215 outpatients suffering from occlusive arterial disease of the lower limbs the authors compared the decrease in the ratio of ankle systolic pressure to brachial systolic pressure according to whether the treadmill exercise was limited to one minute or extended until pain forced the patient to stop. After a one-minute walk the pressure index always decreased significantly, especially when walking was restricted. The decrease in the pressure index was generally greater when the exercise was continued until the absolute walking distance, and the recovery time was usually twice as long. The fall in the pressure index was significantly greater for patients with single and multiple iliac stenoses than for those with stenoses at lower levels. In patients having a diastolic blood flow velocity on Doppler curves at rest, not modified by walking, a maximum drop in peripheral pressure was recorded after walking for one minute. In this instance there was no intensification of the decrease in peripheral pressure, unlike in patients without a diastolic blood flow velocity at rest. This one-minute test is not a maximal hemodynamic response, but it is sufficient for the appreciation of ischemia during exercise, according to the different parameters measured.

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.

[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.

[Neuromuscular complications of D-penicillamine in rheumatoid arthritis]. / Complications neuromusculaires de la D. pénicillamine dans la polyarthrite rhumatoïde.

Between 1979 and 1990 we have seen 8 patients (7 females) with rheumatoid arthritis (RA) who developed a neuro-muscular involvement while on D-penicillamine (D.P.). Five of them had a drug-induced myasthenia. D.P. withdrawal led to a complete recovery in 1.5 to 5 months. Another patient presented with a myopathy which led to the diagnosis of Grave's disease. She was treated with D.P. for 4 months. D.P. was reintroduced and 5 months later a myasthenic syndrome developed. A thymoma was discovered 1 year later. In the last 2 patients D.P. induced polymyositis which, in one, was associated with features of systemic lupus erythematosus. In the other patient, the evolution was fatal in spite of D.P. withdrawal, high dose steroids and plasma exchanges. A literature survey has shown 150 D.P. induced myasthenia and 38 D.P. induced polymyositis cases.

[Thermal treatment in arterial diseases: an expensive placebo or an effective therapy?]. / Le traitement thermal des maladies artérielles: un placebo coûteux ou une thérapeutique à part entière?

Each year, Royat (Auvergne) receives about 20,000 patients (80 per cent with intermittent claudication), treated by thermal gas (99.5 per cent of CO2). CO2 therapy is dispensed with thermal water or with dry gas (general or local immersion and local subcutaneous injections of gas) during 3 weeks. Local vasodilator effects of CO2 have been demonstrated with several methods in Royat. Physiological and therapeutic effects of thermal CO2 therapy, also used in Germany and Central Europe, were precisely reported during the Consensus Congress of Fribourg in Brisgau (1989); more particularly, this treatment seems provide a reduced ability of haemoglobin to fix oxygen, and therefore a release of oxygen within the cells. Patients with peripheral arterial disease (stage 2) have a walking distance increased and post-exercise ankles' pressures improved after a thermal course of treatment in Royat, while a control group has no significant changes. The discussion will concern also the socio-economic aspects of thermal treatment of arterial diseases.

[Treatment of rheumatoid polyarthritis: evolution of concepts and strategies]. / Le traitement de la polyarthrite rhumatoïde. Evolution des idées et des stratégies.

INTRODUCTION: The treatment of rheumatoid arthritis includes non-steroid anti-inflammatory drugs (NSAID), low-dose steroids and drugs which modify the evolution of the disease (disease modifying anti-rheumatic drugs, [DMARD]). In the last few years, the long-term efficiency of the recommended treatment strategies in rheumatoid arthritis has been a matter of debate and their basic assumptions have been challenged. Numerous studies were undertaken to settle the question. They tried to delineate the rules for an optimal use of current drugs and other therapeutic means. CURRENT KNOWLEDGE AND KEY POINTS: Rheumatoid arthritis is a crippling disease. It decreases life expectancy and irreversible bone and joint damage may develop even in the first months of evolution. The sooner the prescription of DMARD, the higher the frequency and quality of rheumatoid arthritis improvement and, in the long-term, the lesser the functional impairment. Low dose steroids, when administered early, can slow down the development of radiologic lesions. Some of their effects are thus closer to those of DMARD than to those of symptomatic treatment. NSAID are at least as equally dangerous as DMARD and possibly more so in terms of the potential number of severe side effects. The combination of several DMARD does not increase their overall toxicity. An evaluation of the most efficient combinations and of the clinical situations in which combinations show promise of improved results is in progress. FUTURE PROSPECTS AND PROJECTS: At present, the tendency is to treat early and intensively, in order to obtain complete remission, improve evolution and reduce functional impairment. This strategy requires early diagnosis and early evaluation of prognosis of rheumatoid arthritis. Rheumatoid arthritis with benign evolution would not warrant intensive treatment. Studies are in progress to evaluate the prognostic factors in early rheumatoid arthritis that would enable us to adapt the strength of initial treatment to the disease's putative severity.

[From sedimentation rate to inflammation profile]. / De la vitesse de sédimentation au profil inflammatoire.

The main biological sign of inflammation is an increase in erythrocyte sedimentation rate (ESR). However it can be falsely normal (polyglobulia, cryoglobulinemia, hemoglobinopathy) or spuriously high in the absence of inflammation (anemia, hypergammaglobulinemia). In cases of doubt, the acute phase reactants (APR) should be measured: C reactive protein (CRP), fibrinogen, haptoglobin, alpha 1 acid glycoprotein. They have different kinetics of variation and various degrees of increase (some--the so called "negative" proteins--actually decrease). Several pitfalls can be avoided if it is remembered that the APR themselves can be modified by causes other than inflammation: low fibrinogen in intravascular coagulation, very low haptoglobin in hemolysis, raised orosomucoide in renal insufficiency and elevated transferrin in iron deficiency. Furthermore liver insufficiency or leakage through the kidney or gut lesions can lower them. In some patients, the observed levels of APR are thus the result of opposite trends. In complex cases, these pathological mechanisms are more apparent on profiles which express the concomitant blood levels of several APR in a normalized or comparative manner. In medical practice, ESR serves first and foremost to detect an inflammatory syndrome. CRP is prominent among the APR because its changes show a great sensitivity, are independant of those of ESR and have a time course fitting closely that of the inflammatory processes. Profiles yield detailed information but rarely provide major evidence in the quest of a diagnosis or the choice of a treatment. Because of their cost they are to be used only in difficult cases.

[Vertebral compression in epilepsy. Analysis of 8 cases]. / Tassements vertébraux de la comitialité. Analyse de 8 cas.

Epileptic seizures can produce dislocations or fractures of the limbs and vertebral compression fractures. We tried to determine the clinical and radiological features of the latter in 8 patients: 6 men and 2 women including one aged only 41 years. The often multiple compression fractures involved the first thoracic (n = 3) and the intermediate thoracic (n = 3) or lower lumbar (n = 2) vertebrae but, contrary to common osteoporosis, never the thoracolumbar hinge. In 2 cases, the appearance of the fracture and the neurological signs led to surgery. Posterior dislocation of the shoulder was associated with the fractures in 2 cases. Chronic alcoholism (4 cases), anti-epileptic drugs (1 case) or corticosteroids (1 case) might have facilitated a demineralization which was however not obvious on X-ray films. The seizure was a first ever event in 6 cases. In the absence of controls the fracture was considered to be spontaneous. These particularities explain why a metastatic compression fracture was initially suspected in 3 cases, leading to explorations which sometimes were aggressive. In the presence of a suspicious vertebral compression fracture the clinician must consider the possibility of an epileptic seizure, a trauma which is sufficient to explain the fracture, as shown by the complications of electro-convulsive therapy.

[Primary antiphospholipid syndrome of fatal course and osteoarticular cytosteatonecrosis]. / Syndrome primaire des antiphospholipides d'évolution fatale et cytostéatonécrose ostéoarticulaire.

The antiphospholipid syndrome produces acute occlusions of arteries and veins. This syndrome can cause a multiple organ systems failure whose outcome is often fatal. The authors report a case of the primary, antiphospholipid syndrome characterized by this fatal outcome, a so-called "devastating" syndrome following pulse steroids. In this patient, the antiphospholipid antibodies had been found after presenting bone-marrow fat necrosis, which led to extensive lesions of knees, hips and shoulders. Damage to the cell membranes in necrotic lesions might have promoted the immune response against phospholipids. The potential risks of pulse doses of steroids in the antiphospholipid syndrome are documented by the present observation, which also suggests that antiphospholipid antibodies should be determined in cases of fat necrosis of all origins.

[Prognosis of multiple myeloma treated with conventional chemotherapy has not improved in 20 years]. / Le pronostic du myélome traité chimiothérapie conventionnelle ne s'est pas amélioré en 20 ans.

The treatment of multiple myeloma has changed over the last 20 years. We investigated the effects of theses changes on patient survival in the current practice of a rheumatology ward. Two hundred and seventy-nine patients were hospitalised between 1972 and 1993: 30 from 1972 to 1976, 70 from 1977 to 1981, 86 from 1982 to 1986, 75 from 1987 to 1991 and 18 from 1992 to 1993. Staging according to Durie and Salmon was I in 8%, II in 29% and III in 65%. In principle, the initial therapy was monochemotherapy in 65% of the cases and polychemotherapy in 35%. At the time of the present study, 197 patients have died. The actuarial curves of survival were similar in all historical classes defined by the date of first admission. Curves of median of follow-up and of floating means were level between 1972 and 1990. No correlation was found between the date of first admission and survival in the 174 patients who died between 1972 and 1987. The following parameters were associated with longer survival: achievement of an objective response on chemotherapy, lower patient's age, high haemoglobin, low creatinine, low stage according to Durie and Salmon, low number of plasma cells in bone marrow, low calcemia and low levels of IgA, monoclonal component. The comparison of prognosis factors in historical classes showed a difference only for haemoglobin which was lower in the earlier class. The type of the first chemotherapy regimen varied widely between historical classes. The number of responders was significantly greater after polychemotherapy than after monochemotherapy but no correlation was observed between the type of chemotherapy and survival. The frequencies of early death, and the causes of death in general, were not different in the historical classes. The lack of improvement of survival over the last 20 years shows that the efficacy of current chemotherapies is limited, a conclusion which warrants the exploration of other therapeutic avenues.