Joint manifestations revealing inborn metabolic diseases in adults: a narrative review.

Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults. The clinical settings considered were arthralgia and joint stiffness as well as arthritis. Unspecific arthralgias are often the first symptoms of hereditary hemochromatosis, chronic low back pain may reveal an intervertebral disc calcification in relation with alkaptonuria, and progressive joint stiffness may correspond to a mucopolysaccharidosis or mucolipidosis. Gaucher disease is initially revealed by painful acute attacks mimicking joint pain described as "bone crises". Some IMD may induce microcrystalline arthropathy. Beyond classical gout, there are also gouts in connection with purine metabolism disorders known as "enzymopathic gouts". Pyrophosphate arthropathy can also be part of the clinical spectrum of Gitelman syndrome or hypophosphatasia. Oxalate crystals arthritis can reveal a primary hyperoxaluria. Destructive arthritis may be indicative of Wilson's disease. Non-destructive arthritis may be seen in mevalonate kinase deficiency and familial hypercholesterolemia.

Percutaneous laser disc decompression for the treatment of lumbar disc herniation: a review.

BACKGROUND: Discontinuation of the marketing of chymodactin has reawakened interest in other percutaneous techniques for treating lumbar disc herniation. Developed in the 1980s, the concept of laser disc decompression is based on the percutaneous introduction of an optical fiber into the intervertebral disc and administering laser energy. The procedure allows for the vaporization of a small amount of the nucleus pulposus and hence a reduction in the intradisc pressure and relief of radicular pain. OBJECTIVES: To review of the literature and summarize the technical modalities, mechanism, indications for, and results of percutaneous laser disc decompression for treating lumbar disc herniation. METHODS: We identified studies of percutaneous laser disc decompression published between January 1980 and June 2006 in the MEDLINE, EMBASE, and Cochrane Library databases. The search terms used were percutaneous laser disc decompression, laser, and spine or lumbar, disc or disk. The articles underwent a stepwise selection process on the basis of their title, abstract, and full text. RESULTS: Experimental and clinical studies have investigated the modality of percutaneous laser disc decompression, but no consensus exists on the type of laser to use, the wavelength, duration of application, or appropriate energy applied. Studies have evaluated the impact of different techniques on the amount of disc removed, intradisc pressure, and damage to neighboring tissue. Several open studies have been published, but their methodology and conclusions are questionable, and no controlled study has been performed. CONCLUSIONS: Although the concept of laser disc nucleotomy is appealing, this treatment cannot be considered validated for disc herniation-associated radiculopathy resistant to medical treatment.

Brief Report: Relationship Between Serum Infliximab Concentrations and Risk of Infections in Patients Treated for Spondyloarthritis.

OBJECTIVE: Tumor necrosis factor inhibitors are effective in reducing inflammation in rheumatic diseases but increase the risk of infections. This study was undertaken to investigate the relationship between the trough serum concentration of infliximab (IFX) and the risk of a first infection episode. METHODS: We retrospectively included all patients who started IFX treatment for an approved indication in our department. Patients were followed up based on recommended IFX infusion schedules. We studied the relationship between the occurrence of a first infection episode requiring hospitalization, anti-infection treatment, or IFX infusion deferral, and the last trough IFX concentration and mean of the last 3 trough IFX concentrations measured before the infection episode. RESULTS: Of the 201 patients included in the analysis, 173 had spondyloarthritis (SpA). The SpA patients had a mean ± SD age of 46 ± 12 years and a disease duration of 6.2 ± 6.1 years. During a median follow-up of 1.1 year, 87 SpA patients had at least 1 infection episode. Using Cox models, we found that the probability of survival without infection was significantly higher in patients with a mean of the last 3 trough IFX concentrations lower than the median (<11.3 mg/liter) than in patients with a mean concentration greater than the median (P = 0.048 by log-rank test). Glucocorticoid use and IFX concentration were significantly associated with the risk of a first infection episode in the multivariable analysis (P = 0.004 for both). The risk of infection episode was significantly increased in the highest quartile of the mean of the last 3 trough IFX concentrations (>20.3 mg/liter) (hazard ratio 2.65 [95% confidence interval 1.14-6.14], P = 0.023). CONCLUSION: Our findings indicate that a high IFX concentration is correlated with a higher risk of a first infection episode, but these findings need to be replicated in further prospective studies.

Pathophysiology of disk-related low back pain and sciatica. II. Evidence supporting treatment with TNF-alpha antagonists.

Strong evidence suggests that TNF-alpha may be among the chemical factors involved in disk-related sciatica. TNF-alpha is involved in the genesis of nerve pain in animal models and may promote pain-signal production from nerve roots previously subjected to mechanical deformation. In animal experiments, TNF-alpha has been identified in nucleus pulposus and Schwann cells. Local production of endogenous TNF-alpha may occur early in the pathogenic process. Exposure to exogenous TNF-alpha induces electrophysiological, histological, and behavioral changes similar to those seen after exposure to nucleus pulposus, and these changes are more severe when mechanical compression is applied concomitantly. TNF-alpha antagonists diminish or abolish abnormalities in animal models. Other cytokines may be involved also, as suggested by the potent inhibitory effects of compounds such as doxycycline. Two open-label studies in humans suggest dramatic efficacy of TNF-alpha antagonists in alleviating disk-related sciatica. In contrast, the results of the only controlled study available to date do not support a therapeutic effect of TNF-alpha antagonists. Thus, whether TNF-alpha antagonist therapy is warranted in patients with disk-related sciatica remains an open question, and further randomized controlled studies are needed.

Pathophysiology of disk-related sciatica. I.--Evidence supporting a chemical component.

Sciatica in patients with disk disease was long ascribed to pressure put on the sciatic nerve root by a herniated disk. However, a role for chemical factors acting in conjunction with this mechanical insult is suggested by a number of clinical observations: disk surgery does not consistently provide pain relief, large disk herniations are not always symptomatic, severe pain may be present in patients without imaging evidence of nerve root compression, the severity of symptoms and neurological signs is not well correlated with the size of the disk herniation, and conservative therapy is often effective. Experimental studies have provided further evidence for a chemical component: disk herniations can undergo spontaneous resorption, the intervertebral disk is immunogenic, and mediators for inflammation have been identified within intervertebral disk tissue. The current pathophysiological theory incriminates proinflammatory substances secreted by the nucleus pulposus (NP). When preexisting or concomitant mechanical injury to a nerve root occurs, these substances can cause nerve root pain. Animal experiments have established that the NP can induce functional and structural nerve root abnormalities in the absence of mechanical compression and that this effect is mediated by substances located at the surface of NP cells. Methylprednisolone, diclofenac, indomethacin, doxycycline, and cyclosporine induce variable inhibition of this effect. Available information points to tumor necrosis factor-alpha (TNF-alpha) as the main candidate among substances potentially responsible for nerve root pain. Therefore, trials of TNF-alpha antagonists in patients with disk-related sciatica are warranted.

Characteristics of patients with spinal tuberculosis in a French teaching hospital.

OBJECTIVE: To investigate the characteristics of patients managed for spinal tuberculosis at the rheumatology department of the Tours Teaching Hospital, France, between 1986 and 2003. METHODS: Retrospective chart review. The incidence, epidemiology, clinical features, imaging study findings, and diagnostic procedures were recorded. RESULTS: The annual incidence of spinal tuberculosis was stable throughout the study period. There were 24 patients, 15 women and nine men with a mean age of 61 years; 15 patients were of French descent, three were of Portuguese descent, two were Asian, and four were North-African. Risk factors consisted of alcohol abuse in one patient, diabetes in two patients, glucocorticoid therapy in two patients, and a history of tuberculosis in six patients; none of the patients had AIDS. The cervical spine was involved in two patients, the thoracic spine in 11 patients, and the lumbar spine in 12 patients. Mean time from symptom onset to diagnosis was 4.3 months (range, 1-12 months). Percutaneous vertebral biopsy established the diagnosis in 16 of the 20 patients who underwent this procedure. CONCLUSION: The annual incidence of spinal tuberculosis remained unchanged throughout the study period and was not influenced by immigration or the AIDS epidemic. The typical patient was an elderly Caucasian woman of French descent. Reactivation of untreated or inadequately treated tuberculosis was probably the main mechanism.

[Paroxysmal nocturnal hemoglobinuria revealed by hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy]. / Thrombose des veines hépatiques au cours d'un traitement par infliximab (Remicade) révélant une hémoglobinurie paroxystique nocturne.

We report the case of a 41-Year-old man presenting with hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy for ankylosing spondylitis. The systematic work-up revealed paroxysmal nocturnal hemoglobinuria. One Year later the patient was receiving anticoagulation therapy and was in good condition. The role of Infliximab in the development of thrombosis in this patient with rare underlying thrombophilia is discussed.

Is epidural lipomatosis associated with abnormality of body fat distribution? A case report.

CASE REPORT: To report a case of epidural lipomatosis in a patient with abnormal adipose tissue distribution, glucose intolerance and mixed hyperlipidemia. A 63-year-old male patient presented with low back pain radiating to the left calf on standing and walking (walking distance <100 m). He weighed 97.5 kg, was 1.73 m tall (BMI 32.6 kg/m2) and had a waist circumference of 113 cm. He had a glucose intolerance after a 75-g glucose oral load test. CT-Myelography revealed voluminous epidural lipomatosis around L4-L5 and L5-S1. Low calorie diet and reduction in alcohol intake achieved a weight loss of 17.5 kg in 7 months (80 kg, BMI 25.8 kg/m2, waist circumference 94 cm) and dramatic improvement in low back pain, walking distance (>500 m) and reduction of lipomatosis on CT-scan. Our case suggests a relationship between central obesity phenotype and epidural lipomatosis. Specific insulin resistance treatment might be proposed for these patients if this hypothesis is confirmed in further studies.

Ossification of the posterior longitudinal ligament of the cervical spine and SAPHO syndrome.

We describe a case of cervical cord compression due to ossification of the posterior longitudinal ligament of the spine (OPLLS) in a 43-year-old Vietnamese patient with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Idiopathic OPLLS is mainly reported in 50- to 60-year-old men, particularly in Japanese, with a prevalence of 2%. Cervical myelopathy may occur. In addition to OPLLS in patients of Asian origin, the condition has also been described in association with ossifying diseases, including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) but not previously, to our knowledge, with SAPHO syndrome.