Didier Clerc

Detection of Epstein-Barr virus DNA by in Situ hybridization and polymerase chain reaction in salivary gland biopsy specimens from patients with Sjögren's syndrome

PURPOSE To determine whether Epstein-Barr virus (EBV) could be involved in the pathogenesis of Sjögrens syndrome (SS). PATIENTS AND METHODS In situ hybridization using the BamH1-W fragment of EBV DNA was performed using labial salivary gland biopsy specimens from 14 patients with SS (eight with primary SS and six with secondary SS) and 39 control subjects. Furthermore, labial salivary gland biopsy specimens from 12 patients with SS (seven with primary SS and five with secondary SS) and 24 control subjects were submitted to the polymerase chain reaction to detect EBV DNA. RESULTS In situ hybridization detected EBV DNA in epithelial cells of labial salivary gland biopsy specimens from four of eight (50%) patients with primary SS, zero of six patients with secondary SS, and three of 39 (8%) control subjects. The difference between patients with primary SS and control subjects was statistically significant (p less than 0.02). The polymerase chain reaction detected EBV DNA in six of seven (86%) patients with primary SS, three of five (60%) patients with secondary SS, and seven of 24 (29%) control subjects. The difference between patients with primary SS and control subjects was statistically significant (p less than 0.01). CONCLUSION Both newly developed techniques showed that the presence of EBV DNA was significantly increased in patients with primary SS in comparison with control subjects. In all the positive SS patients who underwent in situ hybridization, epithelial cells of the labial salivary gland were the target of EBV infection. Our results suggest that this virus may play a role in the pathogenesis of SS. We cannot yet determine whether EBV is directly responsible for the destruction of the gland, or if its presence is a secondary event following gland injury.

Specific cardiomyopathy in lupus patients: report of three cases.

Clinically important myocarditis is an unusual feature in patients with systemic lupus erythematosus (SLE). We report three consecutive lupus patients over a 1 year period who developed severe left ventricular dysfunction in the absence of coronary artery disease or hypertensive cardiomyopathy. Two of them had clinical and biological flare of the disease whereas the lupus was quiescent in the latter. Two of them had positive IgG anticardiolipin antibodies. High dose steroids were given in two patients; one of them also required cyclophosphamide on account of diffuse proliferative glomerulonephritis. Left ventricular function improved quickly and markedly in these two patients; one of them had recurrence of severe myocarditis at intervals of 6 years and was each time responsive to steroids. Lupus cardiomyopathy, a rare event in the course of SLE, can be related to the disease even in the absence of coronary artery disease or hypertensive cardiomyopathy. It may be improved by steroids and immunosuppressive therapy. Literature concerning this cardiac manifestation in lupus is reviewed.

Treatment of multiple myeloma.

Conventional chemotherapies are no longer the only treatment in multiple myelomatosis. High-dose chemotherapy and autologous transplantation are not curative but do increase relapse-free survival time in young patients. Thalidomide is efficacious in refractory and relapsing myeloma and its evaluation is going on. Curative and preventive treatments of skeletal events, infections and anemia improve quality of life. All together, these strategies imply therapeutic knowledge and choices but allow an about 5-year-long median survival time in modern studies. Treatment options for myeloma now include, not only conventional chemotherapy regimens, but also novel symptomatic drugs and strategies that increase survival and/or quality of life, although they fail to provide a cure. In parallel with this expansion of the treatment armamentarium, physicians must acquire the knowledge needed to select the best treatment for the individual patient. After reviewing the rationale, effectiveness, and safety of each of these treatments, we will discuss the indications that we believe are legitimate.

Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell carcinoma

Interleukin-6 (IL-6) is produced by renal cell carcinoma (RCC) cell lines and primary tumors. Using immunohistochemical staining in two RCC patients with hypercalcemia and high serum levels of free and total IL-6, we showed expression of IL-6 in metastatic bone tissue. The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA).

Isolated thoracic spine lesion: is this the presentation of a SAPHO syndrome? A case report.

A case of an isolated lesion of the thoracic spine attributed to SAPHO syndrome is presented. A 51-year-old man was referred for inflammatory pain in the thoracic spine. The general examination was normal (especially cutaneous and rheumatologic examinations). Laboratory analysis showed only a mild inflammatory reaction. Standard radiographs showed partial condensation of T8. Computed tomography showed osteolysis of the anterior corner of T8, and MRI revealed an abnormal signal of T8, with enlargement of the prevertebral soft tissue. Percutaneous and thoracoscopic biopsies showed a nonspecific inflammatory process, and cultures were sterile. Initially, several diagnoses were advanced: infectious spondylitis, malignant tumor, lymphomas, Paget disease, seronegative spondyloarthropathies and finally atypical SAPHO syndrome. Three months later, the patient experienced more pain. General examination was still normal. The radiological findings worsened, while the inflammatory blood tests were normal. A new thoracoscopic biopsy revealed a nonspecific inflammatory process. A diagnosis of SAPHO syndrome was made, despite the lack of typical lesions. Dramatically improving with anti-inflammatory therapy, the patient’s condition was favorable at 3-year follow-up. This atypical presentation of an isolated lesion in the spine makes the diagnosis of a SAPHO syndrome difficult but possible. Spine surgeons must be aware of this rare entity, to avoid misdiagnosis and unnecessary repeated surgical biopsies.

Cisplatin and Hyponatremia

Excerpt To the editor: Hutchinson and associates (1) reported renal salt wasting in 7 of 70 patients treated with cisplatin. These patients had severe persistent orthostatic hypotension requiring p...

Cervical syphilitic spondylodiscitis associated with neurosyphilis

1 Letko E, Zafirakis P, Baltatzis S et al. Relapsing polychondritis: a clinical review. Semin Arthritis Rheum 2002;31:384 95. 2 McAdam LP, O’Hanlan MA, Bluestone R et al. Relapsing polychondritis: prospective study of 23 patients and review of the literature. Medicine 1976;55:93 215. 3 Yaguchi H, Tsuzaka K, Niino M et al. Aseptic meningitis with relapsing polychondritis mimicking bacterial meningitis. Intern Med 2009;48:1841 4. 4 Erten-Lyon D, Oken B, Woltjer RL et al. Relapsing polychondritis: an uncommon cause of dementia. J Neurol Neurosurg Psychiatry 2008;79:609 10. 5 Stewart SS, Ashizawa T, Dudley AW et al. Cerebral vasculitis in relapsing polychondritis. Neurology 1988;38: 150 2. 6 Taborcias D, Rubiales A, Altadill A et al. Policondritis recidivante y meningoencefalitis. Med Clin 1996;107: 597 8. 7 Goddard P, Cook P, Laszlo G et al. Relapsing polychondritis: report of an unusual case and review of the literature. Br J Radiol 1992;64:1064 7. 8 Brod S, Booss J. Idiopathic CSF pleocytosis in relapsing polychondritis. Neurology 1988;38:322 3. 9 Hoppmann RA, Peden JG, Ober SK. Central nervous system side effects of nonsteroidal anti-inflammatory drugs. Aseptic meningitis, psychosis, and cognitive dysfunction. Arch Intern Med 1991;151:1309 13. 10 Rodriguez SC, Olguin AM, Miralles CP, Viladrich PF. Characteristics of meningitis caused by Ibuprofen: report of 2 cases with recurrent episodes and review of the literature. Medicine 2006;85:214 20. Rheumatology 2011;50:1723 1725 doi:10.1093/rheumatology/ker185 Advance Access publication 26 May 2011

Cardiomyopathies spécifiques au cours du lupus érythémateux systémique : à propos de 3 cas

Resume Une myocardite cliniquement severe est inhabituelle au cours du lupus erythemateux systemique (LES). Nous rapportons 3 cas consecutifs, survenus en une annee, de patients lupiques ayant developpe une insuffisance cardiaque gauche majeure en l’absence de pathologie coronarienne ou de cardiopathie hypertensive. Deux d’entre eux presentaient une poussee clinique et biologique alors que le lupus du dernier patient etait quiescent. Deux d’entre eux avaient des anticorps anticardiolipines de type IgG. Deux patients ont ete traites par de fortes doses de corticosteroides, associees pour l’un d’entre eux a un traitement par cyclophosphamide en raison d’une glomerulonephrite proliferative diffuse. La fonction ventriculaire gauche s’est amelioree rapidement et de maniere notable chez ces 2 patients ; l’un a presente une rechute de myocardite au bout de 6 ans repondant de nouveau au traitement par corticoides. La cardiomyopathie lupique est un evenement rare au cours du LES ; elle peut etre rattachee a la maladie meme en l’absence de pathologie coronarienne ou de cardiopathie hypertensive. Elle peut s’ameliorer sous traitement corticoides ou immunosuppresseur. Une revue de la litterature concernant cette manifestation cardiaque au cours du LES est effectuee.

Traitement du myélome multiple

Resume Le traitement du myelome multiple ne se resume plus aux chimiotherapies conventionnelles. Sans permettre la guerison, la chimiotherapie intensive et l’autogreffe permettent chez les sujets jeunes une prolongation notable de la survie sans rechute. Encore en cours d’evaluation, le thalidomide constitue d’ores et deja une avancee essentielle dans les myelomes refractaires ou en rechute. La prevention et la prise en charge des evenements osseux, des infections et de l’anemie ameliorent la qualite de vie. Ces innovations placent le therapeute face a une obligation de connaissance et aux contraintes d’un choix. Ensemble, elles concourent a l’allongement global de la duree de survie dont la mediane s’eleve dans la plupart des publications modernes a environ 5 ans.