Prognostic factors for lung function in systemic sclerosis: prospective study of 105 cases.

The aims of the present study were to identify prognostic factors for systemic sclerosis (SSc)-related interstitial lung disease and to clarify the possible causative role of manometric oesophageal involvement. Consecutive SSc patients underwent pulmonary function tests and oesophageal manometry. They were included in the study if pulmonary function tests were repeated >12 months after baseline. The primary end-point was a decrease of >or=10% of the predicted value in forced vital capacity (FVC). The secondary end-points were a decrease of >or=15% pred in lung carbon monoxide diffusing capacity (D(L,CO)) and a decrease of >or=20% pred in FVC. Of the 105 patients (45 diffuse SSc; median disease duration 2.0 yrs), 23 (23%) had a FVC of <80% pred, 60 (59%) had a D(L,CO) of <80% pred and 57 (54%) showed severe oesophageal hypomotility at baseline. Over 72+/-46 months, 29 (28%) patients displayed a decrease of >or=10% pred in FVC, 39 (40%) of 98 patients displayed D(L,CO) decline and 19 (18%) patients displayed a decrease of >or=20% pred in FVC. On multivariate analysis, diffuse SSc was a significant predictor for a decrease of >or=10% pred in FVC (p = 0.01). No other predictor of a decrease in pulmonary function was identified. Only diffuse SSc was predictive of a decrease in pulmonary function in this early-SSc cohort. This does not support preliminary data suggestive of a causative role of oesophageal involvement.

Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin.

OBJECTIVE: SSc is a CTD characterized by early generalized microangiopathy with disturbed angiogenesis. Soluble endoglin (sENG), a serum anti-angiogenic protein, has recently been described as a major actor in pre-eclampsia, another severe vascular disease with abnormal angiogenesis. The aim of this study was to investigate, in a cross-sectional study, sENG levels together with other serum vascular markers. METHODS: Serum levels of sENG were assessed by ELISA in consecutive SSc patients and controls matched for age and sex. We also measured by ELISA serum levels of VEGF and asymmetric dimethylarginine (ADMA), as respective markers of angiogenesis and endothelial dysfunction. RESULTS: We included 235 unrelated subjects: 187 SSc patients and 48 controls. Higher concentrations of sENG (P = 0.002) and sVEGF (P < 0.0001) were found in SSc patients compared with controls whereas there was no difference for ADMA. In multivariate analysis, sENG levels were significantly increased in SSc patients with cutaneous ulcerations (P = 0.0003), positive for ACAs (P = 0.009) and with abnormal diffusing capacity for carbon monoxide divided by alveolar volume (P = 0.03). Soluble ENG levels negatively correlated with ADMA, but no relationship was found between sENG and sVEGF. CONCLUSION: This study shows increased values of sENG in a large SSc cohort and a relevant association with a vascular phenotype. The predictive value of the biomarker sENG and its potential role on cellular endothelial disturbances remain to be determined.

[Haematological complications of prostatic cancer: 2 cases, one revealing the neoplasia]. / Complications hématologiques du cancer de prostate: à propos de deux cas dont un révélateur.

INTRODUCTION: We report two cases of patients with prostate cancer who underwent haematological complications from the disease. CLINICAL CASES: Diffuse intravascular coagulopathy (with thrombopenia) was observed in two patients (55 and 59 years-old) diagnosed with prostate cancer. In one patient who had normal prostate at clinical examination, thrombopenia with incomplete diffuse intravascular coagulopathy and biological inflammatory led to diagnosis. It was initially controlled by hormonal therapy and secondary by chemotherapy. In the other patient diffuse intravascular coagulopathy followed introduction of hormonal therapy and lead to the patient's death. DISCUSSION: Patients with metastatic hormone-refractory prostate carcinoma may have life-threatening coagulation complications due to their disease. Diffuse intravascular coagulopathy is the most frequent coagulation complication. Other coagulopathies associated with prostate cancer are thrombocytopenic thrombotic purpura, thrombosis, Trousseau's syndrome and acquired factor VIII inhibitor development. Usually these haematological manifestations complicate the course of the disease and appear to have a bad prognosis. But thrombopenia or haematologic features may lead to the diagnosis of medullary metastatic prostatic cancer, even if the prostate appears normal at the initial clinical examination.

[Knee septic arthritis]. / L'arthrite septique du genou.

The development of antibiotics and arthroscopic treatment have been two major turning points in the management of septic arthritis of the knee joint. We report a retrospective review of 78 patients managed in three surgery units and one rheumatology unit. Management practices varied between the units. Joint aspiration was proposed for all patients seen by rheumatologists. Certain surgeons proposed arthroscopy systematically at admission while others preferred a more selective approach. Arthroscopic wash-out was proposed as the first-line procedure for only 33 patients. All were given systemic antibiotics using a variety of protocols. The course under antibiotic treatment confirmed the potential gravity of septic arthritis of the knee joint since two patients died and 34 required surgery, half of which had more than one operation. The functional outcome at mean 19 months was rather poor. Only 65 knees were free of any implant and only 40 (62%) were pain free. Mean flexion was 116 degrees and 11 patients (17%) had significant flexion contracture. Factors of poor prognosis were initially high sedimentation rate, advanced stage according to Gächter, presence of specific germs (meti-R S. aureus, Gram-negative bacilli), and failure of first-line treatment. A management algorithm was proposed: initial aspiration for evacuation, medical treatment alone if there is no synovitis, and reduction synovectomy otherwise. The key to success is early well adapted treatment.

How to define a Minimal Clinically Individual State (MCIS) with pain VAS in daily practice for patients suffering from musculoskeletal disorders.

OBJECTIVES: Pain is frequently the primary variable in symptomatic clinical trials for the evaluation of rheumatological disorders. The protocol of such trials mention a minimum level of pain as an entry criterion [e.g. a level above the Patient Acceptable Symptoms State (PASS)] and the changes in pain as the primary variable. Usually, the results are expressed at a group level as the mean changes in pain. However, the presentation at an individual level and, in particular, the percentage of patients with a Low Disease Activity State at the end of the study seems more clinically relevant. Pain is usually evaluated using a continuous variable such as a 0-100 visual analogue scale. The cut-offs permitting one to define both the entry criterion and the LDAS are not well established. The objective of this study was to evaluate such cut-offs using a patient-derived perspective. STUDY DESIGN: cross-sectional study. PATIENTS: consecutive out patients suffering from chronic rheumatic diseases familiar with the use of a VAS to evaluate their level of pain. DATA COLLECTED: two questions were asked the patients at the end of the visit: "Based on the experience you have because of your chronic rheumatic disorder, could you please specify the level of pain below which you consider your disease as inactive ? Moreover, could you please also specify the level of pain above which you consider taking a pain killer?" Before answering the second question, it was explained to the patient that their answer to the second question could be similar to their response to the first one. For the two questions, the cumulative percentage of patients (disease inactive and pain killer intake) were calculated for each level of pain. RESULTS: The underlying disease of the 137 evaluated patients (mean age: 57+/-16 and female sex: 76%) was rheumatoid arthritis (n = 59), ankylosing spondylitis (n = 19), SLE (n = 2), back pain (n = 20), or peripheral osteoarthritis (n = 37). The mean disease duration was 12+/-10 years. At the time of the study, the current level of pain evaluated on a 0-100 VAS was 33+/-22. The LDAS was 49, 36 and 25 for our patient population at the 25th, 50th and 75th percentiles, respectively. The pain killer intake level was 32, 48, 64 at the 25th, 50th, 75th percentile respectively. CONCLUSION: This study suggests that LDAS and PASS may be distinct concepts. The methodological approach adopted here could be of interest for specifying the minimum level of symptoms at entry in a symptomatic trial (PASS) and also to present results in terms of the percentage of patients in good condition (LDAS) at the end of a trial.

Benefit/risk of combination therapies.

It is now accepted that rheumatoid arthritis is not a benign disease, and has considerable morbidity and increased mortality rates. Monotherapy with disease modifying anti-rheumatic drugs (DMARDs) is often ineffective, and rarely leads to sustained clinical remission. Many clinical trials suggest the effectiveness of using combination therapies, and also the benefit of aggressive management early in the course of the disease. However, recent publications studying a variety of combination therapies in rheumatoid arthritis have shown diverse results. Drug combinations at an early stage of rheumatoid arthritis which slow radiographic progression appear to be the most convincing. These data suggest that practitioners should begin with intensive therapy in early disease, and not reserve combination therapy for those who fail monotherapy. The therapeutic strategy should be positioned according to the severity of the disease: in RA with markers indicating severity, combination should be initiated at the start of therapy while it should be instituted in a rapid step-up fashion in mild RA if insufficient efficacy is seen for monotherapy. In general, combinations appear safe and well-tolerated, but continued caution with appropriate monitoring of long-term results and possible toxicities is required.

Destructive hip disease complicating traumatic paraplegia.

Recent progress in the management of spinal cord injury has provided longer survivals, and as a result the incidence of secondary bone and joint disorders has increased. Joint lesions due to syringomyelia complicating a cervical spinal cord injury are the most common of these disorders. We report a case of destructive hip disease 7 years after an injury responsible for complete paraplegia with sensory loss. The joint lesions were painless, and there was no local evidence of inflammation. Hip radiographs disclosed atrophic osteoarthropathy with complete destruction of the femoral neck and head. This unusual case raises questions about the pathophysiology of neuropathic osteoarthropathy in paraplegics.

Monostotic fibrous dysplasia of the lumbar spine.

Monostotic fibrous dysplasia is exceedingly rare. We report a case in a 61-year-old woman with a history of recurrent low back pain and sciatica since 35 years of age. While walking, she suddenly experienced pain in her right thigh. The pain spread gradually to the buttock and calf on the same side, becoming increasingly severe. The time pattern was mechanical, with exacerbation during straining. Paresthesia developed over the dorsal aspect of the right foot. Nonsteroidal antiinflammatory drugs were ineffective. Radiographs of the spine showed an expansile and heterogeneous lesion in the body of L2. Hyperactivity of L3 and L4 was seen on the bone scan. Computed tomography demonstrated heterogeneity of L2, L3, and L4, as well as hypertrophy of the neural arch of L3 and of the right posterior lamina and spinous process of L4. Alterations in L2, L3, and L4 were noted on the magnetic resonance imaging study, which showed no evidence of epidural involvement. Laboratory tests were normal. A surgical biopsy of L3 established the diagnosis of fibrous dysplasia. Since the seminal description of fibrous dysplasia in 1891, only 21 cases of monostotic spinal involvement have been published. The spinal lesions can remain clinically silent or cause spinal pain with or without neurological symptoms. Radiographic findings are variable (heterogeneity, osteolysis, expansion without cortical violation or soft tissue involvement). Calcium and phosphate levels are normal. The diagnosis depends on examination of a vertebral biopsy specimen.

[Poisoning with "poppers", a rare cause of methemoglobinemia observed in emergency cases]. / L'intoxication au "poppers", cause rare de méthémoglobinémie observée aux urgences.

BACKGROUND: Methemoglobulinemia should be entertained as a differential diagnosis in patients with cyanosis. Recently in France there has been an increase in the number of cases of acquired methemoglobulinemia due to inhalation of poppers. CASE REPORTS: Four patients were admitted to the emergency room of a Paris hospital in a state of unconsciousness with cyanosis. All four patients had inhaled poppers shortly before admission. The clinical course was rapidly favorable after intravenous infusion of methylene blue in 3 cases. DISCUSSION: Poppers are inorganic aliphatic nitrites used for their relaxing effect on smooth muscle and for their aphrodisiac effect. One poorly recognized effect is the development of methemoglobulinemia. Tissue hypoxia results because methemoglobulin cannot bind oxygen, leading to a brown or blue coloration of the blood. Methemoglobulin usually results from exposure to a wide variety of oxidizing compounds including certain drugs. Methylene blue is the specific treatment for symptomatic methemoglobulinemia. These four cases emphasize the toxic effect of products sold in sex shops and calls attention to the life-threatening risks involved.

[Bone evaluation in ten adults with cutaneous mastocytosis]. / Evaluation de l'état osseux chez dix adultes atteints de mastocytose cutanée.

BACKGROUND: To systematically evaluate the bone status, searching for osteoporosis in patients with cutaneous mastocytosis. PATIENTS AND METHODS: In a prospective study from March 1997 to June 2000, we included all new patients examined for cutaneous signs of mastocytosis. Past history, physical examination, skin biopsy, laboratory tests, bone densitometry, cytology and histopathology of bone marrow and other complementary investigations were performed in all these patients. RESULTS: Ten patients were included. Two patients had osteoporosis. Five others had osteopenia. Four patients had bone marrow involvement due to mastocytosis. One of these four patients had myelodysplasia. DISCUSSION: This study suggests better investigation of bone density and bone marrow in patients who have cutaneous mastocytosis. Systematic histopathology of bone marrow and osteodensitometry help to detect patients with systemic involvement. Bone densitometry is particularly effective for early detection of patients at risk for fracture and is of practical interest since patients with osteoporosis can now be treated with Pamidronate.

[Clinical elements of the diagnostic guidelines for low back pain]. / Eléments cliniques d'orientation diagnostique devant une lombalgie.

If the majority of low back pain spontaneously recover in a few weeks, the main problem is to eliminate the possibility of a specific low back pain due to a serious underlying medical condition with radically different therapeutics and consequences. Medical history and physical examination will make it possible to detect these conditions (tumor, infection, spinal fracture, spondylarthropathy) and to specify useful complementary explorations. The second objective, for which we have few reliable clinical criteria, will consist in specifying the cause of low back problem. Lastly, it will be needed to detect the factors of risk of chronic course in order to improve the medical care which must be early.

Care related pain and functional restoration for chronic low back pain: a prospective study.

OBJECTIVE: To assess care related pain during a program of functional restoration for chronic low back pain. PATIENTS AND METHODS: Chronic low back pain patients were prospectively included in a program of functional restoration. Low back pain was recorded before and after each morning and afternoon sessions, all over the program of functional restoration, for equivalence study. Equivalence was admitted if 95% confidence interval of the difference in pain falled wholly in the interval ± 10/100mm. Medication was recorded during the program. Progression of the patients during the program and 3-month effectiveness were also recorded for internal validity. RESULTS: Thirty-seven patients were included. They underwent a progression in load and spent energy during the program. Follow-up also indicated improvement of functional ability and quality of life. There was no variation in pain during the program however medication intake increased. CONCLUSION: There was no significant care related pain during our program of functional restoration for chronic low back pain. This may be due to adaptation of the medication and suggests the importance of close medical management of patients during functional restoration.

Validation of a French version of Roland-Morris questionnaire in chronic low back pain patients.

OBJECTIVE: To validate a French version of the Roland-Morris Disability Questionnaire (RMDQ) in patients with chronic low back pain (LBP). MATERIAL AND METHODS: Fifty-eight patients due to participate in a functional rehabilitation programme for chronic low back pain were included prospectively. The RMDQ, the Quebec Back Pain Disability Scale (QBPDS) and the "daily activities" subscale of the Dallas Pain Questionnaire (DPQ) were administered. The RMDQ was assessed for internal consistency, reliability, criterion validity and sensitivity to change. RESULTS: Cronbach's alpha for the RMDQ was 0.84. The intraclass correlation coefficient [95% confidence interval] was 0.89 [0.83-0.93]. The RMDQ score was correlated with the QBPDS score (r=0.713) and the DPQ's "daily activities" subscore (r=0.514). The results of assessments before and after functional rehabilitation showed that the French version of the RMDQ had very high sensitivity to change (effect size: 1.49) and was more sensitive than the QBPDS and the DPQ's "daily activities" subscore. CONCLUSIONS: Our study validated the French version of the RMDQ in patients suffering from chronic low back pain. Furthermore, we highlighted the questionnaire's very high sensitivity to change.

High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis.

OBJECTIVE: To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). METHODS: Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. RESULTS: Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P<0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P=0.08), and erythrocyte sedimentation rate >28 mm/hour (P=0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]). CONCLUSION: This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.

Cervical spine involvement in psoriatic arthritis.

UNLABELLED: The clinical and radiographic manifestations of cervical spine involvement in psoriatic arthritis remain incompletely described. Only one case-control study has been reported. OBJECTIVE: To conduct a case-control study of the clinical and radiographic manifestations of cervical spine involvement in psoriatic arthritis. PATIENTS AND METHODS: 30 psoriatic arthritis patients (mean age, 53.3 years (21-78); sex ratio, 1; mean disease duration, 80.4 months (12-204); and mean Ritchie's index, 9.3 (2-30)) were compared with 30 controls with common low back pain (mean age, 53.8 years (21-78)). Each patient underwent a physical examination, completed a questionnaire on function, underwent cervical spine radiography (anteroposterior and lateral views and views in flexion and extension). All radiographs were evaluated by an independent observer. RESULTS: Patients were more likely than controls to have neck pain (22/30 (73%) vs 8/30 (26%) P < 0.001). Among subjects with neck pain, the time pattern was more likely to be inflammatory in the patients than in the controls (14/22 vs 1/8, P < 0.001). Functional impairment and pain severity were significantly greater in the patients. On radiographs, facet joint abnormalities (osteophytes, joint space loss, sclerosis) were significantly more common (P < 0.01) in the patients, particularly at C3-C4 and C4-C5. Also more common in the patients were signs of spondylitis (7 vs 0) and of facet joint arthritis (7 vs 2). No subjects had syndesmophytes. Three (10%) patients had anterior C1-C2 subluxation with an atlas-dens interval greater than 4 mm. Within the patient group, no correlations were found between clinical patterns and radiographic findings. CONCLUSION: Our data confirm that psoriatic arthritis frequently involves the cervical spine, with the facet joints being a preferred target, and can cause anterior C1-C2 subluxation.