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author:("guillemin, L")
1.  EULAR evidence‐based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases 
Annals of the Rheumatic Diseases  2007;66(12):1560-1567.
To develop evidence‐based recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatic diseases.
The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist–epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference.
The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy (ie, non‐steroidal anti‐inflammatory drugs, gastroprotection and cyclo‐oxygenase‐2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice (ie, adrenal insufficiency, pregnancy, growth impairment).
Ten key recommendations for the management of systemic GC‐therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence (ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC‐replacement) and need further research; therefore also a research agenda was composed.
PMCID: PMC2095301  PMID: 17660219
2.  Development and validation of a scale for mouth handicap in systemic sclerosis: the Mouth Handicap in Systemic Sclerosis scale 
Annals of the Rheumatic Diseases  2007;66(12):1651-1655.
To develop and assess the reliability and construct validity of a scale assessing disability involving the mouth in systemic sclerosis (SSc).
We generated a 34‐item provisional scale from mailed responses of patients (n = 74), expert consensus (n = 10) and literature analysis. A total of 71 other SSc patients were recruited. The test–retest reliability was assessed using the intraclass coefficient correlation and divergent validity using the Spearman correlation coefficient. Factor analysis followed by varimax rotation was performed to assess the factorial structure of the scale.
The item reduction process retained 12 items with 5 levels of answers (total score range 0–48). The mean total score of the scale was 20.3 (SD 9.7). The test–retest reliability was 0.96. Divergent validity was confirmed for global disability (Health Assessment Questionnaire (HAQ), r = 0.33), hand function (Cochin Hand Function Scale, r = 0.37), inter‐incisor distance (r = −0.34), handicap (McMaster‐Toronto Arthritis questionnaire (MACTAR), r = 0.24), depression (Hospital Anxiety and Depression (HAD); HADd, r = 0.26) and anxiety (HADa, r = 0.17). Factor analysis extracted 3 factors with eigenvalues of 4.26, 1.76 and 1.47, explaining 63% of the variance. These 3 factors could be clinically characterised. The first factor (5 items) represents handicap induced by the reduction in mouth opening, the second (5 items) handicap induced by sicca syndrome and the third (2 items) aesthetic concerns.
We propose a new scale, the Mouth Handicap in Systemic Sclerosis (MHISS) scale, which has excellent reliability and good construct validity, and assesses specifically disability involving the mouth in patients with SSc.
PMCID: PMC2095324  PMID: 17502364
3.  Radical oxygen species production induced by advanced oxidation protein products predicts clinical evolution and response to treatment in systemic sclerosis 
Annals of the Rheumatic Diseases  2007;66(9):1202-1209.
To investigate the role of reactive oxygen species (ROS) in the development of the various patterns of systemic sclerosis (SSc) and the mechanisms of ROS production by endothelial cells and fibroblasts.
Production of hydrogen peroxide (H2O2), nitric oxide (NO) and cellular proliferation were determined following incubation of endothelial cells and fibroblasts with 56 SSc and 30 healthy sera. Correlations were established between those markers, the type and the severity of the clinical involvements, and the response to treatment. The factors leading to ROS production were determined.
H2O2 production by endothelial cells and fibroblasts was higher after incubation with SSc sera than with normal sera (p<0.001) and with sera from SSc patients with severe complications than sera from other patients (p<0.05). Sera from patients with lung fibrosis triggered the proliferation of fibroblasts more than other SSc sera (p<0.001), whereas sera from patients with vascular complications exerted no proliferative effect on fibroblasts, but inhibited endothelial cell growth (p<0.05) and induced NO overproduction (p<0.05). Bosentan reduced NO release by 32%, whereas N‐acetylcystein potentiated 5‐fluorouracil (5FU) to inhibit fibroblast proliferation by 78%. Those serum‐mediated effects did not involve antibodies but advanced oxidation protein products that selectively triggered cells to produce H2O2 or NO.
SSc sera induce the production of different types of ROS that selectively activate endothelial cells or fibroblasts, leading to vascular or fibrotic complications. Assaying serum‐induced ROS production allows clinical activity of the disease to be followed and appropriate treatments to be selected.
PMCID: PMC1955145  PMID: 17363403
systemic sclerosis; advanced oxidation protein products; reactive oxygen species; endothelial cells; fibroblasts
4.  Vasculitis restricted to the lower limbs: a clinical and histopathological study 
Annals of the Rheumatic Diseases  2006;66(4):554-556.
Rare cases of vasculitis restricted to the lower limbs have been reported, but the characteristics, outcome and response to treatment of this entity are not well known.
To describe the clinical, complementary examinations and response to treatment of this rare entity in the first retrospective series, and to compare data with historical pooled cases.
Retrospective analysis of all biopsy‐proven cases observed over a 10‐year period in four French tertiary medical units. Diagnosis of vasculitis restricted to the lower limb required the absence of any clinical symptom and complementary test finding, suggesting major extramuscular visceral involvement.
11 patients were included. Vasculitis restricted to the lower limb was associated with disabling muscle pain of the calves. Fever was present in 50% of cases; ankle arthralgia in 50% and skin involvement in 40%. MRI was the cornerstone of the diagnosis, showing hyperintense signal in T2 weight and in T1 weight after gadolinium injection. MRI findings correlated well with clinical outcome and were useful in guiding biopsy. Muscle biopsy was consistent with a polyarteritis nodosa‐type vasculitis in only 40% cases, whereas a leucocytoclastic vasculitis was seen for all other cases. Treatment with corticosteroids was effective in all cases, but there were relapses requiring immunosuppressive agents in 54% of cases.
Vasculitis of the calf muscles must be considered for patients with calf pain and with a biological inflammatory syndrome.
PMCID: PMC1856040  PMID: 17068062
5.  Submaximal exercise testing in the assessment of interstitial lung disease secondary to systemic sclerosis: reproducibility and correlations of the 6‐min walk test 
Annals of the Rheumatic Diseases  2006;66(2):169-173.
The 6‐min walk test (6MWT) is increasingly used as an outcome measure in interstitial lung disease (ILD).
To evaluate the usefulness of the 6MWT in a cohort of patients with ILD secondary to systemic sclerosis (SSc) and to correlate with established physiological parameters.
163 patients with SSc‐ILD were recruited for a multicentre, randomised, double‐blind clinical trial. Available data at protocol screening included repeated 6MWTs, pulmonary function testing with diffusing capacity, Doppler echocardiography and high‐resolution computed tomography of the thorax. Borg Dyspnoea Index was evaluated before and after 6MWT.
Mean (standard deviation (SD)) distance walked during walk test 1 was 396.6 (84.55) m compared with 399.5 (86.28) m at walk test 2. The within‐subject, intertest correlation as determined by Pearson's correlation coefficient testing was 0.95 (p<0.001). However, only weak correlations of 6MWT with percentage forced vital capacity and the Borg Dyspnoea Index were observed, and no correlation was observed with percentage diffusing capacity.
These data confirm the high reproducibility of the 6MWT in patients with SSc‐ILD and therefore the validity of the test in this cohort. The lack of correlation of 6MWT with standard physiological parameters of ILD suggests a multifactorial basis for limited exercise capacity in patients with SSc and calls into question the utility of the 6MWT as a measure of outcome in future studies on SSc‐ILD.
PMCID: PMC1798506  PMID: 16868020
6.  Increased prevalence of subclinical atherosclerosis in patients with small‐vessel vasculitis 
Heart  2006;93(1):96-99.
Background and objective
Although changes in smaller vessels is the hallmark of medium‐sized and small‐vessel vasculitis, it has been suggested that large arteries of such patients may also be affected by the early atherosclerotic process because of coexisting risk factors or systemic inflammation. This study aimed to bring additional arguments supporting this hypothesis.
Design, setting and patients
50 consecutive patients with primary systemic necrotising vasculitis and 100 controls matched for age and sex underwent ultrasonic detection of plaque in three peripheral vessels (carotid and femoral arteries and abdominal aorta). Cardiovascular risk factors and inflammation (C reactive protein (CRP)) were concomitantly measured in all participants, and diagnosis of high‐risk status was defined by the presence of known history of cardiovascular disease, type 2 diabetes or 10‐year‐Framingham Risk Score ⩾20%.
Patients had higher frequency of plaque than controls in the carotid arteries (p<0.05), in the aorta (p<0.01) and in the three vessels examined (p<0.001), and adjustment for high‐risk status did not confound such difference in the aorta and in the three vessels. In the overall population of patients and controls, vasculitis was associated with a higher frequency of three‐vessel plaques (p<0.05), independently of high‐risk status and CRP. In patients, the higher frequency of three‐vessel plaques was associated with high‐risk status (p<0.05) but not with CRP, or disease and treatment characteristics.
Small‐vessel vasculitis is associated with more frequent subclinical atherosclerosis, especially extended to multiple peripheral vessels, and such association is not entirely explained by cardiovascular risk factors and systemic inflammation.
PMCID: PMC1861337  PMID: 16940394
7.  Lack of association between the protein tyrosine phosphatase non‐receptor 22 (PTPN22)*620W allele and systemic sclerosis in the French Caucasian population 
Annals of the Rheumatic Diseases  2006;65(9):1230-1232.
The minor allele of the R620W missense single‐nucleotide polymorphism (SNP; rs2476601) in the PTPN22 (protein tyrosine phosphatase non‐receptor 22) gene has been reported to be associated with multiple autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, autoimmune thyroiditis and vitiligo. Systemic sclerosis (SSc) is a connective tissue disease with some autoimmune abnormalities. The aim of our study was to test for association of the PTPN22*620W allele with SSc in a French Caucasian cohort with a case–control study of 121 patients with SSc and 103 controls. All patients and controls were genotyped for the PTPN22*R620W SNP. No association was found between the PTPN22*620W allele and SSc (7% v 9.2%, p = 0.39). The frequency of genotypes carrying at least one 620W allele was similar in both groups (13% v 17%, p =  0.38). The PTPN22*620W allele was also not associated with autoantibody patterns. Thus, the PTPN22*R620W polymorphism cannot be regarded as a genetic susceptibility factor for SSc in the French Caucasian population.
PMCID: PMC1798267  PMID: 16464986
8.  Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better? 
Annals of the Rheumatic Diseases  2006;65(6):826-828.
To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis.
Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media–intima junction or in the media.
Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age <50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of <0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples ⩾0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5).
A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.
PMCID: PMC1798165  PMID: 16699053
giant cell arteritis; temporal artery biopsy; sensitivity
9.  Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension 
Thorax  2005;60(9):765-772.
Background: It has previously been shown that IgG antibodies from patients with limited cutaneous systemic sclerosis (SSc) bind to specific microvascular endothelial cell antigens. Since patients with limited cutaneous SSc are prone to develop pulmonary arterial hypertension (PAH), and since endothelial cell activation is involved in the pathogenesis of idiopathic PAH (IPAH), a study was undertaken to examine the presence of anti-endothelial cell antibodies in patients with idiopathic or SSc associated PAH.
Methods: PAH was confirmed by right heart catheterisation (mean pulmonary artery pressure at rest >25 mm Hg). Serum IgG and IgM reactivities were analysed by immunoblotting on human macrovascular and microvascular lung and dermal endothelial cells from patients with IPAH (n = 35), patients with PAH associated with SSc (n = 10), patients with diffuse (n = 10) or limited cutaneous (n = 10) SSc without PAH, and 65 age and sex matched healthy individuals.
Results: IgG antibodies from patients with IPAH bound to a 36 kDa band in macrovascular endothelial cell extracts with a higher intensity than IgG from other patient groups and controls. IgG antibodies from patients with IPAH bound more strongly to a 58 kDa band in microvascular dermal endothelial cells and to a 53 kDa band in microvascular lung endothelial cells than IgG antibodies from other patients and controls. IgG antibodies from patients with limited cutaneous SSc with or without PAH, but not from other groups or from healthy controls, bound to two major bands (75 kDa and 85 kDa) in microvascular endothelial cells.
Conclusion: IgG antibodies from patients with idiopathic or SSc associated PAH express distinct reactivity profiles with macrovascular and microvascular endothelial cell antigens.
PMCID: PMC1747530  PMID: 16135682
10.  Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases 
Annals of the Rheumatic Diseases  2004;64(6):913-920.
Objective: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice.
Methods: 866 rheumatology and internal medicine practitioners were contacted by email to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated.
Results: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjögren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease.
Conclusions: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.
PMCID: PMC1755517  PMID: 15550531
11.  Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases 
Annals of the Rheumatic Diseases  2007;67(9):1222-1228.
This study investigated the long-term effects of bosentan, an oral endothelin ETA/ETB receptor antagonist, in patients with pulmonary arterial hypertension (PAH) exclusively related to connective tissue diseases (CTD).
A total of 53 patients with PAH related to connective tissue diseases (PAH–CTD) in World Health Organization (WHO) functional class III received bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day for 44 weeks in this open non-comparative study. Assessments at weeks 16 and 48 included WHO class, clinical worsening, quality of life (Short-Form Health Survey (SF-36) and health assessment questionnaire (HAQ) modified for scleroderma), and survival (week 48 only). Safety and tolerability were monitored throughout the study.
At week 48, WHO class improved in 27% of patients (95% CI 16–42%) and worsened in 16% (95% CI 7–29%). Kaplan–Meier estimates were 68% (95% CI 55–82%) for absence of clinical worsening and 92% (95% CI 85–100%) for survival. Overall changes in quality of life were minimal. There were no unexpected side effects observed during the study.
In most patients, bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant achievement in this patient population.
PMCID: PMC2564804  PMID: 18055477
12.  Low grade marginal zone B cell lymphoma of the breast associated with localised amyloidosis and corpora amylacea in a woman with long standing primary Sjögren’s syndrome 
Journal of Clinical Pathology  2003;56(1):74-77.
Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised mammary amyloidosis are exceedingly rare entities. This report describes the case of a woman with long standing Sjögren’s syndrome presenting with asymptomatic MZL of the breast showing plasmacytic differentiation, associated with local ductular amyloidosis. The lesion was discovered incidentally in breast tissue resected for microcalcifications. Immunohistochemistry revealed κ light chain restriction, supporting the neoplastic nature of the infiltrate. A retrospective molecular study of the salivary gland biopsy showed a B cell clone. This is the first report of the association of human mammary ductular amyloidosis with cartwheel shaped material identical to corpora amylacea, usually seen in brain, lung, and prostate, but unknown in the human breast. The excellent outcome without treatment seen in this patient further emphasises the need to distinguish between MZL with plasmacytic differentiation and extramedullary plasmacytoma.
PMCID: PMC1769862  PMID: 12499440
marginal zone B cell lymphoma; breast; amyloidosis; corpora amylacea; ultrastructure; Sjögren’s syndrome
13.  Magnetic resonance imaging of skeletal muscle involvement in limb restricted vasculitis 
Annals of the Rheumatic Diseases  2002;61(12):1107-1109.
Objective: To describe the MRI findings in the legs of three patients with limb restricted vasculitides (two PAN, one isolated vasculitis of the skeletal muscle) with histologically established muscle involvement.
Methods: MRI was carried out on calf muscles and T2 weighted images, unenhanced T1 weighted images, and STIR sequences were obtained.
Results: Muscle damage resulted in oedema-like changes on MRI characterised by hyperintense signals in T2 weighted and slow tau inversion recovery (STIR) sequences and normal unenhanced T1 weighted sequences of one or several leg muscles.
Conclusions: MRI should be considered a useful complementary examination that might facilitate the recognition of limb restricted vasculitides, and possibly indicate the site for muscle biopsy. It could also be useful in monitoring the course of the disease. Future studies should also evaluate MRI for systemic PAN or other systemic vasculitides with muscle involvement.
PMCID: PMC1753964  PMID: 12429545
14.  Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2001;60(12):1141-1144.
OBJECTIVES—To describe infectious complications and analyse their risk factors and prognostic role in adults with systemic lupus erythematosus (SLE).
METHODS—A monocentric cohort of 87 adults with SLE (1960-1997) was studied to determine the risk factors for infection (disease activity evaluated by SLAM and SLEDAI scores, type of organ(s) involved or any biological abnormality, specific treatments) by comparing patients who had suffered at least one infectious episode (n=35; 40%) with non-infected patients (n=52; 60%). Prognostic indicators were assessed by comparing survivors at 10 years with non-survivors.
RESULTS—Of the 57 infectious episodes, 47 (82%) were of bacterial origin, 16 (28%) were pneumonia, and 46 (81%) were community acquired. According to univariate analysis, significant risk factors for infection were: severe flares, lupus glomerulonephritis, oral or intravenous corticosteroids, pulse cyclophosphamide, and/or plasmapheresis. No predictors were identified at the time of SLE diagnosis. Multivariate analyses retained intravenous corticosteroids (p<0.001) and/or immunosuppressants (p<0.01) as independent risk factors for infection, which was the only factor for death after 10 years of evolution (p<0.001).
CONCLUSION—In adults with SLE, infections are common and most often caused by community acquired bacteria. Intravenous corticosteroids and immunosuppressants are independent risk factors for infection, which is the only independent risk factor for death after 10 years of SLE evolution.

PMCID: PMC1753456  PMID: 11709457
15.  Polyarteritis nodosa and mixed cryoglobulinaemia related to hepatitis B and C virus coinfection 
Annals of the Rheumatic Diseases  2001;60(11):1068-1069.
OBJECTIVE—To determine the responsibility of hepatitis B virus (HBV) and hepatitis C virus (HCV) and therapeutic implications in a patient who developed systemic vasculitis.
CASE REPORT—The case of a 38 year old woman who had a past history of addiction to intravenous drugs and developed systemic vasculitis after infection by HBV and HCV is described. The clinical and laboratory findings substantiated not only the diagnosis of polyarteritis nodosa (PAN) but also that of mixed cryoglobulinaemia with a monoclonal IgMκ component.
CONCLUSION—Because cryoglobulins are rarely found in HBV related PAN but often associated with HCV infection, and in light of the histological findings, cryoglobulinaemia was interpreted as being secondary to HCV infection. This example of a highly complex situation emphasises the need to gather all relevant clinical, biological, histological, and complementary data so that the best treatment for overlapping of distinct vasculitides can be selected.

PMCID: PMC1753404  PMID: 11602482
17.  Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis 
Gut  2001;48(3):333-338.
BACKGROUND/AIMS—Cryptogenetic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease whose origin is unknown. The aim of this study was to describe the clinical spectrum of CMUSE, to determine the origin and pathophysiology of the disease, and to propose a treatment strategy.
METHODS—A total of 220 French gastroenterology departments were contacted to review patients with unexplained small bowel strictures. Of 17 responses, 12 corresponded to a diagnosis of CMUSE. These patients were hospitalised between 1965 and 1993 and their medical records were reviewed.
RESULTS—All patients (mean age 42.1 (4.4) years) had intestinal and five had extraintestinal symptoms (peripheral neuropathy, buccal aphthae, sicca syndrome, polyarthralgia, Raynaud's phenomenon, arterial hypertension). One patient had heterozygous type I C2 deficiency (28 base pair gene deletion). Two to 25 (mean 8.3 (1.9)) small intestine strictures were found. Stenoses of the large jejunoileal arteries were observed on two and aneurysms on three of five mesenteric angiograms. Despite surgery, symptoms recurred in seven of 10 patients and strictures in four. Steroid therapy was effective but caused dependence. One untreated patient died. Small bowel pathology showed superficial ulceration of the mucosae and submucosae, and an inflammatory infiltrate made of neutrophils and eosinophils.
CONCLUSIONS—CMUSE is an independent entity characterised by steroid sensitive inflammation of the small bowel which often recurs after surgery. CMUSE may be related to a particular form of polyarteritis nodosa with mainly intestinal expression or with an as yet unclassified vasculitis.

Keywords: cryptogenetic multifocal ulcerous stenosing enteritis; vasculitis; small intestine
PMCID: PMC1760126  PMID: 11171822
18.  111Indium antimyosin antibody imaging of primary myocardial invovement in systemic diseases 
OBJECTIVE—The diagnosis of primary myocardial involvement in systemic diseases is clinically relevant but difficult in the absence of specific criteria. Whatever the underlying disease, myocytes degeneration is observed during the active phase of myocardial damage. The aim of this study was to assess the diagnostic value of scintigraphic imaging with 111Indium antimyosin antibody (AM), a specific marker of the damaged myocyte, for ongoing myocardial damage related to systemic diseases.
METHODS—40 patients with histologically confirmed systemic diseases were studied. They were classified into two groups according to the presence (group 1, n=30), or the absence (group 2, n=10) of clinical, electrocardiographic (ECG) or echocardiographic signs suggestive of myocardial involvement. Planar and tomographic acquisitions were obtained 48 hours after injection of AM (90 MBq). Rest 201thallium (Tl) scintigraphy was also performed to assess myocardial perfusion and scarring. Clinical, ECG, and echocardiographic ± scintigraphic evaluations were repeated during follow up (17 ±19 months) in 36 of 40 patients.
RESULTS—In group 1, 13 of 30 patients (43%) showed diffuse significant AM uptake throughout the left ventricle (LV), and no or mild Tl abnormality. Two of these were asymptomatic, four had normal ECG, and two had no clinical or echographic LV dysfunction. All patients in group 2 had negative AMA scintigraphy and normal Tl scintigraphy. During follow up of 12 AM positive patients, cardiac status improved after immunosuppressive treatment was intensified in nine cases, worsened in two cases, and remained stable in one. During follow up of 24 AM negative patients, cardiac status remained stable in 23 cases despite treatment not being increased in 20, including two patients with sequellary myocardial involvement. The last patient developed mild LV dysfunction after 36 months.
CONCLUSION—AM scintigraphy allows detection of active myocardial damage related to systemic diseases, with increased specificity compared with conventional methods, and increased sensitivity in some cases. Further studies are needed to assess the potential value of AM scintigraphy as a therapeutic guide.

 Keywords: systemic disease; myocarditis; antimyosin antibody; scintigraphy
PMCID: PMC1752830  PMID: 10343523
19.  Factors associated with Pneumocystis carinii pneumonia in Wegener's granulomatosis. 
Annals of the Rheumatic Diseases  1995;54(12):991-994.
OBJECTIVE--To determine the factors associated with the occurrence of Pneumocystis carinii pneumonia (PCP) in Wegener's granulomatosis (WG). METHODS--We retrospectively compared a group of 12 patients with WG and PCP (PCP group), with 32 WG patients without PCP followed over the same period in the same centres (control group). RESULTS--The mean delay of onset of PCP after the start of the immunosuppressive therapy was 127 (SD 128) days. Before treatment, the clinical and biological features of the two groups were similar, except for the mean lymphocyte count which was lower in the PCP group than in the control group (1060/mm3 v 1426/mm3; p = 0.04). During treatment, both groups were lymphopenic. There was a significant difference between the lowest absolute lymphocyte count in each group (244/mm3 in the PCP group v 738/mm3 in the control group; p = 0.001). During the first three months of treatment, the lymphocyte count was less than 600/mm3 at least once in 10 of the 12 patients in the PCP group and in 11 of the 32 patients in the control group (p < 0.01). The mean cumulative dose of cyclophosphamide was greater in the PCP group than in the control group at the end of both the second (1.55 mg/kg/day v 0.99 mg/kg/day; p = 0.05) and the third (1.67 mg/kg/day v 0.97 mg/kg/day; p = 0.03) months. However, in multivariate analysis, the only two factors independently and significantly associated with the occurrence of PCP were the pretreatment lymphocyte count (p = 0.018) and the lymphocyte count three months after the start of the immunosuppressive treatment (p = 0.014). CONCLUSIONS--The severity of lymphocytopenia before and during immunosuppressive treatment is the factor best associated with PCP in WG.
PMCID: PMC1010066  PMID: 8546533
20.  Treatment of polyarteritis nodosa related to hepatitis B virus with interferon-alpha and plasma exchanges. 
Annals of the Rheumatic Diseases  1994;53(5):334-337.
OBJECTIVES--To test the effectiveness of and tolerance to interferon-alpha 2b (INFa2b) in association with plasma exchanges for the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS--A prospective, non blinded, multicentre trial was carried out in which patients with multisystemic HBV-related PAN were included. Each patient received the association of INFa2b and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS--Six patients were included in the study. Each patient had histopathological or arteriographic evidence of vasculitis and was infected with actively replicating HBV. All patients were alive at the end of the study and no longer presented clinical or laboratory evidence of systemic vasculitis. HBeAg/anti-HBeAb seroconversion was observed in four patients (66.6%) and HBsAg/anti-HBsAb in 3/6 (50%). Two patients are still being treated with INFa2b because of chronic active hepatitis. CONCLUSIONS--It is considered that this new therapeutic approach to HBV-related PAN effectively cured systemic vasculitis and was associated with control of HBV infections. Antiviral therapy may have a role to play as the first line treatment regime of virus-induced vasculitis.
PMCID: PMC1005334  PMID: 7912504
21.  Population pharmacokinetic study of teicoplanin in severely neutropenic patients. 
The teicoplanin pharmacokinetics (PK) of 30 febrile and severely neutropenic patients (polymorphonuclear count, < 500/mm3) with hematologic malignancies were compared with those determined for five healthy volunteers (HV). Neutropenic patients were given piperacillin combined with amikacin, and teicoplanin was added to the regimen the day fever developed in patients suspected of having a staphylococcal infection or 48 h later. Teicoplanin was given intravenously at a dosage of 6 mg/kg of body weight at 0, 12, and 24 h and once a day thereafter. Five to eleven blood samples per patient were collected. Teicoplanin concentrations were measured by liquid chromatography. A bicompartmental model was fitted to the data by a nonlinear mixed-effect-model approach. Multiple-linear regression analysis was applied in an attempt to correlate PK parameters to nine covariates. The mean trough concentrations of teicoplanin 48 h after the onset of treatment and 24 h after the last injection (last trough) +/- standard deviations were 8.8 +/- 4.1 and 17.5 +/- 13.5 mg/liter, respectively. A significant increase was noted in the mean rate of elimination clearance of teicoplanin in neutropenic patients compared with that of HV (0.86 versus 0.73 liter/h, P = 0.002), as was the case with rates of distribution clearance (5.89 versus 4.94 liter/h, P = 0.002); the mean half-life of distribution was significantly shorter in patients than in HV (0.43 versus 0.61 h, P = 0.002). In contrast, the volumes of the central compartment (ca. 5.8 liters for both groups), the volumes of distribution at steady state (HV, 37.6 liters; patients, 55.9 liters), and the elimination half-lives (HV, 39.6 h; patients, 52.7 h) were not significantly different between HV and neutropenic patients. Interindividual variabilities of rates of clearance (coefficient of variation [CV], 43%) and elimination half-lives (CV, 56%) were mainly explained by the variabilities among rates of creatinine clearance. Interindividual variabilities of the volumes of the central compartment (CV, 33%) and the volumes of distribution at steady state (CV = 51%) were correlated to interindividual variabilities among numbers of leukocytes and the ages of patients, respectively. On the basis of the population PK model of teicoplanin, simulations were made to optimize the dosing schedule. A supplemental 6 mg/kg dose of teicoplanin at 36 h resulted in a trough concentration at 48 h of 16.0 +/- 4.5 mg/liter, with only 7% of patients having a trough concentration of less than 10 mg/liter, compared with 46% of patients on the usual schedule.
PMCID: PMC163299  PMID: 8723474
22.  New application of myocardial antimyosin scintigraphy: diagnosis of myocardial disease in polymyositis. 
Annals of the Rheumatic Diseases  1993;52(3):235-238.
Heart disease is a rare but important complication of polymyositis. Diagnosis of myocardial disease is usually based on non-specific clinical, electrocardiographic, and echocardiographic data. This paper reports a case of polymyositis with myocardial disease diagnosed by myocardial imaging with radiolabelled antibody to myosin, a specific marker of the necrotic myocardial fibre.
PMCID: PMC1005025  PMID: 8484680
23.  Giant cell arteritis of the female genital tract with temporal arteritis. 
Annals of the Rheumatic Diseases  1992;51(7):900-903.
The clinical and pathological features of a patient with giant cell arteritis of the uterus and ovaries are described. A 61 year old woman had fever and weight loss over a period of eight months. A hysterectomy with bilateral salpingo-oophorectomy was performed for a large cystic ovarian mass. Histological examination showed a benign ovarian cyst and unexpected giant cell arteritis affecting numerous small to medium sized arteries in the ovaries and myometrium. The diagnosis of temporal arteritis was confirmed by a random temporal artery biopsy, despite the absence of symptoms of temporal arteritis. This observation is compared with previously reported cases and the relation between granulomatous arteritis of the genital tract and temporal arteritis is discussed. The main differential diagnosis in this localisation was represented by Wegener's granulomatosis and periarteritis nodosa.
PMCID: PMC1004778  PMID: 1632667
24.  Pharmacokinetics of ceftriaxone during plasma exchange in polyarteritis nodosa patients. 
Plasma exchange (PE) is currently being used to treat a variety of disorders involving immune complexes, such as polyarteritis nodosa. This procedure removes endogenous toxic components that accumulate in patients with this disease, but it also removes drugs. Plasma-protein binding and the volume of distribution (V) are two kinetic parameters which strongly affect the efficiency of drug removal by PE. Drugs that are highly bound to plasma proteins and have a low V may show a marked decrease in plasma levels as a result of PE. Because ceftriaxone exhibits saturable plasma-protein binding, which influences its pharmacokinetic parameters, particularly its V, we evaluated its removal during PE therapy in this nonrandomized crossover study. Twelve polyarteritis nodosa patients undergoing PE were studied. Each patient was given ceftriaxone intravenously in doses of 1 and 3 g on days 4 and 11, respectively, immediately before (n = six patients; group I) and 6 h before (n = six patients; group II) PE. Plasma was assayed for ceftriaxone by high-pressure liquid chromatography. The mean amounts eliminated +/- standard deviations were 230.8 +/- 38.5 mg (1 g) and 750.0 +/- 168.5 mg (3 g) for group I and 161.0 +/- 66.0 mg (1 g) and 347.0 +/- 121.0 mg (3 g) for group II. The drug fractions eliminated by PE were 23.0% +/- 3.9% (1-g dose) and 24.9% +/- 5.6% (3-g dose) for group I (P > 0.05), and 16.6% +/- 5.9% (1-g dose) and 11.5% +/- 4.0% (3-g dose) for group II (P < 0.05). These results showed that the drug fraction eliminated decreased when V increased only when the distribution phase of ceftriaxone had been completed (group II). These findings suggest that PE may influence ceftriaxone disposition and that it would be better to administer the drug after PE to assure its therapeutic efficacy.
PMCID: PMC284586  PMID: 7979282

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