A short anogenital distance on MRI is a marker of endometriosis.

STUDY QUESTION: Could the anogenital distance (AGD) as assessed by MRI (MRI-AGD) be a diagnostic tool for endometriosis? SUMMARY ANSWER: A short MRI-AGD is a strong diagnostic marker of endometriosis. WHAT IS KNOWN ALREADY: A short clinically assessed AGD (C-AGD) is associated with the presence of endometriosis. STUDY DESIGN SIZE DURATION: This study is a re-analysis of previously published data from a case-control study. PARTICIPANTS/MATERIALS SETTING METHODS: Women undergoing pelvic surgery from January 2018 to June 2019 and who had a preoperative pelvic MRI were included. C-AGD was measured at the beginning of the surgery by a different operator who was unaware of the endometriosis status. MRI-AGD was measured retrospectively by a senior radiologist who was blinded to the final diagnosis. Two measurements were made: from the posterior wall of the clitoris to the anterior edge of the anal canal (MRI-AGD-AC), and from the posterior wall of the vagina to the anterior edge of the anal canal (MRI-AGD-AF). MAIN RESULTS AND THE ROLE OF CHANCE: The study compared MRI-AGD of 67 women with endometriosis to 31 without endometriosis (controls). Average MRI-AGD-AF measurements were 13.3 mm (±3.9) and 21.2 mm (±5.4) in the endometriosis and non-endometriosis groups, respectively (P < 10-5). Average MRI-AGD-AC measurements were 40.4 mm (±7.3) and 51.1 mm (±8.6) for the endometriosis and non-endometriosis groups, respectively (P < 10-5). There was no difference of MRI-AGD in women with and without endometrioma (P = 0.21), or digestive involvement (P = 0.26). Moreover, MRI-AGD values were independent of the revised score of the American Society of Reproductive Medicine and the Enzian score. The diagnosis of endometriosis was negatively associated with both the MRI-AGD-AF (ß = -7.79, 95% CI (-9.88; -5.71), P < 0.001) and MRI-AGD-AC (ß = -9.51 mm, 95% CI (-12.7; 6.24), P < 0.001) in multivariable analysis. Age (ß = +0.31 mm, 95% CI (0.09; 0.53), P = 0.006) and BMI (ß = +0.44 mm, 95% CI (0.17; 0.72), P = 0.001) were positively associated with the MRI-AGD-AC measurements in multivariable analysis. MRI-AGD-AF had an AUC of 0.869 (95% CI (0.79; 0.95)) and outperformed C-AGD. Using an optimal cut-off of 20 mm for MRI-AGD-AF, a sensitivity of 97.01% and a specificity of 70.97% were noted. LIMITATIONS REASONS FOR CAUTION: This was a retrospective analysis and no adolescents had been included. WIDER IMPLICATIONS OF THE FINDINGS: This study is consistent with previous works associating a short C-AGD with endometriosis and the absence of correlation with the disease phenotype. MRI-AGD is more accurate than C-AGD in this setting and could be evaluated in the MRI examination of patients with suspected endometriosis. STUDY FUNDING/COMPETING INTERESTS: N/A. TRIAL REGISTRATION NUMBER: The protocol was approved by the 'Groupe Nantais d'Ethique dans le Domaine de la Santé' and registered under reference 02651077.

Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings.

STUDY QUESTION: Could anogenital distance (AGD) be a non-invasive marker of endometriosis and correlated to the American Society for Reproductive Medicine revised score (r-ASRM) and ENZIAN classifications? SUMMARY ANSWER: Surgically and histologically proven endometriosis is associated with a short AGD in women of reproductive age but not correlated either to the severity or to the location of the disease. WHAT IS KNOWN ALREADY: AGD is a marker of intrauterine androgen exposure and exposure to oestrogen-like chemicals such as phthalates. Moreover, exposure to endocrine disruptors, such as organochlorine chemicals, is associated with endometriosis. It has been suggested that a short AGD in women is associated with an increased risk of endometriosis based on clinical and ultrasound exams. STUDY DESIGN SIZE DURATION: A prospective cohort study was conducted from January 2018 to June 2019 in a tertiary-care centre including 168 adult women undergoing pelvic surgery. PARTICIPANTS/MATERIALS SETTING METHODS: Of the 168 women included, 98 patients had endometriosis (endometriosis group) and 70 did not (non-endometriosis group). An operator (not the surgeon) measured the distance from the clitoral surface to the anus (AGD-AC) and from the posterior fourchette to the anus (AGD-AF) before surgery using a millimetre accuracy ruler. Endometriosis was diagnosed on exploration of the abdominopelvic cavity, and the r-ASRM and ENZIAN scores were calculated. All removed tissues underwent pathological examination. MAIN RESULTS AND THE ROLE OF CHANCE: Mean (±SD) AGD-AF measurements were 21.5 mm (±6.4) and 32.3 mm (±8.1), and average AGD-AC measurements were 100.9 mm (±20.6) and 83.8 mm (±12.9) in the endometriosis and non-endometriosis groups (P < 0.001), respectively. Mean AGD-AF and AGD-AC measurements were not related to r-ASRM stage (P = 0.73 and 0.80, respectively) or ENZIAN score (P = 0.62 and 0.21, respectively). AGD-AF had a better predictive value than AGD-AC for discriminating the presence of endometriosis (AUC = 0.840 (95% CI 0.782-0.898) and 0.756 (95% CI 0.684-0.828)), respectively. For AGD-AF, an optimal cut-off of 20 mm had a specificity of 0.986 (95% CI 0.923-0.999), sensitivity of 0.306 (95% CI 26.1-31.6) and positive predictive value of 0.969 (95% CI 0.826-0.998). In multivariable analysis, the diagnosis of endometriosis was the only variable independently associated with the AGD-AF (ß = -9.66 mm 95% CI -12.20--7.12), P < 0.001). LIMITATIONS REASONS FOR CAUTION: The sample size was relatively small with a high proportion of patients with colorectal endometriosis reflecting the activity of an expert centre. Furthermore, we did not include adolescents and the AGD-AF measurement could be particularly relevant in this population. WIDER IMPLICATIONS OF THE FINDINGS: The measurement of AGD could be a useful non-invasive tool to predict endometriosis. This could be especially relevant for adolescents and virgin women to avoid diagnostic laparoscopy and empiric treatment. STUDY FUNDING/COMPETING INTERESTS: None.

[Anti-TNF alpha-induced eruptive nevi: Three cases]. / Nævus éruptifs sous anti-TNF alpha. Trois observations.

BACKGROUND: Eruptive melanocytic nevi (EMN) are a rare phenomenon characterized by simultaneous rapid onset of multiple nevi. The condition has been described in different contexts: immunosuppression, immunosuppressive drugs, targeted therapies, bullous diseases, and chemical melanocytic stimulation. We report 3 cases of EMN following anti-TNF alpha treatment. PATIENTS AND METHODS: Case 1 - A 51-year-old female patient was receiving adalimumab for spondyloarthritis (the first treatment for this patient). A few months after the start of treatment, multiple nevi were noted on the 4 limbs, and in particular on the right palm. The patient confirmed the absence of these lesions before initiation of treatment. A diagnosis was made of adalimumab-induced EMN. Case 2 - A 49-year-old male patient was receiving etanercept for spondyloarthritis (the first biologic in this patient). Multiple small nevi developed on the trunk in the months after the start of treatment. The patient indicated that these lesions had appeared after the start of treatment. A diagnosis was made of etanercept-induced EMN. Case 3 - A 20-year-old woman with hidradenitis suppurativa was treated with infliximab. After 1.5 months, she reported the outbreak of various pigmented lesions 2-3mm in diameter on the trunk and one lesion on her right palm. The clinical diagnosis was EMN. After follow-up of 4 months to 5 years, no transformation to melanoma was noted in any of these 3 patients. CONCLUSION: EMN remains a rare phenomenon in patients on anti-TNF alpha. These cases, associated with the description of a moderate increased risk of developing cutaneous carcinoma under anti-TNF alpha, underscore the need for dermatological follow-up and increased sun protection in patients receiving this treatment.

Veillonella parvula spondylodiscitis.

OBJECTIVES: Veillonella parvula is an anaerobic Gram-negative coccus rarely involved in bone and joint infections. PATIENTS AND METHOD: We report the case of a Veillonella parvula vertebral osteomyelitis (VO) in a female patient without any risk factor. RESULTS: The 35-year-old patient was immunocompetent and presented with Veillonella parvula VO. She was admitted to hospital for inflammatory lower back pain. The discovertebral sample was positive for Veillonella parvula. Literature data on Veillonella VO is scarce. Reported cases usually occurred in immunocompromised patients. Diagnosis delay can be up to four months. Patients are usually afebrile. Outcome with antimicrobial treatment alone is favorable in half of cases. Other patients must undergo surgery. CONCLUSIONS: Veillonella VO may occur in immunocompetent patients and have a clinical spectrum of mechanical lower back pain.

Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography.

OBJECTIVE: To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS). METHODS: CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation. RESULTS: In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years. CONCLUSIONS: Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.

Cost effectiveness of two therapeutic regimens of infliximab in ankylosing spondylitis: economic evaluation within a randomised controlled trial.

OBJECTIVE: To determine the incremental cost-effectiveness ratios (ICERs) of two therapeutic regimens of infliximab for ankylosing spondylitis (AS). METHODS: 230 patients with active AS who were participating in a randomised controlled trial comparing two infliximab infusion modalities-every 6 weeks (Q6) and on demand (DEM)-were included in an economic evaluation within the trial. Data were collected by phone every 3 months for 1 year. Direct and indirect costs were calculated from a payer perspective. Health-related quality of life was assessed with a general health rating scale. ICERs were calculated for one 20% improvement (ASAS20), for one partial remission and for one quality-adjusted life year (QALY) gained. RESULTS: The Q6 regimen was significantly more efficacious than the DEM regimen but also more costly (euro22 388 vs euro17 596; p<0.001), because it required significantly more infliximab infusions per patient (8.4 vs 6.2). The ICERs of the Q6 to DEM regimen were euro15 841 for one ASAS20 response, euro23 296 for one partial remission and euro50 760 for one QALY gained. CONCLUSION: The administration of infliximab every 6 weeks is cost effective as compared with a DEM regimen; however, the ICER is close to the acceptability threshold of euro50 000 for one QALY gained. TRIAL REGISTRATION NUMBER: NCT 00439283.

Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry.

OBJECTIVE: Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. METHODS: We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. RESULTS: We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. CONCLUSION: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open follow-up.

OBJECTIVE: To evaluate the continuation and safety of treatment with infliximab in ankylosing spondylitis (AS) over a 2-yr period. METHODS: This study was an open, observational, 2-yr extension study of an open-label study of three induction infusions of infliximab in refractory AS. The fourth infusion was performed only in case of relapse. Thereafter, infliximab was to be administered as needed according to the rheumatologist's opinion; however, for some patients, infusions were performed systematically. RESULTS: None of the 50 recruited patients was lost to follow-up. Thirteen patients (26%) interrupted their treatment by infliximab: four for inefficacy, seven for adverse events, of which four were for allergic reactions to the infusion, and two for other reasons. For all of the 46 patients who had had three infusions judged efficacious and well tolerated, a fourth infusion was performed because of a flare of the disease, after a mean interval of 20.3+/-9.9 weeks (range 7.3-57.9). Over the 24 months, the mean interval between infusions was 11.6+/-9.0 weeks. This interval was longer when patients were treated only as needed (mean 14.3+/-12.1 weeks) than systematically (mean 9.8+/-5.7 weeks). Side-effects were similar to those noted in shorter-term studies; seven patients suffered serious adverse events. There were no deaths, no malignancies and no tuberculosis. CONCLUSION: This study confirms the long-term treatment continuation of infliximab in AS, and shows an acceptable safety profile. It appears that for some patients the disease can be controlled with long intervals between infusions; these findings warrant further studies.

DNA microarray allows molecular profiling of rheumatoid arthritis and identification of pathophysiological targets.

This study was undertaken to evaluate the possibility to obtain a molecular signature of rheumatoid arthritis (RA) comparatively osteoarthritis (OA), and to lay the bases to develop new diagnostic tools and identify new targets. Microarray technology was used for such an analysis. The gene expression profiles of synovial tissues from patients with confirmed RA, and patients with OA were established and compared. A set of 63 genes was selected, based, more specifically, on their overexpression or underexpression in RA samples compared to OA. Results for six of these genes have been verified by quantitative PCR using both samples identical to those used in the microarray experiments and entirely separate samples. Expression profile of the 48 known genes allowed the correct classification of additional RA and OA patients. Furthermore, the distinct expression of three of the selected genes was also studied by quantitative RT-PCR in cultured synovial cells. Detailed analysis of the expression profile of the selected genes provided evidence for dysregulated biological pathways, pointed out to chromosomal location and revealed novel genes potentially involved in RA. It is proposed that such an approach allows valuable diagnosis/prognostics tools in RA to be established and potential targets for combating the disease to be identified.

Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha.

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with spondyloarthropathy (SpA) treated with infliximab. PATIENTS AND METHODS: 29 patients (six women; 23 men) aged 22-68 years, with persistently active SpA despite a high dose of non-steroidal anti-inflammatory drug and/or treatment with methotrexate or sulfasalazine, were studied. Median duration of disease was 13 years (range 3-30). Twenty five patients were treated with 5 mg/kg and four with 3 mg/kg of infliximab at weeks 0, 2, 6 and then received either no infusion (n=3), or additional infusion of infliximab every other month (n=6), and the remainder received one infusion only in the case of a relapse. Lumbar and femoral BMD was measured by dual energy x ray absorptiometry at baseline and six months later. Serum osteocalcin and urinary deoxypyridinoline were measured in 19 patients at weeks 0, 2, 24, and in 13 patients at all visits. RESULTS: In six months there was a significant increase in BMD at the spine (3.6%, p=0.001), total hip (2.2%, p=0.0012), and trochanter (2.3%, p=0.0012). A trend for increase (1.1%) was observed at the femoral neck. There was an increase in osteocalcin between baseline and week 6 (third infusion)-median 1.45 micro g/l (p=0.013). No change in marker of bone resorption was observed at the same time. There was no change in biochemical markers between baseline and final visits. There was a trend for a correlation between the decrease at six months in erythrocyte sedimentation rate, and lumbar spine BMD change (r(s)=-0.35, p=0.06). CONCLUSION: These data suggest that a benefit of anti-tumour necrosis factor alpha therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells.

Thalidomide in ankylosing spondylitis.

Despite potential side effects dominated by teratogenicity and peripheral neuropathy, thalidomide has recently been used to treat severe ankylosing spondylitis (AS). Over 50 patients have been treated across several 6-12 month open studies. Altogether 68% of the patients improved and the drop-out rate was 19%. Inhibition of NF-kappaB and/or TNFalpha is a putative mechanism for thalidomide efficacy in AS.

Infliximab in spondylarthropathy--influence on bone density.

Osteoporosis is frequently associated with Ankylosing Spondylitis (AS). Bone mineral density (BMD) decreased predominantly in patients with active disease. Moreover, conventional therapy, i.e. NSAID seems to have no influence in the bone loss. It has been suggested that local or systemic inflammatory cytokine release might be implicated in bone loss. Monoclonal antibody to TNFalpha in patients with AS demonstrated significant clinical response with significant reduction in the acute-phase reactants ESR and CRP. We evaluated the changes in bone mineral density (BMD) in patients with Spondylarthropathy (SpA) treated with infliximab (a human/mouse neutralising chimeric monoclonal antibody). We included 29 patients. In 6 months, there was a statistically significant increase in BMD both at the spine and total hip. There was an increase in osteocalcin between baseline and week 6. These data suggest a benefit of anti-TNFalpha therapy on BMD in patients with SpA, may be through an uncoupling effect on bone cells.

Efficacy of infliximab in refractory ankylosing spondylitis: results of a six-month open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a loading regimen of the anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in predominantly axial severe ankylosing spondylitis (AS). METHODS: We enrolled in this study 50 patients (76% males, 87% HLA-B27(+), median age 35 yr, median disease duration 13 yr) with active AS [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >or=30/100 and serum C-reactive protein concentration >or=15 mg/l) despite treatment with a non-steroidal anti-inflammatory drug, and without peripheral arthritis, uveitis or active inflammatory bowel disease. Other disease-modifying anti-rheumatic drugs were discontinued >or=3 months before inclusion and were not allowed during the study. Patients received three infusions of infliximab (5 mg/kg) at weeks 0, 2 and 6 and were monitored clinically and biologically until week 24. RESULTS: Forty-eight patients completed the treatment. In intention-to-treat analysis, all parameters were significantly improved at week 2 and generally reached maximal improvement at week 8. The proportion of responders, defined by a reduction of >or=20% in the global assessment of pain (GAP) or by the AS Assessment Study Group (ASAS 20%) criteria, and the proportion of patients reaching partial remission were 98, 94 and 70% respectively. Relapse, defined as >or=50% loss of maximal GAP improvement, occurred in 73% of completers, with a median delay of 14 weeks after the third infusion. No serious adverse event related to the treatment was observed. CONCLUSIONS: This study confirms, in a large group of severely affected AS patients, the remarkable efficacy of infliximab. Relapse usually occurred after discontinuation of the drug, but almost one-third of completers were still free of relapse 4 months after the last infusion.

Anti-tumour necrosis factor alpha therapy for ankylosing spondylitis: international experience.

The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor alpha (TNFalpha) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFalpha, which have included approximately 300 patients with SpA. Specifically, TNFalpha-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFalpha and other emerging biological agents.

Expression of Fas ligand improves the effect of IL-4 in collagen-induced arthritis.

The present study was aimed at investigating whether the expression of Fas ligand (FasL) by CHO cells transfected with IL-4 (CHO/IL-4) or IL-10 (CHO/IL-10) genes would improve the effect of the cytokine. DBA/ 1 mice immunized with type II collagen were treated with suboptimal doses of transfected CHO cells (a single s. c. injection of 2 x 10(5) cells) around onset of arthritis. Severe collagen-induced arthritis (CIA) developed in the control groups injected with PBS, CHO /beta-galactosidase/FasL, CHO/IL-4 or CHO/IL-10 cells. In contrast, administration of CHO/IL-4/FasL, but not CHO/IL-10/FasL, cells significantly reduced the clinical severity and resulted in rapid and sustained suppressive effect. Amelioration of CIA was not due to a prolonged in vivo secretion of IL-4 since expression of FasL by CHO cells shortened the in vivo survival of the xenogeneic cells. In fact, administration of FasL(+) cells was associated with a decreased proportion of Mac1(+) neutrophils in the blood and an increased expression of myeloperoxidase at the site of engineered cell engraftment. These findings suggest that the mechanism underlying the beneficial effect of IL-4 delivered by cells expressing FasL involves the combination of the anti-inflammatory properties of IL-4 and the apoptosis of Fas(+) Mac1(+) granulocytes participating in the pathogenic process.

Intensified-dose (4 gm/m2) cyclophosphamide and granulocyte colony-stimulating factor administration for hematopoietic stem cell mobilization in refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). METHODS: Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m2) at day 0 followed by G-CSF (5 microg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. RESULTS: For all patients, administration of ID-CYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD34+ cells by positive selection as well as an unselected rescue graft. CONCLUSION: Patients with severe, refractory RA can benefit from ID-CYC. This procedure, followed by G-CSF administration, appears safe and technically suitable. In addition, it allows immediate improvement of RA activity that can occasionally persist beyond 6 months.

[Bone marrow transplantation in the treatment of autoimmune diseases. ISAMAIR Group]. / Les greffes de moelle dans le traitement des maladies auto-immunes. Groupe ISAMAIR.

EXPERIMENTAL BASIS AND CLINICAL OBSERVATIONS: Remission of an autoimmune disease has been observed in certain patients after bone marrow allograft from a healthy donor. Autoimmune disease in the donor can also be transmitted to an unaffected recipient. These phenomena would be hematopoietic-dependent. BONE MARROW ALLOGRAFTS: Indications for the treatment of refractory autoimmune diseases are exceptional due to the related mortality even in patients without malignant hematologic disease. A NEW THERAPEUTIC CONCEPT: Therapeutic intensification, followed with autologous peripheral stem cell grafts, a procedure with a mortality below 3% in 1997, constitutes a therapeutic alternative in these difficult indication concerning severe refractory autoimmune diseases including: sclerodermia, vasculitis, lupus, inflammatory myositis, autoimmune cyopenia.

Concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime-labelled leucocytes and ileocolonoscopy in patients with spondyloarthropathies and without clinical evidence of inflammatory bowel disease.

OBJECTIVE: To study the concordance between abdominal scintigraphy using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocytes (ASTLL) and ileocolonoscopy in patients with spondyloarthropathies (SpA) and without clinical evidence of inflammatory bowel disease (IBD). PATIENTS AND METHODS: Fifteen patients with SpA (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD were studied prospectively with ASTLL and ileocolonoscopy. RESULTS: This cohort consisted of seven men and eight women aged 31.8+/-10.5 yr (18-47) [mean age +/- S.D. (range)] and with a disease duration of 6.0+/-4.4 yr (0.4-15). ASTLL showed abnormal uptake in four patients. Ileocolonoscopy was abnormal in five patients, showing acute inflammatory lesions in one patient with reactive arthritis, undifferentiated chronic inflammatory lesions in two cases, and features indistinguishable from those of Crohn's disease in two cases. ASTLL was negative in two cases in which ileocolonoscopy showed inflammatory lesions and was positive (terminal ileum) in one case with normal ileocolonoscopy. The concordance between the two examinations was statistically significant (kappa = 0.53; P = 0.008). CONCLUSION: ASTLL may be an interesting tool to detect subclinical gut inflammation in patients with SpA.

In vitro differentiation of peripheral blood T cells towards a type 2 phenotype is impaired in rheumatoid arthritis (RA).

We have examined the capacity of peripheral blood T cells from RA patients to be polarized in vitro towards a type 1 (T1) or a type 2 (T2) phenotype. Peripheral blood T cells from RA patients and from healthy donors were primed by 1 week of culture with soluble OKT3 in the presence of polarizing cytokines. The recovered T cells were restimulated and their cytokine secretion profile determined. Priming of T cells from RA patients in the presence of recombinant (r)IL-2 plus rIL-12 induced a shift towards a TI pattern, characterized by increased production of interferon-gamma, that was more pronounced than in the case of healthy donors. Conversely, priming of T cells from RA patients in the presence of IL-4 failed to induce a shift towards a T2 profile after 1 week, whereas it induced T cells from healthy donors to acquire such a profile characterized by heightened production of IL-4, IL-5 and IL-13. However, a T2 polarization profile emerged in T cells from RA patients that were primed in the presence of rIL-4 and subsequently maintained in culture in rIL-2 alone for 1 or 2 additional weeks. We conclude that in vitro differentiation of peripheral T cells towards a type 2 phenotype is impaired in RA. Nevertheless, conditions required to drive peripheral T cells towards a type 2 phenotype were established. Administration of autologous polyclonal T cells expressing a type 2 cytokine secretion profile is proposed as a therapeutic strategy in RA.