[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis.

OBJECTIVE: To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). METHODS: We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. RESULTS: Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. CONCLUSION: This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

Renal and overall outcomes of double-positive (ANCA and anti-GBM antibodies) patients compared to ANCA-associated vasculitis patients with severe renal involvement: A multicenter retrospective study with systematic renal pathology analysis.

OBJECTIVE: Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement. METHOD: This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 µmol/L), all with biopsy-proven nephropathy. RESULTS: All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 µmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients. CONCLUSION: Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.

Schnitzler syndrome: validation and applicability of diagnostic criteria in real-life patients.

BACKGROUND: Schnitzler syndrome is characterized by an urticarial rash, a monoclonal gammopathy, and clinical, histological, and biological signs of neutrophil-mediated inflammation. The aim of this study was to assess the applicability and validity of the existing diagnostic criteria in real-life patients. METHODS: This multicentric study was conducted between 2009 and 2014 in 14 hospitals in which patients with Schnitzler syndrome or controls with related disorders were followed up. We compared the sensitivities and specificities and calculated the positive and negative predictive values of the Lipsker and of the Strasbourg criteria for the patients with Schnitzler syndrome and for the controls. We included 42 patients with Schnitzler syndrome, 12 with adult-onset Still's disease, 7 with cryopyrin-associated periodic disease, 9 with Waldenström disease, and 10 with chronic spontaneous urticaria. RESULTS: All patients with Schnitzler syndrome met the Lipsker criteria. According to the Strasbourg criteria, 34 patients had definite Schnitzler syndrome, five had probable Schnitzler syndrome, and three did not meet the criteria. One control met the Lipsker criteria and had probable Schnitzler syndrome according to the Strasbourg criteria. Sensitivity and specificity of the Lipsker criteria were 100% and 97%, respectively. For the Strasbourg criteria, sensitivity for definite and probable diagnosis was 81% and 93%, respectively, with a corresponding specificity of 100% and 97%. CONCLUSION: Diagnostic criteria currently in use to diagnose Schnitzler syndrome are reliable. More investigations must be done to attest their efficiency in patients with recent-onset manifestations.

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

PURPOSE: Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. METHODS: Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'étude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. RESULTS: The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. CONCLUSIONS: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.

Tobacco differentially affects the clinical-biological phenotypes of ANCA-associated vasculitides.

OBJECTIVES: To describe the clinical-biological phenotype of ANCA-associated vasculitides (AAV) according to tobacco consumption. METHODS: We conducted a descriptive study to describe that phenotype at diagnosis according to tobacco use. AAV patients entered in the French Vasculitis Study Group database with data on smoking habits were analysed. The clinical-biological phenotypes at diagnosis were compared according to current tobacco use (current smokers) or not (including previous and never smokers). RESULTS: AAV diagnoses were: granulomatosis with polyangiitis (GPA) for 583 (50%), eosinophilic granulomatosis with polyangiitis (EGPA) for 326 (28%) and microscopic polyangiitis (MPA) for 256 (22%). Among them, 973 patients (84%) never smoked, 116 (10%) were previous smokers and only 76 (6%) were current smokers. Current smokers were younger age (p=0.01), male gender (p=0.004), less frequently EGPA (p=0.017) and MPA (p=0.036), and had less frequent kidney involvement (p=0.10). Among GPA patients, current smokers, compared to non-current smokers, were younger age (p=0.02), male gender (p=0.08), more frequent skin involvement (p=0.03) and less frequent ENT involvement (p=0.06). Among EGPA patients, current smokers, compared to non-current smokers, were also younger (p=0.028) and had less frequent constitutional symptoms (p=0.02), arthralgias (p=0.04), renal involvement (p=0.025) and MPO-ANCA (p=0.02). Finally, analysis of MPA patients was impossible because only 6 (2%) were current smokers. CONCLUSIONS: These results suggest that tobacco use could differentially affect GPA and EGPA clinical-biological phenotypes, and support the role of environmental exposures in AAV development and its phenotype.

European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: a complete picture of primary Sjögren's syndrome patients.

OBJECTIVE: The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS. METHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sjögren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained. RESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both). CONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. Since these 2 facets weakly overlap, one should identify which of both components is the main target of the treatment to test, when designing clinical trials in primary SS.

Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: Results from the AutoImmunity and Rituximab Registry.

OBJECTIVE: Rituximab improves articular symptoms in rheumatoid arthritis (RA) and it recently has been shown to be an effective induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis. We assessed the efficacy and safety of rituximab in a real-life clinical setting among patients with systemic rheumatoid vasculitis (SRV). METHODS: We analyzed data from the AutoImmunity and Rituximab registry, which includes patients with autoimmune diseases treated with rituximab. RESULTS: Of the 1,994 patients with RA enrolled in the registry, 17 were treated with rituximab for active SRV. At baseline, the mean Birmingham Vasculitis Activity Score for RA (BVAS/RA) was 9.6, with a mean prednisone dosage of 19.2 mg/day. After 6 months of rituximab therapy, 12 patients (71%) achieved complete remission of their vasculitis, 4 had a partial response, and 1 died with uncontrolled vasculitis. Mean BVAS/RA was reduced to 0.6 and mean prednisone dosage to 9.7 mg/day. At 12 months, 14 patients (82%) were in sustained complete remission. Severe infection occurred in 3 patients, corresponding to a 6.4 per 100 patient-years rate. In the 6 patients who received further rituximab as maintenance therapy between months 6 and 12, no relapse of vasculitis was observed. However, among the 9 patients who did not, a relapse was observed in 3 patients who were treated with methotrexate alone. Remission was reestablished by reintroducing rituximab in 2 cases. CONCLUSION: Complete remission of SRV was achieved in nearly three-fourths of patients receiving rituximab in daily practice, with a significant decrease in daily prednisone dosage and an acceptable toxicity profile. Rituximab represents a suitable therapeutic option to induce remission in SRV, but maintenance therapy seems to be necessary.

[Thoraco-abdominal aortitis in ankylosing spondylitis: a case report and review of literature]. / Aortite thoraco-abdominale au cours d'une spondylarthrite ankylosante: un nouveau cas et revue de la littérature.

UNLABELLED: We report a case of aortitis in a patient with ankylosing spondylitis revealed by an unexplained persistent inflammation. CASE STUDY: The diagnosis of ankylosing spondylitis was retained in a 64-year-old woman suffering from inflammatory back and neck pain combined with buttock pain relieved by anti-inflammatory drugs (NSAIDs) since 2004 and more recent bilateral heel pain in the morning since 2006; sacroiliitis was grade 3 on the right and grade 2 on the left (modified New-York criteria). The patient had remained asymptomatic from April 2006 to 2007 with NSAID as needed. Nevertheless, biological inflammation persisted: erythrocyte sedimentation rate 44 to 55 mm/h, activated protein C 34 to 90 mg/L. Complementary examinations are negative: bilateral temporal artery biopsy, endoscopy with duodenal biopsy looking for Tropheryma whipplei. The thoraco-abdominal and pelvic CT scan revealed aortitis extending from the abdominal aorta to the iliac axis. Treatment with prednisone 0.5 mg/kg was started to decrease the inflammatory aortitis. DISCUSSION: The most "classical" cardiovascular damage observed in spondylitis is aortic insufficiency and conduction disturbances. The first cases of aortitis were reported in 1958. CONCLUSION: Inflammatory vascular disease should be evoked as a possible diagnosis in patients with ankylosing spondylitis the presenting an unexplained biological inflammation (ESR and CRP).

Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry.

BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors. METHODS: A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease. RESULTS: 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION: Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use >10 mg/day are independently associated with OI.

STAT4 is a confirmed genetic risk factor for Sjögren's syndrome and could be involved in type 1 interferon pathway signaling.

Signal transducer and activator of transcription 4 (STAT4) is a transcription factor mainly activated by interleukin 12, which promotes the secretion of type 2 interferon (IFN) by T-helper 1 cells. We assessed the association of STAT4 gene polymorphism and primary Sjögren's syndrome (pSS) and its functional relevance. We analyzed STAT4 rs7582694 polymorphism in an exploratory cohort of 186 pSS patients and 152 controls, and in a replication cohort of 192 pSS patients and 483 controls, all Caucasian. mRNA levels of STAT4alpha, STAT4beta, STAT1, and the type 1 IFN-induced genes PKR, MX1 and IFITM1 were assessed in peripheral blood mononuclear cells (PBMCs) from 30 pSS patients. STAT4 rs7582694 C allele was associated with pSS in both cohorts (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.27-1.93, P=2.3 x 10(-5)). The association was increased for homozygous subjects, which suggests a recessive effect of the STAT4 at-risk allele. STAT4alpha, STAT4beta and STAT1 mRNA levels in PBMCs were not significantly associated with rs7582694 genotypes, however the mRNA levels of STAT4alpha and type 1 IFN-induced genes were strongly correlated: PKR (P=4 x 10(-3), r=0.51), MX1 (P=2 x 10(-4), r=0.63) and IFITM1 (P=8 x 10(-3), r=0.47), suggesting that STAT4 might be involved in not only type 2 IFN production but also in type 1 IFN-mediated effects.

[Whipple's disease]. / Maladie de Whipple.

Whipple's disease is a chronic, multisystemic, curable, bacterial infection that usually affects middle-aged men. It has a wide range of clinical manifestations. In the historical presentation, weight loss and diarrhoea are the most common symptoms and are preceded in three-quarters of cases by arthritis for a mean of six years. Long-term, unexplained, seronegative oligoarthritis or polyarthritis of large joints with a palindromic or relapsing course is typical. In most patients, periodic acid-Schiff staining of proximal small bowel biopsy specimens reveals inclusions within the macrophages, corresponding to bacterial structures. However, patients may have no gastrointestinal symptoms, negative jejunum biopsy results and even negative PCR tests. Even in the absence of gastrointestinal symptoms, Whipple's disease should be considered in case of negative blood culture endocarditis, unexplained central neurological manifestations or unexplained arthritis. Identification of the causative bacterium, Tropheryma whipplei, has led to the development of PCR as a diagnostic tool, particularly useful in patients in the early stages of the disease or with atypical disease. The recent cultivation of T. whipplei and the complete sequencing of its genome should improve our understanding and treatment of the disease. The future development of an assay for detection of specific antibodies in the serum and generalization of the immunohistochemical detection of antigenic bacterial structures may allow earlier diagnosis, thereby preventing the development of the severe late systemic and sometimes fatal forms of the disease.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Lyme meningoradiculitis: prospective evaluation of biological diagnosis methods.

The symptoms of Lyme meningoradiculitis and the value of biological examinations in an endemic area were determined in a prospective study in which data were collected on all patients consecutively hospitalised for Lyme meningoradiculitis at our institution during an 18-month period. Specific antibody titres in the serum and cerebrospinal fluid (CSF) were determined by Vidas enzyme-linked-immunosorbent-assay (IgG + IgM), Dade-Behring enzyme immunoassay (EIA) (IgM; IgG) and Western blot analysis (IgG). We also searched for Borrelia burgdorferi in the CSF by PCR analysis and following culture on a specific medium. A control group was recruited, consisting of 16 consecutive patients who had been referred during the same period with suspected but not confirmed Lyme meningoradiculitis. Eleven patients were included. Borrelia EIA of the serum revealed that 40% of the patients had both elevated specific IgM titres and intrathecal synthesis of specific IgG; 40% of the patients was negative for IgM but had isolated intrathecal synthesis of IgG; 20% of the patients had elevated specific IgM titres without intrathecal synthesis of IgG. PCR analysis and the CSF culture were positive in one case only (B. garinii). The results of this study highlight the importance of systematic serological testing for B. burgdorferi in the CSF in the case of early neuroborreliosis suspicion, even in the absence of IgM serum antibodies, which was the case in 40% of the patients in the present study. Nevertheless, intrathecal anti-B. burgdorferi IgG synthesis, which remains the "gold standard" for the diagnosis of neuroborreliosis, was not detectable in 20% of the patients for whom diagnosis was subsequently confirmed by demonstration of specific serum IgM.

[Non antibiotic treatments of Lyme borreliosis]. / Les traitements non antibiotiques de la borréliose de Lyme.

Non-antibiotic treatment of Lyme borreliosis is only indicated in a few specific clinical situations. In chronic Lyme arthritis, intra-articular steroids are useful to immediately relieve symptomatic joint effusion. Nevertheless, 4 studies with weak methodological evidence were convergent enough to recommend not proposing intra-articular injection before or even immediately after antibiotic treatment. The injection can only be recommended in the treatment of patients whose joint effusion persists despite 2 courses of oral antibiotherapy or one course of IV antibiotherapy. For some experts, the injection can only be made after negative PCR assessment of the joint fluid for spirochetes. This recommendation, although logical, has never been evaluated. Radiation synovectomy may be indicated in persistent synovitis after antibiotherapy and before surgical synovectomy. Further studies are mandatory to confirm the role of radiation synovectomy in the local therapy. Arthroscopic synovectomy can reduce the period of joint inflammation when persistent synovitis is associated with significant pain or limited function. Several experts recommend using the procedure only if synovitis persists after 2 months of antibiotherapy and a negative PCR joint fluid assessment. Non-steroidal anti-inflammatory drugs are often prescribed for their symptomatic effects. Experimental data is consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme's disease. In post Lyme's disease syndrome, patient complaints may lead to a multidisciplinary therapeutic management and the use of neuro-psychiatric drugs.

Thromboangiitis obliterans or Buerger's disease: challenges for the rheumatologist.

Thromboangiitis obliterans (Buerger's disease)--a type of vasculitis in young, mostly male subjects--remains strangely linked to smoking, which determines its occurrence, progression and prognosis by currently unknown mechanisms. It affects the small and medium-sized arteries and veins of the limbs. Despite the usual absence of systemic signs and symptoms, initially intermittent arthritis, even if not observed in all cases, confer on this disease the status of a systemic vasculitis. Diagnosis requires the elimination of many other diseases. The severity of the disease lies in the need for amputation in more than a quarter of all patients. Complete cessation of smoking remains the cornerstone of therapy. Local care is the second essential element of treatment. Prostacycline analogues can be used to help the patient through critical ischaemia. Blockade with antagonists of cannabinoid or endothelin receptors and the use of gene- or cell-based therapy to induce therapeutic angiogenesis have opened up new possibilities for treatment.

Effects of corticosteroids and immunosuppressors on idiopathic inflammatory myopathy related myocarditis evaluated by magnetic resonance imaging.

BACKGROUND: Cardiac involvement in idiopathic inflammatory myopathy has been recognised as an important prognostic factor, but treatment remains empirical. OBJECTIVE: To investigate the effects of corticosteroids and immunosuppressors on myocarditis in patients with inflammatory myopathies. METHODS: Patients with inflammatory myositis of recent onset who had not received treatment were evaluated for associated myocarditis by magnetic resonance imaging (MRI) and reinvestigated after treatment with high dose corticosteroids and immunosuppressors. RESULTS: Four patients with histologically proven myositis were included. Two patients with polymyositis had cardiac clinical symptoms. Two other patients with dermatomyositis and diffuse cutaneous systemic sclerosis-polymyositis overlap syndrome were asymptomatic. In three cases the usual conventional screening tests were normal. For all patients an area of contrast enhancement and hypokinesia detected by cardiac MRI was markedly reduced after treatment with corticosteroids and immunosuppressors for 6 months. CONCLUSION: Treatment with intravenous methylprednisolone followed by prednisone and immunosuppressive therapy seems to be effective for treating myocardial involvement in patients with idiopathic inflammatory myopathies, either alone or presenting as overlap syndromes. Cardiovascular MRI is a non-invasive technique that may be a powerful tool for diagnosis and monitoring of myocardial inflammation in this setting.

The usefulness of bone remodelling markers in predicting the efficacy of pamidronate treatment in SAPHO syndrome.

OBJECTIVES: Pamidronate has recently been used in SAPHO syndrome due to its anti-osteoclastic effect. The aim of this study is to determine the usefulness of bone remodelling markers for determining the efficacy of pamidronate treatment. METHODS: Thirteen patients with SAPHO syndrome were treated with pamidronate. The treatment evaluation was done using a visual analogue scale (VAS) and also erythrocyte sedimentation rate, C-reactive protein, serum crosslaps (sCTX) and osteocalcin initially and after 3 months. A relevant clinical response was defined as an improvement in VAS of at least 40%. RESULTS: At 3 months, 7 of 13 patients had a good clinical response, as previously defined. Five of the seven patients maintained the good response over 6 months. Before the first perfusion 6 of the 13 patients had increased sCTX (upper 3250 pmol/l). In this small cohort we tried to analyse whether the increase in bone remodelling markers was associated with a good clinical response. In the responders group the mean levels of sCTX and osteocalcin at baseline were 6783.17 and 24.66, respectively, and in the non-responders group the levels were 2152 and 11.8, respectively. There was a significant difference in sCTX between the responders and the non-responders (P = 0.0044). CONCLUSION: Infusion of pamidronate is effective in SAPHO in some patients. Increased sCTX might be a prognostic marker for a good clinical response but results have to be confirmed in a larger cohort.