The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.

[Lightning strike and lesions outside the brain: Clinical cases and a review of the literature]. / Les atteintes extra-cérébrales de la foudre : vignettes cliniques et revue de la littérature.

INTRODUCTION: Every year, 240,000 people are struck by lightning worldwide, causing injuries leading to significant handicaps. Most of the symptoms involve brain lesions; neuromuscular sequelae and myelopathy are less common. OBSERVATIONS: We describe five cases of patients struck by lightning with various clinical presentations. The first patient presented painful paresthesias in both upper limbs that disappeared 18 months later; the injury was a plexopathy. The second patient developed proximal weakness in the upper-left limb due to a myopathy. Two patients presented with various motor weaknesses in the lower limbs due to motor neuron disease and myelopathy. The last patient had a transient tetraplegy, which resolved in 5minutes; the diagnosis was keraunoparalysis. DISCUSSION: Lightning injuries can have many consequences depending on the different mechanisms involved. The clinical presentation is often due to a very focal lesion without any secondary extension. Motor neuron disease probably results from post-traumatic myelopathy. We discuss the ALS-electrocution association, frequently described in the literature. CONCLUSION: Various peripheral nerve and spinal cord lesions can be seen in lightning strike victims involving myelopathy, motor neuron, muscle and plexus. Clinical syndromes are often atypical but outcome is often favorable.

Fabry disease 'The New Great Imposter': results of the French Observatoire in Internal Medicine Departments (FIMeD).

Fabry disease (FD) is an X-linked lysosomal storage disorder due to α-galactosidase A deficiency. It is associated with a broad range of clinical symptoms, resulting in frequent misdiagnosis and diagnostic delay, which may impact on patient outcomes. This retrospective observational study of 58 FD patients referred to 10 internal medicine departments in France aimed to review differential diagnoses received prior to diagnosis and examines diagnostic delay. The average age at the time of diagnosis was 27.6 years (range: 10-60) and 42.2 years (range: 9-77) among the 23 males and 35 females analyzed, respectively. Most common symptoms that led to FD diagnosis were family history of FD (12 males and 27 females), followed by pain in extremities (10 males and 5 females), and angiokeratoma (8 males and 4 females). Eighteen patients had received alternative diagnoses prior to FD diagnosis, including a female patient with four previous diagnoses. Four case reports are presented, which illustrate the diagnostic 'odyssey' and delayed diagnosis often experienced by patients. Clinicians should consider a diagnosis of FD when presented with a wide range of symptoms, thus helping to shorten the diagnostic delay and facilitating early therapy with enzyme replacement therapy to improve patient outcomes.

Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis.

OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis.

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc. In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng · mL(-1), with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p < 0.001). After a mean ± SD follow-up of 33.7 ± 10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng · mL(-1). The adjusted hazard ratio was 5.36 (95% CI 2.44-11.75; p < 0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population.

BACKGROUND: TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. OBJECTIVE: To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). METHODS: Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel-Haenszel meta-analysis. RESULTS: The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10⁻7), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10⁻8), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10⁻9), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10⁻6) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10⁻5). CONCLUSION: These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.

Impact of glucocorticoid-induced adverse events on adherence in patients receiving long-term systemic glucocorticoid therapy.

BACKGROUND: Factors influencing adherence to long-term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. OBJECTIVE: To evaluate the relationship between glucocorticoid-induced adverse events and therapeutic adherence in patients on long-term glucocorticoid treatment. METHODS: A cross-sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four-item Morisky-Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. RESULTS: A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34-65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8-72); median daily dose 10 mg (IQR 6-20)]. Among these 255 patients, 199 (78%) reported themselves as 'good adherents' and 56 (22%) as 'poor adherents' to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95-0·99, per increasing year; P < 0·01], presence of glucocorticoid-induced epigastralgia (OR 4·02, 95% CI 2·00-8·09; P < 0·01) and presence of glucocorticoid-induced morphological changes (OR 2·49, 95% CI 1·19-5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12-5·26; P = 0·02). CONCLUSIONS: As with other chronic therapies, the presence of glucocorticoid-induced adverse events is associated with an altered self-reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.

Myopathies related to systemic sclerosis: a case-control study of associated clinical and immunological features.

OBJECTIVE: Little is known about systemic sclerosis (SSc)-related myopathy. We aimed to compare the clinical and immunological features of SSc patients with or without associated myopathy. METHODS: Forty SSc patients with myopathy, defined by myalgia or muscle weakness associated with creatine kinase (CK) more than five times the upper limit range or myopathic electromyography (EMG) or abnormal myopathology, were identified from the records of four French hospital centres. For each patient, we selected two SSc controls matched for cutaneous SSc form, sex, age at SSc onset, and disease duration. We performed a case-control study testing clinical and immunological SSc-related features for association with myopathy by conditional logistic regression. RESULTS: Muscle and SSc features of patients with myopathy did not differ significantly among the four centres of origin. Only four (10%) patients with SSc-associated myopathy had anti-polymyositis-scleroderma (PM-Scl) antibodies. Case-control univariate analysis revealed that reduced forced vital capacity (FVC) [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.3-34.9], heart involvement, defined as clinical congestive heart failure, left ventricular ejection fraction (LVEF) < 60%, arrhythmia or conductive abnormalities (OR 2.9, 95% CI 1.3-6.5), and scleroderma renal crisis (OR 3.0, 95% CI 1.3-34.9) were significantly more frequent in patients with myopathy than in controls. Two autoantibodies were more frequent in patients with myopathy: anti-PM-Scl (OR 5.0, 95% CI 1.1-23.9) and anti-RNP (OR 6.9, 95% CI 1.1-64.4). Multivariate analysis retained two variables associated positively with myopathy [reduced FVC (OR 3.1, 95% CI 1.3-9.8) and heart involvement (OR 2.5, 95% CI 1.1-7.1)], while anti-centromere antibodies were associated negatively (OR 0.11, 95% CI 0.03-0.53). CONCLUSION: Heart monitoring of SSc patients with myopathy should be undertaken regularly because of the association of myocardial and skeletal myopathies in such patients.

Is Reynolds syndrome a genetic laminopathy?

Reynolds syndrome is a rare disease associating primary biliary cirrhosis (PBC) and systemic scleroderma (SSc). Although generally considered as an autoimmune disease owing to the presence of typical autoantibodies and to microscopical abnormalities suggesting autoimmunity (lymphoid infiltrate around the biliary ducts and the cutaneous vessels, pericarditis, pleurisy), other causes have been searched for, especially genetic. The discovery of a new mutation in the Lamin receptor B in a French patient suffering from Reynolds syndrome [1] revives this controversy. Laminopathies have a great variety of manifestations, but some are quite comparable with either SSc or PBC, and the new mutation has been found neither in a group of 27 other patients with SSc, nor in 400 normal subjects. After bioinformatics searching, the authors claim that it is plausible that the new mutation is pathogenic. It remains to be shown, however, that this is really the case by testing directly the liver and skin fibroblasts of the patient. Moreover, looking at a series of CBP patients and at a larger SSc sample will be enlightening to appreciate the real value of that discovery.

A descriptive and prognostic study of systemic sclerosis-associated myopathies.

OBJECTIVES: To describe the clinical characteristics and muscle pathological features of patients with systemic sclerosis (SSc) and myopathy and analyse their impact on muscle outcome. METHODS: Thirty-five patients with myopathy and available muscle biopsy were restrospectively investigated from the charts of four hospital centres. RESULTS: Twenty-six (74%) cases had diffuse SSc. The median time from SSc diagnosis was 5 years (range 0-23) at myopathy onset. The main myopathological features were mononuclear inflammation (63%), muscle atrophy (60%), necrosis (59%), regeneration (44%), fibrosis (24%) or microangiopathy (27%). After a median follow-up of 4.4 years, 24 patients (69%) showed complete or partial muscle remission. Only histological muscle inflammation was associated with good muscle prognosis in multivariate analysis (odds ratio 44.7, 95% CI 2.8 to 704.7). Patients without muscle inflammation had a poor response to corticosteroids (38% favourable response vs 90% in patients with inflammation). CONCLUSION: Muscle histopathology is critical in the therapeutic management of SSc-associated myopathy.

Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis.

BACKGROUND AND AIM: Increased alveolar concentration of nitric oxide (CA(NO)) is related to the severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). However, cut-off levels of CA(NO) to rule out, or to rule in, the presence of ILD in individual patients are unknown. We aimed to assess the validity of CA(NO) for the diagnosis of ILD in SSc and to determine the thresholds of CA(NO) that can be used in clinical practice to predict the likelihood of ILD in SSc. METHODS: Lung HRCT scan, PFTs and partitioned exhaled NO measurements were performed in 65 consecutive SSc patients. ILD was diagnosed on pulmonary HRCT according to the presence of ground glass or reticular opacities. Diagnostic performance of CANo for ILD diagnosis was assessed using ROC curves. RESULTS: 38 out of 65 SSc patients had ILD. CA(NO), at a cut-off level of 4.3 ppb, had a sensitivity and specificity for the diagnosis of ILD of 87% (95% CI: 77 to 99) and 59% (95% CI: 41 to 78), respectively. The same cut-off level of CA(NO) could detect impairment of gas exchange with a sensitivity and specificity of 78% (95% CI: 67 to 90) and 73% (95% CI: 46 to 99), respectively. Moreover, ILD could be ruled in (positive predictive value > 95%) when CA(NO) > or = 10.8 ppb, and ruled out C(ANO) values < or = 3.8 ppb (negative predictive value > 95%). CONCLUSION: CA(NO) could be a valid non-invasive biological marker of ILD in SSc, and be of use in clinical practice.

[General practitioners' perception of the impact of corticosteroid-induced adverse events]. / Perception par les médecins généralistes de la gêne induite par les effets indésirables d'une corticothérapie systémique prolongée.

BACKGROUND: General practitioners' perception of the discomfort their patients experience because of corticosteroid-induced adverse events is unknown. METHODS: An observational epidemiological study was conducted in September 2007. Eight hundred and sixty general practitioners belonging to the réseau Sentinelles were asked to complete an electronical questionnaire. The questionnaire aimed to assess their perception of discomfort induced by adverse events induced by a long-term (i.e.,>or=3 months) corticosteroid therapy among their patients. Results were compared with the declaration made by 115 long-term corticosteroid treated patients followed in an internal medicine department. RESULTS: Two hundred and ninety-three general practitioners responded to the questionnaire (response rate: 34%). They were predominantly male (87%). Forty-eight percent of them reported 400 to 600 monthly visits. The mean length of corticosteroid therapy for patients was 44+/-38 months and the mean daily dosage was 15+/-14 mg. They suffered mainly from lupus erythematosus (33%) or giant cell arteritis (15%). The adverse events considered to be the most disturbing by patients were lipodystrophy (25%), followed by weight gain (18%) and neuropsychiatric complaints (16%). Physicians widely overestimated the discomfort caused by weight gain cited as the most disturbing adverse event by 59% of them and underestimated that induced by mood disorders cited as the most disturbing by only 3% of them. CONCLUSION: The discomfort caused by corticosteroid-induced neuropsychiatric adverse events are underestimated by general practitioners.

[DRESS syndrome caused by phenylbutazone]. / DRESS syndrome à la phénylbutazone.

The drug rash with hypereosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity syndrome. We report a 57-year-old woman suffering from a DRESS syndrome 15 days after phenylbutazone exposure. She had a skin eruption, liver involvement and hypereosinophilia. She fully recovered after drug withdrawal.

[Short-term effect of dietary-sodium intake on arterial blood pressure of patients treated with systemic corticosteroids: a prospective, randomised, crossover study]. / Effet à court terme des apports sodés sur la pression artérielle des patients recevant une corticothérapie systémique: étude prospective, randomisée, croisée.

INTRODUCTION: It is unknown if the level of dietary-sodium intake influences blood pressure in patients receiving systemic corticosteroids. METHODS: Randomized, single centre, crossover trial involving patients starting systemic corticosteroid therapy and having initial blood pressure less or equals to 159/99 mm Hg. The first period of sodium regimen was randomized (<3 g/j versus >6 g/j) and each period of sodium regimen lasted 3 weeks. No washout period was performed. Blood pressure was recorded for each patient at inclusion and after 3 weeks and 6 weeks. Moreover, all patients were asked to record on a standardized questionnaire everything they ate during 1 week of each period regimen. Questionnaires were analysed by a dietician for mean daily energy and sodium intakes during each period. Mixed models were used to estimate the relationship between sodium intake and blood pressure variations. RESULTS: Between June 2006 and June 2008, 49 patients were randomized, 24 in group 1 (first period regimen=salt<3g/day; women: 63%; mean age: 56+/-21 years; baseline prednisone dosage: 54+/-19 mg/day) and 25 in group 2 (first period regimen=salt>6g/day; women: 56%; mean age: 60+/-19 years; baseline prednisone dosage: 56+/-16 mg/day). Mean daily salt intakes were 2.5+/-1.8 and 9.3+/-1.9 g/day during the first period and 7.8+/-3.2 and 3.8+/-2.9 g/day during the second period, respectively for group 1 and group 2. Blood pressure variations were not significantly associated with daily salt intakes or with randomisation group. No order effect was evidenced. By comparison with baseline, systolic blood pressure increased by greater than 20 mm Hg at week 6 in five patients (2 in group 1 and 3 in group 2). CONCLUSION: At short-term, sodium intake does not seem to influence blood pressure variations in patients starting systemic corticosteroids therapy.

[Liver infarcts with early HELLP syndrome and probable catastrophic antiphospholipid syndrome]. / Infarctus hépatiques associés à un syndrome HELLP précoce et un probable syndrome catastrophique des antiphospholipides.

INTRODUCTION: Among microangiopathic disorders of pregnancy, catastrophic antiphospholipid syndrome (CAPS) is a maternal and fetal life-threatening disorder. Hepatic involvement of this multi-systemic disorder can be confused with HELLP syndrome, occurring usually later in the course of pregnancy. CASE REPORT: We report a case of probable CAPS with hepatic disease in a pregnant woman at 13 week's gestation, with antiphospholipid syndrome and biological features of HELLP syndrome. Unspecific hepatic imaging, well-described in our case allowed undelayed therapy. CONCLUSION: CAPS and HELLP syndrome, both severe microangiopathic disorders, may be associated. Nosological distinction does not modify treatment strategy, which is a maternal and foetal emergency, but their overlapping requires aggressive and early management.

[Internal medicine physicians' perception of frequency and impact of corticosteroid-induced adverse events]. / Perception par les médecins internistes de la fréquence et de la gêne induite par les effets indésirables d'une corticothérapie systémique prolongée.

INTRODUCTION: Whereas internal medicine physicians frequently prescribe systemic corticosteroids, it is unknown if they assess adequately the frequency and the discomfort caused by corticosteroid-induced adverse events. METHODS: Using an e-mail questionnaire sent to the 813 internal medicine physicians, members of the French National Society of Internal Medicine, we assessed their perception of the frequency and the discomfort induced by the adverse events of long-term (that is, over or at three months) corticosteroid therapy. At the same time, 121 corticosteroid-treated patients, consulting in a department of internal medicine completed an anonymous questionnaire about the frequency and the discomfort caused by the adverse events of their therapy. RESULTS: Three hundred and thirty-six out of 813 internal medicine physicians answered to the questionnaire (response rate: 41%) and 115 of the 121 questionnaires distributed to patients were exploitable. The physicians were predominantly male (71%) working mainly in tertiary centers (53%). The mean length of corticosteroids therapy for patients was 44+/-38 months and the mean daily dosage was 15+/-14mg. Lipodystrophy, trophic skin disorders, neuropsychiatric disorders and insomnia were frequent and reported by more than half of patients. The frequency of neuropsychiatric and skin disorders and of lipodystrophy estimated by practitioners was markedly lower than the frequency reported by patients. If morphological changes (weight-gain and lipodystrophy) were cited by practitioners as the most discomforting adverse event, in agreement with patients' opinion, physicians underestimated the discomfort caused by neuropsychiatric disorders and insomnia. CONCLUSION: Frequency and discomfort caused by corticosteroid-induced neuropsychiatric disorders are underestimated by internal medicine physicians.

[Diagnostic journey of type 1 Gaucher Disease patients: A survey including internists and hematologists]. / Parcours diagnostique des patients atteints de maladie de Gaucher de type 1 : enquête auprès de médecins internistes et hématologues.

INTRODUCTION: Gaucher disease (GD) is a rare genetic lysosomal storage disorder caused by a beta-glucocerebrosidase deficiency and responsible for a lysosomal storage disorder. GD is characterized by haematological, visceral and bone involvements. The aim of this study was to describe the diagnostic journey of type 1 GD patients as well as the role of the internist. METHODS: A retrospective multicentric study involving type 1 GD patients has been conducted in 16 centers, between 2009 and 2011. RESULTS: Fifty-five type 1 GD patients were included, under the care of an internist or an haematologist. They were originally hospitalized in 8 different specialized units. Diagnosis was established by bone-marrow aspiration in 22 patients (40%), by enzymatic assay of glucocerebrosidase activity in 15 patients (27%), and by bone-marrow biopsy in 9 patients (16%). The use of enzymatic assay became more frequent after 1990. The delay between first hospitalization due to GD symptoms and definitive diagnosis was less than one year for 38 patients. Patients with suspected GD were mainly referred to an internist physician. CONCLUSION: GD seems to be better recognized and quickly diagnosed since 1990 in spite of the multiplicity of journeys. The role of the internist seems important.

Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients.

OBJECTIVES: To describe presentation and outcome of patients with scleroderma renal crisis (SRC). METHODS: SRC was defined as rapidly progressive oliguric renal insufficiency and/or rapidly progressive arterial hypertension occurring during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was analysed using multivariate Cox proportional hazards regression models. The risk for developing SRC associated with corticosteroid (CS) exposure during the preceding 1- or 3-month periods was analysed according to a case-crossover design. RESULTS: A total of 50 SSc patients aged 53.3 (14.5) (mean (SD)) years were included in the study. SRC occurred between 1979 and 2003, after a mean (SD) disease duration of 27.7 (49.1) months. A total of 43 (86%) patients had diffuse SSc, 5 (10%) had limited cutaneous SSc and 2 (4%) had SSc sine scleroderma. At the time of SRC, 10 (20%) patients were taking angiotensin converting enzyme inhibitors, and mean creatininaemia was 468 (293) micromol/l. A total of 28 (56%) patients required haemodialysis. In all, 11 patients underwent a renal biopsy, all of them had specific vascular lesions of SRC. Multivariate analyses retained age >53 years and normal blood pressure as independent predictors of decreased dialysis-free survival. Exposure to CS prior to SRC was identified in 30 (60%) patients. The odds ratios for developing SRC associated with CS exposure during the preceding 1- or 3-month periods were 24.1 (95% CI 3.0-193.8) and 17.4 (95% CI 2.1-144.0), respectively. CONCLUSION: SRC remains associated with severe morbidity and mortality. CS might increase the risk of developing SRC. Further studies are needed to confirm these results.