Combined pulmonary fibrosis and emphysema in systemic sclerosis: A syndrome associated with heavy morbidity and mortality.

BACKGROUND: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc). METHODS: In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema. RESULTS: Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10-4), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan-Meier survival analysis) as compared to ILD-SSc controls. CONCLUSIONS: The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

Use of bosentan for digital ulcers related to systemic sclerosis: a real-life retrospective French study of 89 patients treated since specific approval.

OBJECTIVES: Ischaemic digital ulcers (DUs) are a common complication of systemic sclerosis (SSc). This study aimed to characterize patients with SSc and ongoing DUs treated with the endothelin receptor antagonist bosentan in clinical practice in France. METHOD: An observational, retrospective, longitudinal study was conducted in 10 French expert centres. Medical records from randomly selected adult SSc patients who received treatment with bosentan for DU prevention from March 2007 to December 2010 were analysed. The primary objective was to determine the profile of patients at treatment initiation. Secondary objectives were to monitor bosentan dosing, treatment schedule, and reasons for treatment termination. RESULTS: The study included 89 patients (mean age 52 years, 69% female, 44% diffuse cutaneous SSc). At bosentan treatment initiation, the mean duration of Raynaud's phenomenon was 15 ± 12 years, and the mean time since first episode with DU was 6.5 ± 7 years. Most patients had a history of at least two episodes with DUs, separated by < 12 months (61%), and had received intravenous iloprost (63%). Previous DU complications included auto-amputation (8%), surgical amputation (6%), osteitis (6%), and gangrene (4.5%). Active smokers (25%) had a history of significantly more surgical amputation (p = 0.004) and osteitis (p = 0.004) than non-smokers. At least one active DU at bosentan initiation was detected in 82% of patients. Bosentan was used according to prescription guidelines and was well tolerated; six patients (7%) withdrew from treatment because of raised liver enzymes. CONCLUSIONS: Patients treated with bosentan for DU prevention in France have severe, refractory, ongoing ulcerative disease. Active smoking was correlated to a history of DU complications. Tolerance of bosentan was comparable to previous studies.

[Severe cholestatic hepatitis revealing a DRESS syndrome]. / Hépatite cholestatique sévère révélant un Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

INTRODUCTION: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a drug-induced hypersensitivity syndrome, characterized by rash, hyereosinophilia and multiorgan failure, including cytolytic hepatitis. CASE REPORT: A 75-year-old man, treated with amoxicillin/clavulanic acid, presented with jaundice and disabling pruritus associated with severe cholestatic hepatitis, related to a DRESS syndrome. Because of the persistence of cholestasis and the severity of pruritus, a treatment with corticosteroids and plasma exchanges was initiated, allowing a rapid and complete remission. CONCLUSION: Amoxicillin/clavulanic acid, although rarely described in the literature, is a rare cause of DRESS syndrome. Severe cholestatic hepatitis associated with disabling pruritus may be one of the systemic manifestations, with a good prognosis using corticosteroids and plasma exchanges.

[Lymphocytopenia: aetiology and diagnosis, when to think about idiopathic CD4(+) lymphocytopenia?]. / Démarche diagnostique devant une lymphopénie : quand penser à la lymphopénie CD4(+) idiopathique ?

Lymphocytopenia is defined by a lymphocyte count less than 1500/mm(3) in adults and less than 4500/mm(3) in children before the age of 8 months. Lymphocytopenia can be global or selectively affect a peculiar lymphocyte subpopulation. The patient's age, the context as well as the associated clinical manifestations and treatment prescribed must be taken into account in order to identify the etiology of lymphocytopenia. In adults, lymphocytopenia can be caused by: (1) insufficient thymic output (primary immune deficiencies, corticosteroid treatment, zinc deficiency, etc.), (2) increased lymphocyte catabolism (radiotherapy, chemotherapy, immunosuppressant, HIV infection, systemic lupus, etc.), (3) modified lymphocyte distribution (viral infections, septic shock, extensive burns, splenomegaly, granulomatosis, etc.), (4) multifactorial or unknown etiology (end-stage renal disease, lymphoid malignancies, solid tumor, ethnicity, etc.). In children, in addition to these etiologies, other immune deficiencies may be responsible for severe lymphocytopenia (thymocytes apoptosis, cytokine deficiencies, altered B-cell and T-cell receptor synthesis, signal transduction and cellular interactions deficiencies). Idiopathic CD4(+) lymphocytopenia is a rare disorder. It is defined by a persisting lymphocyte CD4(+) count less or equal to 300/mm(3) or less or equal to 20% of total lymphocytes in the absence of alternative diagnosis. Clinical symptoms can be absent or include opportunistic infections, auto-immune manifestations, lymphoma or solid tumors. Treatment is similar to that of HIV-infected patients and sometimes relies on specific immunotherapy even though clinical benefit has not been evaluated.

Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension.

OBJECTIVE: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by obstruction of small pulmonary veins. Pulmonary venous involvement has been reported in pathologic assessment of patients with systemic sclerosis (SSc) presenting with precapillary PH. High-resolution computed tomography (HRCT) of the chest is a noninvasive diagnostic tool used to screen for PVOD. No HRCT data are available on SSc patients with precapillary PH. We undertook this study to evaluate the frequency and effect on prognosis of HRCT signs of PVOD in SSc patients with precapillary PH. METHODS: We reviewed chest HRCT data from 26 SSc patients with precapillary PH and 28 SSc patients without pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD). RESULTS: The radiographic triad of HRCT signs of PVOD (lymph node enlargement [57.7% versus 3.6%], centrilobular ground-glass opacities [46.2% versus 10.7%], and septal lines [88.5% versus 7.1%]) was significantly more frequent in SSc patients with precapillary PH than in SSc patients without PAH or ILD (all P < 0.005). Indeed, 61.5% of SSc patients with precapillary PH had ≥ 2 of these signs. Cardiomegaly (P < 0.0001), pulmonary artery enlargement (P < 0.0001), and pericardial effusion (P < 0.0005) were also significantly more frequent in SSc patients with precapillary PH. Pulmonary venous involvement was histologically confirmed in 2 patients with radiographic signs of PVOD. The presence of ≥ 2 radiographic signs of PVOD was associated with the occurrence of pulmonary edema after initiation of PAH-specific therapy (in 8 of 16 patients) and with more rapid progression from diagnosis of PH to death. CONCLUSION: HRCT signs of PVOD are frequently observed in SSc patients with precapillary PH, correlated with histologic assessment, and were associated with a high risk of pulmonary edema.

[Complaints, needs of patients with systemic sclerosis: a better understanding for a better care]. / Plaintes et besoins des patients atteints de sclérodermie systémique : une meilleure connaissance afin d'améliorer le suivi.

PURPOSE: Systemic sclerosis (ScS) is very heterogeneous in its clinical presentation and its therapeutic care is not codified. A better knowledge of the patients' needs and complaints could improve the patient educational strategies and their global care. METHODS: A self-administered questionnaire aimed to the ScS patient was developed by subspecialty physicians and nurses involved in patient education. It was a cross-sectional study that also included several validated scales: the health control locus scale, the Mactar, HAD and sHAQ scales. RESULTS: One hundred and eight patients (91 women; 18 limited ScS, 71 limited cutaneous ScS, 19 diffuse ScS) filled in the questionnaires. Fatigue was the main complaint in all types of ScS, independently of the ScS type. The aesthetic discomfort mentioned by the patients suffering from cutaneous sclerosis or from telangectasia was important and reached 52±33mm on a 100-mm visual scale. It was more common in the patients presenting a diffuse form of the illness but the difference did not reach a statistical significance (P=0.06). Twenty-seven percent of the patients said they were very or extremely worried because of the degradation of their physical appearance. The functional discomfort linked to the cutaneous sclerosis was rated 50±32mm on a 100-mm visual scale. The intensity of the pain, the importance of the functional discomfort linked to the sclerosis and the intensity of the dyspnea were correlated to the sHAQ (P<0.001). Patients having more frequent recurrent digital ulcers had higher sHAQ scores (P=0.04). The repercussions on the professional life were linked to fatigue first, to the Raynaud's syndrome and to arthralgia. The repercussions on the personal life were mainly linked to the fatigue, the pain and the dyspnea. The patients' compliance was good. CONCLUSION: Fatigue, pain, dyspnea and discomfort linked to sclerosis are major chronic symptoms of the patients with ScS. Identifying the needs and complaints of the patients with ScS should help to improve their care by implementation of an educational program.

Impact of systemic sclerosis on occupational and professional activity with attention to patients with digital ulcers.

OBJECTIVE: To evaluate the impact of systemic sclerosis (SSc; scleroderma) and digital ulcers (DUs) on daily living and professional activities. METHODS: We prospectively evaluated 189 SSc patients for employment status and disability during meetings of the French SSc patient association (n=86, 45.5%) or during hospitalization (n=103, 54.5%). RESULTS: Seventy-eight (41.2%) patients had diffuse SSc. The mean±SD age was 54±13 years, and the mean±SD disease duration was 9.3±8.4 years at the time of evaluation. Sixty (31.7%) patients had at least one DU. Assessed using the Health Assessment Questionnaire (mean±SD 1.12±0.79 versus 1.39±0.84; P=0.001), the Cochin Hand Function Scale (mean±SD 20.2±18.3 versus 27.8±19.1; P<0.0001), and the Hospital Anxiety Scale (mean±SD 9.9±5 versus 8.5±4.2; P=0.04), global disability, hand disability, and anxiety, respectively, were significantly higher in patients with DUs than in others. Most patients reported a limitation in daily activities related to SSc, as assessed by a daily activity limitation scale (mean±SD 4.4±2.9) and an increased need for help in the home. Patients reported needing mean±SD 4±13.5 hours per month of paid household help related to SSc and mean±SD 1.5±10 hours per month related to DUs, with significant differences between patients with or without DUs (P=0.004). Among the 113 patients in the workforce, 67 (59.3%) were employed, 42 (37.2%) were employed full time, 36 (31.8%) received full disability pension, and 27 (23.9%) were on sick leave, with no difference between patients with or without DUs. CONCLUSION: SSc has a significant impact on activities of daily living and work disability. The need for external home help and disability are increased for those patients with DUs.

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.

Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease.

OBJECTIVE: To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients. PATIENTS AND METHODS: In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against alpha-enolase from Saccharomyces cerevisiae and recombinant human (rHu) alpha-enolase, respectively, on ELISA. RESULTS: In the first part, alpha-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae alpha-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu alpha-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae alpha-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu alpha-enolase testing. CONCLUSION: In SSc, AFA recognise alpha-enolase and are associated with ILD and antitopoisomerase antibodies.

Impact of digital ulcers on disability and health-related quality of life in systemic sclerosis.

OBJECTIVE: To assess the impact of digital ulcers (DUs) on disability and health-related quality of life (HRQoL) in systemic sclerosis (SSc). METHODS: Two hundred and thirteen patients with SSc were evaluated at four annual meetings of a patient society between 2004 and 2007 (n = 177) or during hospital stay (n = 36). HRQoL was assessed by the SF-36, global disability by the health assessment questionnaire (HAQ), hand disability by the Cochin Hand Function Scale (CHFS) and global hand and wrist mobility by the Kapandji index. RESULTS: Sixty-seven patients (31.4%) had at least one DU at the time of evaluation. Patients with DUs showed significantly more pitting scars (p<0.001) and calcinosis (p<0.0001) than others. Patients with DU had significantly greater HAQ (mean (SD) 1.218 (0.723) vs 0.930 (0.717), p = 0.008), CHFS (mean (SD) 27.38 (20.68) vs 16.73 (18.19), p<0.0001) and aesthetic prejudice (mean (SD) 6.1 (2.2) vs 3.9 (2.5), p<0.0001) scores than others. Hand and wrist mobility were significantly diminished in patients with DU (mean (SD) Kapandji score 75.3 (22.8) vs 81.7 (19.2), p<0.0001). The presence of a DU did not significantly alter the physical component but influenced the mental component (mean (SD) 43.38 (12.53) vs 39.58 (9.54), p = 0.026) of the SF36. CONCLUSION: Patients with SSc with DUs have reduced wrist and hand mobility, increased global and hand disabilities and decreased mental component of HRQoL.

Factors influencing influenza-vaccination in adults under immunosuppressive therapy for a systemic inflammatory disease.

OBJECTIVE: The aim of this study was to evaluate flu vaccination rates and influencing factors in patients with systemic inflammatory diseases. METHODS: All patients presenting with a systemic inflammatory disease and taking immunosuppressants, who were hospitalized or had consulted in our internal medicine department between January 2 and 31, 2006, were included in the study. The information concerning flu vaccination was collected with a standardized form. RESULTS: One hundred and thirty-seven patients (mean age 53.1+/-17.6years; 40 [29%] male patients) were included: 39 (28%) had received flu vaccination in 2005 including 14 (16.7%) of the 84 patients with no other indication for flu vaccination than IS-induced immunodepression and 25 (47.2%) of the 53 patients with other flu vaccination indication(s) (p<0.001). The most frequent reasons for non-vaccination were: absence of physician recommendation (58%), fear of adverse effects (35%) and concern on vaccine clinical effectiveness (5%). The vaccination rate was significantly higher (49%) among patients who remembered having received a voucher from the French National Health Insurance Agency versus 18% among those who did not (OR=4.2 [95%CI, 1.92-9.19] p<0.05). This correlation remained significant after adjustment for confounding factors in a logistic regression model. CONCLUSION: Influenza-vaccination coverage is low in patients receiving immunosuppressive therapy for systemic inflammatory diseases. We have to increase the influenza-vaccination coverage in this population.

Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients.

OBJECTIVE: To characterise major infectious complications and analyse potential risk factors in patients with Wegener granulomatosis (WG). METHODS: Data from 113 patients with WG (69 male) followed at least once between January 1984 and March 2006 in our internal medicine department, were analysed retrospectively. RESULTS: A total of 35 patients (mean (SD) age at WG diagnosis: 50.2 (13.05) years) developed 53 major infections. Infections were: bronchopneumonias (n = 19), herpes zoster recurrences (n = 9), cellulitis (n = 4), prostatitis (n = 4), spondylodiscitis and septic arthritis (n = 3), digestive tract infections (n = 2), Enterococcus faecalis or Staphylococcus aureus septicaemia (n = 2), viral hepatitis B reactivations (n = 2), post transfusion HIV infection with fatal cerebral toxoplasmosis, oesophageal candidiasis, disseminated herpes simplex and cytomegalovirus infection, cytomegalovirus retinitis, herpetic keratitis, herpetic stomatitis, Serratia sp. node suppuration and fever resolving under broad spectrum antibiotics (n = 1 each). Half of the major infectious episodes occurred within 3 years after WG diagnosis. Eight (7%) patients died, with two (2%) infection-related deaths. Patients diagnosed with WG before 1996 had a significantly higher rate of infection than those diagnosed later (48% vs 24%, p = 0.02). Cyclophosphamide and corticosteroids were independently associated with significantly higher risk of major infection (p<0.05 and <0.001, respectively). All patients treated since 1993 received antipneumocystosis prophylaxis. CONCLUSION: Cyclophosphamide and corticosteroids were associated with higher risk of infection. Despite systematic cotrimoxazole prophylaxis, major infections, mostly bronchopneumonias and herpes zoster recurrences, were still common in the course of WG.

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.

Osteomalacia revealing celiac disease and primary biliary cirrhosis-related Fanconi syndrome in a patient with systemic sclerosis.

Systemic sclerosis (SSc) may affect the gastrointestinal tract and cause very rarely malabsorption syndrome related to bacterial overgrowth. Malabsorption syndrome may be responsible for weight loss, diarrhea, osteomalacia, and iron and vitamins deficiency. We report the case of a SSc patient who developed osteomalacia caused by the combination of two exceptional conditions in the setting of SSc: celiac disease (CD) and primary biliary cirrhosis (PBC)-related Fanconi syndrome. Oral prednisone with angiotensin-converting enzyme inhibitors, was initiated because of active lesions of tubulitis, and led to the complete regression of bone pains, and by the improvement of renal function and regression of the features of proximal tubulopathy. Thus, in the presence of vitamin deficiencies in a patient with SSc, together with a search for malabsorption syndrome secondary to bacterial overgrowth, CD and/or PBC-associated Fanconi syndrome should be investigated.

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.

[Interstitial lung disease in systemic sclerosis]. / Pneumopathie infiltrante diffuse de la sclérodermie systémique.

INTRODUCTION: Interstitial lung diseases (ILD) in systemic sclerosis (SSc) are mainly encountered in patients with diffuse disease although they may occur less frequently in patients with limited cutaneous disease. BACKGROUND: In SSc early detection of ILD should be achieved by high resolution computed tomography and pulmonary function tests, including measurement of DLCO. In total up to 75% of patients with SSc develop ILD but it is progressive in only a minority of patients. Unlike idiopathic ILD, SSc associated ILD corresponds to non-specific interstitial pneumonia rather than usual interstitial pneumonia in the majority of cases. This explains the better prognosis of SSc associated ILD compared with idiopathic ILD. Nevertheless ILD represents one of the two main causes of death in SSc. VIEWPOINT: The treatment of SSc associated ILD is not well established. Anti-fibrosing treatments have failed to demonstrate benefit and cyclophosphamide, which has been used for about 15 years in the treatment of this condition, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. CONCLUSION: A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily, but this remains to be confirmed.

Development and validation of a scale for mouth handicap in systemic sclerosis: the Mouth Handicap in Systemic Sclerosis scale.

OBJECTIVE: To develop and assess the reliability and construct validity of a scale assessing disability involving the mouth in systemic sclerosis (SSc). METHODS: 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. RESULTS: 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. CONCLUSION: 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.