Does oral appliance efficacy in treating obstructive sleep apnea depend on the appliance specialist's experience?

PURPOSE: In France, oral appliances (OAs) are the first-line treatment for moderate and second-line treatment for severe obstructive sleep apnea-hypopnea syndrome. In general, the sleep specialist refers his/her patient to the appliance specialist for the impressions and the fitting. However, is there a relationship between the volume of activity of the appliance specialist and the efficacy of this device? METHODS: Our unit includes seven appliance otolaryngology specialists whose activities are highly variable (number of patients varying by a factor of almost 10). Data from a prospective follow-up registry of patients treated with an OA for moderate and severe obstructive sleep apnea-hypopnea syndrome were studied, and differences in outcomes between practitioners in the team were sought. RESULTS: Among 859 patients, OAs significantly reduced the apnea-hypopnea index. Even if the patients were not completely comparable from one practitioner to another, there was a significant heterogeneity in efficacy (complete or partial response of the apnea-hypopnea index and failure of OAs) between practitioners (p = 0.0038; 0.0011; 0.0007 respectively), with better results in practitioners with a higher level of OA activity. CONCLUSION: The findings suggest that it may be preferable to refer patients to OA practitioners who see a higher volume of patients with moderate or severe obstructive sleep apnea-hypopnea syndrome treated with an OA.

Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care.

OBJECTIVE: To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). METHODS: Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5-6. Incidences of adverse events (AEs) were reported for the entire study period. RESULTS: The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%).The mean (SD) change in SDI was +0.2 (0.48) at study years 5-6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis).Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common. CONCLUSION: Patients with SLE treated with long-term belimumab plus SoC had a low incidence of organ damage accrual and no unexpected AEs. High-risk patients with pre-existing organ damage also had low accrual, suggesting a favorable effect on future damage development.

Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA.

OBJECTIVE: To examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting. METHODS: This observational cohort study was conducted in US clinical practices. Rheumatologists (n=92) identified adults with SLE who had received ≥8 infusions of belimumab plus standard of care (SoC). Physicians assessed disease outcomes at 6-month intervals using patient medical charts, for up to 24 months. The primary outcome was physician-assessed change in SLE disease. Other outcomes included change in steroid use, laboratory tests and healthcare resource utilisation (HCRU). RESULTS: Of 501 patients (intent-to-treat population (ITT)), 446 were female, mean age was 43.3 years and 98% had moderate/severe disease activity at baseline (first dose of belimumab). Data for 277 patients who completed 24 months of belimumab treatment were available. Among the ITT, a ≥50% improvement in overall clinical response between baseline and month 6 was reported for 48.7% of patients; continued improvement was seen at all subsequent 6-month intervals relative to the previous timepoint. The percentage of patients with moderate/severe disease also decreased at each timepoint. At baseline, 77.0% of patients received steroids at a mean (SD) prednisone equivalent dose of 19.9 (14.39) mg/day, which decreased to 8.4 (7.35) mg/day at month 6 and 6.1 (9.31) mg/day at month 24. Abnormal laboratory values typically associated with SLE also demonstrated improvements at month 6, which continued through 24 months. HCRU decreased over the duration of the study. CONCLUSIONS: Patients with SLE who received belimumab plus SoC for up to 24 months demonstrated improvements in disease severity and laboratory values and a reduction in steroid use and HCRU as early as month 6. Improvements continued through 24 months, providing evidence of reduced disease activity among patients taking belimumab in real-world clinical practice.

Elevated BLyS levels in patients with systemic lupus erythematosus: Associated factors and responses to belimumab.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) with B-lymphocyte stimulator (BLyS) levels ≥ 2 ng/mL are at increased risk of flare. A regression analysis was undertaken to identify routine clinical measures that correlate with BLyS ≥ 2 ng/mL. Efficacy and safety of belimumab 10 mg/kg were examined in patients with BLyS ≥ 2 ng/mL and < 2 ng/mL. METHODS: Data from BLISS-52 and -76 (N = 1684) were pooled post hoc. A univariate logistic regression was employed to identify factors predictive of baseline BLyS ≥ 2 ng/mL. Factors significant at the 0.05 level then entered a stepwise logistic regression as covariates. Efficacy endpoints included SLE responder index (SRI), ≥ 4-point reduction in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and risk of severe flare over 52 weeks. Adverse events (AEs) were analyzed for each treatment arm and BLyS subgroup. RESULTS: Baseline predictors of BLyS ≥ 2 ng/mL included positive anti-Smith (≥ 15 U/mL), low complement (C) 3 (< 900 mg/L), anti-double-stranded DNA (anti-dsDNA) 80-200 and ≥ 200 IU/mL, immunosuppressant usage, proteinuria, elevated C-reactive protein (CRP), and low total lymphocyte count for all patients. Belimumab 10 mg/kg led to significantly greater SRI responses over 52 weeks versus placebo in both BLyS subgroups, though treatment differences were numerically greater at Week 52 in the BLyS ≥ 2 ng/mL group (24.1%, p < 0.0001) compared with BLyS < 2 ng/mL (8.2%, p = 0.0158). Results were similar for ≥ 4-point reduction in SELENA-SLEDAI. Risk of severe flare over 52 weeks was significantly reduced with belimumab 10 mg/kg versus placebo in the BLyS ≥ 2 ng/mL group (p = 0.0002). AEs were similar across treatment arms and BLyS subgroups. CONCLUSIONS: Positive anti-Smith, low C3, anti-dsDNA ≥ 80 IU/mL, immunosuppressant usage, proteinuria, elevated CRP, and low total lymphocyte count were predictors of BLyS ≥ 2 ng/mL. Monitoring these factors could identify patients with BLyS ≥ 2 ng/mL who are at risk of flare.

Burden of corticosteroid use in patients with systemic lupus erythematosus: results from a Delphi panel.

Corticosteroid-related adverse events (AEs) are commonly reported in systemic lupus erythematosus (SLE), but are often under-represented in claims data. The most common corticosteroid-related AEs are not necessarily the most costly. The present study aimed to examine corticosteroid-related AE rates and identify the associated cost consequences in patients with SLE from the perspective of rheumatologists treating SLE in the United States (US). A modified Delphi process and RAND Appropriateness Method was used to estimate corticosteroid-related AEs and costs based on data from SLE-treating US rheumatologists and estimates from alternative sources. The panel (n=10) participated in two web-based questionnaires, covering disease severity, corticosteroid use, corticosteroid-related AEs, and resource utilization associated with treatment of the AEs. Eight members of the panel then participated in a guided discussion by interactive teleconference, in which the costs associated with specific corticosteroid-related AEs were also discussed. Consensus was achieved in the teleconference when a single response category (consensus values from 1 to 4 [4=strongly agree, 1=strongly disagree]) accounted for ≥80% of responses. Thirteen consensus statements were developed following two Delphi rounds. Costs were estimated for eight corticosteroid-associated AEs from the panel of rheumatologists. In the patients with SLE treated by these physicians, 41.5% were considered to have mild disease, 36.5% moderate disease, and 22.0% severe disease. The number of specialist visits, corticosteroid use, and corticosteroid dose increased with disease severity. The estimated rates of all AEs (except for cataracts) were at least doubled in patients receiving corticosteroid doses>20 mg/day compared with ≤20 mg/day. The highest estimated mean total costs of an event (for the required treatment duration for one patient) were for avascular necrosis ($14,460) and serious infection ($11,660). The costs of more common AEs, such as osteoporosis, obesity, diabetes, and fractures, ranged from $1190 to $8220. Ten rheumatologists concluded that as disease severity increases, corticosteroid doses increased. Greater utilization of resources is needed to manage patients and corticosteroid-related AEs.

Self-reported health outcomes in patients with psoriasis and psoriatic arthritis randomized to two etanercept regimens.

BACKGROUND: Moderate/severe psoriasis combined with psoriatic arthritis (PsA) impairs health-related quality of life (QoL). Etanercept, a fully human tumour necrosis factor-α receptor fusion protein, is approved for treatment of both diseases. OBJECTIVE: To compare patient-reported health outcomes (PROs) of two etanercept regimens in patients with moderate/severe psoriasis and PsA. METHODS: In this randomized, double-blind, multicenter study, participants received etanercept 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks and open-label etanercept 50 mg QW for 12 additional weeks. PROs included: the EuroQOL-5D (EQ-5D), which measures general health status and consists of the utility index measuring five dimensions of health, and a visual analogue scale (VAS) allowing patients to assess health status; the Dermatology Life Quality Index (DLQI), which measures the impact of skin disease on QoL; the Health Assessment Questionnaire-Disability Index (HAQ-DI), an assessment of physical function; the Hospital Anxiety and Depression Scale (HADS), which screens for anxiety and depression symptoms; and individual questions on general health, disease activity, fatigue, itching, joint pain and morning stiffness. RESULTS: At baseline, patients reported QoL worse than that seen in many chronic medical conditions. Significant within-group improvements in each PRO occurred from baseline to Week 12 (P < 0.001) in both groups and were maintained at Week 24; DLQI, EQ-5D, HAQ-DI and self assessments improved significantly (P < 0.001) from baseline as early as Week 3. At Week 12, but not Week 24, improvement in DLQI, itching and psoriasis activity was greater in the BIW arm (P ≤ 0.004). Improvements in other PROs were always similar between groups. CONCLUSIONS: Greater improvements in PROs specific to skin disorders were seen with etanercept BIW than QW at Week 12, but not at Week 24. Both etanercept regimens led to sustained PRO improvements, starting as early as Week 3.

Combination of skin, joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial.

BACKGROUND: Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). OBJECTIVE: To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. METHODS: Subjects (n=752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n=373) for 12 weeks, followed by open-label ETN 50mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro-QoL (EQ-5D), respectively. RESULTS: By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ-5D VAS >82). CONCLUSION: At 24 weeks, 25.8-30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.

Health-related quality of life and healthcare resource use in European patients with plaque psoriasis: an association independent of observed disease severity.

BACKGROUND: Healthcare resource utilization (HCRU) by patients with plaque psoriasis increases with skin lesion severity; however, the relationship between patient quality of life (QoL), which correlates only weakly with clinical severity, and HCRU is less understood. AIM: To evaluate the relationship between QoL, HCRU and employment in European patients with plaque psoriasis. METHODS: Patients (n = 897) were recruited in five European countries. Data were analysed by group according to the Dermatology Life Quality Index (DLQI): ≤ 10 (better QoL) and > 10 (worse QoL). RESULTS: Mean numbers of primary dermatologist visits and hospitalizations were significantly higher for patients with DLQI > 10. Likewise, significantly more patients with worse QoL reported employment disadvantages. Significant differences were maintained even after adjusting for age, gender and body surface area affected. CONCLUSIONS: In patients with plaque psoriasis, poorer QoL is associated with increased HCRU, independent of clinical severity. This suggests that QoL, in addition to skin lesion severity, should be considered in predicting the economic burden of disease.

The risk of psoriatic arthritis remains constant following initial diagnosis of psoriasis among patients seen in European dermatology clinics.

BACKGROUND: Estimates of psoriatic arthritis (PsA) prevalence among psoriasis patients vary widely (5-40%). The time to development of PsA in patients with plaque psoriasis also remains unclear. OBJECTIVES: To examine whether length of time since diagnosis of psoriasis affects risk of developing PsA, and to assess differences in quality of life (QoL), work-related issues, comorbidities and healthcare resource utilization (HCRU) for patients with PsA vs. psoriasis. METHODS: This large cross-sectional observational study was conducted in the UK, Italy, France, Spain and Germany in 2006. Dermatologists who actively treated patients with psoriasis recruited 10 consecutive patients with psoriasis. Presence of PsA, body surface area (BSA) affected with psoriasis and HCRU were recorded; patients completed EUROQoL (EQ5D) and employment disadvantages questionnaires. RESULTS: Patients with psoriasis (n = 1560) included 126 with PsA. Ninety per cent of these patients with PsA were seen by dermatologists who involved a rheumatologist in the care of their patients with PsA. Survival analysis indicated that the incidence of PsA among psoriasis patients remained constant (74 per 1000 person-years), while the prevalence increased with time since diagnosis of psoriasis, reaching 20.5% after 30 years. In addition, those with high BSA currently affected by psoriasis were more likely to have developed PsA (P < 0.028). PsA patients reported reduced QoL compared with psoriasis patients (EQ5D score: 0.56 vs. 0.82: P < 0.0005), as well as more work problems. PsA patients were more likely to be hospitalized (0.27 +/- 0.84 vs. 0.14 +/- 0.71 per year; P < 0.0005) and have additional comorbidities than those without PsA. CONCLUSIONS: The incidence of PsA was constant after initial diagnosis of psoriasis, leading to a higher prevalence of concomitant PsA over time. PsA is associated with decreased QoL and increased work-related problems, HCRU and comorbidities. Dermatologists should screen for PsA in their patients, especially long-standing patients who did not initially present with PsA.

Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or paused etanercept treatment over 54 weeks: the CRYSTEL study.

OBJECTIVE: To assess patient-reported outcomes (PRO) in patients with moderate-to-severe plaque psoriasis receiving continuous or paused etanercept treatment. METHODS: In a multicentre European open-label study, one group (n = 352) received continuous therapy: 25 mg subcutaneously (SC) twice weekly (BIW) throughout 54-weeks. The other group (n = 359) received paused therapy: 50 mg SC BIW (

Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept.

BACKGROUND: Patients with psoriasis experience remission and gradual reappearance of erythematous and scaly plaques and require individualized treatment over time. A goal of psoriasis treatment is to provide optimal efficacy with a flexible therapeutic regimen that may include treatment pauses. OBJECTIVES: To determine whether patients receiving initial treatment with etanercept who then pause therapy would subsequently recapture response during re-treatment. PATIENTS AND METHODS: A post-hoc analysis of 226 patients with moderate-to-severe psoriasis from a large multicentre trial was performed. Patients had received etanercept 50 mg twice weekly subcutaneously until a target clinical response had been achieved, then had paused treatment and eventually relapsed. They were then re-treated with etanercept 25 mg twice weekly. The number of patients recapturing a Physician Global Assessment (PGA) of psoriasis rating of < or = 2 (clear, almost clear or mild) on first re-treatment was assessed. Patient satisfaction during the initial treatment and first re-treatment period was also determined. RESULTS: A total of 187 (83%) patients recaptured the target clinical response of a PGA of < or = 2 after re-treatment. The majority of patients [219 of 226 (97%)] reported satisfaction with etanercept re-treatment. No new safety concerns emerged during re-treatment. CONCLUSIONS: In this post-hoc analysis, patients with psoriasis who were re-treated with etanercept 25 mg twice weekly effectively recaptured clinical responses that patients found satisfactory. A flexible treatment option is available to dermatologists and patients for individualized care.

Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate-to-severe psoriasis.

BACKGROUND: To determine the prevalence of joint and nail symptoms, impact of these symptoms on health-related quality of life (HR-QoL), and the effects of etanercept on them in patients with moderate-to-severe plaque psoriasis. METHODS: In CRYSTEL, patients with psoriasis received etanercept continuously (n = 357) or as paused therapy (n = 363) for 54 weeks. In post hoc analyses, baseline characteristics and after-treatment changes were evaluated in patients with baseline joint pain or nail psoriasis, pooling across treatment groups. Assessments of symptom severity and HR-QoL included the Subject Global Assessment question on joint pain, NAPSI, DLQI and EQ-5D. RESULTS: Of 711 patients, 64% reported joint pain and 79% nail psoriasis at baseline. Patients with baseline joint pain or nail psoriasis had significantly worse HR-QoL than unaffected patients. Mean baseline differences between patients with and without joint pain in DLQI (3.3), EQ-5D utility (0.2), and EQ-5D VAS (7.3) were clinically meaningful. In patients with nail psoriasis, a clinically meaningful difference in EQ-5D VAS (5.0) was seen. Etanercept significantly improved symptom severity and HR-QoL. Patients with joint pain had improvements of 47%, 61%, 29%, and 23% in mean joint pain score, DLQI, EQ-5D utility, and EQ-5D VAS, respectively, at Week 54. Patients with nail psoriasis had improvements of 51%, 63%, and 24% in NAPSI, DLQI, and EQ-5D VAS. CONCLUSION: In this study of moderate-to-severe plaque psoriasis, joint and nail symptoms were prevalent and patients with these symptoms had significantly greater HR-QoL impairment at baseline than unaffected patients. Etanercept provided significant improvement in symptom severity and HR-QoL.

Wegener's granulomatosis: pitfalls in the management of pulmonary disease: A case of Wegener's granulomatosis with a hilar mass.

Wegener's granulomatosis (WG) is a systemic, granulomatous vasculitis that typically affects the upper airways, lungs, and, in most cases, the kidneys. Lung involvement occurs in 85% of patients. A classic feature of WG is multiple pulmonary nodules, which frequently cavitate. Hilar adenopathy or mediastinal masses are rare. These atypical pulmonary findings should raise suspicion of diseases other than WG and lead to biopsy with cultures, even when the diagnosis of WG appears to be certain. These guidelines proved to be reliable in a patient with WG in whom a hilar mass was associated with tuberculosis.

Labeling of A2A adenosine receptors in human platelets by use of the new nonxanthine antagonist radioligand [3H]SCH 58261.

The present study describes the binding to human platelet A2A adenosine receptors of the new potent and selective antagonist radioligand [3H]5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c] pyrimidine ([3H]SCH 58261). Saturation experiments revealed that [3H]SCH 58261 labels a single class of recognition sites with high affinity (Kd = 0.85 nM), limited capacity (apparent Bmax = 85 fmol/mg of protein) and good specific binding (about 60%). [3H]SCH 58261 binding was not modulated by either the divalent cation Mg(+2) or guanine nucleotides. In competition experiments, a series of both adenosine agonists and antagonists inhibited [3H]SCH 58261 binding to A2A platelet receptors with rank order of potency and affinity similar to those observed in rat striatal membranes with the same radioligand. This confirms that the platelet A2A receptor is similar to that labeled in the brain striatum. Binding data were also found to be in good agreement with the results from functional studies such as A2A agonist-induced stimulation of adenylate cyclase or platelet aggregation inhibition. The present findings indicate that [3H]SCH 58261 is the first radioligand available for the characterization of the A2A receptor subtype in platelets.

Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes.

Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear leukocytes, under recirculating conditions (50 ml), and challenge with A-23187 (0.5 microM) caused an increase in coronary perfusion pressure (from a prechallenge value of 46 +/- 1.1 to 176.2 +/- 29.7 mm Hg, 30 min after challenge, n = 6-4), which was linearly correlated (P < .006) with formation of cysteinyl leukotrienes (29.7 +/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with the leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in significant protection against the increase in coronary perfusion pressure (76.7 +/- 12.8 mm Hg, 30 min after challenge) and in almost complete inhibition of sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml, 30 min after challenge). In in vivo experiments, ligation of the left anterior descending coronary artery in the rabbit (n = 10) resulted in acute myocardial infarction marked by a mortality rate of 60% compared with sham-operated animals (n = 10). Intravenous treatment of the rabbits with BAY X1005 (10 mg/kg/h, for 2 h) (n = 10) markedly reduced the mortality rate (20%), protected the rabbits against the marked electrocardiogram derangement and abolished the significant increase in plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase activity induced by coronary artery ligation. BAY X1005 exerts a significant cardioprotection and suggests that specific leukotriene synthesis inhibitors may lead to innovative therapy in myocardial ischemia.

Childhood-onset systemic lupus erythematosus: antiphospholipid antibodies in 37 patients and their first-degree relatives.

OBJECTIVE: Antiphospholipid antibodies (aPL) are noted with increased frequency in patients with systemic lupus erythematosus (SLE). The main manifestations found to be associated with aPL are arterial and venous thrombotic events, thrombocytopenia, and recurrent pregnancy loss. This study is an attempt to define the incidence of aPL in patients with childhood-onset SLE and in their relatives and to correlate their presence with clinical manifestations, and especially, to evaluate the risk of thrombosis in aPL-positive subjects. METHODOLOGY: We studied 37 unrelated patients and 107 of their first-degree relatives. VDRL, IgG and IgM anticardiolipin, and IgG antiphosphatidylethanolamine antibodies were studied in all probands during periods of clinical remission and in first-degree relatives at the time of interview. Lupus anticoagulant had only been studied in probands during an SLE flare-up. RESULTS: Thirty-eight percent of probands and 19% of relatives were positive for at least one aPL, with little overlap between the different aPL studied. -No aPL-negative proband developed thrombosis. Two of the aPL-positive probands had thrombotic events before testing, and a third one showed thrombosis after testing. Only two probands had high levels of IgG aCL and showed thrombosis. The occurrence of aPL positivity in relatives was not always related to its presence in probands. None of the aPL-positive relatives had had thrombosis, but recurrent fetal loss was noted in one aPL-positive mother with SLE. Although there was a high frequency of SLE, SLE-like disease, auto-immune disorders or positive serological findings for lupus in first-degree relatives, many of these relatives did not test positive for aPL. CONCLUSION: The high levels of IgG aCL may be considered a risk factor for thrombosis. Findings in relatives suggest a multifactorial origin for autoimmune disease and antibody production.

[Profile of antinuclear antibodies in 14 cases of extinct systemic lupus erythematosus for more than 3 years]. / Profil des anticorps antinucléaires dans 14 cas de lupus érythémateux systémiques éteints depuis plus de trois ans.

In order to study the profile of antinuclear antibodies (ANA) and anticytoplasm in the clinical recovery period, we searched for ANA by 4 methods (indirect immunofluorescence on HEp-2 and Crithidia luciliae cells, double diffusion in agar against veal thymus and human spleen, immunoprint with a total extract of HeLa cells) in 14 patients with SLE extinct since more than 3 years. The population under study consisted of 12 women and 2 men, aged 43 years on average at the time of study (extremes: 28-64 years). The average lapse of time between the diagnosis of SLE and date of sampling is of 12.6 years (extremes: 3-22 years). The average remission/clinical recovery time during the study is of 8.9 years (extremes: 3-22 years). Seven patients were administered mild corticotherapy (average dose of prednisone: 4.7 mg/day). All the sera preserved ANA or anticytoplasm, distributed in the following way: presence of antinucleus: 10/14 (71.5%); average titre 40; speckled aspect: 10/10; presence of anti-DNA: 0/14; presence of anti-ECT: 2/14 (14.3%): anti-SSB 1 case, anti-RNP 1 case; positive immunoprint: 12/14 (85.7%): anti-Sm 5 cases (isolated or associated), isolated anti-SSB 2 cases; isolated anti-Ro 2 cases; various unidentified 3 cases. These results suggest that the production of ANA and anticytoplasm other than anti-DNA continues during the period of clinical extinction of SLE, underlining the rarity of a complete biological recovery and the necessity of long term clinical surveillance.

Familial occurrence of systemic sclerosis, rheumatoid arthritis and other immunological disorders: report of two kindreds with study of HLA antigens and review of the literature.

We report two Caucasian families with systemic sclerosis and other connective tissue and immunological disorders, including rheumatoid arthritis, discoid lupus erythematosus, psoriasis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, asthma, Sjögren's syndrome, Raynaud's phenomenon and thyroid disease. In one of these families, two sisters are affected with systemic sclerosis. Clinical, serological, and HLA haplotype results are reported, along with a review of the medical literature on familial occurrence of systemic sclerosis.

HLA DR4 and B27 antigens in familial and sporadic rheumatoid arthritis.

We studied HLA antigens in 105 unrelated American Caucasian patients with rheumatoid arthritis (RA), 70 of them with familial disease. HLA-DR4 was observed in 71% of familial RA, 63% of non-familial RA, and 27% of normal controls, confirming the already well-established association between HLA-DR4 and both familial and non-familial RA. HLA-B27 was present in 14.3% of patients, versus 8% of normal controls (p = 0.04), and was not more common in familial (10 of 70, or 14.3%) versus non-familial (5 of 35, or 14.3%) disease. These results are compared with those observed in Scandinavian patients.