Inhibition of tumor necrosis factor alpha and ankylosing spondylitis.
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Biomedical subjects
Publications and source records attributed to Bertrand Wechsler.
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OBJECTIVE: The use of hydroxychloroquine (HCQ) in pregnancy remains controversial. The recent demonstration that HCQ passes across the placenta, with cord blood concentrations nearly identical to those found in maternal blood, emphasizes the need for careful evaluation of pregnancies in women receiving HCQ. However, only small series of HCQ-treated pregnant women have been reported, and most of these studies had no control group. We now report our experience with 133 pregnancies in women being treated with HCQ, resulting in 117 live births. Results in the HCQ group are compared with those in a control group. METHODS: One hundred thirty-three consecutive pregnancies in 90 women treated with 200 mg of HCQ either twice daily (122 pregnancies) or once daily (11 pregnancies) were studied. These pregnancies were compared with 70 consecutive pregnancies in 53 women with similar disorders who did not receive HCQ. Electrocardiography was performed in 47 children of mothers treated with HCQ and in 45 children in the control group. RESULTS: Eighty-eight percent of pregnancies in the HCQ group and 84% of those in the control group ended successfully with a live birth. The outcomes of pregnancy were not statistically different between groups. One child in each group died of causes related to prematurity. Three malformations were observed in the HCQ group (1 hypospadias, 1 craniostenosis, and 1 cardiac malformation) versus 4 in the control group. On the electrocardiograms, the PR interval and the corrected QT interval were not statistically different between groups. No visual, hearing, growth, or developmental abnormalities were reported in any of the children at the last follow-up (ages 12-108 months; mean age 26 months). CONCLUSION: Our findings support preliminary evidence for the safety of HCQ therapy during pregnancy. This treatment probably should be maintained throughout pregnancy in patients with systemic lupus erythematosus.
PURPOSE: To describe the occurrence of conjunctival ulcers as a manifestation of Behçet's disease. DESIGN: Retrospective, noncomparative, interventional case series with histopathologic correlation. METHODS: Six patients who fulfilled the diagnostic criteria for Behçet's disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin. RESULTS: Although all six patients fulfilled the diagnostic criteria for Behçet's disease, two developed uveitis and other signs of Behçet's disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring. CONCLUSIONS: In addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behçet's disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behçet's disease.
BACKGROUND: Anetoderma is characterized by circumscribed areas of flaccid skin due to the loss of elastic tissue in the dermis. It may be primary or secondary to various dermatoses. The primary form has been reported in association with autoimmune diseases and recently with antiphospholipid antibodies. Its etiology remains unknown. OBJECTIVES: To analyze clinical and laboratory data from a series of patients with anetoderma referred in our university reference center for connective tissue disorders. PATIENTS AND METHODS: All the consecutive patients with histologically confirmed anetoderma followed in our clinic from 1996 to 2001 were enrolled in this study. Laboratory investigations included the screening for prothrombotic abnormalities and classical immunological investigations for systemic lupus erythematosus. Clinical and laboratory data were analyzed retrospectively. RESULTS: Anetoderma was primary in 9 cases and secondary to lupus profundus in 2 cases. Prothrombotic abnormalities were detected in 10 patients (9/9 with primary and 1/2 with secondary anetoderma). Antiphospholipid antibodies were detected in 9 patients. Only 4 patients fulfilled criteria for definite antiphospholipid syndrome which was primary for 3 and associated with systemic lupus erythematosus in the other. CONCLUSION: Patients with anetoderma should be evaluated for the possible presence of a prothrombotic state and warned of its potential risks when present.
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Improvement in the prognosis of SLE prognosis has led to considering infertility therapy. The earliest reports displayed complications such as SLE revealed by ovulation induction or thrombophlebitis. Fertility is known to be normal in women with SLE, excepting amenorrhea accompanying severe flare-ups, renal insufficiency-related hypofertility and ovarian failure secondary to cyclophosphamide therapy. Anti-phospholipid antibodies are suspected to cause defective nidation and placental ischemia. An exponential rise of serum estradiol is observed irrespective of the ovulation induction protocol used, leading to SLE flare-up and thrombosis. We have experience with 114 cycles in 21 women with SLE and/or APS. A complication (fetal loss, SLE flare-up, thrombophlebitis) revealed the underlying disease in 8 women. Eighteen pregnancies led to 9 live-births, 4 fetal deaths and 5 embryonic losses. Pregnancy rate was higher after ovulation induction using gonadotropins (25% per cycle), than clomiphene (4%). Pregnancy rate was similar after IVFETE, whether the protocol was planned or not. However, three-quarters of the pregnancies after unplanned IVFETE led to abortions. On the contrary, 6 out of 7 pregnancies after planned IVFETE led to live-births. Two women developed thrombophlebitis after gonadotropins therapy. A SLE flare-up appeared after 13 out of 62 cycles, with a flare-up rate higher after gonadotropins (27% per cycle) than clomiphene therapy (6%), and after an unplanned (30%) than a planned procedure (10%). In conclusion, ovulation induction therapy can reveal SLE or APS. Clomiphene complications are uncommon. When gonadotropin therapy is considered, a preventive anti-inflammatory therapy should be discussed in SLE patients, in conjunction with heparin and/or anti-aggregate therapy for those with asymptomatic anti-phospholipid antibodies or prior thrombotic events.
OBJECTIVE: Viruses might be one of the elements that trigger systemic lupus erythematosus (SLE). Steroid therapy may influence the natural history of virus infections. The most frequent extrahepatic manifestations of hepatitis C virus (HCV) including arthralgia, myalgia, sicca syndrome, and antinuclear antibodies, may mimic a connective tissue disease, particularly SLE. Reports on the association between SLE and HCV infection are scarce. We investigated the association of HCV infection and SLE. METHODS: Retrospective case-control monocentric study of 19 patients with SLE and anti-HCV antibodies versus 42 randomized SLE patients without anti-HCV antibodies, matched for age and sex, coming from our cohort of 700 patients with SLE. SLE and HCV-infection features were reviewed. RESULTS: Mode of infection was blood product transfusion, drug addiction, or unknown. Prevalence of lupus clinical manifestations, antinuclear, anti-dsDNA, anti-extractable nuclear antigen antibodies, and complement levels was not different between HCV positive and negative SLE patients. Prevalence of cryoglobulin was higher in SLE patients with anti-HCV antibodies (p < 0.04), but none had a mixed cryoglobulinemia syndrome. ALT activity was increased in 11 HCV positive patients and 13 had detectable HCV RNA. Liver biopsy showed cirrhosis in 2 and mild fibrosis and activity in 5. One patient treated with interferon-alpha had a sustained virological response without SLE flare. Steroid therapy did not seem to alter HCV course. CONCLUSION: SLE in HCV positive patients shows higher prevalence of cryoglobulin without mixed cryoglobulinemia syndrome. HCV infection has moderate signs of biochemical and liver pathological severity. SLE by itself or treated with steroids does not seem to worsen HCV infection.
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OBJECTIVE: To analyze the results and complications of ovulation induction therapy (OIT) in women with systemic lupus erythematosus (SLE) and/or the antiphospholipid syndrome (APS). METHODS: A retrospective study of 21 women followed in a single tertiary-referral French center who underwent 114 OIT cycles with or without in vitro fertilization and embryo transfer (IVFET). RESULTS: Before OIT, SLE was present in 6 women, APS in 3, SLE-related APS in 3, and discoid lupus in 1. Eight women had no identified disease and underwent 36 cycles of OIT. Diagnosis (SLE, n = 3; primary APS, n = 5) was made after OIT complication: spontaneous abortion (n = 5), SLE flare (n = 2), and thrombophlebitis (n = 1). Five women with known disease intentionally concealed their history from their gynecologists and underwent 34 cycles. Forty-four cycles were planned in 11 women, in 3 of them after complications of prior OIT performed without particular therapy and monitoring. Eighteen pregnancies occurred, which ended in 9 live births, 4 fetal deaths, and 5 embryonic losses. The pregnancy rate was higher with gonadotropin and/or gonadotropin-releasing hormone analog (GnRHa) (25% of cycles) than with clomiphene (4% of cycles, P <.0001). When the gynecologists did not know the underlying disease, three-quarters of pregnancies induced by OIT with IVFET ended in embryonic losses or fetal deaths. In contrast, 6 of 7 pregnancies induced by planned OIT with IVFET ended in live births (P <.0001). Phlebothromboses were observed only with gonadotropin treatment. The SLE flare rate was higher with gonadotropin and/or GnRHa (27% of cycle) than with clomiphene (6%, NS). It also was higher (30%) when the gynecologists did not know the underlying disease than in the planned procedures (10%, NS). CONCLUSIONS: The OIT may precipitate SLE or APS. A careful review of the patient's history and appropriate laboratory tests should be undertaken before OIT. Clomiphene complications are rare. When gonadotropins are prescribed, preventive anti-inflammatory therapy should be considered in women with SLE, in addition to heparin and/or anti-aggregant therapy in patients with asymptomatic anti-phospholipid antibodies or prior thrombotic events.
Churg-Strauss syndrome (CSS) is characterized by small vessel vasculitis and extravascular granulomas. The American College of Rheumatology classification criteria for CSS include asthma, eosinophili, and clinical manifestation of vasculitis. Gastrointestinal (GI) manifestations occur in 30% of patients, but are inaugural in only 16%. They denote vasculitis of the stomach and small bowel wall, and consist in protean, nonspecific pain. GI involvement is of adverse prognostic significance in CSS. Ulcer formation in the GI tract mucosa is a rarer manifestation, usually discovered upon laparotomy or autopsy. We describe 3 new cases of colonic ulcers in CSS. Unusual features were diagnosis of the ulcers during a delayed relapse and presence of eosinophilic granulomas within the mucosa.
OBJECTIVE: To compare the risk of ovarian failure and the fertility of women treated with intravenous cyclophosphamide (IVCY) according to the underlying inflammatory disease. METHODS: Review of the data of 84 consecutive women: 56 with systemic lupus erythematosus (SLE), 28 with other diseases, mainly Wegener's granulomatosis and systemic vasculitides. RESULTS: The mean age at IVCY initiation was 29 +/- 10 years (range 13-53). The mean dosage was 0.9 +/- 0.14 g per pulse (range 0.5-1), and the mean number of pulses 13 +/- 6.5 (range 3-42). With a mean followup of 5.1 +/- 3.7 years, 23 women developed amenorrhea, with a mean duration of 4 +/- 3.6 months between IVCY initiation and amenorrhea. Amenorrhea was sustained in 19 women (13 with SLE and 6 with other diseases, NS). The mean age at ovarian failure onset was 40 +/- 7.6 years. The risk of ovarian failure correlated with the age at IVCY institution (p < 0.0001), and was independent of underlying inflammatory disease. Eighteen women (13 with SLE and 5 with other diseases) became pregnant during or after CY therapy, with a total of 22 pregnancies. The mean age at IVCY initiation, and the mean number of IVCY (maximum 40 pulses) before pregnancy were similar in women with SLE and those with other diseases. Six pregnancies occurred during IVCY therapy, which ended in induced abortion (n = 3), spontaneous abortion (n = 1), and normal pregnancy after IVCY withdrawal (n = 2) in women who wished to keep their pregnancy despite the risk of teratogenicity. Sixteen pregnancies occurred 2.9 +/- 2.1 years (range 1-9) after IVCY withdrawal. They ended in: 3 induced abortions indicated for severe morphological anomalies (n = 2) and for SLE relapse (n = 1), 3 spontaneous miscarriages, and 10 deliveries of healthy newborns. CONCLUSION: The risk of ovarian failure depends essentially on the age at IVCY initiation. Pregnancy may occur during IVCY therapy, and an efficient contraception is mandatory. After IVCY withdrawal, pregnancy is possible with a favorable outcome in two-thirds of the cases.
The prevalence of systemic diseases depends on patient age. One third to one half of the patients with Wegener's granulomatosis are over 60 years at the diagnosis. In the elderly, renal insufficiency, lymphopenia and central nervous system involvement are more frequent, and upper airways involvement and hemoptysis less frequent. Signs suggestive of temporal arteritis may initiate the disease. Mortality is increased in the elderly, and aging is an independent predictor of poor prognosis. Henoch-Schönlein purpura is uncommon in adulthood; one quarter of adult cases involves an elderly patient. End-stage renal failure and association with neoplasia are common. In some cases, synchronous course of purpura and neoplasia leads to consider it as a true paraneoplastic syndrome. Periarteritis nodosa in the elderly is characterized by an increased frequency of the association with viral B hepatitis and skin vasculitis. Histological location of necrotizing arteritis involving the temporal artery is possible. It should be considered as a borderline disease, and treated as the more severe disease. Aging is predictive of poor prognosis. Cholesterol emboli are a classic complication of atheroembolic disease and may mimic an inflammatory and multisystemic disease with renal, cardiac, pulmonary, digestive, neuropsychiatric, skin and muscle involvements due to ischemic phenomena leading to necrosis. One-year mortality is over 60% in the symptomatic forms.