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Oral contraceptive therapy and systemic lupus erythematosus.

The relationship between oral contraceptive therapy and systemic lupus erythematosus is not well defined. It has been reported that oral contraceptives may induce lupus: they may also exacerbate pre-existing disease. This report concerns a young woman in whom systemic lupus erythematosus developed three weeks after the commencement of oral contraceptive therapy, but who was shown to have had a chronic biological false positive serological test for syphilis for eight months prior to this. The significance of false positive serological tests for syphilis and the effect of female sex hormones on disease activity in systemic lupus erythematosus is discussed.

Adult↗

Orbital infarction and melting in a patient with systemic lupus erythematosus.

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.

Eye Diseases↗

Mechanism of photosensitivity in systemic lupus erythematosus patients.

Patients who have systemic lupus erythematosus have increased numbers of chromosome breaks and rearrangements correlated with a low molecular weight chromosome-damaging agent that is released from their lymphocytes into the serum. This clastogenic factor also produces chromosome breaks and sister chromatid exchanges in healthy persons' lymphocytes when they are incubated in the presence of lupus patients' serum or lymphocytes or purified factor. The lymphocytes from lupus patients are sensitive to near-UV (360- to 400-nm light. This sensitivity seems to be related to the presence of the clastogenic factor in these cells; lymphocytes of healthy persons exposed to the factor also become sensitive to light of the same wavelengths. A significant increase in nonviable cells (trypan blue exclusion test) was observed after 5 min of irradiation with 360- and 380-nm light in the presence of the factor. The number of chromosome aberrations observed after stimulation of the irradiated lymphocytes with phytohemagglutinin was also maximal after irradiation at 380 nm in presence of the factor. The combined action of near-UV light plus clastogenic factor was inhibited by superoxide dismutase if the enzyme were present during irradiation, suggesting that activation involves photoproduction of superoxide ions. Irradiation of the purified factor and immediate addition of it to lymphocytes gave the same results whereas preirradiation of cells or of medium was without effect. The presence of this photoactivated agent explains why patients who have lupus erythematosus show an aggravated condition after exposure to sunlight and the appearance of typical skin lesions.

Cell Survival↗

[Apoptosis in systemic lupus erythematosus].

In autoimmune diseases including systemic lupus erythematosus (SLE), the immune system attacks various autoantigens and causes damage in target organs. Recently, it was found that dead cells serve as a repertoire for autoantigens which can stimulate an autoimmune response in sensitive persons. The mechanisms which lead to induction and progress of apoptosis include extra-cellular stimuli, intra-cellular signals, and cleavage of proteins. During apoptosis, several events occur including migration of intra-cellular components to the cell membrane, removal of apoptotic cells by specific proteins and complement systems, and phagocytosis of apoptotic cells by macrophages. In recent years, evidence has accumulated that the autoimmune response can be initiated as a result of defects in apoptosis and/or removal of apoptotic material. In this article, the association of apoptosis to the pathogenesis of systemic lupus erythematosus is discussed.

Apoptosis↗

Subacute cutaneous lupus erythematosus. Clinical, serologic, and immunogenetic studies of forty-nine patients seen in a nonreferral setting.

Subacute cutaneous lupus erythematosus has been clearly recognized as a distinct cutaneous manifestation of lupus erythematosus. Two forms have been described, an annular erythema and a papulosquamous variant. Previous data have suggested that these patients have a high incidence of mild to moderate systemic disease, anti-Ro (SS-A) antibodies, and human lymphocyte antigen (HLA)-DR3, particularly the annular form. We studied forty-nine patients with subacute cutaneous lupus erythematosus seen in local private practices in our area. Lesions of chronic cutaneous lupus erythematosus were seen in 34.8% of our patients. Twenty-five patients (51%) fulfilled the American Rheumatism Association criteria for the classification of systemic lupus erythematosus, and renal disease was present in nine of these patients (including 3 with decreased function). Antibodies to Ro (SS-A) and/or La (SS-B) were present in only sixteen patients, and HLA-DR3 was found in only seventeen patients. Twenty-two patients had inactive cutaneous disease at follow-up. We concluded that our patient population with subacute cutaneous lupus erythematosus skin lesions is less distinctive than previous literature suggests. The serologic and immunogenetic correlates were not demonstrated. The full range of lupus erythematosus-related disease was seen, although most patients follow a benign course.

Acute Disease↗

Acute adverse reactions to ibuprofen in systemic lupus erythematosus.

Three young women with systemic lupus erythematosus who were given ibuprofen for arthritis voluntarily discontinued taking the drug. On reinstitution of therapy, profound hypotension, fever, and headaches developed within hours, without other identifiable cause. A possible relationship to salicylate intolerance was considered. Because of these apparent side effects, we stress caution in the use of ibuprofen in systemic lupus erythematosus, particularly if there is any history of salicylate intolerance.

Acute Disease↗

Antibodies to single-stranded DNA in patients with discoid lupus erythematosus.

Sera from 31 patients with discoid lupus erythematosus were examined for the presence of antibodies to single-stranded and native DNA. None of these sera had antibodies to native DNA. When rabbit anti-human IgM was used, 6 of 28 patients had elevated binding, whereas only 1 of 29 patients had abnormal binding when antiIgG was used. The IgM nature of this response was confirmed when we demonstrated the binding activity in heavy fractions from gel filtration. We concluded that at least one-fifth of patients with discoid lupus erythematosus have IgM antibodies to single-stranded DNA.

Antibodies↗

Mitral valve replacement and repair. Report of 5 patients with systemic lupus erythematosus.

Severe mitral valve regurgitation due to systemic lupus erythematosus is a rare cause of valvular heart disease, necessitating valve surgery. Currently, there are 36 case reports in the world medical literature of mitral valve replacement or repair in patients who have lupus. The current trend in mitral valve surgery is toward anatomic valve repair. In patients who have systemic lupus erythematosus, however, valve repair often leads to repeat surgery and valve replacement. We report the cases of 5 patients with lupus and severe mitral valve regurgitation who underwent mitral valve surgery. In 3 of these patients, replacement with a mechanical prosthetic mitral valve was performed with good long-term results. In the other 2 patients, mitral valve repair was performed, but only 1 of the repairs was successful. The 2nd patient required subsequent replacement with a mechanical valve. To our knowledge, this report of 5 patients is the largest series of mitral valve surgery in patients with lupus. These results, along with a review of the literature, suggest the superiority of mechanical prosthetic valve replacement to repair in patients who have systemic lupus erythematosus.

Adult↗

Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus.

OBJECTIVE: To examine the relation between postmenopausal hormone use and development of systemic lupus erythematosus. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PATIENTS: 69,435 women aged 30 to 55 years in 1976 who reported that they had completed menopause and did not have systemic lupus erythematosus or any connective tissue disease were followed every 2 years from 1976 to 1990. These women were classified as never- or ever-(current and past) users of postmenopausal hormones. MEASUREMENTS: Incidence rates of systemic lupus erythematosus and classification criteria from the American College of Rheumatology that were confirmed by chart review. RESULTS: With never-users of postmenopausal hormones as the reference group, age-adjusted relative risks for systemic lupus erythematosus (n = 45 women) were 2.1 (95% CI, 1.1 to 4.0) for ever-users, 2.5 (CI, 1.2 to 5.0) for current users, and 1.8 (CI, 0.8 to 4.1) for past users. A proportional increase in the risk for systemic lupus erythematosus was observed that was related to the duration of use of postmenopausal hormones (test for trend, P = 0.011). CONCLUSIONS: Postmenopausal hormone therapy is associated with an increased risk for developing systemic lupus erythematosus.

Adult↗

Risks of ovulation-induction therapy in systemic lupus erythematosus.

We report on four women with systemic lupus erythematosus who developed two types of complications after ovulation-induction therapy for primary or secondary infertility. Primary infertility was associated with endometriosis in one patient. Three had previously known systemic lupus erythematosus. All had inactive disease at onset of ovulation-induction therapy. Three patients developed symptoms consistent with moderate lupus flare a few weeks after the onset of ovulation-induction therapy. One patient developed inferior vena cava and unilateral left renal vein thrombosis. No patient became pregnant. A high oestrogen level induced by ovulation-induction therapy may explain the occurrence of lupus flare in patients with prior inactive lupus. All our patients had prior asymptomatic antiphospholipid antibodies. One patient developed a major thrombotic event. The presence of antiphospholipid antibodies increases the thrombotic risk related to ovulation-induction therapy. We conclude that ovulation-induction therapy should be restricted to patients with long-standing inactive systemic lupus erythematosus. A preventive increase of the corticosteroid dosage should be proposed in addition to heparin or antiaggregant therapy for those with prior asymptomatic antiphospholipid antibodies, or with heparin therapy for those with prior antiphospholipid antibody-related events.

Adult↗

Total lymphoid irradiation in refractory systemic lupus erythematosus.

In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

Adult↗

Iron status alters murine systemic lupus erythematosus.

The effect of Fe status on murine systemic lupus erythematosus was investigated. Weanling female MRL/MPJ-lpr/lpr mice (systemic lupus erythematosus strain) were fed diets with the following levels (mg Fe/kg diet): 3 (severely deficient), 10 (moderately deficient), 35 (control) and 250 (supplemented). A fifth group was pair fed the control diet in the amounts consumed by the severely deficient group. C3H/Hej mice fed the same diets were used as non-lupus controls. Anemia was more severe in severely deficient mice than in all other MRL groups and C3H severely deficient mice. Incidence of skin lesions was highest in MRL severely and moderately deficient mice compared with pair-fed, control and supplemented mice. By 22 wk of age, mortality was higher in supplemented and severely deficient mice than in moderately deficient, pair-fed and control MRL mice. Anti-dsDNA activity in serum was not altered by Fe. In a second experiment, kidney function was examined in mice fed severely deficient, control, supplemented and pair-fed diets. Urine protein concentration was highest in supplemented mice at 14 wk of age. Serum urea nitrogen was significantly higher in MRL severely deficient mice than in pair-fed and control mice at 18 wk of age. Glomerular filtration rate, measured by creatinine clearance, was significantly lower in MRL severely deficient mice than in pair-fed and Fe supplemented mice at 16 wk of age and pair-fed and control mice at 18 wk of age. Renal histopathology was more severe in Fe supplemented mice than in pair-fed and control mice, and more severe in severely deficient and pair-fed mice than in control mice. Fluorescent staining of kidneys with anti-Ig G and anti-C3 fluorescein-conjugated antibodies was most intense in severely deficient mice, and the concentration of circulating immune complexes in serum was significantly higher in severely deficient mice than in all other groups. These data demonstrate that systemic lupus erythematosus in MRL/MPJ-lpr/lpr mice is altered by dietary iron.

Anemia, Iron-Deficiency↗

Rapid appearance of severe mitral regurgitation under high-dosage corticosteroid therapy in a patient with systemic lupus erythematosus.

Survival of patients with systemic lupus erythematosus has increased with corticosteroid therapy. However, adverse effects of corticosteroid therapy on cardiovascular structures, such as scarring and shrinking of affected valves, are not well known. We report the case of a 19-year-old patient who developed severe mitral insufficiency within a few weeks after high-dosage corticosteroid therapy had been instituted for an acute relapse of systemic lupus erythematosus. The rapid development of severe mitral regurgitation was documented by sequential colour Doppler echocardiography.

Adult↗

Aspergillus pneumonia successfully treated with itraconazole in a patient with systemic lupus erythematosus.

The case of a patient with systemic lupus erythematosus who developed pneumonia caused by Aspergillus fumigatus is described. She was treated with itraconazole 200 mg twice daily, with a rapid response. After a follow-up period of 5 years no recurrence of the infection has been detected. To our knowledge this is the first report on the use of itraconazole in patients with systemic lupus erythematosus. Considering the poor prognosis associated with Aspergillus pneumonia in patients with systemic lupus erythematosus, we believe that itraconazole constitutes a safe and effective alternative to amphotericin B in these patients.

Adult↗

Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus.

While modern treatments for systemic lupus erythematosus (SLE) have resulted in greatly improved long term outcome in children and adults, complications of atherosclerosis have become a major cause of morbidity and mortality. Although children and adolescents with SLE rarely experience adverse cardiovascular events before adulthood, dyslipoproteinemia and early evidence of premature atherosclerosis is present much earlier. Accelerated atherogenesis in SLE is multifactorial, most likely reflecting vascular, immune, and inflammatory changes along with medication effects. The long term complications of cardiovascular disease in childhood lupus present a particularly important target for intervention because of the potential return on investment by significantly lengthening life and improving quality of life over many decades. An ongoing multi-center, randomized, controlled trial, Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE), testing the efficacy of statins in preventing premature atherosclerosis in children and adolescents with SLE will guide future therapeutic intervention.

Arteriosclerosis↗

Systemic lupus erythematosus: perinatal and neonatal implications.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost all organ systems in the body. It is most common in women of childbearing age and may cause multiple peripartum complications. This article reviews the pathophysiology of SLE and the effects of SLE on fertility and pregnancy. The complexities of managing a pregnant patient with SLE are reviewed, and the importance of interdisciplinary collaboration discussed, as well as the effects of SLE on the fetus and a review of neonatal lupus erythematosus. Finally, a case report of a pregnant patient with SLE with challenging clinical management issues is presented.

Adolescent↗

Serum factors releasing serotonin from normal platelets: relation to the manifestations of systemic lupus erythematosus.

In 13 patients with systemic lupus erythematosus, globulin fractions of sera from serial bleedings were assayed for the induction of serotonin release from normal platelets. Releasing activity appeared at some time in the sera of seven patients, five of whom had episodes of thrombocytopenia. Conversely, only one patient manifested thrombocytopenia without the occurrence of serotonin releasing activity at any time. In three patients with episodes of thrombocytopenia, increases in serotonin releasing activity temporally coincided with drops in platelet count. These data show that levels of circulating platelet serotonin releasing factor(s) vary in the course of systemic lupus erythematosus and these variations may be inversely related to the platelet count in particular patients.

Adult↗