Menopause hormonal therapy in women with systemic lupus erythematosus

OBJECTIVE: To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus (SLE). METHODS: We conducted a double-blind, randomized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause. Patients received a continuous-sequential estrogen-progestogen regimen (n = 52) or placebo (n = 54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI). The primary outcome measure was global disease activity, estimated by measuring the area under the SLEDAI curve. Secondary outcome measures included maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to flare, medication use, and adverse events. Results were studied using intent-to-treat analysis. RESULTS: At baseline, demographic and disease characteristics were similar in both groups. Mean +/- SD SLEDAI scores were 3.5 +/- 3.3 and 3.1 +/- 3.4 in the menopause hormonal therapy and placebo groups, respectively (P = 0.57). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Median time to flare was 3 months in both groups. Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo. One patient in each group died during the trial due to sepsis. CONCLUSION: Menopause hormonal therapy did not alter disease activity during 2 years of treatment. However, an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy.     

Hormonal regulation of B-cell function and systemic lupus erythematosus

The prevalence of systemic lupus erythematosus (SLE) is far higher in females than in males and numerous investigations to understand this gender bias have been performed, which propose as casual actors genetic predispositions and sex hormones effects. We will describe in this review how the sex hormones estrogen and prolactin influence B cell maturation and selection, permitting B cells to mature to immunocompetence in a mouse model of lupus. Finally, we will discuss the relevance and implications of these results for human disease.     

Cutaneous lupus erythematosus without systemic lupus erythematosus: clinical and laboratory features.

Sixty-seven patients with cutaneous lupus erythematosus (CLE) were followed up as part of a series of 570 lupus erythematosus patients seen in a private practice between 1980 and 1989. Clinical and laboratory features, treatment, and natural course were observed. Findings of interest included (1) a ratio of at least one CLE case for every seven cases of systemic lupus erythematosus (SLE); (2) occurrence of CLE in fewer women and apparently associated with an older age at diagnosis than SLE; (3) similar frequency of cutaneous lupus subsets in CLE and SLE; (4) strong family history for SLE but not CLE in CLE patients; (5) other cutaneous and musculoskeletal features in a majority of CLE patients and constitutional symptoms in 10%; (6) positive ANA titers, high sedimentation rates, and leukopenia common in CLE; (7) anticardiolipin antibody in 31% of CLE patients but not associated with systemic complications; (8) antimalarials required by 75% of patients and systemic steroids by 33%; and (9) an excellent prognosis associated with CLE, organ-threatening disease being rare.     

Factors associated with abnormal Pap results in systemic lupus erythematosus

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.     

Serological and clinical remission in systemic lupus erythematosus

The frequency of a combined clinical and serological remission in patients with systemic lupus erythematosus (SLE) was examined. Thirteen (4%) of 305 patients had both a seroconversion from a positive to a negative ANA and became asymptomatic in respect to their SLE. These remissions lasted from 6 months to 13 years. It is not clear what role, if any, therapy played in these remissions. Nevertheless, these remissions provided hope for the patients and their physicians.     

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.     

Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: clinical, hormonal and therapeutic associations

We have evaluated 36 consecutive systemic lupus erythematosus (SLE) female patients, age 18-39 years, without current or previous alkylating therapy, in order to determine the prevalence of the menstrual disturbances and their clinical, hormonal and therapeutic associations. Seventeen patients presented normal cycles, whereas menstrual alterations were observed in 19. Ovarian function was generally preserved in these groups. Sub-clinical thyroid disease (normal free T4 and elevated TSH) and slightly increased prolactin levels were detected in 8% of patients, with comparable frequencies in both groups. Similarly, the current use of azathioprine was not associated with menstrual disturbances. Percentages of prednisone current use (P = 0.3), mean dose (P = 0.062), and percentages of patients on high doses (> or = 30 mg/day; P = 0.09) were comparable in patients with or without menstrual alterations. In contrast, the mean SLEDAI levels (P = 0.02) and the frequency of patients with SLEDAI > or = 8 (P = 0.008) were higher in patients with irregular cycles. Interestingly, 5/7 (71%) of the patients with menstrual disturbances and a new significant flare (SLEDAI > or = 8) were evaluated before the introduction of high dose steroid, supporting the idea that disease activity is a major factor in menstrual disorders in SLE patients without alkylating therapy.     

Q fever with clinical features resembling systemic lupus erythematosus

A 23-year-old woman with prolonged fever, rash, and pericarditis associated with high titers of antinuclear, anti-Sm, and anti-RNP antibodies was suspected of having systemic lupus erythematosus (SLE). However, we also considered infectious diseases, particularly Q fever, as the C-reactive protein level was elevated and the patient reported contact with zoo animals around two weeks before the onset. The condition responded rapidly to administration of minocycline; symptoms resolved without using steroids. Thereafter, no recurrence of the illness was observed. Titer of Coxiella burnetii antibody was high and the illness was accordingly diagnosed as acute Q fever rather than SLE.     

Tuberculosis in patients with systemic lupus erythematosus.

Tuberculosis associated with systemic lupus erythematosus (SLE) was studied in a cohort of 311 patients seen between 1963 to 1979. There were 16 such patients, giving rise to a prevalence rate of 5%. The characteristics of SLE-associated tuberculosis include a high incidence of miliary and far-advanced pulmonary disease, delay in establishing diagnosis, especially the extrapulmonary form, and tendency to attribute symptoms like fever, malaise, and weight loss to the lupus process. Treatment was successful in 9 patients. Of the 7 death 5 were attributed directly to the mycobacterial infection and 2 to complications of SLE.     

Toxoplasmosis and systemic lupus erythematosus.

The toxoplasma serological status of 50 patients with systemic lupus erythematosus (SLE) was compared with that of 50 healthy controls; high titres of toxoplasma antibody were significantly more common in the patients with SLE. These titres did not correlate with any of the routinely measured indices in SLE nor with the patients' prior treatment. A case history is used to illustrate the difficulty in diagnosing toxoplasmosis in the presence of SLE.     

Amyloidosis and systemic lupus erythematosus.

A patient with systemic lupus erythematosus who developed reactive amyloidosis associated with high levels of serum amyloid-A protein (SAA) is reported. The possible relevance of elevated SAA levels in the aetiology of amyloidosis is discussed.     

Monitoring systemic lupus erythematosus in standard clinical care

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a fluctuating and unpredictable course. Monitoring SLE in the routine clinic setting is a challenge because both the disease and its treatment can result in organ damage. Disease activity indices and a cumulative history summary can be used to track complicated patients over time. Monitoring guidelines for damage from the disease and for the toxicity of treatment are available.     

Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

Ascites in systemic lupus erythematosus.

Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of these complications.     

ANA-negative systemic lupus erythematosus.

The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of systemic lupus erythematosus (SLE). Ten patients with clinical signs of disease but persistent negative tests for ANA are examined in this study. Hair fall, Raynaud's phenomenon and recurrent oral ulcers were common in the ANA-negative group. ANA-negative SLE seems to be a subgroup of SLE that has not previously been given adequate attention.     

Triplets with systemic lupus erythematosus

We present herein the first case report of identical triplets who developed systemic lupus erythematosus (SLE). The children were diagnosed as having SLE in reverse birth order at ages 8, 9, and 11 years. Although genetically identical, each sibling manifested different clinical signs and symptoms; however, all 3 children did manifest skin rash, fatigue, and biopsy-proven glomerulonephritis at different ages. Findings of laboratory studies were similar, including positivity for antinuclear antibodies, anti-native DNA, and anti-double-stranded DNA, as well as low levels of complement. These findings confirmed SLE in each sibling.