Hypocomplementemia with low C1s-C1 inhibitor complex in systemic lupus erythematosus

Ninety-three serum and plasma samples from 45 patients with systemic lupus erythematosus were analyzed for the complex formed by C1s and its inhibitor, as well as for C3, C4, C4a desarginine, and staphylococcal protein A-bound immune complexes. There were statistically significant correlations between C1s-C1 inhibitor complex and CH50, between C1s-C1 inhibitor complex and C4, and between C1s-C1 inhibitor complex and C4a desarginine. Serial studies were performed on 24 patients over a period of 6 months. Seven of 21 patients with hypocomplementemia had persistently normal levels of C1s-C1 inhibitor complex, 7 had transiently abnormal levels of C1s-C1 inhibitor complex, and 7 had sustained abnormal levels of C1s-C1 inhibitor complex. Two of 3 pregnant patients with normal levels of complement had abnormal levels of C1s-C1 inhibitor complex. Staphylococcal protein A-bound immune complexes demonstrated no correlation with any of the complement assays. Complement activation, as measured by C1s-C1 inhibitor complex, is often a transient phenomenon in systemic lupus erythematosus patients with persistent hypocomplementemia.     

Hypocomplementemia in hydralazine-associated systemic lupus erythematosus

Drug-associated lupus erythematosus is said to be differentiated from idiopathic lupus erythematosus by the invariable presence of normal serum complement levels in the former. A unique patient with hydralazine-associated lupus is described in whom activation of the complement system is documented. Other unusual features of hydralazine-associated lupus are discussed.     

Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender (P < 0.001), fever (P = 0.021), nephropathy (P < 0.001), cutaneous vasculitis (P = 0.023), positive anti-dsDNA antibodies (P = 0.012) and cryoglobulinemia (P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia (P = 0.001) and antiphospholipid antibodies (P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis (P = 0.022), thrombocytopenia (P = 0.004), lupus anticoagulant (P = 0.013), positive IgM-aCL (P = 0.039), positive ANA (P = 0.002) and anti-dsDNA (P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.     

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.     

Detection of low avidity anti-dna antibodies in systemic lupus erythematosus

The binding of sonicated, radiolabeled DNA by systemic lupus erythematosus (SLE) sera was measured by a high sensitivity polyethylene glycol (PEG) precipitation assay. This method is considerably more sensitive than currently used techniques. The results suggest that a significant concentration of low avidity antibodies is present in SLE sera; however, these antibodies are not detected by conventional techniques.     

Hyperprolactinaemia in patients with systemic lupus erythematosus

OBJECTIVE: To verify the presence of hyper-PRL in SLE patients, its association with high disease activity, specific organ involvement or presence of anti-ds-DNA antibodies. METHODS: The group under study consisted of 80 patients with systemic lupus erythematosus (SLE), 28 patients with rheumatoid arthritis (RA) and 27 healthy controls. PRL serum levels were assayed using standard commercial kits (Immunotech Prague) with the radioimmunometric method for testing three samples of each of the subjects. The samples were taken in the morning hours (9-11 a.m.) of absolute rest 30 minutes after the introduction of the cannula at 30-minute intervals. RESULTS: A significantly higher rate of elevated PRL levels was found in SLE patients (40.0%) compared with the healthy controls (14.8%, p < 0.017). No proof was found of association with the presence of anti-ds-DNA or with specific organ involvement. Similarly, elevated PRL levels were found in RA patients (39.3%). The PRL elevation tended to decline from the 1st to the 3rd sample in the group of patients with SLE and RA but not in healthy controls. CONCLUSION: As follows from our measurements of prolactin serum values in SLE patients they are varriable by definition. According to our opinion further investigations are needed.     

Infection in patients with systemic lupus erythematosus

We have found subnormal amounts of chemotactic activity in zymosan-treated sera from 13 of 29 patients with systemic lupus erythematosus (SLE). As an explanation for this abnormality, the presence of a uniquely specific, heat-stable inhibitor of complement (C5)-derived chemotactic activity has been documented in sera from 11 of these patients. Sera from 2 other patients contained elevated levels of nonspecific, heat-labile chemotactic factor inactivator (CFI) activity. The serum from 1 patient contained the heat-stable inhibitor as well as elevated levels of CFI. Patients with SLE whose sera contained the heat-stable inhibitor had more active disease clinically, but otherwise they were indistinguishable from patients without the inhibitor. When patients with the heat-stable inhibitor improved clinically, this usually was accompanied by a decrease in serum inhibitory activity. Only one episode of bacterial infection was observed among 16 patients with SLE whose sera yielded normal amounts of chemotactic activity after treatment with zymosan. In contrast, 7 of 11 patients with SLE whose sera contained the heat-stable inhibitor suffered serious bacterial infections. The presence of this heat-stable inhibitor in sera from some patients with SLE may contribute, in part, to their increased susceptibility to infection.     

Osteomyelitis in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the clinical profile of and the risk factors for osteomyelitis in patients with systemic lupus erythematosus (SLE). METHODS: We reviewed 11 consecutive cases of patients with SLE who had also had osteomyelitis between 1981 and 2001 at a medical center in Taiwan, with special attention to predisposing factors, clinical features, laboratory values, and outcomes. RESULTS: The mean age at diagnosis of osteomyelitis was 34.5 +/- 22.0 years and the ratio of females to males was 9:2. The typical initial manifestations were nonspecific focal pain (82%) and fever (64%). The most commonly affected sites were the long bones (6 cases, 54%), followed by the vertebrae (4 cases, 36%). Salmonella (5 cases, 45%) and Staphylococcus aureus (4 cases, 36%) were the major causative organisms. Interestingly, once long bones had become involved, 5 of 6 (83%) isolates proved to be Salmonella, and for vertebral osteomyelitis, 3 of 4 (75%) isolates proved to be S. aureus. Predisposing factors include an active status of SLE (SLEDAI score >/= 4, 100%), coexistent underlying systemic disease (91%), chronic renal disease (82%), and intensified immunosuppressive agent usage (82%). Laboratory values either reflected an acute phase reaction that would be expected in an infection, such as a raised C-reactive protein (100%) and neutrophilia (55%), or reflected features consistent with active lupus disease. Four patients had longterm motor deficits and another patient died. Poor prognostic factors include delayed diagnosis, vertebral involvement, artificial implants in bones, and chronic carrier status. CONCLUSION: In patients with SLE who present with local osteoarticular pain, particularly those whose disease is active and who also have chronic renal disease and were taking intensified immunosuppressive agents, osteomyelitis must be considered seriously. Salmonella should be considered as a potential contributing pathogen for long bone osteomyelitis and S. aureus should be considered for cases of vertebral osteomyelitis when conducting empirical antimicrobial therapy. Early recognition and treatment is essential to avoid longterm sequelae or death.     

Infections in patients with systemic lupus erythematosus

Infection is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). In most clinical series, infection ranks first or second as the most common cause of death in SLE patients worldwide, including Hong Kong. In this article, the spectrum of infections and their protean manifestations in lupus patients will be reviewed with emphasis on clinical data from Hong Kong and other Asian countries. A high index of suspicion and dedicated work‐up to identify the causative pathogens is pivotal to the early diagnosis and effective management of infective complications in patients with SLE.     

Contraception in adolescents with systemic lupus erythematosus

In the management of adolescents with systemic lupus erythematosus (SLE), sexual activity and prevention of unwanted pregnancies are important topics. Many contraceptive methods are available nowadays. Oral contraceptives (OCs) are the preferred choice among adolescents in general. However, the use of these medications in adolescents with SLE raises serious concerns, particularly the risk of thrombotic events from estrogen exposure and the impact of these medications on lupus activity. In this article, different contraceptive methods available are reviewed and their application in adolescents with SLE is discussed. In conclusion, OCs are the methods of choice in adolescents with stable disease and no antiphospholipid antibodies (aPL) detected. In patients with aPL, fewer options are available, and the selection of the preferred form of contraception should be made on an individual basis.     

Narcolepsy associated with systemic lupus erythematosus

Many neurologic and psychiatric manifestations have been associated with systemic lupus erythematosus. Narcolepsy, currently hypothesized as related to an autoimmune process, has been rarely associated with systemic lupus erythematosus. We report a 36-year-old woman who presented with narcolepsy and who subsequently developed systemic lupus erythematosus. Excessive daytime sleepiness resolved after the administration of four intravenous bolus of cyclophosphamide and methylprednisolone followed by maintenance therapy with hydroxychloroquine, aspirine and prednisone. Narcolepsy should be included in the neuropsychiatric manifestations of systemic lupus erythematosus and it may have a parallel clinical course to the activity of the lupus.     

Factors associated with low bone mineral density in female patients with systemic lupus erythematosus

OBJECTIVE: To study risk factors for low bone mineral density (BMD, g/cm) in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-two consecutive patients with SLE followed by rheumatology faculty between 1997 and 1999 completed a questionnaire regarding lifestyle during the clinic visit, a chart review was performed, and data were collected for the time of the first dual energy x-ray absorptiometry (DXA) examination. Univariate and multivariate statistical analyses were used to assess relationships between various risk factors and BMD. RESULTS: Ninety-eight percent of patients had received prednisone, 51% were postmenopausal (9 of whom received hormone replacement therapy), 68% had received hydroxychloroquine, and 15% were osteoporotic. The following factors were found to be significantly related to lower BMD by univariate analysis: Caucasian race, older age at diagnosis, higher age at the time of the first DXA, longer disease duration, higher cumulative corticosteroid dose, higher SLE Damage Index score, and postmenopausal status. In the multivariate analysis only the following factors were significant: Caucasian race, increased number of pregnancies, postmenopausal status, higher SLE Damage Index, and higher cumulative corticosteroid dose. An unexpected finding was that taking hydroxychloroquine was the only factor associated with higher BMD of the hip and spine in the univariate analysis, and it remained predictive of higher BMD of the hip and spine in the multivariate analysis. CONCLUSION: Hydroxychloroquine appears to protect against low BMD in corticosteroid treated patients with SLE.