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Genital involvement is a rare manifestation in discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), and there are few reports on vulvar clinical features. We describe a 41-year old Caucasian woman with bilateral vulvar DLE. Although vulvar lesions in lupus are probably more common than is realized, the present report is the first case of genital DLE documented in a female.
PURPOSE OF REVIEW: It is well recognized that the complement system plays multiple roles in systemic lupus erythematosus. Activation of the classical pathway by immune complexes leads to the generation of inflammatory mediators, thus promoting tissue injury. Complement activation also plays an important role in the maintenance of tolerance to self-antigens. This review discusses recent insights in the role of complement in the pathogenesis of systemic lupus erythematosus. RECENT FINDINGS: The antiphospholipid syndrome is a major feature of systemic lupus erythematosus. New findings have clearly demonstrated that the prothrombotic effects seen in a mouse model of this syndrome depend on complement activation, whereas the protective effects of heparin are due to its anticomplementary effects rather than its anticoagulant action. Secondly, a potential mechanism explaining the association of anti-C1q autoantibodies with lupus glomerulonephritis has been elucidated in a mouse model system. SUMMARY: New findings have helped to reinforce the role of complement in the etiology and tissue damage of systemic lupus erythematosus. These findings point to more precise, mechanism-based therapies for autoimmune and inflammatory disease.
Although myocarditis from a series of autopsies of patients with systemic lupus erythematosus was frequently observed, the incidence of clinically apparent myocardial dysfunction was low. A 30-year-old woman with systemic lupus erythematosus was examined by echocardiography. An acoustic densitometry was followed at the left ventricular posterior wall throughout the clinical course. A decrease in the magnitude of cyclic variation of integrated backscatter (IB) was observed before treatment. Following the combined treatment, steroid and cyclophosphamide, a repeated ultrasonic tissue characterization showed an increase in the magnitude of cyclic variation of IB. It is thought that ultrasonic tissue characterization may be a useful method to evaluate the impairment of contraction, and to follow up the clinical course of myocardial involvement in systemic lupus erythematosus.
A clinical and laboratory survey of systemic lupus erythematosus was conducted in 33 Arab patients in the UAE. Arthropathy (91%) followed by renal involvement (54%) and haematological disorders (45.5%) were the major clinical manifestations. Discoid rash (3%) was the least common. Apart from headaches, other neuropsychiatric symptoms were uncommon or not encountered. A number of distinctive clinical subsets of lupus was also observed. An unusually high prevalence of dsDNA antibodies was detected in the study (97%), compared with a prevalence of 89.5% of ANF. There was a relative paucity of anti-Ro (18.5%), La (7.5%) and RNP (11%) antibodies, but a high rate of anti-Sm(33%). The occurrence of the latter in patients with central nervous system and renal disease was insignificant. C3-Hypocomplementaemia occurred in 38.5% of the patients and a positive VDRL and Coomb's test in 9% and 24%, respectively. This study provides additional information on the characterization of systemic lupus erythematosus in various populations.
Hematopoietic stem cell transplantation was first reported for patients with systemic lupus erythematosus in 1997. The procedure has since been performed worldwide including in Europe, in Brazil, and in China. A National Institutes of Health-funded phase III clinical trial of hematopoietic stem cell transplantation for refractory systemic lupus erythematosus is anticipated to begin in 2003. Encouraging responses are raising new hope about the role of adult hematopoietic stem cells in systemic lupus erythematosus.
Subacute cutaneous lupus erythematosus is extremely rare in childhood. We report the case of a 7 year-old girl who presented annular erythematous infiltrated lesions on sun exposed areas since the age of 2 months. Histopathologic examination showed orthohyperkeratosis, epidermal atrophy, widespread hydropic degeneration of epidermal basal cell layer, and a dermal lymphohistiocytic infiltrate. The lupus band test was negative. The immunological investigations (antinuclear antibodies) were negative. Treatment with antimalarials, topical steroids and sun protection allowed clearance of the cutaneous lesions. Lesions relapsed after antimalarials discontinuation and sun exposure. Four years later, at the age of 11, the antinuclear antibodies became positive. The diagnosis of subacute cutaneous lupus erythematosus is based on the clinical aspect of lesions, topography, histological finding, evolution and immunological profile of the patient.
Photosensitivity is one of the criteria of the American Rheumatism Association for the diagnosis of systemic lupus erythematosus. Although UV irradiation is a major factor in the pathogenesis of photosensitive cutaneous lupus erythematosus, so far the exact pathomechanism is unknown. The following review presents historical, clinical and experimental data on the photobiology of cutaneous lupus erythematosus.
Three patients, 24, 24 and 25 years of age, with systemic lupus erythematosus had signs of myocardial infarction. Two had serial electrocardiographic changes indicative of infarction without any cardiac symptoms. The third patient had clinical evidence of an acute massive myocardial infarction, which was proved at autopsy to be due to coronary atherosclerosis. This case is presented in detail and the association between systemic lupus erythematosus and myocardial infarction is reviewed. It is postulated that the relation between lupus erythematosus and coronary atherosclerosis is more than coincidental.
Seventy-eight consecutive patients with systemic lupus erythematosus were assessed for the presence of livedo reticularis. The possible association of livedo reticularis with other clinical and laboratory features including anticardiolipin antibodies was explored. Thirty-eight patients had livedo reticularis. Four cases were severe, 11 moderate, and 23 mild. There was a statistically significant association between the combined moderate and severe livedo reticularis group and elevated levels of anticardiolipin antibodies. The recognized association of anticardiolipin antibodies with thrombotic events suggests a possible pathogenetic role. The presence or history of central nervous system disease, renal disease, vasculitis, or lupus inhibitor was significantly associated with the moderate and severe livedo reticularis group. Livedo reticularis may be a cutaneous marker for the later development of important systemic events in systemic lupus erythematosus.
OBJECTIVES: To determine the presenting features, prognostic factors, course, and outcome of critically ill patients with systemic lupus erythematosus admitted to the intensive care unit (ICU). DESIGN: Retrospective patient record review. SETTING: Two academic teaching hospitals. PATIENTS: All patients with systemic lupus erythematosus admitted to the ICUs between January 1982 and July 1993. MEASUREMENTS AND MAIN RESULTS: There were 28 female and two male patients. Fifteen patients were white, 11 patients were black, and four patients were Asian. The median age was 29 yrs. The reasons for admission to the ICU were multifactorial. However, most patients were admitted for infective, renal, cardiac, or coagulation complications. Despite aggressive management, 16 (53%) patients died in the ICU or shortly after discharge. The median ICU survival rate (admission to death) was 22 days. The only pretreatment factor that predicted a poor outcome was the presence of renal involvement due to systemic lupus erythematosus. CONCLUSIONS: Our study suggests that patients with systemic lupus erythematosus admitted to an ICU often have florid disease manifestations with multifactorial reasons precipitating the admission. The prognosis for such patients is poor, particularly in the presence of renal involvement.
OBJECTIVE: To describe an infant with neonatal lupus erythematosus associated with aplastic anemia. SETTING: The pediatric department in a tertiary-care hospital. INTERVENTIONS: Packed red blood cell transfusions and a 3-week course of high-dose steroid therapy. MEASUREMENTS/MAIN RESULTS: The patient presented with severe anemia and a circumscribed, reticular, macular rash on the face and neck at 5 months of age. Skin lesion biopsy revealed epidermic hyperkeratosis, hydropic degeneration of the basal layer, and deposition of immunoglobulins and granular C1q at the dermoepidermal junction. Ro/SS-A antibodies were present in the infant. BFU-E (erythroid progenitor burst-forming unit) colonies in bone marrow increased by about tenfold when suppressor CD8+ T lymphocytes were removed, indicating immune suppression of hematopoiesis. High-dose steroid therapy failed. The infant subsequently developed gram-negative sepsis, severe metabolic acidosis, and consumptive coagulopathy and died. CONCLUSIONS: Neonatal lupus erythematosus may present as part of a spectrum. The disease may range from mild and transient to a severe, life-threatening condition requiring immediate intervention, as in the case reported here. This is the first report of neonatal lupus associated with aplastic anemia due to immune-mediated suppression of hematopoiesis.
The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.
All patients with systemic lupus erythematosus (SLE) demonstrated two classes of newly synthesized DNA in sucrose density gradients of PHA (phytohemagglutinin)-stimulated lymphocytes: a large-molecular-weight fraction that comigrates with control DNA and an excess low-molecular-weight DNA (LMW-DNA) fraction not found in control lymphocytes. Excess LMW-DNA was independent of disease activity or drug therapy. LMW-DNA and serologic abnormalities were studied in a four-generation family in which two first cousins had SLE. Excess LMW-DNA was found in the cousins with SLE, sibling parents of the SLE patients, a common grandparent, four of nine siblings of one patient, and five of seven at risk children. Both males and females had excess LMW-DNA. Male-male transmission was observed. The expression of excess LMW-DNA in stimulated lymphocytes is inherited as an autosomal dominant genetic trait in this family. All unaffected adult family members with the marker had positive antinuclear antibodies (ANAs) except the grandmother. However, none of the five children with excess LMW-DNA showed positive ANAs. Excess LMW-DNA precedes the appearance of ANAs when found in children of adults with excess LMW-DNA, and may be a predisposing factor in the development of the immunologic responses of systemic lupus erythematosus.
Systemic Lupus Erythematosus (SLE), a chronic, complex disease, is the prototype for systemic human autoimmune diseases. Although environmental factors are crucial in triggering the condition, twin and family studies, as well as genetic linkage and association studies, have established its strong genetic predisposition. During the past few years, there has been considerable interest in identifying genomic segments linked to SLE through either a whole genome scan or a candidate gene approach. The discoid lupus erythematosus (DLE) skin lesion is one of the major, and discriminating, manifestations in SLE, especially in African American patients. In this study we have identified 58 multiplex families--27 African American, 26 European American, and 5 others--where at least one SLE patient is also reported to be afflicted with DLE. These families were chosen from the collection of families that are part of our ongoing linkage study for SLE. A genome-wide parametric and nonparametric linkage analysis was conducted with 320 markers. Significant evidence of linkage was identified in only one chromosomal location, 11p13, in the African American families. The maximum 2-point linkage was 5.6 in these pedigrees, obtained at a marker located 47 CM away from the pterminal end of chromosome 11. The peak multipoint LOD score of 4.6 was obtained very nearby. The segregation of this gene suggests dominant inheritance. These results reveal an important genetic effect related to discoid rash at 11p13 in African Americans with SLE, and demonstrate, through increasing genetic homogeneity, the power of pedigree stratification to detect linkage in complex diseases.
Squamous-cell carcinoma may arise in scars of chronic discoid lupus erythematosus. Although there have been 19 cases reported previously, detailed histopathologic features of this entity have not been recorded. We report a patient with extensive chronic discoid lupus erythematosus involving the scalp with subsequent development of multiple squamous-cell carcinomas. The tumors were locally aggressive with recurrences and invasion into the underlying skull and dura. The patient died of respiratory failure 4 1/2 years after initial surgical treatment. There was no clinical evidence of metastasis. Squamous carcinoma arising in discoid lupus erythematosus can be regarded as a low-grade carcinoma. Although about 20% of patients developed local recurrences and metastasis developed in about 30%, fatality occurred in only two patients (10.5%). Pertinent literature is reviewed, and the histopathologic findings, differential diagnosis, and biologic behavior of this tumor are discussed.
Cutaneous lupus erythematosus (CLE) is a heterogenous disorder with a wide range of skin manifestations. Therefore, it has been difficult to develop a unifying concept for classifying CLE from the dermatologic perspective in the past. In 2004, the classification system was updated and includes now acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Additional rarely described variants are not listed as separate entities but are included in the classical forms. Diagnosis of the different subtypes of CLE is made by considering genetic, clinical, histopathologic, and immunoserologic findings, with a systematic analysis of individual criteria. In the past years, the etiology and pathogenesis of CLE has been subject of intensive research and it has been shown by several groups that exogenous factors, such as ultraviolet light and drugs, can induce CLE. The first part of this review will enable the reader to identify the various clinical manifestations of CLE and to employ characteristic criteria to assess differential diagnostic considerations.
Invasive aspergillosis is seldomly described in systemic lupus erythematosus. We present two cases of aspergillosis and review 21 cases reported between 1957 and 1994. The typical clinical presentation is fever and cough in a hospitalized SLE patient previously treated with corticosteroids, immunosuppressors, and broad-spectrum antibiotics. Unlike aspergillosis in other conditions, granulocytopenia is uncommon. Chest radiographs show diffuse or patchy infiltration of lung fields. Diagnosis was suspected premortem in 2 patients. Aspergillus fumigatus was identified or isolated in sputum or parenchimal tissues in the majority of cases. Twenty-two patients died (95%). The finding of hyphae in the sputum of a systemic lupus erythematosus patient with a suggestive clinical picture should lead to bronchoscopy, bronchoalveolar lavage, and lung biopsy. Proof of diagnosis will come from the demonstration of hyphae in tissues and isolation of aspergillus from tissue cultures. Long-term therapy with amphotericin B alone or in combination with fluorocytosine or itraconazole may help improve survival.
OBJECTIVE: To examine protein oxidation in systemic lupus erythematosus (SLE) and to correlate levels of protein oxidation products with disease activity. METHODS: Serum was collected from SLE patients and healthy control subjects. Protein-bound carbonyls and the pro-oxidant enzyme myeloperoxidase (MPO) were quantified by enzyme-linked immunosorbent assay. Protein thiols were quantified using 5,5'-dithionitrobenzoic acid. Protein-bound amino acids and methionine, tyrosine, and phenylalanine oxidation products were quantified by acid hydrolysis and high-performance liquid chromatography. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Levels of anti-double-stranded DNA (anti-dsDNA) antibodies were measured by radioimmunoassay. RESULTS: Compared with control subjects, SLE patients exhibited elevated levels of protein carbonyls (0.108 +/- 0.078 versus 0.064 +/- 0.028 nmoles/mg of protein; P = 0.046), decreased levels of protein thiols (3.9 +/- 1.1 versus 4.9 +/- 0.7 nmoles/mg of protein; P = 0.003), decreased levels of protein-bound methionine (P = 0.0007), and increased levels of protein-bound methionine sulfoxide (P = 0.0043) and 3-nitrotyrosine (P = 0.0477). SLE patients with high SLEDAI scores or elevated anti-dsDNA antibody levels exhibited increased oxidation compared with patients with low SLEDAI scores or low antibody levels. Serum MPO levels were decreased in SLE patients (P = 0.03), suggesting that this enzyme is not responsible for the enhanced protein oxidation. CONCLUSION: We found elevated levels of multiple markers of protein oxidation in sera from SLE patients compared with controls, and these levels correlated with disease activity. The findings suggest that protein oxidation may play a role in the pathogenesis of chronic organ damage in SLE.