Lupus erythematosus cells in pleural effusion: the initial manifestation of procainamide-induced lupus erythematosus.

A 63-year-old man developed an asymptomatic pleural effusion following the administration of 500 gm of procainamide hydrochloride over a six-month period. The diagnosis was initially suggested by the finding of lupus erythematosus cells in the pleural fluid. Lupus erythematosus cells and antinuclear antibodies appeared in the blood two months later and remained for a period of six months. The diagnosis was corroborated by the presence of antibodies to denatured DNA, but not to native DNA.     

Shrinking lung syndrome in a 14-year-old boy with systemic lupus erythematosus

Pulmonary complications occur frequently in people with systemic lupus erythematosus. We report on an adolescent with an acute onset of dyspnea and pleuritic chest pain with severe restrictive lung physiology on pulmonary function testing (forced vital capacity, 20% of predicted) who had no evidence of parenchymal lung or pleural disease. He was found to have restricted diaphragmatic movement as assessed by fluoroscopy, without evidence of generalized respiratory muscle weakness. His clinical presentation and results of diagnostic tests were typical for shrinking lung syndrome. Given the rarity of shrinking lung syndrome in the pediatric age range, many clinicians are not aware of it as a clinical entity. Shrinking lung syndrome should be included in the differential diagnosis of dyspnea in both children and adults with systemic lupus erythematosus.     

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.     

Etanercept-induced lupus erythematosus presenting as a unilateral pleural effusion

A 72-year-old man receiving etanercept for the treatment of psoriatic arthritis had an exudative pleural effusion with nonspecific fluid analysis and pleural biopsy findings. He was ultimately found to have drug-induced lupus erythematosus due to the etanercept. The spectrum of autoimmune disease due to the use of tumor necrosis factor inhibitors is reviewed.     

B-cell-depleting therapy in systemic lupus erythematosus

The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus.     

Protein-losing enteropathy in systemic lupus erythematosus

Summary Enteric protein loss resulting in profound hypoalbuminemia and anasarca is an uncommon manifestation of systemic lupus erythematosus and only rarely is the initial presentation of disease. A few patients with SLE and protein-losing enteropathy in the absence of increased central venous pressure or intestinal lymphangiectasia have been reported. We describe the utility alpha-1-antitrypsin clearance in stool for diagnosing and monitoring enteric protein loss during successful immunosuppressive drug therapy in a patient who presented with massive enteric protein loss as the initial manifestation of systemic lupus erythematosus.     

Osteoporosis in systemic lupus erythematosus mechanisms

Osteoporosis is a potentially preventable condition frequently encountered in patients who have systemic lupus erythematosus (SLE). Bone loss in SLE is heterogeneous and likely a multifactorial process involving both traditional and lupus-related risk factors. Recognizing potential contributors to bone loss in the SLE patient may allow for earlier detection of osteoporosis and optimize bone health. This article reviews the current epidemiologic information available on osteoporosis and fracture data in SLE and discusses evaluation and management strategies pertinent to patients who have lupus.     

Opportunistic infections mimicking gastrointestinal vasculitis in systemic lupus erythematosus.

Patients with systemic lupus erythematosus who are on chronic immunosuppressive therapy are at risk for developing infectious complications. We present 2 cases of immunosuppressed patients with systemic lupus erythematosus who presented with abdominal complaints without other systemic lupus symptoms. These patients were initially thought to have gastrointestinal vasculitis based on preliminary pathologic reports; however, further workup and careful review of the pathologic specimens confirmed an opportunistic infection as the etiology in each case. It is critical that physicians maintain a high index of suspicion for infection when treating immunocompromised patients with systemic lupus erythematosus with abdominal complaints to avoid delay in appropriate treatment.     

Interferon pathway activation in systemic lupus erythematosus

The recognition that a multitude of interferon (IFN)-inducible genes are coordinately expressed in peripheral blood cells of patients with systemic lupus erythematosus (SLE) has contributed to considerable interest in the IFN pathway as a therapeutic target in lupus. Together with data that have accumulated over the past four decades implicat-ing IFN-á in SLE, the gene expression data have resulted in emergence of this cytokine pathway as a focal point for understanding mechanisms of autoimmunity and inflamma-tion in systemic autoimmune diseases. Assays that measure IFN-inducible gene expression in patient cells and tissues and plasma assays that quantify IFN-á protein are providing tools for identification of patients with active disease and who may be responsive to inhibition of the innate immune system component of the altered immune response in SLE. In addition, investigations of the mecha-nisms of induction of IFN pathway activation are suggesting clues to the triggers of autoimmunity in SLE.     

A case of systemic lupus erythematosus presenting with protein-losing enteropathy.

We report an unusual case of systemic lupus erythematosus presented with protein-losing enteropathy. A 24-year-old girl was referred to our hospital with generalized edema, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, hypocomplementemia, antinuclear antibody (ANA) (speckled pattern) and anti- SSA/Ro positivities, and elevated CA125 antigen appeared in the blood examination. On the radiological studies, she had mild pleural effusion and moderate ascites which were transudate. A diagnosis of protein-losing enteropathy was made on the basis of increased 99mTc-labelled human immunoglobulin scintigram showing abnormal radioactivity. Endoscopic gastric, duodenal and jejunal biopsies showed chronic inflammation, but vasculitis and immune complex deposition findings were not present. Renal biopsy revealed no definitive findings of lupus nephritis. By the administration of corticosteroids, hypoalbuminemia began to improve, but steroid doses were decreased due to steroid-induced myopathy. Temporary hemiparesis and facial paralysis developed in the patients' follow up. Her cranial magnetic resonance imaging revealed chronic ischemia, and the patient was considered to have neurological involvement due to systemic lupus erythematosus. protein-losing enteropathy and other symptoms then improved dramatically after monthly intravenous cyclophosphamide (three times) combined with oral low-dose corticosteroids. The combination of azathioprine and low-dose steroids was used as maintenance medication. Although about 30 protein-losing enteropathy -associated systemic lupus erythematosus cases have been reported, the patients having initial symptoms as protein-losing enteropathy are rare in the literature. Protein-losing enteropathy -associated systemic lupus erythematosus cases probably represent a subgroup of systemic lupus erythematosus, the characteristics of which are hypocomplementemia, protein-losing enteropathy, ANA positivity showing speckled pattern and anti-ds DNA negativities. In the patients with systemic lupus erythematosus with edema and hypoalbuminemia without renal protein loss, protein-losing enteropathy-associated systemic lupus erythematosus should be kept in mind.     

Epstein-Barr virus and systemic lupus erythematosus

PURPOSE OF REVIEW: Systemic lupus erythematosus is a complex human disease likely influenced by a compilation of necessary, but not individually sufficient, features. Although many genetic and environmental factors are associated, this review will focus on the evolving evidence for key Epstein-Barr virus specific roles. RECENT FINDINGS: Recent studies have shown additional molecular mimicry mechanisms between early events in lupus autoimmunity and specific Epstein-Barr virus responses. In addition, several recent papers have demonstrated increased Epstein-Barr viral load, increased numbers of latently infected peripheral B cells, impaired functional T cell responses, and association of the presence of Epstein-Barr virus DNA in systemic lupus erythematosus patients compared with controls. Additional work has continued to show association of various aspects of Epstein-Barr virus serology with systemic lupus erythematosus and a recent paper outlines differences in the pediatric systemic lupus erythematosus humoral immune response to Epstein-Barr virus nuclear antigen-1 compared with matched controls. SUMMARY: This review will briefly outline the recent advances that show serologic, DNA, gene expression, viral load, T cell responses, humoral fine specificity, and molecular mimicry evidence for differences between systemic lupus erythematosus patients and controls and the impact that these findings have on understanding the role of Epstein-Barr virus in systemic lupus.     

Systemic lupus erythematosus presenting as chronic serositis with no demonstrable antinuclear antibodies

Approximately 5 percent of patients with systemic lupus erythematosus by clinical and pathologic criteria have no demonstrable antinuclear antibodies. This figure is likely to be an underestimate, as it does not include the antinuclear antibody-negative patients with limited manifestations in whom the diagnosis of systemic lupus erythematosus is missed. A 23-year-old woman is described who had a history of perplexing bilateral pleural effusions with development of peritoneal effusion after 18 months and positive antinuclear antibody results after 22 months. Tissue pathologic features, initially interpreted as nonspecific, on review revealed striking lymphocytic periarteritis with endothelial swelling and leukocytoclastic vasculitis often seen in systemic lupus. A selective defect in the suppression of T cell effector function, such as direct cell-mediated cytotoxicity, with intact suppressor systems for B cell effector function, such as antibody production, can be postulated in this patient. This would explain the active cellular tissue pathology with the lack of prominent antinuclear antibody production.     

Anticytokine therapy in systemic lupus erythematosus

Systemic lupus erythematosus is a prototype of heterogeneous autoimmune disease. There have been few newly approved therapeutic agents in lupus treatment for many reasons. Several animal studies and human data have shown that many potential cytokines are related to the pathogenesis and disease activity of systemic lupus erythematosus. Cytokines are produced by many immune cell types and have variable functions in the immune system. Following the success of biological agents in the treatment of inflammatory arthritis, inflammatory bowel disease, and psoriasis, biological targeting to specific cytokines or receptor molecules is now promising in the treatment of systemic lupus erythematosus. In addition to B-cell deleting modalities, clinical trials targeting potential cytokines associated with disease pathogenesis are underway at various clinical stages. Among potential cytokines, targeting agents against B-cell activating factor and interferon-alpha are in the most advanced stage, and belimumab (anti-B-cell activating factor antibody) could be the first biological agent approved in the treatment of systemic lupus erythematosus. Anti-tumor necrosis factor was tried with some success, but with a potential risk of infection in a small number of patients. In this review, we discuss the rationale for anticytokine therapies and review agents currently in clinical trials, and those that could be developed in the near future for systemic lupus erythematosus. We present the results mostly from published trials and data from http://clinicaltrials.gov/ct2/     

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.     

Immunoglobulin deficiency in patients with systemic lupus erythematosus

Hypergammaglobulinemia is a common laboratory finding in patients with active systemic lupus erythematosus; in contrast, immunoglobulin deficiency, except for immunoglobulin A, is unusual. We report 18 patients who developed low immunoglobulin G levels 4 months to 22 years (median = 4 years) following the diagnosis of systemic lupus erythematosus. This phenomenon was transient in 10 patients (median duration 10.5 months). Eight patients had received cytotoxic drugs prior to the development of hypogammaglobulinemia, while all had received prednisone. The nadir levels of serum IgG were 132-550 mg/dl (median = 363 mg/dl). The presence and degree of immunoglobulin G deficiency did not correlate, in general, with the type or dose of medication. None of the patients had renal failure. Only 4 patients developed recurrent infections. Urinary loss of protein was not a cause of this disorder. Study of the in vitro cellular immune responses of peripheral blood lymphocytes in 5 patients showed that excessive 'suppressor' T cell activity and decreased numbers of B cells may be responsible for the development of immunoglobulin deficiency. Serum immunoglobulin levels should not be employed as an indication of disease activity in systemic lupus erythematosus, as all 18 patients continued to have significant clinical disease. Deficiencies of immunoglobulins are often transient and may not require treatment.     

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.     

T-regulatory cells in systemic lupus erythematosus

Thymus-derived CD4(+)CD25(high)Foxp3(+) T-regulatory cells (Tregs) have an important role in the mechanisms of peripheral immune tolerance and in the prevention of pathogenic autoimmunity through the suppression of proliferation and production of pro-inflammatory cytokines in effector immune cells. Some studies have shown that in systemic lupus erythematosus (SLE) the number of circulating Tregs may be decreased during active disease, and that the extent of such decrease may correlate with severity of the disease. Recent data in murine models of lupus have suggested the possibility to target Tregs for the modulation of SLE, and Treg-based intervention has been proposed as a novel therapeutic mean for a better management of the disease. This review provides an update on the role of Tregs in SLE, discussing new findings in relation to possible targeting of Tregs for immune modulation in lupus.     

Minoxidil-induced systemic lupus erythematosus

A patient treated for two months with the antihypertensive agent minoxidil developed pleural and pericardial effusions in association with a positive antinuclear antibody titer. No evidence of central nervous system or renal involvement was present, and results of specific tests for idiopathic systemic lupus erythematosus, including anti-double-stranded DNA and anti-Smith antibodies, were negative. Complement levels were normal. The patient's clinical picture improved and titers of antinuclear antibody decreased after discontinuation of minoxidil therapy, suggesting that minoxidil induced a lupus-like syndrome in this patient.     

Blood rheology in lupus erythematosus.

Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.