Exacerbation Of Systemic Lupus Erythematosus Research Articles

Does HT Exacerbate Lupus

Increased risk for systemic lupus erythematosus (SLE) among women of childbearing age, combined with data from observational studies, has raised concerns about exacerbations of SLE during estrogen administration. However, menopausal symptoms, as well as osteoporosis risk, may warrant hormone therapy in some women. In this NIH-funded, double-blind study, investigators randomized 351 menopausal women with SLE to receive HT (0.625 mg conjugated estrogen …

Infections and SLE

Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.

Influência do estresse psicossocial no lúpus eritematoso sistêmico

Vários estudos mostram que doenças clínicas podem piorar sob a influência de fatores psicologicamente estressantes. Entretanto, poucos estudos foram feitos para estabelecer esta correlação no lúpus eritematoso sistêmico (LES). No presente artigo, revisamos estudos sobre a associação ou influência de estresse psicológico ou social em pacientes com LES. Os estudos foram identificados por uma busca no Medline, através dos termos "stress", "lupus", "disease activity" e "flare". Foram selecionados 14 artigos que apresentaram uma grande variação na metodologia empregada. A maioria falhou em encontrar associações entre a presença de estresse e a piora da atividade laboratorial ou clínica do LES. Apesar disso, foi identificada uma associação positiva entre presença de estresse e pior percepção da saúde física pelo paciente, através de medidas subjetivas. Três estudos de modelo laboratorial de estresse psicológico mostraram que a resposta biológica ao estresse em pacientes com LES difere de controles normais e pacientes com artrite reumatóide. Apenas um estudo mostrou que estresse diário em relações ou obrigações sociais no mês prévio precedia a exacerbação do LES.

Systemic Lupus Erythematosus Complicated by HELLP Syndrome

We describe a pregnant woman with systemic lupus erythematosus, complicated by severe pre-eclampsia (the HELLP syndrome) and adult respiratory distress syndrome, who died in the intensive care unit. A 33-year-old multigravid woman was referred to our university hospital at 17 weeks' gestation because of an exacerbation of systemic lupus erythematosus with elevated liver enzymes and thrombocytopenia. At the time of admission, on physical examination she had revealed a butterfly rash over the cheeks, purpura, acute synovitis and oedema of the legs. Her blood pressure was 180/100 mmHg. The initial laboratory tests and immunological evaluation confirmed active systemic lupus erythematosus complicated by severe pre-eclampsia. One week after admission, she became suddenly confused and had a convulsion with Glascow Coma Score 10 (3+3+4). Therapeutic abortion was induced in the Obstetric Department. She was transferred to the intensive care unit with a diagnosis of respiratory failure, probably due to acute respiratory distress syndrome, and was intubated and ventilated. Dialysis was instituted on two consecutive days from the eighth day. In total she received over 20 units of red blood cells and large quantities of fresh frozen plasma and platelets. On the 24th day her Glascow Coma Score was 2 (1+1+E) and severe hypotension developed. She died from worsening acute respiratory distress syndrome on the 25th day. Women with systemic lupus erythematosus should be advised to become pregnant when the disease is inactive and should be observed at an appropriate centre using a multidisciplinary approach. Therapeutic abortion is an acceptable option if active nephropathy and severe pre-eclampsia are present in early pregnancy.

Estrogen Therapy in Systemic Lupus Erythematosus

Given the female preponderance of systemic lupus erythematosus (SLE) in humans, the adverse effects of female gender and sex hormones in murine lupus, and numerous reports (retrospective, often anecdotal and uncontrolled) that describe a temporal association between estrogen exposure and development or exacerbation of SLE, it is tempting to accept that estrogens and SLE simply do not mix. While there are valid concerns regarding the use of exogenous estrogens in women with SLE, there are also potential health benefits to be considered. Oral contraceptives (OCs) offer effective birth control and may be bone protective in corticosteroid-treated patients. Recent studies, albeit retrospective, suggest that OCs are well tolerated in patients with SLE. Several salutary effects of postmenopausal estrogens assume particular importance in SLE where the risks of osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and corticosteroids, are substantial. However, the results of the Women's Health Initiative trial significantly limit the use of hormone replacement therapy in the general population, and raise particular concern for SLE patients. Other exogenous hormones (clomifene, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous estrogen and to stimulate ovulation in patients with diminished fertility. Patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit from OCs and other hormonal therapies without a change in lupus activity. Large prospective, double-blind, placebo-controlled studies inclusive of all ethnic groups should provide the basis for more definitive recommendations.

Calculating the etiology of systemic lupus erythematosus

Objective was to clarify the etiology and pathogenesis of systemic lupus erythematosus (SLE). Drug-induced lupus (DIL) and SLE are both found in humans, are exacerbated by the same viruses or drugs, and they are both more common in slow acetylators. Thus, DIL can be used as a model for SLE and the Adhami equation of DIL can be applied to SLE. Polyamines are the only possible link between the viral and amine hypotheses of SLE pathogenesis. Based on the Adhami equation, polyamines can explain the actual annual incidence of SLE in the general population. Putrescine is a very weak SLE-causing agent, while spermine and spermidine contribute equally in triggering SLE. The positively charged polyamines bind to negatively charged internucleosomal DNA and change its conformation from B (non-immunogenic) to Z (immunogenic). This is the major contribution of polyamines in triggering SLE. The other effects of polyamines are only secondary. Apoptosis is a necessary step in SLE pathogenesis, because it causes the internucleosomal fragmentation of DNA and exposes Z-DNA to the immune system (due to cell death). The next step is the production of anti-DNA antibodies, followed by other SLE phenomena. Polyamines not only cause SLE, but they are also important in sustaining the disease. Other endogenous and exogenous amines have additive effects with polyamines and may contribute in exacerbating SLE. When SLE is in the active phase, polyamine levels are higher as compared to remissions. Fluctuations in polyamine levels due to diet, metabolic factors, infections, intestinal flora, etc. or the presence of other amines may explain the course of SLE, characterized by remissions and exacerbations. Acetylcysteine is a drug that can be completely metabolized to acetyl groups. As such, this drug is proposed as the ideal acetyl donor for the acetylation of polyamines and other SLE-triggering compounds. Clinical trials will be necessary to test the role of acetylcysteine in the etiologic treatment of SLE. Conclusions: Changes in DNA conformation by polyamines are the first step in SLE pathogenesis. Many genetic and environmental factors may increase or decrease the effects or levels of polyamines, causing SLE exacerbations or remissions. Viruses and other infectious agents may cause SLE by producing polyamines or by increasing the levels of endogenous polyamines. The major autoimmune diseases are characterized by remissions and exacerbations and not by a continuously progressive course, as commonly believed. Consequently, they are not sustained by internal vicious cycles, but by the initial triggering agent(s). While the conventional treatment of autoimmune disorders is important in minimizing tissue damage, the neutralization of their etiology may be important in curing and preventing autoimmunity.

Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE).

We investigated the production of IL-2, IFN-gamma, IL-10 and IL-4 by PBMC from 24 patients with SLE and 10 healthy individuals. Basal and mitogen-stimulated (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was determined in a whole blood assay (WBA). Supernatants were collected and assayed with specific ELISAs. Although the IL-2 and IFN-gamma contents did not differ significantly between patients and controls under both conditions, statistically significant correlations were found between each cytokine and disease activity (SLAM index) after stimulation (respectively, r = 0.501, P = 0.01 and r = 0.631, P = 0.001). PBMC IL-10 production was significantly higher for patients than controls (P = 0.05), but no correlation between IL-10 levels and the SLAM index was obtained. IL-4 production was not statistically different between SLE patients and controls. For stimulated WBAs, the IL-10/IL-2 and IL-10/IFN-gamma ratios were significantly correlated with disease severity (P = 0.02; P = 0.001, respectively). Overall, our data suggest that SLE is characterized by an elevated production of IL-10, reflecting the basal state of activation of the immune system. During exacerbation of SLE, IL-2 and IFN-gamma are synthesized in larger amounts and may cause the tissue damage observed.

Catastrophic Antiphospholipid Syndrome

Catastrophic Antiphospholipid Syndrome

Terbinafine-induced subacute cutaneous lupus erythematosus

Background: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. Objective: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. Methods: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. Results: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 412 months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. Conclusion: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons. (J Am Acad Dermatol 2001;44:925-31.)

Evidence for pleomorphism of estrogen receptor capacity and affinity in liver and thymus of immature BALB/c and (NZB×NZW) F1 mice, a model of systemic lupus erythematosus

Binding properties of estrogen receptors in liver, thymus and uterus of BALB/c and (NZB×NZW) F1 mice were compared. (NZB×NZW) F1 mice spontaneously develop an autoimmune disease resembling human systemic lupus erythematosus (SLE). It is hypothesized that estradiol, through its receptors, mediates the progression of murine SLE. High-speed cytosols were prepared from liver, thymus and uterus and incubated with the synthetic estrogen 3H-moxestrol (NEN). Scatchard plots were derived from binding isotherms obtained. Rectilinear Scatchard plots were obtained from all tissues, which is consistent with the presence of only one class of binding sites, or of more than one class but with the same affinity. There were, however, strain differences in that the affinity of the binding reaction was significantly higher in cytosols from BALB/c liver in males and females. In thymus, the situation was reversed in that the affinity was significantly higher in cytosols from (NZB×NZW) F1 mice. Thymic cytosols from BALB/c mice contained significantly more estrogen receptors per mg cytosol protein than did those from (NZB×NZW) F1 mice. The exacerbation of murine SLE may be due, at least in part, to these properties of estrogen receptors in liver and thymus.

Epoprostenol for Treatment of Pulmonary Hypertension in Patients With Systemic Lupus Erythematosus

Pulmonary hypertension with pathological changes similar to those observed in primary pulmonary hypertension occurs in patients with systemic lupus erythematosus (SLE). The efficacy of chronic epoprostenol therapy in SLE has not been well described. The objective of this paper is to describe our experience with long-term epoprostenol therapy in patients with pulmonary hypertension associated with SLE. Case series of six patients with SLE and associated pulmonary hypertension receiving chronic treatment with epoprostenol. All 6 patients had severe pulmonary hypertension. Mean pulmonary artery pressure (mPAP) was 57 +/- 9 mm Hg (mean +/- SD), and pulmonary vascular resistance was 14 +/- 7 units before beginning therapy with epoprostenol. In 4 patients who underwent repeat hemodynamic evaluation (9 to 16 months after starting epoprostenol), mean pulmonary artery pressure decreased by 38 +/- 21% and pulmonary vascular resistance by 58 +/- 12%. Clinically, all patients improved from New York Heart Association class III or IV to class I or II. Doses of epoprostenol ranged from 4 to 46 ng/kg/min, and the longest duration of therapy has been 2.5 years. Side effects from epoprostenol have not differed from those seen in patients with primary pulmonary hypertension, and except for one patient, there has been no exacerbation of SLE. Epoprostenol was effective for the treatment of pulmonary hypertension in this small group of patients with SLE. Further evaluation of epoprostenol therapy for patients with SLE and other diseases associated with pulmonary hypertension is warranted.

New Zealand mixed mice: a genetic systemic lupus erythematosus model for assessing environmental effects.

Systemic lupus erythematosus (SLE) is a multiphenotypic autoimmune disease. The hallmark of SLE is the production of anti-double-stranded DNA autoantibodies and the deposition of immune complexes in target tissues such as the kidney, skin, and brain. Additional phenotypic traits are the presence of arthritis, anemia, central nervous system involvement, and a variety of autoantibodies. Females of childbearing age are particularly at risk. Recent genetic analysis of murine SLE shows that susceptibility is under complex polygenic control. It is also apparent that environmental factors contribute to the induction and exacerbation of SLE. We describe here the genotypic and phenotypic characterization of a group of recombinant inbred strains of SLE-prone mice that were derived from NZB and NZW progenitors, the parental strains of the classic female F1 hybrid lupus model. Recombination and reassortment of these ancestral genomes resulted in the NZM (New Zealand mixed) strains with strain-specific patterns of renal disease penetrance and other autoimmune traits such as Coombs positive anemia and neurologic deficits. Multiple susceptibility loci of the ancestral strains demonstrate that SLE is inherited as a threshold trait. Because some of these loci co-localize with the susceptibility loci of the insulin-dependent diabetes of nonobese diabetic strain, it is apparent that there are disease-specific as well as autoimmunity-promoting genes. It is proposed that the NZM strains, particularly those with reduced disease penetrance or partial genotypes, provide an improved genetic model for assessment of the effects of environmental agents on SLE and autoimmunity.

Severe exacerbation of systemic lupus erythematosus after hepatitis B vaccination and importance of pneumococcal vaccination in patients with autosplenectomy: Comment on the article by Battafarano et al

Severe exacerbation of systemic lupus erythematosus after hepatitis B vaccination and importance of pneumococcal vaccination in patients with autosplenectomy: Comment on the article by Battafarano et al

Lupuslike Reaction Associated With Minocycline

To the Editor. —Minocycline hydrochloride is a semisynthetic derivative of tetracyline. Although approved by the US Food and Drug Administration (FDA) for the treatment of infections caused by a variety of microorganisms,1recent data indicate that from 1990 through July 1996, approximately 65% of oral minocycline use in the United States was for treatment of acne.2 In a recent article, Gough and colleagues3described cases of autoimmune systemic lupus or both associated with the use of minocycline in the United Kingdom. Lupuslike symptoms and autoimmune hepatitis in association with minocycline use in US patients have not been described in the literature. However, US product labeling for minocycline lists hepatitis, exacerbation of systemic lupus erythematosus, and [a] transient lupus-like syndrome as possible adverse reactions.1 From 1972 through February 1996, the FDA's MEDWatch Reporting Program had received only 1 report of a case resembling the autoimmune

Unusual adverse reaction in a patient sensitized with Photosan 3

Serious side effects of photodynamic therapy (PDT) are rare (A.L. Abramson, M.J. Shikowitz, M.J. Shikowitz, V.M. Mullooly, Clinical effects of photodynamic therapy on recurrent laryngeal papillomas, Arch. Otolaryngology Head Neck Surg., 118 (1992) 25–29; A.L. Abramson, M.J. Shikowitz, Clinical exacerbation of systemic lupus erythematosus after photodynamic therapy of laryngotracheal papillomatosis, Laser Surg. Med., 13 (1993) 677–679). The most frequent side effects of PDT are hypersensitive skin reactions, local edema, nausea, a metallic taste and liver-toxicity (J. Feyh, E. Kastenbauer, Treatment of laryngeal papillomatosis with photodynamic laser therapy, Laryngorhinootologie, 71 (1992) 190–192; J. Feyh, R. Gutmann, A. Leunig, Die Photodynamische Therapie im Bereich der Hals-, Nasen-, Ohrenheilkunde Laryngorhinootologie, 72(6) (1993) 273–278; M.S. Kavuru, A.C. Mekta, Treatment of recurrent respiratory papillomatosis, N. Engl. J. Med., 326 (1992) 204–205; B.L. Wenigg, D.M. Kurtzmann, Photodynamic therapy in the treatment of squamous cell carcinomas of the head and neck, Arch. Otolaryngol Head Neck Surg., 116 (1990) 1267–1270). In this case a patient (aged 57 years) suffering from a recurrent larynx papillomatosis was treated with PDT. He was sensitized with Photosan 3 (DHE) 2.5 mg kg −1 body weight, 24 h to photoradiation. As a light source, an argon dye lase, operating at a wavelength of 630 nm was used, coupled with a cylindrical light applicator. After treatment the patient was admitted to an intensive care unit for 24 h. 3 h after photoradiation, general urticarial wheals arose, as well as techycardia and a decrease in blood pressure followed by all the signs of serious anaphylaxis. 1.5 h after treatment with adrenaline and cortisone and stabilization of the cardiac and circulatory situation no more skin lesions were visible.

End-stage renal disease and systemic lupus erythematosus

To provide an overview of the course of systemic lupus erythematosus (SLE) following the onset of end-stage lupus nephropathy, regarding clinical and serological manifestations, survival on dialysis, and renal transplant outcomes. A review of the pertinent literature, identified by a comprehensive Grateful Med search, was performed. There is a tendency for decreased clinical and serological lupus activity following the onset of end-stage renal disease. The pathophysiology of this quiescence remains unclear. Survival of lupus patients on dialysis is no different from that of non-SLE dialysis patients, and is better than that of several other rheumatic diseases. Following renal transplantation, there is no difference in patient or graft survival in lupus versus nonlupus patients. Like their nonlupus counterparts, SLE transplant patients do better with living relative grafts and/or regimens containing cyclosporin A. Transplantation is not recommended within 3 months of the initiation of dialysis to allow possible recovery from the acute renal failure. Transplantation during an acute exacerbation of SLE is controversial, and may increase the risk of poor outcomes. Recurrence of lupus in transplanted allografts, often with the same histopathology as in the native kidney, occurs at a rate (2.7% to 3.8%) comparable to that for all allograft transplant failures (2% to 4%). End-stage lupus nephropathy patients require less medication owing to decreased disease activity. They are good candidates for dialysis and renal transplantation, with survival and recurrence rates no different from those of other patients with end-stage renal disease.

Parvovirus infection mimicking systemiclupus erythematosus

There are striking similarities between human parvovirus B19 (HPV-B19)infection and systemic lupus erythematosus (SLE): both may present with malar rash, fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 infection mimicking SLE and review 10 other reported cases, all of whom were women. The similarity to a typical SLE presentation was indeed striking: most patients presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, HPV-1319 infection seemed to exacerbate SLE rather then resemble it, and differentiation was difficult. Nearly all patients improved within several weeks. However, a few patients had symptoms and laboratory abnormalities lasting more than 6 months. The possibility of HPV-B19 infection should be entertained in patients presenting with SLE-like features.

Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract.

Experimental data suggest a role for the microflora in the disease expression of systemic lupus erythematosus (SLE). In active SLE anti-ds-DNA antibodies are supposed to be pathogenic by forming immune complexes with DNA. Bacteria might induce the production of anti-ds-DNA antibodies. To explore the relation between the host and his microflora in SLE in comparison with healthy controls we studied the prevalence of systemic antibodies to faecal bacteria that were discriminated by their morphology by indirect immunofluorescence. IgM titres against their own faecal microflora were found to be lower both in active and inactive SLE when compared to healthy individuals. IgG-class antibacterial antibodies were increased in inactive SLE but decreased in active SLE compared to inactive SLE and healthy controls, although plasma levels of total IgG were almost doubled in active SLE. The lower IgG antibacterial antibody titres in active SLE might possibly result from sequestration of these IgG antibodies in immune complexes, indicating a possible role for antibacterial antibodies in exacerbations of SLE.

Plasma thrombomodulin as an indicator of thromboembolic disease in systemic lupus erythematosus

We serially measured the plasma thrombomodulin (TM) levels in systemic lupus erythematosus (SLE) patients and assessed them clinically. The patients who responded to medical treatment experienced a decrease in plasma TM levels. Patients who developed exacerbations of SLE, thrombotic thrombocytopenic purpura or thrombosis, displayed increased plasma TM levels. There was no significant difference between the plasma TM levels of the lupus anticoagulant-positive (LAC-positive) patients and the LAC-negative patients or between the plasma TM levels of the anticardiolipin antibody-positive (aCL-positive) patients and the aCL-negative patients. While LAC and aCL titers did not always coincide with improvement in the patients' clinical course or with aggravation of the disease, the TM values correlated well with the patients' clinical condition. Plasma TM values may be used to evaluate disease activity and may predict the occurrence of thrombosis in SLE.

Systemic lupus erythematosus induced by ovulation induction treatment

Infertile women are treated with various regimens for ovulation induction. The ultimate end-result of these treatments is a significant rise in levels of serum gonadotropins and estradiol--the most potent natural estrogen. Estrogens may affect diverse biologic functions, including immune and inflammatory reactions. A role for estrogens in the development or exacerbation of systemic lupus erythematosus (SLE) has been suggested by many studies. In this report, we present 3 cases of otherwise healthy women who received ovulation induction agents and subsequently developed full-blown SLE. The possible association between this treatment and SLE is discussed.