Systemic Lupus Erythematosus In Men Research Articles

Systemic Lupus Erythematosus in Men: Brief Description of Clinical and Laboratory Findings

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of nuclear autoantibodies, which can cause autoimmune complex formation and inflammation of multiple organs. It is known to affect women more frequently than men and is typically diagnosed during reproductive age, where the female-male ratio has been reported as high as 12:1. The etiology of SLE is not fully understood, but both genetic predisposition and environmental triggers are believed to be involved. Because of the multitude of presentations, manifestations, and serological abnormalities in patients with SLE, diagnosis can be challenging. Chronic discoid lupus and photosensitivity have been found in men with SLE as far as skin findings are concerned, there is less joint involvement in these patients, however, severe systemic findings predominate, such as serositis, pleurisy, central nervous system involvement with the presence of seizures. , thrombotic events and lupus nephropathy of the acute proliferative glomeruonephritis variety, serologically there is no consensus yet, nor in the specific clinical characteristics but the presence of anti-dsDNA anti-Sm antibodies and anticardiolipin antibodies is also frequently found. Therapeutic approaches predominantly involve immunomodulation and immunosuppression and are targeted to be the specific organ manifestation, with the aim of achieving low disease activity. Conclusion: We considered that although male patients with lupus are not commonly seen, the manifestations are life threatening, and timely diagnosis and treatment of the disease will lead to a better outcome for these patients.

Systemic lupus erythematosus: rarer in men than women but more severe

Although systemic lupus erythematosus (SLE) is rarer in men than women, it is more severe. The clinical presentation of SLE is variable and there are sex differences. Given the relative rarity of SLE in men, clinicians should have a low threshold for investigation to avoid delayed diagnosis.

Case of severe heart and kidney damage in a young man with systemic red lupus

Systemic autoimmune diseases remain a complex problem for specialists of different profiles. Despite some progress in their diagnosis and treatment, the incidence of these diseases is now steadily increasing. This is primarily due to polyorganic lesion, which requires a balanced approach to the choice of treatment of the patient, taking into account the functional condition of different organs and systems. Thus in particular systemic lupus erythematosus, which occupies a leading place in the structure of rheumatological pathology, often occurs with kidneys damage, cardiovascular system, hematological disorders. Most studies are based on the systemic lupus erythematosus in women, while the male sex is recognized as a factor of adverse outcomes and severe course of the disease. The article covers the peculiarities of the course of systemic lupus erythematosus in men, considered the variants of heart affection within the systemic process, and also presents a clinical case of systemic lupus erythematosus of high activity in a young man with terminal kidney affection, pancarditis with formation of severe mitral insufficiency, pancytopenia. The aspects of the management of a patient with severe valve disease of the heart in need of renal replacement therapy against the background of drug immunosuppression, the possibility of correction of valve disease. The combination of terminal renal failure and heart failure in a young man in the clinical case cited is an example of the multidiscplinar problem of treating systemic lupus erythematosus.

Particularities of the Evolution and Therapeutic Response in Men with Systemic Lupus Erythematosus and Lupus Nephritis

Abstract Aim. The prevalence ratio of systemic lupus erythematosus in men compared to women is 1:10, with more aggressive forms in men and in children. The incidence of lupus nephritis is of 50-60% in patients with lupus. In this paper, we aim to report on a series of cases that include male patients who had lupus nephritis via renal biopsy and were admitted between January 2011 - December 2017, with or without other SLE manifestations. The aim is to review the particularities and the therapeutic response: age at onset, disease duration, lupus nephritis class, extra-renal organ involvement of lupus disease, paraclinical findings – proteinuria, inflammatory syndrome, renal function, therapeutic response – immunosuppressive regimens used for induction and maintenance, remission onset, remission type, number of flares, side effects of immunosuppressive therapy. Materials and method. We have reviewed the histopathology database of male patients with lupus nephritis revealed via renal biopsy, medical charts and the Hippocrates information system in order to collect patient data. Outcomes. Out of 68 renal biopsies positive for lupus nephritis, 9 were from male patients, which reveals a 6.5:1 ratio. The average age at the time of the renal biopsy is 37. 33 years old. Lupus nephritis class - 8 out of 9 patients were class IV, 1 sample was class IV+V. The duration of the corticosteroid therapy is 6.6 years. In addition, we also reviewed the immunosuppressive agents used, the number of flares, and the side effects of the medication. Conclusions. Our data are similar to the literature data.

Lupus ampolloso: un verdadero reto diagnóstico y terapéutico

El lupus eritematoso sistémico (LES) es una enfermedad de tipo autoinmune en donde existen múltiples factores que inducen una respuesta inmunológica no controlada en un individuo que genéticamente está predispuesto, presentándose una variedad de manifestaciones clínicas que muchas veces se convierten en un verdadero reto diagnóstico y terapéutico como es el caso de sus presentaciones en piel. Describiremos a continuación un caso de un paciente género masculino con diagnostico LES con lesiones cutáneas extensas severas con diagnóstico clínico y histopatológico sugestivo de lupus ampolloso refractarias a tratamiento estándar con corticoterapia e inmunomoduladores con evolución tórpida en su curso, que requiere posteriormente inicio de terapia biológica con Belimumab observándose una remisión clínica significativa de las lesiones y contribuyendo además a disminuir las dosis de corticoides utilizadas desde su ingreso . Se revisarán aspectos en relación del LES en hombres en lo que refiere a epidemiologia, manifestaciones cutáneas, hallazgos histopatológicos, diagnóstico diferencial y opciones terapéuticas actuales.

ANA-Negative Presentation of SLE in Man with Severe Autoimmune Neutropenia.

Background. Systemic lupus erythematosus (SLE) is a chronic, inflammatory, connective tissue disease that commonly affects the joints and a variety of organs due to an overactivation of the body's immune system. There is wide heterogeneity in presentation of SLE patients, including lung, central nervous system, skin, kidney, and hematologic manifestations. Case Presentation. We report a case of atypical manifestation of SLE in a 53-year-old man who presented with neutropenic fever. Physical findings of interest included oral ulcers on the lower lip, a malar-like rash across the bridge of the nose, and a discoid-like rash on extensor surfaces of the elbows and knees. Labs include ANC <100, weakly positive anti-dsDNA, negative ANA, ferritin 1237 ng/mL, low C3/C4, and positive direct Coombs' test. A thorough workup for infection and hematologic malignancy was negative. Two days after initiation of therapy with 25 mg IV solumedrol twice a day, the patient's daily fevers resolved. ANC drastically improved to 2000 after two weeks of steroid treatment. He was later found to have a high titer of anti-neutrophil antibodies. Discussion. Autoimmune leukopenia is a common presentation in SLE, occurring in 50–60% of patients. Severe autoimmune neutropenia is uncommon and may correlate with high anti-neutrophil antibody activity despite a negative ANA. As neutropenia is usually mild, there are currently no guidelines for therapy. For our patient, we started him on low dose IV solumedrol and found that he responded drastically to treatment. Given strongly positive nonspecific anti-neutrophil antibodies in the setting of a negative ANA noted in our patient, it is likely that there are other currently unknown antibodies associated with SLE which may correlate strongly with autoimmune neutropenia.

Interaction of a small molecule Natura-α and STAT3-SH2 domain to block Y705 phosphorylation and inhibit lupus nephritis

A small molecule, Natura-α, a clinical stage investigational new drug for certain inflammatory diseases, has been evaluated for drug interaction with STAT3 and inhibiting systemic lupus erythematosus (SLE). Studies have revealed that it selectively inhibits STAT3-Y705 phosphorylation and, suppresses pro-inflammatory cytokines, stimulates anti-inflammatory cytokine IL-10, thereby skewing T cell differentiation from the Th1/Th17 lineages toward the Treg lineage. The potential binding of the drug to STAT3 protein has been investigated with a computational modeling and docking simulation using X-ray crystal structure of the STAT3β homodimer. Natura-α was shown to directly bind to SH2 domain of STAT3 and forms H-bonds with amino acids Glu594 and Arg609. The phosphorylation of Y705 was prevented and making the formation of STAT3 homodimer impossible, thereby blocking STAT3 activation. The in vivo efficacy of Natura-α in SLE was evaluated in a bioassay with NZB/W female mice. Mice at week 19 were given orally Natura-α at 25 or 75mg/kg, once a day, 5 days per week for 29 weeks. Mice were monitored weekly until 52 weeks of age. Both dosages were effective to reduce proteinuria and significantly improved animal survival rate. The renal functions were preserved with glomerular lesions reversed, which paralleled with decreased C3 deposit. The numbers of kidney cells stained with phosphorylated STAT3-Y705 remarkably decreased, demonstrating blocking of Y-705 phosphorylation by the treatment. Since NZB/W mice develop nephritis which resembles SLE in men, the data strongly suggests that Natura-α may be a potential effective therapeutic agent for lupus.

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States.

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993-2005. SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age- and sex-adjusted incidence and prevalence were standardized to the 2000 US white population. The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0-3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1-5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE.

Clinical and immunological pattern of systemic lupus erythematosus in men in a cohort of 2355 patients

To investigate the impact of gender on expression of systemic lupus erythematosus (SLE) in a cohort of 2355 SLE patients as one of the largest series of cases among the present reports. In this retrospective study we used medical records of all patients (239 male and 2116 female) of the SLE registry of Rheumatology Research Center (RRC), Tehran University of Medical science (TUMS), Iran. Both clinical and paraclinical manifestations of SLE patients have been registered in this database since 1976 and updated during their follow-up. Chi-square test was used to compare the clinical and paraclinical manifestations in men and women at disease onset and during the disease course. We used logistic regression to compute odds ratios with 95% confidence intervals. A P-value < 0.05 was considered as statistically significant. Mean age at disease onset was 25 ± 11.8 and 24.5 ± 10.3 years in men and women, respectively (P = 0.48). Comparison of clinical and immunological manifestations showed that male patients had a higher prevalence of mucocutaneous (43.5% vs. 33.7%, P = 0.005) and a lower prevalence of musculoskeletal symptoms (44% vs. 54.7%, P = 0.003) as the initial manifestation. During the disease course, discoid rash (25.9% vs. 13%, P = 0.000) and type IV lupus nephritis (23.4% vs. 18.1%, P = 0.03) were significantly more common, whereas arthritis (61.1% vs. 71.7%, P = 0.01) and leukopenia (28.5% vs. 35.8%, P = 0.024) were significantly less common in men. This study reveals gender influence on some manifestations of SLE. Considering sex differences is recommended in diagnostic and therapeutic features of the disease.

Development of systemic lupus erythematosus in a male-to-female transsexual: the role of sex hormones revisited

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. The infrequency of SLE in men and disease onset in prepubertal or postmenopausal women suggests a role of estrogen in the predisposition to the disease. Patients with hypergonadotrophic hypogonadism are prone to the development of SLE, and the use of exogenous estrogens in women increases the relative risk of SLE onset and disease flares. These observations provide indirect evidence for an opposite role of estrogens and androgens in the pathogenesis of SLE. We report on a male-to-female transsexual who developed SLE 20 years after sex-reassignment surgery and prolonged estrogen therapy. The role of sex hormones in SLE is revisited.

Sex differences in patients with systemic lupus erythematosus from Northwest Spain

To further establish potential differences according to sex in systemic lupus erythematosus (SLE) patients from Southern Europe. We assessed clinical and epidemiological data of patients diagnosed with SLE according to the 1982 American College of Rheumatology classification criteria at the single hospital for a well-defined population of Northwest Spain, between 1987 and 2006. Prevalence in December 2006 and age-standardized incidence rates in the whole period were estimated. Kaplan-Meier method was used in order to estimate the probability of survivorship. Women outnumbered men [127 (84.7%) vs. 23 (15.3%)]. The median age at the time of disease diagnosis in men was 54 years versus 43 in women (p < 0.001). Annual incidence rates were higher in women [5.9 (95% confidence interval--CI 4.9-7.0) per 100,000 population] than in men [1.1 (95% CI 0.7-1.7) per 100,000 population; p < 0.001]. Raynaud's phenomenon was more common in women (40.9 vs. 3.0%; p = 0.01). While the frequency of secondary Sjögren's syndrome was increased in women (p = 0.02), renal disease at the time of diagnosis (39.1 vs. 15.0%; p < 0.01) and over the course of the disease was more common in men (43.5 vs. 24.4%; p = 0.06). Higher frequency of thrombocytopenia (39.1 vs. 16.5%; p = 0.01) and lower frequency of anti-SSA (13.0 vs. 31.5%; p = 0.08) and anti-SSB (0 vs. 17.7%; p = 0.03) were observed in men. The 5- and 10-year survival probabilities were nonsignificantly reduced in men (91.3 and 78.3 3% vs. 94.6 and 89.2% in women). The frequency of some clinical manifestations is different in men and women with SLE. Higher awareness of these peculiarities may help to establish appropriate diagnosis and management of SLE in men.

A case of simultaneously developed sweet's syndrome and systemic lupus erythematosus in a man

Introduction: Sweet's syndrome is characterized by the development of tender, erythematous plaques, fever, arthralgia and leukocytosis. Sweet's syndrome is reported to be associated with underlying infections, malignant neoplasms, pregnancy, drugs, and autoimmune diseases. However, Sweet's syndrome associated with systemic lupus erythematosus has been rarely reported. Although both Sweet’s syndrome and systemic lupus erythematosus predominantly occur in women, we are reporting a case of simultaneously developed Sweet's syndrome and systemic lupus erythematosus in a man. Case Report: A 48­year­old previously healthy man was admitted for intermittent fevers, arthralgias, and eruption. Laboratory investigations revealed elevated C­reactive protein, lymphocytopenia, and low complements with elevated immune complex. Antinuclear antibodies, anti­DNA antibodies were positive. Systemic lupus erythematosus was diagnosed based on the presence of arthritis, lymphopenia, anti­DNA antibodies and antinuclear antibodies. A biopsy specimen from an erythematous papule from the right sole showed a slight lichenification and an infiltration of neutrophils and lymphocytes in dermis without leukocytoclastic vasculitis. Thus, this case also met the modified criteria for Sweet’s syndrome proposed by von den Driesch. Prednisolone was begun at a dose of 20 mg/day, resulting in diminishing skin eruption and resolution of arthralgia. Conclusion: Sweet's syndrome is categorized into classical, drug­induced, and malignancy­associated form. Only one case of concurrence of classical Sweet’s syndrome and systemic lupus erythematosus has been reported in a man. This is the second case of coincidence of classical Sweet’s syndrome and systemic lupus erythematosus in an adult man.

Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: Support for the notion of a gene‐dose effect from the X chromosome

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that predominantly affects women. Despite isolated reports of patients with coexisting Klinefelter's syndrome (47,XXY) and SLE, no association of Klinefelter's syndrome with SLE or any other autoimmune disease has been established. The present study was undertaken to investigate the prevalence of Klinefelter's syndrome in a large population of patients with SLE. Sex chromosome genotyping was performed in 981 SLE patients, of whom 213 were men. A first group of 844 SLE patients from 378 multiplex families and a second group of 137 men with nonfamilial SLE were evaluated. In selected cases, chromosomes were enumerated by fluorescence in situ hybridization (FISH) and karyotyping in transformed B cell lines. Of 213 men with SLE, 5 had Klinefelter's syndrome (1 in 43). Four of them were heterozygous at X markers, and Klinefelter's syndrome was confirmed by FISH and karyotyping in the fifth. An overall rate of 47,XXY of 235 per 10,000 male SLE patients was found (95% confidence interval 77-539), a dramatic increase over the known prevalence of Klinefelter's syndrome in an unselected population (17 per 10,000 live male births). Asking men with SLE about fertility was highly sensitive (100%) for Klinefelter's syndrome. All 768 women with SLE were heterozygous at X. The frequency of Klinefelter's syndrome (47,XXY), often subclinical, is increased in men with SLE by approximately 14-fold compared with its prevalence in men without SLE. Diagnostic vigilance for 47,XXY in male patients with SLE is warranted. These data are the first to show an association of Klinefelter's syndrome with an autoimmune disease found predominantly in women. The risk of SLE in men with Klinefelter's syndrome is predicted to be similar to the risk in normal women with 46,XX and approximately 14-fold higher than in men with 46,XY, consistent with the notion that SLE susceptibility is partly explained by an X chromosome gene-dose effect.

Pulmonary silicosis and systemic lupus erythematosus in men: a report of two cases

We report two cases of coexistence of pulmonary silicosis and systemic lupus erythematosus (SLE). The patients are two men with SLE exposed to silica for 20 years. The hypothesis that silica exposure is linked to a wide variety of known or suspected autoimmune diseases , including SLE, has been discussed in the last decade but few cases of pulmonary silicosis and SLE were reported. Our purpose was to bring attention to the increasing evidence that silica may also cause or stimulate SLE, and to suggest that the researchers look for occupational exposure, mainly in male SLE patients.

Systemic Lupus Erythematosus in Men: A Retrospective Analysis in a Veterans Administration Healthcare System Population

Systemic lupus erythematosus (SLE), a connective tissue disease of unknown etiology, is generally considered to occur in women of child-bearing age and to be uncommon among men . Because of the female predominance in most studies, less is known about the disease in men. To begin to better understand lupus in men, we retrospectively analyzed all the SLE patients from all the hospitals in the Department of Veterans Affairs (VA) system, a population that is predominantly male. Between 1987 and 1996, 2614 SLE patients were retrieved from the VA databank; 2144 were male, making this the largest group of male patients with SLE reported in United States of America. Age, racial and geographic distribution, comorbidities, and mortality of the SLE patients are reported. This study suggests that SLE men in this population are older at onset of disease, have different comorbidities, and have a higher mortality at 1 year than women with SLE. These findings suggest that men with SLE have a more complex clinical course than women, although the data do not illuminate whether the comorbidities are due to or coincident with SLE. On the basis of these data, practitioners are reminded to consider SLE in the differential diagnosis for older men and be attentive to the frequent presence of comorbidities such as cardiac ischemia and neoplasms. Because of the identified regional variations in demographics, comorbidities, and mortality, this study suggests the need for future SLE studies to include data from multiple geographic areas.

IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus?

Transgenic mice overexpressing IFN-γ in the epidermis develop an inflammatory skin disease resembling cutaneous lupus erythematosus shortly after birth. By 3 months of age, most female transgenics develop a lupus-like syndrome characterised by production of IgG anti-dsDNA, antihistone and antinucleosome autoantibodies. The autoantibodies are nephritogenic, with one-third of females developing a severe immune complex mediated glomerulonephritis. Analysis of these transgenics suggests that pathogenic autoantibodies arise via an antigen-driven T-cell-dependent mechanism with apoptotic keratinocytes acting as a potential source of autoantigen. The mechanism of autoantibody production in IFN-γ transgenics may be relevant to human lupus and is consistent with a central role for cutaneous T cells in the pathogenesis of systemic lupus erythematosus in man.

Side-chain Specificities and Molecular Modelling of Peptide Determinants for Two Anti-Sm B/B′ Autoantibodies

Autoantibodies binding the Sm B and B′ peptides (B/B′) are commonly associated with systemic lupus erythematosus in man and in MRLlpr/lprmice. The linear antigenic regions of two anti-Sm B/B′ murine monoclonal auto-antibodies have been mapped using overlapping octapeptides. Unique epitopes are identified by each antibody. Monoclonal KSm-5 recognizes the peptide, PPPGMRPP, which is repeated three times in the Sm B polypeptide. KSm 3 preferably binds to two similar, almost neighboring octapeptides, PPPGIRGP and PGIRGPPP. The two monoclonal antibodies do not cross react. These regions of Sm B/B′ are major areas of antigenicity in human sera. Amino acid deletion and substitution in antigenic octapeptides show that binding to the KSm-5 epitope is lost with most modifications. Molecular dynamic modelling suggests that when PPPGMRPP is substituted in the sixth position arginine, KSm/5 binding may be associated with a shared peptide backbone structure rather than charge or hydrophobicity of the substituted amino acid. In contrast, binding of KSm-3 to PPPGIRGP is abolished when the sixth position arginine is substituted by any other amino acid. Substitution at arginine and modelling experiments, therefore, suggest very different mech-anisms of binding. Autoantibodies may bind quite different features of similar peptide structures.

Effect of captopril on murine systemic lupus erythematosus disease.

The MRL/1 and New Zealand black-New Zealand white cross (NZB x W) mice spontaneously develop a disease similar to systemic lupus erythematosus in man. The effect of antihypertensive treatment on MRL/1 and NZB x W mice was studied with respect to survival, blood pressure, proteinuria, haematuria and renal histopathology. The treatment consisted of angiotensin converting enzyme (ACE) inhibitors (captopril and enalapril) and bretylium, a sympathetic blocker. Tail systolic blood pressure was measured with a strain gauge technique. All antihypertensive drugs caused a reduction in blood pressure in both strains. In MRL/1 bretylium and both ACE inhibitors improved renal histopathology, but only captopril prolonged survival, and it decreased proteinuria and haematuria. In NZB x W captopril decreased proteinuria but did not influence survival or renal histopathology. Bretylium was without any effect on these parameters. At the doses used captopril improves survival in MRL/1 mice and decreases proteinuria and haematuria in both MRL/1 and NZB x W mice. Since bretylium and enalapril lack this property despite a similar blood pressure reduction, it seems to be a drug-specific action.

Characterization of mouse and human monoclonal antibodies cross-reactive with SLE serum antibodies to guanosine.

Two new monoclonal antibodies, one a mouse IgM and the other a human IgM that reacted with guanosine, were compared to human serum antibodies from patients with systemic lupus erythematosus (SLE). The human monoclonal antibody was polyspecific in its binding to the nucleoside bases, whereas the mouse monoclonal antibody was relatively specific for guanosine when compared by using an enzyme-linked immunosorbent assay (ELISA). Neither antibody bound polyguanylic acid or denatured single-stranded (ss) DNA, however. Serum IgG antibodies from seven patients with SLE cross-reacted with the mouse monoclonal antibody and showed considerable specificity for guanosine. In contrast, the human serum IgG antiguanosine antibodies also bound ssDNA but not dsDNA or polyguanylic acid. Serum IgG antibodies to guanosine measured by ELISA from the seven SLE patients had a decreased response when compared to the total serum IgG response to ssDNA, and most of the antibodies that bound guanosine also bound ssDNA. These studies provide new evidence that there are specific IgG antibodies to guanosine in SLE sera that are a small fraction of the antibodies to ssDNA. Further efforts to define the role of these guanosine antibodies in SLE may provide a better understanding of the basic mechanisms responsible for the development of SLE in man.

Systemic lupus erythematosus in men. Genetic and endocrine features

Systemic lupus erythematosus in men. Genetic and endocrine features