Familial systemic lupus erythematosus in Finland

OBJECTIVE: To perform a cross sectional nation-wide clinical study of familial systemic lupus erythematosus (SLE) in Finland. METHODS: We sought to identify all Finnish families in which at least 2 members satisfied the classification criteria for SLE. About 1,200 patients with SLE (80-85% of all patients attending Finnish hospitals) were contacted. Personal and/or phone interviews and examination of medical records were used to verify the diagnoses. A comparison of clinical characteristics was made between familial cases of SLE and matched sporadic controls. RESULTS: We identified 53 multiplex families with 113 SLE patients. Forty-six families had 2 affected members and 7 families had 3 affected members. There were 3 pairs of monozygotic female twins and one pair of dizygotic twins of the opposite sex concordant for SLE. Eleven (9.7%) of the 113 familial cases of SLE were male. No differences were found in the clinical presentation of SLE between familial and sporadic cases (sex, age at onset, major clinical manifestations, and common laboratory tests). The incidence of familial SLE was approximately 4-5%. CONCLUSION: Our study shows that familial and sporadic SLE are not different disease entities; this means that we can extrapolate the results of future genetic analyses in multiplex SLE families to all patients with SLE.     

Familial systemic lupus erythematosus in males

Several families in which systemic lupus erythematosus predominates in males are presented. The disease primarily manifested itself in the sons and in the male parents. Females in some of the families had other autoimmune diseases such as idiopathic thrombocy-topenic purpura or symptoms suggestive of a lupus diathesis. It is suggested that the sons inherited the disease from their fathers in these families. The disease in the patients had some similarity to the disease in BXSB mice.     

Familial Crohn's disease with systemic lupus erythematosus

We describe a young Japanese woman who was diagnosed with Crohn's disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohn's disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohn's disease with SLE), patients with Crohn's disease who develop such clinical findings might need evaluation for SLE.     

Occupational and environmental exposures as risk factors for systemic lupus erythematosus

Although genetic susceptibility plays a strong role in the etiology of systemic lupus erythematosus (SLE), recent research has provided new evidence of the potential influence of environmental factors in the risk for this disease. This paper describes epidemiologic and experimental research pertaining to occupational and environmental sources of exposure to respirable crystalline silica, solvents and pesticides, and two "lifestyle" factors (smoking and hair dye use). As has been seen with other systemic autoimmune diseases (eg, systemic sclerosis and rheumatoid arthritis), a series of epidemiologic studies, using different designs in different settings, have demonstrated relatively strong and consistent associations between occupational silica exposure and SLE. The type and quality of exposure assessment is an important consideration in evaluating these studies. Recent experimental studies examined the effect of trichloroethylene exposure in MRL+/+ mice, but to date there have been few epidemiologic studies of solvents and SLE. There are numerous avenues with respect to environmental factors in SLE that need additional research.     

Familial alterations of immunoregulation in systemic lupus erythematosus

To better define the relationship between suppressor cell function and number and disease expression, the immunoregulatory profiles of 12 probands with systemic lupus erythematosus (SLE) and 34 of their asymptomatic family members were studied, using concanavalin A induced suppressor cells for functional analysis. SLE family members as a whole showed no impairment of mean suppressor levels, although 7 of 34 had altered suppression of DNA synthesis and 5 of 34 had altered suppression of IgG synthesis. Ratios of OKT4/T8 T cell subsets showed no difference between the study population, although 3 SLE family members had an increased ratio (greater than 2 SD) relative to controls. The 12 family members with either altered suppressor cell number or function had higher antibody levels to dRNA (Poly A . U) than did those with normal suppressor function and number. The results demonstrate that altered suppressor cell number and function occur in certain asymptomatic family members of SLE patients and may be weakly associated with markers of a preceding RNA viral infection.     

Clinical and genetic risk factors for pneumonia in systemic lupus erythematosus

OBJECTIVE: To define the contribution of polymorphisms in genes encoding tumor necrosis factor (TNF), mannose-binding lectin (MBL), and Fcgamma receptor IIa (FCGR2A) as well as clinical factors, to the development of pneumonia in patients with systemic lupus erythematosus (SLE). METHODS: We studied 282 SLE patients from a multiethnic cohort. Pneumonia events and clinical risk factors for pneumonia were identified through medical record review. Genotyping was performed for MBL (+223, +230, and +239), TNF (-308, -238, and +488), and FCGR2A (-131H/R) polymorphisms. Univariate analyses were performed to identify clinical and genetic risk factors for pneumonia. Covariates for multivariate analysis included sex, ethnicity, treatment with immunomodulators, and leukopenia. RESULTS: Forty-two patients (15%) had at least 1 episode of pneumonia. Polymorphism of the TNF gene, particularly the -238A allele and a related haplotype, revealed the most striking and consistent association with pneumonia in univariate analyses. Results of multivariate analyses indicated an odds ratio (OR) for the TNF -238A allele of 3.5 (P = 0.007) and an OR for the related haplotype of 5.4 (P = 0.001). Male sex, treatment with immunomodulators, and leukopenia also influenced the risk of pneumonia. CONCLUSION: These findings suggest that specific TNF variants may identify SLE patients who are at particularly high risk of developing pneumonia. Given the prevalence and excessive morbidity associated with pneumonia in SLE, these findings have clinical relevance and provide insight into the pathogenesis.     

Thrombosis risk in systemic lupus erythematosus: the role of thrombophilic risk factors

OBJECTIVES: Thromboembolic episodes are frequent manifestations of systemic lupus erythematosus (SLE). Although the presence of anti-phospholipid antibodies (aPL) is known to contribute to thromboembolism (TE), the relative contribution of other TE risk factors is unknown. The aim of this study was to determine the prevalence of TE in a Caucasian SLE population, to identify the risk factors of highest importance, and to assess the clinical value of thrombophilia screening among SLE patients. METHODS: Samples from 105 patients were analysed with a screen including aPL, activated protein C resistance, factor V Leiden (FVL) and prothrombin G20210A mutations; protein C, protein S and antithrombin activity; factor VIII (FVIII) and von Willebrand factor (vWF), and homocysteine (Hcy) levels. RESULTS: The annual incidence of arterial and venous TE events in our SLE population was 5.4 and 12.4 per 1000, respectively. The highest risk of thrombosis was carried by the simultaneous presence of lupus anticoagulant (LA) and anti-cardiolipin (aCL) [relative risk (RR) = 4.03, 95% confidence interval (CI) 2.06-7.86] or anti-beta2-glycoprotein I antibodies (abeta2-GPI) (RR = 5.10, 95% CI 2.58-10.1). Positivity for the individual aPL tests all carried an elevated TE risk. The presence of other risk factors seemed to be of less importance. CONCLUSIONS: In SLE patients, the presence of aPL is a more significant risk factor for the development of thrombosis than the known inherited deficiencies. Based on these data, routine screening for additional hereditary risk factors seems to be unwarranted.     

Familial juvenile systemic lupus erythematosus in Arab children

Aim of this study is to analyze the demographic, clinical, and biochemical features, and survival of familial juvenile systemic lupus erythematosus (FJSLE) in Arab children. The medical records of children with FJSLE seen at three pediatric rheumatology clinics in Saudi Arabia and Oman were retrospectively reviewed. All included children have met the following criteria: Arab ethnicity, definite diagnosis of SLE using the revised 1982 American College of Rheumatology classification criteria and family history of more than one affected sibling with SLE. The collected data included: gender, age at diagnosis, clinical and laboratory features at diagnosis. Unusual co-morbidity and mortality associated with the disease were studied. There were 50 children with FJSLE belonging to 18 families; the frequency of FJSLE in our cohort was 20.8%. The mean age at onset of SLE was 86?months (range, 18–168?months), while the mean age at diagnosis was 95?months (range, 24–192?months), and the mean duration of follow-up was 60.9?months (range, 7–132?months). The proportion of girls was predominant (78%). Autosomal recessive mode of inheritance was strongly suggested in number of our families. Mucocutaneous manifestations, arthritis, and nephritis were the most frequent features. Thirty-five patients had renal lesions, 18 of them had class IV nephritis according WHO classification. All patients were treated with different doses of steroid and immunosuppressive drugs; 37 (74%) patients received cyclophosphamide, and 6 patients treated with Rituximab. There were 5 patients required dialysis due to ESRD and 8 deaths related to SLE during the period of follow-up. FJSLE is not uncommon in our society. These findings may be helpful in identifying SLE patients with a stronger genetic predisposition; hopefully, one or more additional risk loci can be identified in multiplex Arab families that are different from what has been reported in other ethnic populations.     

Update on genetic risk factors for systemic lupus erythematosus and rheumatoid arthritis

The results of twin and family studies clearly implicate an important role for genetic factors in the etiology of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, the complex nature of these diseases has hampered progress in defining the genetic determinants. Recent advances in molecular genetic and statistical methodology offer new hope to overcome these challenges. This review highlights recent efforts to identify genetic risk factors for SLE and RA using allele sharing and other linkage methods. In spite of striking differences between these studies, some agreement in terms of the regions providing evidence of linkage also exists. Thus, together these studies highlight regions of the genome that are likely to contain SLE and RA susceptibility genes. In addition, the results of these studies, in conjunction with progress in other complex human diseases, suggest several important considerations for future studies.     

Prognostic factors in systemic lupus erythematosus

Summary In the past 40 years an impressive improvement in the prognosis of SLE patients has occurred. Factors which might be responsible for this improvement are discussed. Two of the factors most frequently cited are the advances in disease recognition and treatment. However, as already noted by Albert (1979) this is questionable, as average disease duration and survival have increased in a linear fashion related to the number of publications devoted to this subject from 1950 on. Further evaluation of the literature shows that the most prominent factors which have an impact on the survival rate are specific disease manifestations (lupus nephritis) and the overall disease course (number of exacerbations). This effect of morbidity on the survival rate is greater than that of factors such as sex and race. Socio-economic factors or age at onset have no effect on the outcome.     

Atherosclerosis risk factors in systemic lupus erythematosus

Cardiovascular disease (CVD) has emerged as a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Growing evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis from initial endothelial dysfunction to rupture of atheromatous plaques. The increased frequency of atherosclerosis in SLE is likely due to a complex interplay among traditional risk factors, disease-related factors such as medications and disease activity, and inflammatory and immunogenic factors. Identification of these novel risk factors will lead to a better understanding of CVD pathogenesis and may also provide targets for potential treatment strategies. When caring for SLE patients, clinicians should be aware of the increased CVD risk and treat the known modifiable risk factors in addition to controlling disease activity and inflammation.     

Clinical and genetic risk factors of herpes zoster in patients with systemic lupus erythematosus

Objective The aim of this study was to determine the clinical and genetic risk factors that influence herpes zoster occurrence in patients with systemic lupus erythematosus (SLE).Methods Three hundred three SLE patients meeting the American College of Rheumatology criteria were enrolled in this study. Herpes zoster was diagnosed when classic grouped vesicles were noted. Medical records were reviewed retrospectively to collect clinical information. For Fc gamma receptor IIa (FcRIIa) and FcRIIIa genotyping, polymerase chain reaction (PCR) using allele-specific primers was performed. The PCR sequence-specific oligonucleotide probe method was utilized in human HLA-DRB1 genotyping.Results Forty-two cases (13.9%) of zoster occurred among 303 SLE patients. The incidence of zoster in patients with SLE was 32.5/1,000 patients per year. Patients who developed zoster had higher rates of lupus nephritis (P=0.018) and positive anti-Sm antibody (P=0.019). However, FcRIIa and FcRIIIa polymorphism and the HLA-DRB1 genotype did not influence herpes zoster occurrence.Conclusion Systemic lupus erythematosus patients with lupus nephritis or anti-Sm antibody are at higher risk of herpes zoster. FcRIIa (H/R131), FcRIIIa (F/V176), and HLA-DRB1 genetic polymorphisms did not influence the occurrence of herpes zoster in these patients.