A prospective study on silicone breast implants and the silicone-related symptom complex

This cohort study prospectively evaluated the prevalence of the silicone-related symptom complex (SRSC) in relation to antinuclear antibodies (ANA) and magnetic resonance imaging (MRI) of silicone breast implants (SBI) 1 year after implantation. A total of 57 women undergoing mastectomy followed by immediate breast reconstruction (IBR) and SBI between March 1995 and March 1997 at the University Hospital Rotterdam/Daniel den Hoed Cancer Centre, were prospectively evaluated. Just before and 1 year after IBR the sera of these women were tested for the presence of ANA and they were screened for the prevalence of SRSC-related symptoms by questionnaire. All prostheses were evaluated by MRI 1 month and 1 year after IBR. Just before operation 11% of the women had a Sj?gren score of more than 2, whereas 30% had such a score 1 year after IBR ( P = 0.01). One year postoperatively women had significantly more RA/Raynaud-related complaints: 21% preoperatively versus 40% 1 year after IBR ( P = 0.03). Within the undefined complaints-related group 19% had a score of 2 or more preoperatively and 33% 1 year after IBR ( P = 0.09). There were no new cases of ANA positivity 1 year after IBR. The linguine sign was seen by MRI in three implants: one 1 month after IBR and two 1 year after IBR. There was no relation to changes in SRSC expression and these MRI findings. In conclusion, 1 year after SBI implantation women had more SRSC-related complaints, especially Sj?gren's and RA/Raynaud's. Moreover there was no correlation between elevated SRSC expression and changes in the presence of ANA or changes in MRI of the SBI 1 year after IBR.     

The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up

The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sj?gren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.     

Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis

Aim: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. Methods: We compared clinicopathological features in patients with ANA-positive NASH (n = 35) and ANA-negative NASH (n = 36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. Results: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. Conclusion: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.     

Antinuclear antibodies in sickle cell disease

The frequency of antinuclear antibodies (ANA) and other antinuclear factors was prospectively evaluated in patients with sickle cell disease (SCD). Ten of 44 patients studied (22.7%) had positive ANA determinations at titers greater than or equal to 1:40 compared to 3 of 46 healthy controls (6.5%; p less than 0.03). Eight SCD patients had ANA titers of 1:160 or greater compared to none of the controls (p less than 0.003). No antibodies directed against other nuclear factors were found. An analysis of the patient histories revealed no statistical differences between the ANA-positive and ANA-negative SCD patients when correlated with disease activity.     

Expression and clinical significance of antinuclear antibody in hepatitis C virus infection

BACKGROUND: The prevalence of antinuclear antibody (ANA) has been documented in patients with hepatitis C virus (HCV) infection. We attempted to determine the titer and to characterize the patterns and clinical significance of ANA in HCV infection. STUDY: Forty-eight consecutive patients with positive anti-HCV antibody and positive HCV RNA were included in this study. Sera from patients were tested for ANA and anti-smooth muscle antibody by indirect immunofluorescence. Serum aminotransferase, alkaline phosphatase, alpha-fetoprotein, and cryoglobulin levels also were determined. RESULTS: Eleven (23%) of 48 HCV-infected patients were positive for ANA. Antinuclear antibody revealed speckled pattern in 10 (91%) of the 11 ANA-positive HCV-infected patients. Twenty (54%) of 37 ANA-negative HCV-infected patients had detectable pattern with equivocal titer (titer <1.5). The ANA pattern was speckled in all 20 patients. Hepatitis C virus-infected patients with positive ANA were older than the HCV-infected patients with negative ANA (62.90 +/- 11.05 years vs. 56.46 +/- 14.94 years, respectively; p < 0.1). Serum levels of aspartate aminotransferase (39.36 +/- 14.98 IU/L vs. 30.70 +/- 23.15 IU/L, p < 0.05), alkaline phosphatase (189.00 +/- 75.63 IU/L vs. 122.41 +/- 40.88 IU/L, p < 0.01), and alpha-fetoprotein (47.72 +/- 80.47 pg/dL vs. 7.00 +/- 8.28 pg/dL, p < 0.01) were higher in ANA-positive HCV-infected patients than in ANA-negative HCV-infected patients, respectively. There were no significant differences in gender, alanine aminotransferase, anti-smooth muscle antibody, or cryoglobulin between the two groups. CONCLUSIONS: Antinuclear antibody was present in 11 (23%) of 48 patients with HCV infection in our study. Speckled pattern is the major expression pattern of ANA in HCV infection. Antinuclear antibody-positive HCV-infected patients have significantly higher serum aspartate aminotransferase, alkaline phosphatase, and alpha-fetoprotein levels than ANA-negative HCV-infected patients.     

Autoantibodies to the chromosomal protein HMG-17 in juvenile rheumatoid arthritis.

OBJECTIVE. To determine the antibody profiles in sera from patients with juvenile rheumatoid arthritis (JRA). METHODS. Immunoblotting using nuclear extracts and recombinant high-mobility group (HMG) nonhistone chromosomal proteins. RESULTS. Antibodies directed against HMG-17 were found in 47% of antinuclear antibody (ANA)-positive patients with pauciarticular-onset JRA and in 16% of ANA-positive patients with polyarticular-onset JRA. HMG-17 values of 6% and 8%, respectively, were detected in ANA-negative patients with JRA and in those with nonrheumatic diseases. CONCLUSION. There is evidence for a high prevalence of anti-HMG-17 antibodies in sera of patients with pauciarticular-onset JRA.     

Autoimmune uveitis in children: clinical correlation between antinuclear antibody positivity and ocular recurrences

OBJECTIVE: The aim of this study was to identify the correlation between antinuclear antibody (ANA) titre and the onset and clinical course of uveitis in children with juvenile idiopathic arthritis (JIA) or without any other systemic autoimmune disease, i.e., idiopathic uveitis (IU). METHODS: Twenty-two patients affected by uveitis were examined. Ten had JIA-associated uveitis, 12 had IU. Follow-up ranged from 7 to 101 months. The ANA were titrated three times per year and additionally in case of ocular recurrences. All patients were treated with immunosuppressive drug combination therapy (IDCT). RESULTS: JIA-associated uveitis: ocular recurrences were noted in three ANA-positive patients and in one ANA-negative patient. IU uveitis: ocular recurrences were noted in one ANA-positive and in one ANA-negative patient. No significant rise in ANA titre was noted in either group during uveitis recurrence. CONCLUSIONS: (1) ANA had no value in predicting the recurrence of uveitis. (2) IDCT does not influence ANA production.     

Autoantibodies to the chromosomal protein HMG-17 in juvenile rheumatoid arthritis

Objective. To determine the antibody profiles in sera from patients with juvenile rheumatoid arthritis (JRA). Methods. Immunoblotting using nuclear extracts and recombinant high-mobility group (HMG) nonhistone chromosomal proteins. Results. Antibodies directed against HMG-17 were found in 47% of antinuclear antibody (ANA)–positive patients with pauciarticular-onset JRA and in 16% of ANA-positive patients with polyarticular-onset JRA. HMG-17 values of 6% and 8%, respectively, were detected in ANA-negative patients with JRA and in those with nonrheumatic diseases. Conclusion. There is evidence for a high prevalence of anti—HMG-17 antibodies in sera of patients with pauciarticular-onset JRA.     

Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. METHODS: Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi2 and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. RESULTS: A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. CONCLUSIONs: ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone.     

Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic arthritis

Objective. To identify a homogeneous entity for antinuclear antibody (ANA)-positive patients suffering from juvenile idiopathic arthritis (JIA).

Methods. All of the clinical features were recorded retrospectively. ANA positivity was defined as more than twice positive results at a titer of > 1:100. The correlation between ANA positivity and clinical parameters was assessed by multiple logistic regression analysis.

Result. Of 120 patients, 49 patients were ANA positive (31 oligoarthritis, 18 rheumatoid factor [RF]-negative polyarthritis) and 71 patients were ANA negative (48 oligoarthritis, 23 RF-negative polyarthritis), and were recruited retrospectively to this study according to the International League of Associations for Rheumatology (ILAR) criteria. In ANA-positive cohort, the characteristics of early-onset age, female predominance, and asymmetric arthritis were observed compared with ANA-negative cohort including oligoarthritis and RF-negative polyarthritis. Correspondingly, we found that ANA-positive cohort had higher cumulative number of joints affected at 9 and 12 months after disease presentation than ANA-negative cohort, had lower frequency of occurrence of image change, and had a different pattern of affected arthritis than ANA-negative cohort, which was more likely to have knee involvement and less likely to have hip and shoulder involvement. ANA positivity correlated strongly with asymmetric arthritis, female predominance and wrist involvement.

Conclusion. This study demonstrates that ANA-positive cohort divided into different subgroups by present ILAR criteria share the similar features and suggests that ANA positivity might serve as a novel potential value for JIA classification.     

Antinuclear Antibody (ANA) and ANA Profile Tests in Children with Autoimmune Disorders: A Retrospective Study

The study objective was to determine the clinical value of positive antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders. A retrospective chart review was carried out of all patients under 18 years of age with a positive ANA test (HEp-2 cell substrate, titre ≥1:40) and ANA profile (ELISA) referred to the paediatric rheumatology service at the authors” institution between 1992 and 1996. Of 245 children with a positive ANA test, 134 (55%) had an autoimmune disease, including juvenile rheumatoid arthritis (n = 49), systemic lupus erythematosus (SLE) (n = 40) and others (n = 45). The remaining 111 patients did not have identifiable autoimmune diseases. Patients with autoimmune disorders had significantly higher ANA titres of ≥1:160 (χ²= 16, P<0.0001). In addition, of the 245 patients with a positive ANA test, 86 had an ANA profile performed; this was positive in 32 and negative in 54. All 32 patients with a positive ANA profile (100%) had an autoimmune disorder, compared to 22 ( 41%) of 54 with a negative ANA profile who had autoimmune disorders. Of 22 SLE patients with a positive ANA profile, 16 (73%) had positive anti-dsDNA and 15 (68%) had positive anti-Sm and positive anti-RNP. A positive ANA profile correlated strongly with an ANA titre ≥1:640 (χ²= 5.7 , P<0.02). The study demonstrated that only 55% of children with a positive ANA test had a definitive diagnosis of autoimmune disorder. These children tend to have higher ANA titres of ≥1:160. However, a positive ANA profile was strongly correlated with an ANA titre ≥1:640 and highly indicative of an autoimmune disorder (100%). We suggest that in order to reduce cost, an ANA profile should not be performed on all patients with positive ANA, but reserved for those with an ANA titre of ≥1:640 and/or those with a high clinical index of suspicion for autoimmune disorder, especially SLE. Received: 14 September 1999 / Accepted: 23 December 1999     

Changes in titers of antimitochondrial and antinuclear antibodies during the course of primary biliary cirrhosis

A case of primary biliary cirrhosis (PBC) in whom a complete biochemical (serum bilirubin, transaminases and alkaline phosphatase) remission was noted after combination treatment with ursodeoxycholic acid (UDCA) and corticosteroid is reported. The antimitochondrial antibody (AMA) detected by indirect immunofluorescence was initially positive, and the antinuclear antibody (ANA) was negative, but these two antibodies subsequently fluctuated independently (AMA-positive/ANA-negative, AMA-negative/ANA-negative, AMA-negative/ANA-positive, AMA-positive/ANA-positive, and again AMA-negative/ANA-positive) in spite of a lack of histopathological improvement in the liver after treatment. The clinical presentation in our case suggests that in some cases the diagnosis of PBC or so-called autoimmune cholangitis (AIC) might depend on the 'phase' of the same disease. Our results also suggest that detailed immunoreactive profiles against 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by using immunoblotting, together with a serial histological examination, should provide more precise information for a diagnosis of PBC.     

Antinuclear antibody-negative systemic sclerosis

ObjectiveTo examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients.MethodsSSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories.ResultsThis study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups (p = 0.28).ConclusionsIn conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement.     

Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of patients with systemic lupus erythematosus

To determine the prevalence of autoimmune diseases and autoantibodies in relatives of Caucasian patients with systemic lupus erythematosus (SLE) we questioned 118 patients for the prevalence of autoimmune diseases in their relatives. Multicase SLE families were selected for further investigation: assessment of the presence of antinuclear antibodies (ANA), thyroid antibodies and IgM rheumatoid factor (IgM-RF). Thirty-three patients reported the presence of 50 autoimmune diseases in 43 relatives. Twenty-two diagnoses could be either confirmed (n=14) or refuted (n=8). SLE clustered significantly within families of SLE patients. Multiple sclerosis and rheumatoid arthritis also seemed to cluster within families of lupus patients. The prevalence of ANA (24%) and thyroid antibodies (44%) in 29 relatives of multicase SLE families was raised (P<0.05). In conclusion, the prevalence of autoimmune diseases is raised in relatives of Caucasian SLE patients. Also, the prevalence of autoantibodies is raised in relatives of multicase SLE families, both suggesting genetic influences in the pathogenesis of the disease. These findings support the genome-wide screening of SLE patients to unravel factors responsible for genetic susceptibility to SLE. Received: 1 March 2001 / Accepted: 20 September 2001     

Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease

OBJECTIVE: We recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA-positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)-negative polyarthritis share homogeneous features and to compare these features with those of ANA-negative patients with JIA in the same categories. METHODS: We identified patients who were followed up during a 15-year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of >or=1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively. RESULTS: A total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF-negative polyarthritis), and 66 were ANA negative (35 had RF-negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female-to-male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA-positive patients with polyarticular disease, ANA-negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis. CONCLUSION: Our results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration.     

Clinical significance of the detection of antinuclear antibodies in patients with acute hepatitis a

Background/Aims

The findings of several recent studies suggest that antinuclear antibodies (ANAs) are frequently detected in patients with acute hepatitis A (AHA). However, the clinical significance of a positive ANA test remains uncertain. This study was performed to evaluate the clinical significance of ANAs in AHA patients.

Methods

All patients admitted with AHA were consecutively enrolled in this study. An ANA assay was performed by indirect immunofluorescence during hospitalization. ANA positivity was defined as an ANA titer ≥1:80. The peak international normalized ratio (INR), peak alanine aminotransferase (ALT) and peak bilirubin levels were assessed over the duration of the hospitalization, and the incidence of AHA complications was evaluated.

Results

A total of 422 patients were enrolled in this study (age, 31±7 years), of which 260 (61.6%) were men. ANAs were detected in 179 AHA patients (42.4%). The proportion of ANA-positive patients varied significantly with AHA status on the day of the ANA assay (4.7% during the prodromal period vs 52.1% during the icteric or recovery period, p<0.001) and sex (56.2% in women vs 33.8% in men, p<0.001). The ANAs became undetectable in all ANA-positive patients within 3 months. The incidence of complications, including mortality, fulminant hepatic failure, renal dysfunction, relapse, and cholestatic hepatitis, did not differ significantly between ANA-positive and ANA-negative patients.

Conclusions

ANAs were detected frequently and transiently in patients with AHA, especially after their peak-ALT day. The presence of ANAs may not be associated with the clinical outcome of AHA, but simply with AHA status on the ANA assay day.     

Non-Organ-Specific Autoantibodies in Nonalcoholic Fatty Liver Disease: Prevalence and Correlates

Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.     

Self-Reported Symptoms among Danish Women following Cosmetic Breast Implant Surgery

The aim of this study was to examine self-reported symptomatology and to identify distinctive characteristics among women with silicone breast implants (SBI). Using the Danish hospital and population registers we identified three groups of women with a hospital diagnosis of muscular rheumatism (a non-specific soft-tissue diagnostic code) who had previously undergone SBI surgery (n= 28), breast reduction surgery (n= 29) or no breast surgery (n= 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n= 21), breast reduction surgery (n= 27) or no breast surgery (n= 56). All study subjects completed a self-administered questionnaire focusing on sociodemographic factors, lifestyle habits, somatic symptoms and psychological symptoms. Women with SBI and women with breast reduction with no previous diagnosis of muscular rheumatism had similar patterns of reporting for most symptoms and characteristics. They reported significantly more somatic symptoms and psychological distress, including somatisation, obsessive–compulsiveness and depression, than women with no breast surgery. No significant differences in self-reported symptomatology and characteristics were observed among the three groups of women with a previous diagnosis of muscular rheumatism. Overall, women with prior muscular rheumatism reported more symptoms than those without. We concluded that self-reported somatic symptoms among women with SBI were similar to those of controls. Women with cosmetic breast surgery appear to have distinctive psychological characteristics. Our study emphasises the importance of taking the psychological profile and previous history of rheumatic diseases into account when examining women with SBI. Received: 28 February 2001 / Accepted: 2 July 2001     

Clinical significance of antinuclear antibodies in malignant diseases: association with rheumatic and connective tissue paraneoplastic syndromes

Our objective was to determine the prevalence of antinuclear antibodies (ANAs) in patients with malignancies and to investigate if their presence might be related with development of musculoskeletal symptoms or paraneoplastic rheumatic syndromes. Antinuclear antibodies were determined by indirect immunofluorescence on Hep-2 cells in 274 neoplastic patients and in a control group of 140 age-adjusted healthy subjects. Antinuclear antibody specificities (anti-DNA and anti-ENA) were investigated in patients with rheumatological symptoms and positive ANA. Antinuclear antibodies were detected in 76 of 274 (27.7%) patients with malignancies and in nine of 140 (6.4%) healthy subjects. Twenty patients reported paraneoplastic rheumatic symptoms or syndromes. Two of them developed clinical symptoms mimicking rheumatoid arthritis (rheumatoid-like arthropathy), one systemic lupus erythematosus (lupus-like syndrome), one dermatomyositis and four cutaneous vasculitides. Musculoskeletal symptoms and paraneoplastic rheumatic symptoms and syndromes were both more frequently observed in patients with positive ANA. Antinuclear antibody specificities were found in only two cases. We can conclude that there is an increased incidence of antinuclear antibodies in malignant conditions. Musculoskeletal symptoms and rheumatic paraneoplastic symptoms and syndromes seem to be more frequent in patients with cancer-related positive ANAs. The failure to find ANA specificities (anti-ENA, anti-DNA) in patients with malignancies and positive ANAs in our study may simply reflect molecular differences between the autoantigens involved in cancer and those characteristically involved in the systemic autoimmune diseases.     

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.