Magnetic resonance sialography of the parotid glands in chronic hepatitis C virus patients with and without vasculitis.

AIM: Hepatitis C virus (HCV) is sialotropic. The pathogenesis of sicca manifestations in patients with chronic HCV infection is not fully understood. We aimed to detect changes in magnetic resonance sialography (MRS) of HCV patients with and without vasculitis. METHOD: We studied 32 HCV patients (19 female, mean age 48.8 ± 10.3 years) and 20 age- and gender-matched healthy controls. Half of the patients had vasculitis. Demographic, clinical and serological data were prospectively evaluated. In patients with vasculitis, the disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). MRS was performed on all patients and controls. RESULTS: Abnormal MRS was found in 25% of patients, (6/16 and 2/16 in patients with and without vasculitis, respectively). Among patients with vasculitis, those with abnormal MRS had longer disease duration, higher leukocytic and lymphocytic counts and more frequent cryoglobulinemia (P < 0.01, P < 0.001, P < 0.001 and P < 0.008, respectively), while BVAS scores were not significantly different. CONCLUSION: Among HCV patients with vasculitis, longer disease duration and cryoglobulinemia were associated with abnormal findings on MRS. To confirm our results, we propose larger-scale, multicentre studies with longer evaluation periods.

The effect of leflunomide on the eye dryness in secondary Sjögren's syndrome associated with rheumatoid arthritis and in rheumatoid arthritis patients.

The aim of this work was to clarify the effect of leflunomide (LEF) on the eye dryness in patients with secondary Sjögren's syndrome associated with rheumatoid arthritis (RA-sSS) and in patients with rheumatoid arthritis (RA). Seventy-five female patients, 45 with RA-sSS (group A) and 30 with RA (group B), taking methotrexate at a dose of 20 mg/week for more than 6 months were enrolled in this study. They all had a loading dose of leflunomide then were maintained at a dose of 20 mg/day in addition to methotrexate for another 3 months. The modified disease activity score (DAS28) was calculated and modified Schirmer's-I test was performed. Assessment of disease parameters was done to all patients before and after 3 months of taking LEF. The mean modified Schirmer's-I test showed a significant decrease after 3 months of taking LEF in group A (3 ± 1.6 before versus 1.9 ± 1.6 after 3 months, P < 0.001), while this difference was non-significant in group B (21.3 ± 10 versus 19.9 ± 11). One patient (group A) developed peripheral ulcerative keratitis (PUK) with exacerbation of disease activity (DAS-28 = 6.9) that improved by taking corticosteroids. Three patients (group A) had aggravation of punctate keratocojunctivitis sicca with punctate erosions without PUK. The condition improved dramatically by stopping LEF and using topical lubricants. We report in this study a significant deterioration of the eye dryness in patients with sSS-RA after 3 months of receiving LEF inspite of the significant improvement of their DAS28. This finding was not clearly detected in RA patients. Close monitoring of eye dryness changes by special tests in patients using LEF is recommended, especially in cases with sSS-RA having very low baseline values.

A retrospective analysis of treatment outcomes in patients with hepatitis C related systemic vasculitis receiving intravenous methylprednisolone and cyclophosphamide.

The aim of this work is to describe the outcome of a series of patients with hepatitis C virus (HCV)-related vasculitis who were treated with corticosteroids and I.V. cyclophosphamide without receiving any antiviral therapy. The data of 16 patients with HCV infection and vasculitis were retrospectively analyzed for the treatment outcome in the present study. Eleven patients were females (68.8%) with a mean age of 49.6 ± 10.0 years. Nine patients (56.2%) had medium-sized vessel vasculitis (group A) and seven patients (43.8%) had small vessel vasculitis (group B). Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS 2003) and organ damage was assessed by the Vasculitis Damage Index (VDI). HCV infection was confirmed in all patients by the detection of antibodies to HCV in serum by ELISA and HCV RNA using qualitative PCR. Quantitative PCR was done using the branched DNA technique. None of our study patients had received antiviral therapy, but they all received I.V.-pulsed cyclophosphamide monthly for 6 months, then every 3 months for six times if needed, preceded by I.V. methylprednisolone. Twelve patients (75%) had undetectable viral load by the quantitative technique. The drop in mean BVAS recorded at different intervals was highly significant. Although there was a drop in the VDI mean between the first and second reading, it was not statistically significant. All patients responded to treatment. Seven patients (43.8%) had relapse. Two patients died (12.5%). One patient died from renal failure (group B) and another died from sepsis (group A). The treatment outcomes were not statistically significant between the two vasculitis groups. A subset of patients with HCV-related vasculitis and with low levels of viremia can be safely treated with corticosteroids and cyclophosphamide alone. Despite successful treatment, a significant proportion of patients relapse and some develop severe complications and death.

Clinical significance of serum anti-annexin V antibodies in Egyptian patients with scleroderma.

The pathogenesis of scleroderma encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations. We investigated the prevalence of anti-annexin V IgG and IgM antibodies in sera of scleroderma patients and their relation to the presence of other antibodies and development of disease morbidity. Sera of 40 scleroderma patients and 15 healthy controls were examined for IgG and IgM anti-annexin V antibodies by ELISA and anticentromere antibodies by indirect immunofluorescence. Serum level of anti-annexin V IgG antibodies in scleroderma patients was significantly higher than that of the control (P < 0.001) and correlated significantly with the presence of digital ischemia (P = 0.023) and pulmonary fibrosis (P = 0.02). IgM isotype was comparable between patients and controls (P = 0.317). Anticentromere antibodies are more prevalent in the limited cutaneous subtype (P = 0.017). In conclusion, measurement of serum anti-annexin V IgG antibodies in scleroderma patients may be important for early diagnosis of vascular and pulmonary complications.

Pulmonary involvement in systemic sclerosis.

Scleroderma, also known as progressive systemic sclerosis (SSc), is a multisystem autoimmune disorder characterized by inflammation and fibrosis involving the skin as well as internal organs such as the vasculature, esophagus, and the respiratory tract. Pulmonary involvement consists most often of interstitial fibrosis and pulmonary vascular disease leading to pulmonary arterial hypertension (PAH). Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis. Pulmonary hemorrhage with acute renal failure and diffuse alveolar hemorrhage in the absence of a history of renal involvement or penicillamine intake have rarely been reported in patients with systemic sclerosis.On high resolution CT, evidence of interstitial disease is seen in approximately 90% of patients, the main findings being a fine reticular pattern involving the subpleural regions of the lower lobe. Other common findings include ground-glass opacities, honeycombing, and parenchymal micronodules. The most distinctive pulmonary histologic findings in patients with scleroderma are the vascular changes found in PAH in the absence of significant interstitial fibrosis.There is no strong evidence that any drug alters the course of the two main types of lung disease in systemic sclerosis. This apparent failure of therapy may reflect the fact that pulmonary involvement is usually identified at an established or late stage. It has been suggested that, for fibrosing alveolitis, corticosteroids are most effective if given in combination with cyclophosphamide. In some patients with SSc, PAH has been considered as a major cause of morbidity and mortality. Centrally infused prostacyclin (epoprostenol) and its subcutaneously infused analog treprostinil improve hemodynamics, as well as the quality of life and survival in these patients. Iloprost has also shown a positive effect on PAH in SSc patients. More recently, bosentan, an endothelin receptor antagonist, has proved effective in controlling PAH after 6 months' treatment. Sildenafil has been used as a selective pulmonary vasodilator in SSc patients with isolated PAH. This drug decreased mean pulmonary artery pressure and pulmonary vascular resistance, and increased cardiac output, with much improvement of the physical condition of the patients. Lung transplant can be considered as a last option.Clinicians must be aware of the possibility of lung disease in patients with SSc so that it can be treated as early as possible.

Cardiac involvement in patients with systemic lupus erythematosus and correlation of valvular lesions with anti-Ro/SS-A and anti-La/SS-B antibody levels.

The aim of this study was to evaluate the incidence of morphologic and functional cardiac abnormalities in patients with systemic lupus erythematosus (SLE) and to correlate the findings with levels of anti-Ro/SS-A, anti-La/SS-B, and anti-cardiolipin antibody (aCL). Sixty-two patients with SLE were enrolled in this study. All patients underwent complete history taking, clinical assessment, and standard two-dimensional and Doppler echocardiography. Anti-Ro/SS-A, anti-La/SS-B, and aCL levels were measured using a standardized ELISA test. The patients were subdivided into two subgroups based on the presence or absence of valvular involvement. The two subgroups were then compared. Valvular involvement was present in 19 patients (30.6%), pericardial effusion in 12 patients (19.4%), impaired left ventricular relaxation abnormalities in 2 patients (3.2%), and pulmonary hypertension in 3 patients (4.8%). More patients in the valvular involvement group had positive anti-Ro/SS-A antibodies than in the valvular noninvolvement group (7/19 vs. 4/43). The difference was significant, with P < 0.01. Serum levels of anti-Ro/SS-A levels were significantly higher in the valvular involvement group (33.7 +/- 36.0 vs. 13.7 +/- 25.1; P < 0.01), as were the serum anti-La/SS-B levels (21.9 +/- 23.5 vs. 10.7 +/- 17.8; P < 0.05). The results suggest a causative correlation between anti-Ro/SS-A and anti-La/SS-B antibodies and the pathogenesis of the valvular lesions in SLE patients.

Tumor necrosis factor-alpha and neuropsychiatric lupus erythematosus: relation to single photon emission computed tomography findings.

Abstract This study was designed to highlight the relation of tumor necrosis factor-α (TNF-α) to neuropsychiatric lupus (NPLE) manifestations. The relation of TNF-α to the type of single photon emission computed tomography (SPECT) findings in this context was also studied. Twenty-one systemic lupus erythematosus (SLE) females, mean age 27.57 ± 9.89 years, and twenty age-matched normal females (controls), were subjected to TNF-α assessment. Different clinical and neuropsychiatric manifestations were evaluated. SPECT was carried out for all patients. The results showed that the mean TNF-α level (pg/ml) was significantly raised in patients compared with controls (167.8 ± 102.5 versus 64 ± 50.2, respectively, P < 0.005). Thirteen patients (69.1%) had NPLE manifestations. NPLE patients had a significantly higher mean TNF-α than patients without NPLE (203 ± 102.8 versus 109 ± 47.3, respectively, P < 0.03). Positive SPECT findings were found in 18 lupus patients (85.7%), including all 13 patients with NPLE (100% sensitivity), with a multiple focal pattern of hypoperfusion being the most frequent type (9/13), followed by diffuse (3/13), and then single focal pattern (1/13). The mean TNF-α was significantly higher in patients with multiple focal pattern (P < 0.001). In conclusion, results of this work support the hypothesis that TNF-α could be involved in the pathogenesis of NPLE, and hence, it could be speculated that the evolving anti-TNF therapy can play a potential role in the management of this disease.

Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography.

Nineteen patients with juvenile chronic arthritis (JCA), ten with systemic (s)-JCA, and nine with polyarticular-onset (p)-JCA were examined for interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-2R, and IL-10 levels. Power Doppler sonography (PDS) for the more affected knee was used in all of them to evaluate soft tissue vascularity. Serum levels of IL-6 were significantly higher in JCA patients than in controls (P<0.007). Patients with p-JCA showed higher levels of IL-6 than patients with s-JCA, and the difference was statistically nonsignificant. Serum IL-6 levels in all patients correlated significantly with the degree of vascularity detected by PDS (P<0.01). This correlation was more pronounced in p-JCA patients (P<0.01 in p-JCA vs P<0.05 in s-JCA). Serum levels of TNF-alpha were higher in patients with JCA than in controls (P<0.0001). Serum levels of TNF-alpha were significantly greater in patients with s-JCA than in p-JCA (P=0.008). Soluble IL-2R levels were higher in patients with JCA than controls (P<0.0002). Serum levels of IL-2R correlated significantly with pannus thickness in p-JCA (P<0.01) and inversely with methoxetrate (MTX) duration in s-JCA (P<0.05). Serum levels of IL-10 were significantly higher in JCA patients than in controls ( P<0.0008). Serum IL-10 levels in all patients correlated significantly inversely with hemoglobin levels (r=-0.50, P<0.05), total leukocytic count (TLC) (r=-0.58, P<0.01), and intra-articular steroid injection (r=+0.56, P<0.01). In s-JCA, IL-10 levels correlated significantly with MTX weekly dose ( P<0.05). In conclusion, a significant correlation of serum IL-6 levels with the degree of knee joint vascularity was found, and this correlation was more pronounced in p-JCA, which may stress the role of IL-6 as an inducer of neoangiogenesis in JCA.