Ewa Wielosz

Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties

We report the case of coexistence of five autoimmune diseases in a 36-year-old woman, who initially developed psoriasis. Several years later, the patient was diagnosed with a mixed connective tissue disease and primary biliary cirrhosis (PBC). On admission to the Department of Rheumatology and Connective Tissue Diseases, the patient fulfilled classification criteria of an overlap syndrome systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome/systemic sclerosis (SSc)/Sjogren’s syndrome (SS) with coexisting PBC and psoriasis. The SLE symptoms included discoid lupus erythematosus, arthritis, pancytopenia, antinuclear antibodies and anticardiolipin antibodies. Moreover, the patient met the criteria of antiphospholipid syndrome diagnosed based on preterm delivery before week 34, and high values of anticardiolipin antibodies were found at repeated determinations. The SSc symptoms included sclerodactyly, pulmonary fibrosis with pulmonary hypertension and esophageal dysfunction. The SS syndrome involved xerostomia, xerophthalmia, the positive Schirmer’s test and presence of anti-SS antibodies. The literature reports overlap syndromes in various combinations; however, the coexistence of five autoimmune diseases is extremely rare.

Antiphospholipid antibodies and kidney involvement in patients with systemic sclerosis

Antiphospholipid (aPL) antibodies are often detected in systemic autoimmune diseases. The aim of the study was to examine the correlation between the presence of aPL and certain markers of renal function in systemic sclerosis (SSc). Fifty patients (pts) with SSc were examined for the presence of antibodies to cardiolipin (aCL) and to anti-beta 2 glycoprotein I (a-B2GPI) in immunoglobulin M (IgM) and IgG class. Moreover, serum levels of creatinine, cystatin C, and glomerular filtration rate (GFR) were determined in all patients. In all studied pts together, three multiple-regression analyses were performed with one set cystatin C as a dependent variable, in the second GFR according to the Cockcroft–Gault formula and in the third creatinine clearance by Modification of Diet in Renal Disease (MDRD) formula. As independent variables, aPL of either type were inserted in addition to disease duration and age. IgG aCL was significantly positively associated with serum cystatin C (p = 0.002), significantly negatively associated with creatinine clearance according to the Cockcroft–Gault and MDRD formula (p = 0.01 and 0.02, respectively). IgG a-B2GPI was significantly negatively associated with creatinine clearance according to the Cockcroft–Gault (p = 0.03) and MDRD (p = 0.01) formula. IgM aCL and IgM a-B2GPI were not associated with any markers of the renal function. Our study suggests the relationship between kidney involvement and the positivity for some aPL in patients with SSc. Positivity for IgG aCL and IgG a-B2GPI in patients with SSc without secondary antiphospholipid syndrome seems to be connected with decrease of glomerular filtration.

Serological profile of patients with systemic sclerosis.

INTRODUCTION The systemic sclerosis-associated autoantibodies include anti-centromere, anti-topoisomerase I (anti-topo I), anti-RNA polymerase III, anti-fibrillarin, anti-Th/To, and anti-PDGFR. A specific serological profile is connected with clinical manifestations and prognosis in systemic sclerosis (SSc). OBJECTIVES The aim of the study was to assess the serological profile in limited cutaneous and diffuse cutaneous SSc (lcSSc and dcSSc). PATIENTS AND METHODS 87 (68 female and 19 male) consecutive SSc patients treated between 2006 and 2011 were assessed. Patients fulfilled the American College of Rheumatology classification criteria of SSc: 35 - dcSSc and 52 - lcSSc. The following marker antibodies were determined: anti-topo I, anti-centromere A and B (CENP A, CENP B), anti-RNA polymerase III (RP11, RP 155), anti-fibrillarin (U3RNP), anti- -NOR90, anti-Th/To, anti-PM-Scl-100, anti-PM-Scl-75, anti-Ku, anti-Ro-52, anti-PDGFR. The presence of antibodies was assessed using a test - EUROLINE Systemic Sclerosis Profile. RESULTS 82 patients (94%) had positive antinuclear antibodies; anti-topo I - 29 patients; anti-CENP-A - 20 and anti-CENP-B - 20; anti-RP11 - 9 and anti-RP155 - 7; anti-U3RNP - 1; anti-NOR90 - 6; anti-Th/ To - 3; anti-PM-Scl-100 - 7; anti-PM-Scl-75 - 11; anti-Ku - 5; anti-Ro-52 - 23 patients. We found significant differences in prevalence of anti-topo I: 25/35 vs. 4/52 p=0.0000; anti-CENP A: 0/35 vs. 20/52 p=0.0001; anti-CENP B: 0/35 vs. 20/52 p=0.0001 between dcSSc and lcSSc. CONCLUSIONS Some antibodies in SSc, e.g. anti-topo I and anti-centromere, are useful in defining the clinical subset of disease and provide prognostic information. There are no significant differences in the prevalence of other autoantibodies associated with SSc between dcSSc and lcSSc patients.

Comparison of clinical and serological parameters in female and male patients with systemic sclerosis

Objectives The course of systemic sclerosis (SSc) can differ in female and male patients. According to the literature the incidence rates of diffuse cutaneous SSc, scleroderma renal crisis and digital ulceration are higher in male patients. The aim of the study was to compare selected clinical and serological parameters in male and female patients with SSc. Material and methods The study encompassed 101 European Caucasian patients with SSc, including 23 men, hospitalized in the Department of Rheumatology. Patients fulfilled the American Rheumatism Association (ARA) classification criteria for SSc. The study groups of men and women were assessed according to the SSc subtype, incidence of internal organ involvement and presence of antinuclear antibodies considered SSc markers. Results Diffuse cutaneous (dc) SSc was observed more commonly in men than in women (13/23 vs. 25/78; p = 0.03). The time from the development of Raynauds phenomenon to the diagnosis was significantly shorter in male compared to female patients (3.2 ±4.7 vs. 7.5 ±7.1; p = 0.01). The incidence of scleroderma renal crisis (SRC) was significantly higher (3/23 vs. 2/78; p = 0.04) and of other calcifications significantly lower in the male group compared to the female group (1/23 vs. 20/78; p = 0.02). Conclusions We concluded that the incidence of dcSSc is higher in men compared to women. The time from the development of Raynauds phenomenon to the diagnosis is shorter in the male compare to female group. The incidence of SRC is higher, whereas that of calcifications is lower in SSc men. The serological profiles of female and male patients with SSc are comparable.

Systemic sclerosis and organ - specific antibodies.

INTRODUCTION According to the literature, organ‑specific antibodies may be present in the course of systemic sclerosis (SSc). OBJECTIVES The aim of this study was to assess the prevalence of antithyroid antibodies (antithyroid peroxidase antibodies [anti‑TPO] and antithyroglobulin antibodies) and of antimitochondrial antibodies (AMAs), as well as to evaluate their clinical significance in patients with SSc. PATIENTS AND METHODS The study involved 86 consecutive in‑hospital patients with SSc (32 patients with diffuse cutaneous SSc [dcSSc] and 54 with limited cutaneous SSc [lcSSc]). Patients were observed for autoimmune thyroid diseases (ATDs) and primary biliary cirrhosis (PBC). Serum samples were obtained from each patient. RESULTS Positive antithyroid antibody titers were observed in 27 patients (31%) and positive AMA titers-in 11 patients (13%). ATD was diagnosed in 26 patients (30%) and PBC-in 10 patients (12%) with SSc. No significant differences in the prevalence of antithyroid antibodies were found between patients with dcSSc and those with lcSSc, but the prevalence of AMAs was significantly higher in patients with lcSSc compared with those with dcSSc. The prevalence of anti‑Ro‑52 antibodies was significantly higher in the SSc group with positive anti‑TPO antibody titers compared with the SSc group with negative anti‑TPO antibody titers. The prevalence of anticentromere antibodies (ACAs) was significantly higher in the SSc group with positive AMA titers compared with the SSc group with negative AMA titers. CONCLUSIONS The prevalence of organ‑specific antibodies in SSc patients is relatively high. The prevalence of AMAs is higher in patients with lcSSc than in those with dcSSc and is strongly associated with the presence of ACAs. Patients with SSc should be evaluated for coexisting ATDs and PBC.

Overlap syndromes in systemic sclerosis

Introduction It is known, that course of the disease differs between overlap syndromes (OS) and systemic sclerosis (SSc) group. Aim To compare the prevalence of OS in limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous SSc (dcSSc) and to analyze the presence of different manifestations in the SSc and OS group. Material and methods The study included 126 European Caucasian SSc patients (99 females and 27 males) hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases. Patients fulfilled the American College of Rheumatology (ACR) classification criteria of SSc (57 – dcSSc and 69 – lcSSc). The study groups were determined according to the subtype of SSc, coexistence of other connective tissue diseases (CTDs), and incidence of clinical and serological manifestations. Results In our SSc study group, 28/126 patients (22%) were affected by more than one CTD. The prevalence of OS was significantly higher in the lcSSc group – 33% (23/69) compared to the dcSSc group – 8% (5/57). We found that mortality and digital ulcers were significantly higher, whereas kidney involvement and arthritis were significantly lower in the SSc group compared to the OS group. The prevalence of anti-topoisomerase I (a-Scl-70) was significantly higher, and prevalence of anti-PM/Scl, anti-Ro-52 antibodies was significantly lower in the SSc group compared to the OS group. Conclusions Overlap syndromes were more common in lcSSc than in dcSSc. The course of the disorder and internal organ involvement were different in OS compared to SSc patients.

Anti-CCP antibodies and rheumatoid factor in systemic sclerosis:Prevalence and relationships with joint manifestations

BACKGROUND It is known that anti-citrullinated protein (a-CCP) antibodies and rheumatoid factor (RF) can be present in systemic sclerosis (SSc) patients, particularly with joint involvement. OBJECTIVES The aim of the study was to assess the prevalence of a-CCP antibodies and immunoglobulin M class (IgM) RF, and the relationships between their presence and joint manifestations in patients with SSc. MATERIAL AND METHODS The study included 100 European Caucasian SSc patients hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases (Lublin, Poland). Anti-citrullinated protein antibodies and IgM RF were determined using a commercial enzyme-linked immunosorbent assay (ELISA) test. RESULTS Anti-citrullinated protein antibodies were found in 10 out of 100 (10%) SSc patients and IgM RF in 71 out of 100 (71%) SSc patients. In the study, 90/100 (90%) SSc patients had joint manifestations (arthralgia or arthritis), 34/100 (34%) had arthritis and 6/100 (6%) had a systemic sclerosis-rheumatoid arthritis (SSc-RA) overlap syndrome. Significantly higher a-CCP antibody levels (p = 0.012), erythrocyte sedimentation rate (ESR) (p = 0.029) and C-reactive protein (CRP) levels (p = 0.020) were observed in the SSc group with arthritis. A significant correlation was found between the group with arthritis and the presence of a-CCP antibodies, and between the arthralgia group and the presence of IgM RF. CONCLUSIONS The prevalence of RF and a-CCP antibodies is relatively high in SSc, and joint involvement occurs frequently. There was a significantly higher prevalence of IgM RF in the group with joint manifestations. About 1/3 of SSc patients had symptoms of arthritis. Arthritis is connected with the presence of a-CCP antibodies, while arthralgia is connected with the presence of IgM RF.

Coexistence of diabetes mellitus type 1 with diffuse systemic sclerosis – case report and literature review

Diabetic sclerodactyly is a frequently recognized skin finding that may occur in patients with diabetes mellitus but coexistence of diabetes and systemic sclerosis is rare. We describe a case of coexistence of type 1 diabetes mellitus and systemic sclerosis in 42-year-old man with the history of Raynaud’s phenomenon, progressive diffuse hardening of the skin and sclerodactyly, slowly worsening with time. The medical history included type 1 diabetes since childhood with microvascular complications. The patient presented a typical capillaroscopic scleroderma-like pattern, antinuclear antibodies and sclerotic lesions in gastrointestinal system. Summing up, our case represents the rare coexistence of autoimmune diseases like diabetes mellitus type 1 and systemic sclerosis.

Influence of antiphospholipid antibody positivity on glomerular filtration rate markers in a group of systemic sclerosis patients – a 24-month observation

Aim of the study The aim of the study was the assessment of changes in the glomerular filtration rate (GFR) during long-term observation in a group of systemic sclerosis (SSc) patients with and without chronic antiphospholipid (aPL) antibody positivity. Material and methods The observation comprised 50 patients – 23 with diffuse cutaneous SSc – dcSSc and 27 limited cutaneous SSc – lcSSc. After 24 months we assessed 27 patients (9 died, 14 lost follow up); 24 patients (88%) were treated chronically with angiotensin-converting-enzyme inhibitors (ACEIs). Patients were investigated for the presence of aPL: to cardiolipin and to β2 glycoprotein I in IgM and IgG classes. Serum levels of creatinine (S-Cr), cystatin C and creatinine clearance values were determined in all patients. According to the presence of a significant level of at least one of aPL antibodies, pts were divided into groups: group I aPL positive: 14 patients, group II aPL negative – 13 patients. Results We did not find significant differences in S-Cr, cystatin C levels and creatinine clearance before and after 24 months of observation between both groups. In follow up observations, the presence of anti-centromere antibodies was significantly more frequent in the aPL positive, as compared to the aPL negative group (p = 0.01). In follow up observations, the level of anticardiolipin antibodies in IgG class was significantly higher in dcSSc compared to lcSSc patients (p = 0.02). Conclusions In long-term observation chronic positivity for aPL antibodies does not significantly decrease the GFR in patients with SSc treated with ACEIs.

AB0594 Anti-RNA Pol III Antibodies in Systemic Sclerosis - The Prevalence and Usefulness

Background Anti-RNA Polimerase III (a-RNA Pol III) antibodies are markers antibodies which are detected in sera of patients with systemic sclerosis (SSc). They are found in approximately 20% of SSc, particularly with diffuse subtype. According to literature a-RNA Pol III antibodies are strongly associated with scleroderma renal crisis (SRC). They are also correlated with higher rate of SSc-related mortality. Additionally, there are many data which reported that, a-RNA Pol III antibodies are associated with an increased risk of malignancy in patients with SSc. Objectives The aim of the study was assess the prevalence of a-RNA Pol III antibodies in patients with systemic sclerosis and to identify differences in the picture of the disease in patients with the presence of a-RNA Pol III. Methods The study was performed in 126 (98-female and 28-male) consecutive SSc patients treated in Department of Rheumatology. Patients fulfilled the ACR classification criteria of SSc (60 have diffuse SSc-dcSSc and 66 limited SSc – lcSSc). The subtype of SSc, incidence of internal organ involvement, the prevalence of malignancy, death and serological profile were determined in the whole data group. The study group were studied according to the presence of antibodies applying commercial test – EUROLINE Systemic Sclerosis Profile. Detection and interpretation of results was carried out electronically using the specific program Euroimmun– EUROLINEScan. Due to the presence of a-RNA Pol III antibodies, patients were divided into two groups a-RNA Pol III(+) SSc – 19 pts and a-RNA Pol III(−) SSc – 107 pts. Results According to our data a- RNA Pol III antibodies were present in 19/126 patients with SSc (15%), including the a-RNA Pol III 11 were present in 16 and a-RNA Pol III 155 in 14. In this group of 13 (68,4%) pts had no other marker to SSc antibodies as a anticentromere, anti-topoisomerase I. Moreover, in our study group, a-RNA Pol III antibodies were more common in patients with dcSSc (p=0,049), compare to lcSSc. We also showed a significant positive association with a-RNA Pol III antibodies and occurrence of malignancy (p=0,007), SRC (p=0,001) and decreased DLCO (p=0,007). There was no relationship between the presence of a-RNA Pol III and other organ involvement, digital ulcerations or calcinosis. Conclusions 1. Anti- a-RNA Pol III antibodies are quite common in patients with systemic sclerosis, particularly with diffuse subtype. 2. In more than 50% of patients a-RNA Pol III antibodies may be present as the sole marker to SSc antibodies. 3. In SSc a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement. Disclosure of Interest None declared