Pulmonary hypertension in systemic lupus erythematosus: relationship with antiphospholipid antibodies and severe disease outcome.

Pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) is associated with an unfavorable prognosis. We investigated the characteristics of SLE patients with PH. The patients with a pulmonary artery systolic pressure more than 30 mmHg at rest on echocardiogram were diagnosed with PH. Echocardiography was done only in patients with clinical or radiological evidence suggesting PH. Right heart catheterization was not performed. We identified 10 SLE patients with PH between 1980 and 2000. We compared their clinical and laboratory parameters with those of 97 consecutive SLE patients without PH. Nine of the ten patients with PH were females. The mean age at the time of SLE onset was 25.2 ± 6.9 years; the mean duration of follow-up was 93.4 ± 52.8 months, and the interval between the onset of SLE and PH diagnosis was 9.0 ± 4.6 (5-21) years. Antiphospholipid antibody positivity was significantly higher in the PH group (80 vs. 36%; p < 0.05), but there was no significant difference between two groups in regard to secondary antiphospholipid syndrome. The frequency of Raynaud's phenomenon was higher in PH group (60 vs. 27%; p < 0.05). Renal involvement (80 vs. 43%; p < 0.05), neuropsychiatric involvement (40 vs. 7.2%; p < 0.005) and serositis (70 vs. 14.4%; p < 0.001) were significantly more frequent in the PH group. The mean damage score in patients with and without PH were 4.0 ± 2.4 and 0.4 ± 1.0, respectively (p < 0.001). Four patients with PH died during the follow-up. This study reveals that the presence of PH defines a subgroup of patients with a severe disease and increased mortality. Antiphospholipid antibodies and Raynaud's phenomenon may contribute to the pathogenesis of PH. We recommend that all patients with SLE, especially those positive for antiphospholipid antibodies and/or with signs of Raynaud's phenomenon should be regularly evaluated for the development of PH.

Predictors of damage and survival in patients with Wegener's granulomatosis: analysis of 50 patients.

OBJECTIVE: To evaluate damage features and impact on survival by Vasculitis Damage Index (VDI) in a cohort of Turkish patients with Wegener's granulomatosis (WG). METHODS: We enrolled 50 (25 female) patients with WG according to ACR criteria. Birmingham Vasculitis Activity Score (BVAS) and VDI were used to analyze disease activity and damage. RESULTS: Patients had kidney (82%), upper airway (72%), lung (70%), and nervous system (15%) involvement. Median age at diagnosis was 45 years, time to diagnosis was 3.5 months, and total followup time was 35.5 months. All but one patient was positive for antineutrophil cytoplasmic antibodies (ANCA). Mean final dose and duration of corticosteroid and cyclophosphamide was 15 +/- 14 g, 39 +/- 33 months and 36 +/- 34 g, 21 +/- 2 months, respectively. Mean early (e) BVAS were 20.2 +/- 7.1 (4-38) (median 21). Mean e-BVAS and e-VDI scores at presentation and final (f)-VDI scores at last visit were 20.2 +/- 7.1 (4-38), 3.1 +/- 1.7 (median 3) (0-7) and 4.4 +/- 2.6 (0-12), consecutively. Disease related damage was prominent in kidneys (50%) and upper airways (27%). Amenorrhea (90%), cataract (28%), and diabetes (24%) were the most frequent treatment related damages. Rapidly progressive glomerulonephritis at presentation (42%) progressed to endstage renal failure in 20%. Relapses occurred in 25% with mean BVAS of 6.5 +/- 2.3 (4-11). Survival rate was 77% at 37 months. Deaths occurred early (90% in the first year). f-VDI was high in patients who relapsed (6 +/- 3 vs 3.8 +/- 2.1, p = 0.03). Logistic regression analysis demonstrated that age at time of diagnosis and e-VDI were lower in survivors with OR = 0.9 (p = 0.06, 95% CI: 0.78-1) and OR = 0.5 (p = 0.04, 95%CI: 0.25-0.98), respectively. In this cohort, e-VDI score of 5 or more was related to death with 98% sensitivity and 56% specificity (p = 0.004) (CI: 0.66-0.95). CONCLUSION: Disease related damage outweighed treatment related damage in our cohort of predominantly generalized disease activity. Early damage and older age were found to be predictors of final damage and death.

Rosai-Dorfman disease with factor XII deficiency.

A 17-year-old female patient presented with chronic symmetrical oligoarthritis of both knees and ankles, xerostomia, xerophthalmia, multiple bilateral lymphadenopathies in the cervical region, and bilateral parotid enlargement with the histological finding of chronic sialoadenitis. She had been already given methotrexate, chloroquine, and corticosteroids with the diagnosis of rheumatoid arthritis (RA) before referral to our outpatient clinic. Because her complaints and the lumps did not remit and she could be classified as neither RA nor primary Sjögren's syndrome (SS) according to 1987 ACR RA criteria or European preliminary criteria for SS, lymph node biopsy was repeated and revealed the diagnosis of Rosai-Dorfman disease (RDD) with the histological findings of histiocytes, phagocyting lymphocytes in enlarged sinuses, and mature plasma cells infiltrating the pulpa. All the medications were stopped after the pathological diagnosis of RDD and consulting with the Division of Hematology. She was reevaluated with magnetic resonance imaging, which showed dense infiltrative areas around knee and ankle joints, and computed tomography that showed a soft tissue mass surrounding the descending aorta and upper part of the abdominal aorta. Activated partial thromboplastin time was found to be prolonged in prebiopsy examinations, and factor XII deficiency was detected after detailed hematological evaluation. The symptoms of joint involvement were relieved with nonsteroidal antiinflammatory drugs. She has been followed-up without medication without obvious clinical or laboratory change. We herein report a patient with RDD mimicking RA and SS. We consider that RDD should be kept in mind especially in patients with resistant symptoms to conventional therapies, younger disease onset, and predominant parotid and lymph node enlargement.

Clinical evaluation and comparison of different criteria for classification in Turkish patients with psoriatic arthritis.

Several criteria are being used for the classification of psoriatic arthritis (PsA) and there is a lack of consensus about PsA as a separate entity. Our aim is to investigate the clinical features of our patients with a clinical diagnosis of PsA, compare the sensitivities of different classification criteria, agreement between the criteria. In this study 86 PsA patients were investigated (48 females, mean age 44). Moll and Wright criteria was fulfilled by 91%, Vasey and Espinoza criteria by 94% and modified European SpA study group criteria by 59%, classification of PsA study group criteria by 86%, modified McGonagle criteria by 96%, Fournie et al. criteria by 84% and Gladman criteria by 95%. Significant agreement was present between criteria but generally kappa-values were less than 0.5. The pattern of PsA can differ with time and the implementation of the available classification criteria showed considerable differences.

Low frequency of HLA-B27 in ankylosing spondylitis patients from Turkey.

OBJECTIVES: Ankylosing spondylitis is strongly associated with HLA-B27. However, the strength of the association with HLA-B27 and the clinical features may vary in different parts of the world. The aim of this study is to compare the clinical features of AS and the frequencies of HLA-B27 and its alleles in patients from Turkey with other series. METHODS: One hundred and twelve patients (72 male/40 female) fulfilling the modified New York criteria for the classification of AS and 55 (27 male/28 female) healthy controls were typed for HLA-B27 and allele frequencies by sequence specific primer (PCR/SSP) method and assessed for clinical manifestations. RESULTS: Male to female ratio was 1.8, mean age at disease onset was 23.5 and 24.1% of patients reported juvenile onset of symptoms. Peripheral arthritis was seen in 52.7% of patients. Family history (p=0.01) and peripheral arthritis (p=0.02) were more frequent in females and spinal involvement in males. HLA-B27 was found to be positive in 70% of patients and associated with younger mean age, uveitis and shorter time elapsed from symptom to diagnosis. The frequency of HLA-B27 alleles associated with SpA was not different between ankylosing spondylitis patients and healthy controls. CONCLUSION: Low frequency of HLA-B27 and clinical variations in ankylosing spondylitis may be due to different genetic and/or environmental factors in Turkey.

Clinical evaluation and comparison of different criteria for classification in Turkish patients with psoriatic arthritis.

Several criteria are being used for the classification of psoriatic arthritis (PsA) and there is a lack of consensus about PsA as a separate entity. Our aim is to investigate the clinical features of our patients with a clinical diagnosis of PsA, compare the sensitivities of different classification criteria and agreement between the criteria. In this study 86 PsA patients were investigated (48 female, mean age 44). Moll and Wright criteria were fulfilled by 91%, Vasey and Espinoza criteria by 94% and modified European SpA study group criteria by 59%, classification of PsA study group criteria by 86%, modified McGonagle criteria by 96%, Fournié et al. criteria by 84%, and Gladman criteria by 95%. Significant agreement was present between criteria but generally kappa values were less than 0.5. The pattern of PsA can differ with time and the implementation of the available classification criteria showed considerable differences.

Safety of high-dose intravenous immunoglobulin in systemic autoimmune diseases.

It is reported that the usage of high-dose intravenous immunoglobulin (HD-IVIG) in systemic autoimmune diseases is associated with various adverse events in a wide range of severity. We aimed to investigate the frequency and profile of adverse events in a group of patients with diffuse connective tissue diseases and Wegener's granulomatosis (WG) who were administrated HD-IVIG for different indications. We recorded the data of 38 patients (25 females and 13 males) aged 38 +/- 15 (12-75) years who were followed up with the diagnosis of systemic autoimmune diseases between 1994 and 2006 according to a predefined protocol. Patients with active disease were treated with HD-IVIG and standard immunosuppressives concomitantly. We evaluated the occurrence of allergy, acute renal failure, thromboembolic events, neutropenia, hemolytic anemia, aseptic meningitis, and vasculitis during infusion therapy of HD-IVIG and in the following 3 weeks. We commenced a total of 130 infusions of HD-IVIG. Patients were administrated 1-12 (3.4 +/- 2.6) infusions of HD-IVIG as needed. Indications for HD-IVIG were unresponsiveness or partial response to standard treatment, severe infections along with disease activity, and severe thrombocytopenia in the preoperative period in 97, 23, and 5% of patients, respectively. Minor adverse events were seen in two patients during HD-IVIG infusions. One patient with WG developed rapidly progressive renal failure during severe disease flare between HD-IVIG infusions. Another patient with WG developed recurrence of deep-vein thrombosis during severe disease flare 3 months after HD-IVIG. Both events were attributed to severe disease activity. Adverse events like allergy, acute renal failure, thromboembolic events, hematological problems, aseptic meningitis, and vasculitis are reported in different frequencies (1-81%) in patients who were administered HD-IVIG for systemic autoimmune diseases. HD-IVIG is considered a safe treatment in selected patients assuring adequate infusion precautions.

Anti-CCP and antikeratin antibodies in rheumatoid arthritis, primary Sjögren's syndrome, and Wegener's granulomatosis.

The objective of this study was to investigate the frequency of antibodies against cyclic citrullinated peptides (anti-CCP) and keratin (AKA) in patients with rheumatoid arthritis (RA) as well as in patients with primary Sjögren's syndrome (pSS) and Wegener's granulomatosis (WG), who may present with rheumatoid factor (RF)-positive arthritis. The study group consisted of 46 patients with RA (26 patients were negative for RF), 32 with pSS, 22 with WG, and 40 healthy controls. The RF, anti-CCP, and AKA were detected in serum using the latex agglutination test, enzyme-linked immunosorbent assay, and indirect immunofluorescence, respectively. The agreement between those tests was evaluated by kappa test. No positive result for AKA was detected in pSS and WG patients, and anti-CCP was found in only one patient with pSS. The results of kappa tests were low, varying between 0.25 (RF-anti-CCP) and 0.02 (RF-AKA). The sensitivity and specificity values were 43 and 44% for RF, 65 and 98% for anti-CCP, and 58 and 100% for AKA, respectively, in RA patients. In the RF-negative RA group, AKA was found to have a high frequency (55%) in comparison to anti-CCP (38%). Seropositivity was found to be 87% for any one of the three autoantibodies tested in RA patients. With a higher specificity, values for RA, anti-CCP, and AKA seem to be helpful for the differential diagnosis of patients with RF-positive arthritis, which may include patients with WG and pSS, and screening of all three antibodies may increase the diagnostic performance.

Experience with monthly, high-dose, intravenous immunoglobulin therapy in patients with different connective tissue diseases.

We aimed to investigate the efficacy and safety profile of high-dose intravenous immunoglobulin (HD-IVIG) therapy in patients with severe systemic lupus erythematosus (SLE), inflammatory muscle disease (IMD), Wegener's granulomatosis (WG), and/or concurrent infection who failed to respond to standard therapies. We evaluated the records of eight patients with SLE, eight with IMD, and four with WG who were treated with HD-IVIG (2 g/kg per month for 1-12 months) for active disease in 19 patients and concurrent infection in three (mycobacterial in two with SLE and cytomegaloviral in one with WG). Systemic lupus erythematosus disease activity index (SLEDAI) scores before and after HD-IVIG were statistically analysed. Remission was achieved in 14 cases (70%). The SLEDAI scores significantly decreased in patients with SLE (P=0.02). No serious side effect was observed. High-dose IVIG may be used as an adjunctive treatment in connective tissue diseases that do not respond to standard therapies or as alternative treatment for patients with concurrent severe infections or for whom immunosuppressives are contraindicated.

Systemic necrotizing vasculitides in Turkey: a comparative analysis of 40 consecutive patients.

OBJECTIVE: The aim of this study was to analyze and compare the demographic and clinical features and prognosis of patients with different systemic necrotizing vasculitides (SNV) in Turkey. PATIENTS AND METHODS: Twenty-three patients with Wegener's granulomatosis (WG), 15 with polyarteritis nodosa (PAN), and two with Churg-Strauss syndrome were included in the study. The clinical and laboratory features of patients with WG and PAN were compared, and survival analysis was performed for the WG patients. RESULTS: Twenty-one patients with WG had systemic disease involving kidneys, and two had localized disease. Fifteen patients were placed in the PAN group, 12 of whom were classified as having classic PAN and three with microscopic polyangiitis. Median follow-up time was 37 months (range 1-81) for WG patients and 41 months (range 5-132) for the PAN group. Upper respiratory tract, pulmonary, and renal involvement were significantly more frequent in the WG group than in PAN. Peripheral nervous system involvement was more frequent in the PAN group. In WG, survival was calculated as 59% at 35 months. High initial vasculitis damage index scores were found to be predictive for mortality. CONCLUSION: This study revealed that the most frequent type of SNV was WG in a tertiary rheumatology setting in Turkey. There was initial organ damage in most of the patients, frequently caused by severe renal involvement. In contrast to other published series, overt cardiovascular and gastrointestinal involvement were not observed in our patients with SNV.

A comparison of clinical findings of familial Mediterranean fever patients with and without amyloidosis.

OBJECTIVE: This study investigates the clinical and demographic characteristics of familial Mediterranean fever (FMF) patients with and without amyloidosis. PATIENTS AND METHODS: The clinical data of 503 patients with FMF (females:males 250:253) were reviewed. Fifty of these patients had amyloidosis (f:m 23:27). RESULTS: The ages of attack onset in patients with and without amyloidosis were 7.8+/-6.2 and 11.1+/-8.5, respectively (P<0.05). The time between disease onset and diagnosis was longer in patients with amyloidosis than those without (187.6+/-99.4 months and 132.5+/-110.2 months, respectively, P<0.001). More patients in the amyloidosis group had positive family histories of FMF (68% vs 54%, P<0.05). The frequencies of chest pain (78% vs 51%, P<0.001), arthritis ( 80% vs 60%, P<0.01), and erysipelas-like erythema (44% vs 16%, P<0.001) were higher in the amyloidosis group. CONCLUSION: In the amyloidosis group, FMF-related manifestations of chest pain, arthritis, and erysipelas-like erythema are more frequent. Our results also support that long periods between disease onset and diagnosis are associated with a high risk of developing amyloidosis.

HLA B-27 subtypes in Turkish patients with spondyloarthropathy and healthy controls.

The frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B*27 was 2.6% in the Turkish population, and B*2705 was the predominant allele among patients with SpA. The difference was mainly between male patients and male controls The proportion of B*2705 among B27-positive patients and controls was significantly different (P=0.02). Our study supports other reports from different populations which showed that B*2705 and B*2702 were more frequent in Caucasian patients with SpA.

A patient with classical polyarteritis nodosa evolving into end stage renal failure.

Classical polyarteritis nodosa (c-PAN) is a form of systemic necrotizing vasculitis mainly affecting medium-size arteries, is not associated with renal glomerular disease and acute renal failure. Perirenal hematoma can be seen in up to fifty percent of c-PAN patients and minority of them develop mild renal impairment. Herein, we describe a 34-year-old male with c-PAN who presented with rapidly progressive renal failure and evolved into end stage renal disease.