The prevalence of non-vascular pulmonary manifestations in Takayasu's Arteritis patients: A Retrospective multi-centred Turkish cohort study.

OBJECTIVES: Takayasu's arteritis (TAK) is a rare vasculitis characterized by inflammation of intermediate- to large-size arteries. Although pulmonary artery involvement (PAI) is an expected finding in some TAK patients, data on non-vascular pulmonary involvement (NVPI) are limited. We aimed to investigate the frequency of NVPI, including parenchymal infiltration, nodules/cavities, pleural effusion, and haemorrhage, in TAK. METHOD: We assembled a retrospective cohort of TAK patients from nine tertiary centres in Turkey. The demographics and clinical characteristics of patients were extracted from medical records and the imaging findings were evaluated for pulmonary manifestations. RESULTS: As of January 2021, 319 TAK patients (female/male 276/43; mean age 42.4 ± 13.5 years) were recruited. Eighty-two patients had cough and/or dyspnoea and four had haemoptysis as pulmonary symptoms. On computed tomography assessment, the overall frequency of NVPI was 7.2%; parenchymal infiltrations were present in 10 (3.1%), pleural effusion in eight (2.5%), nodules/cavities in six (1.9%), and pulmonary haemorrhage in four patients (1.3%). In the whole cohort, 10.3% of patients had pulmonary artery hypertension (PAH) and 5.6% had PAI. Among patients with PAH or PAI, the overall frequency of NVPI was significantly higher than in the rest of the group. CONCLUSIONS: In this TAK cohort from Turkey, we observed NVPI in 7.2% of patients, with parenchymal infiltrations being the most common, followed by pleural effusion. Notably, NVPI was more frequent in patients with PAH or PAI. Although not as common as PAI, NVPI should be kept in mind, especially in TAK patients with PAH or PAI.

Impaired myocardial deformation in psoriatic arthritis patients assessment by speckle tracking echocardiography.

OBJECTIVE: We aimed to evaluate left ventricular (LV) mechanics of patients diagnosed with PsA and no clinical evidence for cardiovascular disease (CVD) using a novel, more sensitive technique which evaluates myocardial deformation in multidimensional planes for the detection of impaired LV function. METHODS: The study enrolled 31 PsA patients and sex-age matched 19 healthy controls. All participants underwent conventional echocardiography and 2-dimensional speckle tracking echocardiography (STE). Global longitudinal, circumferential, and radial strain were measured. RESULTS: Although patients with PsA had normal LV ejection fraction, the myocardial deformation in multidimensional planes was impaired. STE analysis results showed that PsA patients had significantly lower global longitudinal strain (mean±S.D. -17.11±2.83 % and -19.29±2 % respectively, p=0.005), global circumferential strain (mean±S.D. -14.28±3 % and -20.34±4.78 % respectively p<0.001) and global radial strain (mean±S.D. 29.26±10 % and 46.54±17 % respectively, p<0.001) versus control group. However, no correlation was found between longitudinal, radial, and circumferential strains and disease-related risk factors. CONCLUSION: Subclinical impaired myocardial deformation was common in patients with PsA even with no clinical evidence for CVD. Thus, the use of this novel imaging technique could provide additional benefits for determining cardiovascular involvement at an early stage and risk stratification in PsA patients.

The positivity of rheumatoid factor and anti-cyclic citrullinated peptide antibody in nonarthritic patients with chronic hepatitis C infection.

Chronic hepatitis C virus (HCV) has extrahepatic autoimmune properties and a variety of autoantibodies were found in patients with HCV. Patients with HCV infection may have rheumatic symptoms and signs, and 50-70% of the cases may contain rheumatoid factor (RF). The increased prevalence of RF in patients with HCV infection diminishes the diagnostic specificity of serum RF for rheumatoid arthritis (RA) in patients with HCV. Therefore, the presence of RF mostly does not help in distinguishing between RA and HCV-associated rheumatic symptoms. In this study, we studied whether cyclic citrullinated peptide (CCP) antibody, a highly specific biomarker for RA in the general population, was useful for the diagnosis of RA in nonarthritic patients with HCV (hepatitis C virus). Blood samples from 39 patients with chronic HCV infection, 87 normal sera from volunteer blood donors and 108 blood samples from patients with rheumatoid arthritis, from the rheumatology clinic, were taken. RF was measured using the Dade-Behring nephelometer and antibodies to CCP were measured with ELISA. According to statistical analysis, the sensitivity, specificity and positive predictive value of the anti-CCP test was superior to the RF test. Cyclic citrullinated peptide antibody is a more useful test than RF among patients with chronic HCV infection without arthritis.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

The effect of parental consanguinity on the clinical and laboratory findings of rheumatoid arthritis.

AIMS: We aimed to evaluate the frequency of consanguinity among the parents of patients with rheumatoid arthritis (RA) and the influence of parental consanguinity on several clinical and laboratory parameters which reflect the severity of the disease. METHODS AND PATIENTS: The study population consisted of 265 patients with RA which were divided into two groups with respect to the presence or absence of consanguinity between their parents. The frequency of parental consanguinity was compared with the general population. The two groups were compared with respect to family history of RA, the age of onset, the age at which RA was diagnosed, duration of the disease, the presence of rheumatoid nodules, vasculitis, serositis and the need for orthopaedic surgery, amyloidosis, the presence and level of rheumatoid factor and anti-cyclic citrullinated peptide antibodies, erosive changes on radiographs, and the need for anti-tumour necrosis factor therapy. RESULTS: Twenty-one patients (8%) had parents who were consanguineous, which was not more frequent compared with the general population (14%). The mean age of disease onset and the mean age at which RA was diagnosed were lower in patients with parental consanguinity, although the difference was not statistically significant. The other clinical and laboratory parameters were also not different between the two groups. CONCLUSION: The present data suggests that parental consanguinity has no effect on disease severity, and the frequency of consanguinity is not increased among the parents of patients with RA. A possible exception is the earlier disease onset and age at diagnosis which needs to be confirmed by larger studies.

A case of progressive pseudorheumatoid arthropathy of 'childhood' with the diagnosis delayed to the fifth decade.

Progressive pseudorheumatoid arthropathy of childhood (PPAC) is a rare single gene disorder which is frequently misdiagnosed as juvenile rheumatoid arthritis. It is characterised with arthralgia, joint contractures, bony swelling of metacarpophalangeal and interphalangeal joints and platyspondyly. Clinical and laboratory signs of joint inflammation such as synovitis, a high erythrocyte sedimentation rate and an elevated C-reactive protein level are usually absent. Although the disease begins early in life (usually between 3 and 8 years of age), the diagnosis may be delayed. In the present case report, we describe a male patient diagnosed with PPAC at the age of 46 years, although he had been exhibiting the typical radiological and clinical features of the disease since the age of 7 years.

Characteristics of patients with late onset systemic lupus erythematosus in Turkey.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder mainly affecting young women. In this study, we aimed at investigating the clinical, laboratory and management characteristics of our SLE patients with an age of onset > or =50. Twenty patients with late onset SLE (> or =50 years) were identified from the records, on the basis of their first SLE-related symptoms (Group I). A hundred consecutive SLE patients with initial symptoms before the age of 50 were also selected as controls (Group II). Clinical, laboratory and management characteristics of the patients were recorded according to pre-defined protocol and compared by chi(2), Student's t-test and Fisher's exact test. Comparison of the demographic findings between the Group I (F/M: 18/2) and the Group II (F/M: 90/10) were as follows: the mean age of disease onset was 53.9 +/- 4.5 years vs. 26.3 +/- 9.2 years, mean time of follow-up was 44.2 +/- 40.5 months vs. 50.1 +/- 47.4 months, mean damage index was 0.6 +/- 0.6 vs. 0.58 +/- 1.4. There was no significant difference between the two groups with regard to clinical, laboratory parameters, damage index and immunosuppressive treatment characteristics. SLE-related manifestations were similar in two groups except fever (10% in the Group I vs. 41% in the Group II; p = 0.01). The only two patients with pulmonary fibrosis were found in the Group I (p = 0.027). The clinical and laboratory characteristics and the disease outcome in SLE patients with an age of onset > or =50 years did not show significant differences from the control SLE patients with a younger age of onset.

Characteristics of patients with adult-onset familial Mediterranean fever in Turkey: analysis of 401 cases.

It has been generally accepted that the clinical onset of familial Mediterranean fever (FMF) begins before 20 years of age in most patients. In this study, we aimed to investigate the demographic and clinical characteristics of our FMF patients with an age of onset > or =20. Records of 401 patients (female/male: 204/197) that followed up between 1990 and 1999 were reviewed according to a pre-defined protocol. All patients fulfilled the diagnostic criteria of Livneh et al. The demographic and clinical features of adult-onset FMF patients were compared to those of patients with a disease onset before 20 years of age. There were 57 patients (14%) who experienced symptoms of FMF at > or =20 years of age; 34 of them (8.5%) reported their first attack between 20 and 29 years of age; 18 of them (4.5%) between 30 and 39 years of age and five patients (1.25%) had their first attack after 40 years of age. Arthritis (42 vs. 65%, p = 0.001) and erysipelas-like erythema (7 vs. 17%, p = 0.047) were significantly less frequent in patients with adult-onset FMF compared to patients with disease onset before 20 years of age. Arthritis and erysipelas-like erythema were less frequent in adult-onset patients compared to those with an earlier disease onset. Adult-onset FMF may be a form of disease with distinct clinical, demographic and molecular characteristics. Prospective clinical studies and investigation of genotypic features are needed to identify the characteristics of this phenotypic variant.

A case of mandibuloacral dysplasia presenting with features of scleroderma.

Juvenile scleroderma, a relatively rare condition, may be confused with a number of progeroid syndromes like Hutchinson-Gilford syndrome, Werner syndrome and Rothmund-Thomson syndrome. In this case report, we describe a 9-year-old boy who presented with sclerodactyly, acroosteolysis and scleroderma-like involvement of the skin over hands and feet, which suggested a diagnosis of juvenile scleroderma initially. However, absence of Raynaud's phenomenon, sparing of the skin other than hands and feet and negative serological studies did not support this diagnosis. On the basis of additional findings (micrognathia, dental malformation, a 'beaked nose', open cranial sutures and sparse hair), the patient was diagnosed as mandibuloacral dysplasia, a rare autosomal recessive disease. This case demonstrates that mandibuloacral dysplasia should be considered in the differential diagnosis of juvenile scleroderma in the presence of atypical features such as negative serological studies, absence of Raynaud's phenomenon, sparse hair and micrognathia.

Tuberculosis in Turkish patients with systemic lupus erythematosus: increased frequency of extrapulmonary localization.

The objective was to investigate the frequency and characteristics of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE). We reviewed the charts of 556 patients with SLE who were followed up between 1978 and 2001 in our lupus clinic. Patients who developed TB after the diagnosis of SLE were identified (SLE/TB+). Ninety-six consecutive patients with SLE who did not develop TB during the follow-up were evaluated as a control group (SLE/TB-). Clinical, laboratory and management characteristics of these two groups of patients were recorded according to a predefined protocol, and compared. Of the 556 patients evaluated, 20 patients (3.6%) with TB were identified. Nine of the 20 patients (45%) had extrapulmonary TB (vertebral involvement in three patients, meningeal in two, and joint and soft tissue in four). Arthritis and renal involvement were significantly high in the SLE/TB+ group (P = 0.045, P = 0.009, respectively). The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone were significantly higher in the SLE/TB+ group compared to the SLE/TB- group (27 +/- 22 g versus 16 +/- 16 g, 24 +/- 45 mg versus 11 +/- 8.5 mg, respectively). In conclusion, we found an increased frequency of TB infection and a high prevalence of extrapulmonary TB in a large cohort of SLE patients. The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone, which possibly related to disease severity, were important determinants for the increased risk of TB in these patients with SLE.

Expression of KIR and C-type lectin receptors in Behcet's disease.

OBJECTIVE: Behçet's disease (BD) is a multisystemic disorder with a possible underlying pathology of immune-mediated vasculitis. Genetic susceptibility associated with HLA-B*51 and B*2702 has been implicated in its pathogenesis. Considering the recently defined regulatory mechanisms of NK cells through HLA class I binding receptors, we hypothesized that interactions of NK and T cells through the NK receptors may be important in the pathogenesis of BD. METHODS: The impact of different expression patterns of HLA-recognizing receptors on NK or T cells was analysed in 51 patients with BD and 32 healthy controls. We used flow cytometry to investigate the expression of KIR3DL1 from the polymorphic killer immunoglobulin-like receptor (KIR) family, which binds a shared HLA-Bw4 motif on HLA-B51 and *2702 alleles, and CD94 from the conserved C-type lectin receptor family, which binds HLA-E. Thirty-three of the BD patients and 19 of the controls carried the same HLA-Bw4 motif. RESULTS: CD3(+) T cells were increased in patients with BD compared with controls (81 vs 75%, P = 0.001), whereas the NK cells did not show any difference between the two groups. Increased expression of CD94 in BD was observed on CD16(+)CD56(+) cells (66 vs 57, P = 0.04) and on CD3(+) (7.7 vs 4.0, P < 0.001) and CD3(+)CD56(+) (44 vs 35, P = 0.02) T cells. KIR3DL1 expression on the NK and T cells was not statistically different between the two groups. No effect of HLA-Bw4 motif was observed on the expression of CD94 and KIR3DL1 in both the patients and the controls. CONCLUSION: The absence of a correlation between KIR3DL1 expression and HLA-Bw4 motif confirms previous work reporting that the expression of these molecules is regulated separately. Increased expression of CD94 may suggest that NK receptors play a pathogenic or regulatory role in BD.

Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations.

Alkaptonuria (AKU) is a rare metabolic disorder of phenylalanine catabolism that is inherited as an autosomal recessive trait. AKU is caused by loss-of-function mutations in the homogentisate 1,2-dioxygenase (HGO) gene. The deficiency of homogentisate 1,2-dioxygenase activity causes homogentisic aciduria, ochronosis and arthritis. We present the first molecular study of the HGO gene in Turkish AKU patients. Seven unrelated AKU families from different regions in Turkey were analysed. Patients in three families were homozygous for the R58fs mutation; another three families were homozygous for the R225H mutation; and one family was homozygous for the G270R mutation. Analysis of nine intragenic HGO polymorphisms showed that the R58fs, R225H and G270R Turkish AKU mutations are associated with specific HGO haplotypes. The comparison with previously reported haplotypes associated with these mutations from other populations revealed that the R225H is a recurrent mutation in Turkey, whereas G270R most likely has a Slovak origin. Most interestingly, these analyses showed that the Turkish R58fs mutation shares an HGO haplotype with the R58fs mutation found in Finland, Slovakia and India, suggesting that R58fs is an old AKU mutation that probably originated in central Asia and spread throughout Europe and Anatolia during human migrations.

Comparative efficacy of oral and intravenous calcitriol treatment in haemodialysis patients: effects on serum biochemistry and cytokine levels.

This study compared the effects of oral and intravenous calcitriol on serum biochemistry parameters and levels of bone-resorptive cytokines in haemodialysis patients. Patients were randomized to receive oral (n = 18) or intravenous (n = 16) calcitriol treatment for 6 months. Serum levels of total calcium, ionized calcium, intact parathyroid hormone (iPTH), magnesium, alkaline phosphatase, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 were measured at baseline and after 3 and 6 months of treatment. After treatment, serum levels of iPTH, total calcium, ionized calcium, TNF-alpha, IL-1 and IL-6 were not significantly different from baseline. The intravenous calcitriol treatment group showed significant decreases in levels of iPTH, TNF-alpha, IL-1 and IL-6 and a significant increase in total calcium level after 3 and 6 months. There was no significant change in serum ionized calcium levels. Significantly decreased serum alkaline phosphatase and magnesium levels were found in both treatment groups after 3 and 6 months. In conclusion, intravenous calcitriol treatment has a significant depressive effect on iPTH and bone-resorptive cytokines in patients undergoing haemodialysis.