Audiological involvement in patients with systemic sclerosis.

OBJECTIVES: The aim of the present study was to evaluate hearing loss in patients diagnosed with systemic sclerosis (SSc) and to investigate the relation between hearing loss, subtypes of the disease, its duration and clinical findings, and antibody positivity. METHODS: The study included 47 patients with SSc and 44 healthy controls. Audiometric, tympanometric, and otoacoustic emission measurements were applied to both groups. RESULTS: The evaluation of the participants medical history showed that among the patients with SSc, 19.1% experienced ear fullness, 27.7% experienced vertigo, and 36.2% experienced tinnitus. Hearing loss was detected in 23.4% of the patients with SSc. The corresponding result was 4.3% in the control group with a statistically significant difference (p = 0.001). Transient-evoked otoacoustic emission amplitude values were significantly lower in the patients' both ears with SSc than the control group (p < 0.005). Duration of disease was significantly longer, and diffusing capacity of the lungs for carbon monoxide values were significantly higher in the patients with SSc and sensorineural hearing loss. CONCLUSIONS: The present study found that the incidence of hearing loss was significantly higher in the study group than in the healthy control group. In addition to other organ involvements, cochlear involvement occurs in these patients, and further studies are required.

Primary Hypertrophic Osteoarthropathy Mimicking Juvenile Idiopathic Arthritis: A Novel SLCO2A1 Mutation and Imaging Findings.

Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is a rare, multisystemic, autosomal recessive condition typically presenting with digital clubbing, osteoarthropathy, and various skin manifestations. Radiographs show distinctive periosteal reaction and thickening along the long bones. PHO is caused by homozygous mutations in the HPGD gene in chromosome 4q34.1 or the SLCO2A1 gene in 3q22.1q22.2. Here, we report on a 20-year-old male with enlarged and swollen joints with arthralgia, palmoplantar hyperhidrosis, and large hands and feet with marked digital clubbing. We also present radiographic, MRI, and ultrasonographic features of the case. These clinical and imaging findings were compatible with the diagnosis of PHO, and a novel homozygous mutation, c.576C>G, p.Ile192Met, was found in SLCO2A1.

Sexual dysfunction in patients with systemic sclerosis

Background/aim: The aim of the study was to investigate the effect of systemic sclerosis (SSc) on quality of life and sexual function in female patients. Materials and methods: The study included 30 sexually active female patients with SSc and 30 healthy control subjects. For all participants in both the patient and control groups, the female sexual index and SF-36 forms were completed and a detailed medical and sexual history was taken. Results: The mean age was 45.03 ± 9.22 years in the SSc group and 44.6 ± 11.52 years in the control group (P = 0.87). The SF-36 scores in the patient group were significantly lower than those in the control group. Sexual dysfunction was found in 26/30 (86.6%) of the SSc patients and in 6/30 (20%) of the control group (P = 0.0001). Significant differences were determined between the groups with respect to sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and pain. There was no significant relationship between the subgroups of SSc patients, duration of disease, lung involvement, and FSFI scores. Conclusion: Sexual dysfunction and lower health quality are common problems in female patients with systemic sclerosis.

Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever.

OBJECTIVE: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF). METHODS: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2 mg/day before they were considered colchicine-resistant. RESULTS: 24 patients used anakinra (100 mg/day), and 2 used canakinumab (150 mg/month), for -36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case. CONCLUSION: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.

Retro-orbital granuloma associated with granulomatosis with polyangiitis: a series of nine cases.

Retro-orbital granuloma is a rare and devastating component of granulomatosis with polyangiitis (GPA). Current medical treatment protocols are falling short, and outcomes are poor. The aim of the study was to investigate the frequency, clinical features, and treatment outcomes of retro-orbital granuloma in patients with GPA. This is a retrospective, multi-centre study, which involves GPA cohorts from five different clinics. Data were extracted from patient charts including history, physical examination, radiological-laboratory-histological findings, and treatment protocols. Major clinical outcome measures were changes in the volume of the granuloma on comparative MRI, and visual acuity on repeated ophthalmologic examinations. Among 141 GPA patients, nine (five females and four males) were diagnosed with a retro-orbital granuloma. Median duration of disease was 8 years. Proptosis and diplopia were the dominant presenting symptoms (77%), followed by orbital pain (55%). Three out of nine patients had isolated retro-orbital granulomas, without other organ involvement of GPA. Five patients received conventional pulse steroid and pulse cyclophosphamide (CYC) as the first-line remission induction therapy. Four of these patients had progressive disease, and a regression in granuloma size was observed in one patient using this regimen. Two patients were already receiving immunosuppressants when they were diagnosed with retro-orbital granuloma. Six patients had been treated with RTX as the second-line remission induction therapy. None of these patients had progression following RTX therapy. Three patients underwent orbital decompression surgery. The indication for the decision for surgery was either progressive loss of vision or intractable pain. Standard first-line chemotherapy (CYC and steroids) was ineffective against retro-orbital granuloma associated with GPA. RTX could be an alternative in these cases. Surgical intervention may help to decrease the morbidity. Further prospective studies with greater patient numbers are needed to test the clinical efficiency of RTX as a first-line remission induction chemotherapy.

A rare but serious manifestation of Behçet's disease: intracardiac thrombus in 22 patients.

OBJECTIVES: Behçet's disease (BD) is a chronic, multisystemic disorder characterised by recurrent oral aphtous ulcers, genital ulcers and ocular inflammation. Vasculitis and thrombotic events are the most important causes of mortality. Vena cava thrombosis, pulmonary artery aneurysms, Budd-Chiari syndrome, peripheral artery aneurysms, dural sinus thrombosis and abdominal aorta aneurysms are the other less common vascular manifestations of BD. Cardiac involvement in BD is a rare and life-threatening complication. The aim of this study was to assess the clinical characteristics and outcome of patients with BD who have intracardiac thrombus. METHODS: The hospital files of BD patients followed by rheumatology clinics of four medical centres (Ankara University, Ege University, Hacettepe University and Eskisehir Osmangazi University Hospitals) were retrospectively evaluated. Data included patients' demographic and clinical features, laboratory findings and outcome. All patients fulfilled three or more of the International Study Group Criteria for BD. RESULTS: Twenty-two patients with intracardiac thrombus were evaluated. The mean age of patients with intracardiac thrombosis was 29.1 yrs (22-44) and there was a male predominance with a ratio of 20:2. Cardiac involvement was the first clinical manifestation of BD in 9 of the 22 patients. Initial symptoms of the patients were fever (n=18, 81%), dyspnea (n=9, 40%) chest pain (n=9, 40%) and haemoptysis (n=7, 31.8%). Sixteen patients (72%) had pulmonary arteritis and 10 (45%) patients had venous system lesions included deep vein, inferior vena cava and hepatic vein. Intra-cardiac thrombus were found only in the right cavities in 17 patients (77%), only in the left cavities in 2 patients (9%), and in both left and right cavities of the heart in 3 patients (13.6%). Once the cardiac lesion was diagnosed as a complication of BD, high dose (1mg/kg/d) prednisone (n=22, 100%) plus cyclophosphamide (n=18, 81%) or azathioprine (n=3, 13.6%) and warfarin (n=8, 36.3% (after the elimination of pulmonary aneurysm) therapy for anticoagulation was initiated. Four patients (18%) had high dose prednisone plus cyclophosphamide plus interferon-α (IFN-α) combination treatment and two patients (n=2, 9%) had high dose prednisone plus cyclophosphamide or plus azathioprine combination treatment. After treatment, the intra-cardiac thrombus disappeared in 13 cases and the size of the thrombus reduced in 7 cases. One patient died because of recurrent intra-cardiac thrombus and massive pulmonary arteritis in the emergency department. CONCLUSIONS: Intracardiac thrombus in BD is more common in young men. The right side of the heart is usually involved and cardiac involvement is often accompanied by pulmonary artery occlusion possibly due to pulmonary arteritis. Early and aggressive immunosuppressive and/or anticoagulation therapy are life-saving.

Pulmonary arterial hypertension and systemic sclerosis relation: a single centre experience.

AIM: In systemic sclerosis (SSc), this single-centre study aimed to define the frequency and association of pulmonary arterial hypertension (PAH), occurring either alone in SSc-PAH or together with interstitial lung disease (ILD-PH). MATERIAL-METHODS: SSc cases between the years 1990-2011 were reviewed, retrospectively. Patients' clinical, laboratory findings, Modified Rodnan Skin Score and Medsger score, 6-minute walk distance (6MWD), carbon monoxide diffusion test (DLCO), echocardiography, thorax HRCT, and right heart catheterisation findings were recorded. RESULTS: One hundred and forty-one cases (F/M:124/17, diffuse cutaneous SSc (DcSSc)/limited cutaneous SSc (LcSSc): 84/57) were included in the study with the mean age of 52.70±15.17 years and disease duration of 107.07±99.44 months. PaO2, FEV1 and FVC were lower in DcSSc (p<0.05) as compared to LcSSc, but DLCO and 6MWD did not differ significantly, between the two forms. Ground glass opacity (64.7%) and interlobular septal thickening (58.8%) were the most frequent findings on HRCT of such subjects. PAH was detected in 34 subjects (24.1%). Seven of them had SSc associated PAH (SSc-PAH) and 27 ILD-PH. Both frequencies were similar between DcSSc and LcSSc. Mean sPAP was higher in SSc-PAH. CONCLUSION: PAH was observed in approximately one fourth of patients; therefore advanced cardio-pulmonary investigation should be routinely performed in the SSc patients' management.

Peripheral blood mononuclear cell microchimerism in Turkish female patients with systemic sclerosis.

OBJECTIVES: To investigate microchimerism (Mc) in peripheral blood mononuclear cells (PBMC) taken from female patients with systemic sclerosis (SSc) and healthy females. We also intended to research the association between Mc and the clinical subsets. METHODS: This study included 50 females with lcSSc, 30 females with dcSSc and 40 healthy females. The Y-chromosome sequences were studied by RT-PCR in DNA obtained from PBMC. RESULTS: Mc was found in 28 (35 %) patients and 8 (20 %) healthy controls as well as in 6 dcSSc patients with son(s) (27.3 %), 10 lcSSc patients with son(s) (32.3 %) and 7 control females with son(s) (18.9 %) (p > 0.05). Mc was detected in 6 nulliparous lcSSc patients (31.6 %) and in 1 nulliparous dcSSc patient (11.1 %) (p > 0.05). The mean time elapsed between the first pregnancy and the diagnosis of SSc was 3.5 (0-49) years in the Mc-positive patients and 14 (0-55) years in the negative patients (p = 0.020). The mean modified Rodnan skin scores (ModRSS) of the patients with and without Mc was 10 (4-24) and 13 (4-26), respectively (p = 0.038). The relationship between Mc and the system involvement, disease severity, autoantibody profile, number of children and age of children was not found. CONCLUSIONS: Various etiological factors rather than just one play a role in the development of scleroderma. Mc is thought to be one factor that shortens the elapsed time of disease development in SSc. Mc is inversely related to the ModRSS, and no association was detected between Mc and autoantibodies or the clinical subsets.

Comparison of different glomerular filtration methods in the elderly: which formula provides better estimates?

OBJECTIVES: Technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) is an ideal radioisotopic method having a high correlation with inulin clearance for the determination of glomerular filtration rate (GFR). Different formulas like creatinine clearance (CrCl) in 24 h urine samples, Cockroft-Gault formula (CGF), and modification of diet in renal disease (MDRD) are being used to come up with an estimate. In this study, we compared (99m)Tc-DTPA with the formulas mentioned above in an attempt to best identify the method that would yield the nearly ideal GFR estimates in the elderly. MATERIALS AND METHODS: In 76 patients who were admitted to our clinic, we measured 24 h urine volume (V), urine creatinine (Ucr), and serum creatinine (Scr) levels together with CrCl, Scr, serum urea (Su), and albumin (Alb) levels. By using coefficients identified for age, gender, and race, we calculated modification of diet in renal disease 1 (MDRD1). Different from MDRD1, we calculated modification of diet in renal disease 2 (MDRD2) that does not include Su and Alb parameters and formulas like CGF that include Scr, age, gender, and weight parameters to come up with GFR levels. All patients underwent (99m)Tc-DTPA procedure. RESULTS: The mean of the GFR values measured by (99m)Tc-DTPA was 54.3 ± 19.9. The means of GFR values calculated by CrCl, MDRD1, MDRD2, and CGF were 58.0 ± 30.5, 60.9 ± 22.1, 54.4 ± 20.1, and 57.9 ± 22.4, respectively. GFR as measured by (99m)Tc-DTPA showed statistically significant correlations with the results of other methods (p < 0.001 for all methods). The most significant correlation was with MDRD1. CONCLUSION: MDRD1 can be used for next to ideal and accurate predictions of GFR in the elderly in the daily practice.

Plasma paraoxonase activity in patients with systemic sclerosis.

BACKGROUND & OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized vascular damage and fibrosis. The aim of this study was to investigate the possible relation between systemic sclerosis and paraoxonase which is an antioxidant enzyme on the HDL. METHODS: Twenty nine patients with SSc and 16 healthy subjects (control group) participated in the study. Plasma cholesterol levels, anti-centromere antibody (ACA) levels and paraoxonase (PON) activities were measured. RESULTS: Lower level of high-density lipoprotein (HDL) cholesterol was observed in ACA negative SSc patients than in controls. Paraoxonase activity in ACA positive patients was however found to increase relative to control and ACA negative patient groups. INTERPRETATION & CONCLUSION: Our findings suggested that low HDL level in ACA negative SSc patients might be one of the factors leading to some vascular problems, and increased PON activity in ACA positive SSc group might have some role in the limitation of cutaneous sclerotic process observed in these patients. However, these preliminary findings need to be confirmed with a larger sample.

Malondialdehyde and nitric oxide levels in erythrocytes from patients with systemic sclerosis.

OBJECTIVE: To investigate malondialdehyde (MDA) and nitric oxide (NO) levels in the erythrocytes from patients with systemic sclerosis (SSc). SUBJECTS AND METHODS: Twenty-nine patients diagnosed as having SSc and 16 volunteer healthy subjects (as control group) participated in the study. Fasting blood samples were obtained from the patients and healthy subjects in anticoagulated tubes (with EDTA), and the erythrocytes were separated. The MDA and NO levels were measured in the erythrocyte sediments by the spectrophotometric method. RESULTS: The levels of MDA and NO were elevated in the erythrocyte sediments of the patients as compared to those of the control group (1.037 +/- 0.125 vs. 0.951 +/- 0.114 mumol/g Hb, respectively, p = 0.047 for MDA, and 0.340 +/- 0.071 vs. 0.209 +/- 0.074 mmol/g Hb, respectively, p < 0.001 for NO). A weak positive correlation was also observed between MDA and NO levels (r = 0.30, p = 0.15 in the patient group, and r = 0.27, p = 0.49 in the control group). CONCLUSIONS: Our results show higher levels of MDA and NO in the erythrocytes of patients with SSc than normal subjects.

Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: a comparative study.

The value of rheumatoid factor (RF) isotypes for assessing rheumatoid arthritis (RA) remains debatable. In this study, we have examined the relationships between RF isotypes and disease activity and severity in RA patients. Sixty-two patients with RA, 48 women and 14 men, were studied. RF was measured by nephelometry (RF-N) and IgG-, IgA-, and IgM-RF isotypes were measured using enzyme-linked immunosorbent assay. Serum C-reactive protein and erythrocyte sedimentation rate were also determined. The patients were classified according to disease activity, joint damage, functional status, and presence of pulmonary involvement, rheumatoid nodule, and secondary Sjögren's syndrome. Although the patients with active disease had significantly higher IgA-RF and IgM-RF levels compared to inactive patients, IgA-RF and IgM-RF were not found to be independently associated with disease activity in multivariate analysis. In patients with severe joint damage, IgA-RF and RF-N were significantly higher than those of the other patients. Multiple regression analysis showed that IgA-RF was the unique variable independently associated to severe joint damage. The patients with class III and IV functional index had significantly higher IgM-RF, IgA-RF, and RF-N levels compared to the patients with class I and II functional index; however, RFs were not significantly associated with functional status in multivariate analysis. IgA-RF and IgM-RF were significantly associated with pulmonary involvement and rheumatoid nodule, respectively. No significant associations were found between RF isotypes and secondary Sjögren's syndrome. Our results suggest that the clinical usefulness of IgA and IgM isotypes is better than RF-N. Elevated IgA-RF may be a marker of erosive disease. The usefulness of RF isotypes for monitoring disease activity or functional status appears to be limited.

A multicenter study of patients with adult-onset Still's disease compared with systemic juvenile idiopathic arthritis.

Adult-onset Still's disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

Late onset rheumatoid arthritis: clinical and laboratory comparisons with younger onset patients.

We aimed to compare the clinical and laboratory profiles of the patients presenting late onset rheumatoid arthritis (LORA) with younger onset rheumatoid arthritis (YORA) patients. During the period between January 1995 and December 2004, 124 patients with LORA were identified from a retrospective chart review of inpatients and outpatients. They were compared with 150 YORA patients examined during the same period including their clinical and laboratory findings. The mean ages of the patients with LORA and YORA were 71.7+/-5.9 years, and 52.1+/-11.5 years, respectively. The gender ratio (female/male) was 1.48 in LORA and 2.85 in YORA (p = 0.012). The average ages of the disease onset were 42.2+/-10.4 years in YORA and 68.4+/-4.6 years in LORA. The duration of the diagnosis was longer in LORA than in YORA (20.7+/-14.3 months versus 10.3+/-6.2 months, p < 0.001). Rheumatoid arthritis (RA) duration was shorter in LORA than in YORA (43.5+/-64.4 months versus 126.3+/-101.0 months, p < 0.001). Although LORA patients had more significant frequent shoulder joint involvements (p < 0.001), proximal interphalangeal (PIP), metacarpophalangeal (MCP), elbow, metatarsophalangeal (MTP) and ankle involvements were common in YORA. Wrist, knee and hip involvements were not different in the groups. Classical rheumatoid hand deformities, interstitial lung disease and Sjögren's syndrome (SS) were significantly lower in LORA than in YORA. LORA patients had more common weight loss, myalgia, lymphadenopathy, polymyalgia rheumatica (PMR)-like syndrome and neuropathy. The frequencies of RF, ANA, anti-SSA/Ro and anti-SSB/La positivities were lower in LORA than in YORA, whereas elevated erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and anemia associated with chronic disease were higher in LORA. Patients with LORA, according to the accepted international criteria, present with different clinical and laboratory profiles when compared with younger patients. These results suggest that age may influence the presentation of RA at onset.

Neutrophilic Alveolitis and High Serum Pro-Brain Natriuretic Peptide Level may be Indicators of Pulmonary Functional Impairment in Connective Tissue Disorders.

OBJECTIVES: This study aims to assess the role of several diagnostic tests and tools, immune markers, and the association between serum pro-brain natriuretic peptide levels and other parameters in patients with collagen tissue disorders with pulmonary involvement. PATIENTS AND METHODS: In this prospective study, 62 patients (17 males, 45 females; mean age 58.1±13.6 years; range 24 to 87 years) with pulmonary involvement of connective tissue disorders were evaluated using several functional parameters (six-minute walking test, serum pro-brain natriuretic peptide, echocardiographic measurement of the pulmonary pressure, respiratory functional parameters, and blood pressure measurement), bronchoalveolar lavage differential cytology and/or flow cytometric analysis. RESULTS: Duration of disease was 7.6 years. Diagnoses included rheumatoid arthritis (38.7%), scleroderma (38.7%), primary Sjögren's syndrome (16.1%), mixed collagen tissue disorder (4.8%), and systemic lupus erythematosus (1.6%). Pulmonary hypertension was present in 38.7% of the patients with the highest incidence of rheumatoid arthritis showing reduced respiratory functions, partial oxygen pressure, and six-minute walk distance, as well as increased serum pro-brain natriuretic peptide and neutrophilic alveolitis. CONCLUSION: High serum pro-brain natriuretic peptide levels and neutrophilic alveolitis may provide diagnostic clues for a possible diagnosis of pulmonary hypertension and impaired respiratory functions.

Lack of the Association of the PTPN22 C1858T Gene Polymorphism With Susceptibility to Familial Mediterranean Fever.

OBJECTIVES: This study aims to investigate whether the protein tyrosine phosphatase non-receptor type 22 (PTPN22) C1858T gene polymorphism plays a role in the pathogenesis of familial Mediterranean fever (FMF) through T-lymphocyte activation. PATIENTS AND METHODS: We conducted a case-control study with 180 FMF patients (68 males, 112 females; mean age 38.2±1.6 years; range 16 to 81 years) and 184 healthy controls (86 males, 98 females; mean age 32.9±9.2 years; range 18 to 58 years). The PTPN22 C1858T polymorphism (rs2476601) was genotyped by polymerase chain reaction restriction fragment length polymorphism. In patients with FMF, clinical features, disease severity score, the frequencies of amyloidosis, positive family history, and Mediterranean fever gene mutations were determined. RESULTS: The frequencies of heterozygous genotype (CT) were 4.5% in FMF patients and 2.8% in healthy controls, respectively. The frequencies of polymorphic homozygous genotypes (TT) were 0.5% in both FMF patients and healthy controls. There were no statistically significant differences in the frequencies of CT and TT genotypes between FMF patients and healthy controls (odds ratio: 1.65, 95% confidence interval: 0.53-5.14, p>0.05 for CT genotype). The frequencies of clinical features, sex, amyloidosis, positive family history, Mediterranean fever gene mutations, and disease severity score were not significantly different between the patients. CONCLUSION: The distribution of PTPN22 C1858T polymorphism did not reveal any association with FMF in a Turkish population.

Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

Association between single nucleotide polymorphisms in prospective genes and susceptibility to ankylosing spondylitis and inflammatory bowel disease in a single centre in Turkey.

BACKGROUND/AIMS: To establish the prevalence of the single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase 1 (ERAP1), IL-23 receptor (IL-23R), signal transducer and activator of transcription 3 (STAT-3) and Janus kinase 2 (JAK-2) in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) in a Turkish population. MATERIALS AND METHODS: A total of 562 subjects who presented at the Ankara University internal medicine departments of rheumatology and gastroenterology outpatient clinics were recruited in this study, including 365 patients with AS, 197 patients with IBD and 230 healthy controls. ERAP1, IL-23R, STAT-3 and JAK-2) were genotyped in competitive allele-specific polymerase chain reactions. RESULTS: The ERAP1 (rs26653) polymorphism was found to increase the disease risk in patients with AS and IBD compared with the control group (p=0.02 and p=0.01, respectively). In addition, this polymorphism revealed a significant relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) in patients with AS (r=0.829, p < 0.001 and r=0.731, p < 0.001, respectively). CONCLUSION: The ERAP1 gene polymorphism might be a risk factor in the pathogenesis of AS and IBD. In contrast, IL-23R gene polymorphisms may serve a protective role in AS and IBD.

Relationship between HLA-DR, HLA-DQ alleles and MEFV gene mutations in familial Mediterranean fever (FMF) patients.

BACKGROUND/AIMS: Three missense mutations clustered on the carboxyl-terminal portion of the MEFV gene (M680I, M694V, and V726A) have been observed in over 80% of affected alleles in several ethnic groups of familial Mediterranean fever patients. Several immunologic abnormalities were found both in cellular and humoral components in Mediterranean fever patients. Those observations have pointed the way for analysis of the HLA region in Mediterranean fever. We intended to compare HLA DR/DQ alleles with those major mutations in the MEFV gene in Mediterranean fever patients. METHODS: The distribution of MEFV gene mutations and HLA-DR, HLA-DQ alleles were analyzed in 40 index Turkish Mediterranean fever patients, 28 family members and 42 healthy controls. M680I, M694V, and V726A mutations were studied by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) analysis. HLA-DR and DQ allele subgroups were studied using SSP-PCR technique. RESULTS: A total of 37 (92.5%) patients in 40 Mediterranean fever index patients were found to carry one of the three missense mutations. The HLA-DR4 allele frequency was significantly higher in the Mediterranean fever patient group. When comparisons were made between Mediterranean fever mutations and HLA allele frequencies, M694V mutation with HLA DR3, DR11/5 and DR 13/6 and M680I mutation with DR7 allele subgroups were statistically significant. DQ6/1, DQ7/3, and DQ8/3 allele with M694V, DQ2 allele with M680I, and DQ6/1 with V726A mutations were also statistically significant. CONCLUSIONS: Our results indicate a relationship between some HLA-DR/DQ alleles and MEFV mutations in Mediterranean fever patients. We suggest HLA-DR/DQ alleles and their role in the pathogenesis of Mediterranean fever need further analysis and comparative studies.