Juvenile and adult-onset scleroderma: Different clinical phenotypes.

OBJECTIVES: Systemic sclerosis (SSc) represents extremely rare disease with majority of data coming from adults. Studies comparing juvenile- (jSSc) and adult-onset (aSSc) patients are limited. We aimed to compare clinical features, treatment modalities and survival rates of jSSc and aSSc patients. METHODS: A retrospective study among pediatric and adult Scl patients has been performed. Demographic characteristics, clinical features, autoantibody profiles, and treatment data were retrieved from the databases. Survival analysis was done using Kaplan-Meier plot and factors associated with mortality were identified with multiple regression analysis. RESULTS: A total of 158 adults and 58 juvenile Scl patients were identified. The mean age at the disease onset was 37±14.7 vs. 8.8 ± 4.1 years, mean age at diagnosis 42±15.2 vs. 10.4 ± 3.8 years and mean follow-up duration was 6.3 ± 4.9 years vs. 6.6 ± 4.9 years for aSSc and jSSc patients, respectively. The frequency of interstitial lung disease (ILD) (50.9% vs 30%, p<0.001) and systemic hypertension (17.9% vs 0, p = 0.009) was significantly higher among aSSc. While aSSc patients had presented mostly with limited cutaneous subset (74.1%), diffuse cutaneous subset was the dominant subset among jSSc (76.7%), (p<0.001). The mortality rate was significantly higher among adults (p = 0.005). The ILD (p = 0.03) and cardiac insufficiency (p = 0.05) were independent risk factors of mortality in both aSSc and jSSc patients. CONCLUSION: Juvenile and adult-onset Scl represent rarely seen conditions with different clinical phenotypes. Pediatric patients with LS are more commonly seen by pediatric rheumatologists, in contrary to adults. Diffuse disease subset is the dominant form among juvenile patients, whereas limited form is the main disease subset among adults. On the other hand, juvenile-onset patients have a better survival than those with adult-onset.

Patients with rheumatic diseases are ready to use social media in clinical practice; what about rheumatologists? A cross-sectional survey.

Social media can be an innovative communication method between patients and physicians that help to overcome time limitation in outpatient clinics. In this study, we investigated how patients with rheumatic diseases (RD) and physicians use and are willing to use social media platforms to communicate with each other. We used a face-to-face survey that provides information on current social media habits and communication methods of rheumatology patients and physicians. We studied 399 (135 M/262 F) patients with RD with a median age of 45 (IQR: 34) years. We also studied 55 (30 M/25F) rheumatologists with a median age of 37 (IQR:34-44) years. Among patients with RD, 288 (72%) used at least one social media site within the previous month. Facebook was the most preferred social media platform, whereas Twitter and Instagram were favored by males and higher educated patients. While 17% of the patients with RD could communicate with their physicians outside of the hospital, 94% expressed that they would like to. Most patients (74%) defined social media as a reliable source for health-related information, yet 90% declared that they would like to obtain information about their disease using face-to-face communication. Forty-two (83%) rheumatologists were using social media and reported that they already communicate or would like to communicate with their patients outside of the hospital. Internet-based mobile applications and social media platforms are promising communication and educational tools for rheumatology patients.

Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet's disease.

The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.

Behçet's syndrome: a critical digest of the recent literature.

A similar disease severity among men and women in Brasil, a high frequency of gastrointestinal involvement in China, Japan and USA, a low frequency of pathergy positivity in Japan and USA underline the ethnic variations reported in recent studies. Polymorphisms pertaining both to innate and adaptive immunity in genome wide association studies, clusters in phenotype, and new mechanisms for emerging therapeutic implications have been reported. A Th17 dominance seems to be likely with the exception of gastrointestinal involvement. Infliximab, interferon-alpha and cyclosporine-A may be showing their beneficial effects also by affecting the Th17 cells. The clinical course and outcome of isolated pulmonary artery thrombosis is similar to pulmonary artery aneurysms. Parenchymal lesions (nodules, consolidations, cavities and ground glass lesions) are common in patients with pulmonary involvement. Pericarditis is a frequent cardiac manifestation in France. Treatment of BS became more intensive than before. Immunosuppressives and corticosteroids seem to prevent relapses of venous thrombosis. Studies are needed to understand the role of anticoagulants. Interferon alpha-2a appears to be effective at lower dosage, which brings the advantage of decreased cost and increased tolerability. Switching between anti-TNF agents, when needed, is possible. Interleukin-1 and interleukin-6 are new promising targets.

Behçet syndrome: is it one condition?

Behçet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction.

Clinical characteristics of pediatric-onset neuro-Behçet disease.

OBJECTIVES: Neurologic involvement in the pediatric population with Behçet disease (BD) is limited to case reports. The aim of this study is to examine the frequency and type of neurologic involvement in pediatric patients with BD. METHODS: Medical records of 728 patients with a diagnosis of neuro-BD (NBD) of 2 large BD cohorts followed in Istanbul University were included in the study. Patients with an onset of both systemic and neurologic symptoms at or before age 16 (pediatric neuro-BD) were identified. Demographic and clinical characteristics of pediatric patients with NBD were compared with adult patients with NBD. RESULTS: There were 26 cases with pediatric BD (3.6%) and 702 (96.4%) adult-onset patients. Gender ratio was equal in the general pediatric BD cohort, whereas male/female ratio was 5.5/1 in pediatric NBD cases. Mean age at BD onset and neurologic involvement onset were 13.0 ± 3.0 and 13.5 ± 2.4, respectively, and in the adult population mean age at onset of BD was 26.7 ± 8.0 and neurologic involvement occurred a mean of 5.3 ± 4.5 years later. Clinical and MRI evaluation revealed that 3 children had CNS parenchymal involvement and 23 had dural venous sinus thrombosis (88.5%). We observed parenchymal involvement in 74.8% of the adults, contrary to the low 17.2% of cases with venous sinus thrombosis. CONCLUSIONS: Pediatric NBD comprises 3.6% of our whole NBD cohort, with a male predominance, mainly in the form of dural venous sinus thrombosis, whereas in the adult NBD population the dominant form of neurologic involvement is parenchymal, suggesting that the pathogenesis of NBD may be different according to the age at disease onset.

Anti-Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic (ANCA) antibodies are not increased in Takayasu arteritis.

OBJECTIVES: Takayasu arteritis (TA) may be associated with inflammatory bowel disease (IBD). As there is such an overlap and since both diseases show granulomatous histopathological lesions we reasoned similar biological pathways might be implicated in both conditions. Therefore, we investigated the prevalence of anti-Saccharomyces cerevisiae (ASCA) and anti-neutrophil cytoplasmic (ANCA) antibodies - serological markers for IBD-among patients with TA. METHODS: Thirty-two patients with TA, 21 with Crohn's disease (CD), 17 with ulcerative colitis (UC) and 34 healthy controls were studied. Among 32 patients with TA, 2 had CD and one had UC concomitantly. ASCA Ig A and Ig G antibodies were analyzed using a commercial ELISA kit. Immune fluorescence analysis (IFA) was used to assess the presence of ANCA antibodies. RESULTS: Only patients with CD had significantly higher levels of both ASCA Ig A and Ig G, compared to patients with TA and healthy controls. Similarly, the frequency of ASCA positive patients was higher only among patients with CD. ASCA Ig A and Ig G antibodies were found in 16 % (5/32) of patients with TA. Among 3 patients, in whom TA and IBD co-existed, only one (one with CD) had positive ASCA Ig G and A antibodies. The p-ANCA antibodies were present among patients with UC (35 %) and CD (10 %). CONCLUSION: ASCA positivity in TA was similar to that found in UC and healthy controls. No ANCA antibodies were detected among patients with TA.

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.

Prevalence of angina, myocardial infarction and intermittent claudication assessed by Rose Questionnaire among patients with Behcet's syndrome.

OBJECTIVE: To determine the risk of clinical cardiovascular disease in middle-aged patients with Behcet's syndrome (BS) compared with gender-matched non-BS subjects. METHODS: The prevalence of angina, myocardial infarction (MI), doctor diagnosed ischaemic heart disease (IHD) and intermittent claudication were sought by the Rose Angina Questionnaire in 225 (141 M/84 F) BS patients (mean age: 52 +/- 8) with BS and 117 (74 M/43 F) controls (mean age: 50 +/- 5). Information on atherosclerotic risk factors was also collected. RESULTS: The prevalence of angina, MI and doctor-diagnosed IHD were not different between BS patients and non-BS controls in the whole study population and when males and females were separately analysed. Angina tended to be more common among females compared with males among both patients and controls. Intermittent claudication was found to be significantly more common among BS patients, especially in males with venous disease. CONCLUSIONS: The findings in this cross-sectional clinical study are in line with previous observations not indicating accelerated atherosclerosis in BS. Intermittent claudication might not be a suitable tool for the detection of peripheral atherosclerotic disease especially among BS patients having venous disease.

A cost analysis of Behcet's syndrome in Turkey.

OBJECTIVE: Behçet's syndrome (BS), a common chronic inflammatory disease in Turkey, results in considerable morbidity and increased mortality. We aimed to estimate its direct and indirect costs. METHODS: We studied 119 (78 male/41 female) patients with BS at our multidisciplinary BS out-patient clinic in Istanbul, between March and July 2005. The mean age and disease duration were 35 +/- 9 and 10 +/- 6 S.D. yrs. According to the primary clinical problem, patients were divided into: (i) ocular; (ii) vascular; (iii) neurological and (iv) mucocutaneous-joint disease subgroups. They were interviewed with a standardized questionnaire addressing: (a) direct costs such as medication, diagnostic tests, hospital visits, hospitalization fees and lodging and transportation expenses and (b) indirect costs such as lost workdays and wages. The costs were assessed retrospectively by assessing the expenses within a year of the survey and were expressed as US$ mean +/- S.D. RESULTS: The mean annual total cost per patient was US$ 3226 +/- 3488 (S.D.). The direct cost accounted for 68% of the total cost. Medication expenses made up 79% of the total direct cost. About 42% of the patients reported lost workdays that averaged 119 +/- 96 days S.D. Among the clinical subgroups mucocutaneous-joint involvement (US$ 1180 +/- 1053) had the lowest economic impact while the neurological disease (US$ 5005 +/- 2707) had the highest. CONCLUSION: In this first cost of illness study in BS, the neurological involvement had the highest annual cost. Direct costs were higher than the indirect costs. Drug costs were the major cost driver. BS causes considerable economic burden for the health care system in Turkey.

Treatment options in colchicine resistant familial Mediterranean fever patients: thalidomide and etanercept as adjunctive agents.

OBJECTIVE: Regular colchicine treatment cannot control the typical febrile attacks of FMF in about 5-10% of the compliant patients. Here we report the effect of thalidomide and etanercept in 5 colchicine-resistant cases. METHODS: Five (4M/ 1F) FMF patients between April 2005 and March 2006, who were experiencing at least 2 attacks per month, despite regular colchicine were included to the study. Four male patients were given thalidomide 100 mg/d initially. Two of these patients unresponsive to thalidomide were prescribed subcutaneous injections of etanercept 25 mg, twice a week. The female patient received etanercept as the first choice due to potential side effects. She then had to be converted to thalidomide due to a severe injection site reaction. RESULTS: The median follow up period with thalidomide and etanercept was 8 months. Both thalidomide and etanercept lowered the number of the abdominal attacks. CONCLUSION: Thalidomide and etanercept might be effective as additional treatment in colchicine-resistant cases of FMF.

Hair diameter in systemic lupus erythematosus.

It is widely appreciated that patients with systemic lupus erythematosus (SLE) get thinner and shorter hair. However little work has been done to quantitate this. We assessed hair thickness of SLE patients and compared this to that of patients with rheumatoid arthritis (RA) and healthy controls (HC). Fifty-seven female patients with SLE (mean age: 32 +/- 8 years) and 77 female patients with RA (mean age: 50 +/- 12 years) were studied along with 75 healthy women (mean age: 27 +/- 6 years). Five strands of hair were taken from each subset and mounted on glass slides. Two independent observers, blind to the sources of the hair, measured the hair strands under a light microscope, using a micrometer. Finally, the mean hair thickness between each of the three groups was calculated. The hair in both SLE and RA patients was found to be thinner than that of HC by both observers (P < 0.001). Age adjusted analysis between SLE and HC showed similar results. However, there was no significant difference in hair thickness between SLE and RA. SLE patients have thinner hair compared to HC. More studies are needed to investigate the effect of disease activity, therapy and other factors on hair diameter.

Atherosclerosis in Takayasu arteritis.

OBJECTIVE: Chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis. We hypothesised that atherosclerosis may also be increased in Takayasu arteritis. METHODS: The frequency of atherosclerotic plaques and the intima-media thickness (IMT) were investigated in 30 female patients with Takayasu arteritis (mean age (standard deviation), 35.4 (8.0) years), along with 45 sex-matched and age-matched patients with SLE (37.4 (6.8)) and 50 healthy controls (38.2 (5.7)). Plaques were scanned and IMT was measured at both sides of the common carotids, carotid bulb, and internal and external carotid arteries by B-mode ultrasonography. Traditional risk factors for atherosclerosis were also assessed. RESULTS: Most of the atherosclerotic risk factors were comparable between patients with Takayasu arteritis and SLE. More atherosclerotic plaques were observed among patients with Takayasu arteritis (8/30; 27%) and those with SLE (8/45; 18%) than among the healthy controls (1/50; 2%; p = 0.005). Logistic regression analyses showed that the presence of a plaque was associated only with age in both Takayasu arteritis and SLE (p = 0.04 and 0.02, respectively). The mean overall IMT was significantly higher among patients with Takayasu arteritis (0.95+/-0.31 mm) than among the patients with SLE (0.58+/-0.10 mm) and the healthy controls (0.59+/-0.08 mm; p<0.001). CONCLUSION: Patients with Takayasu arteritis have a high rate of atherosclerotic plaques, at least as frequent as that observed among patients with SLE.

Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient.

Colchicine is the treatment of choice in familial Mediterranean fever (FMF) both for attacks and for prevention of secondary amyloidosis. The overall non-responder rate varies from 5-10 to 40%. Thalidomide is known to blunt the acute phase response. We report the efficacy of the addition of thalidomide to colchicine in controlling the febrile attacks and acute phase response in a patient with FMF resistant to 2 mg colchicine per day.