Arif Kaya

The prevalence of fibromyalgia among textile workers in the city of Denizli in Turkey

Aim:  Fibromyalgia (FM) is characterized by chronic widespread pain, fatigue, reduced sleep quality and multiple tender points. A recent population study from Turkey found the prevalence of FM as 3.6%. A prevalence study among workers has not yet been performed. We performed a prevalence survey among working population in the city of Denizli in Turkey.

Minimally invasive minor salivary gland biopsy for the diagnosis of amyloidosis in a rheumatology clinic.

Background. Systemic amyloidosis is a potentially fatal condition, unless diagnosed and treated before development of irreversible organ damage. Demonstration of amyloid deposits within tissue biopsies is only definitive diagnostic method, which makes appropriate selection of biopsy site essential. Herein, we evaluated efficacy of minimally invasive minor salivary gland biopsy (MSGB) for the diagnosis of amyloidosis. Methods. We analyzed 37 biopsies taken from 35 patients. Suggestive findings for amyloidosis were significant proteinuria, renal impairment, refractory diarrhea, neuropathy, and restrictive cardiomyopathy. Minor salivary gland was the initial biopsy site in all subjects. When MSGB was negative but there was a high suspicion for amyloidosis, a kidney, duodenum, or rectal biopsy was performed for further investigation. Results. Mean age of patients was 45.4 and 21 were female. In 11 patients amyloidosis was diagnosed with MSGB. In overall 18 patients were diagnosed with amyloidosis. Sixteen of them were identified as being of AA type and two were AL type amyloidosis. The sensitivity of minimally invasive MSGB is 61.1% for diagnosing amyloidosis in this study. Conclusion. MSGB is a safe and simple method for the diagnosis of amyloidosis which can be performed in an outpatient setting. We suggest extensive use of this minimally invasive method.

An Unusual Case of Madelung's Disease with Multiple Atypical Fractures

Madelungs disease is a rare acquired disorder of fat metabolism characterized by multiple symmetric lipomas with typical distribution mainly around the upper trunk, neck, and shoulders. The condition is strongly associated with chronic alcohol use and has various systemic manifestations like polyneuropathy, muscle weakness, and small bone fractures. Herein, we report a 56-year-old male patient with Madelungs disease and multiple fractures and discuss possible underlying factors leading to multiple fractures.

A variant allele of the Mediterranean-fever gene increases the severity of gout.

Gout is a clinical syndrome that occurs as an inflammatory response to increased concentration of uric acid and monosodium urate crystals. Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease with autosomal recessive inheritance. The Mediterranean fever (MEFV) gene is responsible for FMF and encodes pyrin that suppresses the inflammatory response. Most of the FMF‐related mutations have been identified in exon 2 (e.g., E148Q and R202Q) and exon 10 (M680I, M694V, M694I and V726A) of the MEFV gene, and each missense mutation is known to increase production of interleukin‐1, a proinflammatory cytokine. Our aim was to investigate effects of MEFV variant alleles on the manifestations of gout.

Abdominal pain may dominate the scene of idiopathic aortitis

A 59-year-old man suffering from abdominal pain and having high acute phase reactants was admitted to hospital. Aortitis was discovered incidentally with magnetic resonance that was performed for another prediagnosis. Steroid and azathioprine combination was unsuccessful for remission and preventing relapses. However, steroid and methotrexate combination was successful for clinical and laboratory remissions. Also, the iliac artery occlusion was improved with stent implementation. In general, isolated idiopathic aortitis is a very rare entity and hard to be diagnosed. In this case, we describe a patient with aortitis that has only abdominal pain and treated with steroid and methotrexate combination.

AB0914 Management of Gout in Different Clinical Specialties in Turkey

Background In contrast to many European countries, patients can easily admit to secondary and tertiary centers without referral by the primary care in Turkey. Therefore we also compared the management options for gout preferred in different clinical specialties. Objectives In this study we investigated how gout is treated in Turkey. Methods 319 consecutive patients were included in this multicenter study (mean age 58.60±12.8 years, 44 females, 272 males). All patients filled a standard questionnaire. Results 53 patients were first admitted to primary care (16.6%), 101 patients to orthopedics (31.7%), 29 patients to physical therapy and rehabilitation (9.1%), 70 patients to internal medicine (21.9%), 49 patients to rheumatology departments (15.4%), and 17 patients to other clinical specialties (5.3%). Among those 313 patients admitting to health care with acute gout attack, 40 patients were referred the patient to another center without any treatment (12.8%). Referral rate remarkably higher in the primare care (%28.8). NSAIDs were the most common drugs prescribed for acute attack (60.06%), followed by colchicine (58.15). Allopurinol was given in 12.8%, and steroids in 7.99% of patients during acute attack. Regarding long term treatment, 92 patients had never been treated with allopurinol (28.8%). 29.1% (37/127) patients having less than 2 attacks per year and 28.6% (55/192) of patients having two or more attacks per year had never been treated with allopurinol (p>0.05). Only 89 patients (27.9%) were treated with allopurinol by their first physicians, and 138 patients (43.3%) were treated with allopurinol later in a different specialty. Prescription of allopurinol was more common among the rheumatologists. Diet and life style modifications were recommended in 118 of the patients (37%) by their first physicians. 171 patients (53.6%) were later recommended diet and life style modifications during their follow up in a different clinical specialty (total 289 patients, 90.6%). Diet and life style modifications were recommended more commonly in rheumatology (41 patients, 83.7%). 183 (57.4%) were treated with colchicine by their first physicians, and 114 patients (35.7%) were treated with colchicine by a physician of different specialty (total 297 patients, 93.1%). Significantly more patients were treated with colchicine than with allopurinol during long term management (p<0.001). Conclusions Treatment of gout appears suboptimal in primary care, and more than 25% of patients were referred without any treatment. Long term management also appears suboptimal in both primary care and among some specialists such as orthopedics. Only a minority of patients were recommended allopurinol and/or life style modifications by the doctors first diagnosed gout. Although long term treatment appears better among rheumatologist, still a considerable number of patients were not recommended uric acid lowering approaches in the rheumatology clinics. Disclosure of Interest None declared

MEFV Mutations and CYP3A4 Polymorphisms Do Not Predict "Colchicine Responsiveness" in Familial Mediterranean Fever

Abstract Familial Mediterranean Fever (FMF) is an auto-inflammatory disease caused by mutations in the MEFV gene. Colchicine is the mainstay of FMF treatment. It is metabolised by cytochrome P450-3A4 (CYP3A4) enzyme. About 10-15% of FMF patients do not respond to treatment with colchicine. In this study, the researchers aimed to investigate association of colchicine non-responsiveness with MEFV mutations, CYP3A4*1B, *2, and *17 polymorphisms, and some demographic features of FMF patients. One hundred and ninety-six consecutive FMF patients (170 colchicine responders and 26 non-responders) were included in the study. CYP3A4 polymorphisms were detected using polymerase chain reaction and TaqMan probes.CYP3A4*1B and *17 were not detected in responders or non-responders. CYP3A4*2 was detected in eight responders, all of which were in heterozygous state. However, the difference was not statistically significant. Most patients (165 responders and 25 non-responders) had MEFV gene analysis available prior to participation in the study. Frequencies for M694V, M680I, V726A, and E148Q mutations and M694V/M694V genotype were similar in two groups. Mean body mass index of responders was not significantly different from that of non-responders. Attack frequency and proteinuria level were significantly higher in non-responders than in responders. Earlier age at disease onset was found to be associated with colchicine non-responsiveness. However, neither MEFV mutations nor CYP3A4 mutations were associated with colchicine non-responsiveness.

THU0381 Clinical determinants of attack prodrome in patients wiht familial mediterranean fever

Background Familial Mediterranean fever (FMF) is the most frequent form of periodic fever syndromes which is characterized by recurrent febrile inflammatory attacks of serosal and synovial membranes. Attacks are usually preceded by a prodromal period with great inter-individual differences1. Colchicine reduces severity, frequency and duration of attacks, and prevents development of amyloidosis. Despite regular colchicine use, a considerable number of FMF patients continue to suffer from attacks which cause significant morbidity, impairment in quality of life and loss of work. Anti IL-1 agents are newly introduced and promising agents for the autoinflammatory diseases. Recently, on demand use of anakinra has been shown to be effective in mevolonate kinase deficiency2. Likewise, on demand use of IL-1 antagonists during prodromal period might halt or reduce the severity of attacks in patients with FMF. Therefore, it’s crucial to well-define the prodrom of FMF attacks. Objectives To investigate the prodromal period in FMF and its clinical associations. Methods Eighty-five patients with FMF (51 female, mean ± standart deviation age 36.2±9.9 years) who continued to have attacks despite colchicines theraphy were enrolled. Demographic data, disease characteristics and MEFV genotypes were retrieved from the medical records. Patients were meticulously questioned about the attack characteristics and the prodromal period preceding these attacks. Logistic regression analyzes were used to investigate clinical associations of prodroma. Age, sex, disease duration, MEFV genotypes, education level, attack severity, similarity, duration and presence of triggering factors are included in analyzes. Results Fever, peritonitis, pleuritis, arthritis and erysipeloid-eruption (ELE) had been observed in 66 (77.6%), 82 (96.5%), 50 (58.8%), 58 (68.2) and 32 (37.6%) patients respectively. Sixty-three (76.8%) and 21 (42%) patients had well-characterized prodromata of peritonitis and pleuritis attacks, with a median duration of 4 hours (min 0.5- max 24). About half and one-third of the patients reported attack prodroma in arthritis and ELE with median duration of 3 hours (min 0.5- max 10), respectively. Similarity of attacks [odds ratio 13.6 (95%CI, 1.02-182)] and attack severity [odds ratio 1.62 (95%CI, 1.03-2.53] were found to be the clinical determinants of serosal attacks. Age, sex, disease duration, MEFV genotypes, education level and presence of triggering factors did not associate with attack prodroma. Conclusions Majority of attacks in FMF are preceded with a prodromal period. Similarity and severity of attacks are the clinical predictors for having prodromal period. This period might be a window of opportunity for the acute treatment of an impending attack. References Lidar M, et al. The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol. 2006;33:1089-92. Bodar EJ, et al. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. 2011;70:2155-8. Disclosure of Interest None Declared

THU0497 Serum Antimicrobial Peptides in Patients with Familial Mediterranean Fever

Background Familial Mediterranean fever (FMF) is characterized by recurrent febrile inflammatory attacks of serosal and synovial membranes. Although genetic disorder leading to disease is almost the same, clinical phenotype is quite variable suggesting role of other pathogenetic factors. Serum antimicrobial peptides (AMPs), cathelicidin and defensins, are naturally occurring peptides produced from epithelial tissues and neutrophils. Beside their direct antimicrobial activity, AMPs have immunomodulatory functions including chemotaxis, opsonisation, cytokine, chemokine and compleman activation that may produce or promote inflammation. Their pathogenetic role in numerous autoinflammatory diseases has been reported. Objectives To investigate the serum antimicrobial peptides in patients with FMF and its clinical associations. Methods twenty-three newly diagnosed FMF patients (14 female, mean age 35.6 years) were enrolled and prospectively followed for six months. Demographic data, disease characteristics and MEFV genotypes were obtained with standardized questionnaires. Age- and sex- matched 24 healthy subjects were constituted control group. Serum alpha defensin (HNP1), beta defensins (hBD1 and hBD2) and cathelicidin (LL37) levels were measured with ELISA, before and six months after treatment and if there was an attack in this time period. Results pretreatment concentrations of HNP1, hBD1 and LL37 were significantly higher in FMF patients compared to healthy control subjects and remained throughout after colchicine treatment. HNP1 concentration was reduced to pretreatment levels with colchicine. In six-months follow up period 13 patients experienced at least one attack. During attacks any significant difference observed in any of the serum AMP concentrations. Interestingly, none of serum AMPs correlated with acute phase reactants. Likewise, none of AMPs correlated with frequency of attacks. Conclusions Increased levels of serum AMPs in FMF patients suggest that neutrophils are active in the course of disease despite colchicine treatment. We did not find any correlation between FMF disease characteristics and serum AMPs suggesting they are not associated with clinical phenotype of FMF. Disclosure of Interest None Declared

AB0715 Evaluation of patients with elevated sedimentation and crp levels: attention to non-rheumatological diagnoses!

Background Erythrocyte sedimentation rate (ESR) and high C-reactive protein (CRP) are the most commonly used acute phase reactants to detect and follow up disease activity in rheumatology clinics. Besides rheumatic diseases (RD), infections and malignancies are two of the major causes of high ESR and CRP. The diagnosis canbe challenging especially in serologically unrevealing patients who have nonspecific clinical findings. These patients often require extensive investigations to identify the condition associated with elevated ESR and CRP levels. Objectives In this retrospective study we aimed to determine the definitive diagnosis of undiagnosed and untreated patients with high ESR and CRP. Methods Electronic medical records of patients hospitalized in Rheumatology clinic between January 2010 and May 2011 were retrospectively analysed. Patients demographics, the levels of ESR and CRP on the day of hospitalization and definitive diagnoses were recorded. The definitive diagnoses were divided into three groups: (1) newly diagnosed RD; (2) newly diagnosed non-RD; and (3) flare of RD. Non-RD was than subdivided into infections, malignancies and others. Results Data were collected on 113 patients (84 female), of whom 32 had a newly diagnosed RD, 39 had non-RD (20 infection, 6 malignancy, 13 others) and 36 had flare of RD. The age, ESR, and hospitalization duration did not differ significantly between the groups. CRP was significantly higher in the infection subgroup than in the RD group (p=0.005). CRP level did not differ significantly between the RD group and malignancy subgroup (p=0.055)[Table 1]. The most frequent diagnoses were temporal arteritis and/or polymyalgia rheumatica and seronegative rheumatoid arthritis, respectively in the RD group. Non-RD were infections, malignancies, gastrointestinal diseases and the other causes, respectively [Table 2]. Conclusions In this study, patients with nonspecific clinical findings and high acute phase reactants were more likely to have non-RD compared to newly diagnosed RD. CRP level was significantly higher in infectious diseases than in newly diagnosed RD. Pyhsicians should keep in mind the probability of an infection or a malignancy in patients with high acute phase reactants but no specific clinical findings suggestive of RD. Disclosure of Interest None Declared