Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Importance of hematological markers in familial Mediterranean fever in terms of disease severity and amyloidosis.

There are limited follow-up parameters for familial Mediterranean fever (FMF) related to disease severity and amyloidosis. Some hematological markers are emerging to assess inflammation. In this study, we hypothesized that some hematological parameters could be used to determine disease severity and amyloidosis in FMF. We included 274 adult FMF patients, and evaluated the relationship between neutrophil lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR) and platelet-lymphocyte ratio (PLR), platelet counts and leukocyte counts, mean erythrocyte haemoglobin concentration (MCHC) and mean erythrocyte haemoglobin (MCH) with disease severity and amyloidosis. First, we classified patients according to disease severity and presence of amyloidosis. We then compared the parameters within the groups. In addition, we determined predictive cut-off values with ROC analysis. Finally, we correlated the change in ISSF scores with the change in hematological parameters of 52 patients with follow-up hematological indices after six months. The patients with severe-moderate group had higher CRP levels (p < 0.001), white blood cell (p = 0.002) and neutrophil counts (p = 0.004) and, conversely, lower MCHC levels (p = 0.001) than patients with mild disease severity. FMF patients with amyloidosis had higher neutrophil (p = 0.04) and monocyte count (p = 0.02), increased NLR (p = 0.01) and lower MLR (p = 0.02) levels than those without. In addition, MCHC levels were also lower in the severe-moderate group in the follow-up analyses after sixth months (p = 0.03). MCHC, neutrophil and monocyte counts, NLR, MLR may be associated with poor prognosis in FMF patients. These parameters can be used in conjunction with acute phase reactant and clinical features to assess disease status.

A Case Report of Conjunctival Extranodal Marginal Zone Lymphoma Treated with Intralesional Rituximab Injection Therapy.

PURPOSE: To describe the safety and efficacy of intralesional rituximab (anti-CD 20 monoclonal antibody) therapy in a patient with conjunctival extranodal marginal zone lymphoma. METHODS: A single case report from a tertiary referral center. RESULTS: A 43 years old female patient with low-grade conjunctival extranodal marginal zone lymphoma who was completely and safely treated with intralesional rituximab therapy was presented. After four injections per week, intralesional rituximab injections were given monthly, and the treatment was completed in 6 months. Near-total regression was achieved at the end of the tenth cycle. No recurrence was observed during the 20-month follow-up period. CONCLUSION: The intralesional rituximab is a cost-effective and well-tolerated treatment for low-grade conjunctival lymphoma. The intralesional rituximab therapy may be prefer in the patients with low grade conjunctival lymphoma instead of radiotherapy. There will be needed further researches in this area.

Metabolic syndrome may be more frequent in treatment-naive sarcoidosis patients.

INTRODUCTION: Sarcoidosis is a chronic granulomatous multisystem inflammatory disease. An association between sarcoidosis and subclinical atherosclerosis has recently been demonstrated. However, there are limited publications on metabolic syndrome (MetS) and its metabolic changes in sarcoidosis. In this study, we evaluated our hypothesis that the frequency of MetS may also be increased in treatment-naive, newly diagnosed sarcoidosis patients. METHODS: We included 133 newly diagnosed sarcoidosis patients, 133 age- and sex-matched controls, and 51 untreated rheumatoid arthritis (RA) patients as diseased controls. We then compared the frequency of MetS and MetS-related items in the three groups. The criteria defined for metabolic syndrome in the National Cholesterol Education Program (NCEP) Adult Treatment Panel III report (ATP III) were used to diagnose MetS. RESULTS: MetS was more common in sarcoidosis than controls (odds ratio, OR: 5.3; 95% confidence interval, CI 95%: 2.4-11.5; p < 0.001) and was similar to RA. In addition, triglyceride and glucose levels, diastolic blood pressure measurements, and waist circumference of female sarcoidosis patients were significantly higher than in controls. CONCLUSION: We show that MetS is a frequent feature of sarcoidosis even before treatment is started. Therefore, clinicians should be aware of MetS both during treatment and during the course of the disease to reduce the risk of cardiovascular events.

Colchicine's Effects on Electrocardiographic Parameters in Newly Diagnosed Familial Mediterranean Fever Patients : Colchicine may have Favourable Effects on Parameters Related to Ventricular Arrhythmias in New Diagnosed Familial Mediterranean Fever.

OBJECTIVE: Colchicine may prevent both recurrent serositis attacks and secondary amyloidosis in familial Mediterranean fever (FMF). Furthermore, colchicine may decrease the frequency of atrial fibrillation in some groups of patients without FMF. However, there is no study that evaluates the effect of colchicine on arrhythmogenic electrocardiographic indices in FMF. In this study, we evaluated the impact of 1 year of colchicine treatment on atrial and ventricular arrhythmogenic electrocardiographic (ECG) parameters in newly diagnosed FMF patients. MATERIALS AND METHODS: We enrolled 28 newly diagnosed FMF (20 female, mean age 31.4 ± 8.2 years) patients who fulfilled the modified Tel Hashomer criteria. Electrocardiographic, demographic and laboratory parameters were obtained at the first visit and at the end of the 1­year colchicine treatment. Herein, we assessed P wave dispersion (Pd) for atrial arrhythmia risk and peak-to-end interval of T wave (Tp-E), Tp-E/QT, Tp-E/QTc values for ventricular arrhythmia risk. RESULTS: Colchicine treatment significantly decreased Tp-E and Tp-E/QT values (p = 0.02 and p = 0.01, respectively) by the end of the 1­year treatment. However, Pd values did not change with treatment. CONCLUSION: Colchicine treatment may have a favourable effect on ventricular repolarisation indices that relate to ventricular arrhythmia and sudden death.

IL-1 blockers together with colchicine may be administered as first line therapy in familial Mediterranean fever with amyloidosis.

Colchicine is the first choice of the treatment in familial Mediterranean fever (FMF). However, in FMF patients with amyloidosis, especially during creatinine level >1.5 mg/dL and nephrotic range proteinuria, colchicine may be ineffective. Interleukin-1 (IL-1) blockers could be used in colchicine resistant cases. However, starting IL-1 blocker treatment after colchicine failure may lose opportunity for effective treatment. Therefore, administering IL-1 blocker together with colchicine as first line therapy may increase the chance for suppressing the disease.

Optic Neuropathy and Macular Ischemia Associated with Neurosarcoidosis: A Case Report.

In this study, we present a case of bilateral optic neuropathy and macular ischemia in the right eye associated with neurosarcoidosis. A 26-year-old woman presented to our clinic with complaints of bilateral blurred vision. Bilateral granulomatous anterior uveitis, vitritis, optic neuropathy, and macular ischemia were detected in the right eye in slit-lamp examination. She also reported complaints of fever, weakness, sweating, arthralgia, and headache for 2 months. She was referred to the pulmonary diseases unit of our hospital due to hilar lymphadenopathy seen in her chest x-ray, and biopsies were taken for diagnostic purposes. Histological analysis of the mediastinal lymph node biopsies revealed chronic, non-caseating, granulomatous inflammation. Furthermore, the patient was referred to a neurologist due to concomitant complaint of intense headaches. She was diagnosed with neurosarcoidosis supported by findings on cranial magnetic resonance imaging and lumbar puncture. She received a 3-day course of high-dose (1 g/day) intravenous steroid treatment (methylprednisolone) followed by a tapering dose of oral prednisone. The patient began receiving oral methotrexate 15 mg/week as a steroid-sparing agent. Significant improvement in neurological and ophthalmological symptoms occurred in the first week of treatment. In this case report, we emphasized that neurosarcoidosis should be included in the differential diagnosis of patients with both bilateral optic neuropathy and macular ischemia. Furthermore, early diagnosis and timely treatment of neurosarcoidosis are important for favorable visual outcomes.

Nationwide Experience With Off-Label Use of Interleukin-1 Targeting Treatment in Familial Mediterranean Fever Patients.

OBJECTIVE: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed. RESULTS: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced. CONCLUSION: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients.

High Disease Activity May Increase Fear-Avoidance Beliefs in Rheumatoid Arthritis.

OBJECTIVES: This study aims to compare fear-avoidance (FA) beliefs of rheumatoid arthritis (RA) patients with osteoarthritis (OA) of hand patients and fibromyalgia (FM) patients and evaluate its relationship with RA activity and duration. PATIENTS AND METHODS: The study included 206 patients with RA (34 males, 172 females; mean age 49 years; range 20 to 72 years), 57 patients with FM (57 females; mean age 48 years; range 20 to 71 years), and 50 patients with OA of hand (4 males, 46 females; mean age 43 years; range 43 to 77 years). FA beliefs were assessed with modified Fear-Avoidance Belief Questionnaire (mFABQ). RA patients were dichotomized according to disease activity and disease duration separately; cutoff values were disease activity score 28 of 3.2 and six months of disease activity, respectively. RESULTS: Modified Fear-Avoidance Belief Questionnaire scores were similar in patients with RA, OA of hand, and FM. RA patients in non-remission group had higher mFABQ scores. Moreover, mFABQ scores were similar in RA patients with early and established disease groups. CONCLUSION: Fear-avoidance beliefs of patients with RA were similar with OA of hand patients and FM patients. However, higher disease activity in RA was related with escalated FA beliefs. Further studies focusing on pathophysiology of FA beliefs in patients with RA are warranted for effective pain management of RA.

The management of gout in different clinical specialties in Turkey: a patient-based survey.

Although gout is potentially curable, the management of this disease is often suboptimal. In this study, we investigated the treatment of gout in Turkey and also compared the management approaches to gout in different clinical specialties. Three hundred and nineteen consecutive patients (mean age 58.60 ± 12.8 years; 44 females, 275 males) were included in this multicenter study. A standardized form was generated to collect data about the patient's first admission to health care, the specialty of the doctor first diagnosed the gout, the treatment options for gout including attack management, patient referral, chronic treatment including medical treatment, and life style modifications. Forty patients were referred to another center without any treatment (12.8 %), and referral rate is most common among the primary care physicians (28.8 %). Colchicine was more commonly used for attack prophylaxis than allopurinol. Ninety-two patients had never been treated with allopurinol (28.8 %). Allopurinol prescription was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. Recommendation of diet and life style modifications was less common among the primary care physicians and orthopedists, and highest among the rheumatologists. The rates of life style modification recommendation and long-term allopurinol prescription were 83.7 and 77.6 %, respectively, among the rheumatologists. Both acute and chronic management of gout is suboptimal in Turkey especially among the primary care physicians and orthopedists. Moreover, chronic treatment is even suboptimal among rheumatologists.

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.

Transverse myelitis in Behçet's disease: a series of four cases and review of the literature.

OBJECTIVES: Transverse myelitis (TM) is an uncommon neurologic condition characterised by the segmental involvement of the spinal cord. Although its etiology is unknown, a well established list of associations have been described, many items of which point towards an autoimmune and vasculitic process. TM is also a rare complication of Behçet's disease (BD), an autoimmune process. Herein we present 4 cases of TM associated with BD. METHODS: Retrospective chart reviews of 104 patients were done. Diagnosis of BD was established in each case according to the diagnostic criteria established by the International Study Group for Behçet's Disease. Demographic data, clinical and radiologic presentations of TM, treatment strategies and outcomes were obtained from hospital records. RESULTS: Among the 15 patients with neurological involvement, four cases (3 male, 1 female) of acute TM associated with BD were confirmed. TM associated with BD affected cervical and thoracic levels of the spinal cord. Myelitis involved multiple segments (4 cases). TM developed at any stage of the disease, even as a dramatic initial presentation, leading to the diagnosis of BD (1 case). The longest time elapsed since the diagnosis of BD prior to the development of TM was 10 years. A major association was the history of panuveitis in all four cases. Cyclophosphamide and steroid therapy were the mainstay of the treatment once the TM had developed. Treatment outcomes were variable, depending mostly on the severity of the neurologic involvement at presentation, timing of the initiation of the therapy and patients adherence with the treatment. Two of 4 cases recovered without major sequela. CONCLUSIONS: Although rare, the presented association and its detailed clinical discussions would serve to enhance our understanding of both TM and the spectrum of neurologic complications that BD may harbour. Early recognition and initiation of therapy are crucial for successful outcome.

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

Madelung's 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 Madelung's disease and multiple fractures and discuss possible underlying factors leading to multiple fractures.

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.