Hakan Erdem

Immunopathogenesis of Behçet’s disease with special emphasize on the possible role of antigen presenting cells

Behçet’s disease (BD) is a systemic vasculitis with unclear etiology and pathogenesis. Although several viral and bacterial causes have been investigated in detail for several years, of late it is widely accepted that microorganisms may play a role as a trigger, or as a cross-reactive antigens that interfere with self-antigens, such as heat-shock proteins. Genes such as HLA-B51, MICA and TNF, considered to play a crucial role in the pathogenesis of BD, are located in the major histocompatibility complex (MHC). However, it has been accepted that, only HLA-B51 is directly related with pathogenesis of the disease, and others have strong linkage disequilibrium with HLA-B51. Some other genes such as IL1, Factor V and ICAM-1, KIR and eNOS assumed to take a part in the pathogenesis are settled out of the MHC region. In patients with BD, several abnormalities in innate and acquired immunity were detected. Mainly, the hypersensitivity of T lymphocytes to different types of antigens plays a critical role in the pathogenesis. However, it is not clear that whether defective signal transduction or antigen presenting cell (APC) dysfunction is responsible for T cell hypersensitivity. Cytokines and chemokines secreted from APCs and T cells are suggested to cause the neutrophil hyperactivation. Activated neutrophils secrete some cytokines, which prime themselves and also stimulate Th1 cells. These relationships among APCs, Th1 lymphocytes and neutrophils constitute the basis of immune responses in BD. In this review, we focus on the possible role of APC in the pathogenesis of BD with an attempt to take attention of researchers in this field to these cells at the crossroads of innate and adaptive immunity, and discuss other potential contributors including cells of the immune system and mediators.

Optic neuritis occurring with anti-tumour necrosis factor α therapy

Objective: Various demyelinating disorders have been reported in association with anti-tumour necrosis factor α (TNFα) agents. The objective of this study was to review the occurrence, clinical features and outcome of optic neuritis (ON) during treatment with anti-TNFα agents. Methods: A PubMed search was conducted to identify literature addressing the potential association between anti-TNFα agents and ON, following our experience with a patient having rheumatoid arthritis in whom ON developed while being treated with infliximab. Results: 15 patients including the case presented here with ON in whom the symptoms developed following TNFα antagonist therapy were evaluated. Eight of these patients had received infliximab, five had received etanercept and two patients had received adalimumab. Among them, nine patients experienced complete resolution, and two patients had partial resolution, while four patients continued to have symptoms. Discussion: Patients being treated with a TNFα antagonist should be closely monitored for the development of ophthalmological or neurological signs and symptoms. Furthermore, consideration should be given to avoiding such therapies in patients with a history of demyelinating disease. If clinical evaluation leads to the diagnosis of ON, discontinuation of the medication and institution of steroid treatment should be a priority.

Overview of neurobrucellosis: a pooled analysis of 187 cases

Central nervous system involvement is a serious complication of brucellosis; data found in the literature are generally restricted to case reports and case series. In this study we pooled the data from Turkish medical practice in order to gain a thorough understanding of the subject. A search of Turkish publications on chronic neurobrucellosis was made using both Turkish and international databases. A total of 35 publications were analyzed and 187 neurobrucellosis cases were evaluated. Headache, fever, sweating, weight loss, and back pain were the predominant symptoms, while meningeal irritation, confusion, hepatomegaly, hypoesthesia, and splenomegaly were the most frequent findings. The major complications in patients were cranial nerve involvement, polyneuropathy/radiculopathy, depression, paraplegia, stroke, and abscess formation. Antibiotics were used in different combinations and over different intervals. The duration of antibiotic therapy reported ranged from 2 to 15 months (median 5 months). The mortality was 0.5% with suitable antibiotics. Neurobrucellosis may mimic various pathologies. For this reason, a thorough evaluation of the patient with probable disease is crucial for an accurate diagnosis and proper management of the disease.

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.

Serum interleukin-18 levels in patients with Behçet’s disease. Is its expression associated with disease activity or clinical presentations?

Interleukin (IL)-18 is a proinflammatory cytokine which plays a crucial role in T helper (Th)1 type immune response. The aim of this study is to investigate the relationship of serum levels of IL-18 with disease activity and clinical presentations in patients with Behcet’s disease (BD). Sixty patients with BD and 20 healthy controls were included in the study. Patients were grouped as having active or inactive disease according to the Leeds activity score. They were also separated as a systemic involvement or mucocutaneous symptoms only. Patients with systemic involvement were further grouped according to the presence of ocular, articular and vascular involvement. IL-18 levels were significantly higher in all patient subgroups as compared to healthy controls and found to be correlated with the activity score in patients having active disease. In conclusion, this cytokine participates in the pathogenesis of BD and its levels are correlated with the disease activity. Detection of increased levels of IL-18 in patients with inactive disease implies that Th1 activation and subclinical inflammation persist during the inactive period of the disease.

Does Mud Pack Treatment Have Any Chemical Effect? A Randomized Controlled Clinical Study

OBJECTIVE The aim of this study was to reveal the efficacy of mud pack treatment in patients with knee osteoarthritis and to find the contribution of chemical factors to the build up of these effects. METHODS Sixty patients were randomly assigned to directly applied mud pack (study) group or to nylon-covered mud pack (control) group. Thirty patients in the study group had mud application 15 times to both knees: heated mud, up to 43 degrees C, was applied to skin directly for 30 minutes. Thirty patients in the control group had the same treatment as the study group except heated mud was applied over an impermeable nylon pack. Primary outcome measures of the study were the Western Ontario and McMaster Universities (WOMAC) index, pain intensity on a visual analog scale (VAS), patients assessment of disease severity index, physicians assessment of disease severity index, and analgesic consumption. The patients were evaluated before and after (end of 15th application) the intervention and followed up for 24 weeks at 4-week intervals. The results were assessed on an intent-to-treat basis. RESULTS As compared to the baseline, significant decreases were observed in WOMAC, pain intensity, disease severity index scores, and analgesic consumption in both groups after the intervention. Observed improvements in the study group were found to be superior to the control during the whole postintervention follow-up, except for analgesic consumption in the third week. A significant number of patients in the study group showed minimal clinically important improvement as compared to the control group. CONCLUSION Mud pack treatment significantly improved the pain and functional status of patients with knee osteoarthritis, whether applied directly or coated with nylon. Direct application was found to be superior, which implies chemical properties of the mud contribute to the build up of therapeutic effect.

Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1β play a major role in Behçet’s synovitis?

The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1β) and the tumor necrosis factor-alpha (TNF-α) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1β, TNF-α and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet’s disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1β, TNF-α and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-α and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1β levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1β between BD and RA patients. Among patients with RA, positive correlations were found between TNF-α and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1β, were expressed in relatively small quantities in Behçet’s synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet’s arthritis. We suggest that IL-1β may be involved in the pathogenesis of Behçet’s synovitis.

Saccharomyces boulardii and infection due to Giardia lamblia

Therapy with metronidazole is the recommended option in giardiasis. However, some clinical trial reports suggest the appearance of drug resistance to explain therapeutic failure. Several investigations have been carried out on the effect of probiotic microorganisms for preventing or treating gastrointestinal diseases, but little is known about their efficacy against protozoal infections. The principal objective of our study was to evaluate the efficacy of Saccharomyces boulardii against Giardia lamblia infections. A double-blind, placebo-controlled study was carried out on adult patients with giardiasis. Group 1 (30 patients) included metronidazole 750 mg 3 times daily along with S. boulardii capsules (250 mg b.i.d. orally) for 10 d while group 2 (35 patients) was treated with metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d. Patients were re-examined at 2 and 4 weeks after treatment, and stool examinations were performed. At week 2, G. lamblia cysts were detected in 6 cases (17.1%) of group 2 and none in group 1. At the end of the fourth week, presence of the cysts continued in the same 6 cases in group 2 (control group). These findings indicated that S. boulardii may be effective in treating giardiasis when combined with metronidazole therapy.

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

ABSTRACT No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Nosocomial infection characteristics in a burn intensive care unit: Analysis of an eleven-year active surveillance

AIMS The objective of this study was to describe nosocomial infection (NI) rates, risk factors, etiologic agents, antibiotic susceptibility, invasive device utilization and invasive device associated infection rates in a burn intensive care unit (ICU) in Turkey. METHODS Prospective surveillance of nosocomial infections was performed according to Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) criteria between 2001 and 2012. The data was analyzed retrospectively. RESULTS During the study period 658 burn patients were admitted to our burn ICU. 469 cases acquired 602 NI for an overall NI rate of 23.1 per 1000 patient days. 109 of all the cases (16.5%) died. Pseudomonas aeruginosa (241), Acinetobacter baumannii (186) and Staphylococcus aureus (69) were the most common identified bacteria in 547 strains. CONCLUSION Total burn surface area, full thickness burn, older age, presence of inhalation injury were determined to be the significant risk factors for acquisition of NI. Determining the NI profile at a certain burn ICU can lead the medical staff apply the appropriate treatment regimen and limit the drug resistance. Eleven years surveillance report presented here provides a recent data about the risk factors of NI in a Turkish burn ICU.