Erbil Ünsal

EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation

Objectives To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. Methods The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, κ-agreement) using as ‘gold standard’ the final consensus classification or original treating physician diagnosis. Results A total of 1183/1398 (85%) samples collected were available for analysis: 827 HSP, 150 c-PAN, 60 c-WG, 87 c-TA and 59 c-other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c-vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with a κ-agreement of 0.96 for HSP (95% CI 0.84 to 1), 0.88 for c-WG (95% CI 0.76 to 0.99), 0.84 for c-TA (95% CI 0.73 to 0.96) and 0.73 for c-PAN (95% CI 0.62 to 0.84), with an overall κ of 0.79 (95% CI 0.73 to 0.84). Conclusion EULAR/PRINTO/PRES propose validated classification criteria for HSP, c-PAN, c-WG and c-TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis.

Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study

Objectives Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH‐2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)–associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.

Etanercept for therapy‐resistant macrophage activation syndrome

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of childhood rheumatic diseases, especially systemic onset juvenile idiopathic arthritis (SoJIA). We report a 4‐year‐old girl with probable SoJIA who presented with MAS. She did not respond to pulse methyl prednisolone and Cyclosporine A (CsA). She also failed to respond to intravenous immunoglobulin (IVIG) therapy. Etanercept was started, based on the observation of increased serum levels of tumor necrosis factor‐alpha (TNF‐α) in patients with MAS. Her condition improved following etanercept, suggesting that etanercept might have a therapeutic role in resistant MAS. Pediatr Blood Cancer 2008;50:419–421.

The relationship of neutrophil-to-lymphocyte ratio with gastrointestinal bleeding in Henoch–Schonlein purpura

Henoch–Schönlein purpura (HSP) is the most common systemic vasculitis of childhood. Gastrointestinal (GI) bleeding is one of the major complications of HSP. The blood neutrophil-to-lymphocyte ratio (NLR) is identified as a potentially useful marker of clinical outcome in inflammatory diseases. NLR may be a useful biomarker of GI bleeding in children with HSP, which has a neutrophil-dominated inflammation. The aim of this study was to evaluate NLR in patients with HSP and to investigate the relationship with GI bleeding. The study consisted of 63 HSP patients and 38 age- and sex-matched healthy children. C-reactive protein, white blood cell count, platelet count, mean platelet volume (MPV), hemoglobin level, and NLR were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used to determine the variables associated with GI bleeding. NLR and MPV were the only two indicators associated with GI bleeding in HSP in logistic regression analysis. The area under the ROC curve analysis indicated that NLR could be a more efficient potential predictor of GI bleeding in HSP when compared to MPV. This study suggested that higher NLR might predict GI bleeding in HSP.

Uveitis in juvenile arthritis.

Purpose: To evaluate the clinical features of and determine the risk factors for uveitis in patients with juvenile arthritis. Methods: The prevalence and clinical characteristics of uveitis were studied retrospectively in 90 children diagnosed with arthritis. Patients with uveitis were compared with those who did not have eye involvement. Results: Uveitis was diagnosed in 11 patients (12.2%). Of these, seven (63.6%) had oligoarticular, two (36.4%) had polyarticular, and one (9.1%) had systemic-onset juvenile rheumatoid arthritis (JRA). One patient (9.1%) was diagnosed with enthesitis-related arthritis (ERA) (9.1%). The prevalence of uveitis was significantly higher in patients with oligoarticular JRA. The mean age at onset of arthritis in the uveitis patients was 4.39 years, which was significantly lower than in the non-uveitis group. There was no gender difference in the risk of developing uveitis. Antinuclear antibodies (ANA) was positive in seven (63.6%) of the 11 uveitis patients, confirming ANA as a significant determinant for uveitis in juvenile arthritis. Rheumatoid factor was not found to be a risk factor. One (9.1%) of the 11 patients developed serious sight-threatening complications during the follow-up period. Conclusion: This study confirmed that oligoarticular onset, ANA positivity, and young age are risk factors for developing uveitis in patients with juvenile arthritis. Gender was not found to be a determining factor. Prompt treatment of uveitis effectively decreased the prevalence of visual impairment.

The Interaction of Oxidative Stress Response with Cytokines in the Thyrotoxic Rat: Is There a Link?

Oxidative stress is regarded as a pathogenic factor in hyperthyroidism. Our purpose was to determine the relationship between the oxidative stress and the inflammatory cytokines and to investigate how melatonin affects oxidative damage and cytokine response in thyrotoxic rats. Twenty-one rats were divided into three groups. Group A served as negative controls. Group B had untreated thyrotoxicosis, and Group C received melatonin. Serum malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and nitric oxide derivates (NO•x), and plasma IL-6, IL-10, and TNF-alpha were measured. MDA, GSH, NO•x, IL-10, and TNF-alpha levels increased after L-thyroxine induction. An inhibition of triiodothyronine and thyroxine was detected, as a result of melatonin administration. MDA, GSH, and NO•x levels were also affected by melatonin. Lowest TNF-alpha levels were observed in Group C. This study demonstrates that oxidative stress is related to cytokine response in the thyrotoxic rat. Melatonin treatment suppresses the hyperthyroidism-induced oxidative damage as well as TNF-alpha response.

Short-term follow-up of the juvenile rheumatoid knee with fat-saturated 3D MRI

Objective. To determine the correlation between clinical status and 3D, fat-saturated contrast-enhanced MRI findings in assessing the response to treatment in patients with knee-joint involvement from juvenile rheumatoid arthritis (JRA). Materials and methods. Synovial hypertrophy, effusion, cartilage and epiphyseal status were scored using spin-echo (SE) T1-weighted, SE T2-weighted and contrast-enhanced, fat-suppressed 3D MRI in 42 knees of 21 patients. MRI findings were evaluated by scoring results and compared with the clinical scoring results. Progression, improvement and equivalence were analysed between 0–3 and 3–6 months, both clinically and by MRI. Results. Fat-suppression imaging generated high contrast between cartilage, synovium, effusion and bone. Correlation coefficients according to progression, improvement and equivalent findings of months 1–3 and months 3–6 comparison of clinical and MRI scores were found to be 0.50 and 0.70, respectively. Conclusion. Contrast-enhanced 3D MRI with fat suppression provides good discrimination between synovial hypertrophy and fluid. Fat-suppressed imaging offers better contrast between cartilage and synovium. Long-term MRI follow-up of JRA improves direct follow-up of pathological changes and helps in modifying treatment regimens.

An unusual complication of dorsal penile nerve block for circumcision

SIR—The use of dorsal penile nerve block (DPNB) during circumcision may provide valuable adjunctive intraoperative anesthesia and postoperative analgesia. The placement of this block is very easy and it does not require particular skills. However, it has not been totally free of associated complications. A 9-year-old boy was admitted to the pediatric emergency department with high fever, left thigh pain, and limping for 2 days. His past medical history revealed a circumcision 1 week prior to admission under general anesthesia with an intraoperative DPNB in another hospital. He had no history of previous trauma and systemic or localized infection. On admission, he had an almost healed circumcision scar around the penis without sign of soft tissue infection. The left hip was semiflexed, abducted, and externally rotated. He had pain with motion of the left hip, and he was unable to walk. There was no lesion suggesting an infection or infective septic emboli on the body including the extremities. The remainder of the examination was normal. Laboratory tests revealed an elevated acute phase response. The X-ray of pelvis was normal. Septic arthritis was excluded by a left hip joint aspiration. A computerized tomographic scan (CT) of the pelvis revealed an ischial osteomyelitis with its abscess in the adjacent obturator muscle (Fig 1). Contamination during the DPNB procedure was suspected. According to data obtained from surgeon who circumcised the boy, the surgical area was prepared with betadine solution. DPNB was performed with mixture of equal amount of 25% bupivacaine and 2% prilocaine solution using a sterile disposable 22 G needle. The block needle was first directed against the symphysis pubis and redirected toward the subpubic space after making contact with the ischium. After the procedure, the base of the penis was infiltrated circumferentially with same needle for local anesthesia. Circumcision was performed and was uneventful. As Staphylococcus aureus was the most likely microorganism at this age, the patient was empirically started on vancomycin and ceftriaxone. Simultaneous culture of the blood specimen was negative. The response to parenteral antibiotics was successful with complete resolution of the abscess. Clinically, he was free of fever and pain on the fourth day, and acute phase reactants returned to normal by the second week. The control CT which was performed on the third week of therapy revealed resolution of the abscess and significant regression of the osteomyelitis. The patient completed a 6 weeks of antibiotic therapy. Since 1978, DPNB has been an accepted method for alleviating pain during and after circumcision (1). However, some severe complications such as the toxic absorption of local anesthetic agents and gangrene of the glans penis were reported (2). The most serious complication reported to date occurred in a 2-day-old infant who received a DPNB with a solution accidentally containing epinephrine 1 : 1000 (3). Our patient experienced ischial osteomyelitis with adjacent obturator abscess after DPNB. To the best of our knowledge, such a septic complication from DPNB has not been reported elsewhere. He had neither previous blunt trauma nor obvious infection. So, we suspected the infection resulted from the DPNB needle, which was either contaminated prior to its use or contaminated when it passed through incompletely disinfected skin. It is also possible that transient bacteremia from another source resulted in a local infection in the region disrupted by the block needle. The lateralized localization of the abscess might be related to the direction of the needle during the DPNB. Another possibility is that the bacteremia producing the osteomyelitis and abscess might also have come from the operative procedure or the circumferential infiltration of basal penis. However, our patient had no evidence of soft tissue infection around the penis. Until now, pos-circumcision osteomyelitis has not been described. Only a few cases with penile or scrotal abscess after circumcision have been reported (4,5). Because of the deep localization of the infection, we considered it more likely that the DPNB was the cause rather than circumcision itself. Recently, Soh et al. investigated the complication rate of DPNB for circumcision in a group of 3909 patients. They Figure 1 Ischial osteomyelitis with its abscess in the adjacent obturator muscle (arrows). Pediatric Anesthesia 2006 16: 1094–1101

Decreased vitamin D levels in children with familial Mediterranean fever

To determine the frequency of vitamin D deficiency in children with familial Mediterranean fever (FMF) and to investigate the factors associated with low vitamin D status.