Balahan Makay

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.

Mean Platelet Volume in Obese Adolescents with Nonalcoholic Fatty Liver Disease

ABSTRACT Background: Nonalcoholic fatty liver disease (NAFLD) is the accumulation of excess fat in the liver in the absence of alcohol consumption, which commonly coexists with obesity. NAFLD is associated with increased risk of atherosclerosis and insulin resistance Mean platelet volume (MPV) is a marker of platelet activation, which is a determinant of atherosclerosis. Aims: The first aim of the present study was to investigate the MPV levels in obese adolescents and compare the MPV levels in patients with and without NAFLD and also with healthy controls. The second aim of this study was to evaluate the relationship between IR and MPV. Patients and Methods: Case records of 128 exogenous obese adolescents were retrospectively evaluated. Laboratory parameters were collected by using a computerized patient database. Insulin resistance was calculated by a homeostasis model assessment (HOMA-IR) index. Patients were divided into two groups: patients with NAFLD (Group 1) and patients without NAFLD (Group 2). Forty-seven healthy children constituted the control group. Results: MPV was significantly higher in obese adolescents than their healthy peers. Group 1 had significantly higher MPV than group 2. HOMA-IR was significantly higher in group 1 than group 2. MPV was significantly higher in patients with IR than patients without IR. There was a positive correlation between MPV and HOMA-IR. MPV was inversely correlated with HDL cholesterol and platelet count. Conclusion: MPV may be used as a follow-up marker in patients with NAFLD at the point of atherosclerosis.

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.

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.

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

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Assessment of atherosclerosis in obese adolescents: Positive correlation of mean platelet volume and carotid intima media thickness

This study aims to assess the correlation of mean platelet volume (MPV) and common carotid artery (CCA) thickness in a population of obese adolescents.

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.

Chronic recurrent multifocal osteomyelitis in a patient with selective immunoglobulin M deficiency

Chronic recurrent multifocal osteomyelitis is an unusual inflammatory process of unknown origin involving multiple osseous sites, often recurrently. Selective immunoglobulin M (IgM) deficiency is a rare primary immunodeficiency disease, which can be associated with autoimmune diseases such as systemic lupus erythematosus, Hashimoto’s disease, or hemolytic anemia. Here we report a case of a chronic recurrent multifocal osteomyelitis coexisting with selective IgM deficiency.

Subscapular abscess after blunt trauma.

Infection around the shoulder girdle is an infrequent and difficult diagnosis requiring a high index of suspicion and early evaluation by the physician. An infection within the area of the subscapularis muscle and the chest wall is extremely rare. To the best of our knowledge, only 4 cases of subscapular abscess have been reported. In this article, we present a 7-year-old boy with a subscapular abscess after blunt trauma.