Severe dysphagia in children with eosinophilic esophagitis and esophageal stricture: an indication for balloon dilation?

BACKGROUND: Esophageal stricture is one of the most severe complications in eosinophilic esophagitis (EoE). Clinical practice is based on limited data and some treatments are still considered controversial. We report on our experience in the treatment of severe dysphagia and esophageal strictures in EoE, especially using balloon dilation, showing the clinical practice in our pediatric population. PATIENTS AND METHODS: This was a single-center retrospective study between December 2002 to November 2007, identifying all of the pediatric patients with severe dysphagia in the context of EoE. Demographic data and the results of various treatment regimens were reviewed. RESULTS: Severe dysphagia was identified in 13 cases (77% male, mean age 12.8 +/- 4.4 years). Endoscopic findings were mucosal edema (62%), long segment strictures, esophagitis, and off-white appearance in 31%. Histologically, >20 eosinophils per high-power field were present in all of the patients. Medical treatment consisted of proton pump inhibitor PPI (77%), montelukast (31%), local corticosteroids (54%), systemic corticosteroids (8%), elemental diet (15%), and food elimination diet (61%). A combined therapeutic approach was performed in all of the cases, due to clinical relapse or no response to monotherapy. Good response was obtained clinically in 70%, endoscopically in 62%, and histologically in 75%. Relapses were observed in 46% of the cases. Balloon dilation was necessary in 31% of the cases (mean dilation sessions 3.3 +/- 0.95), being effective in 100% of patients, without complications. CONCLUSIONS: In our pediatric series, combined medical (corticosteroids, elemental diet, and food elimination diet) and endoscopic approach (repeated balloon dilation) were effective and safe in patients with severe EoE and esophageal stricture.

'Renal hypersensitivity' to inulin and IgA nephropathy.

Hypersensitivity to inulin (polyfructan) is a rare event; two cases of food allergy and some patients presenting with allergy and hypersensitivity after inulin infusion have been reported. An 11-year-old boy suffering from severe immunoglobulin (Ig)A nephropathy (IgAN) experienced both anaphylactic reaction and concomitant relapse of his nephropathy following inulin infusion, used for measuring glomerular filtration rate (GFR) 2 years after the appearance of his initial symptoms. Pruritus, wheezing and cough were observed during a first renal function test; results of prick and intradermal tests were negative for inulin. The patient presented with pallor, asthenia and oliguria when a second inulin infusion was performed under dexchlorpheniramine, leading to the immediate cessation of the infusion. He was readmitted 2 days later because of fatigue and nausea related to acute renal failure. A drug-induced acute interstitial nephritis was first suspected. However, due to the presence of macroscopic haematuria and proteinuria, a renal biopsy was performed and showed acute proliferative relapse of IgAN. The underlying mechanism of inulin hypersensitivity is not well known. We can hypothesize that inulin had activated the innate immune system. Inulin may, thus, have been the initiating event of the renal relapse, acting like an infection, in a patient with IgA-mediated immunological dysregulation.

[Renal cyst inducing hiccups]. / Kyste rénal responsable d'un hoquet.

INTRODUCTION: Hiccups are a sudden, irregular and spasmodic contraction of the diaphragm followed by an abrupt closure of the glottis. Besides etiologic treatment, its management is above all symptomatic and based primary on medical treatment. CASE: We report a case of chronic hiccups associated with an abscessed voluminous renal cyst. Drainage of the cyst resolved the hiccups. DISCUSSION: Various symptomatic treatments failed because the hiccups were due to irritation of the phrenic nerve by an abscessed renal cyst. This case reminds us that an extensive etiologic work-up may be necessary when symptomatic treatment of hiccups is ineffective.

Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia.

Ongoing studies in B-cell chronic lymphocytic leukemia are evaluating autologous peripheral blood stem cell (PBSC) transplantation in first remission following fludarabine therapy. However, fludarabine could impair PBSC harvest. In 38 patients after frontline oral fludarabine and cyclophosphamide (FDR-CY) therapy, we prospectively evaluated steady state filgrastim- or lenograstim-primed PBSC mobilization to collect 2.0 x 106/kg or more CD34 cells. The first mobilization, performed a median of 178 days (range, 69-377 days) from the last FDR-CY course, was unsuccessful in 32 patients. This result was significantly associated with a low platelet count before mobilization but not with age, interval from last FDR-CY course, initial stage, remission status, or other blood parameters. Finally, after 1, 2, and 3 mobilizations in 27, 10, and 1 patients, 2.0 x 106/kg or more CD34 cells were collected in only 12. Explorations of the mechanism of poor mobilization and adaptation of PBSC harvest policies after fludarabine treatment are therefore warranted.

Active matrix metalloprotease-9 in and migration pattern of dendritic cells matured in clinical grade culture conditions.

Dendritic cells (DC) represent potent antigen presenting cells (APC) that are capable of generating tumor-specific immunity. In DC-based vaccination the migration of the infused DC from the site of injection to the secondary lymphoid organs might be critical to induce an effective immune response. Therefore we analyzed the migrating properties of maturing DC generated from human blood monocytes under culture conditions in compliance with the good manufacturing practice (GMP) guidelines. Highly purified CD14+ monocytes were differentiated into immature DC (iDC), then optimally matured as evidenced by CD83 expression. Time-lapse videomicroscopy and Transwell migration assays performed with or without Matrigel, proved mature DC (mDC) to be highly migrating cells compared to iDC although mDC migratory response varied markedly according to individuals (n= 15). Moreover, as shown by gelatin zymography and ELISA, mDC predominantly expressed both the active form of the matrix metalloprotease-9 (MMP-9) and low amounts of its physiological inhibitor, the tissue inhibitor of metalloprotease-1 (TIMP-1) which may explain their high migrating capacity through Matrigel layers. Macrophage inflammatory protein-3beta (MIP-3beta), strongly increased mDC migration through Matrigel by up-regulating the membrane MMP-9 active form suggesting that injected mDC could be selectively guided to T-cell areas of lymph nodes by this chemokine. Taken together, we demonstrate for the first time that mDC, but not iDC, prepared in clinical grade conditions are both physiologically invasive cells expressing chemokine-active and -sensitive MMP-9, which may be critical for their trafficking through tissues after injection. Consequently, we argue that migration characteristics should be included into a gold standard for DC administrated to patients.

Transient hyperphosphatasemia after organ transplantation in children.

Transient, isolated hyperphosphatasemia is a rare, benign condition of childhood. Few cases have been described in transplant patients. We report six cases: three after liver transplantation and three after kidney transplantation. Such a phenomenon was found to be as benign after organ transplantation as it is in healthy children. Hence, an isolated increase in the serum alkaline phosphatase level following transplantation should not be of concern in this population of patients.