Lorenza Matarazzo

The Dietary Paradox in Food Allergy: Yesterday's Mistakes, Today's Evidence and Lessons for Tomorrow

During the last decades the prevalence of food allergy has significantly increased among children and antigen avoidance still remains the standard care for the management of this condition. Most reactions are IgE-mediated with a high risk of anaphylaxis requiring emergency medications in case of inadvertent ingestion. Recent studies showed that continuous administration of the offending food, rather than an elimination diet, could promote the development and maintenance of oral tolerance. Indeed, intestinal transit of food proteins and their interaction with gut-associated lymphoid tissue (GALT) is the essential prerequisite for oral tolerance. On the contrary, low-dose cutaneous exposure to environmental foods in children with atopic dermatitis and altered skin barrier facilitates allergic sensitization. The timing and the amount of cutaneous and oral exposure determine whether a child will have allergy or tolerance. Furthermore, previous preventive strategies such as the elimination diet during pregnancy and breastfeeding, prolonged exclusive breastfeeding and delayed weaning to solid foods did not succeed in preventing the development of food allergy. On the other hand, there could be an early narrow window of immunological opportunity to expose children to allergenic foods and induce natural tolerance. Finally, the gradual exposure to the offending food through special protocols of specific oral tolerance induction (SOTI) may be a promising approach to a proactive treatment of food allergy.

Old and New Treatments for Pediatric Autoimmune Hepatitis

BACKGROUND Autoimmune hepatitis is a rare inflammatory disease of the liver that most frequently affects children and young adults. It is a multifactorial disease of unknown etiology, characteristically progressive in nature, and if left untreated, may lead to cirrhosis and terminal liver failure. It has been known for several decades now that immunosuppressive treatment convincingly alters the outcome of most patients with autoimmune hepatitis and as such it should be started as soon as diagnosis is made. Primary goals of treatment are: normalization of hepatocellular function, extinction of the hepatic necroinflammatory process, and maintenance of a stable remission, thus preventing progression to cirrhosis and its complications. This article aims to review old and new treatments for this rare chronic disorder, from the oldest and most frequently used treatment consisting of the association of prednisone and azathioprine, to alternative medical treatments, liver transplant and promising medical strategies currently under investigation. RESULT AND CONCLUSION The review will focus on the efficacy and safety profile of each drug, as well as on the published clinical experience with them in pediatric patients with autoimmune hepatitis.

Vanishing Bile Ducts in the Long Term after Pediatric Hematopoietic Stem Cell Transplantation

There are no structured studies on liver histology after hematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinicopathologic features of liver disease in the long term after HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semiquantitative score evaluating inflammation, cholestasis, and ductopenia (bile ducts-to-portal tracts ratio ≤ .5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. We evaluated 131 biopsies taken in 50 HSCTs performed in 47 children (mean age, 9.7 ± 5.2 years). Pre-HSCT chemotherapy was administered in 36 of 50 (72%). GVHD was diagnosed in 17 of 50 (34%). Over time the overall score decreased from a mean of 6 ± 2.7 to 3.25 ± .96 (P < .01), inflammation from 1.22 ± 1.19 to 1 ± 0 (not significant), and cholestasis from 3.9 ± 2.08 to 1.5 ± .58 (P < .01). Ductopenia, found in 113 of 131 biopsies (93%), worsened from .63 ± .35 to .16 ± .14 (P < .01). On multivariate analysis severe ductopenia (ratio ≤ .2) was associated with previous chemotherapy (P = .04), in particular with thiotepa, but not with history of GVHD. Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow-up will reveal whether these patients are prone to late liver-related morbidity and mortality.

Early Onset Bilateral Anterior Uveitis Preceding a Late Manifestation of Juvenile Idiopathic Arthritis: A Case Report

We report the case of a girl, aged 17 years, who was diagnosed at the age of 3 years with a chronic bilateral iridocyclitis. Visual acuity was light perception in the right eye and 20/80 in the left at presentation. The right eye showed a dense cataract as well as a band keratopathy in addition to diffuse posterior synechiae, with neovascular tufts at the pupillary margin. The left eye had a posterior subcapsular opacity, band keratopathy, and posterior synechiae. A 3þ cellular reaction and 2þ flare were found in the anterior chamber of both eyes. Intraocular pressure was within normal range in both eyes. While vitreoretinal structures of the right eye were not visible, those of the left eye showed no alteration. Blood test results did not show any systemic diseases (inflammatory markers and ANA autoantibody were negative); the condition was thus defined as a primary bilateral anterior uveitis. Topical treatment with dexamethasone 0.2%, atropine sulfate 0.5% and systemic therapy with prednisone 1 mg/kg was initiated. After 4 weeks the decrease of visual acuity in the left eye persisted with increased opacity of the lens. Cyclosporine A therapy was initiated (100 mg/ daily) with only slight reduction of intraocular inflammation. A dramatic decrease of uveitis and neovascularization was recorded after addition of thalidomide (50 mg/daily). The left eye regained a visual acuity of 20/50. The effectiveness of thalidomide in this patient was reported in a previous case report. Once inflammation had been controlled, she underwent bilateral cataract extraction with intraocular lenses implantation. Immunosuppressive therapy was then stopped. Visual acuity improved to 20/20 in both eyes. In the following 9 years the patient was examined every 4–6 months. During this period, only 10 episodes of mild recurrent iridocyclitis occurred, especially in the right eye (7 relapses), without any significant reduction of the visual acuity. We treated these episodes only with short-term topical steroids and cycloplegic eyedrops. At the age of 13 years when the patient developed arthritis at the right ankle and left knee, she was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) with good response to NSAID therapy alone. Blood exams showed positive ANA autoantibody (1:640, positive 41:80), with negative antidsDNA. A few months after the onset of the arthritis the patient showed recurrent relapses of bilateral iridocyclitis; she was diagnosed as a case of JIArelated anterior uveitis and treated with topical and systemic corticosteroids. A progressive decrease in the right visual acuity (20/80) was noticed at the age of 15 years, secondary to the presence of cystoid macular edema and confirmed by OCT (Figure 1). Considering this major complication, therapy with infliximab (7 infusions each of 350 mg every 2, 4, and 8 weeks) and methotrexate (MTX) was immediately started without any side effects. Visual acuity promptly rose to 20/20 and cystoid macular edema resolved. After 1 year, when she was 16 years old, a mild relapse of right

Relapse and metastasis of atypical teratoid/rhabdoid tumor in a boy with neurofibromatosis type 1 treated with recombinant human growth hormone

Even though no increased recurrence rate seems to be reported in patients with brain tumors receiving recombinant human growth hormone (rhGH) replacement, in some patients multiple risk factors could put at higher risk for recurrence. In such cases, the decision to start rhGH therapy should be very cautious. A boy with neurofibromatosis type 1 developed an atypical teratoid/rhabdoid tumor (AT/RT) of right cerebellum, treated with surgery, radiotherapy, and chemotherapy. After 3 years of remission, he started rhGH for growth hormone deficiency, having a negative magnetic resonance imaging (MRI) scan. Ten weeks after starting therapy, the boy became symptomatic and MRI showed relapse of AT/RT in the right cerebellum and a new lesion in the brainstem. The boy died of progressive disease. In this case, the connection between AT/RT recurrence and the beginning of rhGH therapy, with a negative pretreatment MRI, cannot be excluded. Additional caution should be used for rhGH in patients with multiple risk factors.