F Cardella

Stevens-Johnson syndrome and cholestatic hepatitis induced by acute Epstein-Barr virus infection.

She arrived at our clinical division for the exanthema associated with the persistence of fever (4381C). She presented adequate auxological parameters (stature: 90 cm; weight: 13 kg; pubertal stage: PH1B1); pharynx hyperaemia, diffuse and confluent erythemato-pomphoid lesions with hitching; generalized angioedema more severe on the lips; and hepatomegaly. Haematological parameters revealed leukocytes: 10 620/mm; neutrophils/lymphocytes%: 59.8/33.6%; platelets: 342 000/mm; haemoglobin: 12 g/dl; alanine aminotransferase/aspartate aminotransferase: 67/276 IU/ml; g-glutamyl transferase: 201 IU/ml; erythrosedimentation rate (at first hour): 13; and Epstein–Barr virus (EBV) viral-capsid antigen IgM and IgG: positive.

Focal nodular hyperplasia of the liver: an unusual association with diabetes mellitus in a child and review of literature

Hepatic hemangioma, adenoma and focal nodular hyperplasia are the most frequent benign lesions of the liver, but they are all infrequent among pediatric population. The reports of focal nodular hyperplasia in children have recently increased in number, with many cases associated to drug intake, particularly to chemotherapy. We here describe, to our knowledge, the first case of focal nodular hyperplasia in association with diabetes mellitus in childhood.

Infliximab administration effective in the treatment of refractory Kawasaki Disease

Dear Sirs, Kawasaki Disease (KD) is a common vasculitis during the pediatric age. It involves little and medium caliber arteries. A risk of poor outcome is linked to the development of coronary artery aneurysms with sudden thrombo-embolic evolution (1). KD can present either in a classical (fulfilling all the American Reumatism Association (ARA) criteria) or an atypical or an incomplete form. Nowadays, the mainstay therapy for KD consists in high doses of IV administration of Immunoglobulins. Refractory cases, which do not respond to this kind of therapy, are demonstrated (2). Infliximab is a chimerical monoclonal antibody (IgG1) against Tumor Necrosis Factor (TNF) alpha. It belongs to biologic drugs, and it is properly used in the management of IBD, for adult patients in particular. We present a typical case of KD occurred in a 11 months old male child, who did not react both to IVIg administration and methyl prednisolone pulse therapy. A.A. was admitted after 4 days of continuous fever resistant to antibiotic therapy. Cutaneous rash, cheilitis, and conjunctivitis appeared after the fifth day of fever, and neck lymphadenopathy was also present. Phlogistic indexes were high: CrP (12 mg/dl), platelets (650,000/mm). Leucocitosis (WBC 22,000/mm) was present to total blood cell count. The first ultrasound cardiac evaluation showed no specific signs of coronaritis. Ultrasound abdominal evaluation revealed spread gall bladder and a target image of the bowel. A 2 gr/Kg intravenous Immunoglobulins administration was started, together with administration of salicylic acid at 80 mg/kg. The patient did not respond to therapy and fever persisted. A second dose of Ig was administered at the same amount. Ultrasound cardiac evaluation, performed after the first week of disease, showed two light coronary aneurisms. Patient s general conditions got worse. Hepatic serum transaminases also increased (three times normal values). So,methyl prednisolone iv pulse at 30 mg/ Kg was performed for three consecutive days. Fever persisted, CrP (18 mg/dl), platelets (1,400,000/mm), and white blood cells (45,000/ mm) raised. A second cardiac evaluation showed the patient was worsening. As a rescue therapy, Infliximab was started at 5 mg/Kg (3). The total infusion took 6 h and no adverse reaction occurred. The clinical response to Infliximab was excellent. Fever sharply decreased. Twenty-four h after the infusion, CrP (8 mg/dl), white blood cells (21,000), and hepatic serum transaminases (one time and half normal values) strongly decreased. Rash, cheilitis, and conjunctivitis disappeared. Ten days after the infusion, clinical remission persisted and finger desquamation was present to both hands and feet. CrP (0.4 mg/dl), white blood cells, and hepatic serum transaminases reached normal values. The patient was discharged after last cardiac ultrasound evaluation, which expressed a stopped disease, and he entered a strict surveillance follow-up program, ongoing the assumption of salicylic acid at 5 mg/ Kg as antiplatelets aggregation drug. Our report describes the use of Infliximab in the youngest patient affected by refractory KD as long as we know. KD is a reactive inflammatory condition, probably in genetic susceptible individuals (4), and TNF alpha and other pro-inflammatory cytokines may play an active role in its pathogenesis. In particular, patients with refractory KD, who are at significant risk for thromboembolic events because of their higher TNF alpha levels, may also benefit by Infliximab therapy, thanks to the new properties of the biologic drug recently reported by Danese et al. (5) and by Di Sabatino et al. (6). Indeed, Infliximab acts reducing the molecular expression of intestinal endothelial molecules vascular cell Pediatr Allergy Immunol 2010: 21: 1091–1092

Cerebral stroke in a teenage girl with paroxysmal nocturnal hemoglobinuria

We report a case of paroxysmal nocturnal hemoglobinuria (PNH) in a 14 year-old girl presenting a cerebral arterial thrombosis. The initial diagnosis was carential anemia due to menarche following identification of slight macrocytic anemia, leucopenia and mild thrombocytopenia at routine blood analysis. The child was eventually referred to a children’s hospital after the onset of progressive fatigue, anorexia and paleness. Severe anemia (hemoglobin 6 g/dL) with negative Coombs test, mild leucopenia (white blood cells 4.9×109/L) and thrombocytopenia (platelets 97×109/L) and high values of lactate dehydrogenase (2855 U/L) were identified; a packed red cells transfusion was administered. Her condition worsened and she subsequently presented complete right hemiplegia, aphasia and coma; magnetic resonance imaging revealed a massive ischemic lesion. A diagnosis of PNH was eventually made following high sensitivity flow cytometry, which identified a PNH clone (CD66b negative equal to 93.7% of granulocytes). Fast recovery from neurologic and hematological problems occurred in response to anticoagulant therapy and intravenous therapy with eculizumab. We are convinced that PNH should be included in the differential diagnosis of children presenting with cytopenia.

The diabetic ketoacidosis

The Diabetic Ketoacidosis (DKA) is still today a medical emergency in pediatrics. Despite the latest great sensibilization of the population and the doctors, the risk of DKA has not yet been eliminated and this pathology is still occurring in 25 to 40% of diabetes onset cases, in already diagnosed patients with poor compliance (10%), in patients undergoing acute medical or surgical events or in patients in Continuous Subcoutaneous Insulin Therapy (CSII). In toddlers (0-3 years) it is twice more frequent than in the following ages and is characterized by the presence of more serious clinical dehydratation (>10%) and neurological signs (obnubilation 40%). The other category at risk is represented by teen-agers, who may suffer from DKA at diabetes onset (scarce vigilance or reticence on the problems), or in diabetes treatment when there is poor compliance . In affected patients, missed recognition can influence morbility and mortality rates. Despite the improvement in DKA management and therapy, a lot of controversies have been encountered in literature. For the insulin therapy a wide consent exists on the need to use small doses of regular insulin for continuous intravenous administration (0.05- 0.1U/Kg/h). For children hydratation the most recent recommendations are not to overcome 5-10 ml/Kg/h in the first two hours (max 250 ml/h: ISPAD-IDF 2011, ADA 2013) and to continue hydratation slowly calculating the body surface area so as not to exceed 3 lt/mq/day (average 2000-2500 ml/mq/day) . The careful controls of plasmatic electrolytes (opportune integrations particularly of potassium deficit: 20-40 mEq/lt, 50% of KCl + 50% of KPO4) and of glycemia are suggested (to avoid too rapid falls: when glycemia <250- 300 mg/dl replace the sol. NaCl 0.9% N with mixed sol. constituted by 50% of Glucose 10% sol. and 50% of NaCl 0.9% N sol.). The follow-up of clinical patient conditions and the EKG evaluation prevent rapid falls of kaliemia with well-known cardiac consequences . The success of the treatment is nevertheless tightly connected to a correct management of rehydratation, of metabolic acidosis and of electrolyte deficit replacement more than on insulin therapy, aimed at avoiding the most dangerous complication of DKA: cerebral oedema, that seems to be more frequent in patients with more severe onsets, particularly in those with low paCO2 and high levels of urea nitrogen, but seems to be correlated also to the rapid administration of fluids and to the inadequate use of NaHCO3.