Andrea Liotta

Biochemical Selection of Prepubertal Patients with Androgen Insensitivity Syndrome by Sex Hormone-Binding Globulin Response to the Human Chorionic Gonadotropin Test

Before puberty, the diagnosis of androgen insensitivity syndrome (AIS) can be difficult. We studied whether the decrease of sex hormone-binding globulin(SHBG) during the human chorionic gonadotropin (hCG) test may represent a biochemical test to select prepubertal patients with AIS. We examined prepubertal patients with AIS (n = 9, age 0.9-8.2 y), male pseudohermaphroditism not due to AIS (other-MPH) (n = 8, age 0.6-10.7 y), and control boys (n = 12, age 0.8-12.5 y). Testosterone and SHBG levels (mean ± SD) were measured before (d 0) and after (d 5) a hCG test (1500 IU × 3 d). Testosterone levels (nmol/L) increased in all groups [AIS: from 1.5 ± 1.2 to 22.1 ± 11.8 (p < 0.001); other-MPH: from 0.6 ± 0.6 to 9.2 ± 7.4 (p < 0.02); controls: from 1.8 ± 1.4 to 22.8 ± 14.4 (p < 0.001)]. SHBG concentrations (nmol/L) did not change in AIS [from 66.2± 15.1 to 67.5 ± 18.6 (p = NS), Δ-variation 1.7± 12.7%], whereas they were significantly decreased in other-MPH [from 59.9 ± 14.2 to 46.5 ± 18.6 (p < 0.005),Δ-variation -23.7 ± 19.6%] and controls [from 63.0 ± 16.9 to 33.7 ± 14.6 (p < 0.003), Δ-variation -46.9± 15.2%]. Our data suggest that the SHBG changes during the hCG test can be used to assess in vivo the biologic response to androgens in prepubertal patients with ambiguous genitalia, selecting those patients in whom it is worth performing second level investigations to confirm the AIS diagnosis.

Plasma levels of lipoproteins and apolipoproteins in congenital hypothyroidism: Effects of l-thyroxine substitution therapy

Thyroid status in humans is an important factor in the regulation of lipoprotein metabolism. There are several data on hypothyroidism in the adult population, but less information is available about congenital hypothyroidism. Since lipid metabolism at birth is substantially different from that of adults, it is not likely that the same abnormalities that occur in adult hypothyroidism are also present when this is diagnosed at early life. We studied 16 subjects with congenital hypothyroidism, seven at the time of diagnosis and also after normalization of thyroid hormone levels over a period of 2.0 +/- 1.0 months of substitution therapy with L-thyroxine (5.9 +/- 1.2 micrograms/kg/d) and nine already on L-thyroxine therapy for a period of 4.7 +/- 3.2 months. Thirty-nine apparently healthy subjects matched for age were selected as controls. In all subjects, total cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol (HDL-C), apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)] thyrotropin (TSH), (LDL-C), total and free thyroxine (T4), and triiodothyronine (T3) were determined. CHO, HDL-C, and apo A-I levels were significantly higher in patients at the time of diagnosis than in controls (respectively, P = .0079, .0007, and .0004), whereas TG, LDL-C, apo B, and Lp(a) levels were not significantly different. During L-thyroxine substitution therapy in these subjects, HDL-C and apo A-I levels significantly decreased (respectively, by a mean of -36.2% and -24.4%), with similar behavior in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Gluten-Free Diet Impact on Leptin Levels in Asymptomatic Coeliac Adolescents: One Year of Follow-Up

Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5–13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M±DS) was: 4.94 ± 5.53 ng/ml. In 10/14 patients (71%) leptinaemia was ≤2 DS for gender and age. In all the patients, after a period of 6–12 months of gluten-free diet, Leptin levels appreciably raised to 10.8 ± 7.9 ng/ml, with a significant correlation to the time of the diet. Leptinaemia was actually lower in patients with a severe mucosal atrophy, and in these patients it increased more significantly after the diet was started. The removal of gluten itself may reduce immunological hit to adipose tissue and the ‘malnutrition’ of adipocytes: leptin can hence increase despite no significant increase of body mass index occurs. This study could partially explain the correlation between body mass index, Coeliac disease and the deregulation of puberty and fertility, mainly in patients who started the diet late. It could also explain the reversibility of this alteration if the cause is removed.

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

A new case of apo C-II deficiency with a nonsense mutation in the apo C-II gene

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction (PCR). The sequence analysis revealed a substitution of adenosine for cytosine at position 3,002 in exon 3, leading to the introduction of a premature stop codon (TAA) at a position corresponding to aminoacid 37 of mature apo C-II. This mutation creates a new Rsa I restriction enzyme site in the apo C-II gene. Amplification of DNA from family members by PCR and digestion with Rsa I established that the patient is a true homozygote for this mutation. The same nucleotide has been substituted for the mutation apo C-IIPadova and apo C-IIBari previously described in two kindreds from Italy. From these data we speculate that base pair 3,002 in the apo C-II gene may represent a hot spot for mutation.

855 Double Blind Placebo Controlled Food Challenge Useful to Disconfirm Over Estimated Diagnosis of Cmpa in Children

Background and aims: The incidence of CMPA in infancy seems to be approximately 3%. In Italy diagnosis of CMPA is often over estimated. The double-blind, placebo controlled food challenge(DBPCFC) is widely considered as the “gold standard” for the diagnosis of food allergy. Methods: 14 patients, (12 months-12 yrs) previously diagnosed as having CMPA, underwent our diagnostic algorithm in order to confirm or to exclude diagnosis. Diagnostic algorithm includes: total blood cell count, serum IgE assay, RAST, betalactotest, Prick by prick with fresh milk, chemical examination and eosinophilic cell count of the stools. DBPCFC was performed with extensively hydrolyzed formula (as placebo) VS a lactose-free, cow milk derived formula. At discharge a post challenge form was given to parents to record delayed symptoms that might occur at home. Results: 12 out of 14 patients had positive results for skin prick test (prick by prick) and four out of them also presented specific IgE against CMPs. 13 patients showed tolerance to CMP during and after DBPCFC and had no symptoms also in the next 72h. Only one patient, aged 30 months, had to keep CMP avoidance. Conclusion: In our survey DBPCFC demonstrated tolerance to CMP for all but one patients. DBPCFC is effective also to disconfirm diagnosis of CMPA. Skin prick tests and serological specific IgE do not always correlate with oral tolerance test. Subjects with positive skin prick test and high serological specific IgE against CMP but tolerant at DBPCFC may reintroduce cow milk proteins in to their dietary meals.

797 Infliximab in the Treatment of Pediatric Ibd: A Single Centre Experience

Background and aims: The biological treatment of IBD acts on different stages of immunophysiopathological processes of the disease. We describe evolution and clinical response to Infliximab in paediatric patients affected by IBD diagnosed and followed at our centre. Methods: In the last triennial period at our Department of Paediatrics in Palermo 53 infusions of Infliximab were administrated to our patients affected by severe forms of IBD. All patients but one were affected by several forms of CD. Only one child was affected by U.C. associated to pyoderma gangrenosum. The total number of infusions were administrated according the ACCENT 1 study at a dose of 5 mg/Kg. All the infusions were preceded by e.v. administration of chlorpheniramine to avoid immunological reactions. The mean length of time of infusion was of 3 hours. Results: Our experience on this biological drug was positive, in fact treated patients showed a good clinical response. None had adverse reactions. Only a 12 years old female patient with fistulising Crohns disease, presented a flare of the disease one year after discontinuation of IFX. Some other patients, several months after the last infusion of Infliximab, were in remission state. Conclusions: Infliximab has a great potential in improving the treatment also of pediatric IBD. However, its role in long-term therapy is not yet clear and it remains to be determined which is the long term tolerability of the drug and to examine if the effectiveness of the drug is reduced or not by the discontinuation of its administration.

PA83 DOUBLE BLIND PLACEBO CONTROLLED FOOD CHALLENGE USEFUL TO DISCONFIRM OVER ESTIMATED DIAGNOSIS OF CMPA IN CHILDREN

Methods: 14 patients, (12 months-12 yrs) previously diagnosed as having CMPA, underwent our diagnostic algorithm in order to confirm or to exclude diagnosis. Diagnostic algorithm includes: total blood cell count, serum IgE assay, RAST, betalactotest, Prick by prick with fresh milk, chemical examination and eosinophilic cell count of the stools. DBPCFC was performed with extensively hydrolyzed formula (as placebo) VS a lactose-free, cow milk derived formula.