COVID-19 and children with Down syndrome: is there any real reason to worry? Two case reports with severe course.

BACKGROUND: Down syndrome (DS) is characterized by a series of immune dysregulations, of which interferon hyperreactivity is important, as it is responsible for surging antiviral responses and the possible initiation of an amplified cytokine storm. This biological condition is attributed to immune regulators encoded in chromosome 21. Moreover, DS is also characterized by the coexistence of obesity and cardiovascular and respiratory anomalies, which are risk factors for coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CASE PRESENTATION: A total of 55 children were admitted to the pediatric ward in Bergamo, between February and May 2020 for COVID-19. Here, we describe the cases of two children with DS and a confirmed COVID-19 diagnosis who had a severe course. In addition, both cases involved one or more comorbidities, including cardiovascular anomalies, obesity, and/or obstructive sleep apnea. CONCLUSIONS: Our observations indicate that children with DS are at risk for severe COVID-19 disease course.

Dietary protein-induced proctocolitis in childhood.

Cow's milk protein-induced proctocolitis presents with overt rectal bleeding in otherwise healthy infants and is characterized by an eosinophilic infiltrate of the left colonic mucosa. Although it is the most common cause of proctocolitis in infancy, dietary protein-induced proctocolitis had hardly ever been reported in childhood so far. We hereby report 16 otherwise healthy children aged 2-14 yr, who presented over a 6-yr period with persistent or recurrent rectal bleeding related to a mild form of left-sided colitis characterized by a prominent eosinophilic infiltration, focal lymphoid follicle hyperplasia, and a prompt clinical and histological response to a cow's milk-free diet. No patient had a history of food-induced proctocolitis during infancy, and most patients did not show an IgE-mediated response to cow's milk protein. Half of the patients did have other gastrointestinal symptoms, but no systemic symptoms were present and other causes of colitis were excluded by appropriate investigation. Tolerance to cow's milk protein developed in half of the patients within a year. Dietary protein-induced proctocolitis is a relatively common cause of overt rectal bleeding in childhood, and its features are remarkably similar to those of dietary protein-induced proctocolitis of infancy.

Colonic lymphoid nodular hyperplasia in children: relationship to food hypersensitivity.

BACKGROUND & AIMS: The clinical significance of lymphoid nodular hyperplasia (LNH) of the lower gastrointestinal tract is unclear. The aim of this study was to define the frequency and clinical significance of LNH in pediatric patients undergoing colonoscopy. METHODS: Two hundred forty-five children (101 male, 144 female; median age, 8.5 years) for whom colonoscopy had been indicated were evaluated during a 3-year period. Apart from ileocolonoscopy with biopsy, all patients underwent routine biochemistry, serum total and specific IgE, and/or skin prick tests for food allergens. Patients with LNH underwent elimination diet and subsequent food challenges. RESULTS: LNH was observed in 73 of 245 (30%) consecutive colonoscopies. LNH was the only abnormal finding in 52 of the 73 cases (71%). In 43 of these 52 patients a diagnosis of cow's milk or multiple food hypersensitivity was made. Food allergy was significantly more common than in patients without LNH (83% vs 31%; P < .0001). The patients with LNH and food hypersensitivity presented hematochezia (P < .0001), elevated serum anti-beta-lactoglobulin IgG (P < .0001), anemia (P < .005), and failure to thrive (P < .03) more frequently than those without LNH. In the LNH patients histologic examination showed a higher number of lymphoid follicles throughout the colon and the terminal ileum and an increased number of lamina propria and intraepithelial eosinophils. CONCLUSIONS: The presence of LNH in the colon and/or terminal ileum is a frequent finding in symptomatic children undergoing colonoscopy. Unless associated with other specific endoscopic or histologic lesions, LNH is related to a condition of delayed-type food hypersensitivity.

Pulmonary aspiration shown by scintigraphy in gastroesophageal reflux-related respiratory disease.

OBJECTIVES: Gastroesophageal reflux (GER) may underlie respiratory manifestations via vagally mediated airway hyperresponsiveness or microaspiration, and intraesophageal pH monitoring is generally used to identify GER in patients with such manifestations. We aimed to establish the frequency of retrograde pulmonary aspiration in patients with unexplained respiratory manifestations. METHODS: Fifty-one patients with refractory respiratory symptoms (cough, n = 18; pneumonia, n = 14; apnea, n = 8; asthma, n = 7; and laryngitis, n = 4) were prospectively evaluated. They underwent 24-h intraesophageal pH monitoring and gastroesophageal 99Tc scintigraphy with lung scan 18 to 20 h after the test meal. RESULTS: Thirteen of 51 patients (25.5%) had abnormal intraesophageal pH study results (mean reflux index, 11.3%; range, 6.5 to 50%); and in 25 of 51 patients (49%), overnight scintigraphy showed pulmonary aspiration. Nineteen of these 25 patients had entirely normal pH study results, whereas 6 of 13 patients with abnormal pH study results had aspiration. Pulmonary aspiration was demonstrated in all patients with apnea and 61.5% of patients with recurrent pneumonia. Nine of 25 patients (36%) with aspiration had histologic evidence of esophagitis, whereas histologic esophagitis was present in 5 of 13 patients (38.4%) with pathologic GER as shown by intraesophageal pH monitoring. CONCLUSIONS: Pulmonary aspiration as demonstrated by overnight scintigraphy is common in children with unexplained and refractory respiratory manifestations, suggesting that GER could be the underlying cause of these manifestations. Since only a few children with chronic or recurrent respiratory symptoms have a pathologic gastroesophageal acid reflux, a normal intraesophageal pH study result does not rule out GER in these children.

Risk-adapted Treatment for Severe B-Lineage Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation in Children.

BACKGROUND: Optimal management of posttransplant lymphoproliferative disease (PTLD) remains to be defined due to heterogeneity of this condition and lack of predictors of the outcome. Here we report our experience with pediatric PTLD nonresponsive to immunosuppression (IS) withdrawal, managed after stratification into high and low risk according to the presenting features. METHODS: This is a single-center retrospective review of prospectively enrolled patients. From 2001 to 2011, 17 children were diagnosed with severe B-lineage, CD20+, PTLD after a median of 37 months (range, 5-93) from liver (12), heart (4), or multiorgan (1) transplantation. Treatment was tailored on 2 risk groups: (1) standard-risk (SR) patients received IS reduction and rituximab; (2) high-risk (HR) patients received IS discontinuation, rituximab and polychemotherapy. RESULTS: The cumulative incidence of rejection at 1 and 5 years after the diagnosis of PTLD was 35% (95% confidence interval [95% CI], 18-69%) and 53% (33-85%), respectively, whereas the disease-free survival at 1 and 5 years was 94% (95% CI, 65-99%) and 75% (45-90%), respectively. Three children died, PTLD-free, from different transplant-related complications: primary nonfunction after retransplantation (liver), cytomegalovirus disease 21 months after PTLD treatment (liver), graft dysfunction 25 months after PTLD (heart). CONCLUSIONS: Severe B-lineage PTLD after solid organ transplantation may be classified as SR or HR and treated accordingly with a tailored protocol obtaining a satisfactory long-term outcome. This approach accomplishes the control of lymphoproliferation in severe forms as well as the minimization of toxicity in milder PTLDs.

Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy.

OBJECTIVES: It is generally believed that in gluten-sensitive enteropathy or celiac disease (CD), mucosal lesions may have a patchy distribution. We wanted to verify this concept and establish whether one or more biopsy samples are needed in order to make a correct diagnosis of CD. METHODS: One hundred and twelve consecutive children with positive antiendomysium (EMA) or antitissue transglutaminase (tTGA) antibodies, referred to us for suspected CD, were enrolled in a prospective fashion. During upper GI endoscopy four to five biopsies were taken from Treitz and/or distal duodenum (D3), intermediate duodenum (D2), proximal duodenum (D1), and duodenal bulb (B). Histologic lesions were classified according to Marsh criteria modified by Oberhuber. RESULTS: A total of 110 patients, all HLA-DQ2 or DQ8 positive, had a final diagnosis of CD (59 classic, 28 atypical, and 23 silent): 102/110 (92.7%) had type 3 lesion-(a) mild, (b) moderate, or (c) severe-in at least one site and 94/110 (85.4%) had villous atrophy (VA) of some degree in all sites. VA of identical degree was present in all biopsy sites in 55/110 (50%) patients. Total VA (type 3c) was present in at least one site in 85/110 (75%), in all sites in 50/110 (45.4%), and significantly increased in aborad direction ((chi(2) > 26.22 with (= 0.01 and d.f. (degrees of freedom) = 12). Eight out of 110 (7.2%) CD patients had exclusively type 1 or 2 lesions, no patient had lesion variability >1 degree and none had normal biopsies. There was no correlation between type or distribution of histologic lesions and clinical presentation of CD. CONCLUSIONS: Mucosal atrophy is present in 85% of patients with CD and total VA is significantly more frequent in distal duodenum or proximal jejunum. Fifty percent of patients have identical VA throughout the duodenum and no duodenal areas are histologically normal. In genetically susceptible children with positive serology, a diagnosis of CD can reliably be made even if biopsies are not taken from the distal duodenum or jejunum.