Metastatic Crohn's disease in pediatrics.

INTRODUCTION AND OBJECTIVES: Metastatic Crohn's disease (MCD) is an extraintestinal manifestation of Crohn's disease, with biopsy as fundamental diagnostic tool. There are few references to MCD in children, with a 0.5-1% estimated incidence in adults. There is no consensus about its therapeutic approach. We describe our diagnostic and therapeutic experience in MCD. RESULTS: Four cases of MCD are described in our Pediatric Gastroenterology Unit in a tertiary care hospital. The age at diagnosis was between 7 and 13 years. Lesions appeared before the diagnosis of Crohn's disease in three of them, and during the course of the disease in another one, with genital location in three patients and bilateral pretibial region in the other. All four cases demonstrated non-caseificant granulomas on biopsy. Only two patients used exclusive enteral nutrition therapy with complete resolution, while other two cases received a combination of therapies (corticosteroids, azathioprine, tacrolimus, infliximab and adalimumab) because of recurrence. Only one case required surgery after poor clinical control. CONCLUSION: The MCD is infrequent but must always be included in the differential diagnosis of cutaneous lesions in Crohn's disease, considering it could be the debut of the disease. We will rely on biopsy anyway for definitive diagnosis. In this series the genital region is verified as the most commonly affected in children. The therapeutic approach does not differ from the management of intestinal involvement.

Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant.

Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants.

Esophageal multichannel intraluminal impedance and pH testing in the study of apparent life threatening episode incidents in infants.

INTRODUCTION: The conventional 24-hour pH monitoring is the gold standard for the diagnosis of gastro-esophageal reflux (GER), a possible cause of Apparent Life Threatening Episodes (ALTE). However, multichannel intraluminal impedance (MII) may provide advantages. OBJECTIVES: Comparison of the results of MII and pH monitoring in patients undergoing MII-pH monitoring in the 3-year study period because of having suffered from ALTE. MATERIAL AND METHODS: Prospective study of MII-pH monitoring performed in our unit to infants < 12 months of ageadmitted for ALTE for a 3-year period. RESULTS: Thirty nine patients studied. 2,692 pH monitoring episodes, with median of 24 (IQ: 15-44) episodes/patient, 1.30 (IQ: 0.80-2.60) reflux/hour, 1 (IQ: 0-4) reflux episode > 5 min per patient and clearance of 1.20 (IQ: 0.70-2.20) min/reflux. With pH monitoring analysis, 14 children (35.9 %) could have been diagnosed as GER (8 mild, 4 moderate and 2 severe) based on the classical criteria. MII identified a total of 8,895 events; only 3,219 among them were refluxes, with a median of 75 (IQ: 54-111) per patient, 1.30 (IQ: 1.3-2.6) episodes/hour). With MII-pH monitoring combination there were 21.60 (SD 15.21) acid reflux episodes, 67.33 weekly acid (SD 32.09) and 3.34 (SD 7.23) non-acid, being finally diagnosed 33 patients as GER. CONCLUSIONS: The association of pH monitoring and MII provides additional information that improves GER diagnostic performance without posing any additional risk to the infant patient. The non-acid/weekly acid refluxes, not detected by pH monitoring, account for a high percentage of episodes, this may have diagnostic and therapeutic significance, especially in infants. Further studies are needed to assess the normality of MMI in pediatric patients.

Efficacy and safety of adalimumab in the treatment of Crohn´s disease in children.

OBJECTIVES: to describe the efficacy and safety of adalimumab (ADA) in inducing clinical remission and reducing inflammation of intestinal mucosa in children with Crohn´s disease (CD). METHODS: we carried out a descriptive, observational study with all patients diagnosed with CD and treated with ADA between January 2007 and March 2013. Disease activity was determined using the Pediatric Crohn´s Disease Activity Index (PCDAI), and the degree of mucosa inflammation by fecal calprotectin (FC). RESULTS: sixteen patients were included. Mean age at diagnosis was 10.6 ± 2.5 years, with a mean age at start of ADA treatment of 12.4 ± 1.8 years, and a median of 1.4 years (IQR 0.5-3) duration from CD diagnosis to start of treatment. Twelve patients were naïve to anti-TNF-a. The PCDAI score at start of ADA treatment was significantly reduced at 12 weeks of follow-up (31.25 IQR 26.8-37.5 vs. 1.2 IQR 0.0-5.0; p = 0.001). Similarly, the FC level decreased at 12 weeks (749 µg/g IQR 514-898 vs. 126 µg/g IQR 67.7-239.2; p = 0.02). Surgery was performed in 4 patients. Adverse events were reported in 4 patients. One patient developed lymphoma at 4 years of ADA treatment in monotherapy. CONCLUSIONS: ADA has been shown to be effective in children with moderate-to-severe CD. Treatment benefits should be weighed against side effects. Multicenter longitudinal studies with longer follow-up periods are required to determine the true efficacy and safety of long-term ADA treatment.

[A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease]. / Efectividad y seguridad en nuestro entorno de adalimumab como tratamiento anti-TNF de primera linea en niños con enfermedad de Crohn.

BACKGROUND AND OBJECTIVES: Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term effectiveness of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients. MATERIAL AND METHODS: This is a multicentre retrospective study including anti-TNF naïve paediatric CD patients treated with ADA as first-line anti-TNF. RESULTS: Sixty-two patients (34males), with a mean age of 13.0±2.4years and a disease duration of 7.3 (IQR 2.7-21) months were included. Median wPCDAI was 35 (IQR 24.3-47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline. Clinical remission at week12 was achieved in 50 out of 62 (80.6%) and in 57 out of 60 (95.0%) at week52. Eight patients (13%) reported adverse events. Mean height, growth rate and BMI z-scores improved significantly between baseline and week 52, especially in patients with growth failure. CONCLUSIONS: ADA treatment leads to lasting clinical remission in anti-TNF naïve paediatric patients with CD. ADA significantly improved growth rate in children with CD who had growth delay at baseline.

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors]. / Baja densidad mineral ósea en artritis idiopática juvenil: prevalencia y factores relacionados.

INTRODUCTION: Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. OBJECTIVES: To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. METHODS: Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. RESULTS: A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. CONCLUSIONS: Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover.

Successful Mercaptopurine Usage despite Azathioprine-Induced Pancreatitis in Paediatric Crohn's Disease.

BACKGROUND: Azathioprine [AZA] and mercaptopurine [MP] are recommended for maintenance of steroid-free remission in children with Crohn`s disease [CD]. Azathioprine-induced pancreatitis, an idiosyncratic and major side effect, has been considered as an absolute contraindication for the use of a second thiopurine in IBD patients. MATERIALS AND METHODS: We describe two children with CD in whom MP were successfully trialled after a confirmed azathioprine-induced pancreatitis, being well tolerated in both cases. RESULTS: Two boys [13 and 10 years old] started exclusive enteral nutrition after diagnosis of moderate (Pediatric Crohn's Disease Activity Index [wPCDAI] = 45) and mild [wPCDAI = 35] CD. Both developed an acute mild to moderate pancreatitis after 2 and 3 weeks, respectively, of AZA treatment but recovered fully in hospital after AZA withdrawal. They started on MP treatment without any adverse effect. They were tested for the presence of polymorphisms 238G>C, 460G>A, and 719A>G in the TPMT gene and 94C>A and 21>C in the ITPase. Both patients were wild-type for all tested polymorphisms. CONCLUSIONS: Azathioprine-induced acute pancreatitis should not be considered as an absolute contraindication for the use of MP. Further investigation is required to create a better understanding of the mechanism underlying the adverse events and to allow more possibilities for personalised therapy.

Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.