Optimizing Antitumor Necrosis Factor Treatment in Pediatric Inflammatory Bowel Disease With Therapeutic Drug Monitoring.

Biological agents have revolutionized inflammatory bowel disease treatment but primary nonresponse and secondary loss of response are common with resulting adverse outcomes. Clinical trials demonstrated an association between serum drug concentrations, as well as the presence of antidrug antibodies, and loss-of-response. Therapeutic drug monitoring (TDM), defined as the evaluation of drug concentrations and antidrug antibodies, is appearing as a strategy to optimize treatment and take full advantage from these drugs. TDM appears to be a promising tool in clinical practice, especially in pediatric patients, who have pronounced fluctuations in the pharmacokinetics of the drugs.The authors present a literature review about antitumor necrosis factor therapy optimization based on personalized treatment strategies according to TDM and possible strategies to recapture loss of response, including an algorithm for practical management.

Perianal Disease and Granulomas: Think Out of the Box .

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency due to a malfunction of NADPH oxidase. It is characterized by recurrent and severe infections caused by catalase-positive microorganisms and autoinflammatory manifestations. Recently, there has been described an NCF4 gene variant that causes a deficiency of p40phox, a subunit of NADPH oxidase. Patients with this deficiency appear to have a less severe clinical form as compared to classic CGD. CASE: A 15-year-old girl with vulvar lichen planus since she was 2 years old and suspected Crohn's disease (CD) was first seen at our hospital. At the age of 12 years, she had been submitted to sacrococcygeal cyst exeresis, without cicatrization of the surgical wound and extension of the lesion to the perianal area. The diagnosis of CD was questioned, and the patient underwent an endoscopic and radiologic assessment, which was normal. A skin biopsy from the perianal area revealed a granuloma; thus, CD with isolated perianal disease was assumed. After several different treatments including antibiotics, infliximab, and adalimumab, the perianal lesion persisted, with no associated gastrointestinal symptoms. Therefore, the hypothesis of an immunodeficiency was considered. An immunologic and genetic study revealed reduced oxidative burst in the phorbol myristate acetate test, with diminished reactive oxygen species production and a homozygous mutation in the NCF4 gene. The adolescent started prophylactic trimethoprim-sulfamethoxazole and became asymptomatic. CONCLUSIONS: The present case highlights that alternative diagnoses to CD must be considered in the presence of isolated perianal disease with granulomatous inflammation, especially when the disease is refractory to conventional CD therapy.

INTRODUÇÃO: A doença granulomatosa crônica (DGC) é uma imunodeficiência primária devido a uma disfunção da NADPH oxidase. É caracterizada por infeções recorrentes e graves causadas por microrganismos catalase positivos e manifestações auto-inflamatórias. Recentemente, foi identificada uma variante do gene NCF4 responsável por deficiência de p40 phox , uma proteína constituinte da NADPH oxidase e clinicamente esta doença manifesta-se como uma imunodeficiência menos grave quando comparada com a DGC clássica. CASO: Adolescente de 15 anos, com líquen planovulvardesdeos2 anos. Aos 12anos, submetida a exérese de quisto sacrococcígeo não tendo ocorrido cicatrização da ferida cirúrgica e com extensão da lesão para a região perianal. Perante a suspeita de doença Crohn (DC), realizada investigação endoscópica e radiológica que foi normal. A biópsia de pele da lesão perianal identificou granuloma, tendo sido admitido o diagnóstico de DC com apresentação perianal. Foi submetida a vários tratamentos sem resolução da lesão. Aos 15 anos, colocada a hipótese de imunodeficiência primária; o estudo imunológico mostrou diminuição da explosão oxidativa no teste de imunidade com acetato miristato de forbol, com produção reduzida de radicais livres de oxigénio (RLO). Geneticamente identificada mutação homozigótica no gene NCF4. Atualmente, sob antibiótico profilático e clinicamente assintomática. CONCLUSÃO: Este caso permite alertar para a investigação de diagnósticos alternativos à DC perante doença perianal isolada com inflamação granulomatosa, em particular quando é refratária à terapêutica dirigida.

Food protein-induced enterocolitis syndrome: a challenging diagnosis.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity triggered by food proteins. It may present acutely, with repetitive vomiting, diarrhoea and lethargy leading to dehydration and eventually shock or insidiously with intermittent emesis, chronic diarrhoea or failure to thrive. We describe a paediatric male patient with recurrent sepsis-like episodes of fever, lethargy, ashen-grey skin colouration and vomiting followed by diarrhoea. These episodes were triggered by cow's milk formula and grains. Laboratory tests revealed leucocytosis, thrombocytosis, metabolic acidosis and elevated C reactive protein. After exclusion of other differential diagnoses, the diagnosis of FPIES was established on clinical improvement with withdrawal of the offending food and positive oral food challenge. FPIES diagnosis requires a high index of suspicion and is frequently delayed, which contributes to an increased morbidity. This is due to the wide spectrum of clinical presentations and due to the absence of specific diagnostic tests.

Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges.

The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis) and treatment difficulties.

Milk-sensitive eosinophilic gastroenteritis in a 2-month-old boy.

Eosinophilic gastroenteritis is a rare disease of unknown aetiology, characterised by eosinophilic infiltration of the gastrointestinal wall with various gastrointestinal manifestations. Clinical presentation and radiological findings are non-specific and there is an overlap with more frequent childhood diseases requiring a high degree of clinical suspicion for accurate diagnosis. We describe a 2-month-old boy with prolonged diarrhoea, vomiting and food refusal. Diagnosis was settled by histology. The treatment with elemental diet was successful, with clinical resolution and catch-up growth.

How important it is to determine the blood pressure in paediatric patients?

The prevalence of hypertension among the paediatric population is 1%-2%. The emergency physician should recognise potentially harmful blood pressure (BP) levels and ensure they are adequately treated, in order to avoid life-threatening complications. A hypertensive emergency is a severely elevated BP complicated by target organ dysfunction (cardiovascular, cerebrovascular and/or renal). Hypertensive urgency, however, is a severe elevation in BP without target organ dysfunction. This distinction is critical for the clinical approach. The authors present a case of a severe hypertension due to primary focal segmental glomerulosclerosis. In this case, the lack of BP measurement in the infant surveillance and the devaluation of an albuminuria detected in a previous routine urine examination, have culminated in a late diagnosis of a severe hypertension, with subsequent effects on target organs.

Necrotising enterocolitis in a full-term infant with reversed diastolic flow in the descending aorta: what is the diagnosis?

Vein of Galen malformations (VGM) are rare intracranial vascular anomalies that constitute 1% of all intracranial vascular malformations. Untreated VGM have a very poor prognosis. A high proportion of patients who present in the neonatal period rapidly deteriorate and succumb to congestive cardiac failure. The prenatal diagnosis and possible in utero referral to highly specialised centre of postnatal care have resulted in considerable improvement in prognosis. The authors present a case of a postnatally diagnosed VGM in a full-term infant presenting with progressive cardiac failure and necrotising enterocolitis secondary to gut hypoperfusion. They emphasise the importance of prenatal diagnosis by pulsed wave Doppler and colour-velocity imaging for subsequent referral to a centre of excellence in a multidisciplinary approach involving neonatologists, paediatric cardiologists and interventional radiologists in order to optimise the management and limit the neurological sequelae in children with this type of malformation.