Stefano Guarino

Paracetamol: a focus for the general pediatrician

Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever in children. This drug has multiple mechanisms of action, but its pharmacodynamic is still not well known. The central nervous system is the main site of action and it mirrors the paracetamol effect compartment. The recommended dosages and routes of administration should be different whether paracetamol is used for the treatment of pain or fever. For example, the rectal route, while being efficacious for the treatment of fever, should be avoided in pain management. Paracetamol is a safe drug, but some clinical conditions and concomitant drugs, which are frequent in clinical practice, may increase the risk of paracetamol toxicity. Therefore, it is important to optimize its administration to avoid overdoses and maximize its effect. The principal mediator of the paracetamol toxicity is the N-acetyl-p-benzo-quinone imine (NAPQI), a toxic product of the paracetamol metabolism, which could bind cysteine groups on proteins forming paracetamol–protein adduct in the liver. Conclusion: Although frequently prescribed, the concept of “effect compartment concentration” and the possible co-factors that could cause toxicity at recommended doses are not familiar to all pediatricians and general practitioners. We reviewed the literature concerning paracetamol mechanisms of action, we highlighted some relevant pharmacodynamic concepts for clinical practice, and we summarized the possible risk factors for toxicity at therapeutic dosages.

Outcomes of a Cohort of Prenatally Diagnosed and Early Enrolled Patients with Congenital Solitary Functioning Kidney

Purpose: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury. Materials and Methods: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated. Results: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p <0.001), respectively. Of congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney resulted in significant risk factors for renal injury (HR 8.75, 95% CI 2.77–27.65). Conclusions: In an evaluation of a large cohort of patients enrolled early with congenital solitary functioning kidney with a prenatal diagnosis, excluding those with neonatal onset of renal damage, the prevalence of renal damage was 3.9%. Among congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney represented the major risk factor.

An infant with hypercalcemia: Questions

A 6-month-old male infant born by normal vaginal delivery (birth weight 3.150 kg, length 49 cm) and affected by hypospadias underwent renal ultrasound scan (Fig. 1). Expert advice was required after an “uncertain renal US report”. The patient suffered decreased appetite, vomiting, constipation, polyuria and polydipsia during the previous 2 months. At our appointment, we found hypotonia, irritability, failure to thrive, anterior fontanelle 1.5×1 cm, and moderate dehydration. His mother reported that the infant was taking no drugs except prophylaxis with vitamin D (400 IU/day). Serum chemistry was as follows: calcium 18.67 mg/dl (normal range, 8.4–10.2 mg/dl), urea 65 mg/dl (10–50 mg/ dl), creatinine 0.45 mg/dl, phosphorus 5.7 mg/dl, Ca×P 106 mg (normal value <55 mg), venous pH 7.38. Na, K, Cl, Mg, HCO3, ABE, glycemia, AST, ALT, γGT, bilirubin, alkaline phosphatase and complete blood count were within normal limits. Urinary electrolyte concentrations: calcium/ creatinine ratio 1.27 mg/mg, uric acid/creatinine 0.45 mg/dl of glomerulor filtration rate, beta2 microglobulin 0.4 mg/l (nv: <0.3 mg/l). ECG, cardiologic and oculistic examination, and blood pressure monitoring were normal. We started hyperhydration (NaCl 0.9 % 7 ml/kg/h) to reduce calcemia. After 12 h, the blood calcium was 15.2 mg/ dl. Therefore we added furosemide (1 mg/kg intravenously twice a day) and methylprednisolone (1 mg/kg once a day). After 4 days of therapy, the blood calcium was 13.8 mg/dl and urinary calcium/creatinine ratio was 2.61 mg/mg. The clinical conditions of the patient improved after 4 days (no vomiting, increased appetite). The serum level of calcium did not decrease after 6 days of therapy with furosemide and methylprednisolone, remaining at 13.8 mg/dl.

Atopic eczema could be a cause and not an effect of cow's milk protein allergy.

T o the Editor: We read with interest the article published in the August 2012 issue of the Journal of Pediatric Gastroenterology and Nutrition entitled Diagnostic Approach and Management of Cow’s-Milk Protein Allergy in Infants and Children: ESPGHAN GI Committee Practical Guidelines (1). The authors considered atopic eczema (AE) as a possible skin symptom of cow’s milk protein allergy (CMPA) and affirmed that in the children with AE are present positive tests for cow’s milk protein-specific immunoglobulin E. We disagree in considering the AE as an expression of CMPA, because, there is an evidence that the AE is a cause, and it is not an effect of food allergy (2–4). A primary alteration of the epidermal barrier leads to increased permeability to food allergens and secondary sensitization mediated by dendritic cell that enhances TH2 polarization (5). In fact, early-onset atopic dermatitis usually emerges in the absence of detectable immunoglobulin E-mediated allergic sensitization (6). We write this letter to emphasize this interesting evidence that could lead, in the future, to a ‘‘Copernican Revolution’’: CMPA, in the future, may no longer be considered among the causes of AE with important changes in the management of the patients with atopic eczema.

Association between 14 bp insertion/deletion HLA-G functional polymorphism and insulin resistance in a cohort of Italian children with obesity

The non‐classical HLA‐class I molecule‐g (HLA‐G) gene shows a deletion/insertion (del/ins) polymorphism of a 14‐base‐pair sequence (14 bp) in the exon 8 at the 3′ untranslated region. The presence of the 14 bp insertion allele has been associated to lower soluble HLA‐G protein production, a protein with anti‐inflammatory activities. So far, no studies have investigated the relationship between HLA‐G 14 bp del/ins polymorphism and metabolic features of obese children and adolescents. We aimed to assess if the HLA‐G ins/del polymorphism, and in particular the HLA‐G ins/ins genotype determining lower sHLA‐G production, is associated to insulin resistance (evaluated by homeostasis model assessment [HOMA]) in a population of obese children.

Patients affected by dent disease 2 could be predisposed to hidradenitis suppurativa

Dent disease 2 (DD2) is a rare X-Linked disorder characterized by proximal tubule dysfunction. It is considered as mild variant of Lowe Syndrome (LS) and both conditions are secondary to OCRL1 gene mutations.1 Mutations in this gene drastically reduce (<10%) inositol polyphosphate 5-phosphatase (OCRL1) activity.1 This article is protected by copyright. All rights reserved.

Congenital solitary kidney size at birth could predict reduced eGFR levels later in life

ObjectivesTo evaluate the impact of congenital solitary functioning kidney (CSFK) length, measured early in life, on the eGFR levels during the follow-up.Study designWe retrospectively selected 162 CSFK patients undergoing, within 60 days of life, renal length (RL) measurement by ultrasound.We divided the population in:Group 1 = RL ≥ 2 standard deviation score (SDS).Group 2 = RL < 2 SDS and showing RL ≥ 2 SDS during the follow-up.Group 3 = RL < 2 SDS and showing RL < 2 SDS during the follow-up.Primary outcome: development of eGFR below the range of normality.ResultsThe median follow-up period of the overall population was 6.2 years (range 2–21.5 years). The cumulative proportion of patients free of primary outcome at 15 years of age was 96.4% in group 1, 64.6% in group 2, and 45.6% in group 3 (p = 0.03).The RL > 2 SDS within 60 days of life was a significant protective factor (hazard ratio = 0.13; 95% C.I. 0.02–0.97) against development of primary outcome.ConclusionRL ≥ 2 SDS within 60 days of life could identify a population of CSFK with reduced risk of presenting reduced eGFR levels later in life.

Cleaning the genitalia with plain water improves accuracy of urine dipstick in childhood

We evaluated, both in toilet-trained and not-toilet-trained children, the impact of cleaning the genital area with plain water on the false positive rate at urine dipstick, and evaluated which factors could be associated to falsely positive findings. We prospectively enrolled 612 patients consecutively attending our nephro-urological outpatient clinic. Firstly, we performed urine dipsticks on urine samples collected from patients whose genital area had not been cleaned before. Then we collected a second sample from the patients with positive urine dipstick, after their genital area had been cleaned with plain water. The urine dipstick was considered falsely positive if we documented its normalization at urine dipstick made on the urine sample collected after cleaning the genital area. We found a falsely positive urine dipstick in 25.5% of the patients, and more in detail in 22.9% of the not-toilet-trained children, and in 26.6% of the toilet-trained children (p = 0.37). The only factors leading to a significant increased RR to have a false positive were non-retractable foreskin (RR = 4.38; 95% CI, 2.15–8.9; p = 0.0001) and female gender (RR = 2.47; 95% CI, 1.77–3.44; p < 0.0001).Conclusion: Cleaning the genital area with plain water should always be performed before collecting urine samples, even if only a urine dipstick without culture is needed.What is Known:• Cleaning the genital area reduces the urine bacterial contamination rate in populations of toilet-trained pediatric patients.• There are no studies assessing the impact of cleaning the genital area on the quality of the urine dipstick, nor on which factors could affect the urine dipstick findings.What is New:• Falsely positive urine dipstick was found in 25.5% of the 612 prospectively enrolled toilet-trained and not-toilet-trained children.• Non-retractable foreskin and female gender significantly increases the relative risk of falsely positive urine dipsticks.

Twelve-year-old boy presenting with recurrent abdominal pain and 25 urinary calculi

: A 12-year-old boy, with intermittent abdominal pain from 3 years of age, presented with increased frequency of right lower quadrant pain (at least three episodes per week over the past six months) and pain during micturition affecting school attendance. His family history included referred urolithiasis. An abdominal ultrasound performed 1 year before our visit showed a small stone of 4 mm in the right renal pelvis for which he did not receive any therapy. The patient brought 25 hard stones with irregular outline, 2-8 mm in diameter, of deep brown/grey colour that he claimed to have found in his underwear (figure 1). On examination, he looked well with normal vital signs and unremarkable cardiorespiratory and abdominal examinations. Plasma creatinine was 0.41 mg/dL (36.1 μmol/L), urinalysis and urine tests were all normal (including 24 hour calcium, phosphorus, oxalate, citrate, uric acid and cystine). Repeat kidney and urinary tract ultrasound showed no evidence of calculi.edpract;archdischild-2018-315073v1/F1F1F1Figure 1Twenty-five hard formations brought along by the patient from home. QUESTION 1: Which is the most likely diagnosis?Cystinuria.Dent disease.Idiopathic urolithiasis.Factitious disorder imposed on self.Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. QUESTION 2: How would you confirm your diagnostic suspicion?Reassurance and clinical follow-up.Mass spectrometry of stones.CT urography.Increase oral fluid intake and administration of potassium citrate. QUESTION 3: How would you manage this condition?Administration of placebo.Psychological consultation.Observed 24 hour urine collection.All of the above. Answers can be found on page 2.

From oliguria to urinary incontinence: a case of Munchausen's syndrome in an adolescent boy.

Abstract Factitious disorders are characterized by physical or psychological symptoms that are intentionally produced or feigned in order to assume the sick role. “Munchausen’s syndrome” is one of these disorders and often is under-recognized or only suspected after unnecessary investigations. We report the case of a 15-year-old boy who came to our notice because of reduced urine output and recurrent abdominal pain during the previous 3 months. The patient attended several emergency room visits and he had been hospitalized for 1 month in an adult internal medicine department because of “oliguria”. He had undergone several invasive investigations with normal results before the diagnosis of Munchausen’s syndrome was made. General pediatricians and practitioners should be aware that suspecting Munchausen’s syndrome in the first instance in the management of a patient showing discrepancies between reported urinary symptoms and the detectable clinical signs could avoid unnecessary and invasive exams.