Lorenzo Calligaris

The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever

Colchicine is the treatment of choice in familial Mediterranean fever (FMF) for the prevention of both attacks and secondary amyloidosis. The overall nonresponder rate is about 5–10%. Anakinra is known to have good effectiveness in a severe autoinflammatory syndrome [chronic infantile neurological cutaneous and articular (CINCA) syndrome] and other recurrent hereditary periodic fevers. Pyrin—the protein involved in FMF—has a role in activating the proinflammatory cytokine interleukin (IL)-1β. We report the effectiveness of the addition of an IL-1-receptor inhibitor (anakinra) to colchicine in controlling the febrile attacks and acute phase response in an adolescent with FMF resistant to colchicine.

Diagnostics and Therapeutic Insights in a Severe Case of Mevalonate Kinase Deficiency

Mevalonate kinase deficiency is a rare inborn disorder of isoprenoid and sterol biosynthesis characterized by a recurrent autoinflammatory syndrome and, in most severe cases, psychomotor delay. Clinical manifestations can be very complex and, in some cases, mimic a chronic inflammatory disease. Diagnosis is also complex and often requires immunologic, genetic, and biochemical investigations. There is no standardized therapy, but biological agents could help to control inflammatory complaints in some cases. A severe case of mevalonate kinase deficiency that was associated with nephritis and successfully treated with anakinra (interleukin 1 receptor antagonist) is reported here, and new insights into diagnosis and therapy of this complex disorder are discussed.

Current concepts in management of pain in children in the emergency department

Pain is common in children presenting to emergency departments with episodic illnesses, acute injuries, and exacerbation of chronic disorders. We review recognition and assessment of pain in infants and children and discuss the manifestations of pain in children with chronic illness, recurrent pain syndromes, and cognitive impairment, including the difficulties of pain management in these patients. Non-pharmacological interventions, as adjuncts to pharmacological management for acute anxiety and pain, are described by age and development. We discuss the pharmacological management of acute pain and anxiety, reviewing invasive and non-invasive routes of administration, pharmacology, and adverse effects.

Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed Patient

A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.

Re: Tramadol can selectively manage moderate pain in children following European advice limiting codeine use

was present in 114 (49.1%) of patients. While 48 (20.7%) of the patients were addicted to opioids other than tramadol, a large group of patients only abused tramadol on a regular basis (3). The present review may have been more beneficial if the authors had reviewed tramadol intoxication as well, as it seems that toxicity and further respiratory depression or seizure may occur just above the therapeutic dose. A 4to 6-h observation period is recommended for asymptomatic patients, but the data are limited and need to be re-evaluated thoroughly and carefully. I agree with the authors that many of these complications may refer to a high proportion of gene duplication in some regions. As a result, the generalisability of the data quoted in our country may be limited by differences in the frequency of specific genetic polymorphisms in Middle Eastern population compared to other populations. This may result in increased metabolism of the M1 metabolite.

Efficacy of clonidine in hyperammonemia induced hyperexcitability syndrome

and patient was discharged home a week later. Because of the large head, a pressure gradient exists between the heart and the veins of the head in infants predisposing them to VAE (1). We hypothesize that the sudden decrease in raised ICP upon CSF drainage led to rupture of a bridging vein or emissary veins, resulting in venous air embolism (VAE). The reappearance of signs of air embolism after the reintroduction of nitrous oxide was probably because of the expansion of the air which was still present in the circulation (2). Change in position from supine to prone might have played a role in the recurrence of VAE symptoms as well. The change in position could have caused the air bubbles present in the upper part of the right atrium to have floated into the right ventricular out flow tract and subsequently to the pulmonary arteries and pulmonary arterioles producing the symptoms of the second VAE. As compared with hypoxia, tachycardia and hypotension are the most common initial signs of VAE (3). An episode of VAE severe enough to cause hypoxia is likely to be preceded by hemodynamic instability, which was conspicuously absent during the first episode. We suspect pulmonary hypertension following air entrainment resulted in shunt reversal causing hypoxia. Absence of tachycardia and hypotension during the first episode was most likely because of the preservation of sufficient blood flow from right to left atrium preserving adequate cardiac output (4). During the second episode of VAE, the occurrence of hypoxia preceding fall in EtCO2 was most likely because of the persisting pulmonary hypertension. Readministration of the nitrous oxide at this stage aggravated the preexisting pulmonary hypertension resulting in the reappearance of the right to left shunt before the increase in dead space. In presence of right to left shunt, fall in EtCO2 normally seen with VAE, may be absent due to the relatively well preserved left heart filling (4). PFO is very common in newborns and infants (5). Our case emphasizes that because of the high prevalence of PFO in newborn and infants, the signs of VAE in this group may be unusual and a high index of suspicion is needed for timely diagnosis. The increased chance of shunt reversal following hypoxia, hypercarbia, and acidosis predisposes them to the development of paradoxical air embolism with grave consequences. In light of this experience, we also caution the readers against the reintroduction of N2O when a VAE has been suspected earlier, even when all symptoms have abated.

Acute Pseudotumoral Hemicerebellitis in a Child A Rare and Distinct Entity

A pseudotumoral presentation of acute hemicerebellitis is rare in pediatric age. The authors report a new single case study of a 7-year-old child with pseudotumoral unilateral cerebellitis mimicking an intracranial tumor, which clinically presented itself with signs of intracranial hypertension and mild contralateral hemiparesis, completely recovered after anti-inflammatory therapy. Brain magnetic resonance imaging (MRI) was essential for the differential diagnosis between inflammatory and neoplastic processes. The literature highlighting specific clues about pseudotumoral hemicerebellitis as a distinct clinical and radiological entity is reviewed.

Narrative review shows that the short-term use of ketorolac is safe and effective in the management of moderate-to-severe pain in children

In June 2013, the European Medicine Agency recommended limiting codeine use in paediatric patients, creating a void in managing moderate pain. We reviewed the literature published in English (1985–June 2017) on the pharmacokinetic, pharmacodynamic and safety profile of ketorolac, a possible substitute for codeine and opioids, for treating moderate‐to‐severe pain. We found that gastrointestinal side effects were mainly reported with prolonged use, significant bleeding was reported in adenotonsillectomy, and adverse renal effects appeared to be limited to patients with specific coexisting risk factors.

Inclusion cyst of anterior fontanelle

A 10-month-old girl presented with a soft swelling over the head vertex noted at the age of 2 months (figure 1). Physical examination showed a well-defined mass of 2.5 cm × 1.5 cm covered by undamaged skin. The lesion was neither pulsating nor painful. Ultrasonography showed a subcutaneous hypoechogenic cystic lesion without vascularisation. MRI showed a homogeneous T1-weighted hypointense and T2-weighted hyperintense non-vascularised mass without intracranial extension (figure 2); CT scans …

Risk of hospitalisation after early-revisit in the emergency department

Early‐revisits are frequent in the paediatric emergency department (ED) setting, but few data are available about early‐revisited patients. The aim of this study was to investigate the hospitalisation rate of a population of early‐revisited patients and to detect if an early‐revisited patient was at risk of a more severe disease.