Biljana Medjo

Tolerability of meropenem in children with IgE‐mediated hypersensitivity to penicillins

Background:  Administration of meropenem to penicillin‐allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross‐reactivity to imipenem, the prototype of the carbapenem class of β‐lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross‐reactivity between penicillins and both meropenem and imipenem in adults.

Non‐immediate hypersensitivity reactions to beta‐lactam antibiotics in children – our 10‐year experience in allergy work‐up

Non‐immediate reactions to beta‐lactam antibiotics (BL) occur more than one hour after drug administration, and the most common manifestations are maculopapular exanthemas and delayed‐appearing urticaria and/or angioedema. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions (DHR), if a drug is taken at the same time. The most of children are labeled as ‘drug allergic’ after considering only the clinical history.

Stevens–Johnson syndrome and toxic epidermal necrolysis in children

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of hypersensitivity reactions affecting the skin. Current terminology is based on maximal extent of epidermal detachment. SJS indicates cases with epidermal necrolysis that involve less than 10% of the body surface area, TEN with more than 30%, and overlap of SJS/TEN in between (1). Clinically, SJS/TEN are characterized by polymorphic lesions like erythematous macules, papules, plaque, vesicles, and bullae with Nikolsky’s sign positive. Oral, genital, and conjunctival mucosae are often involved in the form of erosion or ulceration (2). Fever and malaise are the first symptoms of the disease (3). Incidence of SJS/TEN is 0.05–3 persons per million populations per year (2, 4). Several drugs are highly suspected to cause SJS/TEN in adults, such as anti-epileptics, anti-infective sulfonamides, nonsteroidal anti-inflammatory drugs, nevirapin, allopurinol, and antimicrobials (cephalosporins, aminopenicillins, quinolones, tetracyclines, and imidazole antifungals) (4–12). The list of causative drugs may vary from country to country (4). In children, anti-infective sulfonamides, phenobarbital, carbamazepine, lamotrigine, and acetaminophen are frequently associated with SJS/TEN (12). However, SJS/TEN are rare in children with mortality rate of 7.5% (12). In this article, evaluation of children with SJS/TEN, investigation of causative drug/drugs, treatment, clinical outcome, and complications are presented in three cases.

Association between pet‐keeping and asthma in school children

The role of pet exposure in childhood asthma and allergy is still controversial. The aim of this study was to investigate the association between pet‐keeping during different periods of childhood and asthma and sensitization in school children.

Childhood-onset myasthenia gravis with thymoma.

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.

[Camptomelic dysplasia--a case report].

Campomelic/camptomelic dysplasia is a very rare, severe osteochondrodysplasia characterised by severe skeletal and nonskeletal malformations and lethal outcome mainly in neonatal period. Characteristic abnormality by which the syndrome got its name is short, bowed long bones of lower extremities, most often of femur, manifested by short and bowed legs. Skin dimpling on tibial anterior side is another prominent characteristic of this syndrome. Severe cases are inherited by autosomal dominant trait, by mutation Sox9 gene on chromosome 17, with lethal outcome in the first days of life. Less severe forms of the disease are due to balanced translocation t (13;17) with life span up to the third decade of life. A majority of karyotypic males present as phenotypic females. We report a case of a female neonate, without consanguinity between parents, with characteristic signs of camptomelic dysplasia with short birth length of 46 cm, macrocephaly (head circumference 39 cm), dolichocephaly, hydrocephalus, short trunk and legs. Narrow rib cage, bowed lower extremities, short hand and foot phalanges, nail hypoplasia were noticed. Anterior fontanelle was enlarged, high forehead, face small and flat, hypertelorism, low nasal bridge, micrognathia, low set ears, cleft palate, were found. Characteristc skin dimpling on anterior side of tibia was present on both legs. Bone X-ray studies presented the following changes: anterior bowing of shortened femurs, hip dislocation, cervical vertebrae, scapulas, eleven pairs of slender ribs. Hip luxation. Karyotype was normal for a female, 46 XX. Respiratory insufficiency was present since birth, exacerbated, and led to lethal outcome in the second day of life, as described in the majority of these patients.

Inhaled nitric oxide therapy for acute respiratory distress syndrome in children.

The aim of this study was to evaluate the effects of inhaled nitric oxide (iNO) therapy on oxygenation and mortality in children with acute respiratory distress syndrome (ARDS). Thirty-three children with ARDS and an arterial SatO2 <88% despite mechanical ventilation were analyzed. Patients in the iNO group were prospectively enrolled and treated with conventional therapy plus iNO. The control group consisted of retrospectively analyzed patients treated only with conventional therapy. A significant increase in PaO2/FiO2 ratio (25.6%) and decrease in oxygenation index (19.5%) was observed after 4 h of iNO treatment, when compared to baseline values. A positive response to iNO was detected in 69% of patients, and there was no difference between pulmonary and extrapulmonary ARDS. There was no difference in mortality and duration of mechanical ventilation between iNO and control group.

Spirometric changes in children with asthma exposed to environmental tobacco smoke and treated with inhaled corticosteroids

Background/Aim. Corticosteroids are the most frequently prescribed anti-inflammatory treatment in asthma. A purpose of this study was to compare the spirometric parameters as a response to inhaled fluticasone propionate (FP) treatment in children with asthma, exposed and nonexposed to environmental tobacco smoke (ETS). Methods. The study included 527 children aged between 1 and 16 years with persistent asthma divided into the groups of ETS exposed (ETSE, n = 337) and ETS free (ETSF, n = 190) children. Spirometry was performed before (1st set of results) and after 6 months of FP treatment (2nd set of results). Good lung function (GLF) was defined as forced expiratory volume in one second (FEV1) ≥ 85%, and “poor lung function” (PLF) as FEV1 < 85%. Results. Among the ETSE children, 208 had one smoking parent, 129 had two, 228 had smoking mothers and 238 smoking fathers. The ETSE children received a higher FP dose (p < 0.0001) which was increased with the increase of the number of smokers in the family. The ETSE children had significantly lower lung function both in the 1st and 2nd sets of tests compared to the ETSF children (p < 0.05). After the FP treatment, both groups improved all spirometric parameters (p < 0.001). In the 2nd set of the spirometric tests, the children of smoking mothers had lower spirometry values compared to the children of smoking fathers (p < 0.05). The proportion of the children improving from the PLF to GLF after 6 months of FP was much higher among the ETSF than the ETSE children (p < 0.05). Conclusions. The ETSE children had lower spirometric values before FP. After 6-months of the FP treatment children in both groups improved the spirometric values, but the improvement was higher in the ETSF children.

Congenital diaphragmatic hernia – a Belgrade single center experience

Abstract Objective: Though the outcome for children with congenital diaphragmal hernia (CDH) is improving, management of seriously compromised respiratory and cardiovascular function remains a great challenge. The aim of this study was to review a tertiary center experience in treating children with CDH. Design: Retrospective observational study from January 2005 to December 2014. Setting: Neonatal Intensive Care Unit (NICU) of University Children Hospital (UCH), Belgrade, Serbia. Patients: Children with CDH. Results: The CDH was diagnosed prenatally in 23% patients. An overall survival rate was 62%. Among those patients who underwent surgical repair 29 (90%) survived. There was statistically significant difference in survival rate between operated patients and total examined population (P=0.020). Prenatally diagnosed neonates with CDH had significantly lower survival rate comparing to those who were postnatally diagnosed (20% vs. 75%; P=0.002). Fatal outcome was more frequent in patients with small birth weight comparing to those with normal birth weight (67% vs. 30%; P=0.046). Conclusions: Our center survival rate for CDH is in accordance with other reported studies. Based on our experience there are potential points for further improvement. First, further increase of prenatal detection, planning for delivery, and coordinated transfer to tertiary institution, in order to avoid transfer of near death patients. Second, preoperative management in the NICU. This could be done by more uniform implementation of current consensual guidelines in monitoring, mechanical ventilation and circulatory support of these delicate patients, together with rationale use of newer therapeutic resources.

Autosomal recessive polycystic kidney disease: Case report

INTRODUCTION Autosomal recessive polycystic kidney disease is the most common heritable cystic renal disease occurring in infancy and childhood. The clinical spectrum of signs and symptoms of this disease is widely variable ranging from perinatal death to a milder progressive form, which cannot be diagnosed until adolescence. CASE OUTLINE A female neonate born in the 35th/36th week of gestation. The findings of all standard medical examinations of the neonate done by the mother were within normal limits. A few days before delivery physicians at a regional medical centre revealed enlarged kidneys and oligohydramnios. The delivery was performed by caesarean section. The vital functions of the newborn were in critical condition so that she was referred to the University Childrens Hospital in Belgrade. Soon after admission, despite all undertaken measures, the infant died. Autopsy was done at the Institute of Pathology of the Belgrade Clinical Centre. All findings were typical for autosomal recessive polycystic kidney disease. The kidneys were hugely enlarged, with cystically dilated collecting ducts that almost completely replaced the renal parenchyma. The lungs were mildly hypoplastic. The liver showed dilated portal spaces, with multiple irregularly branching bile ducts. The cause of death was respiratory distress and renal failure. CONCLUSION In all cases of congenital anomalies of the kidney with lethal ending it is necessary to perform autopsy and aimed genetic investigation.