Current Pediatric Reviews (v.10, #4)

A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer by Prasad L. Gawade, Melissa M. Hudson, Sue C. Kaste, Joseph P. Neglia, Karen Wasilewski- Masker, Louis S. Constine, Leslie L. Robison, Kirsten K. Ness (249-262).
Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormonerelated growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics.

Long-Term Outcome of Infants Born Late Preterm by Despoina Gkentzi, Gabriel Dimitriou (263-267).
Late preterm infants are defined as those born between 340/0 and 366/7 weeks of gestation. This population represents a growing proportion of preterm deliveries and traditionally has been neglected as thought to behave similarly to term infants. However, studies in the last decade have shown that they are vulnerable not only during the first few weeks of life but also later on in infancy and childhood. The aim of this review is to summarize the published literature in the field of the long-term outcomes of the late preterm delivery. The main areas that are affected are the respiratory function and the neurodevelopment of these babies due to the early arrest in the lung and brain development, respectively. Moreover, the overall general health of this population is affected in the long-term and ongoing follow up studies are required to provide a better understanding in the field. Continuous efforts should also be made so that the needs of these infants are recognized and managed in a timely appropriate manner.

Autoimmune Hepatitis by Maria Serena Longhi, Giorgina Mieli-Vergani, Diego Vergani (268-274).
Autoimmune hepatitis (AIH) is a severe hepatopathy characterised by female preponderance, hypertransaminasaemia, elevated levels of immunoglobulin (IgG), presence of serum autoantibodies and, histologically, by interface hepatitis. AIH occurs both in adults and children, being particularly aggressive in the latter. According to the type of serum autoantibodies, AIH can be differentiated in two forms: one positive for smooth muscle antibody (SMA) and/or antinuclear antibody (ANA) (type 1 AIH, AIH-1) and another positive for liver kidney microsomal antibody type 1 (LKM-1) (type 2 AIH, AIH-2). These two forms differ with regard to age at onset (earlier in the case of AIH-2), mode of presentation (fulminant hepatic failure more frequently observed in AIH-2) and association with IgA deficiency (more frequent in AIH-2). AIH responds satisfactorily to immunosuppressive treatment (corticosteroids with or without azathioprine) that should be started as soon as the diagnosis is made. Despite immune suppression, some 40% of patients experience relapse and 9% undergo liver transplantation.
Though the exact mechanism leading to loss of immune-tolerance in AIH is still unclear, recent evidence has pointed to a numerical and functional defect of CD4posCD25pos regulatory T-cells as a factor permitting autoaggressive CD4 and CD8 T-cells to react against liver autoantigens. The generation and expansion of regulatory T-cells with liver autoantigen specificity in vitro represents a potential immunotherapeutic tool for the reconstitution of immune-tolerance in AIH without the drawback of pan-immunosuppression.

Rhinitis and Asthma in Children: Comorbitity or United Airway Disease? by Athina Papadopoulou, Dionysia Tsoukala, Konstantinos Tsoumakas (275-281).
The association of rhinitis with asthma symptoms in children is thought to be part of the united airway disease’s theory which proposed three possible explanatory pathophysiological mechanisms: postnasal dripping, naso-bronchial reflex and systemic immune response. However, it is not clear if the relation is a co-morbid, precipitating or triggering condition or an epiphenomenon as an integrated part of the disease. In an attempt to evaluate the association, a review of all articles that were published in the last 10 years which referred to the relation of childhood rhinitis with asthma were analysed, whereas the recent knowledge on physiology and phenotype was reported as background. Even though both diseases share common etiology, epidemiology and immunology, there are important differences between the upper and lower airway system related both to inner organ cytology, immunity and heredity. Allergy seems to be the major causable factor for rhinitis and asthma association; however, ageenvironment interactions enhance the inspection that in preschoolers the diseases coexist, whereas in older children, they represent the manifestation of one united syndrome.

The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.

Pediatric Oral Lichen Planus: Review and Case Report by Preetika Chandna, Vivek Kumar Adlakha, Gautam Singal, Rohit Sharma (292-296).
Oral Lichen Planus (OLP) is one of the most common dermatologic diseases occurring in the mouth with an overall prevalence of 0.5 - 2.2%. Childhood OLP is rare and follows an atypical course. OLP typically presents clinically as bilateral, symmetrical, flat- topped polygonal papules and plaques that may be symptomatic or asymptomatic. The aim of this article is to present a brief review of OLP with a case report of a 7 year old girl with OLP.

Recurrent apnea is common in preterm infants with consequent episodes of loss of effective breathing and the bronchodilator theophylline prevents apnea and reduces the number of apneic attacks. This drug also reduces hypoxaemic episodes. Theophylline acts on the lungs, kidneys and brain. Theophylline inhibits solute reabsorption in various segments of the nephron and a marked diuresis which occurs immediately after the administration of theophylline. This drug ameliorates kidney dysfunction and prophylaxis given early after birth, preventing vasomotor nephropathy. Theophylline reduces brain activity and reduces the spontaneous activity transients and alters the sleep-wake state in pre-term infants. Theophylline is extensively metabolized in premature infants and its major metabolic product is caffeine. The demethylation pathway occurring predominantly in adults is substituted by N-methylation to caffeine in premature infants. The halflife of theophylline is 5-fold longer in neonates than in adults and reaches the adult value at the age of 55 weeks. Theophylline may be administered trans-cutaneously by applying this drug to the back or abdomen of the infants and the mean fractional absorbance at 30 hours is 0.25. Theophylline is present in saliva and the concentration of this drug in saliva is similar to that in plasma, saliva may be used to monitor theophylline concentration. In conclusion, theophylline is a useful drug to treat apnea and ameliorate kidney dysfunction.

Surgical Treatment of Neonatal Mastitis by Periareolar Drainage by Jan-Philipp Stromps, Hong-Sik Na, Gerrit Grieb, Thorsten Orlikowsky, Christiane Kuhl, Norbert Pallua (304-308).
Purpose: Neonatal mastitis is a rare but challenging problem that commonly appears within the first 8 weeks after birth. Abscess formation in an infant’s breast can lead to acute complications and longterm dysfunction. To our knowledge, no publication focuses on surgical techniques and postoperative care to avoid breast scarring in neonates. We herein present our surgical approach by periareolar drainage to avoid this long term complications.
Methods: After reviewing the medical database of our hospital from 2002 to 2012, 11 cases (6 females and 5 males; 10 unilateral and 1 bilateral) of neonatal mastitis were found. Four cases required surgery, performed by periareolar drainage (n = 4, 4:11). Our data were compared with data obtained from a literature review using Medline and Cochrane databases.
Results: In all our patients that underwent surgery, clinical symptoms were reduced directly after surgery. Our results were comparable with those reported in the literature, which included 163 patients (105 [64.42%] required surgery) from seven publications. Regarding our surgical technique, we have not observed any long-term complications during follow up examinations (range 12-116 months postoperative; mean, 77.36 months), which have been reported in the literature.
Conclusions: Even if the acute infection can be cured by parenteral antibiotics and surgical incision if necessary, the longterm problems of scarring after mastitis, especially from surgical incisions at the site of maximum swelling, can lead to severe functional and aesthetic problems. To avoid such scarring, we herein present our surgical approach to mastitis by periareolar drainage.

Laryngeal Inflammation in the Sudden Infant Death Syndrome by Glenis K. Scadding, Christine Brock, Fazila Chouiali, Qutayaba Hamid (309-313).
Abstract: Objective: Sudden infant death syndrome (SIDS) is marked by ’the sudden death of an infant that is unexpected by history and remains unexplained after a thorough forensic autopsy and a detailed death scene investigation’. The cause is unknown.
Excessive subglottic submucosal glandular tissue and excessive sulphated mucus glycoprotein in the larynges of SIDS babies have been previously reported from our institution. We now report on laryngeal immunohistology.
Methods: Larynges from 7 children who died from Sudden Infant Death Syndrome (SIDS) at under 16 weeks of age were examined immunohistologically and compared to those from 8 age- matched control infants who died from other causes.
Results: The SIDS babies had increased inflammatory changes in the laryngeal epithelium and sub- epithelium with raised numbers of cells staining for elastase (p<0.01), EG2(a marker for activated eosinophils) (p<0.01) and CD4(p<0.05) suggesting that some SIDS deaths involve preceding inflammation.
Conclusions: Although death may be sudden and unexpected it appears that, at least in some SIDS victims, there is a preceding inflammatory process in the larynx which may allow hyper-reactivity of laryngeal reflexes and consequent apnoea. This observation concurs with others in the SIDS literature and offers a field for further research and possible prevention.