Common Pediatric Diseases: an Updated Review

Pediatric health has improved over the past decades and there is a decline in deaths caused by infectious diseases. Yet, the top three causes of disease in children younger than 10 years in 2019 include neonatal disorders, lower respiratory tract infections, and diarrheal diseases. While in the adolescence age group, the major causes are road injuries, headache disorders, and self-harm. Preterm birth complications, pneumonia, and birth asphyxia are the most leading cause of death in children under five years. While in the five to nine years of age group, injuries, including road traffic injuries, drowning, burns, and falls, are the leading causes of death.

Rheumatological disorders pose a challenge to clinicians because of multisystemic involvement, relapsing-remitting course, and nonspecific clinical features, which can mimic infections, malignancies, and even genetic disorders. Common symptoms at presentation are joint pain, fever, weight loss, malaise, muscle weakness, rash, and ulcers. While diseases, such as juvenile idiopathic arthritis, juvenile dermatomyositis, and IgA vasculitis, are relatively easy to diagnose because of typical clinical manifestations, others such as systemic lupus erythematosus, scleroderma, and various vasculitides are much more challenging. No laboratory investigation is diagnostic of a particular rheumatological disorder. Investigations, such as antinuclear antibodies and antineutrophilic cytoplasmic antibodies, are associated with a high false-positive rate and should be used judiciously. Most diseases except for Kawasaki disease and IgA vasculitis are chronic and require long-term immunosuppression for control of disease activity. Long-term prognosis has improved over the past few decades due to better immunosuppressive regimens and better monitoring. With an improvement in mortality rates, many children are living into adulthood and facing issues with persistent disease activity and morbidity related to therapeutic regimens. Future research should focus on finding better therapeutic protocols, which should result in further improvements in survival while simultaneously reducing drug toxicity. There is also an urgent need to define better monitoring tools for most rheumatological conditions.

Oral and dental diseases are among the most common problems in children worldwide. If these problems remain untreated, they can have long-term effects on the orofacial system, chewing and speaking abilities, oral health-related quality of life, and overall health status. Dental caries, periodontitis and gingivitis, dental malocclusion, dental trauma, and some oral soft tissue lesions are among the most common oral disorders in children. Early diagnosis and management of these conditions by pediatric dentists and pediatricians necessitate being aware of the clinical manifestations of each disease at every age. Implementing preventive intervention, accurate diagnosis, proper treatment, and performing regular follow-ups are among the key factors for eliminating harmful long-life consequences of poor oral and dental health status in children and adolescents. 

Metabolic Syndrome (MetS) is considered as the presence of clustering metabolic risk factors. It is rapidly increasing in children and adolescents, notably in low- and middle-income countries. It results from a complex interaction of lifestyle, environmental, and genetic factors. Although its universal definition needs to be determined in the pediatric age group, the main components are obesity, dyslipidemia in terms of elevated triglycerides, and elevated blood pressure. Respectively, fatness and fitness have a direct and inverse association with the development of MetS. Various metabolic responses that are involved in the adipose tissue promote a link between obesity, insulin resistance, inflammation, and future atherogenesis. Management of pediatric MetS would need multidisciplinary interventions, including a multicomponent approach, consisting of healthy eating, reducing screen time, increasing physical activity, as well as providing appropriate duration and quality of sleep. Limiting the exposure of pregnant mothers as well as children and adolescents with endocrine disrupting chemicals is beneficial for preventing the development of MetS. Lifestyle modification and family-centered interventions are the first-line approaches in the treatment of MetS, and the use of medication should be considered only for those who fail to reach healthy weight after lifestyle intervention and for those with underlying disease and complications. Prevention and early management of pediatric MetS are of main strategies for primordial/primary prevention of non communicable diseases.

 This chapter examines the basics of pediatric epilepsy syndromes and the new factors in the field that lead to and result from the disturbed function. Some disorders such as febrile seizures and idiopathic seizure disorders are fairly common in children, and pediatricians should be familiar with the approaches used to investigate such disorders. However, others, such as rare genetic diseases, are increasing in incidence due to the recent advances in genetic testing and personalized medicine. Nevertheless, epilepsy syndromes carry significant morbidity and even mortality in children. The advent of new genetic discoveries has also brought forth new lines of management for previously refractory diseases. The truly intractable epilepsy syndromes might be managed with surgery as a final resort.

Epileptic Encephalopathies (EEs) are a heterogeneous group of epilepsy syndromes predominantly seen in neonatal, infantile, and childhood age groups. EEs present with varied signs and symptoms often pose a diagnostic dilemma for the treating physician. The diagnostic complexities imposed by variable age of presentation and overlapping clinical signs and symptoms in EEs are further increased by exhaustive new information from advanced molecular genetic techniques like nextgeneration sequencing. Taking into account all these challenges, the main objective of this chapter is to briefly outline important diagnostic signs and symptoms, EEG, imaging and genetic findings of common neonatal, infantile and childhood-onset genetic epileptic encephalopathies, and secondly, to draw a simple and pragmatic diagnostic algorithm for the diagnosis of genetic epileptic encephalopathies by the treating physicians. Systematic diagnostic algorithms of commonly occurring EEs would not only guide physicians regarding the management of the patients but also help to counsel parents regarding the prognosis, risk of inheritance, and prenatal testing

Myelin is a protective layer that enwraps the axonal terminals and is an essential component of the central nervous system white matter. Loss of myelin leads to conduction block in the axon leading to demyelinating disorders. Inherited poor formation of myelin is known as hypomyelination, and abnormally formed myelin is called dysmyelination. Demyelinating disorders exclude diseases where degeneration of the axon is the initial event and myelin is degraded secondarily. Most neurologists use the term demyelination only for acquired forms of loss of myelin with relative preservations of axons due to inflammation such as multiple sclerosis. Demyelinating disease in children may be monophasic (e.g., acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis) or chronic (multiple sclerosis and neuromyelitis optica). Pediatric multiple sclerosis is the most common demyelinating disorder in children. Recent genetic and clinical researches have significantly improved our understanding of the diverse spectrum of pediatric demyelinating disorders. In this chapter, an updated summary of the current knowledge on the categories, diagnosis, as well as management of pediatric demyelinating disorders has been presented. 

Atopic dermatitis (AD) or atopic eczema is a complex and multifactorial chronic inflammatory skin disease that is characterized by intense itching and recurrent eczematous lesions. It is very frequent, affecting up to 20% of children in developed countries, and its prevalence has increased worldwide. Patients with AD have an increased risk of developing food allergy, allergic rhinitis, and asthma later in life; but may also present other comorbidities. The main symptom of AD is pruritus, which along with sleep disturbance, decreases the quality of life not only in patients but also in their families. Therapeutic options for AD have historically been limited, but recent advances have increased our understanding of its underlying mechanisms, contributing to the development of new therapies. In this chapter, we review the most recent knowledge about etiology, pathophysiology, clinical manifestations, comorbidities, and treatment options of AD.

Henoch-Schönlein purpura (HSP), currently also known as immunoglobulin A (IgA) vasculitis, is the most common vasculitis in children. It is a systemic autoimmune disease mediated by complexes containing abnormal IgA. The cause of HSP is not well known, but the disease is often triggered by an upper respiratory infection in individuals with genetic susceptibility. The diagnosis relies on internationally agreed criteria, including palpable cutaneous purpura of orthostatic location associated with at least one of the following findings: arthralgia/arthritis, gastrointestinal manifestations, leukocytoclastic vasculitis with IgA deposits and/or renal involvement. The skin lesions are essential for the diagnosis. The digestive symptoms, mostly severe abdominal pain, intestinal bleeding, and more rarely, intussusception, maybe the initial and most worrisome clinical component of HSP during the acute presentation of the disease. Nephropathy determines the long-term prognosis. The clinical course of HSP is, in general, favorable. Bed rest results in remission of the purpura that often recurs as the child restarts standing and walking. Corticosteroids are effective, although not usually required, to treat abdominal pain and other severe manifestations. No medical treatment can avoid the possibility of renal involvement that may occur for several months after resolution of the skin lesions. Corticosteroids are used to treat severe forms of HSP nephropathy, which anatomopathologically corresponds to IgA glomerulonephritis. Active research studies are needed to clarify the pathogenesis, the prognostic factors, and the measures to be taken for the prevention and treatment of renal disease.

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune, and multisystem disease. Childhood-onset SLE (cSLE) contributes up to 20% of all cases of SLE and refers to patients who develop the disease before their 18th anniversary. Impressive discoveries in all aspects of the disease emerge every day; one of the most interesting is whether cSLE is a single or a group of diseases, with diverse physiopathologic processes but sharing a rough phenotype. Patients with early onset disease (<5 years), with associated infections and severe disease manifestations, should urge the possibility of monogenic SLE, which represents a small proportion of all cSLE cases, but often with a more complicated clinical course. Despite its being considered a rare disease, the clinical outcomes could be devastating. Patients with cSLE had higher disease activity indexes than adults. Although the survival has improved, it also implies that patients remain a longer period under the effects of the disease. Enormous advances in the understanding of the physiopathological processes are helping to better diagnose children with lupus; still, we are distant to have a perfectly fitted therapy for all our patients. The outstanding efforts of clinicians and researchers to find new therapeutic strategies are encouraging. In this chapter, you will find a concise description of the novel advancements concerning the disease pathogenesis, classification, assessment of disease activity, treatment, and outcomes. 

Mutations in any one of several genes essential for T lymphocyte development and function cause human Severe Combined Immunodeficiency (SCID), a heterogeneous group of monogenic inborn errors of immunity. Newborns with SCID acquire multiple, persistent, and severe viral, bacterial, and fungal infections shortly after birth and rarely reach their first birthday. SCID is a pediatric emergency: with prompt diagnosis and treatment, essentially every baby with SCID could be cured by hematopoietic stem cell transplantation or gene therapy. Most SCID newborns appear normal and healthy at birth, but SCID is always a prenatal disorder of the development of T lymphocytes, and it is already present at birth. Therefore, SCID is detected by newborn screening through measurement of TRECs (T cell receptor excision circles), which counts naïve T lymphocytes, already absent or markedly reduced. The vast majority of newborns worldwide are not yet screened for SCID. The diagnostic approach and the ‘natural history’ of affected infants and their families are now completely different depending on whether or not neonatal screening for SCID is available, apart from the availability/unavailability of SCID therapies (hematopoietic stem cell transplantation, etc.). 

PFAPA- Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome are the most common autoinflammatory syndromes in children. In this chapter, the characteristic manifestation and clinical criteria of PFAPA, which remain the basis of diagnosis, are presented. The therapeutic options and prognosis are discussed in detail.

The developing human liver is embryologically central in embryogenesis. It plays a significant role as a hematopoietic and endocrine organ. During the development, hepatocytes change their phenotype. They vary from blueish cells to cells with an eosinophilic nuance and decreased nucleus to cytoplasm ratio. Apart from congenital abnormalities of this organ and inflammatory conditions that can populate medical charts in childhood and youth, the liver's neoplastic transformation in childhood and adolescence is a rare event. In children younger than three years, the liver's most dramatic neoplasm is represented by the occurrence of hepatoblastoma. It is an embryologic tumor. It retains the suffix “blastoma,” similar to neuroblastoma as any other embryologic tumor. Hepatoblastoma originates presumably from the primitive embryo-fetal progenitors. In this chapter, we update our knowledge of this pediatric tumor, specifically the pathology and the treatment

Each human cell contains a few hundred mitochondria that are essential for aerobic energy metabolism. Among many fundamental metabolic pathways in mitochondria, the oxidative phosphorylation (OXPHOS) or the respiratory chain (RC) represents the final stage in oxidative metabolism. RC is under the dual control of the mitochondrial genome (mtDNA) and the nuclear genome (nDNA). The proper assembly and functioning of the RC involve many steps. The genetic defects in mtDNA, nDNA, and related functions of mitochondria affect the functioning of RC resulting in insufficient energy production and organ dysfunction. Mitochondrial disorders are increasingly recognized. The clinical manifestations vary widely, causing a significant diagnostic challenge. Manifestations range from lesions of single tissue or structure to widespread lesions, including myopathies, encephalomyopathies, cardiopathies, neurogastrointestinal form, psychiatric symptoms, or complex multisystem syndromes. Coenzyme Q10 deficiency may present with isolated proximal muscle weakness. Leigh syndrome and MELAS are the most common clinical multisystem syndromes. The age at onset ranges from neonatal to adult life. The mortality remains high, and the median survival for early onset severe disease is 12years. Initial evaluations include blood transaminases, lactate-to-pyruvate ratio, amino acids, acylcarnitine profile, creatine kinase, and organic acids. Genetic tests are needed for confirmation. Treatment depends on the specific mitochondrial disorder and its severity. In an acute presentation, an infection should be sought and treated promptly. Coenzyme Q10, thiamine, riboflavin, lipoic acid, L-carnitine, Creatine, and L-Arginine are found to be beneficial. Although there are no cures, treatments reduce symptoms or slow the decline in health.