Volume 20, Nº 4 (2024)

The diagnosis and management of metabolic bone disease among children can be challenging. This difficulty could be due to many factors, including limited awareness of these rare conditions, the complex pathophysiology of calcium and phosphate homeostasis, the overlapping phenotype with more common disorders (such as rickets), and the lack of specific treatments for these rare disorders. As a result, affected individuals could experience delayed diagnosis or misdiagnosis, leading to improper management. In this review, we describe the challenges facing diagnostic and therapeutic approaches to two metabolic bone disorders (MBD) among children: hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). We focus on explaining the pathophysiological processes that conceptually underpin novel therapeutic approaches, as well as these conditions’ clinical or radiological similarity to nutritional rickets. Particularly in areas with limited sun exposure and among patients not supplementing vitamin D, nutritional rickets are still more common than HPP and XLH, and pediatricians and primary physicians frequently encounter this disorder in their practices. More recently, our understanding of these disorders has significantly improved, leading to the development of novel therapies. Asfotas alfa, a recombinant, human- tissue, nonspecific alkaline phosphatase, improved the survival of patients with HPP. Burosumab, a human monoclonal anti-FGF23 antibody, was recently approved as a specific therapy for XLH. We also highlight the current evidence on these two specific therapies’ safety and effectiveness, though long-term data are still needed. Both HPP and XLH are multisystemic disorders that should be managed by multidisciplinary teams. Finally, recognizing these conditions in early stages will enable affected children and young adults to benefit from newly introduced, specific therapies.

Phosphate is indispensable for human life and evolutionary changes over several millions of years have established tightly regulated mechanisms to ensure phosphate homeostasis. In this process, calcium and phosphate metabolism have come to be intricately linked together. Three hor-mones (PTH, FGF23 and Calcitriol) maintain the fine balance of calcium and phosphate metabo-lism through their actions at three sites (the gut, the kidneys and the skeleton). Disorders that disrupt this balance can have serious clinical consequences. Acute changes in serum phosphate levels can result in life threatening complications like respiratory failure and cardiac arrythmias. Chronic hy-pophosphataemia predominantly affects the musculoskeletal system and presents as impaired linear growth, rickets, osteomalacia and dental problems. Hyperphosphataemia is very common in the set-ting of chronic kidney disease and can be difficult to manage. A thorough understanding of calcium and phosphate homeostasis is essential to diagnose and treat conditions associated with hypo and hyperphosphataemia. In this review, we will discuss the calcium and phosphate metabolism, aetiol-ogies and management of hypo and hyperphosphataemia.

With advances in neonatal care, bone fractures prior to discharge from the hospital in preterm infants receiving contemporary neonatal care, are rare. Nevertheless, such fractures do oc-cur in very low birth weight and extremely low birth weight infants who go on to develop metabolic bone disease of prematurity (MBDP), with or without secondary hyperparathyroidism. MBDP is a multifactorial disorder arising from the disruption of bone mass accrual due to premature birth, postnatal immobilisation, and loss of placental oestrogen resulting in bone loss, inadequate provi-sion of bone minerals from enteral and parenteral nutrition, and medications that leach out bone minerals from the skeleton. All of these factors lead to skeletal demineralisation and a decrease in bone strength and an increased risk of fractures of the long bones and ribs. Secondary hyperparathy-roidism resulting from phosphate supplements, or enteral/parenteral feeds with a calcium-to-phosphate ratio op < 0.3:1.0 leads to subperiosteal bone resorption, cortical thinning, and further skeletal weakening. Such fractures may occur from routine handling and procedures such as cannu-lation. Most fractures are asymptomatic and often come to light incidentally on radiographs per-formed for other indications. In 2015, we instituted a comprehensive and multidisciplinary Neonatal Bone Health Programme (NBHP), the purpose of which was to reduce fragility fractures in high-risk neonates, by optimising enteral and parenteral nutrition, including maintaining calcium-to-phosphate ratio ≥1.3:1, milligram to milligram, biochemical monitoring of MBDP, safe-handling of at-risk neonates, without compromising passive physiotherapy and skin-to-skin contact with par-ents. The at-risk infants in the programme had radiographs of the torso and limbs at 4 weeks and af-ter 8 weeks from enrolment into the program or before discharge. Following the introduction of the NBHP, the bone fracture incidence reduced from 12.5% to zero over an 18-month period.

Background:Erythema infectiosum occurs worldwide. School-aged children are most often affected. Since the diagnosis is mainly clinical, physicians should be well-versed in the clini-cal manifestations of erythema infectiosum to avoid misdiagnosis, unnecessary investigations, and mismanagement of the disease.

Objective:The purpose of this article is to familiarize physicians with the wide spectrum of clinical manifestations and complications of erythema infectiosum associated with parvovirus B19 infection.

Methods:A search was conducted in July 2022 in PubMed Clinical Queries using the key terms \"Erythema infectiosum\" OR "Fifth disease" OR "Slapped cheek disease" OR "Parvovirus B19". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.

Results:Erythema infectiosum is a common exanthematous illness of childhood caused by parvovirus B19. Parvovirus B19 spreads mainly by respiratory tract secretions and, to a lesser extent, the saliva of infected individuals. Children between 4 and 10 years of age are most often affected. The incubation period is usually 4 to 14 days. Prodromal symptoms are usually mild and consist of low-grade fever, headache, malaise, and myalgia. The rash typically evolves in 3 stages. The initial stage is an erythematous rash on the cheeks, with a characteristic "slapped cheek" appearance. In the second stage, the rash spreads concurrently or quickly to the trunk, extremities, and buttocks as diffuse macular erythema. The rash tends to be more intense on extensor surfaces. The palms and soles are typically spared. Central clearing of the rash results in a characteristic lacy or reticulated appearance. The rash usually resolves spontaneously within three weeks without sequelae. The third stage is characterized by evanescence and recrudescence. In adults, the rash is less pronounced than that in children and is often atypical. Only approximately 20% of affected adults have an erythematous rash on the face. In adults, the rash is more frequently found on the legs, followed by the trunk, and arms. A reticulated or lacy erythema is noted in 80% of cases which helps to distinguish erythema infectiosum from other exanthems. Pruritus is noted in approximately 50% of cases. The diagnosis is mainly clinical. The many manifestations of parvovirus B19 infection can pose a diagnostic challenge even to the best diagnostician. Complications include arthritis, arthralgia, and transient aplastic crisis. In most cases, treatment is symptomatic and supportive. When parvovirus B19 infection occurs in pregnant women, hydrops fetalis becomes a real concern.

Conclusion:Erythema infectiosum, the most common clinical manifestation of parvovirus B19 in-fection, is characterized by a "slapped cheek" appearance on the face and lacy exanthem on the trunk and extremities. Parvovirus B19 infection is associated with a wide spectrum of clinical mani-festations. Physicians should be aware of potential complications and conditions associated with parvovirus B19 infection, especially in individuals who are immunocompromised, chronically ane-mic, or pregnant.

Background:Allergic contact dermatitis (ACD) is prevalent among pediatric population, adolescent and young adults. Patients with ACD experience a lot of sociopsychological and quality-of-life (QoL) difficulties. Children and their caregivers alike are vulnerable to the burden of ACD.

Objective:We have, in this paper, provided an overview of ACD and discussed common and unu-sual causes of ACD.

Methods:We performed an up-to-date literature review in the English language on "allergic contact dermatitis" via PubMed Clinical Queries, using the keywords "allergic contact dermatitis" in Au-gust 2022. The search included meta-analyses, randomized controlled trials, clinical trials, case-control studies, cohort studies, observational studies, clinical guidelines, case series, case reports, and reviews. The search was restricted to English literature and children.

Results:ACD may be acute or chronic and it affects more than 20% of children and adults with significant quality-of-life impairments. ACD is manifested by varying degrees of cutaneous edema, vesiculation, and erythema. The hypersensitivity reaction is one of the most prevalent forms of im-munotoxicity in humans. Localized acute ACD lesions can be managed with high-potency topical steroids; if ACD is severe or extensive, systemic corticosteroid therapy is often required to provide relief within 24 hours. In patients with more severe dermatitis, oral prednisone should be tapered over 2-3 weeks. Rapid discontinuation of corticosteroids can result in rebound dermatitis. Patch testing should be performed if treatment fails and the specific allergen or diagnosis remains un-known.

Conclusion:ACD is common and can be a physically, psychologically, and economically burden-some disease. Diagnosis of ACD is primarily based on history (exposure to an allergen) and physi-cal examination (morphology and location of the eruption). Skin patch test can help determine the causative allergen. Allergen avoidance is the cornerstone of management. Topical mid- or high-potency corticosteroids are the mainstay of treatment for lesions on less than 20% of the body area. Severe cases of ACD may require treatment with systemic corticosteroids.

Background:Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment.

Objective:The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty.

Methods:A search was conducted in September 2022 in PubMed Clinical Queries using the key term \"Premature thelarche\". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article.

Results:Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an \"overactivation\" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty.

Conclusion:Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow-up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.

Background:From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis.

Objective:The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis.

Methods:A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included meta-analyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis.

Results:Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both vi-ruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may on-ly have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID-19 infections (long COVID-19) have been described but not with influenza infections. Mortality as-sociated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease.

Conclusion:Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.

Introduction:Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children’s Hospital.

Methods:A retrospective review of all PICU admissions from April 2019 to May 2021 was per-formed. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary out-comes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher’s exact test.

Results:There were 692 PICU admissions over the study period from April 2019 to May 2021. The crude mortality was 3% (n=24 death cases) in the PICU. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. Eight (57%) patients were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Ten (71%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. IFIs due to Rhizopus or Aspergillus infection (5/14), or in post-haematopoietic stem cell transplant patients (5/14) were as-sociated with non-survival (p = 0.031).

Conclusion:All patients with IFIs managed in the PICU had haemato-oncology diseases or were recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group were associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.