Paediatria Croatica is a quarterly medical journal focused on publishing original research, case reports and review articles in pediatrics. With an open-access model and indexed in Scopus and Embase, it aims to reach healthcare professionals globally. The journal promotes collaboration and exchange of ideas among professionals and accepts manuscripts in Croatian or English. Rigorous peer review ensures scientific accuracy and reliability, covering a wide range of pediatric topics, from neonatal care to adolescent health.
Klinika za dječje bolesti Zagreb/Children's Hospital Zagreb
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Sudden dyspnea and chest pain in an adolescent: an unexpected diagnostic outcome
Introduction: Acute onset of chest pain and dyspnea in adolescents is an emergency and often a diagnostic challenge. In the differential diagnosis, one of the possible causes of a sudden onset of chest pain and dyspnea is spontaneous pneumomediastinum (SPM). The most common causes of SPM are asthma exacerbation and lower respiratory tract infections. Other predisposing causes are trauma, vomiting, cough, Valsalva maneuver, helium inhalation from a balloon, use of e-cigarettes and vape devices, and drug inhalation. We will present a case of sudden onset of chest pain in an adolescent caused by SPM, which we believe was caused by the consumption of an e-cigarette or vape device. Case report: A 17-year-old male was examined in the pediatric emergency department due to the sudden onset of stabbing chest pain lasting one day, with shortness of breath and a dry cough. From the anamnestic data, we learn that the pain first occurred during physical exertion (stacking wood) and that he smokes an e-cigarette. He denies allergies and asthma. He had not been recently ill. Upon examination, the young man was in good general condition, with cardiopulmonary compensation and normal oxygen saturations on room air, and was afebrile. The chest was sensitive to palpation in the sternum area, with no signs of subcutaneous emphysema. Auscultation revealed normal breath sounds and normal lung sounds on percussion. Radiological work-up (heart and lung X-ray, MSCT of the chest) revealed pneumomediastinum, from the soft tissues of the neck almost to the diaphragm. Laboratory work-up revealed a slightly elevated CRP with a normal complete blood count, acid-base status, normal immunoglobulin, and alpha-antitrypsin values. Skin prick test for inhaled allergens was negative for all tested allergens. He was hospitalized for further observation. Symptomatic therapy and rest were continued during the stay, and gradual recovery of symptoms was monitored. In conclusion, we believe that this is a spontaneous pneumomediastinum most likely caused by the consumption of an e-cigarette or vape device. He is discharged home with recommendations for rest, the use of analgesics as needed, and avoidance of e-cigarette and vape device consumption. Conclusion: SPM caused by the use of vape devices is rare, but with the increasing consumption of such devices, its incidence is increasing, especially in adolescents and young adults. It is known from the literature that the use of vape devices is also associated with more severe clinical conditions, such as spontaneous pneumothorax, pneumorrhagia, and diffuse alveolar hemorrhage, which shows that the use of vape devices in patients with sudden chest pain is an important anamnestic data point.
Chest Pain; Dyspnea; Mediastinal Emphysema; Electronic Nicotine Delivery Systems; Vaping
Copyright (c) 2026 Vinka Knezović, Ana Tripalo Batoš, Ivan Pavić, Maja Bosanac https://creativecommons.org/licenses/by/4.0
Persistently elevated transaminases in a clinically healthy girl – a case report
Introduction: Wilson's disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene, resulting in reduced copper excretion from hepatocytes into bile and its subsequent accumulation, primarily in the liver and central nervous system. The clinical picture includes hepatic, neurological, and psychiatric manifestations. In childhood, the most common presentation is hepatic, often in the form of asymptomatic elevation of aminotransferases. Case: A six-year-old girl, with normal growth and development, without any complaints, came for treatment of elevated aminotransferases. Elevated liver enzyme values ​​were first noted during a respiratory infection, and control findings over 7 months show an increase in alanine aminotransferase (ALT) (maximum 12 times above the upper limit of the reference interval) and mild elevations of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) with normal parameters of liver synthetic function and bilirubin. Infectious and autoimmune causes were ruled out by differential diagnostic processing, lipidogram, alpha-1 antitrypsin, and thyroid hormone values ​​were normal. Ceruloplasmin was normal, but the excretion of copper in the 24-hour urine was elevated, and the finding of the penicillamine test was pathological, so a liver biopsy was performed, the findings of which established macrovesicular steatosis and mild fibrosis with a significantly increased concentration of copper in the dry matter of the liver tissue (399 µg/g). In conclusion, a diagnosis of Wilson's disease was made, and treatment was started with penicillamine in gradually increasing doses, along with vitamin B6 and reduced copper intake. A favorable biochemical response is monitored. Molecular genetic analysis revealed 2 heterozygous mutations of the ATP7B gene, and the diagnosis was confirmed. Conclusion: This review highlights the importance of systematically working up persistently elevated aminotransferases even in asymptomatic children in order to diagnose treatable diseases such as Wilson's disease in a timely manner.
Hepatolenticular Degeneration; Transaminases; Copper-Transporting ATPases; Copper; Penicillamine
Copyright (c) 2026 Ana Golem Kožić, Maja Šalamon Janečić https://creativecommons.org/licenses/by/4.0
Introduction: Headaches in childhood are a common reason for seeking medical care. Headaches are classified as primary or secondary. Primary headaches, most commonly migraine and tension-type headache, are not associated with underlying organic disease, whereas secondary headaches result from other pathological conditions such as infections, trauma, or intracranial processes. Proper recognition and assessment of the type of headache enables a rational diagnostic and therapeutic approach to the patient. In this paper, we present two patients with different types of headaches to illustrate the clinical characteristics and diagnostic approach to various headache disorders. Case report: The first patient is a 13.5-year-old boy who has been under long-term follow-up by a pediatric gastroenterologist and neurologist due to episodic gastrointestinal and neurological symptoms. Symptoms began at the age of four with recurrent episodes of nausea, vomiting, pronounced fatigue, and pallor, which over time became associated with headache. An extensive diagnostic workup was performed (brain MRI, EEG, transcranial color-coded Doppler, metabolic and endocrinological evaluation, and ophthalmologic examination). All findings were normal, and secondary causes of headache were excluded. According to the Rome IV criteria, a diagnosis of cyclic vomiting syndrome was established, which belongs to the spectrum of pediatric episodic syndromes associated with migraine. Prophylactic therapy with cyproheptadine was initiated, resulting in remission of gastrointestinal symptoms. During further follow-up, the patient developed typical and frequent migraine attacks accompanied by autonomic symptoms, predominantly fatigue, exhaustion, loss of appetite, nausea, and occasional vomiting. Prophylactic therapy with topiramate and amitriptyline was introduced but proved ineffective, whereas treatment with sumatriptan showed a good clinical response. The described clinical course corresponds to the progression of cyclic vomiting syndrome into migraine during adolescence. The second patient is an 11-year-old girl who has complained of headaches intermittently since the age of four, with a gradual increase in frequency and duration. The headaches are predominantly frontal, of strong intensity, and of a pressing quality, sometimes lasting several days. They occur without associated nausea, vomiting, photophobia, or phonophobia. A comprehensive diagnostic evaluation was performed. EEG revealed dysrhythmic changes. A brain MRI showed a polycystic pineal gland and an arachnoid cyst in the region of the left lateral cerebellomedullary cistern, without signs of mass effect or hydrocephalus; neurosurgical evaluation did not indicate the need for surgical treatment. Ophthalmologic examination was normal. Laboratory testing revealed subclinical hypothyroidism with autoimmune thyroiditis, which did not require substitution therapy. The clinical picture, characterized by long-lasting headaches without autonomic symptoms and without a clear organic substrate, is consistent with the diagnosis of chronic tension-type headache. In our patient, analgesic therapy did not result in clinical improvement, nor did alternative therapeutic approaches such as laser acupuncture. Currently, prophylactic therapy combined with a psychotherapeutic approach and riboflavin supplementation has been recommended. Such therapeutic response and the need for a multimodal treatment approach are consistent with the known characteristics of chronic tension-type headache, in which analgesics often have limited efficacy, while non-pharmacological and prophylactic measures play a key role in symptom control. Conclusion: The two pediatric patients presented illustrate different phenotypes of primary headaches in childhood. The first case demonstrates migraine in adolescence, while the second case represents chronic tension-type headache, both without an underlying organic substrate and with a limited response to analgesic therapy. These cases highlight the importance of accurate differential diagnosis and an individualized diagnostic and therapeutic approach in the management of different headache entities.
Headache; Migraine Disorders; Vomiting; Tension-Type Headache; Pediatrics
Copyright (c) 2026 Iva Tkalčec, Jadranka Sekelj https://creativecommons.org/licenses/by/4.0
Case report – when symptoms (do not) mislead
Introduction: Tumors of the central nervous system are the most common solid tumors in childhood, with glial and embryonal tumors being the most prevalent. Clinical presentation is often nonspecific and depends on the child’s age and tumor location. Diagnosis relies on neuroradiological evaluation (magnetic resonance imaging and computed tomography), as well as histopathological and molecular tumor analysis. Early recognition of symptoms is crucial for timely treatment, improved outcomes, and quality of life. Case presentation: The first case involves a seven-year-old girl presenting with ataxia, headache, and visual disturbances. Imaging revealed a tumor in the fourth ventricle with hypertensive hydrocephalus, and methylation profiling confirmed medulloblastoma (group 4, subclass 6). The second case is a twelve-year-old boy with frontal headaches and morning vomiting. MRI of the brain and spine showed a tumor in the fourth ventricle with metastases, and molecular analysis confirmed medulloblastoma (group 4, subtype V). The third case concerns a seventeen-year-old girl with fatigue, weight loss, and secondary amenorrhea. Imaging demonstrated a tumor in the suprasellar and pineal regions with a solitary intracranial metastasis, leading to the diagnosis of metastatic bifocal germinoma with negative tumor markers. Conclusion: Evaluation of children with suspected CNS tumors must be systematic, including thorough neurological examination, monitoring of growth and head circumference in younger children, and assessment of pubertal status. The combination of these clinical features warrants prompt neuroradiological evaluation for early detection and initiation of appropriate oncological treatment.
Headache; Ataxia; Hypopituitarism; Neuroimaging; Medulloblastoma; Germinoma
Copyright (c) 2026 Anamaria Uglešić Maurović, Domagoj Buljan, Filip Jadrijević-Cvrlje, Jasminka Stepan Giljević https://creativecommons.org/licenses/by/4.0
Introduction: Polyuria in children is defined as urine production of more than 4 mL/kg/h. The cause of polyuria can be osmotic diuresis (e.g. diabetes mellitus), and primary or secondary disorders of the kidney's ability to concentrate urine (central or nephrogenic diabetes insipidus, chronic kidney disease, obstructive uropathy, etc.). Primary polydipsia is also a possible cause of polyuria. Case: A 17-year-old girl was examined in the nephrology clinic due to polyuria that had been present for the past year. Along with polyuria, nocturia is also present without dysuria and without enuresis. In addition to the above, she was thirsty during the day. She did not lose weight. Family history is unremarkable. Pregnancy and childbirth were normal, as was her previous growth and development. On examination, her vital signs were normal, her somatic status was normal, and her blood pressure was 47.c. for body weight and 32nd centile for height and without clinical or laboratory signs of dehydration. A random urine sample showed urine of normal volume mass (1.09 kg/L), normal pH and sediment, without glucosuria. Ultrasound of the kidneys and urinary tract was normal. Polyuria was objectified by a 48-hour drinking and urination diary, which determined a daily urine volume of 13,360 L (11.13 ml/kg/h), of which 7,475 L was voided during the night period of measurement. The measured bladder capacity was 157% of the expected volume for age - 850mL. Further diagnostic workup was performed through hospitalization. Upon admission, vital parameters were normal again, normal somatic status, no clinical signs of dehydration and normal volume status. The laboratory work-up indicated a normal acid-base status of pH 7.333, normal glycemia (4.4 mmol/L), normal serum concentration of electrolytes and parameters of renal function (eGFR 144 (mL/min/1.73m2). The blood count was normal, without signs of acute infection. A random urine sample was of reduced volumetric mass (1,001 kg/L), no glucosuria, no proteinuria, and regular sediment. Urine osmolality was 49 mOsmol/kg, and serum 288 mOsmol/kg. A thirst test was performed, which determined an increase in urine osmolality up to 956 mOsm/kg in a state of fluid deprivation with maintained serum osmolality, thus confirming the ability to concentrate urine. This girl was diagnosed with primary polydipsia, which caused polyuria, and was advised to limit water intake to physiological needs. Discussion: In this case, an initial laboratory work-up, which indicated normal blood glucose values ​​and the absence of glucose in the urine, ruled out diabetes as the cause of polyuria and polydipsia. A urinary tract infection was ruled out by urine analysis. Ultrasound diagnostics ruled out the presence of renal dysplasia or obstruction of the urinary system, which could lead to polyuria in the stage of tubule damage. A normal acid-base status ruled out the presence of renal tubular acidosis, and the normal values ​​of electrolytes in the portion of urine additionally confirmed that there were no disturbances in the function of the proximal and distal tubules and Henle's loop. What remained to be assessed was the kidney's ability to concentrate urine, which mostly takes place at the level of the collecting ducts, i.e. their sensitivity to ADH. A thirst test was performed, which proved an orderly increase in urine osmolality, and thus the diagnosis of primary polydipsia was made.
Polyuria; Nocturia; Polydipsia, Psychogenic; Osmolar Concentration
Copyright (c) 2026 Franjka Antoliš, Matea Crnković Ćuk https://creativecommons.org/licenses/by/4.0
Congenital adrenal hyperplasia – lessons on growth, development and glucocorticod therapy
Introduction: Congenital adrenal hyperplasia (CAH) includes a group of autosomal recessive disorders of steroidogenesis caused by reduced or absent activity of enzymes involved in the synthesis of steroid hormones from cholesterol. The most common form of CAH, which accounts for 90–95% of cases, is the result of a deficiency of 21-hydroxylase, an enzyme essential for the synthesis of cortisol and aldosterone. The severity of the disease depends on the residual enzymatic activity associated with certain mutations of the CYP21A2 gene, and the main feature of the clinical picture is virilization of the child. We distinguish between the classic form of CAH, which is manifested at birth, and the milder, non-classical form, in which the clinical picture develops later during childhood or adolescence. Virilization in its most severe form in girls is manifested by ambiguous genitalia, while it is more difficult to recognize immediately after birth in boys, but it causes progressive development of the genitals and accelerated growth and physical development, which can lead to true precocious puberty and compromise final height. The most severe form of the disease, classic salt-wasting CAH, if untreated or treated inappropriately, can lead to life-threatening adrenal crisis. Using the example of a boy with precocious puberty, we would like to demonstrate the method and importance of early diagnosis, the modalities and challenges of hormone replacement therapy in these patients, the importance of monitoring growth and development, and the timely recognition of metabolic and endocrinological complications. Patient case: We present a boy who was referred to an endocrinologist at the age of three and a half years due to suspected precocious puberty. The boy had not previously suffered from any serious illness or condition that would indicate the development of an adrenal crisis. The clinical status includes signs of false precocious puberty: tall stature, blackheads on the nose and ears, a deeper voice, and inappropriately large genitalia for his age (Tanner II-III) with pubic hair (Tanner II), while the testicles are of prepubescent size (2 according to Prader). Laboratory workup revealed a diagnosis of classical CAH with markedly accelerated bone maturation (10 years), and replacement therapy with hydrocortisone was initiated. The diagnosis was also confirmed by evidence of a CYP21A2 gene mutation. During follow-up, the boy developed true precocious puberty at the age of 6, which is why treatment with luteinizing hormone-releasing hormone (LHRH) agonists was initiated. The challenges of treatment and monitoring are listed below: titration of the hydrocortisone dose - a dose that will suppress androgen secretion without compromising growth; dose adjustment in acute stressful situations; new hydrocortisone formulations; recognition of the risk and development of true precocious puberty and its timely treatment; recognition of growth patterns that indicate (in)appropriate treatment of the boy. Conclusion: Congenital adrenal hyperplasia requires early recognition, timely treatment, and monitoring to prevent acute and long-term complications of the disease and to enable the child's growth and development to be as appropriate as possible.
Adrenal Hyperplasia, Congenital; Steroid 21-Hydroxylase; Puberty, Precocious; Hydrocortisone
Copyright (c) 2026 Marija Obad Tomić, Anita Špehar Uroić, Lana Njavro https://creativecommons.org/licenses/by/4.0
Fulminant cerebellitis as a rare complication of a common infection: a challenge in pediatrics
Introduction: Acute cerebellitis is a rare inflammatory disease with a variable course, from a benign self-limiting condition with minimal symptoms to fulminant cerebellitis associated with a high risk of morbidity and mortality. The etiology of the disease is most often infectious or post-infectious, and rotavirus has been described as one of the possible causes. Complications of the disease are the result of acute cerebellar edema that compresses the structures of the posterior cranial fossa and brainstem and leads to the development of obstructive hydrocephalus, intracranial hypertension with impaired consciousness up to status epilepticus, and a fatal outcome due to herniation of the cerebellar tonsils. Children usually have generalized symptoms with nausea, headache, rapid impairment of consciousness, and later mutism. Pleocytosis is present in the cerebrospinal fluid, and brain imaging studies show progressive, significant cerebellar atrophy. If not treated promptly, death can occur. Case report: We present a 6-year-old girl admitted to the Children's Hospital Zagreb with acute ataxia and somnolence. On admission, the Glasgow Coma Scale (GCS) was 13/15. The evening before admission, she vomited 3-4 times, had dyskinesias, was irritable, and made unusual noises. Initial laboratory findings, electroencephalogram, and magnetic resonance imaging (MRI) were normal. Within 12 hours, she developed progressive impairment of consciousness to coma (GCS 5), was intubated, and transferred to the Intensive Care Unit. Repeated MRI scans showed the development of diffuse cerebellitis, hypertensive hydrocephalus, and encephalitis, which were treated with acyclovir, ceftriaxone, intravenous immunoglobulins, and corticosteroids, and external cerebrospinal fluid drainage. The clinical picture was further complicated by the occurrence of recurrent epileptic seizures and the development of status epilepticus, which were treated with levetiracetam and midazolam. After three weeks, all of the above changes regressed. After two months, she was discharged from the hospital for inpatient rehabilitation with a very slow recovery and dominant mutism. A slight improvement in neurological status was gradually noted (GCS 9). Five months after the onset of the disease, with home physical therapy, the girl made significant progress, walking and speaking (GCS 14). She recovered completely. Conclusion: The presented case of fulminant cerebellitis as a rare complication of a common infection emphasizes the importance of early recognition of the disease, repeated neuroradiological examinations, and timely and intensive therapy. Despite the severe initial clinical picture and numerous complications, with adequate treatment and rehabilitation, a full recovery is possible.
Ataxia; Sleepiness; Glasgow Coma Scale; Hydrocephalus; Encephalitis; Seizures
Copyright (c) 2026 Jure Jakovljević, Anamarija Jagić, Vlasta Đuranović https://creativecommons.org/licenses/by/4.0
Functional gastrointestinal disorders in infancy
Functional gastrointestinal disorders in infancy, also referred to as disorders of gut–brain interaction, are common symptom-based conditions diagnosed according to the Rome IV criteria in the absence of organic disease. The most frequent disorders include infant regurgitation, infantile colic, and functional constipation, which often coexist and may significantly affect family well-being and health-care utilization. This article reviews the epidemiology, diagnostic approach, and evidence-based management of functional gastrointestinal disorders in infancy, with emphasis on recognizing alarm signs and applying conservative, non-pharmacological treatment strategies. Most conditions have a benign, self-limiting course; therefore, parental education, reassurance, and standardized diagnostic criteria are central to effective management. Appropriate care in primary health settings may reduce unnecessary investigations and ineffective treatments.
Gastrointestinal Diseases; Infant; Colic; Constipation
Copyright (c) 2026 Ana Močić Pavić https://creativecommons.org/licenses/by/4.0
The impact of procalcitonin levels on antibiotic administration
Differentiating benign viral illnesses from serious bacterial infections (SBIs) is still challenging when treating pediatric patients. Young febrile infants, particularly those ≤90 days of age, carry a disproportionately high risk of invasive bacterial infections (IBIs) due to immunologic immaturity and subtle clinical presentations. Given increasing antimicrobial resistance, there is a critical need for reliable biomarkers capable of supporting early and accurate diagnostic decision-making. Procalcitonin (PCT), an acute-phase biomarker with rapid induction during bacterial infection, has emerged as one of the most promising tools. Compared with C-reactive protein (CRP), PCT demonstrates faster kinetics, stronger correlation with disease severity, and superior diagnostic accuracy in multiple pediatric settings, including neonatal sepsis, febrile infants, neutropenia, meningitis, bronchiolitis, and lower respiratory tract infections. Age-specific reference ranges improve interpretability in neonates, and serial PCT measurements have been successfully incorporated into antibiotic stewardship protocols. Numerous multicenter studies and randomized trials show that PCT-guided management reduces unnecessary antibiotic exposure without compromising clinical safety or increasing treatment failure. Despite its advantages, PCT is not without limitations, as transient elevations may occur in noninfectious conditions and levels can remain low in the earliest phases of infection. Nevertheless, accumulating evidence demonstrates that low PCT values reliably indicate a low probability of bacterial infection, enabling safer reduction in antibiotic use. Overall, PCT represents a valuable biomarker for improving diagnostic accuracy and promoting rational antibiotic therapy in pediatric practice.
Fever; Procalcitonin; Infections; Anti-Bacterial Agents
Copyright (c) 2026 Dina Mrčela, Joško Markić https://creativecommons.org/licenses/by/4.0
Pneumonia that does not go away: a review of two challenging clinical cases
Introduction: Persistent pulmonary infiltrates in children, despite adequate antibiotic therapy, represent a diagnostic challenge and require an extended diagnostic workup. Although most often it has an infectious etiology, other causes such as congenital malformations or tumor processes should be considered. Objective: To highlight the importance of further diagnostic workup in children with persistent infiltrative opacities on lung radiological images initially treated as pneumonia, and to emphasize the importance of timely differential diagnosis. Case report: Two pediatric patients with persistent pulmonary infiltrates are presented. The first case refers to a seven-year-old girl with a normal personal and family history who was hospitalized due to cough and fever with moderately elevated inflammatory parameters. Radiologically, right-sided lobar pneumonia was suspected, but despite parenteral dual antibiotic therapy, the infiltrate persisted. Further work-up (CT and MR of the chest) revealed a tumor formation, which was completely surgically removed. Pathohistological findings confirmed ganglioneuroma. The second case presents a ten-year-old boy with a history of esophageal atresia with tracheoesophageal fistula, surgically treated in infancy. From the age of six, he was frequently treated for right-sided bronchopneumonia with incomplete radiological regression. CT of the chest revealed a congenital lung malformation, which was surgically removed and pathohistologically confirmed as cystic adenomatoid lung malformation. Conclusion: In children with persistent pulmonary infiltrates after adequate antibiotic treatment, it is necessary to perform an extended diagnostic work-up in a timely manner. Early recognition of non-infectious causes allows for timely treatment and prevention of possible complications.
Pneumonia; Ganglioneuroma; Esophageal Atresia; Tracheoesophageal Fistula
Copyright (c) 2026 Borna Vulić, Vedran Šurija, Ivan Pavić https://creativecommons.org/licenses/by/4.0
Passive smoking and children's health: influence on lung function, aerobic capacity, and body mass index
Introduction: Passive smoking (PS) is a significant public health problem, especially in children whose respiratory and immune systems are still developing. Although the harmful effects of tobacco smoke on adult health are well known, data on its simultaneous impact on lung function, aerobic capacity, and body mass index (BMI) in children are limited. The aim of this study was to assess the association of prenatal and postnatal exposure to passive smoking with these health indicators in children. Methods: A cross-sectional study was conducted on 157 children aged 10 to 14 years (89 boys, 68 girls), students of the Elementary School "Trilj" in Trilj, Croatia. Exposure to PS was assessed using a structured questionnaire completed by children and parents. According to the smoking status of their parents, the subjects were divided into children exposed to PS and a control group. BMI was calculated using anthropometric measurements. Pulmonary function was assessed by spirometry (FVC, FEV1, FEV1/FVC, PEF), while aerobic capacity was assessed by the BEEP test. Descriptive statistics, t-test, Kruskal–Wallis test, χ² test, Spearman's correlation, and logistic regression were used for statistical analysis. Results: 62.4% of children were exposed to passive smoking, with 61.2% already exposed to PP during pregnancy. Children exposed to PP, including prenatal exposure, had significantly lower FVC, FEV1, FEV1/FVC, and PEF values ​​compared to non-exposed children (p < 0.05). Also, a statistically significant increase in BMI was recorded in children exposed to PP. A lower level of aerobic fitness was associated with worse lung function and higher BMI. No significant differences were observed according to gender or level of physical activity. Conclusion: Exposure to passive smoking, particularly during pregnancy and in the home environment, is associated with reduced lung function, poorer aerobic fitness, and increased BMI in children. The results highlight the need for stronger public health interventions aimed at reducing children's exposure to tobacco smoke and promoting smoke-free home environments.
Tobacco Smoke Pollution; Body Mass Index; Public Health; Home Environment
Copyright (c) 2026 Sara Žaja, Iva Topalušić, Tamara Poljičanin, Ozana Hofmann Jaeger, Asja Stipić Marković, Ivan Pavić https://creativecommons.org/licenses/by/4.0
Laryngopharyngeal reflux in children: a rarely recognized cause of respiratory symptoms
Introduction: Laryngopharyngeal reflux (LPR) is an extraesophageal manifestation of gastroesophageal reflux disease (GERD) and is associated with numerous respiratory symptoms, especially in childhood. Diagnosis is often difficult due to the nonspecific clinical picture and the frequent absence of typical esophageal symptoms. It is based on anamnesis, clinical and fiberendoscopic ENT examination, and is confirmed by 24-hour multichannel intraluminal impedance with pH-metry (24h MII-pH). The use of 24h MII-pH allows the detection of acidic, weakly acidic, and weakly alkaline reflux episodes and their temporal relationship with symptoms. Treatment begins with hygiene and dietary measures, and if necessary, drug therapy with proton pump inhibitors is introduced, while surgical treatment is reserved for severe and therapy-resistant cases. Case report: We present the case of a boy aged 4.5. years with complex respiratory symptoms, in whom a detailed diagnostic work-up, including fiber-endoscopic ENT examination and 24h MII-pH, led to the diagnosis of LPR as the cause of his complaints. After the therapy, there was a significant clinical and endoscopic improvement. Conclusion: Given that extraesophageal manifestations of GER are often not accompanied by typical esophageal symptoms and can be caused by various types of reflux, 24h MII-pH represents a key diagnostic method in the evaluation of children with suspected LPR. Timely recognition and adequate treatment of LPR can significantly improve clinical outcomes and change the therapeutic approach in numerous respiratory and ENT diseases in childhood.
Laryngopharyngeal Reflux; Proton Pump Inhibitors; Otorhinolaryngologic Diseases
Copyright (c) 2026 Antonio Rajić, Luka Vulić, Ivan Pavić https://creativecommons.org/licenses/by/4.0
When vaccination is not enough: Streptococcus pneumoniae serotype 3 as a cause of necrotizing pneumonia in a child
Introduction: Necrotizing pneumonia is a rare but severe complication of bacterial pneumonia in children, most often associated with Streptococcus pneumoniae infection. Despite successful vaccination programs, certain serotypes not covered by vaccines continue to pose a significant clinical problem. Case report: We present the case of a 1.5-year-old boy who was admitted due to high fever, respiratory distress, and general poor condition. The child was properly vaccinated according to the national vaccination program, including the 10-valent pneumococcal vaccine. Radiological workup (chest X-ray and MSCT) revealed necrotizing pneumonia with the formation of cavitary lesions. Streptococcus pneumoniae serotype 3 was isolated from the pleural puncture. Despite initial antibiotic therapy, the clinical course was complicated, requiring prolonged hospitalization and adjustments to antibiotic therapy. The child gradually recovered without lasting consequences. Discussion: Streptococcus pneumoniae serotype 3 is known for its high virulence and tendency to cause severe pneumonia, including necrotizing pneumonia. This serotype is not covered by the 10-valent pneumococcal vaccine, which explains the occurrence of invasive pneumococcal disease in a properly vaccinated child. The presented case highlights the limitations of current vaccination programs and the importance of clinical suspicion of severe complications of pneumonia, even in vaccinated children. Conclusion: Necrotizing pneumonia caused by Streptococcus pneumoniae serotype 3 can occur even in properly vaccinated children. This case highlights the need for timely diagnosis, adequate treatment, and consideration of wider serotype coverage of pneumococcal vaccines in the prevention of severe forms of the disease.
Pneumonia, Necrotizing; Vaccination; 10-valent pneumococcal vaccine; Streptococcus pneumoniae
Copyright (c) 2026 Mateo Raboteg, Josip Županović, Ivan Pavić https://creativecommons.org/licenses/by/4.0
The systematic collection of data from personal and family history, clinical examination, and diagnostic work-up allows for the establishment or exclusion of suspicion of a genetic etiology of the disease. Anamnestic indicators of a genetic disease include the simultaneous presence of multiple unrelated diagnoses, early onset of the disease, bilateral or multifocal manifestation, repeated spontaneous abortions, lack of a clear diagnosis despite extensive work-up, multiple affected family members, consanguinity of parents, marriages within limited communities, and membership in certain ethnic and geographic groups. Clinical and diagnostic indicators of a genetic etiology include dysmorphic features, growth and somatic development disorders, anomalies of the limbs and musculoskeletal system, especially the hands and feet, neurological and neurocognitive manifestations (developmental delay, intellectual disorders, epilepsy, learning and attention disorders, behavioral and emotional disorders, hypotonia, ataxia, tremor, and fine and gross motor disorders), as well as additional somatic signs such as hair, dental, skin pigmentation, and sweating disorders. By integrating history, clinical examination, and diagnostic processing, it is possible to suspect a specific genetic disease or a narrower group of diseases, which enables targeted guidance of further diagnostics and, in case of confirmation, assessment of individual and family risk.
Genetic Diseases, Inborn; Medical History Taking; Congenital Abnormalities; Growth Disorders; Neurodevelopmental Disorders
Copyright (c) 2026 Bernarda Lozić, Ante Tavra, Dora Knezović, Tomislav Smoljo, Marina Ogorevc https://creativecommons.org/licenses/by/4.0
Polyuria - cause or consequence - systematic diagnostic algorithm in the pediatric population
Polyuria is excessive urine output, which in children is defined as urine production of more than 4 ml/kg/hour or more than 2 l/m2 of body surface area over 24 hours. Aim: The aim of this review is to present a systematic algorithm for the etiological workup of polyuria in children. The focus is on the rapid exclusion of secondary metabolic causes and the correct triage placement of polyuria into one of the clinical categories: secondary metabolic sign, urinary concentrating disorder, or consequence of excessive fluid intake. Methods: The work is based on a systematic analysis and synthesis of relevant medical literature, including clinical guidelines, textbooks, and scientific papers. Clinical and pathophysiological knowledge in pediatrics was used to establish a structured diagnostic protocol. Emphasis is placed on triage: quantification of polyuria, assessment of volume status, and interpretation of initial laboratory work-up (glucose, electrolytes, calcium, renal function). For the final differentiation of primary disorders, functional testing, i.e., the thirst test, is used. Results: Polyuria is often a secondary sign of osmotic diuresis caused by metabolic disorders such as hyperglycemia (diabetes mellitus 1, DM1), hypercalcemia, and hypokalemia. If these causes are excluded, polyuria passes into the domain of primary disorders of urine concentration, predominantly Diabetes Insipidus (DI) or Primary Polydipsia (PP). Definitive diagnosis of DI (central versus nephrogenic) is established by thirst test and change in urine osmolality upon administration of desmopressin. Key differential findings include hypernatremia and high plasma osmolality in DI and euvolemia/mild hyponatremia in PP. Conclusion: A systematic, step-by-step approach to the diagnosis of polyuria is essential in pediatrics. It is essential to first treat acute dehydration and urgently rule out secondary metabolic causes, while a functional thirst test is essential for the final etiological diagnosis of DI or PP. Proper application of the diagnostic algorithm ensures a correct diagnostic and therapeutic approach.
Polyuria; Polydipsia; Diabetes Insipidus; Hypernatremia; Diuresis
Copyright (c) 2026 Matea Crnković Ćuk https://creativecommons.org/licenses/by/4.0
The contribution of healthcare staff communication skills to patient satisfaction and better treatment outcomes
Within healthcare practice, the influence of digital technologies, which are changing the dynamics and patterns of communication, is becoming increasingly prominent. However, personal encounters and spoken communication remain key elements of a successful relationship between healthcare professionals and patients, as they enable deeper understanding, empathy, and the creation of trust that technology cannot fully replace. The aim of this paper is to highlight the importance of effective communication, supported by research on how satisfied patients are with the communication skills of healthcare staff, whether there is a difference in patient satisfaction between primary and secondary healthcare services, and how patients perceive their own communication skills and their potential contribution to a positive course of illness. A combined quantitative and qualitative study was conducted on a sample of respondents selected through random sampling, using an online survey form (Google Forms). A total of 219 respondents completed the survey, and the data were analyzed using IBM SPSS Statistics. The average satisfaction score obtained was 3.37 to 3.46 for primary healthcare compared to 3.02 for secondary healthcare. The findings clearly indicate the need for more systematic investment in communication skills training for healthcare personnel. It is encouraging that as many as 84.9 % of participants emphasized that the communication skills of healthcare staff are extremely important. Furthermore, 91.8 % believe that communication skills contribute to better treatment outcomes, and 87.1 % think that their own personal skills also contribute to improved communication as an essential factor in preventing and mitigating conflicts that may arise due to differences in attitudes or expectations. There is no doubt that effective communication plays a crucial role in improving the quality of healthcare, increasing patient satisfaction, contributing to better therapeutic outcomes, reducing costs, and enabling a fairer allocation of resources based on priority.
Communication; Patient Satisfaction; Treatment Outcome.
Copyright (c) 2026 Mirjana Kolarek Karakaš, Martina Jukić https://creativecommons.org/licenses/by/4.0
Dyspnea is a subjective sensation of breathing difficulty, which can result from various organic disorders as well as psychological factors. Dyspnea occurring during physical exertion represents a distinct entity and is a common reason for referring children to a pulmonologist. Common causes of exertional dyspnea include asthma, dysfunctional breathing, physical deconditioning, and obesity. These causes often coexist, trigger one another, and present with overlapping symptoms, which complicates establishing a clear diagnosis and selecting appropriate treatment. Although most frequently associated with asthma, exertional dyspnea should not be considered synonymous with exercise-induced bronchoconstriction. A detailed medical history and clinical examination are essential for establishing an accurate diagnosis and planning further diagnostic procedures. The exercise challenge test is a highly specific and most commonly performed indirect bronchoprovocation test that differentiates exercise-induced bronchoconstriction from other causes of dyspnea.
Dyspnea; Asthma, Exercise-Induced; Respiratory Function Tests; Exercise Test
Copyright (c) 2026 Maja Bosanac, Iva Topalušić, Marta Navratil, Manuela Radić https://creativecommons.org/licenses/by/4.0
When to suspect a malignant hematological disease in children?
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, affecting a quarter of pediatric oncology patients (1). It occurs most frequently in children under the age of five, while Hodgkin lymphoma (HL) is the dominant malignant neoplasm in adolescents, and the incidence of Non-Hodgkin lymphoma (NHL) is highest in primary school-aged children. Given that acute leukemias (AL) and lymphomas together account for slightly less than half of all malignant diseases in children, and often present with nonspecific symptoms that may resemble benign conditions typical of childhood, early recognition of these diseases is essential as the first step towards successful treatment. The high five-year survival rates in developed countries, approximately 85% for leukemias and 94% for lymphomas, are largely attributed to modern treatment protocols and significantly improved supportive care (2). However, it is equally important to suspect malignancy in a timely manner and promptly begin treatment. The length of the diagnostic interval often depends on the child's age, the type of tumor, and the physician of first contact or the initial healthcare institution. Most of the first signs and symptoms of ALL are nonspecific and difficult to distinguish from common, self-limiting acute diseases in children, and include symptomatology that is a result of the bone marrow, lymphatic system, and extramedullary sites infiltration. The clinical presentation of acute myeloid leukemia (AML) is mostly indistinguishable from the clinical picture of ALL. Laboratory abnormalities are also a consequence of the leukemia cells burden, medullary and extramedullary propagation. The presence of blasts in the peripheral blood accelerates the path to diagnosis. The diagnosis of AL is made by the analysis of blasts in the bone marrow, while imaging, in addition to lumbar puncture, is necessary to assess the involvement of extramedullary localizations. The most common clinical presentations of pediatric ALL and AML are shown in Table 1 (3, 4). HL most often presents as cervical lymphadenopathy, in contrast to the highly heterogeneous presentation and localization of NHL. In general, a peripheral lymph node larger than 2 cm in diameter, painless and firm, with an inadequate response to antibiotic therapy administered for 4–6 weeks, is considered suspicious. While HL is characterized by relatively slow growth, NHL is often characterized by rapid progression that commonly causes an oncological emergency. Namely, in practically every second pediatric patient with a mediastinal mass lymphoma is present, especially if cervical lymphadenopathy is also present. In the case of thoracic localization, it is most likely lymphoblastic lymphoma (LL) as a variant of NHL, with the possibility of propagation to the bone marrow and central nervous system (CNS). The digestive tract is often the site of B-NHL, such as Burkitt's lymphoma (BL) and diffuse large cell B-lymphoma (DLCBL), while the fourth type of NHL in the pediatric population, anaplastic large cell lymphoma (ALCL), often presents as a systemic disease with involvement of numerous organs. B symptoms, which include fever (> 38 °C), weight loss, and profuse sweating, occur in slightly less than half of patients with lymphoma. Although the combination of lymphadenopathy and B symptoms is highly suspicious for lymphoproliferative disease, it should also be suspected in gastrointestinal symptoms and signs such as abdominal pain, palpable abdominal mass, intussusception or intestinal obstruction, respiratory symptoms such as stridor, in the case of asymmetrically enlarged tonsils, or in the case of bone pain. While laboratory deviations in HL are absent or minimal, in NHL, the presence of cytopenias and metabolic disturbances due to spontaneous tumor lysis syndrome is possible. Imaging methods (computed tomography, CT; magnetic resonance, MR; positron emission tomography, PET-CT) assess the extent of the disease in NHL with bone marrow and lumbar puncture, while a histopathological analysis of the tumor tissue is necessary for the final diagnosis. The most common clinical presentations of pediatric lymphomas are shown in Table 2 (5, 6). In conclusion, the clinical picture of pediatric hematological neoplasms, although often non-specific, combined with a carefully taken history, a detailed clinical examination, and correctly interpreted laboratory and imaging findings must raise the suspicion of hemoblastosis or malignant lymphoproliferation in the physician of the first contact, with the aim of timely initiation of the diagnostic and therapeutic process and an optimal final outcome.
Leukemia, Lymphoid; Lymphoma; Children; Signs and Symptoms; Early diagnosis
Copyright (c) 2026 Izabela Kranjčec https://creativecommons.org/licenses/by/4.0
Primary headaches in children represent a significant public health problem due to high prevalence, estimated at around 60 %. The most common types include migraine and tension-type headache. The diagnostic criteria for headaches in children are the same as those in adults and are based on the third edition of the International Classification of Headache Disorders (ICHD-3), but the clinical presentation of primary headaches in children may differ from that of headaches in adults. The diagnosis of primary headaches in children is based on a careful history and clinical examination, which is important to exclude secondary causes of headaches. Most primary headaches can be diagnosed without the need for neuroimaging. A longer course of headache increases the risk of developing chronic headache and associated comorbidities, so it is important to establish a diagnosis as early as possible and implement preventive measures. Acute therapy includes medications such as analgesics (paracetamol, ibuprofen) or triptans for migraine treatment, while prevention is based on lifestyle changes, cognitive-behavioral therapy, and drug intervention. An individualized approach is the key to successful treatment of primary headaches in children.
Migraine disorders; Tension-Type Headache; Child
Copyright (c) 2026 Jadranka Sekelj, Sanja Pejić Roško, Lana Lončar, Ivana Đaković, Andrijana Pilon Far, Maja Fureš, Vlasta Đuranović https://creativecommons.org/licenses/by/4.0
Early recognition of central nervous system tumors
Central nervous system tumors in children represent the second most common group of malignant neoplasms after acute leukemias and are the leading cause of morbidity and mortality in the pediatric oncology population. It is a heterogeneous group of tumors that differ in histological, molecular, and clinical features. The clinical presentation is often nonspecific and depends on the child's age and the localization of the tumor. The most common symptoms include headache, nausea and vomiting, gait and coordination disorders, epileptic seizures, visual disturbances, and cognitive and behavioral dysfunction. In infancy, macrocephaly may be the first and only sign of intracranial pathology. Children with neurocutaneous syndromes, especially neurofibromatosis type 1 and tuberous sclerosis, have a significantly increased risk of developing central nervous system tumors, including optic pathway gliomas and subependymal giant cell astrocytomas. Recognition of these syndromes allows for timely monitoring and early diagnosis of potential complications. Timely recognition of early symptoms and signs is crucial for referring the child for neuroradiological diagnostic work-up. Magnetic resonance imaging is the method of choice in the evaluation of intracranial lesions due to its high resolution and ability to distinguish parenchymal structures. Early diagnosis allows for optimal planning of a multimodal therapeutic approach, including surgical, oncological, and radiotherapy treatment, which significantly improves outcomes and reduces the risk of permanent neurological damage.
Headache; Magnetic Resonance Imaging; Neurocutaneous Syndromes; Vomiting;Central Nervous System Neoplasms
Copyright (c) 2026 Domagoj Buljan, Filip Jadrijević Cvrlje, Jasminka Stepan Giljević https://creativecommons.org/licenses/by/4.0
Assessment of vascular involvement in children with hypercholesterolemia
Familial hypercholesterolemia (FH) is a common hereditary disorder that leads to early development of atherosclerosis and increases the risk of premature cardiovascular disease. Children with heterozygous FH already show increased carotid intima-media thickness (cIMT) at 6–8 years of age compared with their healthy siblings, confirming the early onset of subclinical changes. Endothelial dysfunction, detectable before structural alterations, correlates with cIMT and represents an important early marker of vascular damage. Arterial stiffness, measured by pulse wave velocity (PWV), together with cIMT, provides independent prognostic value for cardiovascular events, even when traditional risk factors such as low-density lipoprotein cholesterol (LDL-C) are considered. In homozygous FH, atherosclerotic changes occur at a very early age, justifying the use of imaging methods (ultrasound, magnetic resonance imaging, computed tomography angiography) for early detection and monitoring of therapeutic effects. cIMT has proven to be the most valid and widely used marker in pediatric populations, while early statin intervention can improve endothelial function and slow progression of vascular atherosclerotic changes. However, heterogeneity of measurement techniques highlights the need for standardisation and longitudinal studies. FH in childhood represents a unique opportunity for intervention at the earliest stage of the atherosclerotic process. Non-invasive methods for assessing subclinical atherosclerosis play a crucial role in early detection of vascular changes, guiding therapeutic decisions, and monitoring treatment efficacy, thereby ensuring long-term health and reducing cardiovascular risk in children with FH.
Hyperlipoproteinemia Type 2A; Child; Carotid Intima-Media Thickness; Pulse Wave Analysis; Atherosclerosis
Copyright (c) 2026 Marin Petković, Višnja Tokić Pivac, Maja Vugrinec Mamić, Jakov Mamić https://creativecommons.org/licenses/by/4.0
Adrenal insufficiency and stress-management in a child on chronic glucocorticoid therapy
Adrenal insufficiency is a frequently underestimated disorder that, if unrecognized, increases the risk of adverse outcomes during acute illnesses and diagnostic or therapeutic interventions. The rising incidence of chronic diseases commonly treated with glucocorticoids has made iatrogenic adrenal insufficiency a significant concern even within the pediatric population. The aim of this paper is to emphasize the importance of acknowledging and promptly recognizing signs of adrenal insufficiency in children, both in those receiving chronic hydrocortisone replacement therapy for previously diagnosed adrenal insufficiency and in those on long-term glucocorticoid therapy in whom adrenal insufficiency may remain undetected. Through a systematic review and analysis of relevant scientific literature, clinical guidelines, and textbooks, we provide an overview of the pathophysiology underlying adrenal insufficiency, its recognition, and management, with special emphasis on adrenal insufficiency induced by chronic glucocorticoid therapy. By synthesizing available recommendations and guidelines, we outline strategies for identifying risk factors for adrenal insufficiency, offer management recommendations for acute illness and stress, and propose guidance for the safe tapering and discontinuation of chronic glucocorticoid therapy. Raising awareness of iatrogenic adrenal insufficiency in children treated with long-term glucocorticoids, recognizing that these patients are unable to mount an adequate stress response, and educating physicians and caregivers on timely action in emergencies are fundamental steps toward reducing the risk of severe complications.
Adrenal insufficiency; Glucocorticoids; Hydrocortisone; Risk factors
Copyright (c) 2026 Anita Špehar Uroić, Lana Njavro https://creativecommons.org/licenses/by/4.0
Erythrocyte sedimentation rate, C - reactive protein and procalcitonin: When, who and why
Inflammatory biomarkers are an integral part of daily clinical practice in paediatric primary care. Although erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) are frequently used together, they differ in biological function, response kinetics, and clinical relevance. Awareness of these differences allows a more rational diagnostic approach, reduces unnecessary antibiotic prescribing, and supports optimal management of inflammatory conditions in children. The distinct kinetics of individual inflammatory markers underlie their clinical utility. Figure 1 presents the characteristic time course (rise and fall) of the most common inflammatory markers after the onset of the inflammatory process and during recovery. The most common inflammatory markers used in clinical practice are the total and differential leukocyte count (L), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT). The values of leukocytes, neutrophils, and lymphocytes are strongly age dependent. Children physiologically have higher leukocyte values, especially up to 5 years of age, and they must always be compared with age-related reference values. Diagnostic algorithms commonly used to evaluate newborns, infants, or children with fever include interpreting total and differential leukocyte counts. Among febrile children, a total leukocyte count < 5 or ≥ 15 x 109/L represents an increased risk of serious infection, although some studies have shown that both the total and differential L counts are not reliable or accurate indicators of serious infection in febrile infants (1). Erythrocyte Sedimentation Rate Erythrocyte sedimentation rate (ESR) is the oldest laboratory indicator of inflammation, but it still has its significance in everyday practice. It is blood test that measures how fast red blood cells settle in a blood test tube over one hour and which depends primarily on the concentration of plasma proteins, especially fibrinogen and immunoglobulins (2). An elevated sedimentation rate indicates the presence of an inflammatory process but is not specific for any condition. It may be elevated in infections, autoimmune diseases, malignancies, anemia and pregnancy, and decreased in polycythemia, hypofibrinogenemia and heart failure. Any condition that affects red blood cells and fibrinogen will affect the ESR value. The ESR increases within 24-48 hours of the onset of inflammation and slowly decreases as the inflammation resolves. However, an ESR >100 mm/hour requires a search for an underlying etiology. A high ESR has a high specificity: 0.96 for malignant neoplasms, 0.97 for infections and 0.99 as an indicator of disease (3,4). The main advantage of ESR is its simplicity and availability, while its main limitation is its slow increase and slow normalization after the end of inflammation. Therefore, it has a greater diagnostic value in chronic and rheumatological diseases, where it helps in monitoring disease activity. C - reactive protein C-reactive protein (CRP) is the principal acute-phase reactant, synthesized in the liver under the influence of interleukin-6 and other pro-inflammatory cytokines. Following the onset of inflammation, CRP begins to rise within 4–6 hours, doubles approximately every 8 hours, and reaches its peak within 36–50 hours. Its half-life is approximately 19 hours. This rapid kinetic profile makes CRP the most useful biomarker of acute inflammation in primary care settings (5). Normal CRP values are generally below 2 mg/L, although values up to 10 mg/L may still be considered normal. Levels above 40 mg/L usually suggest a bacterial etiology, whereas lower values are more commonly associated with viral infections or mild inflammatory conditions. Very high CRP concentrations (>200 mg/L) are typically observed in severe bacterial infections, sepsis, or extensive tissue inflammation (5). In non-hospitalized children, the sensitivity and specificity of CRP for diagnosing serious bacterial infection are approximately 77% and 79%, respectively. Serial CRP measurements provide greater predictive value: an elevated CRP increases the probability of infection by 11%, whereas a normal CRP reduces it by 33%. Serial CRP monitoring may also indicate the appropriateness of antibiotic therapy; for example, if CRP remains unchanged or increases after 48 hours of antibiotic treatment, therapeutic failure should be suspected. Additionally, serial CRP values are useful in neonates with sepsis for assessing antibiotic response within the first 48 hours of therapy, as a decline in CRP during this period shows a sensitivity of 89% and specificity of 90%. CRP levels do not reliably decrease in immunosuppressed patients; therefore, its diagnostic accuracy for severe infection in patients with malignancy and febrile neutropenia is lower compared with biomarkers such as procalcitonin (6). CRP is the most widely used biomarker of inflammation. It is easy to perform, available in most laboratories, inexpensive, and straightforward to interpret. Procalcitonin Procalcitonin (PCT) is the precursor of the hormone calcitonin, which under physiological conditions is produced by the parafollicular (C) cells of the thyroid gland. In the presence of systemic bacterial infection, PCT is also released from other tissues (lungs, intestines, pancreas) under the influence of bacterial endotoxins and cytokines such as TNF-α and IL-6. In contrast, during viral infections, its production is suppressed by interferon-γ (7). Unlike CRP, PCT does not increase significantly in viral infections or non-infectious inflammatory conditions, making it a highly specific marker for bacterial infections and sepsis. Normal serum PCT concentrations are below 0.05 ng/mL. PCT levels rise within 3–4 hours after infection onset and peak within 6–24 hours. Elevated PCT values are not observed in inflammatory conditions such as systemic lupus erythematosus, gout, juvenile rheumatoid arthritis, or inflammatory bowel disease, but transient increases may occur following massive trauma, such as severe burns. PCT values below 0.05 ng/mL are considered normal, whereas levels above 0.5 ng/mL suggest bacterial infection. Concentrations exceeding 2 ng/mL strongly indicate sepsis or severe systemic infection, while values above 10 ng/mL are typically associated with septic shock (2). The kinetic profile of PCT is characterized by a rapid increase (within 3–4 hours) following exposure to bacterial endotoxins and a short elimination half-life of approximately 24 hours. This makes PCT particularly useful for (a) early identification of bacterial sepsis, (b) assessment of infection severity, and (c) guiding antibiotic therapy and monitoring treatment response (6,8). A daily reduction of PCT levels by approximately 50% indicates a favorable therapeutic response (8). Special Considerations in the Pediatric Population In children, ESR demonstrates (a) lower reference values than in adults (Table 2), (b) less sensitive to inflammation than CRP, and (c) ESR is strongly influenced by hematologic parameters—particularly anemia and hematocrit (10). CRP does not show major age-related differences except during the first 24–48 hours of life (Table 3). Neonates may exhibit falsely elevated CRP levels due to delivery, stress, or perinatal asphyxia; therefore, a single CRP measurement is insufficient for therapeutic decision-making. In pediatric patients, CRP effectively differentiates bacterial from viral infections but is less specific than PCT (11). For PCT, age specificity is particularly important (Table 4). PCT should not be interpreted as a marker of sepsis within the first 72 hours of life without serial measurements. Beyond the neonatal period, PCT represents the most reliable marker of bacterial infection and sepsis in children, as it rises and falls more rapidly than CRP and is not elevated in viral infections (12). Clinical Application of Inflammatory Biomarkers in Primary Care Mild respiratory infections: CRP alone is usually sufficient; values below 40 mg/L generally suggest a viral etiology. Bronchitis and pneumonia: CRP and, if necessary, PCT may aid in decisions regarding antibiotic therapy. Urinary tract infections: In febrile patients, PCT may help differentiate pyelonephritis from cystitis. Autoimmune diseases: A combination of ESR and CRP is optimal for monitoring disease activity. Chronic infections (e.g., endocarditis, tuberculosis): ESR often remains elevated even after CRP normalization. Suspected sepsis: Combined measurement of CRP and PCT provides the greatest diagnostic and prognostic value. Conclusion ESR, CRP, and PCT are not competing but complementary inflammatory markers. ESR remains useful in the assessment of chronic and systemic diseases, CRP is the gold standard for rapid detection and monitoring of acute inflammation, while PCT is the most valuable marker for bacterial sepsis and rational antibiotic therapy. Appropriate indication and interpretation of these markers, particularly in the context of clinical presentation and symptom duration, enable more rational antibiotic prescribing, earlier detection of serious infections, and improved collaboration between primary care and laboratory medicine.
Acute-Phase Proteins; Blood Sedimentation; C-Reactive Protein; Procalcitonin
Copyright (c) 2026 Jasna Leniček Krleža https://creativecommons.org/licenses/by/4.0
Treatment options for obesity in children
Childhood obesity is a global public health problem of the 21st century. Today, childhood obesity is considered a complex chronic, relapsing disease that negatively affects the quality of life, not only by causing unnecessary accumulation of adipose tissue, excessive body weight, but also by triggering severe health complications that have traditionally been described in adults. These complications include type 2 diabetes, hyperlipidemia, and cardiovascular disease, as well as many other negative health consequences. The etiology of obesity is multifactorial and includes genetic predisposition, environmental factors, socio-economic and behavioral factors. Obesity that begins in early childhood often continues into adolescence. It has been observed that obese adolescents have a higher risk of remaining obese in adulthood. Treatment of obesity in children requires a comprehensive approach, including changes in health behavior and lifestyle, pharmacological, psychological, motivational, metabolic and surgical interventions. The first step in treating childhood obesity is considered to be changing unhealthy behavior and lifestyle. This intervention is considered safe in almost all age groups of children and includes nutritional interventions aimed at changing unhealthy eating habits and establishing long-term healthy eating habits and can be combined with motivational and psychological support. If necessary, this intervention may be combined with other treatment modalities including pharmacotherapy and surgery. It is also considered that this intervention should be individually tailored personalized. Such an approach also requires a comprehensive understanding of the polygenic factors that contribute to obesity and their interactions with genetic factors, pathogenic environmental factors, and the impact on the outcomes of different treatment strategies. Also, a personalized approach to the treatment of obesity in children aims to increase the effectiveness of interventions and reduce side effects. Interventions that include changes in health behavior and lifestyle, however, require further research. The addition of anti-obesity medication to an intervention that changes health behavior and lifestyle is considered a step that should be taken immediately after the diagnosis of obesity in children. This combination shows promise for the effective management of obesity in children (1-4). The use of anti-obesity medications in children must be rational because it is still unknown whether and what the negative effects of these medications on the child's growth and development may be. Data on the efficacy and safety of anti-obesity medications in children mainly come from not so many clinical trials, and long-term effects on weight loss, adherence to treatment, and side effects require long-term evaluation. Poor reimbursement for anti-obesity medications, a lack of prevention programs, and a widespread belief that obesity is not a chronic disease are also issues that limit the practice of initiating treatment for obesity in childhood. Effective treatment of childhood obesity requires a comprehensive, multidisciplinary approach that addresses not only the physical aspects of obesity, but also social, socioeconomic, and other factors. Overcoming the barriers to treating childhood obesity will require firm efforts by health care providers, researchers, policymakers, and families.
Copyright (c) 2026 Ivana Unić Šabašov https://creativecommons.org/licenses/by/4.0
Ten steps in the prevention and treatment of food allergy and anaphylaxis
Serious allergic reactions develop within minutes or several hours after exposure to an allergen. In children, the majority of serious allergic reactions are caused by food allergens. Anaphylaxis is a serious allergic reaction that occurs rapidly and can cause death. Intramuscularly applied adrenaline is the first-line therapy for the treatment of anaphylaxis. Adrenaline autoinjectors should be prescribed to all patients who have had an anaphylactic reaction or are at high risk of developing one. Adrenaline autoinjectors should be used by parents, teachers, or older children in all anaphylactic reactions, including those less severe. Parents, children, and teachers should be regularly educated on how to use adrenaline autoinjectors. Children with severe food allergies and their parents face a high risk of severe allergic reactions during everyday life. The collaboration of children, parents, teachers, primary care specialists and allergologists, as well as the healthcare system and food industry is important to minimize the burden of severe food allergy.
Food Hypersensitivity; Anaphylaxis; Epinephrine; Delivery of Health Care; Parents
Copyright (c) 2026 Iva Topalušić, Ozana Hofmann Jaeger, Maja Bosanac, Ivan Pavić https://creativecommons.org/licenses/by/4.0
Probiotics in paediatric gastroenterology
INTRODUCTION Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (1). In paediatric gastroenterology, their use has expanded substantially in recent years, driven by an increasing understanding of the role of the gut microbiota in the pathogenesis of various gastrointestinal diseases. However, numerous studies have demonstrated that the effects of probiotics cannot be considered a class effect of all products, but are strictly strain-specific and dependent on dose, duration of administration, and the specific clinical indication. This has direct implications for clinical practice, as probiotics that are effective for one indication may not be effective for another. The 2023 recommendations of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) represent the most comprehensive and methodologically robust evaluation of the evidence regarding the use of probiotics in children with gastrointestinal disorders (2). This document systematically analysed randomized controlled trials (RCTs), meta-analyses, and systematic reviews using the GRADE methodology, allowing an objective assessment of the quality of evidence and strength of recommendations. More recent publications largely confirm these conclusions, emphasizing the need for a critical approach and discouraging uncritical, routine use of probiotics in everyday paediatric practice. GASTROENTEROLOGICAL INDICATIONS FOR PROBIOTIC USE Acute gastroenteritis Acute gastroenteritis is one of the most common indications for probiotic use in children. The ESPGHAN document analysed more than 30 randomized controlled trials involving several thousand children of different ages and with various causes of diarrhoea. The best-documented probiotic strains are Lacticaseibacillus rhamnosus GG (LGG), Saccharomyces (S.) boulardii, and Limosilactobacillus (L.) reuteri DSM 17938. Meta-analyses indicate that these strains may reduce the duration of diarrhoea by approximately 20–24 hours, decrease the need for hospitalization, and shorten the length of hospital stay (3–6). However, heterogeneity among studies, differences in dosage and duration of treatment, and changes in the epidemiology of gastroenteritis—particularly following the introduction of rotavirus vaccination—limit the clinical applicability of these findings. Therefore, probiotics are recommended only as an adjunct to standard therapy (oral rehydration), not as a replacement for established treatment measures. Antibiotic-associated diarrhoea (AAD) Antibiotic-associated diarrhoea is a common adverse effect of antibiotic therapy, particularly in young children and hospitalized patients. Analysis of more than 20 RCTs and several large meta-analyses has shown that probiotics, especially LGG and S. boulardii, can reduce the risk of AAD from approximately 19% to 8–10% (7, 8). The effect is particularly pronounced when high doses (≥5 × 10⁹ CFU/day) are used and in children with additional risk factors, such as prolonged antibiotic treatment, hospitalization, or comorbidities. These probiotic strains are recommended to be initiated early, ideally at the start of antibiotic therapy. Nevertheless, there are currently no clear recommendations for routine probiotic use in all children receiving antibiotics, and a selective approach targeting high-risk children appears more pragmatic. Prevention of nosocomial diarrhoea Nosocomial diarrhoea represents a significant problem in hospital settings, particularly in paediatric wards. More than 10 studies, primarily involving hospitalized young children, have been analysed. The strongest evidence supports the use of LGG, which has been shown to reduce the incidence of hospital-acquired diarrhoea, particularly rotavirus-associated diarrhoea (9, 10). In contrast, L. reuteri DSM 17938 has not demonstrated consistent benefit in this indication and is therefore not recommended for the prevention of nosocomial diarrhoea. Functional gastrointestinal disorders (disorders of gut–brain interaction) Infantile colic is a functional disorder with a substantial impact on the quality of life of the entire family. More than 15 RCTs and several meta-analyses have evaluated the efficacy of probiotics in this condition (11–20). The strongest evidence supports the use of L. reuteri DSM 17938 in breastfed infants, in whom it significantly reduces crying time and increases the proportion of infants achieving clinically meaningful improvement. Bifidobacterium (B.) lactis BB-12 has also shown beneficial effects, although fewer studies are available. In formula-fed infants, evidence remains limited and inconsistent. As no causal therapy exists for pain-related functional gastrointestinal disorders in older children, a number of studies have investigated the effects of probiotics in functional abdominal pain (FAP) and irritable bowel syndrome (IBS). Approximately 15–20 studies including children diagnosed according to Rome IV criteria have been analysed (21–23). Probiotics—particularly L. reuteri DSM 17938 in FAP and LGG in IBS—have demonstrated moderate reductions in pain intensity and frequency, but without a clear impact on quality of life or long-term outcomes. Due to heterogeneity and variability in study results, recommendations for probiotic use in these indications are weak. For functional constipation in children, more than 10 RCTs are available, but results are inconsistent (21, 24, 25). Most studies have not demonstrated clinically meaningful improvements compared with placebo, either in stool frequency or subjective symptom relief. Consequently, probiotics are not recommended as a standard component of therapy for functional constipation. Helicobacter pylori infection Approximately 10 studies have investigated the use of probiotics as adjuncts to eradication therapy (26, 27). Saccharomyces boulardii has been shown to reduce treatment-related adverse effects and to slightly increase eradication rates, although without achieving optimal eradication outcomes. Chronic inflammatory bowel disease (ulcerative colitis and Crohn’s disease) In the paediatric population, there are very few high-quality RCTs evaluating the efficacy of probiotics in the treatment of chronic inflammatory bowel disease. Most available evidence is derived from adult studies, which limits its applicability to children. At present, there is insufficient evidence to support routine probiotic use in paediatric IBD (2). Coeliac disease, small intestinal bacterial overgrowth (SIBO), and pancreatitis Available studies in these indications are scarce, small, and heterogeneous. There is insufficient evidence to recommend probiotics as part of standard clinical practice (2). CONCLUSION Probiotics have a role in selected areas of paediatric gastroenterology, but their use must be strictly indication-specific and evidence-based. The greatest benefit has been documented in acute gastroenteritis, prevention of antibiotic-associated diarrhoea, and infantile colic, whereas evidence for other indications is limited or lacking. Appropriate use requires careful selection of the probiotic strain, dose, and duration of therapy, as well as the use of products of verified quality.
Child; Gastrointestinal Diseases; Gastrointestinal Microbiome
Copyright (c) 2026 Iva Hojsak https://creativecommons.org/licenses/by/4.0
Autoimmune encephalitis (AE) is a rare disease with a wide spectrum of symptoms, which in most cases presents with nonspecific symptoms. Distinguishing AE from infectious encephalitis is a key challenge. According to the subcommittee of the International Working Group on Autoimmune Encephalitis, the criteria for the classification of pediatric adverse events and the algorithm for early diagnosis in children with acute or subacute onset of neuropsychiatric symptoms include EEG, blood, urine, and CSF samples for AE antibodies and, as soon as possible, brain MRI. The most common AEs are Anti-NMDAR (Anti-N-methyl-D-aspartate receptor) encephalitis, Anti-MOG (Anti-myelin oligodendrocyte glycoprotein) encephalitis, Rasmussen encephalitis, paraneoplastic encephalitis, and Hashimoto's encephalitis. Screening for malignancies and receiving appropriate and timely treatment are particularly important for achieving better treatment outcomes, although some patients may take weeks, months, or even years to recover. Therefore, MRI monitoring over a longer period is justified.
Autoimmune Diseases of the Nervous System; Infectious Encephalitis; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Rare Diseases
Copyright (c) 2026 Ana Tripalo Batoš https://creativecommons.org/licenses/by/4.0
Corticophobia in pediatric practice – challenges and strategies in the use of topical corticosteroids
Corticophobia, defined as excessive fear, concern, or distrust of the use of corticosteroids, is common in pediatric practice, particularly in the treatment of atopic dermatitis. Although topical corticosteroids are the mainstay of anti-inflammatory treatment for atopic dermatitis and, when used correctly, are effective and safe, parental and patient fears often lead to underuse or misuse, resulting in poor disease control. The most common concerns include the possibility of skin thinning, immunosuppression, growth retardation, and the occurrence of “steroid addiction,” with significant influence from information from the Internet, social media, and advice from the community. Corticophobia is also prevalent among healthcare professionals, particularly pharmacists and family physicians, which further contributes to inconsistent recommendations and parental uncertainty. The TOPICOP scale, a validated instrument for assessing corticophobia, allows for the identification of specific beliefs and concerns that affect adherence. According to the literature, corticophobia is present in 21–77% of parents of children with atopic dermatitis and in 36–84% of adult patients. Key interventions for its reduction include structured education, demonstration of the correct application of topical preparations, clear and consistent recommendations from health professionals, and emotional support for parents. Building trust and personalized communication often have a greater impact than simply informing about the safety of medications. Successful recognition and targeted reduction of corticophobia is crucial for achieving good adherence and optimal therapeutic outcomes in children with atopic dermatitis. Fear should be transformed into knowledge, and education should be an integral part of treatment to ensure the effective and safe use of topical corticosteroids.
Treatment Adherence and Compliance; Dermatitis, Atopic; Child; Administration, Topical
Copyright (c) 2026 Arnes Rešić, Sanita Maleškić Kapo, Nives Pustišek https://creativecommons.org/licenses/by/4.0
Perforation of an subacutely inflammed apendix with formation of an intrahepatic abscess - a case report
Intrahepatic perforation of an inflamed appendix is an exceptionally rare condition, attributed both to its atypical clinical presentation and the anatomycal variability in the position of the appendix, posing a distinctive diagnostic and therapeutic challenge. Typically, appendicitis as an entity results in a localized infection or abscess formation within the right lower quadrant of the abdomen. Here, we report a case demonstrating a specific anatomical variation, presenting with intrahepatic perforation and subsequent hepatic abscess formation in a two-year-old child with atypical clinical presentation. This case report discusses the underlying pathophysiological mechanisms, diagnostic workup, management strategies, and clinical implications of intrahepatic appendiceal perforation.
Copyright (c) 2025 Marko Mesić, Ljudevit Sović, Nina Krajcar, Maja Vrdoljak Pažur, Tonči Grmoja, Ana Močić Pavić, Fran Štampalija, Mario Kopljar https://creativecommons.org/licenses/by/4.0
Neonatal chylopericardium: Coincidence or complication related to vascular access?
Introduction: Chylopericardium is a rare entity characterized by the accumulation of lipid-rich, milky fluid in the pericardial cavity, which may evolve into life-threatening complications such as cardiac tamponade. In neonates, most cases are idiopathic, though secondary causes include surgical injury, trauma, or lymphatic malformations. Clinical presentation ranges from incidental findings to acute hemodynamic collapse, representing a diagnostic challenge in fragile populations such as preterm infants. Case report: We report the case of a preterm male infant, born at 31 weeks’ gestation by cesarean section for severe preeclampsia. Shortly after birth he developed respiratory distress requiring surfactant therapy, invasive ventilation, and multiple central line attempts, complicated by malpositioned catheters. On the fifth day of life, progressive tachycardia, worsening respiratory distress, and anuria prompted echocardiography, which revealed a significant pericardial effusion. Ultrasound-guided pericardiocentesis yielded 21 mL of chylous fluid with triglyceride levels of 691 mg/dL and sterile cultures, confirming neonatal chylopericardium. Conservative management was initiated, including drainage, total parenteral nutrition, suspension of enteral feeding, and gradual reintroduction of adapted enteral nutrition. The infant showed favorable progression, with no recurrence of effusion, and was eventually discharged to intermediate care in stable condition. Conclusion: This case highlights the diagnostic and therapeutic challenges of neonatal chylopericardium, particularly in preterm infants where vascular trauma may be suspected but not evident. Early recognition combined with conservative management can be effective, avoiding surgical interventions and improving outcomes in this vulnerable population.
Copyright (c) 2025 Carlos Hugo Torres-Salinas, Gabriela Espinoza-Alvarez, Ernesto Leiva-Quintanilla https://creativecommons.org/licenses/by/4.0