Nusa Matijasic

Background and Clinical Significance: Skin-limited Langerhans cell histiocytosis (LCH) is a clinically heterogeneous disease, ranging from self-healing forms to fulminant multi-organ failure, the latter being more often described in infants, especially preterm neonates. The optimal therapy for cutaneous LCH remains controversial; the possibilities vary from a watchful waiting approach to systemic chemotherapy. Case Presentation: This case report describes an exceptionally rare and clinically challenging course of skin-limited LCH in a prematurely born infant treated at the Department of Oncology and Hematology, Children’s Hospital Zagreb, Croatia. At presentation, the patient exhibited several features suggestive of aggressive disease biology. However, therapeutic decision-making was complicated by extreme prematurity and young age, both of which significantly increased vulnerability to treatment-related toxicity. Following failure of topical therapy, systemic treatment was initiated according to the LCH-IV trial, primarily due to concerns regarding potential evolution into multisystem LCH. During treatment, the patient developed multiple life-threatening complications, namely severe infections (Staphylococcus aureus endocarditis, Pneumocystis jirovecii pneumonia, and Enterobacter cloacae sepsis), aggravated by secondary hypogammaglobulinemia, neutropenia, and iatrogenic adrenal insufficiency. Conclusions: The varied nature of cutaneous LCH underscores the necessity for a tailored treatment approach. When deciding on the treatment modality, clinicians should weigh the benefits of aggressive therapies, ensuring better disease control, against the potential for severe adverse effects, particularly in young, fragile infants with immature immunity.

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5–93.2%). Hospital admission rates varied among the centers (9.4–35%), and so did transfusion policies (6.4–22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3–21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

Introduction: The use of complementary and alternative medicine (CAM) has become a customary practice among pediatric cancer patients worldwide. The frequency of its use by pediatric cancer patients in Croatia has not been previously determined. Methodology: In order to establish the frequency and detect factors affecting the use of CAM, a single-center, observational, cross-sectional study was conducted at the Children's Hospital Zagreb during a two-year period. The patients' parents and caregivers were offered an anonymous, multi-item questionnaire that collected socio-economic and clinical data, as well as details on CAM and dietary supplement practice. Results: Almost half of the participants reported CAM and more than two-thirds reported dietary supplement consumption, predominantly in the intensive phase of the treatment. Factors regarding children or parents had no effect on CAM and supplement utilization. Herbal medicine, vitamins, and minerals were among the most commonly used items. Every 10th child experienced at least one adverse event during CAM and supplement use. Conclusion: Awareness of the CAM and dietary supplement application in pediatric oncology patients needs to be raised due to the potential interactions with conventional treatment modalities. For this reason, it is extremely important to inform parents and caregivers of pediatric oncology patients about the use of CAM and dietary supplements to predict and mitigate the occurrence and intensity of the side effects. In the majority of our cases, the patient's guardians informed the healthcare professionals about the CAM and supplement implementation in their children, therefore, they were offered additional information about the possible negative impact of CAM and supplement use on standard medical care in a timely manner.

Achromobacter xylosoxidans is an aerobic, Gram-negative rod with a broad intrinsic and acquired antimicrobial resistance, usually isolated in patients with cystic fibrosis (CF), immunodeficiencies, or those undergoing invasive procedures. We report a case of a previously healthy 14-year-old girl who was hospitalized in our institution due to a prolonged, progressive cough and exertional dyspnea, which started after a mild viral respiratory tract infection. To elucidate the cause of her symptoms, a bronchoscopy was finally performed, showing bilateral purulent bronchitis caused by A. xylosoxidans, isolated from bronchoalveolar lavage (BAL) sample. Since the patient had positive serological testing for coronavirus disease 2019 (COVID-19), we concluded that it was the initial viral infection, although of a mild clinical course, the one that created favorable conditions for proliferation and further inflammation caused by A. xylosoxidans.

Our goal was to describe demographic characteristics, course and outcome of neutropenic patients. We used descriptive statistics to demonstrate demographic and clinical characteristics of patients who were referred to pediatric hematologist’s examination or hospitalized in the Department of Hematology and Oncology, Children’s Hospital Zagreb, due to neutropenia from January 1st, 2009 to December 31st, 2019. Oncology patients with febrile neutropenia were excluded from the study. Altogether, 100 children were examined or hospitalized in our Department during the 11-year period due to neutropenia, of which 56 were males, with an average age of 3.48 years. The cause of a low absolute neutrophil count (ANC) was autoimmune neutropenia in 37 patients, 31 had chronic idiopathic neutropenia, 27 had infectious neutropenia, 3 had cyclic neutropenia, while 2 were diagnosed with alloimmune neonatal neutropenia. The mean value of ANC at presentation was 732/mm3, and the mean lowest ANC detected during disease course was 600/mm3. Among the 5 diagnostic subgroups, both values were the lowest in patients with cyclic neutropenia in which mean ANC at presentation was 420/mm3 and mean lowest ANC detected during disease course was 180/mm3. Granulocyte colony-stimulating factor (GCS-F) was given to only 3 patients, whose mean ANC at presentation was 140/mm3. Besides the laboratory finding of persistent severe neutropenia, all 3 patients were prone to recurrent infections. Twenty-three patients had additional cytopenia, out of which 4 had pancytopenia, 13 had anemia and 6 patients had thrombocytopenia. Among patients with additional cytopenia, 5 had positive anti-granulocyte antibodies (21.7%). The mean time to disease resolution was 10.2 months, being the longest in the cyclic neutropenia subgroup, while patients with infectious neutropenia mainly recovered after 21.3 days. The mean follow-up time was 1.6 years. According to data from our Department, neutropenia is most commonly diagnosed in pre-school children, boys being more frequently affected than girls. More than one third of patients have positive anti-granulocyte antibodies. However, the condition is usually benign, it resolves mainly spontaneously in less than a year, and patients generally do not require G-CSF.

Introduction Autosplenectomy defines spontaneous splenic infarction leading to hyposplenism. It occurs mainly as a complication of sickle cell anemia, pneumococcal sepsis or systemic lupus erythematosus, but may also be associated with various other conditions. An anatomical variation of the spleen’s position, the wandering spleen, has been reported as an underlying cause in less than 0.5% of autosplenectomy cases. Case Report A 9.5-month-old female was admitted to the Department of Oncology and Hematology of the Children’s Hospital Zagreb due to a prolonged fever of an unknown origin and splenomegaly. Laboratory findings detected profound normocytic anaemia, attributed to splenic sequestration. Abdominal ultrasound detected multiple hypoechoic areas in the spleen, indicating splenic infarction, confirmed by MR angiography. An extensive work-up excluded sickle cell anemia, thalassemia, hematological malignancies, myeloproliferative disorders, thrombophilia, autoimmune vasculitis, Kawasaki disease and infection as a cause of the condition. However, repeated ultrasound examination revealed an aberrant, ventrally positioned spleen, which most likely led to an inadequate blood supply and consequently splenic infarction. Antiplatelet therapy and antibiotic prophylaxis were initiated, along with pneumococcal and meningococcal vaccines. The patient is still monitored regularly, currently with normal hematological laboratory findings and none of the complications possibly attributed to hyposplenism. Conclusion Autosplenectomy in children, although rarely, may result from an aberrant spleen’s position. Congenital weakness of the splenic ligaments, allowing its mobility, causes torsion of the splenic artery, leading to blood supply failure and tissue damage. Given the wide differential diagnosis of splenic infarction, it is necessary to exclude numerous underlying medical conditions, primarily sickle cell anemia. A conservative approach is currently the treatment of choice. Hyposplenism, leading to susceptibility to sepsis caused by encapsulated bacteria, requires appropriate antibiotic prophylaxis and vaccination of such patients.

Background: Impaired lung function has been detected in up to 65% of all childhood cancer survivors. It is often caused by exposure to radiation therapy and various chemotherapeutics. The first cytotoxic drug ever identified as a causative agent of lung injury was busulfan, reported in the early 1960s. Signs and symptoms of busulfan lung are nonspecific and it is therefore difficult to differentiate the condition from pulmonary impairment caused by other pulmotoxic agents, infections, pulmonary metastases, graft-versus-host disease, or other noninfectious post-transplant complications involving the lungs. Methods: A case example is provided to illustrate the difficulties in management of busulfan-induced lung injury in children. A retrospective review of cases of busulfan-induced lung injury indexed in PubMed until March 2019 was performed. Inclusion criteria for articles was available in full text in English. Results: Impaired lung function caused by busulfan may become an increasing problem for young survivors. Conclusion: Newly developed dyspnea or subclinical damage detected on pulmonary function tests, indicating primarily restrictive disease, should always arouse suspicion of busulfan-induced lung injury in a child conditioned with busulfan, especially after excluding other leading culprits of pulmonary damage affecting oncology patients.