Characteristics and treatment results of refractory and relapsed acute myeloid leukaemia in paediatric patients treated in Polish Paediatric Leukaemia/Lymphoma Study Group institutions according to the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 and a review of novel treatment possibilities in paediatric acute myeloid leukaemia.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.

Isolated central nervous system relapses in patients with high-risk neuroblastoma -clinical presentation and prognosis: experience of the Polish Paediatric Solid Tumours Study Group.

Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.

Serum heat shock protein 90 as a future predictive biomarker in childhood acute lymphoblastic leukemia.

Heat shock proteins (HSPs) attract the attention of scientists and clinicians due to their potential role as diagnostic and prognostic factors in a variety of cancers. HSP90 is one of the most important and well-known family members, necessary for maintaining intracellular homeostasis. In the extracellular space, it is responsible for the transmission of alarm signals to the immune system. Numerous reports have indicated that the level of intra - and extracellular HSP90 can correlate either with a poorer prognosis or with a better outcome, depending on the type of cancer. Still, little is known why the level of this chaperone is increased in some tumors and decreased in others, reflecting dual role of protein in cell death processes. Currently, there is no database reporting levels of serum HSP90 in children with acute lymphoblastic leukemia (ALL). As such, using enzyme-linked immunosorbent assay (ELISA) method, we aimed to determine this parameter in a group of 21 patients with newly diagnosed ALL. We found decreased protein serum levels in patients at disease presentation and after induction block of chemotherapy in comparison to healthy controls. Furthermore, we observed a negative correlation between HSP90 serum levels and one of the earliest prognostic factors of the treatment response - peripheral blood lymphoblasts on the 8th day of treatment. Our results indicate that HSP90 serum may play an important role in leukemogenesis and could be used as a marker to predict treatment failure in children with ALL.

Tumour expressions of hypoxic markers predict the response to neo-adjuvant chemotherapy in children with inoperable rhabdomyosarcoma.

Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992-2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72-125.75; p = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.

Endometrial glial polyp and peritoneal gliomatosis: Neuropathological lesions in gynecological biopsy.

The wide scope of neuropathology is also connected to different systemic pathology findings. Neuroectodermal-type female genital tract lesions are not frequent. This article presents a short review of such entities in gynecological pathology and reports on two rare cases. The first described lesion is an endometrial glial polyp in a young woman. The second is a mature cystic teratoma accompanied by a peritoneal gliomatosis in an adolescent girl. Both presented entities posed diagnostic difficulties from the clinical and pathological perspective. They demanded careful sampling, immunophenotyping, as well as neuropathological consultation.

Sonographic Image of Solitary Kidney in Wilms Tumour Survivors.

BACKGROUND/AIMS: This study presents an analysis of the sonographic and laboratory parameters of solitary kidney in Wilms tumour survivors (TWs) and compares these parameters with those of healthy individuals. METHODS: Fifty-three TWs who completed treatment for Wilms tumour and 44 healthy individuals were enrolled. The study protocol consisted of completing a medical history, sonographic examination of the solitary kidney, estimation of glomerular filtration rate (eGFR) by the Schwartz or MDRD formulas, albumin urine excretion and BP measurement. RESULTS: Sonographic signs of kidney damage were observed in 22 (41,5%) TWs. The most frequently detected abnormalities are hyperechoic rings around renal pyramids (28,3% TWs). Hypertrophy of the solitary kidney occurred in 71,7% of cases. The mean volume of the solitary kidney was 77% of the sum of the two kidney volumes in the control group. The median eGFR in the TWs group was 117 with 25Q-105,5, 75Q-130 ml/min/1,73 m2 vs 131,8 with 25Q-124, 75Q-140 ml/min/1,73 m2 in the control group (p=0,000). Six TWs (11,3%) had a value of eGFR below 90 ml/min/1,73 m2. Increased urine albumin excretion (> 30 mg/g) was observed in 7 TWs (13,2%) and in 3 (6,8%) individuals in the control group. CONCLUSION: Ultrasonographic abnormalities in solitary kidney of TWs are frequent. The most frequently detected abnormalities are hyperechoic rings around renal pyramids. Sonographic examination of TWs ought to be performed not only to detect tumour recurrence but also to assess the signs of kidney damage and their progression.

Rosai-Dorfman disease as a rare cause of cervical lymphadenopathy - case report and literature review.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, benign clinical entity of unknown cause. RDD is characterised by the overproduction and accumulation of histiocytes, primarily in the lymph nodes, although it may affect every organ and system. It predominantly affects children and young adults. Typically, patients are in good general condition, with massive cervical lymphadenopathy and fever. In about 40% of cases extranodal localisation of RDD is diagnosed. In laboratory tests the most common abnormalities are increased erythrocyte sedimentation rate (ESR), leukocytosis with neutrophilia, normocytic anaemia, and hypergammaglobulinaemia. Histopathological examination remains the mainstay of diagnosis - lymph nodes have massive sinusoidal dilation, containing histiocytes positive for S-100 and CD68, and negative for CD1a. Most patients do not require treatment as spontaneous remissions are observed. We present a brief review of the literature and the case of a six-year-old boy with cervical lymphadenopathy diagnosed with RDD. So far, the patient has not required systemic treatment and has been kept under observation.

Sinusoidal obstruction syndrome in a paediatric patient with acute lymphoblastic leukaemia after completion of reinduction therapy according to ALL Intercontinental Berlin-Frankfurt-Münster 2009.

Sinusoidal obstruction syndrome (SOS), also termed veno-occlusive disease (VOD) of the liver, is a well-known complication of haematopoietic stem cell transplantation (HSCT) both in children and adults. In the medical literature there are occasional reports of SOS in patients receiving conventional chemotherapy. In children with solid tumours this entity occurs during treatment of nephroblastoma, rhabdomyosarcoma, and medulloblastoma. In the late 1990s SOS was quite often observed as the complication of oral 6-thioguanine (6-TG) in patients suffering from acute lymphoblastic leukaemia (ALL), who received 6-TG throughout maintenance. In current protocols, the syndrome has become uncommon because treatment with 6-TG is limited to two weeks of oral therapy. Here, we report a case of a nine-year-old boy with ALL, who developed sinusoidal obstruction syndrome shortly after completing the reinduction block of chemotherapy (cyclophosphamide, cytarabine, thioguanine) according to the ALL Intercontinental Berlin-Frankfurt-Münster 2009 (ALL IC BFM 2009) treatment protocol.

HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

Outcome of acute lymphoblastic leukemia in children with down syndrome-Polish pediatric leukemia and lymphoma study group report.

Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared with the general population. The aim of the study was to analyze the outcome of patients diagnosed with Down syndrome and acute lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those, 41 (2.2%) had DS. The children were classified into three risk groups: a standard-risk group-14 patients, an intermediate-risk group-24, a high-risk group-3. All patients were treated according to ALLIC 2002 protocol. The median observation time of all patients was 6.1 years, and in patients with DS 5.3 years. Five-year overall survival (OS) was the same in all patients (86% vs 86%, long-rank test, p = .9). The relapse-free survival (RFS) was calculated as 73% in patients with DS and 81% in patients without DS during a median observation time (long-rank test, p = .3). No statistically significant differences were found in the incidence of nonrelapse mortality between those two groups of patients (p = .72). The study was based on children with ALL and Down syndrome who were treated with an identical therapy schedule as ALL patients without DS, according to risk group. This fact can increase the value of the presented results.

Comparative genomic analysis of intracranial germ cell tumors - the preliminary study focused on Sonic Hedgehog signaling pathway.

AIM OF THE STUDY: Examination of copy number changes in a group of intracranial germ cell tumors (GCTs) with particular focus on putative aberrations of the main genes coding SHh pathway proteins. MATERIAL AND METHODS: The study was performed on DNA isolated from fresh-frozen tumor tissue samples from eight GCTs, including six intracranial GCTs. The intracranial group consisted of three germinomas, two mature teratomas and one mixed germ cell tumor. Comparative genomic profiling analysis was carried out using microarray-CGH method (Cytosure ISCA UPD 4×180k, OGT). The results were analyzed with Feature Extraction (Agilent Technologies) and Nexus Copy Number (BioDiscovery) softwares. RESULTS AND CONCLUSIONS: Chromosomal aberrations were found in two intracranial germinomas. These tumors were characterized by complex genomic profiles encompassing chromosomes 7, 8, 9, 10, 11, 12, 16, 17 and 19. Common findings were gain at 12p13.33p11.1 of 35 Mbp and gain at 17q11.1q25.3 of 55 Mbp. In one tumor, also SHh (7q36.3), SMO (7q32.1) and GLI3 (7p14.1) copy gains occurred together with 9q21.11q34.3 loss, including PTCH1, all being elements of SHh signaling pathway. Moreover, both tumors showed various copy gain of genes being ligands, regulators, receptors or target genes of SHh (MTSS1; PRKACA and FKBP8) as well as gain of genes of SHh coopting WNT pathway (WNT3, WNT5B, WNT9B in both tumors; WNT16, WNT2 in pineal lesion). Further studies on larger group are needed to characterize SHh-related gene alterations in intracranial GCTs and for searching genotype-phenotype relations.

Determination of Bendamustine in Human Plasma and Urine by LC-FL Methods: Application in a Drug Monitoring.

Simple and sensitive liquid chromatography (LC) methods with fluorescence (FL) detection for the determination of bendamustine (BM) in human plasma and urine were developed and validated. The procedure of BM extraction from a plasma sample involved solid-phase extraction with a C18 SPE column, while liquid-liquid extraction with dichloromethane was applied for a urine sample. In both methods, cinoxacin was used as the internal standard. Chromatographic separations were performed on a Synergi Max-RP column, while FL detector was set at the excitation wavelength of 328 nm and the emission wavelength of 420 nm. The LC-FL methods were validated for accuracy, precision, selectivity, linearity, recovery, and stability. The detection limits for BM were 0.5 and 2.5 ng mL-1 in plasma and urine, respectively. The intra-day and inter-day precisions were less than 9.86 %, while the accuracies were higher than 92.63 and 94.29 % for BM in plasma and urine, respectively. The proposed LC-FL methods were sensitive, robust, and specific, allowing reliable drug quantification in plasma and urine samples. The methodologies were successfully applied to monitoring of BM in a child with cancer treated with BM.

Transient hypogammaglobulinaemia of infants in children with mastocytosis - strengthened indications for vaccinations.

Mastocytosis is a disease caused by the accumulation of mast cells (MC) in the skin and/or in other tissues. Both the cutaneous form of the disease (CM) predominating in children and the systemic form (SM) typical for adults are associated with the occurrence of MC mediator-related symptoms. The release of mediators can be induced by physical stimuli and/or specific triggering factors. The routine vaccination program performed in the majority of children in infancy can be considered as an additional factor provoking exacerbation of CM. Conscious of the important role of MC in the innate immunity, we have analysed retrospective data concerning the levels of immunoglobulins, an adaptive factor, in a group of 74 infants and toddlers with CM. The values corresponding to transient hypogammaglobulinaemia of infants (THI) were found in 8 (10.81%) of cases. Classification of the antibody deficiency was done according to the working definitions for clinical diagnosis of primary immunodeficiency of the European Society of Immunodeficiencies (ESID) Registry - version May 11, 2015. Following the retrospective data, the final diagnosis of THI cannot be made due to the young age of the study group. The percentage may significantly exceed the published incidence of THI, i.e. about 0.11%. The results of our study may indicate, importantly, a higher incidence of THI in childhood-onset mastocytosis than in the general paediatric population and strengthen indications for vaccinations. In conclusion, we suggest that THI may be considered as a new aspect of paediatric mastocytosis that requires further investigation.

[Hereditary hemochromatosis in children].

Iron is a micronutrient which is essential for the existence of organisms. This element participates in oxygen transport, as well as energetic, metabolic and immunologiocal processes. Disturbances of iron homeostasis lead to multiorgan dysfunction. Iron deficiency anemia is a common disorder in childhood, while iron overload is rarely observed in the developmental age. There are primary and secondary reasons for iron overload. Hereditary hemochromatosis is a metabolic disorder caused by the mutations of genes that control iron metabolism leading to increased intestinal absorption. Secondary hemochromatosis is caused by multiple transfusions, chronic hemolysis, or iron pills and iron-rich food intake. The article reviews the literature devoted to primary iron overload in childhood.

[Prolonged leucopenia in asymptomatic children]. / Przedluzajaca sie leukopenia u dzieci bez objawów chorobowych.

INTRODUCTION: The term leucopenia is still a challenge for clinicists in cases of unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons: some drugs, infections, viral mainly, autoimmune diseases, haematological abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this investigation was an analysis of asymptomatic, lasting over three months leucopenia myelograms of childhood. MATERIAL AND METHODS: 21 children (6 girls and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The children were referred to our clinic by family physicians to investigate the reason of asymptomatic, lasting over three months leucopenia. These children are still under our observation from one till four years. Despite the fact of lasting over three months leucopenia, the general condition of the patients is good. In all the patients the myelogram analysis was performed after May-Grumwald-Giemsa dying, three slides of one hundred cells were counted. Statistical analysis was made using STATISTICA (Stat Soft Polska) programme. RESULTS: Mean number of leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to 3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l, values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets number were normal. Mean number of marrow cells were within references. However mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than mean number of general population marrow cells (p<0.05). Mean values of myeloblasts, neutrophils, and monocytes were statistically higher than in general population (p<0.05). CONCLUSIONS: 1. Hypothesis of obtained differencess in numer of marrow cells would need to be investigated in broad population of patients. 2. Considering that three children presented with positive familial leucopenia history (in one of them grandmother, in two anothers fathers) genetic predisposition can be expected.

Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005-2011 - experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG).

AIM OF THE STUDY: Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005-2011. MATERIAL AND METHODS: The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. RESULTS: Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. CONCLUSIONS: The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

Acute Pancreatitis in Pediatric Acute Lymphoblastic Leukemia (AcuPA Study): A Nationwide Survey in Poland.

PURPOSE: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. METHODS: The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL. RESULTS: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006-1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively). CONCLUSIONS: The incidence of AP in children with ALL is low and related to patients' age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.

Deregulated systemic IL-10/IL-12 balance in advanced and poor prognosis paediatric soft tissue sarcomas.

CONTEXT: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear. OBJECTIVE: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS). MATERIALS AND METHODS: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls. RESULTS: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis. CONCLUSION: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS.

Pediatrician! Do you know the symptoms of DRESS syndrome? A case report of a 4-year-old girl.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity syndrome and may be observed after administration of many drugs. Clinical symptoms usually occur 2 to 8 weeks after drug introduction. Because DRESS syndrome is potentially life threatening, it is especially important to diagnose it early. Withdrawal of the drug which induced symptoms is the most important therapeutic option. DRESS syndrome appears mostly in adults. There are relatively few articles on the DRESS syndrome in children. The article presents a case of a 4-year-old girl with a life-threatening clinical course of DRESS syndrome with massive pulmonary involvement. The knowledge of DRESS syndrome clinical symptoms is essential for doctors of various specialties. It is especially important that general practitioners, pediatricians, and pediatric neurologists should be able to take this life-threatening syndrome into consideration for differential diagnosis.