Analysis of various factors influencing the development of birthmarks and cutaneous lesions in newborn infants / A születési jegyek és az újszülöttkori borgyógyászati elváltozások kialakulásában szerepet játszó tényezok vizsgálata.

Összefoglaló. Bevezetés: A szakirodalomban számos felmérés született az újszülöttkori borelváltozások elofordulási gyakoriságának vizsgálatára. Az epidemiológiai vizsgálatok eredményei azonban nem mindig adaptálhatók, hiszen jelentos különbségeket találunk az egyes népcsoportok bormanifesztációi között, emellett kevés és ellentmondásos adat áll rendelkezésre arról, hogy milyen tényezok befolyásolják ezen bortünetek kialakulását. Célkituzés: Prospektív kohorszvizsgálatunk fo célkituzése az volt, hogy felmérjük az alapvetoen egészséges, érett újszülöttek borgyógyászati elváltozásainak elofordulási gyakoriságát, illetve megvizsgáljuk az ezen elváltozások kialakulásában szerepet játszó tényezoket. Módszer: Vizsgálatunkat a Szegedi Tudományegyetem Szülészeti és Nogyógyászati Klinikájának Újszülött Osztályán végeztük 2014 áprilisa és 2015 áprilisa között. Az újszülöttek borgyógyászati vizsgálatát követoen az édesanyák 50 kérdést tartalmazó, standardizált kérdoívet töltöttek ki. Az újszülöttekre, illetve a szülés körülményeire vonatkozó adatokat a hivatalos betegdokumentáció adatainak felhasználásával elemeztük. Eredmények: A vizsgálatban összesen 1629, kaukázusi típusú újszülött vett részt. 88,15%-uknál diagnosztizáltunk legalább egyfajta borgyógyászati eltérést. Vizsgálatunkban számos esetben szignifikáns korrelációt találtunk az újszülöttek neme, gestatiós kora és súlya, valamint az újszülöttkori borelváltozások elofordulási gyakorisága között. Emellett a szociodemográfiai tényezok, a szülok fenotípusos jellegzetességei, az édesanya betegségei, gyógyszerszedési szokásai, káros szenvedélyei is hatást gyakorolhatnak a laesiók kialakulására. Következtetés: Az irodalmi adatok áttekintését követoen elmondhatjuk, hogy vizsgálatunk rendkívül átfogó, új adatokat szolgáltat a neonatalis bortünetek elofordulási gyakoriságáról és a kialakulásukban potenciálisan szerepet játszó tényezok kapcsolatáról hazánkban és világviszonylatban is. Orv Hetil. 2022; 163(13): 513-522. INTRODUCTION: Cutaneous lesions are very frequent in neonates. Despite the fact that the incidence of neonatal skin disorders has been reported in several studies, very few reports address the factors that influence the appearance of birthmarks. OBJECTIVE: In this cross-sectional study, we aimed to record cutaneous findings in essentially healthy, term and late preterm neonates, and to use this data to assess the associations between various factors and the appearance of birthmarks. METHOD: The study was conducted on consecutive neonates born between April 2014 and April 2015 at the Department of Obstetrics and Gynecology at the University of Szeged. After the whole-body skin examination, a standardized questionnaire consisting of 50 questions was completed by the mothers. Data relating to the neonatal history of the participating neonates were obtained from the official neonatal medical charts. RESULTS: A total of 1629 Caucasian neonates were included in the study. Of these, 88.15% exhibited at least one skin manifestation. Significant correlations were found between the newborn gender, gestational age and weight and the presence of many skin manifestations. Furthermore, sociodemographic factors, parental phenotypic characteristics, maternal diseases and medicine-taking habits also have impact on the development of certain cutaneous lesions. CONCLUSION: By examining a large number of newborns and by providing detailed analysis of several neonatal, perinatal and parental factors, our study contributes to a deeper understanding of the development of the examined cutaneous lesions. Orv Hetil. 2022; 163(13): 513-522.

New Treatment Option for Capillary Lymphangioma: Bleomycin-Based Electrochemotherapy of an Infant.

The treatment of microcystic and combined lymphangiomas, especially in the head and neck region, is still a challenge because the lymphangiomas do not respond to conventional therapies and their recurrence rate is high, regardless of the treatment choice. Complete surgical resection is the main treatment of lymphangiomas, but because of localization perioperative complications, such as bleeding, neural damage and airway obstruction are common disadvantages of this method. Bleomycin-based sclerotherapy is another common therapeutic approach, in which the lymphocysts are aspirated, and 25% to 50% of their volumes are replaced with a sclerotisant drug. This is an effective treatment in cases in which the vessels are large enough for an intravascular or intracystic injection, but because of the small size of vessels and cysts, the microcystic and combined lymphangiomas are not suitable for sclerotherapy. Delivery of drugs for treating sclerosis to endothelial cells can be achieved by electroporation (electrochemotherapy), even for capillary malformations. A congenital, rapidly growing combined lymphangioma of the left cervicofacial region was treated with one session of bleomycin-based electrochemotherapy. Seven months after treatment, the growth-corrected target volume decrease was 63% and the dislocation of the trachea and blood vessels previously observed had ceased. We suggest that bleomycin-based electrochemotherapy is a feasible alternative treatment option for capillary malformations.

[Successful treatment of facial angiofibromas with local sirolimus in childhood in Bourneville-Pringle disease]. / Lokális szirolimuszterápia sikeres alkalmazása facialis angiofibromák kezelésére Bourneville­Pringle-kórban szenvedo gyermekeken.

Facial angiofibroma is the characteristic symptom and also a major diagnostic criterion for Bourneville-Pringle disease. The centrofacially localized hamartomatous tumours start to appear in early childhood, and progress over time. Facial angiofibromas represent a significant cosmetological problem for the patients and a therapeutic challenge for the physician. Beside the traditional invasive treating methods, topical sirolimus is a new, promising and well-tolerated treatment modality. Several studies and case reports have been published on this new therapeutic approach, but recommendation for the optimal sirolimus concentration still does not exist. We report here two cases when children were successfully treated with topical sirolimus. Orv Hetil. 2019; 160(13): 516-520.

Cutaneous lesions and disorders in healthy neonates and their relationships with maternal-neonatal factors: a cross-sectional study.

BACKGROUND: Cutaneous lesions are very common in neonates. Although a number of studies have reported on their incidence, very little is known about the factors that influence them. We set out to investigate a large population of neonates with the aims of achieving an overall picture of neonatal skin manifestations, and examining their relationships with various maternal, neonatal and perinatal factors. METHODS: This study was conducted on neonates born at the Department of Obstetrics and Gynaecology at the University of Szeged between June 2013 and July 2015. A total of 4658 consecutive infants underwent a whole-body skin examination within the first 72 hours of extrauterine life. The official neonatal medical charts were used to collect data on the history of the participating neonates and on maternal factors. RESULTS: 74.35% of the neonates exhibited at least one skin manifestation. The major diagnosis groups were transient, benign cutaneous lesions; vascular lesions; traumatic, iatrogenic, congenital or acquired disorders with skin injuries; pigmented lesions; and developmental abnormalities or benign skin tumours. The relationships between the skin findings and six neonatal or maternal factors were examined: gender, gestational age and birth weight of the neonates; maternal age and the number of previous pregnancies of the mothers, and mode and circumstances of the delivery. CONCLUSIONS: We found several significant correlations between the examined maternal/neonatal factors and the occurrence of birthmarks and neonatal skin disorders. Of course, further studies are required to confirm and better understand these associations.

[Infantile haemangioma: clinical and demographic characteristics, experiences in the treatment]. / Infantilis haemangioma: klinikai és demográfiai jellemzok, kezelési-gondozási tapasztalatok.

INTRODUCTION: Infantile haemangiomas are the most common vascular tumours of infancy. The vast majority of the lesions do not require dermatological treatment due to their unique clinical course and the high rate of spontaneous regression. Approximately 10-15% of the tumours result in severe complications and sequale, requiring special management and close follow-up. AIM: The aim of the present study was to assess the data of the patients treated with infantile haemangiomas, and to summarize the results of the therapy during 4.5 years of study period, in the Paediatric Dermatology Outpatient Clinic of the Department of Dermatology and Allergology, at the University of Szeged. METHOD: Demographic data of the infants (gender, gestational age and weight, perinatal history of the infant and medical history of mothers), exact date of the visits at Paediatric Dermatology Outpatient Clinic and tumour characteristics (number, subtype, anatomical localisation and complications) were analysed in details. Treatment modalities and therapy intervals, outcomes and the adverse events of the therapies were also discussed in the survey. RESULTS: During the study period, 96 infants with 163 infantile haemangiomas were observed. 54 patients required regular observations, while 42 infants required local or systemic beta-blocker therapy. All of the tumours treated with local or systemic therapy showed marked clinical regression; adverse effects were observed in only 6 cases. The gestational age and gestational weight of infants requiring beta-blocker therapy was significantly lower as compared to children needed only observation. CONCLUSIONS: Systemic propranolol is currently the first-line treatment modality for complicated infantile haemangiomas. Our results confirm the significant therapeutic efficacy of propranolol. Early introduction of the treatment is relevant; unfortunately a great proportion of patients are referred late to Paediatric Dermatology Centres. Orv Hetil. 2017; 158(39): 1535-1544.

Delineating the genetic heterogeneity of OCA in Hungarian patients.

BACKGROUND: Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1-7). METHODS: The most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients (n = 13). Mutation screening and polymorphism analysis were performed by direct sequencing on TYR, OCA2, SLC45A2 genes. RESULTS: Although the clinical features of the investigated Hungarian OCA patients were identical, the molecular genetic data suggested OCA1 subtype in eight cases and OCA4 subtype in two cases. The molecular diagnosis was not clearly identifiable in three cases. In four patients, two different heterozygous known pathogenic or predicted to be pathogenic mutations were present. Seven patients had only one pathogenic mutation, which was associated with non-pathogenic variants in six cases. In two patients no pathogenic mutation was identified. CONCLUSIONS: Our results suggest that the concomitant screening of the non-pathogenic variants-which alone do not cause the development of OCA, but might have clinical significance in association with a pathogenic variant-is important. Our results also show significant variation in the disease spectrum compared to other populations. These data also confirm that the concomitant analysis of OCA genes is critical, providing new insights to the phenotypic diversity of OCA and expanding the mutation spectrum of OCA genes in Hungarian patients.

Lesions requiring wound management in a central tertiary neonatal intensive care unit.

BACKGROUND: Most of the skin disorders that occur in neonatal intensive care units are due in part to the immaturity and vulnerability of the neonatal skin. Various iatrogenic diagnostic and therapeutic procedures are also conducive to iatrogenic damage. This study was to review the neonates admitted to our neonatal intensive care unit who needed wound management, and to assess the most common skin injuries and wounds, and their aetiology. METHODS: Data were extracted from medical records of neonates who needed wound management in our Neonatal Intensive Care Unit between January 31, 2012 and January 31, 2013. Information about gestational age, sex, birth weight, area of involvement, wound aetiology, and therapy were collected. RESULTS: Among the 211 neonates observed, wound management was required in 10 cases of diaper dermatitis, 7 epidermal stripping, 6 extravasation injuries, 5 pressure ulcers, 1 surgical wound and infection, 1 thermal burn, and 5 other lesions. CONCLUSIONS: International guidelines in neonatal wound care practice are not available, and further research concerns are clearly needed. Dressings and antiseptic agents should be chosen with great care for application to neonates, with particular attention to the prevention of adverse events in this sensitive population. Team work among dermatologists, neonatologists and nurses is crucial for the successful treatment of neonates.

Iatrogenic Skin Disorders and Related Factors in Newborn Infants.

BACKGROUND/OBJECTIVES: Recent technological advances and diagnostic and therapeutic innovations have resulted in an impressive improvement in the survival of newborn infants requiring intensive care. Consequently, with the use of modern invasive diagnostic and therapeutic procedures, the incidence of iatrogenic events has also increased. The aim of this study was to assess various iatrogenic complications in neonates requiring intensive care and determine possible contributing factors to the injuries. METHODS: Our prospective cross-sectional cohort survey was conducted in a central regional level III neonatal intensive care unit (NICU). Correlations between intensive therapeutic interventions, complications, factors influencing attendance and prognosis, and the prevalence of iatrogenic skin injuries (ISIs) were investigated over a 2-year study period. RESULTS: Between January 31, 2012, and January 31, 2014, 460 neonates were admitted to the NICU, 83 of whom exhibited some kind of ISI. The major risk factors for ISIs were low birthweight, young gestational age, long NICU stay, use of the intubation-surfactant-extubation (INSURE) technique, surfactant use, mechanical ventilation, insertion of an umbilical arterial catheter, circulatory and cardiac support with dopamine or dobutamine, pulmonary hemorrhage, intracranial hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia, and positive microbiology culture results. CONCLUSION: To prevent ISIs, careful consideration of risk factors and the creation of protocols ensuring efficient treatment of injuries are needed.

Pharmacological Targeting of the Epidermal Barrier.

The most important function of the skin is to form a barrier between the body and the external environment. The epidermal barrier prevents transepidermal water loss from the skin, but also serves as a barrier to the entry of harmful environmental allergic, toxic or infectious substances. Inherited defects in the genes encoding the components of the epidermal barrier result in the development of rare genetic disorders, whereas polymorphisms in these genes together with environmental factors cause frequent inflammatory skin diseases, such as atopic dermatitis. In this review, components of the skin-barrier function will be reviewed with special emphasis on how the altered epidermal barrier might be repaired. The different strategies to increase the transdermal penetration of drugs is also discussed.

Overview of dermatologic disorders of neonates in a central regional intensive care unit in Hungary.

The immaturity and vulnerability of the skin and epidermal barrier function and the frequent iatrogenic complications following diagnostic and therapeutic procedures are often associated with skin manifestations in infants in neonatal intensive care units (NICUs). The aim of the current study was to investigate dermatologic disorders in neonates in our NICU. A prospective cohort study was conducted in the NICU at the Department of Pediatrics at the University of Szeged between January 2012 and January 2013. All full- and preterm infants hospitalized in the NICU underwent whole-body skin examinations and all dermatologic disorders and treatment modalities were recorded. Eighty-nine dermatologic conditions were detected in 64 of the 211 neonates admitted to the NICU. A wide variety of clinical symptoms accompanied these conditions in these preterm and severely ill full-term infants. A considerable proportion of the disorders that were seen resulted from the immaturity of the skin and various iatrogenic complications. Dermatologic disorders are frequent in neonates requiring intensive care. Prevention, early detection, and optimal treatment of these disorders with modern, standardized skin care management strategies can result in significant improvements in barrier function and in the integrity of the skin, increasing the overall efficacy of neonatal intensive care.

[Neonatal skin care in tertiary Neonatal Intensive Care Units in Hungary]. / Borápolási gyakorlat a Neonatális Intenzív Centrumokban Magyarországon.

INTRODUCTION: Skin physiology of neonates and preterm infants and evidence-based skin care are not well explored for health care providers. AIM: The aim of our present study was to investigate the skin care methods of the tertiary Neonatal Intensive Care Units in Hungary. METHOD: A standardized questionnaire was distributed among the 22 tertiary Neonatal Intensive Care Units with questions regarding skin care methods, bathing, emollition, skin disinfection, umbilical cord care, treatment of diaper dermatitis, and use of adhesive tapes. RESULTS: The skin care methods of the centres were similar in several aspects, but there were significant differences between the applied skin care and disinfectant products. CONCLUSIONS: The results of this survey facilitate the establishment of a standardized skin care protocol for tertiary Neonatal Intensive Care Units with the cooperation of dermatologists, neonatologists and pharmacists.

CTSC and Papillon-Lefèvre syndrome: detection of recurrent mutations in Hungarian patients, a review of published variants and database update.

Papillon-Lefèvre syndrome (PLS; OMIM 245000) is an autosomal recessive condition characterized by palmoplantar hyperkeratosis and periodontitis. In 1997, the gene locus for PLS was mapped to 11q14-21, and in 1999, variants in the cathepsin C gene (CTSC) were identified as causing PLS. To date, a total of 75 different disease-causing mutations have been published for the CTSC gene. A summary of recurrent mutations identified in Hungarian patients and a review of published mutations is presented in this update. Comparison of clinical features in affected families with the same mutation strongly confirm that identical mutations of the CTSC gene can give rise to multiple different phenotypes, making genotype-phenotype correlations difficult. Variable expression of the phenotype associated with the same CTSC mutation may reflect the influence of other genetic and/or environmental factors. Most mutations are missense (53%), nonsense (23%), or frameshift (17%); however, in-frame deletions, one splicing variant, and one 5' untranslated region (UTR) mutation have also been reported. The majority of the mutations are located in exons 5-7, which encodes the heavy chain of the cathepsin C protein, suggesting that tetramerization is important for cathepsin C enzymatic activity. All the data reviewed here have been submitted to the CTSC base, a mutation registry for PLS at http://bioinf.uta.fi/CTSCbase/.

Successful postoperative treatment of a lumbosacral ulcer in a neonate after myelomeningocele.

Wound care in neonates demands special awareness of the anatomical and physiological characteristics of their skin, and the danger of adverse mechanical and toxicological events. Here, we present the case of a full-term neonate born with myelomeningocele. Following the closing surgery on the 3rd day of postuterine life, the operated region became inflamed, the sutures opened and a necrotic discharging ulcer developed. Besides parenteral antibiotic treatment based on the microbiological findings, intelligent hydrofiber dressings were applied to the wound with regard to the special characteristics of wound care in neonates. After 72 days, the ulcer had healed with a small residual scar, and the infant is currently demonstrating normal physical and mental development.

[Birth marks and neonatal skin disorders. From angel kiss to epidermolysis bullosa]. / Születési jegyek, újszülöttkori borelváltozások. Az angyalcsóktól az epidermolysis bullosáig.

INTRODUCTION: At present there are no exact epidemiologic data on the prevalence of neonatal skin disorders and birth marks in Hungary. AIM: The aim of the authors was to investigate the prevalence of skin disorders in mature healthy neonates after birth. METHOD: The survey was carried out in the Neonatal Care Unit at the Department of Obstetrics and Gynaecology at the University of Szeged between April, 2012 and May, 2013. RESULTS: A total of 2289 newborn infants underwent whole-body screening skin examinations. At least one skin manifestation was found in 63% of the neonates. The major groups of skin disorders were transient benign cutaneous lesions, vascular lesions, pigmented lesions, traumatic, iatrogenic, congenital or acquired disorders with skin injuries, developmental abnormalities and benign skin tumours. The most frequent transient cutaneous lesions were erythema toxicum neonatorum, sebaceous hyperplasia and desquamation. The most common vascular lesions were naevus simplex, haemangioma and haemangioma precursor lesion, while the most frequently observed pigmented lesions were congenital melanocytic naevi and Mongolian spot. CONCLUSIONS: In the vast majority of cases, special treatment was not necessary, but 5.27% of the neonates required local dermatologic therapy, and in 9.2% of neonates follow up was recommended.

A novel seven-base deletion of the CTSC gene identified in a Hungarian family with Papillon-Lefèvre syndrome.

Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives.

Neonatal blue light phototherapy and melanocytic nevi: a twin study.

BACKGROUND: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development. OBJECTIVE: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation. METHODS: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twin members received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphism of histidine ammonia-lyase genes were also determined in the enrolled twins. RESULTS: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group. CONCLUSIONS: Our data suggest that NBLP could well be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects.

Intranasal phototherapy is more effective than fexofenadine hydrochloride in the treatment of seasonal allergic rhinitis: results of a pilot study.

We recently showed that intranasal phototherapy represents an efficient therapeutic modality for the treatment of patients with seasonal allergic rhinitis (SAR). The aim of this pilot study was to compare the efficacy of intranasal phototherapy with that of the new generation antihistamine fexofenadine HCl in SAR. A randomized open study was conducted in patients with a history of moderate-to-severe ragweed-induced SAR. Thirty-one patients were randomly assigned to receive either intranasal irradiation three times a week for 2 weeks, or 180 mg fexofenadine HCl per day for 2 weeks. Each patient kept a diary of symptoms for nasal obstruction, nasal itching, rhinorrhea, sneezing and palate itching. Total nasal score (TNS), a sum of scores for nasal symptoms, was also calculated. In the rhinophototherapy group the individual scores significantly decreased compared with baseline for all of the parameters. In the fexofenadine HCl group none of the scores improved significantly at the end of the treatment except sneezing. TNS was significantly decreased in the rhinophototherapy group, but no significant change was observed in the fexofenadine HCl group after 2 weeks of treatment. In conclusion, we found that intranasal phototherapy is more efficient than fexofenadine HCl in reducing clinical symptoms for SAR.

[The prevalence of melanocytic naevi among teenagers]. / A festéksejtes anyajegyek elofordulása tinédzsereken.

UNLABELLED: Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, are indispensable steps in all primary prevention efforts. AIM: The objective of the present study was to assess the prevalence of different pigmented lesions among schoolchildren, and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. METHODS: A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. RESULTS: Between 1-10 common melanocytic naevi were found in 27% of the participants, and naevi numbers were in the range between 10-100 in 67%. 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Congenital naevi were detected in 6.2% of the schoolchildren. A statistically significant association was found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, the history of severe painful sunburns, and the family history of a large number of melanocytic naevi. CONCLUSIONS: Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.