Publications by authors named "Andrea Diociaiuti"

70 Publications

Operative Management of Neonatal Lymphatic Malformations: Lesson Learned From 57 Consecutive Cases.

Front Pediatr 2021 18;9:709223. Epub 2021 Aug 18.

Neonatal Surgery Unit, Medical and Surgical Department of the Fetus, Newborn, and Infant, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Lymphatic malformations (LMs) are rare entities, sometimes difficult to treat, that may be life-threatening when intricately connected to airway structures. Invasive treatments are occasionally required, with sclerotherapy considered the treatment of choice and surgery as a second-line approach. The aim of the present study was to evaluate our multidisciplinary team experience in treating newborns affected by LMs requiring operative management, while defining early outcomes. Retrospective review of all consecutive patients admitted for LMs requiring operative management between January 2000 and January 2019. Patients were mainly characterized based on anatomical district of the LM (and further stratified based on the development of respiratory distress), need for tracheostomy, number of sclerotherapies, indication for surgery, and residual disease beyond the 1st year. Morbidity and mortality were also evaluated. Fisher exact test and Mann-Whitney test were used as appropriate. Statistical significance was set at < 0.05. Fifty-seven patients were included in the study, 36 with cervicofacial and/or mediastinal LMs and 21 with LMs of other anatomical districts. Due to the risk of developing respiratory distress at birth, patients with cervicofacial and/or mediastinal LMs were divided into two groups (8/36 group A vs. 28/36 group B). Group A patients are at higher risk for tracheostomy (7/8 group A vs. 1/28 group B, = 0.0001) and more often require surgical reduction of the residual lymphatic abnormality (5/8 group A vs. 4/28 group B, = 0.013). They also require sclerotherapies more often, but the difference is not statistically significant (8/8 group A vs. 19/28 group B, = 0.15). Patients with cervicofacial/mediastinal LMs frequently suffer from persistent residual disease beyond the 1st year of life, significantly more often in group A (7/8 group A vs. 12/28 group B, = 0.043). LMs are rare conditions with potential life-threatening behavior. Their intrinsic clinical complexity requires a multidisciplinary approach to the affected patients. Planning a long-term follow-up is essential because of the late-term problems those patients may experience.
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http://dx.doi.org/10.3389/fped.2021.709223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416514PMC
August 2021

The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature.

Brain Sci 2021 Jun 16;11(6). Epub 2021 Jun 16.

Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, Italy.

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.
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http://dx.doi.org/10.3390/brainsci11060793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234150PMC
June 2021

Congenital self-healing reticulohistiocytosis in a newborn: unusual oral and cutaneous manifestations.

Ital J Pediatr 2021 Jun 10;47(1):135. Epub 2021 Jun 10.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio, 4, 00165, Rome, Italy.

Background: Congenital self-healing reticulohistiocytosis (CSHRH), also called Hashimoto-Pritzker disease, is a rare and benign variant of Langerhans cell histiocytosis, characterized by cutaneous lesions without extracutaneous involvement.

Case Presentation: We present a case of CSHRH with diffuse skin lesions and erosions in the oral mucosa, present since birth and lasting for 2 months, and we perform a review of the literature on Pubmed in the last 10 years.

Conclusions: Our case confirm that lesions on oral mucosa, actually underestimated, may be present in patients with CSHRH. Patients affected by CSHRH require a close follow-up until the first years of life, due to the unpredictable course of Langerhans cell histiocytosis, in order to avoid missing diagnosis of more aggressive types of this disorder.
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http://dx.doi.org/10.1186/s13052-021-01082-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194160PMC
June 2021

Ectodermal Dysplasia-Syndactyly Syndrome with Toe-Only Minimal Syndactyly Due to a Novel Mutation in NECTIN4: A Case Report and Literature Review.

Genes (Basel) 2021 05 17;12(5). Epub 2021 May 17.

Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.

Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is characterized by cutaneous syndactyly of the toes and fingers and abnormalities of the hair and teeth, variably associated with nail dystrophy and palmoplantar keratoderma (PPK). EDSS1 is caused by biallelic mutations in the NECTIN4 gene, encoding the adherens junction component nectin-4. Nine EDSS1 cases have been described to date. We report a 5.5-year-old female child affected with EDSS1 due to the novel homozygous frameshift mutation c.1150delC (p.Gln384ArgfsTer7) in the NECTIN4 gene. The patient presents brittle scalp hair, sparse eyebrows and eyelashes, widely spaced conical teeth and dental agenesis, as well as toenail dystrophy and mild PPK. She has minimal proximal syndactyly limited to toes 2-3, which makes the phenotype of our patient peculiar as the overt involvement of both fingers and toes is typical of EDSS1. All previously described mutations are located in the nectin-4 extracellular portion, whereas p.Gln384ArgfsTer7 occurs within the cytoplasmic domain of the protein. This mutation is predicted to affect the interaction with afadin, suggesting that impaired afadin activation is sufficient to determine EDSS1. Our case, which represents the first report of a NECTIN4 mutation with toe-only minimal syndactyly, expands the phenotypic and molecular spectrum of EDSS1.
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http://dx.doi.org/10.3390/genes12050748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156511PMC
May 2021

The Burden of Autosomal Recessive Congenital Ichthyoses on Patients and their Families: An Italian Multicentre Study.

Acta Derm Venereol 2021 Jun 22;101(6):adv00477. Epub 2021 Jun 22.

IDI-IRCCS (Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Dermatological Research Hospital), Via Monti di Creta 104, IT-00167 Rome, Italy.

Autosomal recessive congenital ichthyoses (ARCI) are characterized by generalized skin scaling, hyperkeratosis, erythroderma, and disabling features affecting the skin (palmoplantar keratoderma, fissures, pain, itch), eyes, ears, and joints. Disease severity and chronicity, patient disfigurement, and time and costs required for care impose a major burden on quality of life. This multicentre cross-sectional study investigated the impact of ARCI on quality of life of patients and families, using the Dermatology Life Quality Index (DLQI), the Children DLQI (CDLQI) and Family Burden of Ichthyosis (FBI) questionnaires. Disease severity was assessed by a dermatologist. A total of 94 patients were recruited, of whom 52 (55.3%) children. Mean age was 20.1 (median 13.5) years. The mean CDLQI/DLQI score was 7.8, and 21 patients scored >10, indicating a major impairment in quality of life: symptoms, feelings and treatment problems were the most affected domains of quality of life. FBI showed a major repercussion on psychological factors and work. The results of this study highlight the impact of ARCI on specific aspects of patient and family life, underlining the need for psychological support.
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http://dx.doi.org/10.2340/00015555-3822DOI Listing
June 2021

Xanthomatous nevus: A potential new entity.

JAAD Case Rep 2021 May 27;11:117-119. Epub 2021 Mar 27.

Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

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http://dx.doi.org/10.1016/j.jdcr.2021.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081870PMC
May 2021

Cutaneous venous malformations as a clue for possible gastrointestinal tract involvement: Diagnosis and treatment of six cases.

Dermatol Ther 2021 05 18;34(3):e14932. Epub 2021 Mar 18.

Dermatology Unit and Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Venous malformation (VM) is the most common type among vascular malformations classified by the International Society for the Study of Vascular Anomalies. Most VMs are sporadic (94%), caused in 40% of cases by somatic mutation of TEK gene. VMs can be cutaneous, visceral, or combined. Visceral involvement is rare, and gastrointestinal (GI) tract is the most common localization. Visceral VMs, usually asymptomatic, may manifest with bleeding, anemia, and consumptive coagulopathy, which sometimes require an emergency treatment. Our aim is to study the possible GI involvement in patients with only one cutaneous VM. We analyzed a series of six patients who presented with a single cutaneous VM and have subsequently manifested intestinal involvement at our reference center for vascular anomalies since 2010. In our patients, cutaneous VMs were located on lower or upper limbs, and GI involvement manifested from 3 to 10 years after skin diagnosis. Our experience urges to early diagnose a GI involvement also in patients with only one skin VM and to prevent severe complications. A multidisciplinary approach is mandatory for the diagnosis and treatment of these patients.
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http://dx.doi.org/10.1111/dth.14932DOI Listing
May 2021

Two Italian Patients with -Related Neuro-Ichthyosis:  Expanding the Genotypic and Phenotypic Spectrum and Ultrastructural Characterization.

Genes (Basel) 2021 02 26;12(3). Epub 2021 Feb 26.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.

Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) is a fatty acid elongase responsible for very long-chain fatty acid biosynthesis in the brain, retina, and skin. Heterozygous mutations in gene cause Stargardt-like macular dystrophy and spinocerebellar ataxia type-34, while different homozygous mutations have been associated with ichthyosis, spastic quadriplegia, and mental retardation syndrome in three kindred. We report the first two Italian children affected with neuro-ichthyosis due to the previously undescribed homozygous frameshift variant c.435dupT (p.Ile146TyrfsTer29), and compound heterozygous variants c.208C>T (p.Arg70Ter) and c.487T>C (p.Cys163Arg), respectively. Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy. Visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces. Our findings contribute to expanding the phenotypic and genotypic features of ELOVL4-related neuro-ichthyosis.
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http://dx.doi.org/10.3390/genes12030343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996761PMC
February 2021

Severe adverse events during sirolimus "off-label" therapy for vascular anomalies.

Pediatr Blood Cancer 2021 Aug 13;68(8):e28936. Epub 2021 Feb 13.

Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives: Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during "off-label use" for vascular anomalies.

Methods: We performed a retrospective, multicenter chart review for SAEs during "off-label" sirolimus therapy for vascular anomalies and analyzed these cases by a predesigned workflow.

Results: We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n = 4), Gorham-Stout disease (n = 2), central conducting lymphatic anomaly (n = 1), lymphatic malformation (n = 4), tufted angioma (n = 1), kaposiform hemangioendothelioma (n = 1), and venous malformation in a patient with CLOVES syndrome (n = 1). Three patients presented two SAEs each. The age at initiation of sirolimus therapy was under 2 years (n = 5), 2-6 years (n = 5), and older than 12 years (n = 4). SAEs occurred during the first 3 months of sirolimus therapy (n = 7), between 3 and 12 months (n = 7) and after 1 year of therapy (n = 3). The most frequent SAE was viral pneumonia (n = 8) resulting in one death due to a metapneumovirus infection in a 3 months old and a generalized adenovirus infection in a 28-month-old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis.

Conclusions: Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence of other risk factors, that is, underlying vascular anomaly or immune status, may contribute to the risk of SAEs. Sirolimus is an important therapeutic option for vascular anomalies, but patients and physicians need to be aware that adequate monitoring is necessary, especially in patients with complex lymphatic anomalies that are overrepresented in our cohort of SAEs.
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http://dx.doi.org/10.1002/pbc.28936DOI Listing
August 2021

First Case of Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses.

Int J Mol Sci 2020 Oct 18;21(20). Epub 2020 Oct 18.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio, 4, 00165 Rome, Italy.

Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in , , or genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to or mutations (7 and 9 cases, respectively); (ii) -mutated ichthyosis with confetti (2 cases); (iii) -mutated superficial epidermolytic ichthyosis (5 cases); and (iv) -mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic mutation.
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http://dx.doi.org/10.3390/ijms21207707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593923PMC
October 2020

A retrospective study on clinical subtypes and management of morphea in 10 Italian Dermatological Units.

G Ital Dermatol Venereol 2020 Oct 16. Epub 2020 Oct 16.

Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi, Hospital, University of Bologna, Bologna, Italy.

Background: There are still few dermatological studies on morphea. We evaluated the epidemiological and clinical features and management of pediatric morphea, reporting dermatologists experience.

Methods: A multicentre retrospective observational study was carried out on the epidemiological and clinical features and management of the disease between 01/01/2009 and 01/10/2014 in 10 Italian Dermatological Units.

Results: We collected the data of 69 children affected by: circumscribed morphea (39.1%); linear morphea of trunk and limbs (14.5%); en coupe de sabre morphea (ECDS) (14.5%); progressive facial hemiatrophy (8.7%); generalized form (18.8%); mixed morphea (4.4%). The mean age at onset was 6.86±3.21 years, mainly between 2 and 8 years, but is statistically significantly lower for ECDS (4.5±3.03). Localizations were: head/neck (30.4%), limbs (26.1%), trunk (14.5%), 2 or more sites (29%), most often the trunk plus limbs. Extracutaneous manifestations were observed in 26.1% patients. 10 patients presented a second autoimmune disorder. Treatments were topical in 26.1% cases and systemic (alone or associated with topical treatments) in 68.1%.

Conclusions: There was a lack of uniformity in the management of patients and an increasing awareness of dermatologists on the use of systemic therapies, in particular of methotrexate, which is no longer exclusive to rheumatologists. Methotrexate causes stabilization and improvement of the clinical signs, but topical creams are still considered adjuvant or maintenance therapies during/after the use of systemic drugs.
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http://dx.doi.org/10.23736/S0392-0488.20.06632-8DOI Listing
October 2020

Membranous aplasia cutis congenita in trisomy 18.

Ital J Pediatr 2020 Aug 27;46(1):120. Epub 2020 Aug 27.

Unit of Dentistry, Bambino Gesù Children Hospital and Research Institute, Rome, Italy.

Background: Aplasia cutis congenita (ACC) is a rare congenital condition characterized by the absence of skin layers and sometimes other underlying structures, in a localized or widespread area. The exact etiopathogenesis is not yet completely understood. Membranous ACC (MACC) also described as bullous or cystic ACC is a clinical subtype of ACC, covered with a membranous or glistening surface, and appears as a flat scar. There are less than 20 cases reported in the literature. It has been proposed an abortive form of a defective closure of the neural tube. On the other hand, the trisomy 18 is a chromosomal abnormality characterized by a broad clinical spectrum and the presence of defective closure of the neural tube.

Case Presentation: We report on an 18-months-old Venezuelan boy, who presented on the parietal scalp a distinctive localized MACC appearing as an oval lesion covered with a membranous surface, characterized by the absence of hairs and the presence of a sharp hair collar. The karyotype in peripheral blood was 47,XY,+ 18.

Conclusions: This is the second case report of ACC in trisomy 18 and reinforces the interpretation of a non-fortuitous association as well as of a defective closure of the neural tube as pathogenetic mechanism. The case highlights the importance of examining for dermatological alterations such as ACC in cases of chromosomopathy.
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http://dx.doi.org/10.1186/s13052-020-00885-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450555PMC
August 2020

Cutaneous Infantile Haemangiomas with Intracranial and Intraspinal Involvement: A European Multicentre Experience and Review.

Acta Derm Venereol 2020 Sep 8;100(16):adv00255. Epub 2020 Sep 8.

Dermatology Unit, Bambino Gesù Childrens Hospital, IRCCS, IT-00165 Rome, Italy.

Infantile haemangiomas are very common benign tumours in the first months of life. They are mostly cutaneous; however, extracutaneous lesions are possible, and occur in very rare cases in the central nervous system. A European multicentre observational retrospective study was conducted in the last 5 years. Seven patients with intracranial or intraspinal infantile haemangiomas were selected and treated with oral propranolol. Propranolol was interrupted after complete or almost complete resolution of infantile haemangiomas. All patients tolerated the treatment well without side-effects. Central nervous system infantile haemangiomas are probably underestimated due to the frequent absence of symptoms and their spontaneous involution. However, they should be investigated in case of segmental cutaneous infantile haemangiomas, particularly on the head, neck, upper trunk, lumbar or sacral area in order to diagnosis intra-central nervous system involvement at an early stage.
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http://dx.doi.org/10.2340/00015555-3608DOI Listing
September 2020

Diffuse infantile hepatic hemangiomas in a patient with Beckwith-Wiedemann syndrome: A new association?

Am J Med Genet A 2020 08 23;182(8):1972-1976. Epub 2020 Jun 23.

Rare Diseases and Clinical Genetics Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome, caused by alterations in a cluster of imprinted genes located within the chromosome region 11p15.5. Common clinical features are overgrowth, macroglossia, lateralized overgrowth, abdominal wall defects, neonatal hypoglycemia and an increased risk of embryonal tumors, such as hepatoblastomas. Periodic screening for abdominal tumors is recommended. Vascular tumors are uncommon in BWS. Diffuse infantile hepatic hemangiomas (DIHHs) are rare vascular tumors with potentially lethal complications, in particular acquired consumptive hypothyroidism, high-output cardiac failure, liver failure and abdominal compartment syndrome. We describe a 2-month-old patient with hallmark clinical features of BWS and confirmed a genetic diagnosis with mosaic paternal uniparental disomy of chromosome 11p15.5 (UPD[11]pat). The patient developed hepatomegaly and elevated alpha-fetoprotein (AFP) and was therefore suspected of having a hepatoblastoma. Abdominal echo-color Doppler and a CT-scan allowed diagnosis of DIHHs. She was closely monitored and underwent treatment with propranolol. Oral propranolol was effective in reducing hepatic lesions without side effects. This report may suggest that vascular tumors can also be associated with BWS.
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http://dx.doi.org/10.1002/ajmg.a.61718DOI Listing
August 2020

Successful topical treatment of anal giant condylomata acuminata in an infant.

Dermatol Ther 2020 07 5;33(4):e13624. Epub 2020 Jun 5.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Anogenital condylomata acuminata are induced by human papillomavirus (HPV) and they rarely manifest in immunocompetent children. Therapeutic options depend on patient's age and general conditions and extension of the lesions. However, management is still a challenge and recurrences are frequent. Cryotherapy, laser, and surgical treatments in children are painful and frequently require general anesthesia. Imiquimod is a topical immune response modifier and constitutes a noninvasive alternative for the treatment of anogenital condylomata acuminata. Here, we report an infant admitted to our hospital with a giant vegetative papillomatous lesion on the perianal region surrounded by small satellites papules. PCR for HPV confirmed the clinical diagnosis of giant condylomata acuminata due to HPV type 6. The child has been successfully treated with topical 5% imiquimod cream without side effects. Although topical imiquimod is not licensed for pediatric age, this report highlights the potential benefits of its use in selected pediatric cases.
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http://dx.doi.org/10.1111/dth.13624DOI Listing
July 2020

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review.

Ital J Pediatr 2020 Apr 15;46(1):44. Epub 2020 Apr 15.

Pediatric Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge.

Case Presentation: We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate.

Conclusions: The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.
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http://dx.doi.org/10.1186/s13052-020-0817-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158043PMC
April 2020

Correction to: Italian translation, cultural adaptation, and pilot testing of a questionnaire to assess family burden in inherited ichthyoses.

Ital J Pediatr 2020 03 11;46(1):30. Epub 2020 Mar 11.

Department of Dermatology, Necker-Enfants Malades Hospital, Centre de Référence National pour les Maladies Génétiques à Expression Cutanée (MAGEC), APHP, Paris, France.

The original article contains a misspelling of co-author, Christine Bodemer's name which is presented correctly in this Correction article.
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http://dx.doi.org/10.1186/s13052-020-0791-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065451PMC
March 2020

Hoarse cry in a newborn with epidermolysis bullosa simplex, generalized severe.

Pediatr Dermatol 2020 Mar 19;37(2):393-395. Epub 2020 Jan 19.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Hoarse cry and respiratory stridor are the signs of potentially life-threatening laryngeal involvement in selected severe and frequently early lethal subtypes of inherited epidermolysis bullosa (EB). We present a newborn with generalized skin blistering and onychodystrophy who developed a hoarse cry and inspiratory stridor. Ultrastructural skin examination revealed tonofilament clumping in basal keratinocytes and genetic testing identified the de novo missense mutation p.Arg125Cys in the KRT14 gene, consistent with EB simplex generalized severe, which is characterized by major morbidity in infancy but a favorable long-term prognosis. The present case underlines the importance to consider EB simplex generalized severe in the differential diagnosis of EB infants presenting hoarseness and stridor.
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http://dx.doi.org/10.1111/pde.14105DOI Listing
March 2020

EGFR inhibition for metastasized cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa.

Orphanet J Rare Dis 2019 12 3;14(1):278. Epub 2019 Dec 3.

Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 7, 79104, Freiburg, Germany.

Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early development of aggressive cutaneous squamous cell carcinomas (SCC). For patients with locally advanced or metastasized SCCs treatment with cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), has been proposed and so far, treatment of five DEB patients with cetuximab has been published. With this report, we extend the spectrum of EB patients treated with cetuximab by adding two additional patients. Taking together all DEB cases treated with cetuximab, we propose that cetuximab should be administered as early as possible, since it seems to be more efficient and is accompanied by rather mild adverse effects. We also show that EGFR is frequently expressed in DEB-associated SCCs, although there were noticeable differences in the level of expression, which may influence responsiveness to EGFR-targeting therapies. Although only limited experiences with targeted cancer treatments in EB exist, such reports highlight the treatments' effects in this specific cohort and assist our therapeutic decisions.
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http://dx.doi.org/10.1186/s13023-019-1262-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889571PMC
December 2019

Management of chronic urticaria in children: a clinical guideline.

Ital J Pediatr 2019 Aug 15;45(1):101. Epub 2019 Aug 15.

UOC di Pediatria Generale e Malattie Infettive, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.
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http://dx.doi.org/10.1186/s13052-019-0695-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694633PMC
August 2019

Fibrolipomatous hamartomas not only on the soles.

Pediatr Dermatol 2019 Sep 27;36(5):728-729. Epub 2019 Jun 27.

Dermatology Unit, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy.

Fibrolipomatous hamartomas are asymptomatic, subcutaneous lumps usually located on the infant's heels. There is wide heterogeneity in the naming of and management of this condition. Ultrasound examination permits a clear distinction from other disorders. We report herein a case of palmoplantar fibrolipomatous hamartomas.
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http://dx.doi.org/10.1111/pde.13874DOI Listing
September 2019

Novel clinical features associated with Clouston syndrome.

Int J Dermatol 2019 Aug 5;58(8):e143-e146. Epub 2019 Jun 5.

Unit of Dentistry, Bambino Gesù Children Hospital and Research Institute, Rome, Italy.

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http://dx.doi.org/10.1111/ijd.14507DOI Listing
August 2019

Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome.

J Clin Immunol 2019 07 29;39(5):476-485. Epub 2019 May 29.

U.O.C. Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Objectives: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib.

Methods: We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis.

Results: We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease.

Conclusions: We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.
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http://dx.doi.org/10.1007/s10875-019-00645-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086512PMC
July 2019

Angioma serpiginosum: a case report and review of the literature.

Ital J Pediatr 2019 Apr 27;45(1):53. Epub 2019 Apr 27.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, 00165, Rome, Italy.

Background: Angioma serpiginosum is a rare vascular anomaly whose pathogenesis is still unknown. It is characterized by the onset of vascular reddish macules and papules during childhood, lesions are usually monolateral with a linear serpiginous pattern. It is rarely associated with extracutaneous findings. This entity has not yet been included in the classification of the International Society for the Study of Vascular Anomalies.

Case Presentation: We describe the first Italian report of angioma serpiginosum with a congenital symmetrical presentation. The patient had a further extension of macules during puberty involving both of the soles. No extracutaneous manifestations were present. Diagnosis was confirmed with dermoscopy and light microscopy that revealed the typical clusters of dilated, thickened and PAS+ capillaries in the upper dermis. Moreover, Immunohistochemistry showed positive WT-1 staining. Genetic analysis with next generation sequencing did not detected any mutation.

Conclusions: Our patient presented a peculiar symmetrical and planar extension with a serpiginous linear pattern. The proliferative nature of this condition has been widely discussed in literature. In our case immunohistochemistry was positive for Wilms tumor-1, a new endothelial marker expressed during angiogenesis in reparative processes and endothelial tumors. Clinical evolution, histological and immunohistochemical findings suggest that angioma serpiginosum should be considered as a vascular proliferation. For these reasons we think it should be included in the international classification as a tumor.
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http://dx.doi.org/10.1186/s13052-019-0644-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487031PMC
April 2019

Italian translation, cultural adaptation, and pilot testing of a questionnaire to assess family burden in inherited ichthyoses.

Ital J Pediatr 2019 02 19;45(1):26. Epub 2019 Feb 19.

Department of Dermatology, Necker-Enfants Malades Hospital, Centre de Référence National pour les Maladies Génétiques à Expression Cutanée (MAGEC), APHP, Paris, France.

Background: Inherited ichthyoses are rare disorders characterized by generalized skin scaling. Among them, autosomal recessive congenital ichthyoses (ARCI) form a major subgroup presenting lifelong and severely disabling cutaneous and extracutaneous features and symptoms for which no curative treatment is available. Management relies on daily time-consuming and distressing topical medications. Disease manifestations, symptoms, and daily care affect not only the patient self-perception, but also different dimensions of patient and family life. To date, there is only a French validated ichthyosis-specific questionnaire, "Family Burden in Ichthyosis" (FBI), for the evaluation of family disease burden. It addresses economical aspects, daily life, familial and personal relationships, work, and psychological impact. The aim of our study was to develop an Italian translation of the French FBI questionnaire and to pilot-test it in ARCI patients.

Methods: The guidelines for cross-cultural adaptation of health-related quality of life measures were followed. Specifically, two independent forward translations were produced, followed by a reconciliation step by a multidisciplinary expert committee and back-translation. Revision of the original text and all translations was performed by the expert committee leading to a final version, which was pilot-tested by cognitive debriefing on 10 caregivers whose comments were evaluated by the committee.

Results: The translation and reconciliation process led to minor changes in five items in order to clarify the questions in relation to the possible answers or to obtain semantic/idiomatic/cultural equivalence of the Italian version with the French one. The cognitive debriefing process resulted into further minor wording modifications in four items to describe more precisely the disease impact according to parents' comments. The FBI developer approved the final Italian FBI version.

Conclusions: The Italian version of the FBI generated in the present study is a useful instrument to measure the impact of ichthyosis on family daily life, education and working activities, psychological implications, and the disease economic load. The questionnaire will be further validated through a multicenter Italian study on burden of ARCI. A validated Italian questionnaire is a valuable tool for future clinical trials. In addition, it can be used to rapidly identify family distressing situations, which require attention and prompt intervention.
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http://dx.doi.org/10.1186/s13052-019-0618-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381706PMC
February 2019

Common Community-acquired Bacterial Skin and Soft-tissue Infections in Children: an Intersociety Consensus on Impetigo, Abscess, and Cellulitis Treatment.

Clin Ther 2019 03 15;41(3):532-551.e17. Epub 2019 Feb 15.

Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Purpose: The main objective of this article was to offer practical suggestions, given the existing evidence, for identifying and managing bacterial impetigo, abscess, and cellulitis in ambulatory and hospital settings.

Methods: Five Italian pediatric societies appointed a core working group. In selected conditions, specially trained personnel evaluated quality assessment of treatment strategies according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Only randomized controlled trials (RCTs) and observational studies were included for quality assessment according to the GRADE methodology. MEDLINE, Ovid MEDLINE, EMBASE, and Cochrane Library databases were searched with a strategy combining MeSH and free text terms.

Findings: The literature review included 364 articles focusing on impetigo, skin abscess, and cellulitis/orbital cellulitis. The articles included for quality assessment according to the GRADE methodology for impetigo comprised 5 RCTs and 1 observational study; for skin abscess, 10 RCTs and 3 observational studies were included; for cellulitis and erysipelas, 5 RCTs and 5 observational studies were included; and for orbital cellulitis, 8 observational studies were included. Recommendations were formulated according to 4 grades of strength for each specific topic (impetigo, skin abscesses, cellulitis, and orbital cellulitis). Where controversies arose and expert opinion was considered fundamental due to lack of evidence, agreement according to Delphi consensus recommendations was included.

Implications: Based on a literature review and on local epidemiology, this article offers practical suggestions for use in both ambulatory and hospital settings for managing the most common bacterial SSTIs.
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http://dx.doi.org/10.1016/j.clinthera.2019.01.010DOI Listing
March 2019
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