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Trichothiodystrophy (TTD) is a rare congenital disorder caused by genetic mutations, leading to hair and skin abnormalities. We report successful treatment of a TTD case using dupilumab, a monoclonal antibody targeting IL-4Rα. The patient, a 7-year-old boy, exhibited significant improvement in skin and hair conditions, suggesting the potential of dupilumab as a therapeutic option for TTD. Further research is needed to elucidate its mechanism and efficacy in TTD treatment.
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Escabiosis , Niño , Humanos , Escabiosis/tratamiento farmacológico , Pomadas , Azufre/uso terapéutico , Ivermectina , Administración TópicaRESUMEN
Rubinstein-Taybi Syndrome is a rare congenital multisystem syndrome inherited in an autosomal dominant pattern caused by mutations in CREBBP and EP300 genes in approximately 60% and 10% respectively. These genes encode two highly evolutionarily conserved, ubiquitously expressed, and homologous lysine-acetyltransferases, that are involved in number of basic cellular activities, such as DNA repair, cell proliferation, growth, differentiation, apoptosis of cells, and tumor suppression. It is mainly characterized by global developmental delay, moderate to severe intellectual disability, postnatal retardation, microcephaly, skeletal anomalies including broad/short, angled thumbs and/or large first toes, short stature, and dysmorphic facial features. There is an increased risk to develop tumors mainly meningiomas and pilomatrixomas, without a clear genotype-phenotype correlation. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with this entity. Both susceptibility to the formation of keloids and pilomatricomas are the most often associated cutaneous features. In this review, we discuss the genetics, diagnosis, and clinical features in Rubinstein-Taybi Syndrome with a review of the major dermatological manifestations.
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Discapacidad Intelectual , Pilomatrixoma , Síndrome de Rubinstein-Taybi , Neoplasias Cutáneas , Humanos , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/diagnóstico , Síndrome de Rubinstein-Taybi/patología , Mutación , Estudios de Asociación Genética , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.
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COVID-19 , Eritema Pernio , Exantema , Adulto , Femenino , Humanos , Adolescente , Niño , Lactante , Preescolar , Masculino , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/epidemiología , Eritema Pernio/diagnóstico , Eritema Pernio/etiología , Eritema Pernio/epidemiología , Estudios Retrospectivos , Pandemias , SARS-CoV-2 , Eritema/complicaciones , Exantema/complicaciones , Italia/epidemiología , Vesícula/complicaciones , Cianosis/complicacionesRESUMEN
BACKGROUND: Ectodermal dysplasias (EDs) are a large and complex group of disorders affecting the ectoderm-derived organs; the clinical and genetic heterogeneity of these conditions renders an accurate diagnosis more challenging. The aim of this study is to demonstrate the clinical utility of a targeted resequencing panel through enhancing the molecular and clinical diagnosis of EDs. Given the recent developments in gene and protein-based therapies for X-linked hypohidrotic ectodermal dysplasia, there is a re-emerging interest in identifying the genetic basis of EDs and the respective phenotypic presentations, in an aim to facilitate potential treatments for affected families. METHODS: We assessed seventeen individuals, from three unrelated families, who presented with diverse phenotypes suggestive of ED. An extensive multidisciplinary clinical evaluation was performed followed by a targeted exome resequencing panel (including genes that are known to cause EDs). MiSeqTM data software was used, variants with Qscore >30 were accepted. RESULTS: Three different previously reported hemizygous EDA mutations were found in the families. However, a complete genotype-phenotype correlation could not be established, neither in our patients nor in the previously reported patients. CONCLUSIONS: Targeted exome resequencing can provide a rapid and accurate diagnosis of EDs, while further contributing to the existing ED genetic data. Moreover, the identification of the disease-causing mutation in an affected family is crucial for proper genetic counseling and the establishment of a genotype-phenotype correlation which will subsequently provide the affected individuals with a more suitable treatment plan.
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Displasia Ectodermal Anhidrótica Tipo 1 , Displasia Ectodérmica Hipohidrótica Autosómica Recesiva , Displasia Ectodérmica , Humanos , Ectodisplasinas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodermal Anhidrótica Tipo 1/diagnóstico , Displasia Ectodermal Anhidrótica Tipo 1/genética , MutaciónRESUMEN
Infantile perianal pyramidal protrusion (IPPP) is a benign condition generally noted in childhood but may persist for several years. Dermoscopy may help to distinguish it from other conditions, particularly genital warts. We report six cases of IPPP and describe the dermoscopic features that will distinguish these lesions from verrucae.
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Dermoscopía , Neoplasias Cutáneas , Humanos , Perineo/patología , Neoplasias Cutáneas/patologíaRESUMEN
Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ââis a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.
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Dermatitis Atópica , Dermatología , Pediatría , Adolescente , Niño , Dermatitis Atópica/terapia , Humanos , Hiperplasia , PediatrasRESUMEN
INTRODUCTION: Primary cutaneous adenoid-cystic carcinoma (PCACC) is a rare malignant tumour reported in only about 450 cases in the literature, with only two adolescent cases reported. PCACC seems to occur between the fifth and seventh decade of life, and the most frequent regions involved are head and neck (46%). Aplasia cutis congenita (ACC) has an incidence of 1:10,000, and it seems to be rarely associated with neoplastic lesions. Interestingly, the association between PCACC and ACC has, so far, never been described. METHODS: We report a case of PCACC in the scalp associated with ACC in a four-year-old patient. DISCUSSION: The patient was under follow-up at the dermatology unit, but suddenly a red lesion appeared within the ACC. This red, ulcerated area increased rapidly over six months, so it was surgically removed, and the pathological examination results were suggestive for cribriform PCACC. According to the guidelines for skin tumours, the patient underwent widening resection, and an advancement-sliding skin flap was performed to recreate the scalp. After one year of follow-up, the patient has no local or widespread recurrence of the PCACC, and the surgical scar appears to have healed well. CONCLUSIONS: This clinical case is the first known patient with PCACC associated with ACC. A skin excision biopsy should be performed with wide margins to avoid a second widening resection of skin in a similar scenario. Genetic studies may help to identify the origin of this rare association.
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Netherton syndrome (NS) is a rare and potentially life-threatening genetic skin disease responsible for skin inflammation and scaling, hair abnormalities and severe allergic manifestations. NS is caused by loss-of-function variants in Serine Peptidase Inhibitor Kazal-Type 5 (SPINK5), encoding the serine protease inhibitor LEKTI. NS patients have a profound skin barrier defect caused by unopposed kallikrein-related proteases activity (KLKs). They develop severe skin inflammation with eczematous-like lesions and high serum IgE levels. Multiomics studies have revealed that the IL-17/IL-36 pathway is the most predominant upregulated pathway in NS. It is associated with a Th2 signature with complement activation in the ichthyosis linearis circumflexa subtype, and with interferon and Th9 activation in the scaly erythrodermic form. Several case reports proved the efficacy of different biotherapies targeting IL-17A, IL-12/IL-23, IL-4R and IL-13R, TNF-a and IL-1ß in pediatric NS patients. Intravenous immunoglobulins (IVIG) have also shown efficacy. These studies showed no severe side effects. At present, IL-17 blockade seems to be the most efficient treatment, but case reports remain limited with small numbers of patients and no placebo-control. Additional pathways must also be explored, and more efficient strategies could be used to block IL-17 and IL-23 pathways. In the future, the combination of specific strategies aiming at repairing the initial skin barrier defect could potentiate the efficacy of biologics. The current reports suggest that biological therapy is safe and often effective at pediatric age. However, controlled clinical trials that include a larger number of patients need to be conducted to reach more reliable conclusions.
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BACKGROUND: Propranolol (antagonist of ß1-/ß2-AR but minimally active against ß3-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of ß2-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of ß3-ARs, we evaluated a possible relationship between ß3-AR expression and response to propranolol. METHODS: Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of ß1-, ß2-, and ß3-ARs positively stained area was compared between the two groups. RESULTS: While no difference was found in both ß1- and ß2-AR expression level, a statistically significant increase of ß3-AR positively stained area was observed in the nonresponder group. CONCLUSIONS: Although the number of biopsies is insufficient to draw definitive conclusions, and the different ß-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between ß3-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH. IMPACT: Propranolol (unselective antagonist of ß1 and ß2-ARs) is currently the first-line treatment for IHs, with a success rate of ~60%. Its effectiveness has been attributed to its ability to block ß2-ARs. However, ß3-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of ß3-ARs in hemangioma pathogenesis and a possible new therapeutic target.
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Antagonistas Adrenérgicos beta/farmacología , Hemangioma/metabolismo , Propranolol/farmacología , Receptores Adrenérgicos beta 3/efectos de los fármacos , Humanos , Lactante , Receptores Adrenérgicos beta 3/metabolismoRESUMEN
PIK3CA-related overgrowth spectrum (PROS) is an umbrella term referring to various clinical entities, which share the same pathogenetic mechanism. These conditions are caused by somatic gain-of-function mutations in PIK3CA, which encodes the 110-kD catalytic α subunit of PI3K (p110α). These PIK3CA mutations occur as post-zygotic events and lead to a gain of function of PI3K, with consequent constitutional activation of the downstream cascades (e.g., AKT/mTOR pathway), involved in cellular proliferation, survival and growth, as well as in vascular development in the embryonic stage. PIK3CA-related cancers and PROS share almost the same PIK3CA mutational profile, with about 80% of mutations occurring at three hotspots, E542, E545, and H1047. These hotspot mutations show the most potent effect on enzymatic activation of PI3K and consequent downstream biological responses. If present at the germinal level, these gain-of-function mutations would be lethal to the embryo, therefore we only see them in the mosaic state. The common clinical denominator of PROS disorders is that they are sporadic conditions, presenting with congenital or early childhood onset overgrowth with a typical mosaic distribution. However, the severity of PROS is highly variable, ranging from localized and apparently isolate overgrowth to progressive and extensive lipomatous overgrowth associated with life-threatening vascular malformations, as seen in CLOVES syndrome. Traditional therapeutic approaches, such as sclerotherapy and surgical debulking, are often not curative in PROS patients, leading to a recrudescence of the overgrowth in the treated area. Specific attention has been recently paid to molecules that are used and studied in the oncogenic setting and that are targeted on specific alterations of the pathway PI3K/AKT/mTOR. In June 2018, Venot et al. showed the effect of Alpelisib (BYL719), a specific inhibitor for the p110α subunit of PI3K, in patients with PROS disorders who had severe or life-threatening complications and were not sensitive to any other treatment. In these cases, dramatic anatomical and functional improvements occurred in all patients across many types of affected organ. Molecular testing in PROS patients is a crucial step in providing the conclusive diagnosis and then the opportunity for tailored therapy. The somatic nature of this group of diseases makes challenging to reach a molecular diagnosis, requiring deep sequencing methods that have to be performed on DNA extracted from affected tissue. Moreover, even analyzing the DNA extracted from affected tissue there is no guarantee to succeed in detection of the casual somatic mutation, since the affected tissue itself is highly heterogeneous and biopsy approaches can be burdened by incorrect sampling or inadequate tissue sample. We present an 8-year-old girl with CLOVES syndrome, born with a large cystic lymphangioma involving the left hemithorax and flank, multiple lipomas, and hypertrophy of the left foot and leg. She developed severe scoliosis. Many therapeutic approaches have been attempted, including Sildenafil treatment, scleroembolization, laser therapy, and multiple debulking surgeries, but none of these were of benefit to our patient's clinical status. She then started treatment with Rapamycin from May 2019, without significant improvement in both vascular malformation and leg hypertrophy. A high-coverage Whole Exome Sequencing analysis performed on DNA extracted from a skin sample showed a mosaic gain-of-function variant in the PIK3CA gene (p.H1047R, 11% of variant allele frequency). Once molecular confirmation of our clinical suspicion was obtained, after a multidisciplinary evaluation, we decided to discontinue Sirolimus and start targeted therapy with Alpelisib (50 mg/day). We noticed a decrease in fibroadipose overgrowth at the dorsal level, an improvement in in posture and excellent tolerability. The treatment is still ongoing.
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Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children's University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.
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Degranulación de la Célula , Liberación de Histamina , Inmunización Secundaria/efectos adversos , Vacunas contra la Influenza/efectos adversos , Mastocitos/inmunología , Enfermedades Cutáneas Vesiculoampollosas/inducido químicamente , Urticaria Pigmentosa/inmunología , Vacunas Combinadas/efectos adversos , Adolescente , Corticoesteroides/administración & dosificación , Degranulación de la Célula/efectos de los fármacos , Femenino , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Liberación de Histamina/efectos de los fármacos , Humanos , Esquemas de Inmunización , Vacunas contra la Influenza/administración & dosificación , Mastocitos/efectos de los fármacos , Premedicación , Factores de Riesgo , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Enfermedades Cutáneas Vesiculoampollosas/prevención & control , Resultado del Tratamiento , Urticaria Pigmentosa/diagnóstico , Vacunas Combinadas/administración & dosificaciónRESUMEN
Netherton syndrome (NS) is a genetic, multisystemic disease classically distinguished by a triad of clinical manifestations: congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation. Due to the complex pathogenesis of the disease, there are no specific therapies currently accessible for patients with NS. An early diagnosis is crucial to start the correct management of these patients. A multidisciplinary approach, including specialists in immunology, allergology, and dermatology, is necessary to set up the best therapeutic pathway. We conducted a review with the aim to summarize the different therapeutic strategies currently accessible and potentially available in the future for children with NS. However, given the limited data in the literature, the best-tailored management should be decided upon the basis of the specific clinical characteristics of the patients with this rare clinical condition. Further comprehension of the pathophysiology of the disease could lead to more efficacious specific therapeutic options, which could allow a change in the natural history of NS.
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BACKGROUND/OBJECTIVES: Nail alterations are commonly seen in cases of idiopathic clubfoot and may cause parental concern. The nature of and whether these changes are congenital or develop secondary to treatment has been poorly investigated. The aim of this study was to evaluate toenail morphology in clubfoot patients at presentation, to re-evaluate them during the course of treatment for the clubfoot, and to analyze findings in the light of the few literature reports for healthy children of the same age. METHODS: Thirty infants (21 males and 9 females) with idiopathic clubfoot were prospectively enrolled at the Anna Meyer Children's University Hospital. Nails of affected and non-affected feet were evaluated by a team of pediatric dermatologists at presentation and re-evaluated once per patient during the bracing period of Ponseti treatment. RESULTS: Toenails of affected (47) and non-affected (13) feet were abnormal at presentation in 43.3% of patients, in both clubfeet (40.4%) and non-affected feet (38.5%), but most changes were physiologic or transitory alterations, commonly found in healthy children, with nail concavity (koilonychia) being the most common finding (29.7%). Changes were not related to clubfoot severity or laterality (P > .05). In most (76.9%) unilateral cases, there was concordance of nail changes between clubfoot and non-affected foot. At re-evaluation (follow-up time 410 ± 207 days), nail problems were more frequent (53.3%); ingrown toenail was the most common (21.6%). CONCLUSIONS: The presence of nail alterations seems not to be caused by clubfoot pathology and could be related to unfavorable local condition in the brace.
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Pie Equinovaro , Enfermedades de la Uña , Tirantes , Niño , Pie Equinovaro/epidemiología , Pie Equinovaro/terapia , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Uñas , Resultado del TratamientoRESUMEN
BACKGROUND: Several studies have investigated the efficacy of balneotherapy in atopic dermatitis (AD), including a pediatric open randomized clinical trial conducted at the Comano thermal spring water center, which showed a significant reduction in AD severity and an improvement of the quality of life. However, so far many studies on balneotherapy in pediatric AD have included relatively small populations without identifying patients' characteristics associated with their response. The aim of the present study was to identify any features associated with the clinical response to the Comano thermal spring water balneotherapy in a large cohort of pediatric AD patients. METHODS: An observational study was conducted on 867 children aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with mild to severe AD who underwent balneotherapy at the Comano thermal spring water center (Comano, Trentino, Italy) from April to October 2014. Patients were stratified according to their disease severity, which was evaluated using five SCORing Atopic Dermatitis (SCORAD) categories before and immediately after a thermal spring water balneotherapy course. Potential characteristics associated with the patients' clinical response to Comano thermal spring water balneotherapy were investigated. RESULTS: A statistically significant improvement in AD severity was observed after Comano thermal spring water balneotherapy (p < 0.0001). A significantly higher percentage of patients achieving improvement in AD severity was reported among children ≤4 years old (p < 0.0001) with early-onset AD (p < 0.0001), severe AD (p < 0.0001) or coexistent reported food allergies (p < 0.01). The therapy was well tolerated, and no relevant adverse effects were reported during the treatment course. CONCLUSIONS: Comano thermal spring water balneotherapy is a safe complementary treatment for pediatric patients with AD, as it was able to reduce the disease severity, especially in children ≤4 years old, with early onset AD, severe AD or concomitant food allergies.
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Balneología , Dermatitis Atópica/terapia , Niño , Preescolar , Dermatitis Atópica/complicaciones , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Humanos , Italia , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Background: Gianotti Crosti syndrome (GCS) is a self-healing condition with a spontaneous resolution in 2-6 weeks but, even if rarely, recurrent episodes have been reported. Objective: The aim of this observational study is to investigate serum Immunoglobulin E (IgE) level in children with GCS, evaluating if there is a relationship between IgE level and clinical course of the disease. Methods: Children with GCS diagnosed at a tertiary care children's university hospital between June 2018 and November 2019 were prospectively enrolled. Demographic, clinical and hematochemical data of children investigated were collected. In particular, IgE level were investigated at symptoms onset and, if available, at the following blood tests. Patients were divided in 2 groups on the bases of the clinical course: children with a chronic relapsing course and children who did not present any relapse. Results: Among 29 patients enrolled in this study, 14 (48.3%) children had a chronic relapsing course and 15 (51.7%) did not present any relapse. A statistically significant difference was present considering the length of the disease: 210 days (IQR: 161.25-255) for patients with a chronic relapsing course compared to 40 days (IQR: 30-75) for the other group (p < 0.0001). About the median IgE level in the 2 groups, a value about 10 time higher was found in children with chronic course compared to the other group (1,144 vs. 116 U/mL) with a statistically significant difference (p < 0.0001). Conclusion: Despite the study limitations, a significant correlation between higher IgE levels and chronic-relapsing course of the GCS can be assumed.