Manifestaciones dermatológicas en una lactante con síndrome de kwashiorkor Claves para el diagnóstico y tratamiento oportuno / Dermatological Manifestations in an Infant with Kwashiorkor Syndrome: Keys for Diagnosis and Timely Treatment

Resumen El síndrome de kwashiorkor se caracteriza por malnutrición proteica y edema generalizado; algunos de los factores de riesgo que se asocian a su aparición son: vivir en pobreza, el destete reciente, las infecciones y las dietas basadas en maíz y arroz. Este síndrome puede generar manifestaciones cutáneas como piel delgada y seca, hiperpigmentación, áreas confluentes de descamación, cabello seco, hipopigmentado y desprendible, así como una dermatitis erosiva con predominio en pliegues cutáneos. El diagnóstico se basa principalmente en una evaluación nutricional integral, exploración física y estudios de laboratorio, y el éxito del tratamiento se basa en la rehabilitación nutricional temprana. Caso clínico: lactante del sexo femenino de 8 meses de edad, que acudió al Instituto Nacional de Pediatría (INP), por presentar una dermatosis generalizada de tipo descamativa de 1 mes de evolución, que fue tratada con ketoconazol tópico. Al interrogatorio la madre refiere alimentación exclusiva con atole de maíz por un diagnóstico de "alergia a la leche" y falta de recursos económicos para comprar la fórmula hidrolizada. La paciente presentaba una dermatosis diseminada que afectaba todos los segmentos corporales, caracterizada por placas hiperpigmentadas, bien definidas, de forma irregular, con descamación en láminas gruesas en región perioral y extremidades, así como áreas erosionadas, pálidas y edema generalizado en extremidades. Se realizaron exámenes de laboratorio que mostraron que la paciente tenía anemia (Hb 11.2 g/dL) e hipoalbuminemia (3.3 g/dL) que, en conjunto con las manifestaciones clínicas, integraron el diagnóstico de síndrome de Kwashiorkor. Se informaron los hallazgos clínicos y de laboratorio al servicio de Gastroenterología y Nutrición, quienes realizaron una valoración nutricional integral y decidieron iniciar tratamiento nutricional; por parte del servicio de Dermatología, se indicó el uso de emolientes y cuidados generales de la piel. Veinte días después la dermatosis y el edema habían remitido.

Abstract Kwashiorkor syndrome is characterized by protein malnutrition and edema, risk factors are recent weaning, infections, and diets based on corn and rice. This malnutrition can lead to skin manifestations such as thin, dry skin, hyperpigmentation, confluent areas of scaling, dry, hypopigmented, and detachable hair, as well as erosive dermatitis, predominantly in skin folds. The diagnosis is based on a nutritional evaluation exam, physical examination and laboratory finding, the treatment is based on early nutritional rehabilitation. Clinical case: 8-month-old female infant who attended the Instituto Nacional de Pediatría, presenting a scaling dermatosis of 1 month's evolution that was treated with topical ketoconazole. The mother reported exclusive feeding with corn gruel due to the diagnosis of "lactose allergy" and commented not enough resources to buy hydrolyzed formula. The patient presented a disseminated dermatosis to all body segments, characterized by well-defined, irregularly shaped, hyperpigmented plaques with scaling in thick sheets in the perioral region and extremities, as well as areas of eroded skin and paleness and edema of extremities. Laboratory tests were taken, where anemia (Hb 11.2 g/dl) and hipoalbuminemia (3.3 g/dl) were documented, the diagnosis of kwashiorkor syndrome was integrated. The clinical and laboratory findings were reported to the Gastroenterology and Nutrition service, who performed a nutritional assessment, and began nutritional treatment, emollients and general skin care were documented; twenty days later, the dermatosis and edema had subsided.

The use of mTOR inhibitors for the treatment of kaposiform hemangioendothelioma. A systematic review.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a locally aggressive and potentially lethal vascular tumor of infancy. Current consensus recommendations include the use of vincristine and/or systemic steroids as first-line treatment. Mammalian target of rapamycin (mTOR) inhibitors represent a promising therapy for patients with KHE. The goal of our study is to critically assess the existing literature on outcomes of patients with KHE treated with mTOR inhibitors. METHODS: We conducted a literature search from 1 January 2000, to 30 April 2022. Articles reporting outcomes of patients treated with mTOR inhibitors for KHE were included. Descriptive statistics were used to describe and summarize the outcomes of the treatment. RESULTS: We included 327 patients with a mean age at diagnosis of 9.1 months (SD ± 9). Patients were treated with an mTOR inhibitor for a mean of 15.2 months (SD ± 4.1). A total of 315 (96.3%) patients had positive outcomes including improvement of the tumor size, symptoms and/or laboratory parameters in 227 (85%) and complete remission in 38 (12%). Seven (2%) patients did not respond to treatment and seven (2%) died of sepsis (4), Kasabach-Merritt phenomenon complications (1), cardiac and liver failure due to ductus arteriosus (1), or metastatic disease (1). CONCLUSION: This systematic review supports the efficacy and safety of mTOR inhibitors for KHE. Their use resulted in positive outcomes in terms of decreased symptoms, reduction in tumor size and improvement in biochemical parameters with a mortality rate of 2%. According to these findings, we suggest revised consensus treatment guidelines for KHE with mTOR inhibitors potentially considered first-line therapy.

North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein.

Epidermolysis Bullosa Acquisita: A Rare Autoimmune Blistering Disease in Children.

A 7-year-old girl presented with a 2-year history of recurrent blisters on the skin and oral mucosa. The patient was otherwise healthy, and her family history was unremarkable for any dermatologic or other medical disease. Examination revealed multiple tense vesicles, milia, and atrophic scars present over the extensor surface of the extremities and erosions on the oral mucosa (Figure 1). A skin biopsy established a pauci-inflammatory subepidermal blister (Figure 2a). Direct immunofluorescence (DIF) evidenced the linear deposition of immunoglobulin G (IgG), immunoglobulin M (IgM), and κ and λ chains at the dermal-epithelial junction (DEJ). Indirect immunofluorescence (IIF), using the salt-split technique, established anti-epithelial antibodies on the dermal side (Figure 2b). An enzyme-linked immunosorbent assay (ELISA) was positive for Collagen Type VII (COL7) antibodies. A diagnosis of epidermolysis bullosa acquisita (EBA) was made, and treatment with azathioprine and deflazacort was administered for 8 months with progressive lessening of her symptomatology and complete clinical response at 2-year follow-up. (SKINmed. 2022;20:460-462).

Covid-19 mortality in children and adolescents in Mexico / Mortalidad por Covid-19 en niños y adolescentes en México

Abstract: Objective: To estimate Covid-19 and pre-pandemic low respiratory infection (LRI) mortality in children and adolescents in Mexico. Materials and methods: We estimated the percentage of total mortality attributable to Covid-19 (95% confidence intervals; 95%CI) and made the corresponding estimates for pre-pandemic LRI mortality. Results: In 2019, LRIs represented 8.6% (95%CI 8.3, 8.9) of deaths in children aged 0-9 years, and 2.0% (95%CI 1.8, 2.3) in those aged 10-19 years. In 2020, the corresponding estimates for Covid-19 were 4.4% (95%CI 4.1, 4.6) and 3.7% (95%CI 3.4, 4.1). Conclusions: Relative to LRI, Covid-19 may be exerting a considerable mortality burden, particularly in older children and adolescents.

Resumen: Objetivo: Estimar la mortalidad por Covid-19 e infección respiratoria baja (IRB) pre-pandémica en niños y adolescentes en México. Material y métodos: Se estimó el porcentaje de mortalidad atribuible a Covid-19 (intervalos de confianza 95%; IC95%) y se realizaron las estimaciones correspondientes para IRB pre-pandémica. Resultados: En 2019, las IRB representaron 8.6% (IC95% 8.3, 8.9) de las muertes en niños de 0-9 años y 2.0% (IC95% 1.8, 2.3) en aquéllos entre 10-19 años. Los valores correspondientes en 2020 para Covid-19 fueron 4.4% (IC95% 4.1, 4.6) y 3.7% (IC95% 3.4, 4.1). Conclusiones: En comparación con IRB, Covid-19 puede estar ejerciendo una carga de mortalidad considerable, particularmente en niños mayores y adolescentes.

Usefulness of Trichoscopy over Hair Light Microscopy in Menkes Disease.

Menkes disease (MD) is a rare X-linked recessive neurodegenerative disorder caused by mutations in the ATP7A gene, with a high mortality rate within the first 3 years of life. It typically affects males and is characterized by impaired copper distribution and malfunction of several copper-dependent enzymes. Patients develop progressive muscle hypotonia associated with neurological damage and hair shaft dysplasia - particularly pili torti. Pili torti is usually very subtle in the first 3 months of life and gradually increases during the first year. Light microscopy examination in search for pili torti requires the observation of more than 50 hair shafts. In contrast, trichoscopy with a hand-held dermatoscope allows to easily identify the hair shaft defect. We report a case of a Hispanic male infant with MD in whom we show that trichoscopy is superior to hair light microscopy in revealing pili torti.

Primary cutaneous blastic plasmacytoid dendritic cell neoplasm in a child: A challenging diagnosis and management.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy of the skin and hematopoietic system. There are few pediatric cases reported in the literature. Management of primary cutaneous BPDCN is challenging because, despite an apparently indolent clinical presentation, rapid dissemination with high mortality can occur. We describe a child with isolated cutaneous involvement who had a good response to chemotherapy as first-line treatment of BPDCN.

Early clinical, histological, and immunohistochemical findings in suspected acute graft-versus-host disease and their association with patient outcomes.

BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (aGVHD) is a serious condition after allogeneic hematopoietic stem cell transplantation (HSCT), frequently involving skin, gut, and liver. It can be difficult to diagnose early, yet this is vital for adequate management. We sought to identify initial clinical and histopathological features in children with suspected GVHD and the association with clinical course and outcomes. METHODS: Retrospective study of patients with skin biopsies for suspected aGVHD from 2006 to 2016. We collected demographic and clinical information, histologic, and immunohistochemical (IHC) findings, and outcomes during follow-up. Bivariate and multivariate analyses were done to identify risk factors associated with remission, development of severe/life-threatening aGVHD, and mortality. RESULTS: We included 42 patients, 15 females. Skin manifestations occurred 51 days (median) after HSCT. On biopsy, 76.2% had mild (stage 1-2) skin aGVHD; during the course of the disease, severity and systemic involvement increased to global grade III/IV in 66.6%. All patients received treatment; 15 are in remission from aGVHD and 23 have died. Histologic features were diagnostic in 83.3%. On bivariate and multivariate analysis, we identified initial clinical and histologic findings that were associated with the measured outcomes: odds of remission from aGVHD were increased when focal vacuolar changes were found on skin biopsy (OR 6.028; 95%CI:1.253-28.992) but decreased by initial hepatic aGVHD (OR 0.112; 95%CI: 0.017-0.748); severe/life-threatening aGVHD was associated with initial gastrointestinal aGVHD (OR 6.054; 95%CI:1.257-29.159); and odds of mortality were decreased with male donor (OR 0.056; 95%CI:0.004-0.804), nulliparous female donor (OR 0.076; 95%CI:0.009-0.669), and focal vacuolar changes on skin biopsy (OR 0.113; 95%CI:0.017-0.770). CONCLUSIONS: We found novel indicators predictive of remission, severity, and mortality in children with aGVHD. Further studies of this condition in children are needed.

Morphea: a practical review of its diagnosis, classification and treatment

Morphea, or localized scleroderma, is a rare disease of the connective tissue that manifests itself with localized sclerosis of the skin and, in some cases, with extracutaneous manifestations. Its etiology is not fully understood, but it is believed that there is genetic predisposition, in addition to environmental triggering factors. Classification of the disease is not simple due to its multiple presentations; however, it is useful in order to define the treatment, which should be individualized and started early to avoid cosmetic and functional complications. In this review, we summarize the most important practical aspects of the classification, diagnostic methods and evaluation of morphea activity, as well as available therapeutic options, with an emphasis on existing clinical evidence regarding their efficacy and safety.

Epidermólisis ampollosa: análisis de costo de la atención médica en México / Epidermolysis bullosas: An analysis of the cost of medical care in Mexico

Resumen: ANTECEDENTES: La epidermólisis ampollosa es un conjunto de enfermedades hereditarias en las que la fragilidad mecánica en tejidos epiteliales produce ampollas, ulceraciones de repetición y cicatrices, así como diversas complicaciones multiorgánicas y psicosociales. OBJETIVO: Determinar el costo económico de la atención médica de pacientes con epidermólisis ampollosa distrófica recesiva durante una hospitalización prototípica, así como durante un año de atención ambulatoria en la Clínica de Epidermólisis Ampollosa del Instituto Nacional de Pediatría, Ciudad de México. MATERIAL Y MÉTODO: Se seleccionó el caso prototípico de un paciente de ocho años de edad con diagnóstico de epidermólisis ampollosa distrófica recesiva, del que se calcularon los gastos generados durante la hospitalización más reciente en el Instituto Nacional de Pediatría, así como los producidos durante un año de tratamiento (2016-2017) dentro de la Clínica de Epidermólisis Ampollosa. RESULTADOS: El costo total de hospitalización fue de 194,757.38 y 345,402.55 pesos según cálculos realizados con precios de medicamentos en el IMSS y farmacias extrahospitalarias, respectivamente, el gasto por medicamentos representó la mayor aportación del total. El costo por un año de atención dentro de la Clínica de Epidermólisis Ampollosa fue de 604,927.25 pesos, los productos para el manejo de la piel representaron el rubro con mayor costo. CONCLUSIONES: La epidermólisis ampollosa tiene alto costo económico a corto y largo plazos, debido a que los pacientes necesitan permanentemente múltiples medicamentos, artículos y atención médica especializada, costo que pocos sectores de la población mexicana pueden solventar.

Abstract: BACKGROUND: The epidermolysis bullosas are a group of hereditary diseases in which the mechanic fragility of epithelial tissue produces blisters, repetitive ulcerations and scarring, as well as several multiorgan and psychosocial complications. OBJECTIVE: To determine the economic cost for medical care in patients with recessive dystrophic epidermolysis bullosa within their prototypical hospital stay, as well as within a year of ambulatory caregiving at the Epidermolysis Bullosa Clinic at the National Institute for Pediatrics in Mexico City (INP). MATERIAL AND METHOD: A prototypical case of an eight-year-old patient diagnosed with recessive dystrophic epidermolysis bullosa was selected and the costs of the most recent hospitalization at INP were calculated, along with other costs produced during a year of care (2016-2017) at the Epidermolysis Bullosa Clinic. RESULTS: The final cost for hospitalization were between 194,757.38 and 345,402.55 Mexican pesos, according to calculations based on medicine prices from the social security system and out-of-hospital pharmacies, respectively. The cost of medicines represented the highest input within the total. The final cost of a year of ambulatory care given by the Epidermolysis Bullosa Clinic was of 604,927.25 Mexican pesos, of which special dressing products represented the highest cost entry. CONCLUSIONS: Epidermolysis bullosa generates high economic cost for patients and health care systems in the short and long term, due to permanent need of multiple medicines, utensils and specialized medical assistance, all of these costs that most of the Mexican population cannot afford.

Mosaic Neurofibromatosis Type 1 in Children: A Single-Institution Experience.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by loss-of-function mutation in the NF1 gene. Segmental or mosaic NF1 (MNF) is an uncommon presentation of the NF1 result of postzygotic mutations that present with subtle localised clinical findings. OBJECTIVES: Our study's objectives were to describe the clinical characteristics of children with MNF. METHODS: We conducted a cross-sectional study of children diagnosed with MNF at the Hospital for Sick Children in Toronto, Canada, from January 1992 to September 2012. Data were abstracted from health records and analysed using a standardised data collection form approved by our hospital Research Ethics Board. RESULTS: We identified 60 patients with MNF; 32 of 60 (53.3%) were female. Mean ± SD age at first assessment was 10.6 ± 4.6 years. The most common initial physical manifestation in 39 of 60 (65.0%) patients was localised pigmentary changes only, followed by plexiform neurofibromas only in 10 of 60 (16.7%) and neurofibromas only in 9 of 60 (15.0%). Unilateral findings were seen in 46 of 60 (76.7%) patients. Most common associations identified included learning disabilities (7/60; 12%) and bony abnormalities (6/60; 10.0%). CONCLUSIONS: MNF is an underrecognised condition with potential implications for patients. Children mostly present with pigmentary anomalies only. Most patients do not develop associated findings or complications before adulthood, but long-term follow-up will help determine outcomes and possible associations. Recognition and confirmation of the diagnosis is important to provide follow-up and genetic counselling to patients.

Rebound Growth of Infantile Hemangiomas After Propranolol Therapy.

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth. METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients' responses to propranolol were evaluated through a visual analog scale. RESULTS: A total of 997 patients were enrolled. The incidence of rebound growth was 231 of 912 patients (25.3%). Mean age at initial rebound was 17.1 months. The odds of rebound among those who discontinued therapy at <9 months was 2.4 (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.3 to 4.5; P = .004) compared with those who discontinued therapy between 12 to 15 months of life. Female gender, location on head and neck, segmental pattern, and deep or mixed skin involvement were associated with rebound on univariate analysis. With multivariate analysis, only deep IHs (OR: 3.3; 95% CI: 1.9 to 6.0; P < .001) and female gender (OR: 1.7; 95% CI: 1.1 to 2.6; P = .03) were associated. Of those with rebound growth, 83% required therapeutic modification including 62% of patients with modifications in their propranolol therapy. CONCLUSIONS: Rebound growth occurred in 25% of patients, requiring modification of systemic therapy in 15%. Predictive factors for rebound growth included age of discontinuation, deep IH component, and female gender. Patients with these predictive factors may require a prolonged course of therapy.

Mosaic Neurofibromatosis Type 1: A Systematic Review.

Confusion is widespread regarding segmental or mosaic neurofibromatosis type 1 (MNF1). Physicians should use the same terms and be aware of its comorbidities and risks. The objective of the current study was to identify and synthesize data for cases of MNF1 published from 1977 to 2012 to better understand its significance and associations. After a literature search in PubMed, we reviewed all available relevant articles and abstracted and synthetized the relevant clinical data about manifestations, associated findings, family history and genetic testing. We identified 111 articles reporting 320 individuals. Most had pigmentary changes or neurofibromas only. Individuals with pigmentary changes alone were identified at a younger age. Seventy-six percent had localized MNF1 restricted to one segment; the remainder had generalized MNF1. Of 157 case reports, 29% had complications associated with NF1. In one large case series, 6.5% had offspring with complete NF1. The terms "segmental" and "type V" neurofibromatosis should be abandoned, and the correct term, mosaic NF1 (MNF1), should be used. All individuals with suspected MNF1 should have a complete physical examination, genetic testing of blood and skin, counseling, and health surveillance.

Oral Nadolol for the Treatment of Infantile Hemangiomas: A Single-Institution Retrospective Cohort Study.

BACKGROUND: Beta-blockers have become the treatment of choice for problematic infantile hemangiomas (IHs). Nadolol, a nonselective beta-blocker with potential dosing advantages and a better safety profile than that of other beta-blockers, has been studied as an alternative therapeutic option. Our objective was to characterize the efficacy and safety of oral nadolol in the treatment of proliferating IHs. METHODS: A retrospective cohort study was conducted at the Hospital for Sick Children between February 2010 and April 2012 in patients treated with nadolol for proliferating IHs causing functional impairment or cosmetic disfigurement. The primary outcome was the percentage involution measured independently by two assessors who scored changes in the extent of IHs by comparing serial photographs using a 100-mm visual analogue scale (VAS), on which 5 mm represented 10% change. RESULTS: Forty-four patients treated with nadolol for IHs with adequate photographic documentation were identified. The median age at presentation was 4.5 months (interquartile range 1.5-7.9 mos). There was a mean improvement of 91.8 ± 11.1%. At least 50% improvement was noted in 42 (95%) patients and 75% improvement in 39 (89%) patients. The mean time to 50% and 75% improvement was 2.9 and 3.7 months, respectively. Analysis of variance showed that younger age at the time of treatment start was associated with a higher mean VAS score (% involution) (p < 0.05). Treatment duration (mean 9.5 ± 5.6 months) had no significant effect on VAS score. Test of interobserver correlation showed good agreement (intraclass correlation coefficient = 0.86, p = 0.001). CONCLUSIONS: Oral nadolol is efficacious in patients with problematic IHs. Further large-scale prospective comparative studies are warranted to compare nadolol with other beta-blockers.

Pediatric Sweet syndrome. A retrospective study.

INTRODUCTION: Sweet syndrome (SS) is a relatively rare pediatric diagnosis, with fewer than 80 pediatric cases reported in the literature, characterized by tender erythematous plaques and nodules associated with systemic inflammation. MATERIALS AND METHODS: We retrospectively reviewed the charts of pediatric patients diagnosed with SS both clinically and histologically at our reference hospital between the years of 2000 and 2012. Clinical, laboratory, and pathologic data were analyzed. RESULTS: We found five patients; four were male, aged between 9 and 14 years. All had fever, elevated markers of systemic inflammation, and typical skin lesions. SS was associated with underlying hematologic malignancy in one patient; all-trans retinoic acid in another; infection in two patients; and in one patient, no identifiable cause was found. Three of the five patients treated with systemic corticosteroids had excellent response, and two had recurrences and received additional treatment with dapsone and saturated solution of potassium iodide. CONCLUSIONS: Sweet syndrome is an extremely rare diagnosis in children. It is associated with the same conditions as in adults, but it is more frequently associated with infections than malignancies. In general, prognosis is good, but recurrences occur and second-line treatment may be needed.