Infantile haemangioma Léauté-Labrèze, Christine, Dr; Harper, John I, Prof; Hoeger, Peter H, Prof
The Lancet (British edition),
07/2017, Letnik:
390, Številka:
10089
Journal Article
Recenzirano
Summary With a prevalence of 4·5%, infantile haemangiomas are the most common benign tumours of infancy, arising in the first few weeks of life and exhibiting a characteristic sequence of growth and ...spontaneous involution. Most infantile haemangiomas do not require therapy. However, to identify at-risk haemangiomas, close follow-up is crucial in the first weeks of life; 80% of all haemangiomas reach their final size by 3 months of age. The main indications for treatment are life-threatening infantile haemangioma (causing heart failure or respiratory distress), tumours posing functional risks (eg, visual obstruction, amblyopia, or feeding difficulties), ulceration, and severe anatomic distortion, especially on the face. Oral propranolol is now the first-line treatment, which should be administered as early as possible to avoid potential complications. Haemangioma shrinkage is rapidly observed with oral propranolol, but a minimum of 6 months of therapy is recommended.
Summary
Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85–90% regress spontaneously, some may become life‐ or function‐threatening and ...require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, α‐interferon or cyclophosphamide, all bearing the risk of serious side‐effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long‐term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1–3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long‐term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.
Summary
Vascular malformations (VMs) are caused by localized defects of vascular development. Most VMs are due to sporadic, postzygotic mutations, while some are the result of autosomal dominant ...germline mutations. Genotype–phenotype correlation is influenced by many factors. Individual genes can induce different phenotypes (pleiotropy), and similar phenotypes can be due to different genes/mutations (redundancy). The phenotypic spectrum of somatic mutations is wide, and depends on variant allele frequency, timing during embryogenesis, cell type(s) involved and type of mutation. The phenotype of germline mutations is determined by penetrance and expressivity, and is influenced by epigenetic factors (DNA methylation, histone modification) or ‘second‐hit’ somatic mutations. Except for disorders with pathognomonic phenotypes such as Proteus syndrome or a characteristic constellation of symptoms such as CLOVES congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal naevi and scoliosis/skeletal/spinal anomalies or PIK3CA‐related overgrowth spectrum syndrome, differential diagnosis of VM is therefore difficult. It will be greatly facilitated with increasing analytic sensitivity of sequencing techniques such as next‐generation sequencing. High‐sensitivity molecular techniques are a prerequisite for targeted pharmacotherapy, i.e. selective therapeutic inhibition of activating mutations underlying VM, which has shown promising results in preliminary studies.
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Background Safe and effective therapies are needed for pediatric patients with psoriasis. Objective The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had ...moderate-to-severe psoriasis. Methods Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg ≤60 kg, 45 mg >60-≤100 kg, and 90 mg >100 kg) or half-standard dosing (HSD; 0.375 mg/kg ≤60 kg, 22.5 mg >60-≤100 kg, and 45 mg >100 kg) at weeks 0 and 4 and every 12 weeks or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12. Clinical assessments included the proportion of patients achieving a Physician's Global Assessment of cleared/minimal (PGA 0/1), at least 75% improvement in Psoriasis Area and Severity Index (PASI 75), and at least 90% in PASI (PASI 90). Adverse events (AEs) were monitored through week 60. Results At week 12, 67.6% and 69.4% of patients receiving ustekinumab HSD and SD, respectively, achieved PGA 0/1 versus 5.4% for placebo ( P < .001). Significantly greater proportions receiving ustekinumab achieved PASI 75 (HSD, 78.4%; SD, 80.6%; placebo, 10.8%) or PASI 90 (HSD, 54.1%; SD, 61.1%; placebo, 5.4%) at week 12 ( P < .001). Through week 12, 56.8% of placebo patients, 51.4% of HSD patients, and 44.4% of SD patients reported at least one AE; through week 60, 81.8% reported AEs. Limitations The study was small relative to adult trials. Conclusions In this patient population (12–17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year.
Summary
Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular ...tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review.
With a prevalence of 2.6–4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of ...IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have become obsolete. This paper summarizes current recommendations for management of complicated IH. These recommendations have been written by an expert group after a consensus process including bibliographic review, several drafts of synthesis, meetings with quantitative voting system and redaction of an approved final manuscript.
Conclusion
: Oral propranolol is the first-line agent for the treatment of complicated IH.
What is Known:
•
Infantile haemangiomas (IH) are the most common tumours of infancy. Within a very short period after its discovery and long before the publication of randomized controlled trials, propranolol has become the number one agent for the treatment of complicated IH.
What is New:
•
We report IH treatment recommendations of an international, interdisciplinary team of experts, based on an up-to-date review of the literature.
Dupilumab: Two sides of a side‐effect Hoeger, Peter H.
Pediatric dermatology,
January/February 2024, 2024 Jan-Feb, 2024-01-00, 20240101, Letnik:
41, Številka:
1
Journal Article
Recenzirano
The purported antiviral effect of dupilumab may be considered a positive side effect. Its mechanism, however, points to an underlying immunomodulation with potentially far‐reaching consequences.
Summary
Background
Adalimumab (ADA) (Humira®, AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis.
Objectives
To evaluate the ...long‐term efficacy and safety of ADA in children with severe plaque psoriasis.
Methods
Results are presented from the 52‐week long‐term extension (LTE) of the randomized, double‐blind, double‐dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg−1 (40 mg maximum) or 0·4 mg kg−1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1–0·4 mg kg−1 (25 mg maximum) weekly. The 16‐week initial treatment (IT) period was followed by a 36‐week withdrawal period and a 16‐week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg−1 (blinded or open label) or ADA 0·4 mg kg−1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods.
Results
Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg−1. Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31–86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28–47%; ADA 0·8(IT)/0·8(LTE) 50–72%. No serious infections occurred in the LTE.
Conclusions
After 52 weeks of long‐term ADA treatment in children aged 4–18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified.
What's already known about this topic?
The results from the first three periods of this phase III trial in children aged 4–18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population.
What does this study add?
This is the first study to evaluate long‐term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population.
Linked Comment: Belloni Fortina and Caroppo. Br J Dermatol 2019; 181:1127–1128.
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