Summary
Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and ...course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male‐to‐female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.
What's already known about this topic?
The clinical and genetic features and outcomes of mastocytosis differ for the adult and paediatric forms.
Since paediatric mastocytosis was linked to mutations in c‐Kit in 2010, it has been considered a clonal disease.
In 1963, Caplan reported that spontaneous regression occurs in the majority of cases of paediatric mastocytosis, and no predictive factors have been identified.
What does this study add?
This extensive review points out that the outcome in some paediatric cases is fatal, that KIT mutations are rarely studied and that predictive factors are still unknown.
We suggest that long‐term follow‐up of children is necessary and that prospective studies are warranted to evaluate the prognostic value of sequencing KIT.
Summary
Background
Mastocytosis is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells. The adult and paediatric forms differ in their clinical and ...genetic features and outcomes.
Objectives
To describe the clinical evolution of a well‐characterized cohort of paediatric mastocytosis (PM), and to analyse the relationship between KIT mutation and the clinical course.
Methods
This was a prospective cohort study performed at the National Clinical Reference Center for Mastocytosis. Diagnosis was confirmed by identification of KIT mutation on lesional skin biopsy. Mastocytosis subtype, mast cell mediator‐related symptoms (MC MRS) and clinical course were recorded. Fifty‐three patients with PM and > 4 years of disease course were enrolled. The mean ± SD age at the final evaluation was 13·2 ± 4·8 years. The main outcome was the type of KIT mutation as a predictor of evolution and clinical characteristics.
Results
Patients presented with maculopapular cutaneous mastocytosis (n = 44), diffuse cutaneous mastocytosis (n = 6) or mastocytoma (n = 3). The mean duration of disease was 12·1 years. Substantial or partial cutaneous regression (18 of 53 and 16 of 53), stabilization or aggravation (16 of 53) and complete cutaneous regression (three of 53) were noted. MC MRS mainly regressed (21 of 53). For 22 patients, evolution of MC MRS and evolution of cutaneous lesions were different. No significant association between evolution and KIT mutation or between evolution and type of cutaneous mastocytosis was found. A late onset of the disease (after 2 years) is associated with worse evolution.
Conclusions
PM is not systematically self‐regressive. MC MRS manifestations and cutaneous lesions can persist or increase overtime. KIT mutation is not a predictor of evolution.
What's already known about this topic?
The clinical and genetic features and outcomes of mastocytosis differ between the adult and paediatric forms.
Paediatric mastocytosis is also a clonal disease.
Spontaneous regression occurs in the majority of cases and no predictive factors have been identified.
What does this study add?
This prospective study of 53 patients shows that KIT mutation is not a predictor of evolution. However, characteristics such as age at disease onset could be predictors.
Paediatric mastocytosis evolution is not systematically regressive, and adolescents can experience only partial regression or aggravation, including both cutaneous and mast cell mediator‐related symptoms.
A long‐term follow‐up study of paediatric patients with mastocytosis is needed.
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Systemic auto-inflammatory diseases (SAIDs) are disorders associated with deregulation of innate immunity in which patients present classically with systemic inflammatory manifestations, in ...particular fever, skin-mucosal rashes, arthromyalgia and abdominal pain, with an increase in blood biomarkers of inflammation. At the time of their discovery, these diseases were associated with constitutional mutations in genes encoding proteins involved in innate immunity, and it was then considered that they had to begin in childhood. This dogma of constitutional mutations in SAIDs is no longer so unquestionable, since 2005 several cases of mosaicism have been reported in the literature, initially in cryopyrinopathies, but also in other SAIDs in patients with obvious clinical phenotypes and late onset of disease expression, in particular in the VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic Syndrome) and very recently in MEVF gene. Next-generation sequencing techniques are more sensitive than Sanger for detecting mosaicisms. So, when a clinical diagnosis seems obvious but no constitutional mutation is found by low-depth genetic analysis, it is useful to discuss with expert geneticists whether to consider another genetic approach in a child or an adult. This modifies the situations in which clinicians can evoke these diseases. This review provides an update on mosaicism in SAIDs.
Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already ...described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.
Auto-inflammatory diseases (AIDs) are diseases resulting from an inappropriate activation of innate immunity in the absence of any infection. The field of monogenic AIDs is constantly expanding, with ...the discovery of new pathologies and pathophysiological mechanisms thanks to pangenomic sequencing. Actinopathies with auto-inflammatory manifestations are a new emerging group of AIDs, linked to defects in the regulation of the actin cytoskeleton dynamics. These diseases most often begin in the neonatal period and combine to varying degrees a more or less severe primary immune deficiency, cytopenias (especially thrombocytopenia), auto-inflammatory manifestations (especially cutaneous and digestive), atopic and auto-immune manifestations. The diagnosis is to be evoked essentially in front of a cutaneous-digestive auto-inflammation picture of early onset, associated with a primary immune deficiency and thrombocytopenia or a tendency to bleed. Some of these diseases have specificities, including a risk of macrophagic activation syndrome or a tendency to atopy or lymphoproliferation. We propose here a review of the literature on these new diseases, with a proposal for a practical approach according to the main associated biological abnormalities and some clinical particularities. However, the diagnosis remains genetic, and several differential diagnoses must be considered. The pathophysiology of these diseases is not yet fully elucidated, and studies are needed to better clarify the inherent mechanisms that can guide the choice of therapies. In most cases, the severity of the picture indicates allogeneic marrow transplantation.
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