Mastocytosis In Children Research Articles

Treatment Approaches for Diffuse Cutaneous Mastocytosis in Children: Literature Review and Actual Clinical Experience

Background. Mastocytosis is a very rare disease with various manifestations, based on abnormal clonal proliferation of mast cells in organs and tissues, such as: skin, bone marrow, lymph nodes, liver, spleen, and gastrointestinal tract. The diagnosis can be established according to clinical manifestations, laboratory, and instrumental data. Darier’s sign and histological examination are crucial for mastocytosis diagnosis. The presented clinical case describes very rare cutaneous form of mastocytosis. Clinical case description. The girl, 2.5 years old, was hospitalized with multiple erythematous papules on her body, face, and limbs. Comprehensive examination, including bone marrow biopsy and positron-emission tomography, allowed us to exclude mastocytosis systemic manifestations. Conclusion. Despite the fact that mastocytosis in children is mostly represented by skin form, it is necessary to perform complex patient examination on any systemic damage. Antihistamines in combination with topical and/or systemic glucocorticoids are often effective, but complete response does not always occur. Implementation of other therapeutic options, such as targeted drugs (tyrosine kinase inhibitors), is suggested In case of no or insufficient therapeutic effect.

Clinical and epidemiological features of cutaneous mastocytosis among the pediatric population of Moscow

BACKGROUND: Cutaneous mastocytosis is a rare disease that primarily develops in childhood.
 AIM: This study aimed to determine the clinical and epidemiological characteristics and frequency of detection of cutaneous mastocytosis among children in Moscow.
 MATERIALS AND METHODS: A single-center epidemiological retrospective study was conducted. Data from Form № 12 of the federal statistical observation "Information on the number of diseases registered in patients living in the service area of a medical organization" were used as a statistical source of information. To calculate the incidence rate in intensive indicators per 100 thousand population, data on the population of Moscow for the period 2019–2022 were used.
 RESULTS: Over the period 2019–2022, a gradual trend towards an increase in the number of newly identified cases of cutaneous mastocytosis in children and adolescents in Moscow was revealed. Number of initial applications from children and adolescents (0–17 years old) for this period increased by 4.8 times. The share of cutaneous mastocytosis in the structure of skin diseases and congenital anomalies (malformations) of the skin increases every year. In 2019, for every 1,834 pediatric visits (age category 0–17 years) regarding skin diseases, there was 1 case of mastocytosis; in 2020 the ratio was 1,863:1; in 2021 ― 491:1; in 2022 ― 376:1. Since 2019, there has been an increase in the primary incidence of cutaneous mastocytosis from 3.63 cases per 100,000 child population to 16.61 cases per 100,000 child population in 2022.
 CONCLUSION: The increase in incidence in the pediatric population and the share of cutaneous mastocytosis in the structure of skin diseases in recent years demonstrates the need to generate interest and attention of the medical community to this pathology.

Mastocytosis in children

Mastocytosis in children

Cutaneous mastocytosis and allergic diseases in children: A cross-sectional study

BACKGROUND: Mastocytosis is a heterogeneous group of diseases characterized by abnormal accumulation of clonal mast cells in one or more organs. Comorbidities in patients with mastocytosis include IgE-dependent allergies, psychiatric or psychological disorders, and vitamin D deficiency. Despite the clinical similarities between allergies and mastocytosis, only a few European studies have considered these comorbidities.
 AIM: To analyze the frequency of concomitant-allergic diseases in children with cutaneous mastocytosis.
 MATERIALS AND METHODS: Data of 248 children aged 6 months to 17 years who were diagnosed with cutaneous mastocytosis and received outpatient treatment and observation at the Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology between March 2022 and June 2023 were analyzed. Serum levels of total and allergen-specific IgE were analyzed in children with and without allergic diseases. In addition, a positive history of allergy was analyzed in close relatives of children with cutaneous mastocytosis.
 RESULTS: Every third child (36.7%) with cutaneous mastocytosis had a concomitant allergic disease. Relatives of 27.4% of the examined children had allergic diseases. The process was significantly more often accompanied by allergic diseases in children with mastocytomas than in those with maculopapular cutaneous mastocytosis (χ2=45.46; p=0.001). The level of total IgE was not a statistically significant sign of the presence of allergic diseases in cutaneous mastocytosis (χ2=1.161; p=0.3). Allergen-specific IgE was detected in 47.2% of the children with allergic diseases. Among children without signs of food allergy and pollinosis, asymptomatic low and moderate sensitization to any plant product and birch was detected in 26.5%. Sensitization to respiratory allergens was found in 8% of children with cutaneous mastocytosis without allergic diseases.
 CONCLUSIONS: In Russia, this study demonstrated for the first time a high incidence of allergic diseases in children with cutaneous mastocytosis. The results showed that all clinical forms of mastocytosis in children, including cutaneous mastocytosis, should be subjected to interdisciplinary observation and examination. The timely detection of comorbid allergic diseases contributes to the development of individual techniques for the treatment and prevention of complications and anaphylaxis.

Photo gallery. Rare dermatoses. Part I

Orphan dermatoses are caused by both genetic causes and a number of autoimmune, inflammatory and infectious processes in the body. Congenital giant nevus is associated with serious complications: malignant melanoma, CNS lesions (neurocutaneous melanosis). Multiple epidermoid cysts are often a component of Gardner's syndrome. Angiolymphoid hyperplasia with eosinophilia, a vascular tumor formation with proliferation of histiocytoid endothelial cells, with severe lymphocytic and eosinophilic infiltration, recurs in 1/3 of cases. Morbigan's disease is persistent erythema and swelling of the middle third and upper part of the face. Skin mastocytosis in children is prone to spontaneous resolution during puberty. Squamous cell skin cancer accounts for 20% of all skin cancers and has a high risk of recurrence, metastasis, and death. Buschke's scleroderma is a scleroderma-like disease that causes progressive fibrous-mucinous thickening of the skin affecting the neck, shoulders, proximal upper extremities, and face. Fulminant (lightning) acne is a sharply exacerbated form of acne vulgaris, characterized by an acute onset and the appearance of confluent abscesses. Cases of acne fulminans have been observed during treatment with isotretinoin. Norwegian (crustose) scabies is associated with a compromised immune response, which allows the mites to multiply and can number in the millions. Pretibial myxedema (thyroid dermopathy) is a rare extrathyroid manifestation of Graves' disease along with thyrotoxicosis, thyroid hypertrophy, ophthalmopathy, and acropachy. Porokeratosis Mibelli predisposing factors of development are immunosuppressive conditions, malignancy is possible. Osteomas are formations from bone tissue in the dermis or subcutaneous fat as a result of metaplasia of fibroblasts into osteoblasts, or differentiation of primitive mesenchymal cells into osteoblasts and their migration to an ectopic site. Sarcoidosis of the skin is characterized by a variety of clinical forms, rarely observed before 40 years. Xanthomas with histiocytosis X ― a violation of lipid metabolism. The rural type of leishmaniasis (acute necrotizing) has a short incubation period, a significant spread of rashes and healing with the formation of scar tissue. The giant condyloma of BuschkeLevenshtein is characterized by progressive growth, large size and recurrent course, it can transform into squamous cell carcinoma. Degos disease ― malignant atrophic papulosis ― a rare disease caused by blockage of the arteries and veins.

Mastocytosis in children

Mastocytosis in children is arare disease characterized by an abnormal accumulation of tissue mast cells. Mastocytosis in children presents with typical skin alterations that are classified as maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, or mastocytoma. Some patients also develop mast cell mediator symptoms, such as pruritus, flush, and anaphylaxis. In many children, the disease is characterized by abenign and usually self-limiting course; systemic mastocytosis with extracutaneous involvement and achronic or progressive course is found only rarely. Therapeutically, H1 antihistamines are primarily used on an as-needed basis or as continuous treatment, depending on the severity. Children, parents and caregivers should be thoroughly educated about the clinical picture and possible trigger factors of mast cell mediator release. For children with extensive skin alterations and severe symptoms, the prescription of an epinephrine auto-injector is recommended for emergency treatment.

Mastocytosis in children

ZusammenfassungDie Mastozytose bei Kindern ist eine seltene Erkrankung, die durch eine abnorme Vermehrung von Gewebemastzellen gekennzeichnet ist. Es zeigen sich typische Hautveränderungen, die als makulopapulöse kutane Mastozytose, diffuse kutane Mastozytose oder Mastozytom klassifiziert werden. Ein Teil der Patientinnen und Patienten weist zudem Mastzellmediatorsymptome wie Juckreiz, Flush und Anaphylaxie auf. Bei vielen Kindern ist die Erkrankung durch einen benignen, meist selbstlimitierenden Verlauf charakterisiert; nur selten findet sich eine systemische Mastozytose mit extrakutaner Beteiligung und chronischem oder progressivem Verlauf. Therapeutisch werden in erster Linie H1-Antihistaminika eingesetzt, je nach Schwere bedarfsorientiert oder als Dauertherapie. Kinder, Eltern und Betreuungspersonen sollten sorgfältig über das Krankheitsbild und mögliche Trigger-Faktoren der Mastzellmediatorfreisetzung aufgeklärt werden. Für Kinder mit ausgeprägten Hautveränderungen und schweren Symptomen ist die Verordnung eines Adrenalin-Autoinjektors zur Notfallbehandlung empfehlenswert.

Mastocytosis in children: a single-center long-term follow-up study.

Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis of cutaneous mastocytosis (CM) is based on clinical findings, positive Darier's sign, and histopathology, if necessary. Medical records of 86 children with CM diagnosed during a 35-year long period were reviewed. Most patients (93%) developed CM during the first year of life (median age 3 months). Clinical features at presentation and during the follow-up period were analyzed. Baseline serum tryptase level was measured in 28 patients. Atotalof85% of patients had maculopapular cutaneous mastocytosis/urticaria pigmentosa (MPCM/UP), 9% had mastocytoma, and 6% had diffuse cutaneous mastocytosis (DCM). Boy to girl ratio was 1.1:1. Fifty-fourof86 patients (63%) were followed from 2 to 37 years (median 13 years). Complete resolution was registered in 14% of mastocytoma cases, 14% of MCPM/UP, and in 25% of DCM patients. After the age of 18, skin lesion persisted in 14% mastocytoma, 7% MCPM/UP, and 25% children with DCM. Atopic dermatitis was diagnosed in 9.6% ofpatients with MPCM/UP. Threeof28 patients had elevated serum tryptase. Prognosis in all patients was good, and there were no signs of progression to systemic mastocytosis (SM). To the best of our knowledge, our results represent the longest single-center follow-up study of childhood-onset CM. We found no complications of massive mast cell degranulation or progression to SM.

Histopathological characteristics are instrumental to distinguish monomorphic from polymorphic maculopapular cutaneous mastocytosis in children.

BackgroundMastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric mastocytosis cases persist after puberty. In particular, monomorphic maculopapular cutaneous mastocytosis (mMPCM) is often persistent and associated with systemic mastocytosis. However, clinical differentiation of MPCM from polymorphic (p)MPCM can be difficult.AimTo identify histopathological features that can help to distinguish mMPCM from other subtypes of paediatric mastocytosis.MethodsThis was a retrospective study using skin biopsies from patients with any subtype of mastocytosis. The localization and density of the MC infiltrate, MC morphology and expression of aberrant markers were evaluated and correlated with clinical characteristics.ResultsIn total, 33 biopsies were available for evaluation from 26 children [(10 with mMPCM, 5 with mastocytoma, 3 with diffuse cutaneous mastocytosis (DCM), 8 with pMPCM)] and 7 adults with MPCM. The MC number was increased in all patients, but was higher in children than adults (P < 0.01). The presence of mMPCM was associated with sparing of the papillary dermis from MC infiltration, whereas MC density in the papillary dermis was highest in pMPCM and DCM (P < 0.01). The positive predictive value of the presence of a reticular MC infiltrate for mMPCM was 72.7% (95% CI 51.4–87.0), and the negative predictive value was 83.3% (95% CI 42.2–97.2). There were no relevant differences in the expression of CD2, CD25 or CD30 between the different subtypes.ConclusionSkin histopathology might enhance the phenotypical differentiation of mMPCM from other subtypes in children, thereby increasing the accuracy of one's prognosis.

Mastocytosis in children. Clinical features are more useful than laboratory examinations.

Starting from the analysis of a clinical case of infantile mastocytosis followed for 18 years, the role of the history is emphasized both from the diagnostic and clinical monitoring point of view. The history is so significant that in most cases it is not necessary to perform a histological examination and sometimes even to evoke Darier’s sign to be sure of the diagnosis. And to monitor the clinical course of mastocytosis, which in the child is almost always characterized by spontaneous regression, it is sufficient for the mother to record the episodes of flushing, blisters, and wheals: their rarefaction with time attests to the regression of the disease. Systemic mastocytosis in the child is practically non-existent, so the dosage of serum tryptase is of little importance.

Cutaneous Mastocytosis in Children: Is It Just a Skin Disease?

Introduction: Mastocytosis is characterized by the excessive proliferation and accumulation of mast cells in organs such as the spleen, liver, lymph nodes, skin, gastrointestinal tract, and bone marrow. Cutaneous mastocytosis, which is only presented with skin involvement, is frequently seen in childhood. Objective: It was aimed to determine the demographic and clinical characteristics of patients with cutaneous mastocytosis and the knowledge level of families about the disease, and to raise awareness about this disease. Material and Methods: The records of 25 cases with cutaneous mastocytosis were evaluated retrospectively and the knowledge levels of the families were measured with a questionnaire. Results: The mean follow-up period of 25 patients was 39 months. The most common type of the disease was urticaria pigmentosa (60%). Itching (n=14) was the most common symptom in patients. Only 2 patients were carrying adrenaline auto-injectors. While 60% of the families (n=15) had fears about the disease; of these 15 families, 53.3% (n=8) were afraid of the re-spread of the disease, 13.3% (n=2) turning of the disease into skin cancer, 13.3% (n=2) occupation of the internal organs, 13.3% (n=2) having a new attack, and 0.4% (n=1) re-forming of the spots. Conclusion: The cutaneous forms of mastocytosis are mostly observed in childhood, and systemic involvement is rare. Mastocytosis progresses with rashes in childhood and its findings are limited to the skin. Families should be better informed about mastocytosis and the need for patients to carry an adrenaline auto-injector due to the risk of attacks should be explained to them.

Solitary Mastocytoma in Children: Case Report

Solitary mastocytoma is the most common form of mastocytosis in children. The main symptom is pruritus. The treatment is symptomatic and it’s based on Topical corticosteroids. The prognosis is good with possibility of spontaneous regression at adulthood. This case report is about a 7-month-old infant that presented with an erythromatous papular lesion on the left temple. The patient responded well to topical steroids and antihistamines.

Clinical and Demographic Characteristics of Cutaneous Mastocytosis in Childhood: Single-center Experience.

Mastocytosis is a rare and heterogenous disease, and in children it is generally limited to the skin and tends to regress spontaneously in adolescence. In this study, demographic, clinical, and laboratory characteristics of pediatric patients with mastocytosis, and also coexisting diseases were investigated. A total of 61 pediatric patients were included in the study. The male-to-female ratio was 2.2, the median age was 2 years (range, 0.25 to 19 y), and the median follow-up period was 2.0 years (range, 0.25 to 19 y). Types of clinical presentation at diagnosis consisted of mainly urticaria pigmentosa (45.9%). Seven patients were further investigated with suspicion of systemic mastocytosis, they were followed up, median of 9 years (range, 2.5 to 16 y), and none of them developed systemic disease. Coexisting allergic diseases were recorded in total 5 patients (8.2%). Three patients had immunoglobulin A deficiency, 1 patient had elevated immunoglobulin E level. A patient developed mature B-cell lymphoma with a heterozygous mutation in c-KIT exon 11. Cutaneous mastocytosis in children may present as a complex disease with different clinical signs and symptoms. Standardized clinical criteria and guidelines for the follow-up of children with mastocytosis are required.

Systemic Mastocytosis in Children: About a Case

Systemic Mastocytosis in Children: About a Case

Analysis of Risk Factors Affecting Skin Mastocytosis in Children: Cross-Sectional Study

Background. Skin mastocytosis is rare disease that is diagnosed in most children under the age of 2 years. The date on rash regression dynamics and disease symptoms is not fully presented in the literature.Objective. The aim of the study was to analyze risk factors associated with clinical manifestations and regression time of skin mastocytosis in children.Methods. The study includes data on 28 children aged from 3 months to 12 years who has undergone outpatient care and observation in Moscow Scientific and Research Center of Dermatovenerology and Cosmetology of Moscow City Health Department in the period between January 2016 and November 2019. The data about diagnosis was obtained from medical records.Results. Maculopapular skin mastocytosis (MPSM) was diagnosed in 28.6% of children, solitary mastocytoma — in 71.4%. The analysis of clinical course of skin mastocytosis has shown constantly relapsing process and slow spontaneous rash regression in more than 50% of children. Diffuse skin rash, flushing reactions, persistent skin itching or its combination with hepatomegaly or neurological symptoms were prevalent among MPSM manifestations. Risk factors affecting delayed regression of skin mastocytosis in children with MPSM are: late onset, area of skin lesions, comorbidities, severity of reticular vascular pattern at dermatoscopy. Severity of skin lesions did not affect the tryptase activity. The major risk factor affecting the delayed regression of solitary mastocytoma is rash injury (OR 6.10, 95% CI 3.66–16.73). The severity of reticular vascular pattern in skin mastocytosis foci has varied depending on the severity of skin lesions.Conclusion. Half of all children with skin forms of mastocytosis have delayed rash regression. This causes high concern among parents and violates social adaptation of children. Timely assessment of risk factors alongside with dynamic assessment of the dermatoscopy patterns and tryptase activity are important for implementation of correct follow-up monitoring and management for children. Rash (of any localization) injuries should be avoided to prevent delayed regression of the disease in children with skin forms of mastocytosis.

Immune response against HtrA proteases in children with cutaneous mastocytosis.

Mast cells play an important role in both, the innate and adaptive immunity, however, clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. A skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are related to development of several pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM. Levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n=36) and in healthy controls (n=62) were assayed. Anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera, levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased when compared to the control group, while the HtrA protein levels were comparable. No significant differences in the anti-HtrA2 IgG level were found; for the anti-HtrA4 IgGs lower levels in CM group were revealed. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4, but not against HtrA2, increase with age.

Experimental and clinical study of the efficacy of medicines containing omega-3 and 6 polyunsaturated fatty acids, in the treatment of inflammatory skin diseases

Introduction: Over the recent years, the attention of scientists regarding the search for alternative means of treatment, including local therapy, of inflammatory skin diseases, has been focused in recent years on medicines containing omega-3 and 6 polyunsaturated fatty acids (PUFA).&#x0D; Objectives: to substantiate the feasibility of using medicines containing omega-3 and 6 polyunsaturated fatty acids and antioxidants in the treatment of inflammatory skin diseases.&#x0D; Methods:The studies were carried out on 224 conventional white rats of the Wistar line in compliance with the international principles of the European Convention for the Protection of Vertebrates. A burn injury was used to cause experimental simple irritant contact dermatitis. After trying various treatment options with using Omegaven, histopathological examinations of 18 fragments of affected skin of white rats with cross sections stained with hematoxylin–eosin and pikrofuxin by Van Gieson’s method. The state of lipid peroxidation (LPO) in blood and affected skin was evaluated in the animals. One hundred forty-six patients with inflammatory skin diseases (dermatitis simple irritant contact, allergic contact dermatitis, atopic dermatitis, neurodermatitis, psoriasis, cutaneous mastocytosis in children) were observed. In treatment, there were used medicines with omega-3 and 6 PUFA or an antioxidant medicines.&#x0D; Results and discussion: Skin reactions of dermatitis simple irritant contact in rats after burn injury were evaluated at different points of time. The observations showed higher efficacy of medicines containing PUFA than standard anti-inflammatory agents in the treatment of simple irritant contact dermatitis. Histopathological examination of the skin of white rats with simple irritant contact dermatitis after the 11-day treatment revealed that the expression and composition of the cellular reaction in the lesions with a predominating lymphocytes and macrophages (mainly cell response) differ significantly from those trated with Radevit ointment (segmented neutrophil leukocytes, eosinophils – delay in the acute phase of inflammation). There was identified a smaller thickness (up to 1/3) of the strips of granulation tissue under the actively proliferating cells of the epidermis. It was possible to demonstrate the superiority with respect to reducing the activity of LPO medicines containing omega-3 and 6 PUFA, over those with anti-inflammatory action. The clinical observations of patients showed high efficacy of the local treatment with medicines containing omega-3 and 6 PUFA, or antioxidant.&#x0D; Conclusion: For the first time, the mechanism of implementing an anti-inflammatory effect of the experimental medicines containing omega-3 and 6 polyunsaturated fatty acids (Omegaven, Vitamin F99 cream rich), – an antioxidant effect - when treating simple irritant contact dermatitis when treating simple irritant contact dermatitis; that is the weakening of the severity of oxidative stress. For the first time, the greatest contribution of an increased activity of catalase to the weakening of oxidative stress in the affected skin is shown.

Solitary mastocytoma arising from a tight infant identification bracelet

Mastocytosis is characterized by a proliferation of mast cells in the skin and extracutaneous organs. Cutaneous mastocytoma is the second most common presentation of mastocytosis in children and has been reported to arise post-trauma. We report herein the second case of solitary mastocytoma resulting from application of an excessively tight infant identification bracelet and the first in the English literature.

Mastocytosis in Children.

In this review, we examine the current understanding of the pathogenesis, clinical presentations, diagnostic tools, and treatment options of pediatric mastocytosis as well as the natural history of the disease. We discuss the emerging concept of mast cell activation syndrome. Mastocytosis in children presents most commonly as isolated cutaneous lesions and is a relatively rare occurrence with excellent prognosis and spontaneous regression often occurring by adolescence. Systemic mastocytosis with organ system involvement is a more serious condition and is likely to persist into adulthood.

Longitudinal Study of Pediatric Urticaria Pigmentosa.

Urticaria pigmentosa (UP) is the most common form of mastocytosis in children and is associated with systemic signs, symptoms, and triggers. To our knowledge, the effect of UP on children's quality of life has not been studied. The objective of the current study was to characterize the natural history, triggers, and complications of pediatric UP, identify prognostic indicators, and determine its effect on quality of life. Between 2002 and 2007, children with three or more mastocytomas diagnosed by a pediatric dermatologist were recruited during visits at the Children's Hospital of Wisconsin Dermatology Clinic (Milwaukee, WI). Research visits were conducted every 3 years and telephone interviews yearly. The Children's Dermatology Life Quality Index was administered to subjects 4 years of age and older at enrollment. Laboratory test results were collected for subjects younger than 4 years at enrollment. Subjects were followed until UP resolution or study end in August 2015. The final cohort size was 43 subjects followed for a median of 8.1 years. Twenty-six subjects were followed through study completion. At age 12 years, 6 patients had disease resolution and 14 remained active. Patients who had disease resolution before age 12 years were more likely to be male and had fewer years of age and smaller lesions, fewer affected areas, and earlier onset. Common medications and anesthetics resulted in no serious reactions. Hymenoptera stings occurred in 51%, with no reports of anaphylaxis. No patient reported a severe effect on quality of life, with most indicating mild to no effect. Severe complications are not common with historically identified triggers. Disease does not resolve before adolescence in most children. UP has a minimal effect on quality of life for most children.