Pediatric Mastocytosis: An Update Giona, Fiorina
Mediterranean journal of hematology and infectious diseases,
11/2021, Letnik:
13, Številka:
1
Journal Article
Odprti dostop
Mastocytosis is a rare clonal disorder characterized by excessive proliferation and accumulation of mast cells (MC) in various organs and tissues. Cutaneous mastocytosis (CM), the most common form in ...children, is defined when MC infiltration is limited to the skin. In adults, the most common form is systemic mastocytosis (SM), characterized by MC proliferation and accumulation in organs, such as bone marrow, lymph nodes, liver, and spleen.
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Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis, enhancing MC survival and subsequent accumulation in organs and tissues.
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CM includes three forms: solitary mastocytoma, maculopapular cutaneous mastocytosis (MPCM), and diffuse cutaneous mastocytosis (DCM). In most children with CM, skin lesions regress spontaneously around puberty; unfortunately, it is not always a self-limiting disease.
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Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. Children with mastocytosis often suffer from MC mediator-related symptoms, the most common of which is itching, often triggered by rubbing the lesions. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers. Treatment with H1 and H2 histamine receptor blockers on demand and the availability of epinephrine auto-injectors for the patients to use in case of severe anaphylactic reactions are recommended.
Chronic myeloid leukemia (CML) in childhood represents only 3% of newly diagnosed pediatric leukemia. The diagnostic hallmark of CML is the Philadelphia (Ph) chromosome, which derives from the fusion ...of the ABL1-oncogene located on chromosome 9 to the breakpoint cluster region (BCR) gene on chromosome 22, resulting in a constitutively dysregulated ABL1 tyrosine kinase, either as 210 kDa or 190 kDa. Depending on the localization of the breakpoint site within the major BCR region, the majority of CML patients exhibit transcripts with either the b3a2 or b2a2 junction, or both. Several questions are still open with regard to childhood CML, especially concerning the biologic and clinical features of the disease, and the treatment of choice for pediatric patients with CML. Moreover, over the last few years, several tyrosine kinase inhibitors (TKIs) have been available for children and adolescents with CML, and current clinical practice investigates what the effective and optimal doses of TKIs are in these two categories of patients. The use of TKIs in pediatric patients with CML has also opened up questions on the following items: (1) the long-term effects of these drugs on children; (2) the management of pediatric CML forms resistant or intolerant to TKIs; (3) the monitoring of disease outcomes during treatment; (4) and the right timing to discontinue therapy. Despite the efficacy of TKIs also in the pediatric population, the potential late adverse effects, and the drug resistance, leave open the possibility of allogeneic hematopoietic stem cell transplantation as a treatment option in pediatric CML. Published data and personal experiences regarding these issues will be analyzed and discussed.
The differential diagnosis of marrow failure (MF) is crucial in the diagnostic work‐up, since genetic forms require specific care. We retrospectively studied all patients with single/multi‐lineage MF ...evaluated in a single‐center to identify the type and incidence of underlying molecular defects. The diepoxybutane test was used to screen Fanconi Anemia. Other congenital MFs have been searched using Sanger and/or Next Generation Sequencing analysis, depending on the available tools over the years. Between 2009–2019, 97 patients (aged 0–32 years‐median 5) with single‐lineage (29%) or multilineage (68%) MF were evaluated. Fifty‐three (54%) and 28 (29%) were diagnosed with acquired and congenital MF, respectively. The remaining 16 (17%), with trilinear (n=9) and monolinear (n=7) MF, were found to have an underlying primary immunodeficiency (PID) and showed clinical and biochemical signs of immune‐dysregulation in 10/16 (62%) and in 14/16 (87%) of cases, respectively. Clinical signs were also found in 22/53 (41%) and 8/28 (28%) patients with idiopathic and classical cMF, respectively. Eight out of 16 PIDs patients were successfully transplanted, four received immunosuppression, two did not require treatment, and the remaining two died. We show that patients with single/multi‐lineage MF may have underlying PIDs in a considerable number of cases and that MF may represent a relevant clinical sign in patients with PIDs, thus widening their clinical phenotype. An accurate immunological work‐up should be performed in all patients with MF, and PID‐related genes should be considered when screening MF in order to identify disorders that may receive targeted treatments and/or appropriate conditioning regimens before transplant.
Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of ...neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.
Summary
The most frequent forms of inherited thrombocytopenia (IT) are characterized by platelet size abnormalities and it has been suggested that this parameter is useful for their differentiation ...from immune thrombocytopenia (ITP). Recently, a monocentric study identified cut‐off values for mean platelet volume (MPV) and mean platelet diameter (MPD) with good diagnostic accuracy in this respect. To validate these cut‐off values in a different and larger case series of patients, we enrolled 130 subjects with ITP and 113 with IT in six different centres. The platelet count and MPV was each measured by the instrument routinely used in each institution. In some centres, platelet count was also measured by optical microscopy. MPD was evaluated centrally by image analysis of peripheral blood films. The previously identified cut‐off value for MPV had 91% specificity in distinguishing ITP from inherited macrothrombocytopenias (mono and biallelic Bernard‐Soulier, MYH9‐related disease), while its sensitivity was greatly variable depending on the instrument used. With an appropriate instrument, specificity was 83%. The diagnostic accuracy of MPD was lower than that obtained with MPV. We concluded that MPV is a useful parameter for differentiating ITP from IT provided that it is measured by appropriate cell counters.
Background
Fatigue is an important clinical and psychological aspect for a significant number of children affected by immune thrombocytopenia (ITP). To date, few studies have explored fatigue and its ...relationship with chronic ITP in pediatric age. The aim of the present multicentric pilot study is to determine fatigue perception in a large group of children with chronic ITP and their caregivers using the PedsQL Multidimensional Fatigue Scale (PedsQL MFS), and to compare the results with those of healthy control subjects.
Procedure
Children with chronic ITP aged 5‐18 years and/or caregivers of children aged 2‐18 years were enrolled. Child/adolescent self‐report was used for patients aged 5‐18 years, and parent proxy‐report for patients aged 2‐18 years. The questionnaire was offered as online survey. PedsQL MFS is composed of 18 items covering three dimensions: General Fatigue Scale, Sleep/Rest Fatigue Scale, and Cognitive Fatigue Scale.
Results
One hundred ninety‐one patients affected by chronic ITP and 248 caregivers answered the PedsQL MFS. We have highlighted that lower values of PedsQL MFS scores are obtained in the 13‐18 age group. Moreover, sleep/rest fatigue domain appears to be more compromised in all age groups. For all PedsQL MFS scores, pediatric patients with chronic ITP and their caregivers reported statistically significant worse fatigue than healthy children.
Conclusions
This study suggests that fatigue is relevant among children and adolescents affected by chronic ITP. The PedsQL MFS represents an adequate instrument for measuring fatigue in patients with chronic ITP. Therefore, symptoms of fatigue should be routinely assessed in clinical practice.
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