Progression of mast cell diseases (Part 5)

What is the typical age of onset for children with mastocytosis?

“Mastocytosis [cutaneous, in children]… 55% of cases presenting from birth to 2 years of age, 10% in children younger than 15 years old, and 35% in those over the age of 15. There has, however, been no gender bias noted in the cases of pediatric mastocytosis.” (Frieri 2013)

 

Do symptoms outside of the skin mean my child has systemic, not cutaneous, mastocytosis?

“Systemic symptoms are typically a result of mast-cell mediator release but do not prove systemic mast-cell hyperplasia [overproliferation].” (Frieri 2013)

“Clinical presentation was evaluated in an earlier study conducted by the National Institutes of Health (NIH) in which 83% of the children presented with pruritis, 65% with flushing, 53% with vesicles, 41% with abdominal pain, 18% with bone pain, and least commonly 12% with headache.” (Frieri 2013)

“Systemic mastocytosis in children is extremely rare.” (Frieri 2013)

 

What do studies say about kids growing out of mastocytosis?

“Pediatric mastocytosis is generally a benign disease that is transient in nature, as there is generally a spontaneous regression of the condition by puberty.” (Frieri 2013)

“There was complete regression of disease as defined by cutaneous findings and symptoms (clinical disease severity) in 10 of 15 patients (67%). Three patients had major (20%) and two had partial regression of disease (13%). Repeat marrow examinations on three patients with persistent disease documented systemic mastocytosis based on marrow findings in one patient who had partial regression of disease and was the only patient with initial [] evidence of systemic disease. Of the remaining two patients, one demonstrated partial regression and the other major regression of disease; and neither had evidence of systemic mastocytosis.” (Frieri 2013)

“10 of 15 of patients had complete resolution of cutaneous disease and symptoms at follow-up approximately 20 years later. This resolution of disease, based on cutaneous findings and symptom scores, occurred in the absence of use of topical or systemic steroids, PUVA or cytoreductive agents including imatinib… the natural history of disease is improvement.” (Uzzaman 2009)

“In one [] pediatric report where records and follow-up examinations were available for 25 children with UP, and an average follow-up was approximately 5 years, 76 % improved, 16 % remained unchanged, one had complete disease resolution, and one was worse.” (Uzzaman 2009)

“In a second [] study, 55 children with UP were followed for at least two years after initial examination, during which time 9% had involution of all lesions. In this study, where the average follow-up was 4.1 years, 36% had shown improvement over 6.1 years, and in 55% disease remained unchanged.” (Uzzaman 2009)

“In a third [] study, records of mastocytosis patients [] were available to assess disease outcome over a 1–15 year period. Thirty-five of 62 patients with UP (56%) showed complete disease resolution.” (Uzzaman 2009)

“In a fourth [] study, of 72 cases of UP, 20% cleared disease over an average of 13 years, while 50% improved, 18% were no different, and 10% were worse.” (Uzzaman 2009)

“The age of inception of pediatric-onset cutaneous mastocytosis has been reported to have prognostic implications. In previous studies, skin lesions characterized as hyperpigmented red brown macules or papules typically were reported to appear prior to two years of age. In five such studies with 180, 112, 71, 55 and 17 patients, disease-onset prior to age 2 years was seen in 78, 92, 98, 92, and 82%, respectively. In the majority of patients, these lesions were reported to fade or resolve by late adolescence or early adulthood. Fading or resolution of UP is also reported in some adults (around 20%), although bone marrow disease persisted.” (Uzzaman 2009)

 

How do biopsies of children with mastocytosis differ from adults with mastocytosis?

“In order to analyze the extent of mast-cell hyperplasia, [] bone-marrow biopsies were performed and analyzed. In one study, it was found that in 10 of 17 children with mastocytosis, there were focal areas of mast-cell hyperplasia, which had [] aggregates of mast cells, eosinophils, and early myeloid cells.(Frieri 2013)

“Another study found that the bone-marrow lesions of children had small, [] clusters of mast cells with round and oval nuclei rather than spindle-shaped mast cells, as found in adult bone-marrow lesions.” (Frieri 2013)

“Overall when quantifying mast-cell hyperplasia, there was a higher load of mast cells in children with mastocytosis than in adults with mastocytosis.” (Frieri 2013)

“[T]he difference in presentation between adult and pediatric cases of mastocytosis may result from the difference not only in the mast-cell load but also the distribution of where the mast cells are most likely to be found.” (Frieri 2013)

 

Do increased mast cells in the bone marrow mean my child will not grow out of their disease?

“Five patients had increased mast cells and three patients had spindle shaped mast cells on the initial bone marrow biopsy. One of these patients had complete resolution of clinical and constitutional symptoms at follow-up. Three of the remaining four patients were re-evaluated. One of these was the patient with continued systemic disease, one had persistent DCM and one had continued UP. However, two other patients with continued UP had neither an increase in mast cells nor spindle shaped mast cells noted on original bone marrow examination. Thus, while the presence of increased mast cells and of spindle-shaped mast cells was more often observed in those with persistent disease, the association was not sufficient to predict outcome.” (Uzzaman 2009)

 

Are children with mastocytosis CKIT+?

“Earlier studies by Verzijl found that 25% of pediatric patients with UP had an activating D816V mutation present. Another Longley study found that 36% of pediatric patients had another mutation at codon 816. (This is where the D816V mutation is found.)…One study found that 25% of pediatric patients with the UP form of mastocytosis had a D816V mutation. It was also found that 10 out of 12 patients had another [non-D816V] mutation at the location.” (Frieri 2013)

“A later study by Bodemer in 50 pediatric patients with ages ranging from birth to 16 years found 86% of them had a c-KIT mutation, with 36% being a D816V point mutation, 2 out of 50 cases being a D816Y mutation, and one case being a D816I mutation. There were also 29 of 50 patients with [no mutation] at the 816 codon.” (Frieri 2013)

“44% of the patients were found to have a mutation outside of c-KIT with the mutations lying in exons 8, 9, and 11. There was also a subset of 28% of the patients with a M541L mutation at exon 10. [T]he patients with a M541L mutation had [no mutation] at codon 816. When the blood sample of 13 patients was analyzed, it was found that there was no c-KIT mutation, which suggests that the mutation is somatic rather than germline, meaning that this mutation is not inherited from a patient’s parents.” (Frieri 2013)

 

Do mastocytosis children generally have problems with anesthesia?

Note: always follow appropriate premedication protocols for mast cell patients and work with managing physician.

“Twenty-two patients with pediatric mastocytosis, with a median age of 3.2 years (range 6 months to 20 years) at the time of the procedure, were anesthetized for 29 diagnostic and surgical procedures. All variants of the disease are represented in this series. Most patients had a history of flushing, pruritus, gastroesophageal refux disease (GERD), and abdominal pain; one patient had history of spontaneous anaphylaxis. Routine anesthetic techniques were used, and despite the complexity of the disease, the perioperative courses were uncomplicated and without serious adverse events.” (Frieri 2013)

 

Note: These quotes are all drawn from two papers which extensively referenced previous publications. I ran down the articles referenced, but felt that these two reviews gave excellent summaries, and so I quoted them exclusively.

 

References:

Frieri, Marianne, et al. Pediatric mastocytosis: A review of the literature. Pediatr Allergy Immunol Pulmonol. Dec 1, 2013; 26(4): 175-180.

Uzzaman, Ashraf, et al. Pediatric-onset Mastocytosis: A long term clinical follow-up and correlation with bone marrow histopathology. Pediatr Blood Cancer. Oct 2009; 53 (4): 629-634.

Kettelhut BV., Metcalfe DD. Mastocytosis. J Invest Dermatol 1991; 96:115S–118S.

Lange M., Bogusław Nedoszytko B., Górska A., Żawrocki A., Sobjanek M., Kozłowski D. Mastocytosis in children and adults: clinical disease heterogeneity. Arch Med Sci 2012; 8:533–541.

Bodemer C., Hermine O., Palmérini F., Yang Y., Grandpeix-Guyodo C., Leventhal PS., Hadj-Rabia S., Nasca L., Georgin-Lavialle S., Cohen-Akenine A., Launay JM., Barete S., Feger F., Arock M., Catteau B., Sans B., Stalder JF., Skowron F., Thomas L., Lorette G.Plantin P, Bordigoni P, Lortholary O, de Prost Y, Moussy A, Sobol H, Dubreuil P. Pediatric mastocytosis is a colonal disease associated with D816V and other activating C-KIT mutations. J Invest Dermatol 2010; 130:804–815.

 

2 Responses

  1. Yvonne January 21, 2015 / 12:26 am

    How intersting that most of the children got better at puberty.

    Otherwise people with mast cell disease usually find onset post puberty and middle age…

    I found my symptoms became MUCH worse after pregnancy. And I’m not alone.

    Hormones usually make women more symptomatic but in children the opposite is true. How strange!

    Any thoughts…

    • Lisa Klimas January 21, 2015 / 12:33 am

      I think it is a really complex interplay of genetics and environment. But I honestly am starting to feel that mastocytosis in children should be considered a distinct entity, as it is truly different than in adults. The shape of the cells, even most of the mutations, the markers, everything. Hormone levels and when puberty starts is also a complex interplay; maybe it’s a turn off for some and a turn on for others.

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