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CASE REPORT
Year : 2016  |  Volume : 17  |  Issue : 4  |  Page : 306-308

Indolent systemic mastocytosis in a child: A rare and difficult diagnosis


1 Department of Pediatric Hematology, Kayseri Training and Research Hospital, Kayseri, Turkey
2 Department of Pediatrics, Kayseri Training and Research Hospital, Kayseri, Turkey
3 Department of Pediatric Hematology, Bursa Dortcelik Children Hospital, Bursa, Turkey
4 Department of Immunology, Kayseri Training and Research Hospital, Kayseri, Turkey

Date of Web Publication7-Oct-2016

Correspondence Address:
Yasemin Altuner Torun
Department of Pediatric Hematology, Kayseri Training and Research Hospital, Emel Mehmet Tarman Children Hospital, Kayseri
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2319-7250.184333

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  Abstract 

Mastocytosis is a sporadic disease characterized by an abnormal accumulation of mast cells (MCs) in single or multiple organs. A 5-year-old girl who was diagnosed as cutaneous mastocytosis by our Dermatology Department when she was 4 months of age was admitted to our Pediatric Hematology Department by hepatosplenomegaly. Diagnosis of systemic mastocytosis (SM) was verified by one major and one minor WHO criteria: presence of multifocal, dense aggregates of MCs in bone marrow (major criteria) and confirmed by expression of CD2, CD25, and CD117 in bone marrow (minor criteria). During follow-up, systemic anaphylaxis was determined and treated for 3 times. We here present the first report of use of interferon-α-2a, methylprednisolone, and montelukast in life-threatening SM to achieve remission, suggesting a new option for treatment of SM in childhood.

Keywords: Anaphylaxis, childhood, systemic mastocytosis


How to cite this article:
Torun YA, Ergul AB, Kazancı EG, Serbetci MC, Sarıguzel FM. Indolent systemic mastocytosis in a child: A rare and difficult diagnosis. Indian J Paediatr Dermatol 2016;17:306-8

How to cite this URL:
Torun YA, Ergul AB, Kazancı EG, Serbetci MC, Sarıguzel FM. Indolent systemic mastocytosis in a child: A rare and difficult diagnosis. Indian J Paediatr Dermatol [serial online] 2016 [cited 2019 Oct 19];17:306-8. Available from: http://www.ijpd.in/text.asp?2016/17/4/306/184333


  Introduction Top


Mastocytosis refers to a group of myeloproliferative disorders characterized by excessive proliferation and accumulation of mast cells (MCs) in tissues. It is rare in both adults and children and occurs in < 0.01% of the general population.[1]

The most common form of mastocytosis in the pediatric population is cutaneous mastocytosis (CM), in which the MC hyperplasia occurs in the skin. Systemic mastocytosis (SM) is a rare, heterogeneous, and progressive disease, characterized by the accumulation of atypical MCs in various organ systems with or without skin involvement.[2] Treatment of CM is still based on symptomatic treatment as most of the pediatric cases are known to resolve spontaneously by puberty. No standard treatment exists for SM. Histamine receptor antagonists, proton pump inhibitors, corticosteroids, interferon (IFN), and oral cromolyn sodium are recommended as the basis of the therapy.[1]

Thus, we reported the first case of indolent SM that was successfully treated with montelukast, IFN-α-2a, and methylprednisolone in a child.


  Case Report Top


A 5-year-old girl presented with a history of itchy skin lesions over the face, trunk, and extremities associated with recurrent anaphylactic reactions since 4 months of age. She diagnosed CM by our Dermatology Department. On her physical examination, there were multiple and itchy monomorphic red-brown macules and papules which were most numerous on her trunk and proximal extremities and noticeably her face, palms, and soles with a positive Darier's sign. She has hepatosplenomegaly but no palpable peripheral lymphadenopathy. A preliminary blood test revealed an elevated serum tryptase level (356 ng/ml), and normal blood count, renal function, and liver function.

Bone marrow aspiration showed infiltration by MCs (rate >10%) [Figure 1]. Flow cytometry of bone marrow sample revealed that there was CD117/CD25 positivity of 18.4% and CD117/CD2 positivity of 0.7% [Figure 2]. A punch biopsy confirmed the diagnosis of mastocytosis.
Figure 1: The assessment of bone marrow aspiration was found to be consistent with mast cells

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Figure 2: Flow cytometry on bone marrow sample revealed that there was CD117/CD25 positivity of 18.4% and CD117/CD2 positivity of 0.7%

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Diagnosis of SM was verified by one major and one minor WHO criteria: Presence of multifocal dense aggregates of MCs in bone marrow (major criteria) and confirmed by expression of CD2, CD25, and CD117 in bone marrow (minor criteria). Our patient was diagnosed as indolent SM because of high serum tryptase level, organomegaly, and infiltration of MCs in the bone marrow.

During follow-up, systemic anaphylaxis was determined and treated for 3 times. We recommended the self-administration of epinephrine on demand for anaphylactoid episodes. Montelukast (0.3 mg/kg/day) was given to relieve symptoms of prevent anaphylaxis. IFN-α-2a (0.15 MU/kg/day) and methylprednisolone (2 mg/kg/day) were added to the treatment for SM. It was planned to maintain low-dose methylprednisolone therapy for 12 months and to withdraw gradually after 11 months.

Treatment with montelukast, IFN-α-2a, and methylprednisolone resulted in symptom improvement and sustained reduction of her symptoms, cutaneous lesion, and tryptase level [Figure 3]. Anaphylactic reactions have never repeated after treatment.
Figure 3: Appearance of cutaneous lesion

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  Discussion Top


Mastocytosis is diagnosed on the basis of history, clinical manifestations, and histopathology and laboratory evaluation. Bone marrow is the most common extracutaneous site involved by SM, and bone marrow biopsy or bone marrow aspiration is preferable for morphologic diagnosis.[1] In our patient's bone marrow aspiration, there were multifocal, dense aggregates of MCs. SM is very rare in pediatric population. Hannaford and Rogers described 173 pediatric cases of mastocytosis; only two of them which were systemic disease.[3] The symptoms – bone marrow infiltration and hepatosplenomegaly – are strong evidence for SM in our patient.

Indolent SM patients have a different clinical presentation, ranging from predominantly cutaneous symptoms to recurrent systemic symptoms (e.g., flushing, palpitations, dyspepsia, diarrhea, bone pain) that can be severe and potentially life-threatening (anaphylaxis).[4],[5] The patient was considered as indolent SM, because she has urticaria pigmentosa-like cutaneous lesions and anaphylaxis for 3 times. Anaphylaxis which caused induced massive degranulation of MC is the most important manifestation and it is particularly seen in the patient with SM and it is not rarely seen.[6],[7] We recommended the self-administration of epinephrine to the patient on demand for anaphylactoid episodes.

The WHO diagnostic major criterion for SM includes multifocal, dense aggregates of MCs (15 or more) detected in sections of bone marrow and confirmed by tryptase immunohistochemistry or other special stains, whereas minor criteria are as follows: (a) In biopsy section, more than 25% of the MCs in the infiltrate have atypical morphology or of all the MCs in the aspirate smear, more than 25% are immature or atypical; (b) MCs co-express CD117 with CD2 and/or CD25; (c) detection of KIT point mutation at codon 816 in bone marrow, blood, or other extracutaneous organs; (d) serum total tryptase persistently > 20 ng/mL (not a valid criterion in cases of SM with associated clonal hematologic non-MC lineage disease.[4] Immunohistochemistry and flow cytometry immunophenotypic analysis are commonly used methods for diagnosing and monitoring patients with SM. Antibodies specific for tryptase and CD117 are most widely used and are useful for highlighting MCs.[8],[9] Aberrant expression of CD2 or CD25 by MCs in the bone marrow is more useful for diagnosis because both antigens are not expressed in normal or reactive MCs whereas neoplastic MCs. CD 117 also used to distinguish SM from CM. The diagnosis of our SM patient was verified by one major and one minor WHO criteria: Presence of multifocal, dense aggregates of MCs in bone marrow (major criteria) and confirmed by expression of CD2, CD25, and CD117 in bone marrow (minor criteria). [4]

We used combined therapy (IFN-α-2a, methylprednisolone, and montelukast) to reduce progressive symptoms. IFN-α as the first-line cytoreductive agent, is effective for relieving mediator release and gastrointestinal symptoms, skin rash, osteoporosis, cytopenias, ascites, and hepatosplenomegaly. Systemic corticosteroids can be used to control severe mediator-related symptoms. Systemic steroids are also employed with IFN-α in cytoreductive therapy. The use of chemotherapy, including kinase inhibitors, is strongly discouraged unless severe hematologic disease is present since malignant evolution is extremely rare.[1],[9] Imatinib role in the treatment of indolent and CM is less well established.[10]


  Conclusion Top


SM, the rarest form of mastocytosis in pediatric population, is often misdiagnosed as atopic dermatitis or other dermatological disorders with itchy lesions. This patient has been treated successfully with combination therapy. Further studies are needed to develop new therapeutic approaches for pediatric SM.

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Fernandes EI, de Faria BC, Cartell A, dos Santos BA, Cestari TF. Systemic mastocytosis in childhood: Report of 3 cases. J Pediatr (Rio J) 2002;78:176-80.  Back to cited text no. 1
    
2.
Frieri M, Quershi M. Pediatric mastocytosis: A review of the literature. Pediatr Allergy Immunol Pulmonol 2013;26:175-80.  Back to cited text no. 2
    
3.
Hannaford R, Rogers M. Presentation of cutaneous mastocytosis in 173 children. Australas J Dermatol 2001;42:15-21.  Back to cited text no. 3
    
4.
Valent P, Sperr WR, Schwartz LB, Horny HP. Diagnosis and classification of mast cell proliferative disorders: Delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol 2004;114:3-11.  Back to cited text no. 4
    
5.
Gülen T, Hägglund H, Dahlén B, Nilsson G. High prevalence of anaphylaxis in patients with systemic mastocytosis – A single-centre experience. Clin Exp Allergy 2014;44:121-9.  Back to cited text no. 5
    
6.
Ludolph-Hauser D, Ruëff F, Fries C, Schöpf P, Przybilla B. Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet 2001;357:361-2.  Back to cited text no. 6
    
7.
Górska A, Niedoszytko M, Lange M, Chelminska M, Nedoszytko B, Wasag B, et al. Risk factors for anaphylaxis in patients with mastocytosis. Pol Arch Med Wewn 2015;125:46-53.  Back to cited text no. 7
    
8.
Patnaik MM, Rindos M, Kouides PA, Tefferi A, Pardanani A. Systemic mastocytosis: A concise clinical and laboratory review. Arch Pathol Lab Med 2007;131:784-91.  Back to cited text no. 8
    
9.
Pardanani A. Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management. Am J Hematol 2015;90:250-62.  Back to cited text no. 9
    
10.
Agarwala MK, George R, Mathews V, Balasubramanian P, Thomas M, Nair S. Role of imatinib in the treatment of pediatric onset indolent systemic mastocytosis: A case report. J Dermatolog Treat 2013;24:481-3.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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