Skip to main content
SpringerLink
Log in

Diagnosis and Treatment of Cutaneous Mastocytosis in Children

Practical Recommendations

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Cutaneous mastocytosis in children is a generally benign disease that can present at birth and is often associated with mast cell mediator-related symptoms including pruritus, flushing, and abdominal pain with diarrhea. The most common form of presentation is urticaria pigmentosa, also referred to as maculopapular mastocytosis. Flares of lesions are induced by triggers such as physical stimuli, changes in temperature, anxiety, medications, and exercise. The skin lesions are typically present on the extremities. Symptoms respond to topical and systemic anti-mediator therapy including antihistamines and cromolyn sodium. Remission at puberty is seen in a majority of cases. Progression to systemic mastocytosis with involvement of extracutaneous organs is not common.

The cause of cutaneous mastocytosis is unknown and familial cases are rare. Mutations of c-kit have been observed in the skin of those affected. The diagnosis is established on clinical grounds and the findings on skin biopsy. Bone marrow studies are recommended if there is suspicion of progression of disease to an adult form, if cytoreductive therapy is contemplated, or if skin lesions remain present and/or tryptase levels remain elevated after puberty. The use of chemotherapy, including kinase inhibitors, is strongly discouraged unless severe hematologic disease is present, since malignant evolution is extremely rare.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Table I
Table II
Table III

Similar content being viewed by others

References

  1. Nettleship J, Tay W. Rare forms of urticaria. BMJ 1869; 2: 323–4

    Article  Google Scholar 

  2. Sangster A. An anomalous mottled rash, accompanied by pruritus, factitious urticaria and pigmentation, ‘urticaria pigmentosa (?)’ [letter]. Trans Clin Soc London 1878; 11: 161

    Google Scholar 

  3. Ellis J. Urticaria pigmentosa: a report of a case of autopsy. Arch Pathol 1949; 48: 426–35

    CAS  Google Scholar 

  4. Degos R. Urticaria pigmentosa and other types of mastocytosis; attempted classification of cutaneous mastocytoses [in Spanish]. Actas Dermosifiliogr 1955; 46 (9): 759–85

    PubMed  CAS  Google Scholar 

  5. Valent P, Horny HP, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 2001; 25: 603–25

    Article  PubMed  CAS  Google Scholar 

  6. Valent P, Akin C, Escribano L, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest 2007; 37 (6): 435–53

    Article  PubMed  CAS  Google Scholar 

  7. Horny HP, Metcalfe DD, Bennet JM, et al. Mastocytosis. In: Swerdlow SH, Campo E, Harris NL, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC, 2008: 54–63

    Google Scholar 

  8. Kettelhut BV, Parker RI, Travis WD, et al. Hematopathology of the bone marrow in pediatric cutaneous mastocytosis: a study of 17 patients. AmJ Clin Pathol 1989; 91 (5): 558–62

    CAS  Google Scholar 

  9. Kettelhut BV, Metcalfe DD. Pediatric mastocytosis. J Invest Dermatol 1991; 96 (3 Suppl.): 15S–8S

    Article  Google Scholar 

  10. Soter NA. The skin in mastocytosis. J Invest Dermatol 1991; 96 (3 Suppl.): 32S–8S

    Article  Google Scholar 

  11. Azana JM, Torrelo A, Mediero IG, et al. Urticaria pigmentosa: a review of 67 pediatric cases. Pediatr Dermatol 1994; 11 (2): 102–6

    Article  PubMed  CAS  Google Scholar 

  12. Caplan RM. The natural course of urticaria pigmentosa: analysis and followup of 112 cases. Arch Dermatol 1963; 87: 146–57

    Article  PubMed  CAS  Google Scholar 

  13. Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res 2001; 25 (7): 519–28

    Article  PubMed  CAS  Google Scholar 

  14. Hartmann K, Henz BM. Classification of cutaneous mastocytosis: a modified consensus proposal. Leuk Res 2002; 26 (5): 483–4

    Article  PubMed  Google Scholar 

  15. Worobec AS, Akin C, Scott LM, et al. Cytogenetic abnormalities and their lack of relationship to the Asp816Val c-kit mutation in the pathogenesis of mastocytosis. J Allergy Clin Immunol 1998; 102 (3): 523–4

    Article  PubMed  CAS  Google Scholar 

  16. Sotlar K, Escribano L, Landt O, et al. One-step detection of c-kit point mutations using PNA-mediated PCR-clamping and hybridization probes. Am J Pathol 2003; 162 (3): 737–46

    Article  PubMed  CAS  Google Scholar 

  17. Yanagihori H, Oyama N, Nakamura K, et al. c-kit mutations in patients with childhood-onset mastocytosis and genotype-phenotype correlation. J Mol Diagn 2005; 7 (2): 252–7

    Article  PubMed  CAS  Google Scholar 

  18. Kasper CS, Tharp MD. Quantification of cutaneous mast cells using morphometric point counting and a conjugated avidin stain. J Am Acad Dermatol 1987; 16: 326–31

    Article  PubMed  CAS  Google Scholar 

  19. Garriga MM, Friedman MM, Metcalfe DD. A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders. J Allergy Clin Immunol 1988; 82 (3 Pt 1): 425–32

    Article  PubMed  CAS  Google Scholar 

  20. Gonzalez de Olano D, Alvarez-Twose I, Esteban-Lopez MI, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol 2008; 121 (2): 519–26

    Article  Google Scholar 

  21. Murphy M, Walsh D, Drumm B, et al. Bullous mastocytosis: a fatal outcome. Pediatr Dermatol 1999; 16 (6): 452–5

    Article  PubMed  CAS  Google Scholar 

  22. Walker T, von Komorowski G, Scheurlen W, et al. Neonatal mastocytosis with pachydermic bullous skin without c-Kit 816 mutation. Dermatology 2006; 212 (1): 70–2

    Article  PubMed  CAS  Google Scholar 

  23. Asboe-Hansen G, Clausen J. Mastocytosis (urticaria pigmentosa) with urinary excretion of hyaluronic acid and chondroitin sulfuric acid: changes induced by polymyxin B. Am J Med 1964; 36: 144–50

    Article  PubMed  CAS  Google Scholar 

  24. Macpherson JL, Kemp A, Rogers M, et al. Occurrence of platelet-activating factor (PAF) and an endogenous inhibitor of platelet aggregation in diffuse cutaneous mastocytosis. Clin Exp Immunol 1989; 77: 391–6

    PubMed  CAS  Google Scholar 

  25. Van Gysel D, Oranje AP, Vermeiden I, et al. Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Dermatol 1996; 35 (4): 556–8

    Article  PubMed  Google Scholar 

  26. Brockow K, Akin C, Huber M, et al. Assessment of the extent of cutaneous involvement in children and adults with mastocytosis: relationship to symptomatology, tryptase levels, and bone marrow pathology. J Am Acad Dermatol 2003; 48 (4): 508–16

    Article  PubMed  Google Scholar 

  27. Heide R, van Doorn K, Mulder PG, et al. Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease severity parameters in childhood and adult cutaneous mastocytosis. Clin Exp Dermatol 2009 Jun; 34 (4): 462–8

  28. Hannaford R, Rogers M. Presentation of cutaneous mastocytosis in 173 children. Australas J Dermatol 2001; 42 (1): 15–21

    Article  PubMed  CAS  Google Scholar 

  29. Akoglu G, Erkin G, Cakir B, et al. Cutaneous mastocytosis: demographic aspects and clinical features of 55 patient. J Eur Acad Dermatol Venereol 2006; 20 (8): 969–73

    PubMed  CAS  Google Scholar 

  30. Kiszewski AE, Duran-Mckinster C, Orozco-Covarrubias L, et al. Cutaneous mastocytosis in children: a clinical analysis of 71 cases. J Eur Acad Dermatol Venereol 2004; 18 (3): 285-90

    Google Scholar 

  31. Ben-Amitai D, Metzker A, Cohen HA. Pediatric cutaneous mastocytosis: a review of 180 patients. Isr Med Assoc J 2005; 7 (5): 320–2

    PubMed  Google Scholar 

  32. Worobec AS, Metcalfe DD. Mastocytosis: current treatment concepts. Int Arch Allergy Immunol 2002; 127 (2): 153–5

    Article  PubMed  Google Scholar 

  33. Worobec AS. Treatment of systemic mast cell disorders. Hematol Oncol Clin North Am 2000; 14 (3): 659–87

    Article  PubMed  CAS  Google Scholar 

  34. Apter AJ, Rothe MJ. Referred for management of mastocytosis. Ann Allergy Asthma Immunol 1997; 79 (1): 21–6

    Article  PubMed  CAS  Google Scholar 

  35. Golkar L, Bernhard JD. Mastocytosis. Lancet 1997; 349 (9062): 1379–85

    Article  PubMed  CAS  Google Scholar 

  36. Kurosawa M, Amano H, Kanbe N, et al. Heterogeneity of mast cells in mastocytosis and inhibitory effect of ketotifen and ranitidine on indolent systemic mastocytosis. J Allergy Clin Immunol 1997; 100 (6 Pt 2): S25–32

    Article  Google Scholar 

  37. Longley J, Duffy TP, Kohn S. The mast cell and mast cell disease. J Am Acad Dermatol 1995; 32: 545–61

    Article  PubMed  CAS  Google Scholar 

  38. Friedman BS, Santiago ML, Berkebile C, et al. Comparison of azelastine and chlorpheniramine in the treatment of mastocytosis. J Allergy Clin Immunol 1993; 92: 520–6

    Article  PubMed  CAS  Google Scholar 

  39. Austen KF. Systemic mastocytosis. N Engl J Med 1992; 326: 639–40

    Article  PubMed  CAS  Google Scholar 

  40. Metcalfe DD. The treatment of mastocytosis: an overview. J Invest Dermatol 1991; 96 (3 Suppl.): 55S–6S

    Article  Google Scholar 

  41. Welch EA, Alper JC, Bogaars H, et al. Treatment of bullous mastocytosis with disodium cromoglycate. J Am Acad Dermatol 1983; 9 (3): 349–53

    Article  PubMed  CAS  Google Scholar 

  42. Escribano L, García-Belmonte D, Hernández-González A, et al. Successful management of a case of diffuse cutaneous mastocytosis with recurrent anaphylactoid episodes and hypertension [abstract]. J Allergy Clin Immunol 2004; 113 (2): S335

    Article  Google Scholar 

  43. Bianchine PJ, Metcalfe DD. Systemic mastocytosis. In: Kaplan AP, editor. Allergy. Philadelphia (PA): WB Saunders, 1997: 854–60

    Google Scholar 

  44. Marone G, Spadaro G, Granata F, et al. Treatment of mastocytosis: pharmacologic basis and current concepts. Leuk Res 2001; 25 (7): 583–94

    Article  PubMed  CAS  Google Scholar 

  45. Metcalfe DD. Clinical advances in mastocytosis: an interdisciplinary roundtable discussion. J Invest Dermatol 1991; 96 Suppl.: 1S–65S

    Article  Google Scholar 

  46. Zhang MQ. Chemistry underlying the cardiotoxicity of antihistamines. Curr Med Chem 1997; 4 (3): 171–84

    CAS  Google Scholar 

  47. Fenske NA, Lober CW, Pautler SE. Congenital bullous urticaria pigmentosa: treatment with concomitant use of H1- and H2-receptor antagonists. Arch Dermatol 1985; 121 (1): 115–8

    Article  PubMed  CAS  Google Scholar 

  48. Frieri M, Alling DW, Metcalfe DD. Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis: results of a double-blind clinical trial. Am J Med 1985; 78 (1): 9–14

    Article  PubMed  CAS  Google Scholar 

  49. Gasior-Chrzan B, Falk ES. Systemic mastocytosis treated with histamine H1 and H2 receptor antagonists. Dermatologica 1992; 184: 149–52

    Article  CAS  Google Scholar 

  50. Hirschowitz BI, Groarke JF. Effect of cimetidine on gastric hypersecretion and diarrhea in systemic mastocytosis. Ann Intern Med 1979; 90 (5): 769–71

    PubMed  CAS  Google Scholar 

  51. Johnson GJ, Silvis SE, Roitman B, et al. Long-term treatment of systemic mastocytosis with histamine H2 receptor antagonists. Am J Gastroenterol 1980; 74 (6): 485–9

    PubMed  CAS  Google Scholar 

  52. Berg MJ, Bernhard H, Schentag JJ. Cimetidine in systemic mastocytosis. Drug Intell Clin Pharm 1981; 15 (3): 180–3

    PubMed  CAS  Google Scholar 

  53. Collen MJ, Howard JM, McArthur KE, et al. Comparison of ranitidine and cimetidine in the treatment of gastric hypersecretion. Ann Intern Med 1984; 100 (1): 52–8

    PubMed  CAS  Google Scholar 

  54. Debeuckelaere S, Schoors DF, Devis G. Systemic mast cell disease: a review of the literature with special focus on the gastrointestinal manifestations. Acta Clin Belg 1991; 46 (4): 226–32

    PubMed  CAS  Google Scholar 

  55. Goto T, Sakashita H, Murakami K, et al. Novel histamine H3 receptor antagonists: synthesis and evaluation of formamidine and S-methylisothiourea derivatives. Chem Pharm Bull (Tokyo) 1997; 45 (2): 305–11

    Article  PubMed  CAS  Google Scholar 

  56. Van Cauwenberge PB, De Moor SEG. Physiopathology of H3-receptors and pharmacology of betahistine. Acta Otolaryngol (Stockh) 1997; 117: 43–6

    Article  Google Scholar 

  57. Linney ID, Buck IM, Harper EA, et al. Design, synthesis, and structure-activity relationships of novel non-imidazole histamine H3 receptor antagonists. J Med Chem 2000; 43 (12): 2362–70

    Article  PubMed  CAS  Google Scholar 

  58. Blandizzi C, Colucci R, Tognetti M, et al. H3 receptor-mediated inhibition of intestinal acetylcholine release: pharmacological characterization of signal transduction pathways. Naunyn Schmiedebergs Arch Pharmacol 2001; 363 (2): 193–202

    Article  PubMed  CAS  Google Scholar 

  59. Dolovich J, Punthakee ND, MacMillan AB, et al. Systemic mastocytosis: control of lifelong diarrhea by ingested disodium cromoglycate. Can Med Assoc J 1974; 111 (7): 684–5

    PubMed  CAS  Google Scholar 

  60. Soter NA, Austen KF, Wasserman SI. Oral disodium cromoglycate in the treatment of systemic mastocytosis. N Engl J Med 1979; 301: 465–9

    Article  PubMed  CAS  Google Scholar 

  61. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 1990; 85 (5): 852–5

    Article  PubMed  CAS  Google Scholar 

  62. Haustein UF, Bedri M. Bullous mastocytosis in a child [in German]. Hautarzt 1997; 48 (2): 127–9

    Article  PubMed  CAS  Google Scholar 

  63. Leaf FA, Jaecks EP, Rodriguez DR. Bullous urticaria pigmentosa. Cutis 1996; 58 (5): 358–60

    PubMed  CAS  Google Scholar 

  64. Mackey S, Pride HB, Tyler WB. Diffuse cutaneous mastocytosis: treatment with oral psoralen plus UV-A. Arch Dermatol 1996; 132 (12): 1429–30

    Article  PubMed  CAS  Google Scholar 

  65. Smith ML, Orton PW, Chu H, et al. Photochemotherapy of dominant, diffuse, cutaneous mastocytosis. Pediatr Dermatol 1990; 7 (4): 251–5

    Article  PubMed  CAS  Google Scholar 

  66. van Furth AM, van de Rhee HJ, van Zwieten PH, et al. Congenital bullous urticaria pigmentosa [in Dutch]. Tijdschr Kindergeneeskd 1993; 61 (2): 58–62

    PubMed  Google Scholar 

  67. Abdullah AN, Keczkes K. Cutaneous and ocular side-effects of PUVA photochemotherapy: a 10-year follow-up study. Clin Exp Dermatol 1989; 14 (6): 421–4

    Article  PubMed  CAS  Google Scholar 

  68. Stern RS, Nichols KT, Vakeva LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA): the PUVA Follow-Up Study. N Engl J Med 1997; 336 (15): 1041–5

    Article  PubMed  CAS  Google Scholar 

  69. Wallenfang K, Stadler R. Association between UVA1 and PUVA bath therapy and development of malignant melanoma [in German]. Hautarzt 2001; 52 (8): 705–7

    Article  PubMed  CAS  Google Scholar 

  70. Greenblatt EP, Chen L. Urticaria pigmentosa: an anesthetic challenge. J Clin Anesth 1990; 2: 108–15

    Article  PubMed  CAS  Google Scholar 

  71. Stellato C, De Paulis A, Cirillo R, et al. Heterogeneity of human mast cells and basophils in response to muscle relaxants. Anesthesiology 1991; 74: 1078–86

    Article  PubMed  CAS  Google Scholar 

  72. Scott Jr HW, Parris WC, Sandidge PC, et al. Hazards in operative management of patients with systemic mastocytosis. Ann Surg 1983; 197 (5): 507–14

    Article  PubMed  Google Scholar 

  73. Hosking MP, Warner MA. Sudden intraoperative hypotension in a patient with asymptomatic urticaria pigmentosa. Anesth Analg 1987; 66 (4): 344–6

    Article  PubMed  CAS  Google Scholar 

  74. Lerno G, Slaats G, Coenen E, et al. Anaesthetic management of systemic mastocytosis. Br J Anaesth 1990; 65 (2): 254–7

    Article  PubMed  CAS  Google Scholar 

  75. Borgeat A, Ruetsch YA. Anesthesia in a patient with malignant systemic mastocytosis using a total intravenous anesthetic technique. Anesth Analg 1998; 86 (2): 442–4

    PubMed  CAS  Google Scholar 

  76. Carter MC, Uzzaman A, Scott LM, et al. Pediatric mastocytosis: routine anesthetic management for a complex disease. Anesth Analg 2008; 107 (2): 422–7

    Article  PubMed  Google Scholar 

  77. Coleman MA, Liberthson RR, Crone RK, et al. General anesthesia in a child with urticaria pigmentosa. Anesth Analg 1980; 59 (9): 704–6

    Article  PubMed  CAS  Google Scholar 

  78. James PD, Krafchik BR, Johnston AE. Cutaneous mastocytosis in children: anaesthetic considerations. Can J Anaesth 1987; 34 (5): 522–4

    Article  PubMed  CAS  Google Scholar 

  79. Brodier C, Guyot E, Palot M, et al. Anesthesia of a child with a cutaneous mastocytosis [in French]. Cah Anesthesiol 1993; 41 (1): 77–9

    PubMed  CAS  Google Scholar 

  80. Tirel O, Chaumont A, Ecoffey C. Circulatory arrest in the course of anesthesia for a child with mastocytosis [in French]. Ann Fr Anesth Reanim 2001; 20 (10): 874–5

    Article  PubMed  CAS  Google Scholar 

  81. Nelson LP, Savelli-Castillo I. Dental management of a pediatric patient with mastocytosis: a case report. Pediatr Dent 2002; 24 (4): 343–6

    PubMed  Google Scholar 

  82. Lorenz W. Histamine release in man. Agents Actions 1975; 5 (5): 402–16

    Article  PubMed  CAS  Google Scholar 

  83. Booij LH, Krieg N, Crul JF. Intradermal histamine releasing effect caused by Org-NC 45: a comparison with pancuronium, metocurine and d-tubocurarine. Acta Anaesthesiol Scand 1980; 24 (5): 393–4

    Article  PubMed  CAS  Google Scholar 

  84. Flacke JW, Flacke WE, Bloor BC, et al. Histamine release by four narcotics: a double-blind study in humans. Anesth Analg 1987; 66 (8): 723–30

    Article  PubMed  CAS  Google Scholar 

  85. Fisher MM, Baldo BA. Mast cell tryptase in anaesthetic anaphylactoid reactions. Br J Anaesth 1998; 80 (1): 26–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was in part supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) and in part by a grant from The Mastocytosis Society towards funding the Mastocytosis Registry at BWH, headed by Dr Mariana Castells. Research funding was received from the Foundation for Research of Castilla La Mancha (FISCAM 2007/36, FISCAM 2008/46), the Ministry of Health (FIS PS09/00032), and the Spanish Mastocytosis Foundation (FEM 2010).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham & Women’s Hospital, Harvard Medical School, 02115, Jimmy Fund Way, Smith Building Room 626D, Boston, Massachusetts, USA

    Mariana Castells

  2. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH), Bethesda, Maryland, USA

    Dean D. Metcalfe

  3. Mastocytosis Institute of Castilla La Mancha, Hospital Virgen del Valle, Toledo, Spain

    Luis Escribano

Authors
  1. Mariana Castells
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dean D. Metcalfe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis Escribano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariana Castells.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Castells, M., Metcalfe, D.D. & Escribano, L. Diagnosis and Treatment of Cutaneous Mastocytosis in Children. Am J Clin Dermatol 12, 259–270 (2011). https://doi.org/10.2165/11588890-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11588890-000000000-00000

Keywords

Search

Navigation