What Are Some Mast Cell Disorders?

Patient Presentation
A 4 month-old male came to clinic for his health maintenance appointment. The parents had no concerns. The patient had been noted to have a single brown lesion on his trunk a couple weeks after birth that would get larger and have some mild erythema around it, and then resolve. The dermatologist thought that it was a solitary mastocytoma and he was started on an antihistamine medication. The parents said that they had not noted any other changes other than it had gotten slightly bigger which they had been told that it could do naturally. “Maybe he’s a little fussier when it gets bigger but it’s hard to tell because of his age,” the mother remarked.

The pertinent physical exam showed a smiling infant with growth parameters around the 10%. The lesion on his right flank was a uniform brown color with discrete edges measuring 18 mm x 15 mm which was slightly larger than the 14 mm x 12 mm measured by the dermatologist. The rest of his examination was normal. The diagnosis of a healthy male with a presumed solitary mastocytoma was made. The parents had an appointment for follow up with dermatology and were to call if they noticed anything different with the lesion especially any systemic problems.

Mast cells (MCs) were first discovered by Paul Ehrlich in 1878. Previously in 1869, Nettleship and Tay described a toddler with chronic urticaria and a brown skin lesion which is believed to be the first reported case of mastocytosis. Urticaria pigmentosa was a term first used by Sangster in 1878, and in 1936 the term mastocytosis was used.

“Mast cells first evolved 500 million years ago in Ascidians (sea squirts), providing host innate immunity against bacteria and parasites….MCs gained additional functions regulating inflammation, wound healing, coagulation, adaptive immunity and acute allergic responses.” In the bone marrow they differentiate from common myeloid precursors and the immature MCs leave the bone marrow and begin residing in tissues contacting the external environment such as the skin, gastrointestinal and respiratory tracts. They also reside in spaces surround nerves. MCs mature in their terminal location. MC release a variety of inflammatory mediators when activated including storage granules containing histamine, tryptase and other substances, phospholipid membrane metabolism substances and by synthesizing additional substances such as cytokines and chemokines. Mature MCs have two major subpopulations with one type residing in a particular location but there is interconversion between the two depending on the microenvironment.

Learning Point
As the understanding of mast cells has evolved so has the terminology and classification, and this can be confusing as clinical presentations can have overlapping symptoms as well.

Primary MC disorders are categorized into those that arise because of clonal proliferation (due to a KIT mutation in the growth factor), and those that have exaggerated release of MC contents (possibly due to gene duplication in a trypase gene). In general, children have more cutaneous disease that often resolves. Adults more often have systemic disease and it may not resolve.

Presentations of MC disorders include:

  • Cutaneous
    • Treatment usually is with second or third generation antihistamines and supportive care
    • Common triggers are cutaneous rubbing and exposure to extreme temperatures (especially hot but also cold – which can make bathing difficult). Other triggers include drugs, insect venom, fever, and premenstrual timing in adults.
    • Evaluation can be extensive. Serum typtase may help classify the various types. Bone marrow biopsy may be necessary.
    • Mastocytoma
      • Usually solitary but can be up to 3 lesions
      • Brown to yellow color
      • Trunk and extremities but can affect any area
      • Often present at birth but can show up in first few months of life. Rare in adults
    • Diffuse cutaneous mastocytosis
      • Usually extensive (but not always) involvement with a thickening of the skin. Often referred to as “peau d’orange” or elephant or crocodile skin.
      • Children often have episodic generalized blistering and blistering has worse long-term prognosis
      • Presents at birth or soon after resolves by adolescence usually
      • Can be associated with systemic symptoms such as flushing, gastrointestinal symptoms and rarely hypotension
    • Maculopapular cutaneous mastocytosis/urticaria pigmentosa
      • There are two different subtypes as well
      • Multiple brown to red color lesions that are oval to round in shape. They can coalesce.
      • Can be seen in children with regression by adolescence but usually seen in adults
      • If does not regress, more systemic symptoms are seen in adults.
  • Systemic involvement
    • Treatment is second or third generation antihistamines, MC stabilizing drugs, immunomodulators
    • Mainly seen in adults
    • Problems can include flushing, abdominal pain, diarrhea, muscle aches, bone pain, hypotension, and psychiatry and neurological symptoms.
  • Primary Mast cell activation syndrome
    • Mainly seen in adults
    • Similar presentations for systemic involvement above
  • MC leukemia – can present with fever, hepatosplenomegaly, and weight loss. Prognosis is poor.
  • Other Associations
    • Associated with inflammatory disorders such as asthma, inflammatory bowel disease, chronic urticaria
    • Associated with vascular remodeling in disorders such as retinopathy of prematurity, hypoxic-ischemic encephalopathy and bronchopulmonary dysplasia. Possibly also in sudden infant death syndrome.

Questions for Further Discussion
1. What are common causes of anaphylaxis? A review can be found here
2. What are indications for a bone marrow biopsy?
3. What causes flushing? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Immune System Disorders and Skin Pigmentation Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Matito A, Azana JM, Torrelo A, Alvarez-Twose I. Cutaneous Mastocytosis in Adults and Children. Immunology and Allergy Clinics of North America. 2018;38(3):351-363. doi:10.1016/j.iac.2018.04.001

Bahri R, Custovic A, Korosec P, et al. Mast cell activation test in the diagnosis of allergic disease and anaphylaxis. J Allergy Clin Immunol. 2018;142(2):485-496.e16. doi:10.1016/j.jaci.2018.01.043

Wilcock A, Bahri R, Bulfone-Paus S, Arkwright PD. Mast cell disorders: From infancy to maturity. Allergy. 2019;74(1):53-63. doi:10.1111/all.13657

Donna M. D’Alessandro, MD
Professor of P