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Abstract and Introduction
Abstract
Mastocytosis is a cutaneous disorder that may progress to a life-threatening, multi-organ systemic disease. Adults
are more likely to experience systemic disease than children. A discussion of the disease process, treatment
modalities, and practical strategies for patient care is presented.
Introduction
Mastocytosis (MC) is a rare, heterogeneous disorder, characterized by a marked increase in mast cells in the skin
and occasionally in the bone marrow, liver, spleen, gastrointestinal tract, and other various organ systems. Mast
cells are produced in the bone marrow and contain mediators for inflammatory and allergenic responses. When
these cells are triggered, a degranulation event occurs in which mediators such as histamine, prostaglandins,
leukotrienes, heparin, tryptase, and other chemicals are released from the mast cell and into the systemic circulation
(Alto & Clarcq, 1999; Hartmann, Bruns, & Henz, 2001).
Systemic manifestations are dependent on the number of mast cells, or mast cell burden, and the degree of
degranulation. Manifestations can vary from mild, not requiring therapy, to severe and life threatening, requiring
immediate medical attention. Severe mediatorrelated symptoms may include vasodilatation with flushing, syncope
and shock, and abdominal pain, peptic ulcer, and bone pain (Kambe & Miyachi, 2002; Valent et al., 2001).
Mastocytosis was first reported in the literature in 1933, while urticaria pigmentosa (UP), a cutaneous lesion most
commonly associated with the disease, was first described in 1869. It is estimated that 1 in 4,000 persons
(approximately 65,000 persons) in the United States may have MC. It occurs equally in men and women and in all
ethnic backgrounds. The peak incidence is during infancy, early childhood, and middle age (Alto & Clarcq, 1999;
Longley, Duffy, & Kohn, 1995; Tharp & Longley, 2001). MC usually, but not always, manifests itself with various skin
lesions. It may also have systemic involvement ranging from an indolent systemic mastocytosis with a good
prognosis, to a high-grade malignant mast cell disease known as mast cell leukemia (MCL) with a poor prognosis.
Additional variants include mast cell sarcoma and extracutaneous mastocytoma.
Mastocytosis may mimic other chronic diseases making it difficult to determine a definitive diagnosis. This can lead
to delayed medical and nursing interventions, especially when life-threatening mediator response occurs or a life-
threatening form of the disease is present. Therefore, it is important for nurses to understand the pathophysiology,
clinical findings, and medical treatment when assessing and developing a plan of care for patients with MC.
Mastocytosis Classification
In September of 2000, the world's leading experts in MC met to discuss and present data at the "Year 2000 Working
Conference on Mastocytosis," held in Vienna, Austria. presents a uniform classification system for MC developed at
this conference (Valent et al., 2001).
Table 1. Table 1. Mastocytosis Classification System Year 2000 Working Conference on Mastocytosis
Unmasking Mastocytosis
Richard L. Pullen, Jr., EdD, RN, Kim Carrington Wright, MSN(c), RN
Dermatology Nursing. 2003;15(1)
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Cutaneous Mastocytosis
Approximately 90% of patients with MC manifest only cutaneous lesions, and do not have serious hematologic
disorders (Alto & Clarcq, 1999). Cutaneous mastocytosis (CM) has a low incidence of systemic involvement in
children, whereas, systemic mastocytosis (SM) occurs in greater than 25% of adults with CM (Hartmann & Metcalfe,
2000; Koeppel et al., 1998; Kuznar, 1998; Wolff, Komar, & Petzelbauer, 2001).
Cutaneous mastocytosis has typical skin lesions with infiltrates of mast cells in the dermis. Types of cutaneous
lesions include UP, which is the most common, diffuse cutaneous mastocytosis (DCM), and mastocytoma of the
skin. Cutaneous manifestations are due to abnormal mast cell proliferation, melanocyte proliferation, and melanin
pigment production that causes the hyperpigmentation associated with the lesions in mastocytosis (Hogan & Lewis,
2002; Roberts, Anthony, & Oates, 1998).
Urticaria pigmentosa is manifested as small, persistent, pigmented lesions that are often a centimeter or less in
diameter. UP lesions will urticate when stroked with a blunt object. This is known as Darier's sign and is a diagnostic
feature of mastocytosis (Hogan & Lewis, 2002; Kuznar, 1998; Leaf, Jaecks, & Rodriquez, 1996). UP lesions are tan
or red-brown in adults (see Figures 1-4) and are generally macular or slightly raised and appear most frequently on
the trunk and proximal extremities. UP is often pruritic and may cause considerable discomfort. When unaffected
areas of the skin are stroked, dermatographia may be elicited (Roberts et al., 1998).
Figure 1.
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Slightly raised tan to reddish-brown urticaria pigmentosa lesions of the hand.
Figure 2.

Urticaria pigmentosa seen in systemic mastocytosis. These lesions have a reddish-brown to slightly purple hue.
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Figure 3.

Diffuse macular reddish-brown lesions of urticaria pigmentosa seen in systemic mastocytosis.
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Figure 4.

Scattered macular lesions of urticaria pigmentosa. Slight rubbing of the lesions causes pruritus and edema. This is
known as Darier's sign.
A rare form of UP that primarily occurs in adults is telangiectasia macularis eruptiva perstans (TMEP). TMEP lesions
are diffuse red patches that are approximately 2 to 6 mm in diameter without sharply demarcated borders. The
lesions are associated with overlying telangiectasis (dilated capillaries). The lesions in TMEP are not pruritic and do
not produce Darier's sign because mast cell proliferation may not be sufficient to produce significant degranulation
(Alto & Clarcq, 1999; Hogan & Lewis, 2002; Kettelhut & Metcalfe, 1994).
A mastocytoma is rare and is predominantly seen in pediatric patients within the first 3 months of life. The pruritic
lesion is usually larger than UP and may present with a single or multiple lesions. A mastocytoma most frequently
occurs on an extremity and will usually resolve spontaneously. In contrast, the skin with DCM may appear normal or
have an abnormal appearance. The skin may have a generalized, diffuse edema with thickening of the skin and a
doughy consistency. The skin may also have a red-yellow-brown color or have an orange-peel appearance. Urticaria
and formation of hemorrhagic blisters and bullae are common. The bullae may rupture leaving erosions and crusts
(Soter, 2000). presents specific characteristics of cutaneous lesions observed in a patient with MC (Hogan & Lewis,
2002).
Table 2. Specific Characteristics of Cutaneous Lesions
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Systemic Mastocytosis
Systemic mastocytosis (SM) includes indolent systemic mastocytosis (ISM); systemic mastocytosis with an
associated hematologic clonal, nonmast cell lineage disease (SM-AHNMD); aggressive systemic mastocytosis
(ASM); or mast cell leukemia (MCL). Systemic mastocytosis is diagnosed if one major and one minor criterion are
met, or three minor criteria are fulfilled as outlined at the "Year 2000 Working Conference on Mastocytosis" (Valent
et al., 2001). A major criterion is multifocal dense infiltrates of mast cells (>15 MC aggregating) detected in sections
of bone marrow and/or of other extracutaneous organ(s) by tryptase-immunohisto-chemistry or other stains. Minor
criteria are:

In mast cell infiltrates detected in sections of bone marrow or other extracutaneous organs, >25% of mast
cells are spindle shaped or, in bone marrow smears, atypical mast cells compose >25% of all mast cells.
Detection of a c-kit point mutation at codon 816 in bone marrow or blood or other extracutaneous organ(s).
Kit mast cells in bone marrow or blood or other extracutaneous organ(s) co-express CD2 and/or CD25.
Serum total tryptase concentration >20 ng/ml (in case of an AHNMD, this is not valid) (Valent et al., 2001).

Mast cells of MC may or may not have typical properties, and this makes it difficult to diagnose by routine histology.
In skin, the accumulation of mast cells along with clinical symptoms will lead to the diagnosis. In bone marrow,
mastocytosis mast cells may have cytoplasmic extensions such as spindles or fusiform shapes, oval nuclei with
excentric positioning, and/or hypogranulated cytoplasm with focal accumulations of granules with or without granule
fusions. In a small number of patients, bone marrow MC mast cells may resemble normal mast cells (Valent et al.,
2001).
A genetic marker used to diagnose the disease and track its progress is a mutation in the C-Kit gene. CD117 (Kit) or
C-Kit is a growth factor receptor on mast cells. When a molecule called stem cell factor attaches to C-Kit, the
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development of mast cells results. A mutation of the receptor causes it to remain in the "on" position. As a result,
numerous identical mast cells are produced. This mutation has been identified in several types of SM-ISM,
SMAHNMD, and MCL (N. Gould, RN, personal communication, June 20, 2002).
CD117 (Kit) and CD25 are markers associated with the mast cell membrane. CD117 (Kit) is found on all mast cells
and their progenitors and is a marker for MC. CD25 is a portion of an interleukin-2 receptor expressed on the
surface of mast cells in the bone marrow of patients with systemic MC. This interleukin-2 receptor is involved in
inflammatory or cell-mediated immune responses. Due to proteolytic activity, these markers exist in soluble forms,
soluble CD117 (Kit) and Soluble CD25, and may be detected in circulation (Akin & Metcalfe, 2002).
CD2 is another marker present on the surface of mast cells in most patients with adult-onset systemic MC. CD2,
which is similar to CD25, is normally expressed by T-lymphocytes in the bone marrow and peripheral blood. It is also
present on the surface of mast cells in most patients with adult-onset mastocytosis, and thus together with CD25,
can be used as a diagnostic marker in flow cytometric analysis of bone marrow mast cells (C. Akin, MD, personal
communication, July 19, 2002).
Serum tryptase is the most commonly used disease marker of MC. Immunoassay of tryptase in serum or plasma
measures the sum of alpha and beta tryptases. It is believed that alpha tryptase is continuously secreted from the
mast cell, while beta tryptase is stored in mast cell granules and released after mast cell activation, such as
anaphylaxis. Normally, beta tryptase is undetectable; therefore, total tryptase levels are primarily an indicator of
alpha tryptase. A total tryptase level appears to correlate with mast cell number (Akin & Metcalfe, 2002). A total
tryptase level greater than 20 ng/mL is suggestive of mastocytosis and is a minor criterion in diagnosing systemic
mastocytosis (Valent et al., 2001).
Indolent systemic mastocytosis has skin involvement in almost all cases. Mast cell infiltrates may be detected in
various organ systems, including the liver, spleen, or GI tract. The bone marrow is affected in nearly 100% of cases
and contains multifocal dense infiltrates of mast cells. There is a rather low infiltration grade in bone marrow (<30%).
A characteristic finding in ISM is osteosclerosis and bone marrow fibrosis. There is a modestly elevated burden of
mast cells. The majority of patients have serum tryptase >20 ng/ml, but usually do not exceed 500 ng/ml. Mediator
symptoms are often recorded. There is an indolent clinical course, with a good prognosis (Valent et al., 2001).
Systemic mastocytosis with an associated hematologic clonal, non-mast cell lineage disease (SMAHNMD) is
another subtype of SM. Up to 20% of patients with systemic mastocytosis develop an AHNMD. Any type of clonal
hematologic malignancy may occur. Myeloproliferative syndrome, myelodysplastic syndrome, and acute myeloid
leukemia occur with much higher frequency than non-Hodgkin's lymphomas or other lymphoid neoplasms.
Chemotherapy may be used as a treatment for SMAHNMD (Valent et al., 2001).
Aggressive systemic mastocytosis manifests with organ impairment due to mast cell infiltrates. The most common
organs affected are liver, bone marrow, spleen, and GI tract. Cutaneous mast cell-like lesions are frequently absent.
Patients exhibit one of the following: (a) abnormal myelopoiesis with significant blood count abnormalities, (b)
hepatomegaly with impairment of liver function due to MC infiltration (often with ascites), (c) large osteolyses
(sometimes with pathologic fractures), (d) malabsorption with weight loss due to GI-tract infiltration, (e)
splenomegaly with hypersplenism, or (f) life-threatening impairment or organ function in other organ systems. ASM
may have a slow or rapid progression. Bone marrow infiltrates vary, as well as mast cell characteristics. Mast cells
usually compose less than 20% of nucleated cells in bone marrow smears.
Significant abnormalities in differential blood counts may be found in ASM such as cytopenia(s), leukocytosis,
eosinophilia, monocytosis, basophilia, or thrombocytosis. Serum calcium and alkaline phosphatase levels may be
elevated due to osteolysis. Serum tryptase levels are usually elevated, and may be very high reflecting a significant
mast cell burden.
Mast cell leukemia is a systemic mast cell disease with a significant number of leukemic mast cells in peripheral
blood and/or immature mast cells (>20% in the bone marrow smears). Most patients are adults and cutaneous
lesions are typically absent. Multi-organ failure occurs.
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Patients may complain of mediatorrelated symptoms; and later weight loss, bone pain, and organomegaly. Bone
marrow failure develops within weeks to months as bone marrow is replaced by mast cells. Severe bleeding often
occurs in the GI tract and other organ systems. Serum tryptase levels are significantly elevated, and other laboratory
parameters are abnormal. There is no known curative therapy and only a few patients survive more than 1 year
(Kuznar, 1998; Valent et al., 2001).
Sarcoma and Extracutaneous Mastocytoma
Mast cell sarcoma is rare. There is destructive growth of a local tumor consisting of poorly differentiated mast cells
without systemic involvement. Mast cell sarcoma develops into a terminal phase. The prognosis is grave.
Extracutaneous mastocytoma is a benign, low-grade tumor without destructive growth. In contrast to mastocytoma
of the skin, mastocytomas in extracutaneous organs are very rare. They have primarily been detected in the lungs.
The prognosis is good without progression to aggressive disease or MCL.
Diagnostic Laboratory and Imaging Studies
It is necessary for the health care provider to consider differential diagnoses when mastocytosis is suspected (see ).
The standard for diagnosing MC is a tissue biopsy demonstrating a pathologic increase in the number of mast cells.
Table 3. Mastocytosis, Differential Diagnosis
There is an increase in the number of mast cells in the skin; however, no precise mast cell concentration defines
cutaneous mastocytosis. The number of mast cells in the skin is increased even when lesions are not present. In
UP, the number of mast cells in the papillary dermis is increased, particularly around blood vessels. If a lesion has
been traumatized, edema of the tissue may be noted along with infiltrating cells that include eosinophils. Mast cells
in a patient with MC are generally larger than normal mast cells when analyzed with an electron microscope. It is
more difficult to establish a diagnosis by histology in mastocytosis with diffuse infiltrates and telangiectatic variants
(Soter, 2000; Tharp, 1995; Valent et al., 2001).
Systemic mastocytosis is usually diagnosed by examining bone marrow biopsy and aspirate tissue. The bone
marrow is the organ system most often affected by systemic disease. The MC lesion is usually multi-focal dense
with sharply demarcated infiltrate. MC can be a diffuse bone marrow lesion, which makes diagnosis of systemic
mastocytosis more difficult. In all patients with systemic disease, the grade of bone marrow infiltration should be
estimated on a tryptase-stained bone marrow biopsy section (Valent et al., 2001).
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Mast cell membrane and genetic markers, which have previously been discussed, may also be used to diagnose
MC. A genetic marker is the mutation in C-Kit. Mast cell membrane markers detected in circulation are Soluble
CD117 (Kit) and Soluble CD25. CD117 (Kit) and CD25 are elevated in circulation and are indicative of MC, severity
of disease, and bone marrow involvement (Akin et al., 2000). CD2 is present on bone marrow mast cells in most
patients with adult-onset systemic mastocytosis.
Histamine is a mediator found in the granules of mast cells. Levels of serum or urine histamine vary; therefore,
measurement of metabolites in a 24-hour urine specimen is the preferred method of assessing baseline histamine
levels. Metabolites measured in a 24-hour urine specimen are N-methylhistamine (NMH) and methylimidazoleacetic
acid. NMH levels correlate directly with the extent of skin lesions (Hogan & Lewis, 2002). An allergic reaction during
the 24-hour urine collection can increase histamine metabolite levels. During the 24-hour collection of urine, patients
should avoid foods high in histamine including dairy products, cheese, fish, sausage, pickles, and yeast products.
A bone scan and radiographic studies may be necessary when the patient is experiencing musculoskeletal
symptoms. The symptoms may be related to the presence of bone lesions, osteoporosis, or osteosclerosis
subsequent to systemic mastocytosis. An upper gastrointestinal series, small bowel x-ray, endoscopy, computerized
axial tomography, and magnetic resonance imaging may identify peptic ulcers, abnormal mucosal patterns, or
motility disorders when the patient has gastrointestinal symptoms (Hogan & Lewis, 2002). It is important to avoid the
use of iodinated radiocontrast dyes during these exams, as this agent is a direct mast cell activator that causes
degranulation and may result in severe adverse reactions (Worobec, 2000).
Treatment of Mastocytosis
A standard treatment for mastocytosis is difficult to apply to individual patients based on the variable clinical course.
A general consensus for using antimediator agents such as antihistamines, cromolyn sodium, or ketotifen is
recommended. These agents can be introduced based on the clinical course of the patient.
Many patients require a combination of H1 and H2 antihistamines. H1 antihistamines such as diphenhydramine,
hydroxyzine, doxepin, loratadine, fexofenadine, or cetirizine may be used to treat symptoms of mastocytosis.
Diphenhydramine, hydroxyzine, and doxepin have been used for flushing, pruritus, tachycardia, and in some cases,
gastrointestinal cramping (Worobec, 2000). Loratadine or fexofenadine may be used if patient sedation or
anticholinergic side effects are of concern (Worobec, 2000).
H2 antihistamines, such as ranitidine, cimetidine, or famotidine, are used to treat gastric hypersecretion and peptic
ulcer disease associated with histamine release in mastocytosis (Worobec, 2000). H2 antihistamines have little or
no effect on symptoms such as diarrhea and malabsorption (Worobec, 2000). Omeprazole, a proton pump inhibitor,
has been reported to decrease diarrhea and control hypersecretion of gastric acid (Worobec, 2000).
Ketotifen, a mast cell stabilizer, is only available as an eye drop (Zaditor) in the United States at this time. It may
be purchased outside of the United States with a prescription. It is recommended for patients with bone pain and/or
flushing. Ketotifen has been used for pruritus and whealing, but seems to offer no advantage over hydroxyzine
(Worobec, 2000).
Disodium cromolyn is a mast cell stabilizer that is believed to act by decreasing mast cell degranulation, therefore it
treats the symptoms but does not change the progression of the disease (Worobec, 2000). Orally administered
disodium cromolyn relieves diarrhea and abdominal cramping. Disodium cromolyn reduces bone pain, headaches,
and improves cognitive abilities and cutaneous symptoms (Worobec, 2000). Additional treatment modalities may
also include (Kuznar, 1998):

Psoralens and ultraviolet-A (PUVA) or corticosteroids to reduce pruritus and whealing.
Interferon alpha-2b (aggressive forms of mastocytosis).
Chemotherapy (aggressive systemic mastocytosis).
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Local radiation for bone pain.
Splenectomy

Low-dose aspirin is helpful in some patients, because it causes continuous degranulation and prevents extreme
peaks of histamine release from mast cells. Doses of 40 mg per day have been used, and this dose is increased
gradually based on patient response. Close monitoring is necessary because salicylates can cause severe adverse
effects, and may not be tolerated in some patients. Aspirin has been reported to cause death in one patient with
mastocytosis (Oklahoma: An Educational Success, 2002). Mast cell mediator release may lead to anaphylaxis.
Patients should be prepared to administer epinephrine with a self-injecting pen at all times. Acute treatment with
epinephrine is 0.3 mL of a 1:1000 dilution in adults, and 0.01 mL/kg of a 1:1000 dilution in children (up to 0.3 mL)
administered every 10 to 15 minutes subcutaneously (Worobec, 2000).
A patient should be taken to a medical facility immediately by emergency personnel educated in advanced cardiac
life support when a life-threatening reaction occurs. Avoiding triggers is essential in preventing potentially life-
threatening mast cell mediator release (see ).
Table 4. Triggers That Stimulate Mast Cell Mediator Release
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Nursing Care and Patient Education
Determining a diagnosis of MC may take time. This may cause the patient anxiety and frustration. It is important to
encourage the patient to tell his/her story during the health history interview. Active listening is essential. This helps
to establish a caring and collaborative relationship between the patient and nurse. This relationship will help to
enhance patient education and compliance. A head-to-toe assessment is vital. It is important for the patient to have
regular examinations by health care providers who are knowledgeable about MC. This includes assessing for
lesions, blood abnormalities, systemic symptoms, effects of pharmacotherapy, and patient comfort. Enlist the patient
to become a partner in his or her care that encourages independence and perseverance while the health care
provider arrives at a diagnosis of mastocytosis. To promote physical and emotional health, encourage the patient to:

1. Minimize stress. Exercises such as yoga and walking can be helpful. Vigorous exercise tends to stimulate
mast cell mediator release.
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2. Rest. Have restful periods throughout the day and plan to have at least 8 hours of sleep each night.
3. Avoid substances (triggers) that induce mast cell mediator release, such as peanuts, crawfish, lobster,
alcohol, spicy foods, hot beverages, and cheese.
4. Avoid orange juice and tomato juice due to high aspirin content (Oklahoma: An Educational Success, 2002).
5. Avoid or minimize exposure to environmental stimuli that induce mast cell mediator release such as sunlight
and bee stings.
6. Wear a Medic-alert bracelet and carry an Epi-pen.
7. Avoid rubbing, scratching, or traumatizing the lesions of cutaneous mastocytosis.
8. Avoid temperature extremes. A cool environment in the home, car, and workplace promotes comfort from
flushing. Avoid hot baths and hot tubs.
9. Keep a journal of their experiences.
10. Participate in self-help groups to share experiences and help others with mastocytosis (see Table 5).

Conclusion
Although MC is a rare disorder, it is affecting the lives of at least 65,000 persons in the United States. Further
research is necessary to enhance understanding of MC and improve medical and nursing care. This can best be
accomplished through a collaborative relationship between the nurse, physician, and multidisciplinary team.
CME Information
The print version of this article was originally certified for CE credit. For accreditation details, contact the publisher.
Jannetti Pulications, Inc. East Holly Avenue Box 56, Pitman, NJ; phone (856) 256-2300.
Dermatology Nursing. 2003;15(1) 2003 Jannetti Publications, Inc.

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