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976 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells Chapter 63: Basophils, Mast Cells, and Related Disorders 977

At presentation, patients with mastocytosis may complain of vague syndrome. When episodic hypertension is a major finding, pheochro-
and nonspecific constitutional symptoms, such as fatigue, weakness, mocytoma should be considered. Significant unexplained gastroduode-
flushing, and musculoskeletal pain. Some patients experience fever nal ulcer disease requires that Zollinger-Ellison gastrinoma syndrome
and/or weight loss. 152,186 A subset of patients may present with recur- be ruled out. Helicobacter pylori infection should be considered in all
198
rent episodes of unexplained anaphylaxis. However, most patients patients with ulcer disease, including patients with mastocytosis.
with mastocytosis and a hematologic disorder are diagnosed based on Some diseases have hematologic findings that overlap with those
marrow biopsy findings, during the investigation of their hematologic of systemic mastocytosis. These disorders include tryptase-positive
disease. 187,189 Patients with aggressive disease often present with unex- AML, CML with accumulation of tryptase-positive cells, primary mye-
plained lymphadenopathy and splenomegaly and/or hepatomegaly. lofibrosis with mast cell accumulation, and acute or chronic basophilic
Gastrointestinal disease and associated symptoms are commonly leukemia.
associated with systemic mastocytosis, either at presentation or as the A somatic mutation in KIT at codon 816 (most commonly
disease progresses. 174,199 Findings include nausea, vomiting, abdom- Asp816Val) is associated especially with adult-onset systemic mastocy-
inal pain, and diarrhea. Peptic ulcer disease, which is thought to tosis. Demonstration of a codon 816 gain-of-function mutation, where
reflect, at least in part, the promotion of gastric acid secretion by ele- the most sensitive approach is to look for its presence in sorted mar-
vated histamine levels, occurs in up to 50 percent of patients with sys- row-derived mast cells, is a minor criterion in the diagnosis of mastocy-
199
temic disease. With progressive disease, patients may develop mild tosis (see Table 63–6).
malabsorption. 199
If systemic involvement is advanced at the time of diagnosis,
patients may exhibit lymphadenopathy, hepatomegaly, and splenomeg- THERAPY
aly during the initial evaluation. Because osteoporosis may accom- Mastocytosis currently has no cure. In addition, no evidence indicates
152
202
pany systemic disease, pathologic fractures may occur. that symptomatic therapy significantly alters the course of the underly-
ing disease.
LABORATORY FEATURES Avoiding Triggers
When systemic mastocytosis is suspected in patients based on a Management of mastocytosis includes instructing the patient on the
combination of: reports of symptoms consistent with mediator avoidance of factors that may trigger symptoms (presumably by direct
release, identification of classical skin lesions showing a 10-fold or or indirect activation of mast cell mediator production). Such fac-
greater increase in mast cell numbers, an elevation in serum trypt- tors can include temperature extremes, physical exertion, or, in some
ase of greater than 20 ng/mL and documentation of organomegaly, unusual cases, ingestion of ethanol, nonsteroidal antiinflammatory
200
an appropriate next step is to perform a marrow biopsy and aspi- drugs, or opiate analgesics. 174
rate. 152,176,201 Additional studies, including a gastrointestinal evalu-
ation involving radiographic studies of the upper gastrointestinal Epinephrine and H or H Antihistamines
2
1
tract and small intestines, computed tomographic scan of the abdo- Anaphylaxis may follow insect stings, even in the absence of evidence
men, and endoscopy, also may be justified. of allergic sensitivity. Epinephrine-filled syringes and instructions on
198
Plasma and/or urinary histamine levels may be increased in sys- their use can be given to patients considered at risk for such a reaction.
temic mastocytosis. However, the isolated findings of increased levels Patients with mast cell disease and a history of anaphylaxis should be
186
of histamine or histamine metabolites may reflect a number of other sit- advised to carry epinephrine-filled syringes, instructed on their use,
uations, including anaphylaxis. Furthermore, the accuracy of laboratory and taught to self-medicate, if necessary. These patients also may benefit
measurement of histamine depends on the assay used. Urine histamine from the concurrent use of H and H antihistamines prophylactically.
levels may be falsely elevated as a result of bacterial contamination, Patients may experience severe reactions to iodinated contrast materi-
1
2
pharmacologic agents and their metabolites excreted in the urine, or als. Thus, consideration should be given to premedicating mastocytosis
diets rich in histamine or histamine precursors. Similarly, serum trypt- patients with H and H antihistamines and prednisone. Nonsedative
ase may be elevated after anaphylaxis. Thus, no single laboratory test H antihistamines decrease skin irritability and pruritus. 186,202 Pruritus
2
1
showing an elevation in a mast cell mediator is diagnostic of mastocy- may be relieved by approaches that maintain skin hydration. H anti-
1
2
tosis. Rather, the demonstration of such mediators in blood or urine histamines, including ranitidine and famotidine, are used to treat the
should prompt the clinician to investigate further for the presence of gastritis and peptic ulcer disease associated with mastocytosis. 186,202–204
mastocytosis. H antihistamines may be titrated based on symptom control or to a
2
There are patients who have symptoms of mediator release but no particular level of gastric secretion. Proton pump inhibitors are useful
mastocytosis in the skin or organomegaly. Some of these patients may for management of gastric hypersecretion. 199,204
have experienced venom-induced anaphylaxis. These patients may also
exhibit elevations in tryptase but below the 20 ng/mL which is used as
a minor diagnostic criterion. In such situations, reports have suggested
the detection of the D816V mutation in blood using a highly sensitive OTHER DRUG THERAPY
allele-specific quantitative polymerase chain reaction (qPCR) may be use- Disodium Cromoglycate; Ketotifen
ful as a diagnostic parameter. At the time of writing of this chapter, this Oral administration of disodium cromoglycate may be useful for treat-
201
test is not widely available and it is being used largely in referral centers. ment of gastrointestinal cramping and diarrhea. 186,202,205 The agent has
186
been beneficial in cutaneous mast cell disease in children and infants.
Other symptoms, including headache, have improved with adminis-
DIFFERENTIAL DIAGNOSIS tration of cromolyn sodium. Ketotifen reportedly has been effective in
The differential diagnosis of systemic mastocytosis includes allergic dis- relieving pruritus and wheal formation in cutaneous mastocytosis. By
206
eases; hereditary or acquired angioneurotic edema; idiopathic flushing, contrast, one pediatric study found ketotifen was no more effective than
urticaria, and anaphylaxis; carcinoid tumor; and idiopathic capillary leak hydroxyzine. 207

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