Mast Cell Disease (Urticaria Pigmentosa)

 Synonyms: Urticaria pigmentosa, telangiectasia macularis eruptive
perstans, mastocytoma, mastocytosis
 Etiology: Unknown
 Associations: Nausea, vomiting, diarrhea, syncope, mast cell leukemia,
other hematologic malignancies
 Clinical: Papules or nodules with or without associated
hyperpigmentation and telangiectasia; positive Darier’s
 Histology: Increased dermal mast cells perivascular or as tumor
nodules, basilar hyperpigmentation, vascular ectasia
 IHC repertoire: CD117 (c-kit) and mast cell tryptase positive
 Staging: Bone marrow involvement conveys poor prognosis
 Prognosis: Varies with subtype of disease; benign in children
 Adverse variables: Bone marrow involvement
 Treatment: Chemotherapy including interferon alfa if bone marrow
involvement; topical steroids; close clinical follow-up in
patients with adult-onset disease

Cutaneous mast cell disease has several different manifes- Bullous lesions may be present due to extensive papillary
tations. It can present during the neonatal period or dermal edema secondary to histamine release from mast
throughout life. Different age populations generally cells. Vesicles do not generally occur as part of cutaneous
develop different clinical manifestations and different mast cell disease in patients older than 10 years of age.
associated conditions. It is the systemic form of mastocy- Rarely, children with diffuse mast cell disease may present
tosis in adults that has the most potentially severe com- with erythroderma (Figure 6.2). Despite the absence of
plications. It has been estimated that from 15% to 50% of systemic disease, these children are at risk for hypoten-
patients with adult-onset mast cell disease will have sys- sion, shock, and even death.
temic involvement (1,2). However, for the sake of com- Adults with mast cell disease are more likely to present
pleteness, the other variants of this disease spectrum will with a widely scattered macular eruption. Individual
also be considered. Urticaria pigmentosa is the global lesions are often red-brown or hyperpigmented. The
term for all conditions that are characterized by increased lesions are randomly distributed and generalized, but are
numbers of mast cells within the dermis. There is no accentuated on the chest. Petechiae and ecchymoses may
gender predilection. occur. Depending upon the mast cell burden within each
Mast cell disease in childhood is only rarely associated lesion, an urticarial reaction can be elicited by gently
with systemic disease (less than 2% of the time in one stroking these lesions. Pruritus is the most common
series). About one-third of all patients with mast cell symptom. Less commonly, nausea, vomiting, diarrhea,
disease are less than 15 years old (3). The disease resolves and abdominal pain may be reported. These symptoms
spontaneously in two to three years in the vast majority occur in patients with limited cutaneous disease as fre-
of these patients, by adolescence in virtually all. Children quently as those with systemic involvement. One type of
with mast cell disease often have single or a few large, adult-onset form of the disease is known as telangiectasia
nodular lesions called mastocytomas (Figure 6.1). These macularis eruptive perstans (TMEP). In this variant,
most commonly appear within the first three years of life. abundant hyperpigmented 2–6-mm macules are present
These lesions urticate easily with stroking (Darier’s sign). on the back and chest in concert with telangiectasias. Pru-

hyperpigmented eruption. There is no difference in the age fall into two general categories. decade. Eosinophilia is present in 15% of all patients with systemic disease. often with Neither pattern is predictive of systemic involvement. but in most cases is relatively slight.28 Deadly Dermatologic Diseases In adults with cutaneous mast cell disease. Erythematous/tan plaque of mastocytosis in a mon. as much as 20 years separating these findings from the though the superficial perivascular pattern is more initial cutaneous presentation (3). It is currently not edema leads to a subepidermal bulla. Mast cells may be distrib- of presentation between those with and without systemic uted in a perivascular pattern or diffusely (Figure 6. correlating with the possible to distinguish adult patients with disease limited blisters encountered clinically. The bone marrow is the most frequently involved extracutaneous site. Lymph node involvement is not uncommon. hepato- splenomegaly is often seen in addition to the macular.1. The number of perivascular mast cells varies disease may remain alive with persistent disease for many widely. In some cases. often filling the entire dermis and extending into the subcuta- neous fat. prominent papillary dermal ritis and urtication are not common. with only a years.3A involvement.3B). The mean age of presentation is in the fourth and 6. levels of t-methyl histamine may also be detected in these patients (5). to the skin from those with systemic disease based purely The histologic findings in adult-onset mast cell disease on the cutaneous disease. Patients with systemic common (3). Involvement of the gas- trointestinal tract has been reported but is very uncom- FIGURE 6. Systemic disease presents much later. pancytopenia may be present and a bone marrow biopsy and aspiration is necessary to eliminate the presence of mastocytosis or leukemia (mast cell leukemia or chronic myelogenous leukemia). Osteoblastic lesions can be detected with radiographs. . or may succumb to their illness. Erythroderma with islands of sparring and hepato- splenomegaly associated with par- enchymal organ infiltration in systemic mastocytosis. The histologic findings in child-onset mast cell disease include a very dense dermal infiltrate of mast cells. Leukemia is reported to develop in 4%–5% of patients with systemic mastocytosis (4). In these patients. FIGURE 6.2. Increased serum tryptase and increased urinary child. minimal increase in cellularity over physiologic levels.

(B) Low power photomicrograph depicting superficial dermal infil- trate of mastocytosis in adult T.4). prominent nuclear atypia and presence granules (7). an admixture of nucleoli and multinucleation may be present. monly (Figure 6. (A) Low power photo- micrograph depicting superficial dermal infiltrate of mastocytosis. cell disease (Figure 6.P. there is a nine-to-160. Mast Cell Disease (Urticaria Pigmentosa) 29 FIGURE 6.M. pared with normal patients (6). of lymphocytes and eosinophils are present within .5).E. mast cells from patients with systemic disease are larger. In biopsies from both patterns. A B Morphometric point counting has suggested that while these findings do not associate invariably with systemic the absolute numbers may be small. and have more cytoplasm and larger cytoplasmic In these cases.6. Mitotic activity is rare in all cases of mast fold increase in numbers of mast cells in these cases com.3. electron microscopy suggested that within the papillary dermis are encountered less com. involvement. however. Dense diffuse infiltrates In one study.

6). skin involve. In more subtle cases. .9). staining with CD117 (c-kit) or mast cell tryptase Cutaneous lesions can be watched or treated with topical (Figure 6. or more specifi. Conversely. Treatment options vary with the extent of disease. interferon. limited cutaneous disease (3). mast cell numbers ment is not present in all cases of systemic mast cell disease can be better assessed with special stains such (8. High power photo- micrograph depicting uniform population of rounded cells pos- sessing oval nuclei with ampho- philic staining cytoplasm. be very focal and a negative biopsy does not guarantee chemotherapy.5. steroids or even surgical excision of limited lesions. More Bone marrow involvement with mast cell disease may extensive disease requires topical steroids. FIGURE 6. the dermis. as toluidine blue or Giemsa’s stains.30 Deadly Dermatologic Diseases FIGURE 6.4. cally. and ultraviolet light therapy. None of these options are entirely effective. antihistamines. Medium power photo- micrograph depicting uniform population of epithelioid cells within the superficial dermis.

subsets using a morphometric point counting technique. 2. Arch Dermatol 1986. The natural course of urticaria pigmentosa. Freeman RG. J Invest Dermatol 1991. Ultmann JE. Mastocytosis and the mast cell. 84: disease. The skin in mastocytosis. . Tannenbaum M. Olafsson JH. Mast Cell Disease (Urticaria Pigmentosa) 31 FIGURE 6. Mutter RD. 1. N Eng J Med 2002. Li C-Y. Soter NA. Cirardet C. 9. 1963: 59: 887–906.6. Kaspar CS. 3. Ridell B. Rodjer Arch Dermatol 1987. S. Travis WD. Am J Clin Pathol 1985. DiBacco RS. Systemic mast-cell disease (masto- cytosis): Letter to the editor. Systemic mast cell and systemic mast cell disease. Fields JP. Adult-onset urticaria pigmentosa 8. DeLeo VA. References 5. Oates JA. Arch 6. 7: 709–722. Giesma stains reveal metachromatic staining of cyto- plasmic granules within mast cells. 346: 174. Swolin B. Asmis LM. 710–714.6. J Am caria pigmentosa: A frequently unrecognized cause of recur- Acad Dermatol 1982. systemic mastocytosis. 96: 32S–39S. Enerback L. 123: 1017–1021. 122: 422–427. Granerus G. 85: 36–41. Tharp MD. Trans Assoc Am Physicians 1982. Su WPD. Mastocytosis without urti- 4. 87: 146–157. Diagnosis of mastocytosis Dermatol 1983. rent syncope. The bone marrow in urticaria pigmentosas and 7. Caplan RM. Roberts LJ II. Roupe G. Ann Int Med.