ARTICLE Telangiectasia
macularis eruptiva perstans (TMEP) is a rare form
of cutaneous mastocytosis, characterized by multiple brownish-red confluent
macules and telangiectasia [1]. Most patients with this disease have only
skin lesions with a good prognosis. However, some cases exhibit systemic
involvement, such as hematologic disorders. There have been 5 cases of mastocytosis
with polycythemia rubra reported in the literature [2-6]. Four of 5 patients
had skin lesions diagnosed as urticaria pigmentosa [2-4, 6], and the other
was systemic mastocytosis without a skin eruption [5]. In this report, we
describe a patient with TMEP who had suffered from the typical cutaneous
disorder for 20 years and developed polycythemia rubra vera 10 years after
the onset of the skin manifestation.
Case report
A 65-year-old Japanese man was seen with a 20-year history of a cutaneous
eruption, which had occurred on his arms and later spread to the trunk,
legs, and face. He had no flushing, wheezing, or diarrhea. The patient
had been diagnosed as having polycythemia rubra vera 10 years previously,
which was followed up without medication, and duodenal ulcer 8 years previously,
treated with H2 blocker. There was no family history of a similar
eruption.
Physical examination revealed multiple reddish-brown macules distributed
over the arm, trunk, leg, face with scattered telangiectasias (Fig.
1).
Neither Darier's sign nor other symptoms of mastocytosis was present.
A biopsy specimen from a duodenum ulcer showed no mucosal involvement
of mast cells. Lymphadenopathy was absent.
Results of the following laboratory examinations were either normal
or negative: leukocyte counts, platelet counts, blood chemistry studies,
blood coagulation test, serum protein electrophoresis, serum histamine
concentration, and urinalysis. The data of polycythemia included elevated
values of erythrocytes (6.4 x 1012/l; normal, 4.3-5.7 x 1012/l),
hemoglobin (20.4 g/dl; normal, 13.5-17.6 g/dl), hematocrit (59.2%; normal,
39.8-51.8%), erythropoietin (1.0 mU/ml; normal, 8-36 mU/ml), folic acid
(11.4 ng/ml; normal, 2.4-9.8 ng/ml), and vitamine B12 (589
pg/ml; normal, 233-914 pg/ml); and normal levels of thyroid profile, renin,
and aldosteron. Philadelphia chromosome was not found, and the neutrophil
alkaline phosphatase (NAP) rate and score were normal. A gastrointestinal
evaluation and aspiration of bone marrow revealed no pathologic infiltation
of mast cells.
A skin biopsy specimen was obtained from the forearm. There was a thick
epidermis with a hyperpigmented basal layer and there were dilated capillaries
in the dermis. Mononuclear cells infiltrated markedly in the upper dermis,
and had round or oval nuclei and a small amount of cytoplasm (Fig.
2a).
Toluidine blue staining revealed that these cells were mast cells with
metachromatic cytoplasmic granules. Immunohistochemically, the mast cells
were positive for tryptase (Fig.
2b) and chymase.
The patient was treated with a H1 blocker chloropheniramine
[7], 6 mg daily for 6 months to inhibit possible histamine-induced formation
of skin lesions, but no therapeutic effectiveness was noted. Currently,
his skin eruption remains unchanged.
Discussion
Cutaneous mastocytosis includes mastocytoma, urticaria pigmentosa, diffuse
cutaneous mastocytosis, and TMEP [8]. We diagnosed this patient as TMEP
because of the typical clinical appearance and histopathologic findings.
Systemic mastocytosis involves extracutaneous organs, including bone
marrow, gastrointestinal tract, liver, spleen, or lymph node, with or
without cutaneous lesions. Such extracutaneous organ involvement was not
found in our patient. Metcalfe [2] classifies mastocytosis on the basis
of the presence or absence of associated hematologic disorders, for example,
leukemia, lymphoma, myelodysplastic and myeloproliferative disorder. According
to his classification, this patient belongs to "mastocytosis with an associated
hematologic disorder".
There have been 5 cases of mastocytosis with polycythemia rubra vera
reported in the literature [2-6]. Four of 5 patients had skin lesions
diagnosed as urticaria pigmentosa [2-4, 6], and the other was systemic
mastocytosis without a skin eruption [5]. Only multiple myeloma was reported
as a hematological disorder associated with TMEP [9]. Thus, this is the
first case of TMEP associated with polycythemia rubra vera.
Mastocytes are divides into two subtypes
by the presence of serine proteases, typtase and chymase [10, 11]. The
first subtype has both tryptase and chymase (MCTC) and exists
mainly in skin and submucosal tissue of the small intestine. The second
subtype, possesses only tryptase (MCT) and resides in the lung
and mucosa of the small intestine. Based on this staining pattern, mastocytosis
double-positive for the two proteases is considered to be of cutaneous
but not systemic type. It has been reported that the patients with hematological
disorder have a poor prognosis [12], and one case of TMEP with bone marrow
infiltration of mast cells has been reported [13]. Since the mast cells
in our patient were positive for both typtase and chymase, we diagnosed
this patient as indolent, nonsystemic mastocytosis with a good prognosis.
It is thought that its nature is proliferation of skin mastocytes in the
cutaneous milieu but not neoplastic proliferation of bone marrow-derived
mastocytes. In fact, our patient has a 20-year history of the disease
without progressive systemic conditions.
Tebbe et al. [12] reported that all of their 14 adult patients
with cutaneous mastocytosis had some extracutaneous involvement. A recent
study demonstrated a point mutation in c-kit gene in a mastocytosis patient
with a hematologic disorder [14]. These findings provide the possibility
that even cases with a skin-limited manifestation have a systemic potential
or nonovert systemic involvement. It should be kept in mind that such
a serious systemic condition might occur in this patient.
Article accepted on 6/01/02
REFERENCES
1. Parkes Weber F, Hellenschmied R. Telangiectasia macularis eruptiva
perstans. Br J Dermatol Syph 1930; 42: 374-82.
2. Bowlder AJ, Tullett GL. Urticaria pigmentosa and polycythemia
vera: a case report. Br Med J 1960; i: 396.
3. Brink AJ, Marshall J. Mastocytosis (uriticaria pigmentosa)
and polycythemia rubra vera. South African Med J 1963; 37: 1307.
4. Diamond JH, Gross L. Urticaria pigmentosa complicated by polycythemia
vera. Report of a case. Blood 1966; 27: 253-7.
5. Eagan JW Jr, Baughman KL, Miller S, Conley CL, Eggleston JC.
Systemic mastocytosis in a patient with polycythemia vera treated with
radioactive phosphorus. Blood 1977; 49: 563-71.
6. Handler G, Isenberg L, Greaves MW. Concurrence of urticaria
pigmentosa and polycythemia rubra vera. Clin Exp Dermatol 1981;
6: 43-6.
7. Reqena L. Erythrodermic mastocytosis. Cutis 1992; 49:
189-92.
8. Metcalfe DD. Classification and diagnosis of mastocytosis:
current status. J Invest Dermatol 1991; 96: 2S.
9. Bachmeyer C, Guillemaette J, Blum L, Turc Y, Dhote R, Fermand
JP, et al. Telangiectasia macularis eruptiva perstans and multiple
myeloma. J Am Acad Dermatol 2000; 43: 972-4.
10. Irani AM, Bradford TR, Kepley CL, Schechter NM, Schwartz
LB. Detection of MCT and METC types of human mast cells by immunohistochemistry
using new monoclonal anti-tryptase and chymase antibodies. J Histichem
Cytochem 1989; 37: 1509-15.
11. Irani AA, Garriga MM, Metcalfe DD, Schwartz K. Mast cells
in cutaneous mastocytosis: accumulation of the MCTC type. Clin Exp
Allergy 1990; 20: 53-8.
12. Tebbe B, Stavropopulos PG, Krasagakis K, Orfanos CE. Cutaneous
mastocytosis in adults. evaluation of 14 patients with respect to systemic
disease manifestations. Dermatology 1998; 197: 101-8.
13. Allen BR. Telangiectasia macularis perstans. Br J Dermatol
1978; 99 (suppl. 16): 28-9.
14. Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S,
Suzuki Y, Metcalfe DD. Identification of a moint mutation in the catalytic
domain of the protooncogene c-kit in peripheral blood mononuclear cells
of patients who have mastocytosis with an associated hematological disorder.
Proc Natl Acad Sci USA 1995; 92: 10560-4.
|
Version imprimable
