ARTICLE
Auteur(s) : Caroline Bussmann, Tobias Hagemann, Julia
Hanfland, Gerhard Haidl, Thomas Bieber, Natalija Novak
Department of Dermatology, University of Bonn,
Sigmund-Freud-Str. 25, 53105 Bonn, Germany
accepté le 15 Février 2007
Mastocytomas are infiltrates of mast cells in the upper corium and
appear as brownish-reddish maculae or plaques. Together with
urticaria pigmentosa mastocytosis, which consists of a diffuse mast
cell infiltration of the skin with multiple, ovoid red-brown
macules which can involve the entire integument, solitary
mastocytomas represent one of the most common forms of cutaneous
mastocytosis in childhood. While in adult mastocytosis systemic
involvement occurs in 40-90% of the patients, mastocytosis in
childhood is limited to the skin in more than 80% of the cases [1,
2] with a tendency to spontaneous resolution before puberty [3].
Solitary mastocytomas usually show up immediately at birth or
during the first months of life and only very rarely later [4, 5].
The course is benign and they show spontaneous involution with
symptoms and lesions resolving by adolescence in most of the cases
[6]. Usually, they measure 0.5-3 cm at the largest diameter
and might appear on the trunk, neck, the face or on the
extremities. Vesiculation or frank blistering of the lesions occurs
very frequently in infancy [7]. Solitary mastocytomas are sometimes
associated with flushing and abdominal pain. In addition, there are
single reports of convulsions in response to stroking of a
mastocytoma or mastocytoma symptoms which resemble seizure
disorders [8, 9]. In rare cases a general histamine-flush might
appear [10, 11]. Differential diagnoses which need to be considered
include xanthomas, juvenile xanthogranulomas or melanocytic naevi,
bullous impetigo or epidermolysis bullosa. Physical stimulation of
the lesions with a blunt instrument or rubbing promotes the rapid
degranulation of mast cells accompanied by local erythema, oedema
and pruritus known as the Darier’s sign [12]. Histopathological
examinations reveal a dense infiltrate of mast cells in the upper
dermis.Treatment to control flushing or blistering consists of the
application of antihistamines, or alternatively hydrocolloid
dressings to cover the lesions [10].
Case report
We report the case of a 5-month old boy, who presented a 3 ×
5 cm sized, brownish-yellow, shiny infiltrated plaque with a
peau d’orange surface on the back of his right hand (figure 1). His parents
reported the occurrence of swelling and blistering of the lesion
about twenty times from the first month of life. Additionally they
referred to recurrent severe flushing reactions of unknown origin,
which occurred initially every two weeks with a decreasing
frequency during the last months. General laboratory examinations
did not show any abnormal blood counts besides a mild
lymphocytosis. The total serum IgE level was 20.1 kU/L and
corresponded to normal age-ranges. There was no allergen-specific
IgE detectable. To exclude an occult mastocytosis, we measured the
serum tryptase, which was within normal range (5.55 μg/L) at
baseline (mean of normal range 5.6 μg/L).
After mechanical irritation of the mastocytoma with a spattle
during the examination the boy immediately developed flushing of
the head, trunk (figure
2A, B) and extremities accompanied by cough and a bilateral
miosis. The symptoms disappeared within minutes after oral
administration of 7 drops of dimetinden. Two hours after this
incident the serum tryptase was measured again and revealed a-more
than quintuple increase up to a total value of 29.3 μg/L.
We diagnosed a solitary mastocytoma with episodes of general
flushing. We recommended daily intake of 2.5 mL of dimetinden
sirup and the avoidance of mechanical irritation of the skin lesion
in order to prevent further episodes of flushing and informed the
parents about the potential of histamine liberating drugs as
additional trigger factors of flush reactions. Under this treatment
the flushing episodes occurred less frequently and in a milder
form. In a follow-up control after one year a slight size reduction
of the skin lesion was observed.
Discussion
The great increase of serum tryptase after mechanical irritation of
the mastocytoma from normal to elevated ranges implicates a strong
degranulation of mast cells within the lesion, provoking not only
locally restricted, but also systemic effects such as flushing,
cough and miosis. Most strikingly, mast cells in a rather small
lesion seem to be able to release high amounts of tryptase leading
to an increase of the serum tryptase of more than 5-old the
baseline level.
Tryptase, as one of the various mediators derived from activated
mast cells, can be used as a specific marker and diagnostic tool to
evaluate the degree of mast cell activation [13]. The best
described mast cell product is the biogenic amine histamine, which
binds to the histamine receptors (H1R-H4R) expressed on different
cell types. Among multiple other effects, histamine leads to
vasodilatation via the H1-receptor by stimulating endothelial cells
to produce vascular smooth muscle relaxants such as prostacycline
and nitric oxide, which are assumed to be the main
pathophysiological correlates of histamine mediated flush
reactions. Histamine provokes bronchospasm and increased
peristalsis of smooth muscles of the bronchial and the respiratory
tract [14]. In this context, the strong release of histamine and
other mediators by mechanically activated mast cells derived from
the solitary mastocytoma might be responsible for the flushing and
the systemic reactions in our patient. For this reason the
prophylactic administration of antihistamines, which block H1R, is
necessary and should be strongly recommended to prevent episodes of
histamine provoked systemic reactions in severe cases of solitary
mastocytoma, as has already been established for the treatment of
urticaria pigmentosa [6, 15]. In addition, the administration of
mast cell stabilizators [16], topical application or intralesional
injection of corticosteroids [17], covering the lesion with
hydrocolloid dressings [10, 18] and excision [19] have been
described to be effective in the management of solitary
mastocytoma.
Physicians should avoid uncontrolled irritation of the
mastocytoma in order to provoke the Darier’s sign because of the
risk of systemic reactions, inform the parents about the connection
between the skin lesion and the systemic symptoms and instruct them
how to avoid mechanical irritation of the mastocytoma or intake of
histamine liberating agents. Furthermore an emergency kit
consisting of a liquid or suppository glucocorticosteroid and a
liquid H1R blocker should always be recommended and carried along
with the child.
Pronounced flushing episodes after irritation of mastocytoma
have been described in the literature before [6, 10, 20-24] and
have been shown to accompany increased histamine levels in urine
after the flush reactions, in some cases [25]. To our knowledge,
this is the first report about increased systemic tryptase levels
occurring after mechanical provocation of a solitary mastocytoma.
Therefore, measurement of serum tryptase after controlled
mechanical irritation of the mastocytoma might represent a helpful
diagnostic tool to identify patients with solitary mastocytoma with
an increased risk for systemic reactions, who might benefit from
transient prophylactic treatment with anstihistamines, to avoid
recurrent flush reactions.
Acknowledgements
Financial support: none. Conflict of interest: none.
Natalija Novak is supported by a Heisenberg-Fellowship of the
DFG no 454/3-1
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