ARTICLE
Dermatofibromas (DFs) are acquired benign dermal nodules of unknown etiology
commonly present on the lower extremities of adults, particularly women
[1, 2].
Usually a single lesion is present [1], three or more dermatofibromas
are possible, but multiple lesions (15 or more) grown with an eruptive
feature are rarely encountered [3-5].
The appearance of numerous lesions may be associated with systemic disorders,
more often with an autoimmune origin [6].
Generally, multiple dermatofibromas may be locally widespread [7, 8],
but the eruptive pattern is not frequently observed [9, 10].
We describe a case of several eruptive DFs involving the legs of a woman
with a 20 year history of mycosis fungoides treated, 9 months before,
with corticosteroideal systemic therapy for interstitial pneumonia.
Case report
A 51 year-old white woman presented to our dermatology clinic with recurring
erythematous-squamous plaques of mycosis fungoides on the trunk and arms
and with multiple papulo-nodular lesions of an eruptive appearance on
her legs. Personal anamnestical history revealed a 16 year history of
mycosis fungoides (cutaneous T cell lymphoma) for which she was repeatedly
treated with PUVA therapy (4 courses during the last 16 years) and UVB
therapy (2 courses in the last 2 years). For over 10 years she had suffered
from blood arterial hypertension and adult diabetes mellitus, and she
was being treated with oral alpha and ß blockers drugs and oral
sulphonil ureas. In March 1997, she underwent a protracted course of oral
antibiotics for fever, cough and dispnea, then finally hospitalized, in
June 1997, with a diagnosis of bilateral interstitial pneumonia. The therapy
was prednisone 25 mg twice daily for 3 weeks, progressively reduced to
37,5 mg every day for 3 weeks, then to 15 mg a day.
An antitubercular prophilaxis was necessary with Isoniazide 200 mg per
day and B6 vitamin 300 mg per day. In October 1997 she presented to us
for the recurrence of the lesions of mycosis fungoides and for the eruptive
appearance, for 2 months, of multiple nodular lesions on her legs. On
physical examination, leaving out the erythematous-squamous plaques and
macules, 14 firm, purple-red, randomly dispersed non-tender papules and
nodules ranging in size from 3 to 18 mm were noted on the anterior and
posterior surface of the legs: 10 on the right and 4 on the left leg (Fig.
1).
A cycle of UVB phototherapy (3 times/week for
1 month) reduced the lesions of mycosis fungoides.
One papular lesion of the leg was surgically removed.
Under a slightly acanthotic epidermis, a poorly demarcated dermal nodule
composed of irregularly interdigitating spindle-shaped fibrohistiocytotic
cells infiltrating between thickened collagen bundles and dilatated blood
vessels in the upper dermis was seen (Figs.
2 and 3).
This picture was consistent with the diagnosis of dermatofibroma. Immunohistochemical
studies for dermatofibromas disclosed: Vimentin (V9): positive, CD68 (KP1):
positive, S100 negative. In situ immunohistochemical analyses were
also made on cutaneous lesions of mycosis fungoides, disclosing a prevalent
population of atypical lymphocytes CD4+ with epidermal involvement
and the dermal component mainly composed of lymphocytes CD4+
with a minor population of lymphocytes CD8+. CD1 for Langerhans
cellls was not performed.
Peripheric population of lymphocytes was abnormal, disclosing an altered
ratio between CD4+ and CD8+, characterized by a
value of 4 (n.v. 1.20-2.00), as a result of an increased level of CD4+
(absolute number/mmc: 1020, n.v./mmc: 493-1772) and a reduction of CD8+
(absolute number/mmc: 255, , n.v./mmc 194-1129).
Laboratory findings showed a blood glucose level of 121 mg/dl, gamma
GT 61 U/L and GPT 62 U/L and no reduction of gammaglobulins. DR to bacterial
antigens was not performed.
Discussion
The occurrence of multiple dermatofibromas (DFs) is rare. The number
of 15 DFs in an individual was suggested to define the presence of multiple
DFs, although this number was arbitrarily chosen [7].
They have been reported in 21 patients with altered immune system. In
this group, association with SLE, myastenia gravis, Sijogren's syndrome,
ulcerative colitis, pemphigus vulgaris, atopic dermatitis and HIV infection
have been observed [11].
Moreover a history of immunosuppressive therapy before the onset of
the DFs was recorded in at least 11 cases. The autoimmune disease, the
immunosuppressive therapy or both may have promoted the development of
these lesions [12].
In the literature, drugs linked to the presence of multiple DFs, besides
corticosteroids, have been cyclophosphamide [5], azathioprine [12, 13]
and partially interferon alpha[14].
Moreover other 11 patients have been reported
to have multiple DFs without having an autoimmune disorder or receiving
immunosuppressive therapy [7, 15].
Five of these patients had additional medical conditions such as: diabetes
mellitus, obesity, hypercholesterolemia and/or hyperlipemia, hydronephosis
and hypertension [8, 15-17].
Similar to the location of DFs in healthy patients, the lower extremities
were the most common site in patients with multiple DFs, trunk and arms
being the other preferred locations.
Interestingly, most patients had DFs located at more than one site [12];
localized multiple DFs as in our case, have been reported very less frequently
[9, 10]. A predisposing condition linked to the presence of multiple DFs
in a particularly body site has not been discussed, but apparently was
excluded by the authors.
Our case seems to include all the described characteristics of multiple
DFs: the eruptive localized presence on a body area, the previous immunosuppressive
therapy with corticosteroids, the association with a systemic condition
like mycosis fungoides and the location on the legs in a female subject.
It is not known whether DFs represent a reactive [18] hyperplasia in
response to a trauma, such as insect bite or a true neoplasm.
The hypothesis of an arthropod bite has been debated [19], but the authors
concluded that the mechanical presence of arthropod tissue was not essential
for the growth of DFs.
An alternative emerging hypothesis as to the origin of dermatofibromas
[20] attributes their growth to an abortive immunoreactive process mediated
by dendritic cells which are strong antigen presenting-cells [21].
This proposed immune system disfunction could explain the increased
incidence of multiple DFs in immunocompromised patients, whatever the
cause.
REFERENCES
1. Fitzpatrick TB, Gilchrest BA. Dimple sign to differentiate benign
from malignant pigmented cutaneous lesions. N Engl J Med 1977;
296: 1518.
2. Niemi KN. The benign fibrohistiocytotic tumours of the skin. Acta
Derm Venereol (Stockh) 1970; 101: 588-90.
3. Rentiers PL, Montgomery H. Nodular subepidermal fibrosis (dermatofibroma
versus histiocytoma). Arch Dermatol 1949; 59: 568-83.
4. Berbis P, Benderitter T, Perier C, et al. Multiple clustered
dermatofibromas: evolution over 20 years. Dermatologica 1988; 177:
185-8.
5. Bargman HB, Fefferman I. Multiple dermatofibromas in a patient with
myastenia gravis treated with prednisone and cyclophosphamide. J Am
Acad Dermatol 1986; 14: 351-2.
6. Lu I, Cohen PR, Grossans ME. Multiple dermatofibromas in a woman
with HIV infection and systemic lupus erythematosus. J Am Acad Dermatol
1995; 32: 901-3.
7. Baraf CS, Shapiro L. Multiple histiocytoma. Arch Dermatol
1970; 101: 588-90.
8. Gelfarb M, Hyman AB. Multiple noduli cutanei: an unusual case of
multiple noduli cutanei in a patient with hydronephrosis. Arch Dermatol
1962; 85: 89-94.
9. Veraldi S, Boccor M, Gianotti R, et al. Multiple eruptive
dermatofibroma localized exclusively to the buttock. Int J Dermatol
1991; 30: 507-8.
10. Bedi TR, Pandhi RK, Bhutani LK. Multiple palmo-plantar histiocytomas.
Arch Dermatol 1976; 112: 1001-3.
11. Ammirati CT, Mann C, Hornstra IK. Multiple eruptive dermatofibromas
in three men with HIV infection. Dermatology 1997; 194 (4): 344-8.
12. Cohen PR. Multiple dermatofibromas in patients with autoimmune disorders
receiving immunosuppressive therapy. Int J Dermatol 1991; 30: 266-70.
13. Newmann DM, Walter JB. Multiple dermatofibromas in patients with
systemic lupus erythematosus on immunosuppressive therapy. N Engl J
Med 1973; 289: 842-3.
14. Murphy SC, Lowitt MH, Kao GF. Multiple dermatofibromas in an HIV-positive
man. Dermatology 1995; 190: 309-12.
15. Touraine A. Une nouvelle "chaîne" héréditaire:
fibromes cutanés, diabète, obésité. Ann
Dermatol Vénéréol 1951; 78: 409-16.
16. Omelucki A, Skwaczynska-Banys E, Zalewaska A, et al. An unusual
case of giant dermatofibroma in a patient with diabetes mellitus and necrobiosis
lipoidica. Cutis 1996; 58: 282-5.
17. Piérard J, Pernay R. Histiocytomes xanthomitisés multiples
de la peau. Arch Belg Derm Syphiligr 1952; 8: 122-6.
18. Barker SM, Winkelmann RK. Inflammatory lymphadenoid reactions with
dermatofibroma histiocytoma. J Cutan Pathol 1986; 13: 222-6.
19. Evans J, Clarke T, Mattacks CA, et al. Dermatofibromas and
arthropod bites: is there any evidence to link the two? Lancet
1989; 2: 36-7.
20. Nestle FO, Nickoloff BJ, Burg G. Dermatofibroma: an abortive immunoreactive
process mediated by dermal dendritic cells? Dermatology 1995; 190:
265-8.
21. Cerio R, Spaull J, Jones EW. Histiocytoma cutis: a tumour of dermal
dendrocytes (dermal dendrocytoma). Br J Dermatol 1989; 120: 197-206.
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