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[Dermatology Reports 2010; 2:e17] [page 45]

The interaction of inflammatory
cells in granuloma faciale 
Takeshi Nakahara,1 Yoichi Moroi,1
Akari Tashiro,1 Hiromaro Kiryu,2
Masutaka Furue1
1Department of Dermatology, Graduate
School of Medical Sciences, Kyushu
University, Fukuoka, Japan;
2Department of Dermatopathology, Kiryu
Clinic, Fukuoka, Japan

Abstract 

Granuloma faciale (GF) is a rare chronic
inflammatory skin disease characterized by
single or multiple reddish-brown cutaneous
plaques or nodules. Although this condition is
benign, its clinical course is extremely chronic
with poor response to therapy. The typical
histopathological features of GF include vas-
culitis with mixed cellular infiltration; howev-
er, its etiopathogenesis remains unknown.
Here, we describe the case of a 76-year-old
man with GF resistant to topical steroids.
Biopsy of the lesion revealed i) dense mixed
inflammatory cellular infiltrates of lympho-
cytes, histiocytes, neutrophils, and eosino -
phils, ii) mild perivascular nuclear dust and
swollen endothelium of blood vessels, and iii)
a narrow Grenz zone beneath the epidermis.
Immunohistochemical staining demonstrated
mixed cellular infiltrates intermixed with
CD1a+ dendritic cells, CD68+ histiocytes, and
CD4+ and CD8+ T cells. 

Introduction

Granuloma faciale (GF) is a chronic inflamma-
tory skin disorder appearing as a solitary lesion or
multiple reddish-brown infiltrating lesions on the
face, usually on the cheeks, nose, and forehead.
Although its etiopathogenesis remains unknown,
vasculitis with mixed cell inflammation is consid-
ered to be the typical histological feature.1

Exposure to sunlight is regarded as a triggering
factor; however, other causative factors such as
infections, immunological disorders and associat-
ed malignancies might be responsible for its
pathogenesis.2 Recently, the production of inter-
leukin (IL)-5 by the clonal T-cell population has
been implicated in the attraction of eosinophils to
the lesions.3 Here, we report a male patient who
was clinically and histopathologically diagnosed
with GF. Mixed cellular infiltrates intermixed with
CD1a+ dendritic cells (DCs), CD68+ histiocytes,
and CD4+ and CD8+ T cells were detected
immunohistochemically. 

Case Report

The patient was a 76-year-old male who
developed a reddish-brown cutaneous plaque
with exaggerated follicular openings on the left
cheek (Figure 1a and b). The lesion was slight-
ly elevated and slowly progressive, and showed
no response to topical steroids. No underlying
associated disease was detected, and his rou-
tine laboratory examinations were all within
the normal limits. Screening for antinuclear
antibodies was negative. Clinically, GF, sar-
coidosis, discoid lupus erythematosus, follicular
mucinosis and pseudolymphoma were consid-
ered as differential diagnosis.

Punch biopsy from the lesion showed a dense
dermal inflammatory and granulomatous infil-
trate of mononuclear cells with numerous
eosinophils and neutrophils. The features of
mild leukocytoclastic vasculitis: perivascular
neutrophilic infiltrate with debris and swollen
endothelium of blood vessels were also evident.
Stromal fibrosis was found around the granulo-
matous lesions. A narrow Grenz zone was also
observed beneath the epidermis, and adnexal
structure was intact (Figure 2a and b). These
histopathological findings were consistent with
GF. Immunohistochemically, both CD8+ lympho-
cytes and CD68+ histiocytes were present main-
ly inside the granulomatous lesions (Figures 3a
and b), whereas scattered CD4+ lymphocytes
and CD1a+ DCs surrounded the lesions, and to a
lesser extent, occurred within the lesions
(Figure 3c and d). The cutaneous plaque lesion
was treated with local injection of a corticos-
teroid. In a few months of treatment, infiltration
was reduced but the reddish-brown cutaneous
plaque lesion persisted. 

Discussion 

GF is a rare inflammatory skin disease
with typical clinical and histopathological
entity. A previous extensive review of GF
comprising 66 patients revealed that more
than 90% of the patients had only facial
lesions and 62% of the patients of this series
had a solitary lesion. GF has a tendency to
appear in areas exposed to sunlight, such as
the forehead, cheek, and nose.4 It is mostly
asymptomatic but occasional burning or itch-
ing sensation is experienced. Dense granulo-
matous infiltration of lymphocytes, plasma
cells, neutrophils, histiocytes and eosino -
phils is observed in the reticular dermis.
Interestingly, a typical granulomatous lesion
predominantly composed of histiocytes does not
normally occur in GF, making GF one of the mis-
nomers in dermatology. Fibrous tissue accompa-
nying capillary proliferation can be observed in
old lesions. One of the most important

Dermatology Reports 2010; volume 2:e17

Correspondence: Takeshi Nakahara, 3-1-1
Maidashi, Higashiku, Fukuoka 812-8582, Japan,
E-mail: nakahara@dermatol.med.kyushu-u.ac.jp

Key words: granuloma faciale, dendritic cells,
helper T cells, histiocytes

Received for publication: 2 August 2010.
Revision received: 25 October 20010.
Accepted for publication: 1 November 2010.

This work is licensed under a Creative Commons
Attribution 3.0 License (by-nc 3.0).

©Copyright T. Nakahara et al., 2010
Licensee PAGEPress, Italy
Dermatology Reports 2010; 2:e17
doi:10.4081/dr.2010.e17

Figure 1. (a) Solitary, reddish-brown
plaque on the left cheek. (b) Exaggerated
follicular openings on the plaque.

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[page 46] [Dermatology Reports 2010; 2:e17]

histopathological findings in GF is the presence
of the Grenz zone, which is an area between the
epidermis and the upper dermis devoid of cells.1,4

Thus, the present case showed representative
clinical and histopathological features of GF.

For the clinical differential diagnosis, sar-
coidosis, lupus vulgaris, fungal infections, dis-
coid lupus erythematosus, follicular mucinosis,
and pseudolymphoma should be considered.1-4

Histopathological examination is useful in dis-
tinguishing GF from other diseases.
Histopathological differential diagnosis of GF
should be made with erythema elevatum
diutinum (EED). Similar to GF, EED starts with
the appearance of neutrophils and neutrophilic
nuclear dust around small vessels containing
fibrin in their wall.5 In most EED cases, the erup-
tion is bilateral and symmetric. Histopa -
thologically, eosinophils are few or absent and
neutrophils predominate with plasma cells only
present episodically. The sites of EED predilec-
tion are different – the face is usually spared,
and the skin on the dorsal aspects of joints is
usually the target site. 

Different etiologies regarding the pathogene-
sis of GF have been suggested, but most of them
remain controversial. Because light-exposed
areas are favored as exemplified in the majority
of GF cases with facial involvement, actinic
exposure has been suggested to play an impor-
tant role.4 It is suggested that it may be a form of
vasculitis mediated by localized Arthus-like

response.6 It might also be due to a localized per-
sistent immune complex disease or persistent
allergic hypersensitivity reaction to a retained
antigen or both.6 Selvaag and Roald showed in
their immunohistochemical study of GF that
eosinophils have a strong reaction to eosinophil
cationic protein antibodies, and are activated;
thus, they claimed that eosinophils play an
important etiologic role.7 Immunohisto -
chemically, CD4+ lymphocytes and a high lesion-
al production of IL-5, a cytokine important for
eosinophil recruitment3 were observed. In line
with previous reports, our results suggest that
the interaction between DCs and helper T cells
might be one of the important factors for the for-

mation of lesions because DCs can modulate
helper T cell functions such as cytokine produc-
tion. Although multiple treatments of GF have
been attempted, beneficial therapeutic effects
have not yet been observed. Local therapies have
also been used, including surgical excision,
cryotherapy, and laser therapy;8 however, most of
these may result in pigmentation changes or
scarring. Recently, a number of reports on the
successful use of tacrolimus in GF have been
published.9,10 Tacrolimus decreases the number
of Langerhans cells and antigen-presenting cells
in the skin and inhibits the propagation of the
inflammatory cascade. Because an immunopa -
thological etiology is suspected in our study and
previous reports, it was assumed that local con-
trol of the interaction of DCs and helper T cells
by topical immunosuppressants may show a pos-
itive therapeutic effect.

References

1. LeBoit PE. Granuloma faciale: a diagnosis
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2. De D, Kanwar AJ, Radotra BD, Gupta S.
Extrafacial granuloma faciale: report of a
case. J Eur Acad Dermatol Venereol 2007;21:
1284-6. 

3. Gauger A, Ronet C, Schnopp C, et al. M. High
local interleukin 5 production in granuloma
faciale (eosinophilicum): role of clonally
expanded skin-specific CD4+ cells. Br J
Dermatol 2005;153:454-7. 

4. Ortonne N, Wechsler J, Bagot M, et al.
Granuloma faciale: a clinicopathologic study
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5. Konohana A. Extrafacial granuloma faciale. J
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6. Marcoval J, Moreno A, Peyr J. Granuloma
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7. Selvaag E, Roald B. Immunohistochemical
findings in granuloma faciale. The role of
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Dermatol Venereol 2000;14:517-8. 

8. Ludwig E, Allam JP, Bieber T, Novak N. New
treatment modalities for granuloma faciale.
Br J Dermatol 2003;149:634-7.

9. Marcoval J, Moreno A, Bordas X, Peyrí J.
Granuloma faciale: treatment with topical
tacrolimus. J Am Acad Dermatol 2006;55:
S110-1.

10. Tomson N, Sterling JC, Salvary I. Granuloma
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Case Report

Figure 2. Histopathological characteristics
of the plaque lesion. (a) A dense dermal
inflammatory and granulomatous infil-
trate of mononuclear cells with numerous
eosinophils and neutrophils.(original mag-
nification x40). (b) Mild leukocytoclastic
vasculitis: perivascular neutrophilic infil-
trate with debris and swollen endothelium
of blood vessels are evident. Stromal fibro-
sis is observed around the granulomatous
lesions. (original magnification x400).

Figure 3. Predominant infiltration of
CD68+ histiocytes (a) and CD8+ lympho-
cytes (b) into the granulomatous lesions,
and CD4+ lymphocytes (c) and CD1a+
dendritic cells (d) around the lesions. 

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