ARTICLE
Elastolysis and giant cells phagocytosing elastic fibers with granuloma
formation have been observed in annular elastolytic giant cell granuloma
(AEGCG) [1], and generalized granuloma annulare (GA) [2]. Annular centrifugal
lesions with a raised erythematous border are typical clinical manifestations
in AEGCG. However, as clinical variants, papules associated with annular
lesions have been reported in generalized GA [3] as well as AEGCG [4,5].
Herein, we report a case of elastolytic giant cell granuloma with papular
lesions but not annular lesions.
Case report
A 71-year-old Japanese man consulted us for red papules on the trunk
and upper arms, which were not pruritic. The individual papules were surrounded
by red halos, and tended to coalesce into papular plaques (Fig.
1a). These papular lesions resembled generalized granuloma annulare.
No centrifugal annular lesion was observed. Laboratory examination showed
elevated serum lysozyme (8.7 µg/ml, normal: 3.4-8.6), serum IgE (590
IU/ml, normal: < 165) and amylase (124 IU/l, normal: 43-116). The 75
g oral glucose tolerance test revealed impaired glucose tolerance. Other
hematological and biochemical examinations including serum angiotensine
converting enzyme showed no abnormality. Initially, he was treated with
oxatomide (60 mg/d) and topical steroid ointment (diflorasone diacetate)
for a month. The lesions responded poorly to the therapy. Biopsy of a
fresh papule of the back showed normal epidermis and intact collagen fibers.
However, epithelioid and many multinucleated giant cells in the upper
and mid dermis were observed (Fig. 2a,
b). Elastica van Gieson staining showed that elastic fibers in
the dermis were decreased in amount and fragmented, where multinucleated
giant cells phagocytosed fragmented elastic fibers (Fig.
2c). Necrobiosis or mucinous deposition was absent (Fig.
2d). These findings were consistent with AEGCG. Thereafter, we
treated him with tranilast (300 mg/d) replacing oxatomide. The papules
on the back gradually flattened and finally disappeared, leaving residual
pigmentation (Fig. 1b).
Discussion
In 1979, Hanke et al. [1] compared their five cases with atypical
necrobiosis lipoidica of the face and scalp [6], Mieschner's granuloma
of the face [7], and actinic granuloma [8], and proposed a new disease
entity, "annular elastolytic giant cell granuloma" (AEGCG). Histopathological
findings of AEGCG are characterized by loss of elastic fibers, no mucinous
deposition, without necrobiosis, and many multinucleated giant cells phagocyting
elastic material. AEGCG tends to accompany diabetes mellitus. The characteristic
clinical feature of AEGCG is centrifugal annular patches on sun-exposed
areas.
Generalized granuloma annulare (GA) is the most important differential
diagnosis from AEGCG, because elastophagocytosis is frequently observed
in generalized GA. The main differentiating points are that AEGCG shows
(1) absence of necrobiosis or mucinous deposition, and (2) several giant
cells in the dermis [1, 2]. In our case, histopathology showed scattered
epithelioid cells and many multinucleated giant cells in the upper and
mid dermis, loss and fragmention of elastic fibers, elastophagocytosis
by giant cells, without necrobiosis or mucinous deposition. These findings
were consistent with AEGCG. However, the lesions are not annular lesions
but papules on non-exposed areas, which is quite different from the original
AEGCG described by Hanke et al. [1].
As an unusual clinical variant, papular lesions
associated with AEGCG have been reported in two cases [4, 5]. It is generally
believed that the initial lesion of AEGCG consists of papules, which then
extend centrifugally and assume an annular pattern [5]. Ragaz and Ackerman
[9] considered that elastophagocytosis in AEGCG on exposed areas results
from non-specific skin damage caused by ultraviolet light (UV). These
views suggest that the papules in our case are very early lesions of AEGCG
and failed to form annular pattern, because they are located in sun-protected
skin. However, the case report [5] in which papular lesions with AEGCG
appear on exposed areas indicates that annular formation is also regulated
by other factors than UV.
Annular lesions with a similar histopathology to AEGCG have been also
reported in two case of sarcoidosis [10, 11]. However, in our case, the
abberrant laboratory data peculiar to sarcoidosis were not revealed. Together
with the histopathological findings, sarcoidosis would be ruled out in
our case.
Finally, tranilast was effective for the treatment.
Tranilast has been recommended as an alternative therapy for granulomatous
diseases, such as granuloma annulare [12] or cutaneous sarcoidosis [13].
Tranilast has three major pharmacological activities: (1) inhibition of
histamine release from mast cells; (2) inhibition of reactive oxygen species
generated by xanthine-xanthine oxidase; (3) anti-fibrotic activity due
to direct inihibiton of collagen synthesis of fibroblast [13]. The anti-fibrotic
activity seems to be a major mechanism of tranilast in resolving granulomatous
diseases [13]. Oral steroids [1], chloroquine [2], retinoid-PUVA [14],
cyclosporin [15] and dapsone [16] are effective systemic therapy for AEGCG.
However, they often provoke side effects, especially after long-term administration.
On the other hand, tranilast has been proved to have fewer major side
effects for long-term administration for the treatment of allergic diseases.
In this regard, tranilast is worth trying for the treatment of elastophagocytic
granuloma.
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