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Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy,
SHML) is a rare, non-hereditary, benign histiocytic proliferative
disorder mainly affecting young people with common clinical
characteristics such as painless bilateral cervical lymphadenopathy,
fever, leukocytosis and polyclonal gammopathy. Extranodal
manifestations have been reported in 28-43% of cases. Eye
involvement is relatively uncommon (8.5%), and most of cases
have presented as lymphoproliferation in the soft tissues
of the orbit and eyelids. Uveitis is an even more rare presentation
as a review of all the literature. We describe a 63-year-old
man with SHML with unusual ophthalmic manifestations of relapsing
uveitis and bilateral subconjunctival masses. The results
of biopsies were compatible with the characteristic histopathological
findings of SHML: focal aggregations of S100-positive foamy
histiocytes and the existence of lymphocytophagocytosis. During
the clinical course, the patient relapsed but the relapse
was relatively benign and the patient showed fair response
to topical as well as systemic corticosteroid treatment. Here
we describe this unusual presentation of SHML to inform physicians
of the possibility for this systemic granulomatous disease
to contribute to relapsing uveitis. (Chang Gung Med J 2002;25;621-5)
Key words: Rosai-Dorfman disease, uveitis, subconjunctival
mass.
Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy,
SHML) is a rare, idiopathic, benign proliferative histiocytic
disorder, which was first describeed by Rosai and Dorfman
in 1969 and 1972, respectively.(1,2) It affects mainly young
people with the slight predominance in the male population.
The characteristics of Rosai-Dorfman disease are bilateral
painless lymphadenopathy, fever, leukocytosis, and polyclonal
gammopathy. Extranodal involvement had been reported in 28-43%
of the cases with the skin as the most commonly involved site.
Ocular involvement is relatively rare (8.5%), and mostly manifested
as lymphoproliferation in the soft tissues of the orbit and
the eyelids.(1,2) Here we describe an unusual case of SHML
with ophthalmic manifestations of relapsing uveitis and bilateral
subconjunctival masses.
CASE REPORT
We describe a 63-year-old man who initially presented with
congested left eye for 2 months. On examination, bilateral
subconjunctival infiltrative lesions were noted (Fig. 1).
Under the suggestion of lymphoma, conjunctival biopsies as
well as systemic investigations were performed. The results
of biopsies showed only infiltration of reactive lymphoid
tissue initially. No systemic correlated symptoms such as
fever coexisted. Hence, due to the concomitant existence of
right-sided post-auricular lymphadenopathy and vocal cord
nodule, which was found due to symptom of hoarseness, biopsies
for were performed thereafter. The pathological result showed
infiltration of foamy and granular histiocytes along with
aggregation of plasma cells and lymphocytes, with the existence
of lymphocytophagocytosis. In addition, immunohistochemical
studies showed positive results for S100 protein and CD68,
all which were compatible with the histopathological characteristics
of SHML. Therefore, another conjunctival biopsy was performed
and the pathological and immunohistochemical reports confirmed
the diagnosis of SHML (Fig. 2). Laboratory investigation results
including hemogram, erythrocyte sedimentation rate (ESR),
serologic tests, and abdominal computed tomography scan, showed
positive results of minimal leukocytosis (10200/mm3), mildly
elevated ESR level (17 mm/hr), weakly positive anti-nuclear-antibody
titer (1:40), and elevated Epstein-Barr virus IgG titer (1:640),
without typical polycloncal gammopathy. Meanwhile, several
episodes of anterior as well as posterior uveitis developed
in his left eye during follow-up with manifestations of keratic
precipitates, cell/flare in anterior chamber, and vitreous
cell/opacity (Fig. 3), which showed fair response to systemic
oral and topical corticosteroid. Recurrence of bilateral conjunctival
masses was also noted during the 2-year follow-up period.
Cataract surgery and subsequent vitrectomy for cystoid macular
edema were performed in his left eye during the follow-up
period. At the last visit, the best corrected visual acuity
was 0.9 (od) and 0.4 (os), respectively without signs of uveitis
or subconjunctival masses noted.
DISCUSSION
SHML is a rare, idiopathic, benign proliferative histiocytic
disorder, which was established as a clinical entity by Rosai
and Dorfman in 1969 and 1972, respectively.(1,2) It affects
predominantly young people with the mean age at onset of 20
years.(3) Compared with the mean age, our patient is relatively
old (63 years old). The characteristics of SHML are bilateral
painless lymphadenopathy (90%), fever, leukocytosis and polyclonal
gammopathy.(3) The etiology of SHML remains unknown, may be
a reactive process to infection such as Epstein-Barr virus,
etc.(3) In our patient, we found only a possible correlation
in increased levels of IgG anti-Epstein-Barr-virus (1:640).
The diagnosis of SHML is histopathologic, based on the characteristics
of the proliferation of foamy histiocytes with round vesicular
nuclei and abundant, pale cytoplasm, showing lymphocytophagocytosis,(3)
and a S100 immunophenotype protein.(4) The prevalence of extranodal
involvement have been reported in 28-43% of cases, including
the skin, upper respiratory tract, salivary glands, epidural
space, bone and ocular adnexa. Ocular involvement is rare.
In the largest series of 243 cases reported by Foucar in 1990,
the eye was involved in 36 cases (8.5%) and was highly associated
with nasal sinuses involvement. Soft tissue of the orbit and
the eyelids infiltrations were the most common manifestations
of ocular involvement.(3,5) In addition, infiltration of the
lacrimal system, conjunctiva/subconjunctiva, cornea, uveal
tract, and optic nerve, have all been reported.(1-3,5-11)
Uveitis was present in six cases as found in a literature
reviewed: three isolated anterior uveitis,(3,5,6,10) one with
coexistent corneal infiltration,(11) one with coexistent papilledema,(12)
and one diagnosed pathologically after enucleation due to
post-traumatic uveitis.(3,5) Five cases had lymphadenopathy(3,5,6,11,12)
and one had only cutaneous involvement.(10) It had been proposed
as the expression of a proliferative process involving the
uveal tract (pseudouveitis). There was only one case histopathologically
confirmed with typical histiocytic infiltration in the uveal
tract after enucleation because of post-traumatic uveitis.
The rest were not histopathologically proven because it was
unnecessary to perform an ocular biopsy for such a benign
course. In our patient, the diagnosis was made using histopathologic
confirmation by biopsies of conjunctival lesions, lymph node,
and vocal cord nodule. Although intraocular biopsy were not
performed either, the concomitant existence of several documented
involving sites convinced us of the correlation of his relapsing
uveitis and underlying SHML.
The natural course of SHML is highly variable but relatively
benign and self-limiting, usually with spontaneous regression
after years.(3,13) Therefore the indications for treatment
remain obscure. Most often, an excisional biopsy is required
to establish the diagnosis. Surgery, radiotherapy, and chemotherapy
including vinca alkaloid, alkylating agents, and corticosteroids
are all options of treatment for those life-threatening or
function-threatening conditions, although the treatment might
not always be effective.(13,14) Excision of epibulbar lesion
has both diagnostic and therapeutic effects. Unlike our case,
no recurrence ever occurred after tumor excised in previous
reports.(7-9) Regarding the treatment of uveitis, the results
seem less efficient, as in our case. Topical and systemic
corticosteroids were administered in most cases with fair
results. Recurrence occurred in three cases, including our
case. Several episodes of recurrence developed in our patient
during the 2 years of follow up, with fair response to corticosteroids.
In spite of the setbacks, the disease course was relatively
benign.
In conclusion, we presented an unusual case of SHML with ophthalmic
manifestation as recurrent uveitis and subconjunctival masses,
which showed fair response to corticosteroid therapy. The
clinical course relapsed but was relatively benign. The subsequent
lymphadenopathy drew our attention to the fact that the systemic
granulomatous disease might contribute to the unusual presentation
of relapsing uveitis and subconjunctival masses.
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