Ocular Immunology and Inflammation, 14:305–307, 2006Copyright ©c Informa HealthcareISSN: 0927-3948 print; 1744-5078 onlineDOI: 10.1080/09273940600878829

CASE REPORT

Uveitic Glaucoma and Rosai-DorfmanDisease (Sinus Histiocytosis)

Robert E. MacLarenHillingdon Hospital,Uxbridge, UK; andInstitute of Ophthalmology,University College, London, UK

Kulwinder S. HundalHillingdon Hospital,Uxbridge, UK

Peter TrittibachInstitute of Ophthalmology,University College, London, UK

Philip A. BloomHillingdon Hospital,Uxbridge, UK

ABSTRACT Purpose: To report a novel association of uveitic glaucoma withRosai-Dorfman disease. Methods: Case report. Results: A 67-year-old Caucasianwoman presented with a chronic bilateral granulomatous uveitis which did notrespond to conventional topical steroid therapy. She also had raised intraocularpressures, glaucomatous optic disc changes and diffuse nodular fibrous skin le-sions. Subsequent skin biopsy immuno-cytochemistry showed S-100 staining,consistent with Rosai-Dorfman disease. The uveitis and glaucoma were highlyresistant to standard medical treatments, but completely resolved together withthe systemic features of the disease after six months. Conclusions: Rosai-Dorfmandisease has not previously been reported to cause uveitic glaucoma and shouldbe considered in non-responsive cases presenting with a rash. The disease isentirely self-limiting and early diagnosis may therefore avoid unnecessary tra-beculectomy and/or systemic immune suppression.

KEYWORDS Uveitic glaucoma; Rosai-Dorfman disease; sinus histiocytosis

INTRODUCTIONRosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive

lymphadenopathy (SHML), is a rare, self-limiting, acute inflammatory condi-tion characterized by idiopathic histiocytic proliferation. It presents typicallywith massive painless cervical lymphadenopathy, fever, malaise, weight loss,and leucocytosis, but usually resolves within 2–3 years.1−2 RDD can also in-volve extra-nodal sites, most commonly the orbit, skin, paranasal sinuses, bone,salivary glands and, in rare cases, the central nervous system.3–6 Ocular involve-ment, however, is extremely rare and there are few cases reported in which RDDlesions have appeared coincident with bilateral uveitis.7−8 RDD causing glau-coma, however, has not previously been described, and here we report a novelassociation of RDD with uveitic glaucoma. The uveitis and glaucoma regressedspontaneously with the skin rash, which was initially presumed to be related tothe patient’s topical glaucoma medication.

Accepted 22 June 2006.

Correspondence and reprint requeststo: Robert E. MacLaren, Departmentof Ophthalmology, HillingdonHospital, Uxbridge, UK UB8 3NN. Tel:+44 7702 727853; E-mail: maclaren@herald.ox.ac.uk

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CASE REPORTA 67-year-old Caucasian woman presented with a

five-day history of painful red eyes, photophobia, andblurred vision. This was associated with a five-weekhistory of a sore throat and loss of voice, nasal si-nus pain, tiredness, weight loss, and pain in the smalljoints of her hands. She had no past ocular historyand previous optician readings of intraocular pres-sure (IOP) had been normal. General medical historyconsisted of diverticulitis and mild chronic obstruc-tive airways disease; the patient was an ex-smoker of1 year.

On examination the right eye visual acuity was Log-MAR 0.6 (0.4 with pinhole), and in the left eye wasLogMAR 0.32 (0.3 with pinhole). There was a bilateralinjection of the conjunctival limbus and sclerae, with2+ of cells in both anterior chambers. IOPs were raisedat 33 mmHg right eye and 34 mmHg left eye. Dilatedexamination showed that the vitreous was quiet bilat-erally, and the retina was normal. The optic discs werecupped, with a cup to disc ratio of 0.6 on the right and0.7 on the left. No focal notching of the optic discs wasnoted at this stage.

She was treated with topical dexamethasone 0.1%hourly, cyclopentolate 1% BD, and brimonidine 0.2%BD. Two weeks later, there was no improvement inher vision or symptoms, but the IOPs had reduced to23mmHg right and 25mmHg left. One month later, shereported having developed a rash over her neck, chest,back, and limbs (Fig. 1A). This was initially assumed tobe an allergic reaction to the topical brimonidine eyedrops.

Laboratory investigations, however, revealed sys-temic upset, with a normochromic normocyticanaemia, a raised ESR (112 mm/hr) and C-reactive pro-tein (73 mmol/l). She was also found to be mildly hy-pothyroid. ANCA and syphilis serology was negative.Serum ACE levels, glucose, calcium and electrolyteswere all normal, as were complement levels. She wasreferred to a dermatologist for further management. Asinus X-ray was clear, and a chest-ray showed apical cal-cification consistent with old tuberculosis. Her derma-tological assessment is described in detail elsewhere,9

but in brief, the diagnosis of RDD was confirmed by askin biopsy which revealed numerous histiocytes withlarge vesicular nuclei and abundant clear cytoplasm ex-pressing the S-100 antigen (Fig. 1B). She did not develop

FIGURE 1 (A) Macular rash appearing on the upper limb onemonth after the onset of symptoms in this case and initially be-lieved incorrectly to be an allergic reaction to the topical brimoni-dine eye drops. A similar pattern of rash was seen on the neck,chest and lower limbs. (B) Haematoxylin and eosin stain of askin biopsy shows typical histiocytes (ringed) which have palenuclei compared to infiltrating monocytes (arrows). Scale bar =100 µm.

the lymphadenopathy that is often associated with thedisease.

IOP was not controlled adequately on standard top-ical medications and subsequent ophthalmological ex-amination four months later revealed inferior notchingof the optic disc on the left side and a corresponding leftsuperior arcuate field defect. After a protracted courseof six months, however, the granulomatous uveitis re-solved spontaneously and the IOP returned to normal.The glaucoma therapy was discontinued shortly after-wards and the patient has remained disease free for thelast four years of follow-up.

DISCUSSIONRDD is a rare, benign disorder characterized by id-

iopathic histiocytosis of non-Langerhans cells and, al-though orbital involvement may be seen in 10% ofcases, intraocular involvement is extremely rare.1−2,6−7

The aetiology of this condition is unclear, althoughsome reports have suggested it may be related to

R.E. MacLaren et al. 306

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concurrent immune dysfunction, involving primarilyT-lymphocytes in exaggerated reaction to an infectiousagent.10 The presumed previous subclinical infectionof pulmonary tuberculosis in this case may thus besignificant. Conversely, in situ hybridization of RDDhistiocytes has demonstrated the presence of mRNAtranscripts for markers specific for cells of the mono-cyte/macrophage lineage.11 RDD has also been re-ported to cause a mild autoimmune thyroiditis andthe hypothyroid status of this patient may also berelevant.12

This case is interesting from the ophthalmologicalperspective for two principal reasons. First, uveitic glau-coma has not previously been reported in associationwith RDD. Without a biopsy it is not possible to besure whether the glaucoma occurred secondary to adeposition of anterior chamber cells in the trabecularmeshwork, or by direct trabecular infiltration with his-tiocytes. Nevertheless and in contrast to primary openangle glaucoma, the IOP returned to normal coincidentwith the regression of ocular and systemic symptoms,which makes the association with RDD highly likely.Second, the rash appeared one month after starting top-ical glaucoma medications and was initially believed tobe an allergic reaction to brimonidine.13 Fortunatelyan abnormal blood test led to a skin biopsy, which con-firmed the diagnosis. Since RDD is rarely considered asa cause of uveitis, it might be easy to ascribe the subse-quent skin rash to a non-specific vasculitis or medicalallergy. For this reason, RDD and its association withuveitis may be under-diagnosed. In this case the earlydiagnosis of RDD, which is an entirely self-limiting con-dition, avoided an unnecessary trabeculectomy and sys-temic immune suppression.

REFERENCES[1] Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopa-

thy. A newly recognized benign clinicopathological entity. ArchPathol. 1969;87:63–70.

[2] Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lym-phadenopathy (Rosai–Dorfman disease): review of the entity. SeminDiagn Pathol.1990;7:19–73.

[3] Wenig BM, Abbondanzo SL, Childers EL, Kapadia SB, Heffner DR.Extra nodal sinus histiocytosis with massive lymphadenopathy(Rosai–Dorfman disease) of the head and neck. Hum Pathol.1993;24:483–492.

[4] Katz DS, Poe LB, Corona RJ Jr. Sinus histiocytosis with massive lym-phadenopathy: a case of simultaneous upper respiratory tract andCNS disease without lymphadenopathy. AJNR. 1993;14:219–222.

[5] Asai A, Matsutani M, Kohno T, Fujimaki T, Tanaka H, KawaguchiK, Koike M, Takakura K. Leptomeningeal and orbital benign lym-phophagocytic histiocytosis. J Neurosurg. 1988;69:610–612.

[6] Resnick DK, Johnson BL, Lovely TJ. Rosai–Dorfman disease present-ing with multiple orbital and cranial masses. Acta Neuropathol (Berl).1996;91:554–557.

[7] Gaviria JG, Johnson DA, Kinney MC, Proffer LH, Losi-Sasaki JM,Kraus EW. Bilateral anterior granulomatous uveitis associated withcutaneous Rosai-Dorfman disease. Graefes Arch Clin Exp Ophthal-mol. 2005;243:281–284.

[8] Pivetti-Pezzi P, Torce C, Colabelli-Gisoldi RA, Vitale A, Baccari A,Pacchiarotti A. Relapsing bilateral uveitis and papilledema in sinushistiocytosis with massive lymphadenopathy (Rosai-Dorfman dis-ease). Eur J Ophthalmol. 1995;5:59–62.

[9] Salim A, Williamson M, Barker F, Hughes J. Steroid responsive cuta-neous Rosai-Dorfman disease associated with uveitis and hypothy-roidism. Clin Exp Dermatol. 2002;27:277–279.

[10] Perry BP, Gregg CM, Myers S, Lilly S, Mann KP, Prieto V. Rosai-Dorfman disease (extranodal sinus histiocytosis) in a patient withHIV. Ear Nose Throat J. 1998;77:855–858.

[11] Middel P, Hemmerlein B, Fayyazi A, Kaboth U, Radzun H-J.Sinus histiocytosis with massive lymphadenopathy: evidence for itsrelationship to macrophages and for a cytokine-related disorder.Histopathology. 1999;35:525–533.

[12] Tamouridis N, Deladetsima JK, Kastanias I, Delis S, Bramis J, ZervaCA, Anapliotou ML. Cold thyroid nodule as the sole manifestationof Rosai-Dorfman disease with mild lymphadenopathy, coexistingwith chronic autoimmune thyroiditis. J Endocrinol Invest.1999;22:866–870.

[13] Osborne SA, Montgomery DM, Morris D, McKay IC. Alphaganallergy may increase the propensity for multiple eye-drop allergy.Eye. 2005;19:129–137.

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