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usually deferred for 1–2 weeks, although the timing isa controversial issue.6 For an anticoagulated patient onwarfarin, this allows time for the warfarin to bestopped or the patient to be heparinised prior tosurgery.

Our patient had systemic risk factors associated withsuprachoroidal haemorrhage, namely advanced ageand atherosclerosis. In this case, we hypothesize thatthe macular disciform lesion bled and the haemorrhageextended extensively due to the increased clotting timeinduced by the warfarin.

This case illustrates the risk of visual loss due toocular haemorrhage in patients on anticoagulanttherapy. Medical staff should be aware of thepotentially devastating visual consequences ofanticoagulation above the normal therapeutic range.

References

1 Manuchehri K, Loo A, Ramchandani M, Kirkby GR.Acute suprachoroidal haemorrhage in a patient treatedwith streptokinase for myocardial infarction. Eye 1999; 13:685–686.

2 Edwards P. Massive choroidal hemorrhage in age-relatedmacular degeneration: a complication of anticoagulanttherapy. J Am Optom Assoc 1996; 67: 223–226.

3 Alexandrakis G, Chaudhry NA, Liggett PE, Weitzman M.Spontaneous suprachoroidal hemorrhage in age-relatedmacular degeneration presenting as angle-closureglaucoma. Retina 1998; 18: 485–486.

4 Khawly JA, Ferrone PJ, Holck DEE. Choroidalhemorrhage associated with systemic tissue plasminogenactivator. Am J Ophthalmol 1996; 121: 577–578.

5 Wong JS. Spontaneous suprachoroidal haemorrhage in apatient receiving low-molecular-weight heparin(fraxiparine) therapy. Aust NZ J Ophthalmol 1999; 27: 433–434.

6 Chu TG, Green RL. Suprachoroidal hemorrhage. SurvOphthalmol 1999; 43: 471–486.

FA Knox and PB Johnston

Department of OphthalmologyRoyal Victoria HospitalGrosvenor RdBelfast BT12 6BA, N Ireland

Correspondence: FA KnoxTel: 028 90 240503 ext 3612Fax 028 90 330 744E-mail: betty.doherty�royalhospitals.n-i.nh

Sir,

Orbital nodular-granuloma annulare in a juvenilediabeticEye (2002) 16, 670–673. doi:10.1038/sj.eye.6700184

Granuloma annulare is a benign granulomatousprocess of the dermis that commonly occurs inchildren and young adults, but may occur in any agegroup.1 The common, superficial lesions consist ofsmall, firm, asymptomatic papules grouped in a ring-like or circinate fashion.1 The less common variantsare: a generalised form consisting of hundreds ofpapules, perforating granuloma annulare, erythematousgranuloma annulare, subcutaneous granuloma annulareand a very rare deep destructive granuloma annulare.1

Granuloma annulare involving the peri-ocular dermishas been well documented.2–7 However orbitalgranuloma annulare is very rare.2,4,8,9 Although anassociation between dermal granuloma annulare anddiabetes has been documented, orbital granulomaannulare in insulin-dependent diabetes had not beenreported previously.10,11 We report a case of orbital,nodular-granuloma annulare occurring in a juvenilediabetic associated with a partial third nerve palsy.

Case report

A 29-year-old female insulin-dependent diabeticpresented with a 10-day history of left-sided red eye,double vision, abnormally large left pupil and ptosis.The visual acuity was normal in both eyes. In the leftproptotic eye, there was soft tissue mass bulgingthrough the superior and inferior bulbar conjunctiva ofthe left eye (Figures 1 and 2). The eye was proptotic.

Figure 1 Photograph of the left eye showing the soft tissuemass bulging through the superior bulbar conjunctiva—leftdown gaze.

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Figure 2 Photograph of the left eye showing the soft tissuemass bulging through the superior bulbar conjunctiva—rightdown gaze.

In addition, adduction and vertical eye movementswere limited in the left eye. The pupil was dilated onthe left side with an efferent pupillary defect. A Hesschart recording was in keeping with partial third nervepalsy. Except for background diabetic retinopathy therewere no other intra-ocular abnormalities. Also thepatient had a papular rash over the legs but there wasno systemic evidence of any connective tissue diseaseor arthritis. The ESR was 9 mm for the first hour andthe full blood and differential count was within normalrange. Serum rheumatoid factor was negative on twooccasions 6 months apart. Liver function tests werenormal. A chest x-ray was within normal limitswithout any evidence of hilar shadowing. The serologyfor ANF, ANCA, double stranded DNA, anti-treponemal antibodies were negative and angiotensinconverting enzyme was within normal range. CT andMRI scans of the orbit showed soft tissue thickeningcircumferential and right around the left globe (Figures3 and 4). Scanning of the brain was normal. A biopsyof the lesion was performed through a superior andinferior conjunctiva and fixed in formaldehyde.

Pathological examination

A biopsy was obtained through an inferior approach.The biopsy consisted of fibrous connective tissueshowing focal fibrinoid degeneration of collagen inwhich occasional karorrhectic nuclear fragments wereseen. This was surrounded by a palisade of epithelioidmacrophages, forming a granulomatous response(Figure 5). Surrounding lymphocytes were also presentbut neutrophils were not conspicuous. The necroticcentre of the granuloma showed a positive stainingreaction with alcian blue, a stain for mucin. Specialstains for organisms including bacteria,

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Figure 3 A CT scan of the orbit showing soft tissue thickeningcircumferential and right around the globe.

Figure 4 An MRI scan of the orbit showing soft tissue thicken-ing circumferential and right around the globe.

mycobacterium, atypical mycobacterium and fungi,were negative. Immunohistochemistry demonstratedexpression of the macrophage marker CD68 in manycells. Immunohistochemistry to CD3 demonstrated amoderate number of T cells, but very few B cells (CD20) were present. The biopsy through the superiorconjunctival biopsy also showed similar granuloma.

Postoperatively the eye was treated with topicalsteroid drops. The orbital lesion and the partial thirdnerve palsy resolved spontaneously over a period of 6months. Based on the clinico-pathological evidence adiagnosis of orbital nodular granuloma annulare wasmade which was thought to cause a partial third nervepalsy.

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Figure 5 Phtomicrograph showing focus of necrosis withfibrinoid material surrounded by a palisade of epitheliod cellsforming a granuloma (H&E × 200).

Comment

Granuloma annulare is a benign necrobiotic granulomawhich commonly affects the dermis in a localised ordisseminated form.1 Clinically the presentation may beclassified into papular, annular, perforating,erythematous and subcutaneous forms. The deep anddisseminated form of granuloma annulare was veryuncommon.1 Histologically, granuloma annulare showsinfiltrates of macrophages and epithelioid cells thatmay vary between a spectrum of an interstitial patternand a well-developed palisading granuloma. Thesesurround areas of collagen degeneration which showincreased amounts of dermal mucin.1,2,6–8 This feature,a hallmark of granuloma annulare, may be identifiedby a mucin stain such as alcian blue.1

The subcutaneous form of granuloma annularehistologically resembles the nodules of rheumatoidarthritis and rheumatic fever, which is characterised byareas of collagen degeneration in mucinous matrixsurrounded by palisading macrophages with epitheliodfeatures.1,12 The aetiology and pathogenesis of theselesions are not clear. Cell-mediated immune responseappears to be involved and is associated with releaseof lysosomal enzymes from macrophages into theextracellular space.1 Although vascular deposits of IgMand the third component of complement (C3) havebeen observed by some investigators, existence of avasculitic process has not been substantiated.1

Mesara et al introduced the term pseudorheumatoidnodule to describe subcutaneous nodules in children,indistinguishable from rheumatoid nodules, who hadno evidence of rheumatoid arthritis or rheumaticfever.12 In the ophthalmic literature, clinically andpathologically, identical ocular lesions have beenindependently reported as pseudorheumatoidnodules3,7–9,13 and granuloma annulare.4–6 To describe

these identical ocular lesions and to unify generalpathological, dermatological and ophthalmicdescription, Burnstine et al proposed the termgranuloma annulare-nodular type.2

Granuloma annulare may occur as an isolatedprocess, but a clear association has been foundbetween granuloma annulare and insulin-dependentdiabetes.1,11,12

Less commonly, similar lesions have been associatedwith a variety of conditions that include insect bites,herpes zoster, sarcoidosis, AIDS, systemic lupuserythematosus, and immunoglobulin mediatedvasculitis.1,10 Histopathologically granuloma annularemay resemble necrobiosis lipodica and both types ofgranulomas are known to occur in insulin-dependentdiabetics.1,10 Lipid-laden macrophages and fat necrosisare distinguishing features of necrobiosis lipoidica, andthe absence of these features eliminates necrobiosislipoidica in our patient.

The ophthalmic literature contains five cases oforbital granuloma annulare or pseudorheumatoidnodules in otherwise healthy young patients.4,7–9,13

Although Roa et al were probably the first to describeorbital involvement, their report lacked clinicalinformation and the anatomical site was not clearlystated.7 Floyd reported the first well-defined case ofgranuloma annulare in a healthy 8-year-old boy withrecurrent redness, proptosis and swelling of the rightlower lid simulating orbital cellulitis.9 In this childorbital extension from the lower lid was noted duringsurgical exploration. Ross et al reported a case ofgranuloma annulare involving the orbit and epi-sclerain a 29-year-old female patient with radiologicalevidence of retrobulbar extension.13 Orbital granulomaannulare, occurring as an isolated nodule in the lateralrectus has been recorded in a 13-year-old otherwisehealthy boy.8 The youngest patient with orbitalinvolvement reported was 2 years old presenting withnon-tender right superotemporal orbital mass.4 Theorbital involvement is usually non-tender and may beassociated with proptosis.4,8,9,13 Orbital granulomaannulare can be associated with episcleral, peri-ocularand general cutaneous involvement.4,13 Clinicallygranuloma annulare may simulate lymphomas,leukaemia, orbital pseudo tumours and metastatictumours and histological confirmation is essential. Inthe case we report, the CT and MRI scan of the brainwere normal and the partial third nerve palsy wasvery likely to be due to involvement of the nerve inthe orbit. Although orbital inflammatory conditionsmay involve orbital nerves, similar involvement inorbital granuloma annulare has not been reportedpreviously. Recovery of the nerve palsy occurredspontaneously, without any intervention and coincided

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with the resolution of the orbital lesion. The nervepalsy was painless and did not relate to diabetes. Theother causes of third nerve palsy were excluded. Basedon these observations we believe the nerve palsy couldbe related to the orbital granuloma. Resolutionoccurred spontaneously and many authorities haveadvised simple observation, while others advocateintra-lesional corticosteroids.2

In the case we report, no evidence for connectivetissue diseases was found and infective causes wereeliminated. Although orbital granuloma annulare indiabetes mellitus has not been reported previously, theassociation between granuloma annulare in severalother sites including the lid has been welldocumented.1,14,15 In this patient the orbital granulomaannulare may be related to diabetes. While orbitalgranuloma annulare is rare, it should be considered inthe differential diagnosis of granulomas affecting theorbit, especially diabetic patients.

References

1 Shapiro PE. Noninfectious granulomas. In: Elder D (ed).Lever’s Histopathology of the Skin. 8th edn. Lippincott-Raven: Philadelphia, 1997, pp 317–340.

2 Burnstine MA, Headington JT, Reifler DM, OestreicherJH, Elner VM. Periocular granuloma annulare, nodulartype. Occurrence in late middle age. Arch Ophthalmol1994; 112: 1590–1593.

3 Ferry AP. Subcutaneous granuloma annulare(‘pseudorheumatoid nodule’) of the eyebrow. J PediatrOphthalmol 1977; 14: 154–157.

4 Lawton AW, Karesh JW. Periocular granuloma annulare.Surv Ophthalmol 1987; 31: 285–290.

5 Mauriello JA Jr, Lambert WC, Mostafavi R. Granulomaannulare of the eyelid. Ophthal Plast Reconstr Surg 1996;12: 141–145.

6 McFarland JP, Kauh YC, Luscombe HA. Periorbitalgranuloma annulare. Arch Dermatol 1982; 118: 190–191.

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7 Rao NA, Font RL. Pseudorheumatoid nodule of theocular adnexa. Am J Ophthalmol 1975; 79: 471–478.

8 Choi KH, Wilbur AC, Duvall J, Miale TD, Tan WS.Orbital pseudorheumatoid nodule. Am J Neuroradiol 1985;6: 828–829.

9 Floyd BB, Brown B, Isaacs H, Minckler DS.Pseudorheumatoid nodule involving the orbit. ArchOphthalmol 1982; 100: 1478–1480.

10 Magro CM, Crowson AN, Regauer S. Granulomaannulare and necrobiosis lipoidica tissue reactions as amanifestation of systemic disease. Hum Pathol 1996; 27:50–56.

11 Romaine R, Rudner EJ, Altman J. Papular granulomaannulare and diabetes mellitus. Report of cases. ArchDermatol 1968; 98: 152–154.

12 Mesara BW, Brody GL, Oberman HA.‘Pseudorheumatoid’ subcutaneous nodules. Am J ClinPathol 1966; 45: 684–691.

13 Ross MJ, Cohen KL, Peiffer RL Jr, Grimson BS. Episcleraland orbital pseudorheumatoid nodules. Arch Ophthalmol1983; 101: 418–421.

14 Jelinek JE. Cutaneous manifestations of diabetes mellitus.Int J Dermatol 1994; 33: 605–617.

15 Haim S, Friedman-Birnbaum R, Shafrir A. Generalizedgranuloma annulare: relationship to diabetes mellitus asrevealed in 8 cases. Br J Dermatol 1970; 83: 302–305.

K Ramaesh1, S Bhagat1, SB Wharton2 and J Singh1

1Princess Alexandra Eye PavillionChalmer’s Street, Edinburgh, UK2Neuropathology LaboratoryDepartment of PathologyWestern General HospitalEdinburgh, UK

Correspondence: K RamaeshTel: 0131 536 1674Fax: 0131 536 3735E-mail: k.ramaesh�talk21.com