REFERENCES

1. Shimomaye S. Recent developments in the treatment ofhuman papilloma virus. West J Med 1994;160:365–366.

2. Michel JL, Guigven Y, Leger F. Papilloma conjunctival a virusdes papillomes humains 6/11. Ann Dermatol Venereol 1996;123:90–92.

3. Vann RR, Karp CL. Perilesional and topical interferonAlfa-2b for conjunctival and corneal neoplasia. Ophthalmol-ogy 1999;106:91–97.

4. Schechter BA, Schrier A, Nagler RS, et al. Regression ofpresumed primary conjunctival and corneal intraepithelialneoplasia with topical interferon Alfa-2b. Cornea 2002;21:6–11.

5. Edwards I, Berman B, Rapini RP, et al. Treatment of cutane-ous squamous cell carcinomas by intralesional interferonAlfa-2b therapy. Arch Dermatol 1992;128:1486–1489.

Multiple Bilateral Eyelid MolluscumContagiosum Lesions Associated WithTNF�-antibody and MethotrexateTherapyClaus Cursiefen, MD, Mathias Grunke, MD,Claudia Dechant, MD, Christian Antoni, MD,Anselm Junemann, MD, andLeonard M. Holbach, MD

PURPOSE: To demonstrate a patient developing multiplebilateral eyelid molluscum contagiosum lesions after ini-tiation of TNF�-antibody therapy for rheumatoid arthri-tis.DESIGN: Single interventional case report.METHODS: Clinical, histopathologic, and immunologic-serological findings are presented.RESULTS: A 67-year-old patient with a 5-year history ofrheumatoid arthritis had been treated with prednisoneand methotrexate for the last 5 years. After initiation ofadditional TNF�-antibody treatment, complaints fromrheumatoid arthritis subsided, but multiple bilateral mol-luscum contagiosum lesions of upper and lower eyelidsoccurred despite normal or only slightly reduced CD4

(420-178/�l) and CD8 counts (143-58/�l). Histopatho-logic evaluation of the excised warts confirmed theclinical diagnosis. Under continued therapy, the wartshave been recurring for 12 months.CONCLUSION: TNF�-antibody treatment for rheumatoidarthritis may compromise the host response to mollus-cum contagiosum, especially if methotrexate is given

additionally. Patients should be informed about thispotential complication. (Am J Ophthalmol 2002;134:270–271. © 2002 by Elsevier Science Inc. All rightsreserved.)

MOLLUSCUM CONTAGIOSUM IS A POXVIRUS-INDUCED

skin tumor that usually is found only in children andimmunocompromised adults, for example, with AIDS oran iatrogenic reduction of CD4 counts.1,2 Occurrence ofmolluscum contagiosum in AIDS patients inversely corre-lates with CD4 counts and usually starts only if these fallbelow 100/�l, suggesting molluscum lesions to be a cuta-neous correlate of cellular immune deficiency.1,2 The meanCD4 count was 85.7/�l in a review of 27 HIV-patientswith molluscum contagiosum.1

We report on a 67-year-old woman who presented withmultiple bilateral molluscum contagiosum lesions of theupper and lower eyelids and predominantly normal CD4

and CD8 counts (Figure 1, top). The warts were surgicallyremoved three times over the last 12 months, but they stillrecurred. Histopathologic evaluation demonstrated typicalmolluscum contagiosum warts with viral inclusion bodies(Figure 1, bottom). Ophthalmic history and examinationwere otherwise unremarkable. General medical historyrevealed rheumatoid arthritis known for 5 years, which hadbeen treated with methotrexate (20 mg/week) and pred-nisone (5 mg/day) for the last 5 years. The onset ofmultiple bilateral molluscum warts followed initiation ofadditional continuous therapy with Infliximab, a TNF�-antibody,3,4 by 6 months (300 mg/every 6 to 8 weeks).TNF�-antibodies such as Infliximab have recently gaineda wider use for therapy of rheumatoid arthritis, inflamma-tory bowel, and inflammatory eye diseases.3,4 They inhibitthe proinflammatory effect of TNF�. Ocular side effectshave yet, to our knowledge, not been reported. The CD4

counts and CD4/CD8 ratio of the patient were nearlynormal or only moderately reduced during treatment withthe TNF�-antibody and in the time when mollusca oc-curred and recurred (CD4: 420-178/�l; CD8: 143-58/�l;CD4/CD8 ratio: 2.9). The patient had previously under-gone a 12-month and a 6-month course of Infliximab (3and 2 years ago); at the end of the 12-month course (3years ago), two unilateral skin lesions suggestive of mol-luscum warts had been removed by the primary carephysician (no histology or clinical picture is available, sothe true nature cannot be determined now).

Molluscum contagiosum has been shown to evade hostimmune responses by interfering with the TNF-receptor 1induced apoptosis (cell suicide) of virus-infected cells.5

Expression of viral proteins (such as MC159) interfereswith TNF-receptor 1 apoptotic signaling pathways, sug-gesting the existence of a strategy employed by viruses toattenuate host immune killing mechanisms.5 The TNF-mediated antiviral defense may be even further compro-mised in patients additionally receiving TNF�-antibodies,

Accepted for publication March 7, 2002.From the Department of Ophthalmology and University Eye Hospital

(C.C., A.J., L.M.H.) and the Department of Internal Medicine III(Immunology and Rheumatology) (M.G., C.D., C.A.), Friedrich-Alex-ander-University Erlangen-Nurnberg, Erlangen, Germany.

Inquiries to Claus Cursiefen, MD, Department of Ophthalmology andUniversity Eye Hospital, University of Erlangen-Nurnberg, Erlangen,Germany; fax: (�49) 9131-8536401; email: claus.cursiefen@augen.med.uni-erlangen.de

AMERICAN JOURNAL OF OPHTHALMOLOGY270 AUGUST 2002

for example, for rheumatoid arthritis. This may explain theoccurrence of multiple molluscum contagiosum warts de-spite CD4 and CD8 counts being normal or only moder-ately reduced during most of the time. This is in contrastto low CD4 counts associated with multiple molluscumlesions in immunocompromised patients, for example,with AIDS. Because we report only a single case, a merecoincidence of TNF�-antibody therapy and molluscumwarts or an association with methotrexate therapy2 cannotbe excluded. But the time sequence of initiation of therapyand the occurrence of warts, pathophysiologic plausibility,nearly normal CD4 and CD8 counts at the time oftreatment, and recurrence of molluscum warts under ther-apy argue in favor of an association of drug and molluscumlesions. Because this association has not been reportedbefore (http://www.remicade-ra.com) and may be related

to concomitant use of methotrexate in this patient, a largerseries of patients undergoing therapy with TNF�-antibodyshould be studied, and patients receiving TNF�-antibodiesshould be informed of this potential complication.

REFERENCES

1. Schwartz JJ, Myskowski PL. Molluscum contagiosum in pa-tients with human immunodeficiency virus infection: a reviewof twenty-seven patients. J Am Acad Dermatol 1992;27:58–588.

2. Cursiefen C, Holbach LM. Molluscum contagiosum in immu-nosuppression with methotrexate: multiple warts with centraldepression of the eyelids [in German]. Klin Monatsbl Augen-heilkd 1998;212:123–124.

3. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximaband methotrexate in the treatment of rheumatoid arthritis.Anti-tumor necrosis factor trial in rheumatoid arthritis withconcomitant therapy study group. N Engl J Med 2000;343:1594–1602.

4. Smith JR, Levinson RD, Holland GN, et al. Differentialefficacy of tumor necrosis factor inhibition in the managementinflammatory eye disease and associated rheumatic diseases.Arthritis Rheum 2001;45:252–257.

5. Hu S, Vincenz C, Buller M, Dixit VM. A novel family of viraldeath effector domain-containing molecules that inhibit bothCD-95- and tumor necrosis factor receptor-1-induced apopto-sis. J Biol Chem 1997;272:9621–9624.

Trypan Blue Capsular Staining to“Find” the Leading Edge of a “Lost”CapsulorhexisPeter W. T. de Waard, MD,Camille J. Budo, MD, andGerrit R. J. Melles, MD, PhD

PURPOSE: To describe an effective surgical technique tovisualize an obscured leading edge of a capsulorhexis.DESIGN: Prospective, interventional case series.METHODS: In six eyes of six patients in which thecapsulorhexis was started but could no longer be seenduring surgery, the anterior chamber was irrigated toremove all viscoelastic, and 0.3-ml trypan blue 0.06%was applied onto the anterior lens capsule to stain andvisualize the leading edge of the capsulorhexis.RESULTS: In all patients, the leading edge of the capsulo-rhexis was quickly visualized by using the dye. Noadverse reactions were observed up to 1 year aftersurgery.

Accepted for publication Feb 20, 2002.From the Rotterdam Eye Hospital, Rotterdam, The Netherlands

(P.W.T.d.W.), the Budo-Oogheelkunde, Sint-Truiden,Belgium (C.J.B.),and the Netherlands Institute for Innovative Ocular Surgery, Rotterdam,The Netherlands (G.R.J.M.).

Inquiries to Gerrit R. J. Melles, MD, PhD, Netherlands Institute forInnovative Ocular Surgery, H.A. Maaskantstraat 31, 3071 MJ Rotterdam,The Netherlands; fax: (�31) 10-485-2419; e-mail: melles@niioc.nl

FIGURE 1. (Top) Clinical aspect of one of multiple bilateralmolluscum contagiosum warts involving upper and lower eye-lids in a 67-year-old patient. The warts occurred after initiationof TNF�-antibody therapy for rheumatoid arthritis (in additionto steroids and methotrexate; arrow). (Bottom) Histopathologicsection of an excised molluscum wart demonstrates typicalmaturation of intracytoplasmic viral inclusion bodies from basalto superficial epithelium (arrow; hematoxylin and eosin, �25).

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