We present two cases of Behcet\u27s Disease with severe eye problems along with oral and genital ulcerations. Both cases, initially were treated with steroids and oral immunosuppressive agents, but did not show a response and ocular disease became worse. Both the cases were kept on Infliximab therapy. an immediate positive response with improvement in vision and symptoms was seen. After initial infusions the ocular damage in both the cases stopped

Ishaq, Saliha

Jawad, Majid

Saeed, Anum

English

eCommons@AKU

eCommons@AKUSection of Internal Medicine Department of MedicineNovember 2012Regression of severe Behcet's eye disease withinfliximab therapy; first two cases treated inPakistanSaliha IshaqAga Khan University, saliha.ishaq@aku.eduAnum SaeedMajid JawadFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_medRecommended CitationIshaq, S., Saeed, A., Jawad, M. (2012). Regression of severe Behcet's eye disease with infliximab therapy; first two cases treated inPakistan. Journal of Pakistan Medical Association, 62(11), 1242-1244.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_med/90AbstractWe present two cases of Behcet's Disease withsevere eye problems along with oral and genital ulcerations.Both cases, initially were treated with steroids and oralimmunosuppressive agents, but did not show a response andocular disease became worse. Both the cases were kept onInfliximab therapy. an immediate positive response withimprovement in vision and symptoms was seen. After initialinfusions the ocular damage in both the cases stopped.Keywords: Behcet's disease, Ocular disease, Uveitis,Infliximab, Anti TNF-alpha drugs.IntroductionBehçet's Disease (BD) is rare chronic multisystemimmune-mediated inflammatory disorder, characterized byrecurrent oral and genital mucocutaneous ulcerations witharticular, neurological, gastrointestinal andophthalmological and neurological disease involvement.Ocular involvement presents as bilateral non granulomatouspanuveitis, retinal and choroidal vasculitis, optic neuritisand retinal vascular occlusion. Although, BD has aworldwide distribution, it is rare in North Americanpopulation and Europe. Prevalence is higher in Turkey,Middle and Far East region, affecting mainly young adults,having more severe vascular complications.1According to the International Study Group criteria,the diagnosis of BD requires the presence of recurrent oralulceration along with any two conditions: recurrent genitalulceration, eye lesions, skin lesions or a positive skin test.The diagnosis is clinical because there is no specificevidence, pathognomonic symptoms or specific laboratoryfindings.1Behçet's entails recurrent attacks of acuteinflammation and generally, does not run a chronicpersistent course. Involvement of gastrointestinal tract,central nervous system, and large vessels is occasional,and can be life-threatening.1 The most fearedcomplication of BD is irreversible vision loss.Susceptibility to BD is associated with HLA-B51 allele.Environmental factors such as infectious agents havebeen implicated in its pathogenesis. Corticosteroids and immunosuppressants are themainstay for treating this disease, however, an increasingnumber of refractory cases occur. Recently, Infliximab andother tumour necrosis factor inhibitors have shown dramaticresults in treating various manifestations of BD. Case PresentationCase-1:A 23-year male, presented with history of recurrentulcers in mouth and genital tract, blurring of vision andarthralgias, since one year. The patient had apthous ulcersin the mouth, on glans penis and scrotum. He alsocomplained of occasional redness in the eyes along withgradual decrease in vision and arthralgias. A diagnosis ofBD was made. On eye examination patient was found tohave a low visual acuity (V/A). The left eye had a V/A of20/400 while right eye V/A was worse at, "counting fingersat 2 feet" secondary to severe panuveitis. The IOP wasnormal at 14 mmHg bilaterally. ESR was 51, CRP was high23. He was kept on Prednisolone and Azathioprine. In thenext few months, his follow up visits showed worseningV/A secondary to repeated attacks of uveitis in both eyesdespite getting Azathioprine, three bilateral intraocularinjections of Bevacizumab and, systemic as well asintraocular steroids. The patient's V/A detoriated furtherduring therapy, patient had "Perception of Light" bilaterallya month ago, before referral to Rheumatology clinic. Hewas then switched to Infliximab therapy. An immediateeffect was seen after the first dose leading to stabilizedvision. He received three doses of Infliximab over a periodof seven months (total time for his treatment at AKU wastwo years) until his uveitis attacks got settled. Patient's V/Aimproved to "Counting Fingers at 4 feet" bilaterally, he wascontinued on Azathioprine and low dose Steroids formaintenance therapy. Case-2:A 29-year-old male presented with history ofrecurrent oral and genital ulcers, vision problems and lowVol. 62, No. 11, November 2012 1242Regression of severe Behcet’s eye disease with Infliximabtherapy; first two cases treated in PakistanSaliha Ishaq,1 Anum Saeed,2 Majid Jawad3Department of Medicine, Aga Khan University Hospital,1 Ziauddin University Hospital,2,3 Karachi.Corresponding Author: Saliha Ishaq. Email: saliha.ishaq@aku.eduCase Reportgrade fever for few months. His major complaint wasdecreased vision with redness and pain in both eyes. Onexamination, the patient had numerous apthous ulcers in themouth and on glans penis. Eye exam showed diffuseanterior uveitis and V/A of "counting fingers at 2 feet" and"20/400" in right and left eye, respectively. The IOP wasmeasured to be at 18 mmHg (within normal range of 10-21mmHg). Diagnosis of BD was made. His ESR was 62, CRPwas 12 and a positive ANA was present. Oral steroids withAzathioprine were started. Despite high dose therapy for afew months, his V/A continued to deteriorate with relapsesof anterior uveitis. He was then started on intravenousInfliximab therapy. After the first two doses the intensity ofocular inflammation weaned off gradually. However, afterthe second dose of Infliximab, the patient developedreactivation of pulmonary Tuberculosis thus the drug waswithheld. Confirmed by a Purified protein derivative (PPD)test and a chest radiograph, acute tuberculous treatment(ATT) was given for 6 months. He recovered frompulmonary tuberculosis successfully, Infliximab was thenstarted. Patient's Intraoccular pressure (IOP) remained atbaseline 18 mmHg throughout his treatment. Patient's righteye vision was lost due to recurrent attacks of Uveitis andretinal vasculitis, however, the left eye vision (V/A 20/400)has been sustained after treatment with Infliximab. DiscussionBD was first depicted in 1937 by a Turkishdermatologist named Hulusi Behçet. Behçet referred to BDas a "complex of recurrent oral ulcers, genital sores, andhypopyon uveitis that could lead to blindness."2 Ocularinvolvement of BD, which is basically in the form ofanterior and posterior uveitis, cataracts, conjunctivitis orretinal vasculitis, is the most feared symptom of the disease.Eye inflammation, which occurs in 70% of cases,1 isconsidered one of the major criteria upon which thediagnosis is based. The ocular disease is characterized byrepetitive and explosive inflammatory attacks, which cansubside spontaneously or with treatment. Disease affectingthe back of eye, is sight threatening, may produce macularoedema, retinal swelling and haemorrhage, andinflammation of blood vessels. Despite therapeuticintervention, about 25% of people with ocular lesionbecome blind.3 Early age of onset and male gender are badprognostic factors for ocular disease.4 In a study of BD,ocular disease was bilateral in 78.1% and panuveitis was themost common finding. Risk of losing vision within 10 yearswas 30% for men and 17% for women.5Corticosteroids and immunosuppressants have beenthe drugs of choice for BD. Topical mydriatic agents andcorticosteroids are used initially for mild disease withrecurrences if steroids are used as a monotherapy. Trialshave shown that Azathioprine and Cyclosporine, Colchicineare effective for treatment of Behcets uveitis.6,7Recent advances in medical treatment of BD haveshown TNF-Alpha inhibitors as a new effective drug.8,9Infliximab, a chimeric monoclonal antibody to TNF-α, wasinitially developed to treat systemic inflammatory disorderssuch as rheumatoid arthritis and Crohn's disease. Levels ofTNF-α (as well as other pro inflammatory cytokines) areelevated in active BD thereby suggesting that anti-TNF-αtherapy is valuable. Clinically, significant improvement ofvarious BD manifestations with infliximab therapy, andother Anti-TNF therapies, has been reported in literature.9Biologics like Infliximab have successfully beenreported to treat resistant Neuro- Bechets disease, eyethreatening panuveitis and severe mucocutaneouslesions.8,10 The success of this drug in treating acute uveitisin patients with BD is secondary to high serum levels thedrug can achieve. A Japanese study of relationship betweenserum Infliximab levels and acute uveitis, done in 2010,concluded that serum concentration of Infliximab in eachpatient was significantly correlated with its effectiveness insettling recurrent episodes of uveitis.11 An Open Label Trialconducted recently, showed that infliximab is effective insuppressing the occurrence of uveitis attacks and also has asignificant corticosteroid sparing effect.12Here, we reported two cases of severe Bechets eyedisease treated successfully with Infliximab.Despite one of our patients developing reactivationof Pulmonary Tuberculosis after second Infliximab waswithheld and resumed after 6 months, which was theduration for which ATT was given.ConclusionBD can be incapacitating if not treated aggressively,its complications, include complete blindness. There is asevere need to assess patients by a multi-disciplinary teamto start and adjust therapy on time to prevent complications.As per our reports, Infliximab is an effective therapeuticchoice for steroid and other immunosuppressant resistantocular involvement of BD. References1. Sakane T, Suzuki N, Inaba G, Takeno M. Behçet's disease. N Engl J Med1999; 341: 1284-91.2. Akpe EK, Weinber RS. Uveitis society. (Online) 2003 (Cited 2011 Aug 14).Available from URL: http://www.uveitissociety.org/pages/diseases/behcets.pdf.3. Nussenblatt RB. Uveitis in Behçet's disease. Int Rev Immunol 1997; 14:67-79.4. Kastner DL. Intermittent and periodic arthritic syndromes. In: Koopman WJ,ed. Arthritis and allied conditions: a textbook of rheumatology. 13th ed.Baltimore: Williams & Wilkins, 1997; 1279-306.5. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huserin Altumbas H,Urqancioqlu M et al. Uveitis in Behçet disease: an analysis of 880 patients.1243 J Pak Med AssocAm J Ophthalmol 2004; 138: 373-80.6. Masuda K, Urayama A, Kogure M, Nakajima A, Nakae K, Inaba G. Double-masked trial of cyclosporin versus colchicines and long-term open study ofcyclosporin in Behcet's disease. Lancet 1989; 1: 1093-6.7. Ozyazgan Y, Yurdakul S, Yazici H, Tuzun B, Iscimen A, Tuzun Y. Low dosecyclosporin A versus pulsed cyclophosphamide in Behc¸et's syndrome: asingle masked trial. Br J Ophthalmol 1992; 76: 241-3.8. Almoznino G, Ben-chetrit E. Infliximab for the treatment of resistant oralulcers in Behçet's disease: a case report and review of the literature. Clin ExpRheumatol 2007; 25: S99-102.9. Curigliano V, Giovinale M, Fonnesu C, Cerquaglia C, Verrecchia E, Turco S,et al. Efficacy of etanercept in the treatment of a patient with Behçet's disease.Clin Rheumatol 2008; 27: 933-6.10. Ribi C, Sztajzel R, Delavelle J, Chizzolin C. Efficacy of TNF [alpha] blockadein cyclophosphamide resistant neuro-Behcet disease. J Neurol NeurosurgPsychiatry 2005; 76: 1733-5.11. Sugita S, Yamada Y, Mochizuki M. Relationship between serum infliximablevels and acute uveitis attacks in patients with Behçet disease. Br JOphthalmol 2011; 95: 549-52.12. Tugal-tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu E, Inanc M,Gül A. Efficacy of infliximab in the treatment of uveitis that is resistant totreatment with the combination of azathioprine, cyclosporine, andcorticosteroids in Behçet's disease: an open-label trial. Arthritis Rheum 2005;52: 2478-84.Vol. 62, No. 11, November 2012 1244

Regression of severe Behcet\u27s eye disease with infliximab therapy; first two cases treated in Pakistan

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Regression of severe Behcet\u27s eye disease with infliximab therapy; first two cases treated in Pakistan

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