Clin Rheumatol (2012) 31:1403–1405 DOI 10.1007/s10067-012-2035-z
CASE BASED REVIEW
Risedronate-associated scleritis: a case report and review of the literature Iman Hemmati & John Wade & John Kelsall
Received: 14 June 2012 / Accepted: 4 July 2012 / Published online: 5 August 2012 # Clinical Rheumatology 2012
Abstract This paper presents the first reported case of risedronate-associated scleritis and conducts a review of bisphosphonates and inflammatory eye diseases. A case of scleritis associated with risedronate use in a 73-year-old Chinese woman is reported. The English medical literature was reviewed for bisphosphonates and their association with inflammatory eye diseases. Cases of ocular inflammation in patients taking bisphosphonates have been reported since the early 1990s. Reported cases include both nitrogen- and nonnitrogen-containing bisphosphonates and with both intravenous and oral use. We report the first case of risedronateinduced scleritis. The case involves a 73-year-old woman who developed scleritis following exposure to risedronate in 2007 with recurrence of scleritis upon risedronate exposure again in 2009. Discontinuation of risedronate and treatment with intravenous and topical corticosteroids resulted in both clinical and radiological improvements within 24 h. Applying Naranjo's adverse drug reaction probability scale, a causality assessment was made which categorized this reaction as definite with a score of 9. In our case, there was a strong causal relationship between the use of risedronate and scleritis. Although rare, ocular adverse effects of bisphosphonates may be serious and should be made known to prescribing physicians. This is important in the practice of rheumatology as many of the patients are prescribed this class of medication for either prevention or treatment of osteoporosis. Moreover, ocular
I. Hemmati Department of Medicine, University of British Columbia, 202-1160 Burrard Street, Vancouver, BC, Canada V6Z 2E8 J. Wade : J. Kelsall (*) Division of Rheumatology, Department of Medicine, University of British Columbia, 202-1160 Burrard Street, Vancouver, BC, Canada V6Z 2E8 e-mail:
[email protected]
inflammation can be a sign of systemic disease, and such patients may be referred to a rheumatologist. Keywords Bisphosphonates . Ocular inflammation . Risedronate . Scleritis
Case Our patient was a 73-year-old woman of Chinese origin who presented to the emergency department with a 9-day history of ocular pain, periorbital edema, and decreased vision in the eyes bilaterally. Her past medical history was significant for osteoporosis and hypercholesterolemia. She had no known drug allergies. Her medications at the time of admission included risedronate 150 mg orally once monthly that was started on the day her ocular symptoms began. Initial assessment by the ophthalmology service revealed best corrected visual acuity of 20/400 in the right eye and 20/70 in her left eye and decreased abduction in the right eye. Examination of the anterior chamber was significant for occasional cells, significant chemosis and lid swelling, as well as significant corneal edema with Descemet's folds in the right eye. Similar, though less dramatic, findings were present in the left eye. There was a 3+ nuclear sclerotic change bilaterally. The examination of the posterior chamber was unremarkable. Connective tissue disease screening was negative. The patient denied any constitutional symptoms. Physical examination was unremarkable except for the findings on her eye exam. In particular, there were no cutaneous signs of vasculitis on examination. The review of systems was unremarkable. Further history revealed similar eye symptoms 2 years earlier when the patient had taken a single dose of risedronate 35 mg orally per week. At that time, she had a good response to oral corticosteroid therapy. Risedronate had
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Fig. 1 CT of orbits from 2007 revealing scleral thickening
been discontinued although its relationship with the eye condition was not identified. A CT scan from that episode was consistent with scleritis (Fig. 1). CT scans of orbits performed on this admission revealed diffuse thickening of the sclera of the right globe with abnormal enhancement along with subretinal edema, but no pre-septal or post-septal collections (Fig. 2a, b). Sinuses were normal. Laboratory investigations revealed normal: CBC, differentials, electrolytes, renal function, urinalysis, liver enzymes, and liver functions. ESR and CRP were 100 mm/h and 40.4 mg/L, respectively. ANA and ENA screen, and anti-dsDNA antibody were negative. ANCA Fig. 3 a Post-treatment coronal CT of orbits and b post-treatment axial CT of orbits from 2009 revealing significant improvement in scleral thickening
by Immunofluoresce, anti-MPO, and PR3 ELISA were negative. Chest radiograph was normal. Blood cultures were negative. The patient was treated with methylprednisolone 125 mg intravenously (IV) four times daily. She had significant improvement 24 h post therapy initiation. Three days after her admission, her ESR and CRP dropped to 10.1 mm/h and 84 mg/L, respectively, and her repeat CT scan showed significant improvement in scleral thickening (Fig. 3). Methylprednisolone was reduced to 250 mg IV daily for four more days followed up by tapering dose of oral prednisone starting at 20 mg orally per day. She was also started
Table 1 Summary of reported ocular inflammation and adverse events associated with bisphosphonates
Fig. 2 a Coronal and b axial CT of orbits from 2009 revealing diffuse scleral thickening of the right globe
Bisphosphonate
Reported ocular inflammation/adverse event
Alendronate
Conjunctivitis [9], nodular scleritis [10], scleritis [11] Anterior uveitis [5, 12] Myasthenia gravis [13] Anterior uveitis [14], iritis [15] Uveitis [16]
Zoledronic acid Risedronate Pamidronate Clodronate
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on prednisolone acetate 1 % eye drops. Three-month followup revealed resolution of the symptoms completely.
Discussion Bisphosphonates are frequently used for the prevention and/ or treatment of osteoporosis including glucocorticoidinduced osteoporosis. Risedronate sodium is a nitrogencontaining pyridinyl bisphosphonate that inhibits farnesyl diphosphate synthetase leading to cell (osteoclast) apoptosis. Bisphosphonates are also known to interact with the immune system and activate gamma delta T cells [1]. It is currently indicated in postmenopausal women for the prevention and treatment of osteoporosis and for the treatment of Paget's disease [1]. Cases of ocular inflammation in patients taking bisphosphonates have been reported since the early 1990s [2]. Reported cases include both nitrogen and non-nitrogen-containing bisphosphonates and also after intravenous or oral use. The interval between exposure and symptoms tends to be less with intravenous administrations with onset as early as 6 h with intravenous use and more typically several days of oral use [3]. The exact mechanism of orbital inflammation by bisphosphonates is unknown. However, increases in inflammatory factors of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 have been detected in patients after bisphosphonate use that may play a role in inducing inflammation in the eye [4]. Table 1 summarizes some of the reported cases of ocular inflammation associated with bisphosphonate therapy. Reviewing the English literature for eye disease and risedronate therapy resulted in one case of risedronateinduced transient myasthenia gravis [5]. However, there is one case of risedronate-induced episcleritis reported by Vinas and colleagues in Spanish [6]. We report the first case of risedronate-induced scleritis in a 73-yearold Chinese woman with a similar episode upon initial exposure to this medication. The onset of ocular symptoms in our case was less than 24 h. Discontinuation of risedronate and treatment with intravenous corticosteroid resulted in improvement of symptoms within 24 h. Applying Naranjo's adverse drug reaction probability scale, a causality assessment was made which categorized this reaction as definite with a score of 9 [7]. An observational study, using prescription–event monitoring, on 13,164 patients prescribed risedronate in primary care in England reported 19 adverse events related to the eye including specific diagnoses of conjunctivitis (three)and episcleritis (one) [8]. Although rare, ocular adverse effects of bisphosphonates may be serious and should be made known to
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prescribing physicians. This is important in the practice of rheumatology as many of our patients are prescribed this class of medication for either prevention or treatment of osteoporosis. Moreover, ocular inflammation can be a sign of systemic disease, and such patients may be referred to a rheumatologist. Acknowledgments We would like to thank Ms. Sonja Detillieux for her contribution to this case. Disclosures None.
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