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A 51-year-old man diagnosed as having acute promyelocytic leukemia, undergoing induction therapy with all-trans-retinoic acid (ATRA) and arsenic trioxide that were started 2 weeks prior, presented with sudden loss of vision. Hospital course was complicated by neutropenic fever, receiving cefepime, acyclovir, vancomycin, and voriconazole for prophylaxis. Laboratory test results were remarkable for pancytopenia. On initial examination, his visual acuity was count fingers at 3 ft in both eyes. Intraocular pressures were 10 mm Hg OD and 11 mm Hg OS. Pupils were round and reactive without a relative afferent pupillary defect. Color plates were 1 of 8 OU, with 50% brightness desaturation in the right eye and no red desaturation. Extraocular movements were full. Slitlamp examination was negative for any signs of inflammation. Dilated fundus examination demonstrated bilateral choroidal effusions with diffuse serous retinal detachments (RD) involving the macula without vitritis as well as white centered intraretinal hemorrhages along peripapillary and superior and inferior arcade distributions in both eyes (Figure, A). Optical coherence tomography demonstrated irregular inner retinal surface and subretinal fluid with septae with loss of the ellipsoid zone (Figure, B). Review of systems was positive for fever, tachycardia, odynophagia, productive cough with wheezing, and marked peripheral edema in upper extremities and negative for headache, nausea, vomiting, dysacusis, meningismus, or skin changes.
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Differentiation syndrome secondary to all-trans-retinoic acid and arsenic trioxide
C. Stop the ATRA and start steroids
Acute promyelocytic leukemia (APL) is an aggressive acute myeloid leukemia characterized by a balanced reciprocal translocation between chromosomes 15 and 17 resulting in a PML-RARα fusion gene; it is also characterized by coagulopathy with lymphocytic blast cell morphology.1 The mainstay of induction therapy for APL is ATRA with arsenic trioxide, with or without anthracycline-based chemotherapy. All-trans-retinoic acid induction therapy leads to terminal differentiation of the malignant blast cell progenitors.
Differentiation syndrome (DS) is a well-known, life-threatening complication of induction therapy with ATRA and arsenic trioxide. The incidence of DS after starting induction therapy ranges from 2.5% to 31%.2 Luesink et al2 suggest that DS is caused by excessive systemic inflammation from chemokines inducing a life-threatening capillary leak syndrome. It classically presents with unexplained fever, respiratory distress, hemodynamic instability, peripheral edema, acute kidney injury, and pleuropericardial effusions. Our patient demonstrated fever, wheezing with pulmonary infiltrates, and bilateral upper extremity edema. On literature search, we found 3 other documented cases of DS presenting with bilateral serous RD, manifesting with only subretinal fluid and no intraretinal fluid or choroidal effusions.3,4 In 2 of these 3 cases, ATRA was discontinued and steroids were started, leading to resolution of the subretinal fluid. Our case would represent, to our knowledge, the first reported ophthalmic DS with choroidal effusion and serous RD with intraretinal fluid. Treatment of DS typically entails pausing ATRA and starting systemic steroids.3,4 Given this patient’s constellation of systemic symptoms and prior reports of serous RD in the setting of DS, the patient started receiving intravenous dexamethasone (choice C).
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Corresponding Author: Andrew A. Moshfeghi, MD, University of Southern California Roski Eye Institute, 1450 San Pablo St, Los Angeles, CA 90033 (email@example.com).
Published Online: December 5, 2019. doi:10.1001/jamaophthalmol.2019.4838
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
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