A Case of Recurrent Orbital Inflammation Secondary to Acute Myeloblastic Leukemia

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD A Case of Recurrent Orbital Inflammation Secondary to Acute Myeloblastic Leukemia Geoffrey Collett, MD, Narmien Haddad, BS, Crandall E. Peeler, MD, Alberto G. Distefano, MD I diopathic orbital inflammation (IOI) is an entity characterized by orbital inflammation lacking an identifiable local or systemic etiology. The clinical presentation typically involves acute unilateral pain, redness, proptosis, and periorbital edema. Vision changes and diplopia may also occur (1). IOI is a diagnosis of exclusion and the work-up should focus on ruling out infectious, rheumatologic, or neoplastic causes. Here, we present the clinical, histopathologic, and neuroradiologic findings of a presumed IOI case that was difficult to control. A 71-year-old man with a history of bilateral pseudophakia, prostatectomy and radiation therapy for prostate cancer, partial nephrectomy for renal cell carcinoma, and cervical stenosis presented with a 2 week history of left eye pain with redness and 1 day of blurred vision. The bestcorrected visual acuity (BCVA) was 20/20 in the right eye and 20/200 in the left eye. The right pupil was unreactive because of previous surgery; the left was round and reactive with no relative afferent pupillary defect. Intraocular pressure was 10 mm Hg on the right and 22 on the left. Ductions were full on the right and globally reduced on the left. External and slit-lamp examination showed mild periorbital edema and proptosis of the left eye with bullous chemosis and diffuse injection. There was 2+ cell in the left anterior chamber and anterior vitreous. MRI of the orbits with contrast showed enhancement of the left choroid and sclera, a subchoroidal effusion, and mild enlargement and enhancement of the left lacrimal gland (Fig. 1). Negative or normal serologic testing included a syphilis screen, Lyme antibodies, IgG4 level, rheumatoid factor, angiotensin-converting enzyme, and ANCA. The only abnormal results were a new, mild anemia (Hb 10.8 g/dL, reference range 13.5– 17.5, CBC otherwise normal), a C-reactive protein of 87.2 mg/L (reference range 0–5), and a positive ANA screen (follow-up anti-dsDNA was negative). Chest x-ray Departments of Ophthalmology (GC, NH, CEP, AGD); and Neurology (CEP), Boston Medical Center, Boston University School of Medicine, Boston, MA. The authors report no conflicts of interest. Address correspondence to Geoffrey Collett, MD, Department of Ophthalmology, Boston Medical Center, Boston University School of Medicine, 305-910-6032, One Boston Medical Center Place, Boston, MA 02118; E-mail: [e-mail] Collett et al: J Neuro-Ophthalmol 2021; 41: e319-e321 was normal. At this point, the diagnosis was felt to be most consistent with IOI. He received intravenous methylprednisolone with clinical improvement and was transitioned to an oral prednisone taper (starting dose 100 mg daily). The patient completed his first steroid taper over the course of 3 months and remained asymptomatic for a subsequent 3-month time period. He then returned to the clinic with recurrent left eye pain and redness. Examination showed unchanged BCVA of 20/20 in both eyes and new left eye conjunctival injection temporally, with mild tortuous vessels. He was restarted on oral prednisone 60 mg daily. Over the next week, he experienced increasing pain, but his examination remained stable; prednisone was increased to 80 mg daily. Four days later, the patient developed new, mild periorbital swelling and rare cell in the anterior chamber. BCVA remained 20/20 in both eyes; prednisone was increased to 100 mg daily and symptoms improved. A biopsy of the persistently enlarged left lacrimal gland was suggested on multiple occasions during this recurrence but was declined by the patient. A prednisone taper was again attempted with a severe recurrence of his ocular symptoms on reaching 40 mg daily. Examination was nearly identical to the initial encounter, now 7 months prior. At this point, a repeat CBC with differential showed severe anemia (Hb 4.9 g/dL), thrombocytopenia (platelets 21 K/mL, range 150–400), and leukocytosis (WBC 18.8 K/mL, range 4–11) with 11% blasts. The patient was admitted for an urgent bone marrow biopsy (Fig. 2), which was consistent with acute myeloblastic leukemia (AML). Karyotype analysis demonstrated a partial deletion of chromosome 7 and a translocation of chromosomes 11 and 19. His ocular symptoms again improved with intravenous methylprednisolone and he was also started on venetoclax, a Bcl-2 inhibitor, and azacitidine, a DNA hypomethylating agent, for treatment of his AML. He tolerated chemotherapy well, although a repeat bone marrow biopsy showed relapse after the fourth treatment cycle. The patient achieved remission with daunorubicin, an intercalating agent, and cytarabine, an antimetabolite, and he has now undergone an allogeneic stem cell transplant. From an ocular perspective, his e319 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. T1, postgadolinium, axial (A) and sagittal (B) MRI: enhancement of the left choroid and sclera with subchoroidal effusions; mild enlargement and enhancement of the left lacrimal gland; the optic nerve, its sheath complex, and extraocular muscles are unremarkable. symptoms have not recurred since starting AML therapy, and corticosteroid therapy was successfully discontinued. At his most recent visit, the BCVA was 20/20 in both eyes, and extraocular motility was full. We report a patient presenting with what appeared to be classic IOI. The initial serologic work-up was extensive, yet revealed only a few nonspecific findings including a mild anemia. There was low suspicion for a neoplastic process at that time, but a thorough anemia investigation was not performed. As previously mentioned, the patient deferred biopsy of his persistently enlarged left lacrimal gland multiple times. Although it is not unusual for the eye and/or orbit to be affected by acute or chronic leukemias, it is rare for these to be the FIG. 2. Histopathology: atypical immature myeloid cells accounted for 70% of the bone marrow cellularity on H&E (A), 10% of these appeared to be myeloblasts; CD34 stain (B) used to identify blasts; MPO stain (C) helps differentiate blasts of myeloid vs lymphoid lineage (MPO present in myeloid leukocytes form an insoluble brown/blue substrate in the presence of hydrogen peroxide). e320 Collett et al: J Neuro-Ophthalmol 2021; 41: e319-e321 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence only extramedullary sites involved in the initial/recurrent leukemic process (2). In our patient, it is unclear whether biopsy would have demonstrated nonspecific orbital inflammation or extramedullary AML, but early tissue sampling may have been valuable. AML can present with a multitude of ocular manifestations and should be considered in the differential for IOI. In 2003, Reddy et al published a case series of ocular and orbital lesions in patients with newly diagnosed leukemia (3). In this cohort, ocular manifestations such as retinopathy (35%) were significantly more common than orbital findings (2%). We suspect our patient’s unusual recurrent orbital inflammation was due to AML since treatment of this led to symptom resolution, allowed for successful steroid taper, and has thus far prevented further recurrence. In patients with chronic, recurrent episodes of presumed IOI, work-up for hematologic malignancies should be considered. Collett et al: J Neuro-Ophthalmol 2021; 41: e319-e321 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: G. Collett, N. Haddad, C. E. Peeler, and A. G. Distefano; b. Acquisition of data: G. Collett, N. Haddad, C. E. Peeler, and A. G. Distefano; c. Analysis and interpretation of data. Category 2: a. Drafting the manuscript: G. Collett, N. Haddad, C. E. Peeler, and A. G. Distefano; b. Revising it for intellectual content: C. E. Peeler and A. G. Distefano. Category 3: a. Final approval of the completed manuscript: C. E. Peeler and A. G. Distefano. REFERENCES 1. Swamy BN, McCluskey P, Nemet A, Crouch R. Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes. Br J Ophthalmol. 2003;91:1667–1670. 2. Rosenthal RA. Ocular manifestations of leukemia. Ophthalmology. 1983;90:899–905. 3. Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia—a study of 288 cases. Ophthalmologica. 2003;217:441–445. e321 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.