Strabismus Associated With the Good Syndrome (Immunodeficiency and Thymoma)

Clinical Correspondence Strabismus Associated With the Good Syndrome (Immunodeficiency and Thymoma) Akash Gupta, BA, Mohammad Pakravan, MD, MBA, Chaow Charoenkijkajorn, MD, Andrew G. Lee, MD F irst described in 1954, Good syndrome (GS) is a rare disorder found in adults that consists of the unique combination of a thymoma and immunodeficiency.1 Thymomas have been associated with several syndromes such as myasthenia gravis (MG).2 Of patients with thymomas, between 30% and 50% develop MG, and approximately 0.2%–6% of thymomas are associated with GS.3 We present a case of Good syndrome presenting with binocular diplopia and review the literature on GS. To our knowledge, this is a unique description and review in the English language, ophthalmic literature of GS. A 44-year-old man presented with acute, intermittent binocular vertical and horizontal diplopia worse on leftward gaze. The past medical history included chronic immunodeficiency with multiple recurrent dermatologic and respiratory infections. Computed tomography (CT) of the chest showed a large (Masoaka Stage IIA Type AB) thymoma. He had a gross total thymoma resection followed by targeted proton beam external radiation because of contiguous pulmonary lesions. Family history was significant for retinal detachment, pancreatic cancer, hypertension, amblyopia, strabismus, diabetes, psoriasis, psoriatic arthritis, fibromyalgia, polycystic ovarian disease, latent autoimmune diabetes in adult in his mother, and kidney cancer in his uncle. The patient denied consuming alcohol, smoking cigarettes, or any allergies. His only current medication was monthly intravenous immune globulin (IVIG) for his immunodeficiency. Neuro-ophthalmic examination showed a visual acuity of 20/20 in both eyes. External examination showed no ptosis and there was no variability or fatigue. There was no lid retraction, lid lag, proptosis, orbicularis weakness, or cranial nerve V dysfunction. Pupils were isocoric and Baylor College of Medicine (AG); Department of Ophthalmology (MP, CC, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Gupta et al: J Neuro-Ophthalmol 2024; 44: e417-e418 without a relative afferent pupillary defect. Intraocular pressure measurements, automated visual field testing, slitlamp biomicroscopy, and dilated fundus examinations were normal both eyes. Motility examination showed a right hypotropia (RHT) of 10 prism diopters that increased on leftward gaze and leftward tilt consistent with a right inferior oblique paresis. His ductions and versions demonstrated a mild right inferior oblique underaction. Serum laboratory testing revealed elevated levels of thyroperoxidase (TPO) antibody of 14.1 IU/mL (normal 0.0–9.0 IU/mL) and glutamic acid decarboxylase (GAD) antibody of 63.7 IU/mL (normal 0.0–5.0 IU/mL). Serum free thyroxine (T4), free triiodothyronine (T3), thyroid stimulating hormone, thyroid stimulating immunoglobulin, anti-acetylcholine receptor binding, blocking, and modulating antibody, titin antibody, striated muscle antibody, and muscle-specific kinase antibodies were all negative. Serum HIV, hepatitis C virus, and antinuclear antibodies were negative. MRI of the head and orbit was normal. MR angiography (MRA) showed a 1–2-mm left posterior communicating artery infundibulum. Orbital ultrasound showed slight thickening and hypoechogenicity of the left inferior oblique. Bone marrow biopsy showed a low absolute neutrophil count, but was negative for abnormal myelodysplastic precursors. Subcutaneous IVIG treatment (8 g weekly) was continued with immune globulin (Hizentra). The platelet count was stable at 130,000/mm3 (normal 150,000– 400,000/mm3) secondary to immune-mediated thrombocytopenia, and he was stable at his baseline CD4 of 115 cells/mm3 (normal 500–1,500 cells/mm3). After treatment, the patient was asymptomatic with no ocular misalignment in primary position. GS is the association of a thymoma and immunodeficiency. The thymoma and immunodeficiency in GS can predispose to or precipitate binocular diplopia. Thymomas are well known to be associated with MG including ocular MG. The exact pathogenesis of thymoma in GS remains illdefined, but a unifying autoimmune mechanism has been proposed affecting bone marrow (leading to defective cellmediated immunity) and thymoma (immune modulation of T cells).1,2 In our case, the diplopia could have been thymomaassociated MG. The patient was triple seronegative for e417 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence MG, however (e.g., anti-acetylcholine receptor, MuSK, and striated muscle antibodies were negative). Interestingly, however, anti-GAD antibody was positive. In addition, although serum thyroid function tests were normal, euthyroid thyroid eye disease (TED) could not be excluded because of positive anti-TPO antibodies. Although the ultrasound results were not diagnostic of TED in either eye, they indicated a possible inflammatory process in the left inferior oblique as well. No neuroimaging evidence was found for alternative intracranial neurogenic etiologies (e.g., secondary intracranial infection or orbital abscess). Primary antibody deficiency (up to 1%–2%) in GS is typically treated with immunoglobulin replacement1 and the incidence of hypogammaglobulinemia in GS is up to 6%–11%.1 Prior presentations of ophthalmoplegia in relation to GS include a patient with a right sixth cranial nerve palsy associated with MG and a thymoma.2 Another patient presented with a right sixth cranial nerve palsy as a manifestation of an opportunistic central nervous system infection with Herpes Simplex Virus-2 secondary to GS immunodeficiency.4 In addition, 3 patients have previously presented with intermittment diplopia months before the development of cerebellar ataxia who were found to have elevated levels of anti-GAD antibody, which is associated with thymomas.5 To our knowledge, this case is a unique presentation of presumed autoimmune euthyroid Graves orbitopathy presenting with diplopia. Clinicians should be aware of the differential diagnosis of diplopia in GS including thymoma-related MG, autoimmune TED, antibody e418 mediated ophthalmoplegia, and secondary infectious etiologies because of immunodeficiency. STATEMENT OF AUTHORSHIP Conception and design: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee; Acquisition of data: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee; Analysis and interpretation of data: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee. Drafting the manuscript: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee; Revising the manuscript for intellectual content: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee. Final approval of the completed manuscript: A. Gupta, M. Pakravan, C. Charoenkijkajorn, A. G. Lee. REFERENCES 1. Kelleher P, Misbah SA. What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56:12–16. 2. Paranavitane S, Handagala S, De Silva R, Chang T. Thymoma complicated with myasthenia gravis and Good syndrome—a therapeutic conundrum: a case report. J Med Case Rep. 2019;13:348. 3. Malphettes M, Gérard L, Galicier L, et al. Good syndrome: an adult-onset immunodeficiency remarkable for its high incidence of invasive infections and autoimmune complications. Clin Infect Dis. 2015;61:e13–e19. 4. Matta L, Ramírez-Velasco MC, Zea-Vera AF. Herpes simplex virus type 2 meningitis as a manifestation of Good’s syndrome. J Neurovirol. 2020;26:429–432. 5. Ariño H, Gresa-Arribas N, Blanco Y, et al. Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy. JAMA Neurol. 2014;71:1009–1016. Gupta et al: J Neuro-Ophthalmol 2024; 44: e417-e418 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.