| Identifier |
walsh_2016_s2_c5 |
| Title |
It is, is it not? - Presentation PPT |
| Creator |
Ivana Vodopivec; Derek H. Oakley; Nagagopal Venna; John H. Stone; E. Tessa Hedley-Whyte; Sashank Prasad |
| Affiliation |
(IV) MEEI, Neuro-ophthalmology Boston, MA; (DHO) (ETH) MGH, Neuropathology Boston, MA; (IV) (NV) MGH, Neurology Boston, MA; (JHS) MGH, Rheumatology Boston, MA; (IV) (SP) BWH, Neuro-ophthalmology Boston, MA |
| Subject |
Vasculopathy; Retinopathy; Cerebral Calcifications; Nephropathy; Retinal Vasculopathy with Cerebral Leukodystrophy |
| Description |
Lacrimal gland biopsy revealed sclerotic tissue to gross inspection. Microscopic analysis revealed fibroadipose tissue, xanthogranulomas with touton giant cells, lymphoid follicles and scattered plasma cells. Flow cytometry was negative for lymphoproliferative disorder. The IgG4+/IgG+ plasma cell ratio was 60% with 96 IgG4+ plasma cells per high power field, just under the diagnostic cut-off of 100 for IgG4 related orbital disease (ROD) (Deshpande, 2012). Given her asthma, dermatological and histopathologic findings, a diagnosis of adult-onset asthma with periocular xanthogranuloma (APX) was made. APX is a rare non-Langerhans histiocytosis belonging to a spectrum of xanthogranulomatous diseases including Erdheim-Chester disease and necrobiotic xanthogranuloma. The latter two are important to distinguish from APX due to their poor prognosis related to paraproteinemia and multiple myeloma. APX is rarely associated with lymphoproliferative disorders, diabetes, and lymphoplasmacytic sclerosing pancreatitis. APX signs include bilateral yellow-orange, elevated, indurated eyelid masses with inflammation of orbital fat, lacrimal glands and/or extra ocular muscles. There is no consensus on treatment, but immunosuppressive agents are mainstay treatment, and our patient was treated with high dose IV steroids followed by oral steroid taper. One week later, her right eye vision had improved to 20/50 with 1+ anterior cell. A unique feature APX in our patient was a marked anterior chamber reaction in the active eye with evidence of prior uveitis in the fellow eye. Although uveitis has been reported in IOI in children (Mottow-Lippa 1981) and rarely in adults (Xu 2013), it has not previously been described in association with APX. This case illustrates the arbitrary nature of cut off values for IgG4 ROD. An association has been described between xanthogranulomatous inflammation of the orbit and a prominent population of IgG4-positive plasma cells, suggesting that it is a variant of IgG4 sclerosing disease (Mudhar, 2011). |
| History |
A 44-year-old man presented with visual loss, confusion, apraxia, and left-sided weakness. His medical history included retinal vasculopathy, chronic kidney disease, hypertension, and hypertensive cardiomyopathy that had presented over the preceding six years. The retinal vasculopathy had been termed 'posterior uveitis with retinal vasculitis.' The condition had been treated with several immunosuppressive medications, including prednisone, cyclosporine, mycophenolate mofetil, adalimumab, methotrexate, and interferon-alpha. Additional treatments included retinal laser photocoagulation, intravitreal glucocorticoids, and bevacizumab. The patient had undergone two kidney biopsies, which were reported to show focal segmental glomerulosclerosis with thrombotic microangiopathy and mild nephrosclerosis. No tubulointerstitial disease was present. His father had died at age 36 years from Hodgkin lymphoma. His paternal uncle had died in his early forties from unclear causes, accompanied by renal dysfunction. The patient denied any history of oral, genital, or skin lesions, sicca symptoms, musculoskeletal, respiratory or gastrointestinal symptoms. He had undergone extensive diagnostic evaluations, including two brain biopsies, at another hospital. Glucocorticoids had been prescribed for cerebral edema. After five weeks, the patient was transferred to our institution for further management. On arrival, physical examination was remarkable for an irregularly irregular pulse and 3+ pitting edema of the lower extremities. Best-corrected visual acuity was 20/80 in the right eye and 20/50-1 in the left eye. There was bilateral dyschromatopsia. A relative afferent pupillary defect was not present. Slit lamp examination showed moderate bilateral symmetrical optic disc pallor, epiretinal membranes, cotton wool spots, retinal arteriole obstruction with sclerosis and resulting ghost vessels, and extensive pan-retinal photocoagulation scars. Neurological examination was remarkable for nonspecific visual field defects on confrontation testing, mild left lower facial weakness, mild left pronator drift, and unsteady gait. Cognitive abnormalities documented five weeks earlier were no longer present. Brain MRI revealed a right temporo-parieto-occipital tumefactive lesion with vasogenic edema extending through the splenium of the corpus callosum and the left periventricular white matter. Laboratory evaluations for systemic and CNS-related autoimmunity and inflammation, HLA-B51 antigen, and analysis of blood and cerebrospinal fluid for various infectious agents were negative. Specimens from the two brain biopsies demonstrated a vasculopathy with abnormally thickened vessel walls and focal necrosis of the white matter with areas of dystrophic calcification. Because the retinal vasculopathy, in combination with the tumefactive cerebral lesion, raised the possibility of Behçet disease or other inflammatory conditions, high-dose dexamethasone, weekly adalimumab, and daily cyclophosphamide were initiated. Decrease in the vasogenic edema with resolution of the mass effect was noted after 10 weeks of dexamethasone. His vision, however, continued to deteriorate. We took a direct approach toward reaching a diagnosis. |
| Disease/Diagnosis |
Retinal vasculopathy with cerebral leukodystrophy due to a novel mutation of TREX1 gene. |
| Date |
2016-02 |
| References |
1. Kolar GR, Kothari PH, Khanlou N, Jen JC, Schmidt RE, Vinters HV. Neuropathology and genetics of cerebroretinal vasculopathies. Brain Pathol. 24:510-8, 2014 2. Richards A, van den Maagdenberg AM, Jen JC, Kavanagh D, Bertram P, et al. C-terminal truncations in human 3'- 5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet. 39:1068-70, 2007 3. DiFrancesco JC, Novara F, Zuffardi O, Forlino A, Gioia R, et al. TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy. Neurol Sci. 36:323-30, 2015 4. Schuh E, Ertl-Wagner B, Lohse P, Wolf W, Mann JF,et al. Multiple sclerosis-like lesions and type I interferon signature in a patient with RVCL. Neurol Neuroimmunol Neuroinflamm. 2:e55, 2015 |
| Language |
eng |
| Format |
application/pdf |
| Format Creation |
Microsoft PowerPoint |
| Type |
Text |
| Source |
48th Annual Frank Walsh Society Meeting |
| Relation is Part of |
NANOS Annual Meeting 2016 |
| Collection |
Neuro-Ophthalmology Virtual Education Library: Walsh Session Annual Meeting Archives: https://novel.utah.edu/Walsh/ |
| Publisher |
North American Neuro-Ophthalmology Society |
| Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
| Rights Management |
Copyright 2016. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
| ARK |
ark:/87278/s6f50ksm |
| Setname |
ehsl_novel_fbw |
| ID |
179349 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6f50ksm |
