A Audemard

Alberto Neri

B Taillan

CH Churchill

Claudio Macaluso

E Desport

JK Rao

K Landau

M Hamidou

N Srinivasulu

P Hausfater

P Lafforgue

Pierangela Rubino

SS Hayreh

Stefano A Gandolfi

Y Ishikawa

BMC Ophthalmology

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Neri et al. BMC Ophthalmology 2013, 13:82http://www.biomedcentral.com/1471-2415/13/82CASE REPORT Open AccessLight-chain amyloidosis mimicking giant cellarteritis in a bilateral anterior ischemic opticneuropathy caseAlberto Neri*, Pierangela Rubino, Claudio Macaluso and Stefano A GandolfiAbstractBackground: Herein we report a case of bilateral anterior ischemic optic neuropathy (AION) showinghistopathologic evidence of AL-amyloidosis of the temporal arteries. It is known that light-chain (AL) amyloidosismay rarely affect the temporal arteries, mimicking giant cell arteritis, while, to our knowledge, the associationbetween AL-amyloidosis and AION was not previously described.Case presentation: A 64 year-old woman with AL-amyloidosis secondary to a monoclonal gammopathy ofundetermined significance (MGUS) referred to our hospital for acute painless drop of vision due to bilateral AION.Age greater than 50 years, high erythrocyte sedimentation rate (ESR), and bilateral AION were suggestive of giantcell arteritis (GCA). However, a temporal artery biopsy excluded GCA, showing segmental stenosis of the lumencaused by amyloidosis of the artery wall.Conclusions: The present case shows that AL-amyloidosis may present with AION, high ESR, and temporal arteryinvolvement, mimicking GCA. In patients with monoclonal gammopathies, C-reactive protein may be a morespecific index of GCA compared with the ESR. Patient medical history and pathology are crucial for a correctdiagnosis.Keywords: Ischemic optic neuropathy, Giant cell arteritis, Horton’s disease, Amyloidosis, Light-chain, MonoclonalgammopathyBackgroundArteritic Anterior Ischemic Optic Neuropathy (Arteritic-AION) is one of the most serious complications of giantcell arteritis (GCA) or Horton’s disease, and it is caused bythe occlusion of the posterior ciliary arteries, supplyingthe optic nerve head (ONH) [1]. Arteritic-AION is themost frequent ophthalmological complication of GCA(81.2%), followed by central retinal artery occlusion(14.1%), retrobulbar ischemic optic neuropathy (7%), andocular ischemia (1.2%) [1].Light-chain (AL) amyloidosis, or primary amyloidosis, isa hematological disease characterized by the deposition intissues of monoclonal light-chain variable-region im-munoglobulin fragments, which may involve any tissue ororgan. It is usually associated with monoclonal gammopathy* Correspondence: neri.mail2@gmail.comOphthalmology, University Hospital of Parma, Via Gramsci 14, Parma, PR43100, Italy© 2013 Neri et al.; licensee BioMed Central LtdCommons Attribution License (http://creativecreproduction in any medium, provided the orof undetermined significance (MGUS) or smolderingmyeloma, less frequently with symptomatic multiple mye-loma [2]. The vascular system is often involved by thedeposition of the amyloidal-proteins, which principallyaffect the small-caliber vessels [2]. The localization tomedium- or large-size vessels is less frequent; nonetheless,deposits of the amyloidal-protein were found in thecoronary arteries [3], and arterial thromboembolic eventsassociated with cardiac AL-amyloidosis were reported [4].AL-amyloidosis of the temporal arteries has also beenshown in patients with symptoms and signs suggestive ofGCA [5-10].Here we report a case of bilateral AION showingclinical and laboratory signs suggestive of GCA, whichwas subsequently excluded by pathology and furtherlaboratory findings. Positivity of the temporal arterybiopsy (TAB) for light-chain amyloidosis prompted us toevaluate the possibility that AL-amyloidosis may be a -. This is an open access article distributed under the terms of the Creativeommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andiginal work is properly cited.Neri et al. BMC Ophthalmology 2013, 13:82 Page 2 of 5http://www.biomedcentral.com/1471-2415/13/82yet undescribed - cause of bilateral AION, mimickingGCA.Case presentationA 64 year-old woman referred to the emergency service ofour department for acute painless drop of vision. Thepatient reported a complete loss of vision in the right eyeand a loss of the inferior visual field in the left eye sincewaking up in the morning. Past medical history revealedAL-amyloidosis secondary to monoclonal gammopathy ofFigure 1 Visual field examination at presentation. Kinetic (upside) andpresentation, showing an altitudinal scotoma affecting the inferior visual fieunknown origin (immunoglobulin G light chain k, IgGk)with main involvement of kidneys (nephrosic syndrome),arterial hypertension, and hypercolesterolemia. The diag-nosis of AL-amyloidosis had been posed two years beforeby biopsy of both kidney and periumbilical fat, whilenegative bone marrow puncture confirmed MGUS. Dur-ing the previous year the patient had been treated foramyloidosis (one week per month, for 8 months) withdexamethasone (40 mg/day), bortezomib (1.3 mg/m2 twotimes weekly), and cyclophosphamide (20 mg/Kg oncestatic (downside) perimetry of the left eye of the patient atld. Visual field examination was not executable in the right eye.Figure 2 Optic nerve head evaluation at one-year of follow-up.A. Color pictures of the optic nerve head of the right and left eyeof the patient at one-year of follow-up. B. Optical coherencetomography evaluation of the Retinal Nerve Fiber Layer thickness(RNFL thickness) at one-year of follow-up, showing relative preservationof the ganglion cell fibers in the inferior quadrants of the left eye,compared with the diffuse reduction of RNFL thickness in the right eye.Neri et al. BMC Ophthalmology 2013, 13:82 Page 3 of 5http://www.biomedcentral.com/1471-2415/13/82monthly). However, the therapy for amyloidosis wassuspended because of hepatic toxicity two months beforethe presentation of the visual symptoms. At presentationthe patient treatment included omeprazole 20 mg/day,ramipril 2.5 mg/day, furosemide 100 mg/day, spironolac-tone 25 mg/every other day, and atorvastatin 20 mg/day.Lens corrected visual acuity at presentation was lightperception in the right eye and 20/20 in the left eye.Pupil light reflex examination showed a marked relativeafferent defect (RAPD) of the right eye. Visual fieldexamination was not executable in the right eye, whilein the left eye it revealed an inferior altitudinal scotoma(Figure 1). Biomicroscopy showed normal anteriorsegment, while at fundoscopy an ONH edema was foundin both eyes: in the right eye the edema involved theentire ONH, while in the left eye there was limited in-volvement of the superior half of the ONH, in keepingwith the visual field examination (Figure 1).Blood analyses were performed at presentation, re-vealing abnormally high erythrocyte sedimentation rate(ESR = 78 mm/h, laboratory range 2-30 mm), as well ashigh serum levels of both fibrinogen (745 mg/dL, labora-tory range 150-400 mg/dL) and D-dimer (331 ng,laboratory range 0-245 ng). Serum levels of C-reactiveprotein were within the normal range (CRP = 0.41 mg/dL,laboratory range 0.001-5.0 mg/dL). Recent medical historywas negative for claudicatio mandibularis or temporaltenderness.The patient was admitted to the rheumatology serviceof our hospital for suspect silent GCA, and high dosecorticosteroid therapy was immediately started (1 gmethilprednisolone/day i.v. in the first three days, thenoral prednisone 50 mg/day). The patient did not reportany change of the visual symptoms after starting thecorticosteroid therapy. A brain MRI was performed threedays after presentation, showing bilateral optic nerve headthickening and multiple chronic ischemic lacunae in sub-cortical and profound white matter. The ultrasoundstudy of the temporal arteries showed tortuosity andsegmental stenosis of the arterial lumen, without sig-nificant limitation of the blood flow. Ultrasound mor-phologic alterations typical of GCA (hypo-ecogenicconcentric mural thickening) were not found. CarotidDoppler-ultrasound did not identify significant alter-ations of blood flow.A biopsy of the right temporal artery was obtainedand analyzed histopathologically ten days after presenta-tion, showing diffuse mural infiltration of amyloidalsubstance, causing the segmental stenosis of the arteriallumen. The amyloid substance showed immunologicpositivity for immunoglobulin k light chains and foramyloidal P-substance, and the tunica intima was thick-ened by fibrosis and calcific deposits, with subocclusionof the vessel. No pathologic signs of GCA were found.Acetylsalicylic acid 100 mg/day p.o. was consequentlystarted, and steroids were slowly tapered.An ophthalmological evaluation was repeated onemonth and one year after presentation. At one-monththe ONH edema had almost disappeared, and just aslight masking of the peripapillary vessels was noticeable.At one-year a pallid atrophic ONH was observed in theright eye, and sector atrophy of the ONH was present inthe left eye (Figure 2A). Optical coherence tomography(OCT) study of the retinal nerve fiber layer (RNFL)showed a uniformly reduced thickness of the retinalNeri et al. BMC Ophthalmology 2013, 13:82 Page 4 of 5http://www.biomedcentral.com/1471-2415/13/82nerve fiber layer (RNFL) in the right eye, and sectorreduction of RFNL thickness in the inferior quadrants inthe left eye (Figure 2B). Visual acuity and visual fieldexamination remained stable during the follow-up.ConclusionsThe case herein described presented a problematicdifferential between arteritic (AAION) and non-arteriticanterior optic neuropathy (NAION). In fact, age greaterthan fifty years, bilateral eye involvement, and high ESR atpresentation were suggestive of a diagnosis of AAION.However, a high ESR is a common laboratory finding inpatients with serous monoclonal gammopathies [11],hence its specificity for the diagnosis of AAION may bescarce in these patients. CRP values, instead, were withinthe normal range in the present case, suggesting that CRPcould be a more specific index of AAION in patients withcoexisting plasma cell dyscrasias.The TAB excluded the diagnosis of GCA in the presentcase, showing diffuse amyloid infiltration of the arterywall. A possible hypothesis explaining the pathogenesis ofthe optic nerve head ischemia is that the AL-amyloiddeposition found in the temporal artery specimen mayalso have affected the posterior ciliary arteries, causingarterial stenosis and insufficiency, or reduced adaptabilityto blood pressure variations. As the pathological processescharacteristics of GCA commonly involve the posteriorciliary arteries, it is possible that the arteries of this districtshare with the temporal arteries common histologicalfeatures causing their preferential susceptibility to GCA.Similarly, the posterior ciliary arteries could share with thetemporal arteries a common susceptibility to the depos-ition of amyloid substance. High blood viscosity due toMGUS, arterial hypertension, and hypercholesterolemiawere other factors increasing the risk of NAION inour patient.The presentation of AION at the awakening in themorning further supports this hypothesis. In fact, bloodpressure dips are more commonly encountered duringthe night, and they are associated to a higher risk ofNAION [12-14]. The arterial stenosis combined with ahypotensive dip of the arterial blood pressure couldhave caused bilateral optic nerve head ischemia inour patient.AION is rarely bilateral at its exordium [15]. In thepresent case it can’t be excluded that the patient was notaware of a preexistent monolateral AION until thecontralateral eye was involved. However, the appearanceof the optic discs at presentation was symmetrical, andindicative for a recent exordium of the ischemia in boththe eyes.Maybe fluorescein angiography (FA) could have pro-vided useful elements for the diagnosis and characteri-zation of the present clinical case. Unfortunately, in ourhospital FA is not performed routinely in patients withdiagnosis of AION, relying on TAB findings for diffe-rential diagnosis between AAION and NAION. When thepatient was controlled after the TAB response one monthhad passed from presentation and the ONH edema hadpartially regressed, hence it was decided not to performthe angiography.In conclusion, the present case shows that AL-amyloidosis may present with bilateral AION, mimickinggiant cell arteritis not only for the visual symptoms, butalso for high ESR values and temporal artery involve-ment. Moreover, AL-amyloidosis and giant cell arteritismight share similar pathogenetical mechanisms, leadingto affect the same small arterial districts. Patient medicalhistory and pathology are crucial for a correct diagnosis.ConsentWritten informed consent was obtained from the patientfor publication of this Case report and any accompany-ing images. A copy of the written consent is available forreview by the Editor of this journal.AbbreviationsAAION: Arteritic anterior ischemic optic neuropathy; AION: Anterior ischemicoptic neuropathy; AL-amyloidosis: Light-chain amyloidosis; CRP: C-reactiveprotein; ESR: Erythrocyte sedimentation rate; FA: Fluorescein angiography;GCA: Giant cell arteritis; IgGk: Immunoglobulin G light-chain k;MGUS: Monoclonal gammopathy of undetermined significance; NAION: Nonarteritic anterior ischemic optic neuropathy; OCT: Optical coherencetomography; ONH: Optic nerve head; RAPD: Relative afferent pupillary defect;RNFL: Retinal nerve fiber layer; TAB: Temporal arteries biopsy.Competing interestThe authors declare that they have no competing interests. Supported inpart by funding from University and IMEM-CNR of Parma, Parma, Italy, andfrom Grant "eRare RHORCOD".Authors’ contributionAN contributed to the clinical management, acquisition and analysis of data,and drafted the manuscript. PR was responsible of the clinical managementof the patient. CM have been involved in drafting the manuscript. SAGparticipated in the design of the case report and revised the manuscript.All authors read and approved the final manuscript.Received: 27 April 2013 Accepted: 10 December 2013Published: 20 December 2013References1. Hayreh SS, Podhajsky PA, Zimmerman B: Ocular manifestations of giantcell arteritis. Am J Ophthalmol 1998, 125(4):509–520.2. Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N,Lacombe C, Goujon JM, Lavergne D, et al: AL Amyloidosis. Orphanet J RareDis 2012, 7(1):54.3. Ishikawa Y, Ishii T, Masuda S, Asuwa N, Kiguchi H, Hirai S, Murayama A:Myocardial ischemia due to vascular systemic amyloidosis: a quantitativeanalysis of autopsy findings on stenosis of the intramural coronaryarteries. Pathol Int 1996, 46(3):189–194.4. Hausfater P, Costedoat-Chalumeau N, Amoura Z, Cacoub P, Papo T, GrateauG, Leblond V, Godeau P, Piette JC: AL cardiac amyloidosis and arterialthromboembolic events. Scand J Rheumatol 2005, 34(4):315–319.5. Audemard A, Boutemy J, Galateau-Salle F, Macro M, Bienvenu B: ALamyloidosis with temporal artery involvement simulates giant-cellarteritis. Joint Bone Spine 2012, 79(2):195–197.Neri et al. BMC Ophthalmology 2013, 13:82 Page 5 of 5http://www.biomedcentral.com/1471-2415/13/826. Churchill CH, Abril A, Krishna M, Callman ML, Ginsburg WW: Jawclaudication in primary amyloidosis: unusual presentation of a raredisease. J Rheumatol 2003, 30(10):2283–2286.7. Hamidou M, Buzelin F, Rojouan J, Barrier JH, Briseau JM, Grolleau JY:[Temporal artery syndrome in amyloidosis AL associated with myeloma].Rev Med Interne 1991, 12(4):306–308.8. Lafforgue P, Senbel E, Figarella-Branger D, Boucraut J, Horschowsky N,Pellissier JF, Acquaviva PC: Systemic amyloidosis AL with temporal arteryinvolvement revealing lymphoplasmacytic malignancy in a manpresenting as polymyalgia rheumatica. Ann Rheum Dis 1993,52(2):158–160.9. Rao JK, Allen NB: Primary systemic amyloidosis masquerading as giantcell arteritis. Case report and review of the literature. Arthritis Rheum1993, 36(3):422–425.10. Taillan B, Fuzibet JG, Vinti H, Pesce A, Dujardin P: AL amyloid deposits intemporal artery mimicking giant cell arteritis. Clin Rheumatol 1990,9(2):256.11. Srinivasulu N, Sharma V, Samant R: Monoclonal gammopathies presentingas inflammatory arthritis: uncommon but important–a case series.Int J Rheum Dis 2012, 15(3):336–339.12. Hayreh SS, Podhajsky P, Zimmerman MB: Role of nocturnal arterialhypotension in optic nerve head ischemic disorders. Ophthalmologica1999, 213(2):76–96.13. Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL: Nocturnal arterialhypotension and its role in optic nerve head and ocular ischemicdisorders. Am J Ophthalmol 1994, 117(5):603–624.14. Landau K, Winterkorn JM, Mailloux LU, Vetter W, Napolitano B: 24-hourblood pressure monitoring in patients with anterior ischemic opticneuropathy. Arch Ophthalmol 1996, 114(5):570–575.15. Hayreh SS: Ischemic optic neuropathy. Prog Retin Eye Res 2009,28(1):34–62.doi:10.1186/1471-2415-13-82Cite this article as: Neri et al.: Light-chain amyloidosis mimicking giantcell arteritis in a bilateral anterior ischemic optic neuropathy case. 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Light-chain amyloidosis mimicking giant cell arteritis in a bilateral anterior ischemic optic neuropathy case

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Light-chain amyloidosis mimicking giant cell arteritis in a bilateral anterior ischemic optic neuropathy case

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