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Systemic amyloidosis with bilateral conjunctival involvement: a case report
© Correa et al. 2015
Received: 5 April 2015
Accepted: 14 July 2015
Published: 19 July 2015
Conjunctival amyloidosis is a very rare condition, generally unilateral, and presents mostly as an isolated condition without systemic compromise. Our purpose is to present a new case of systemic amyloidosis with a bilateral conjunctival involvement.
A 66-years-old caucasian female complaining of conjunctival hemorrhage and chemosis in both eyes for the last five years had been discontinuously treated with topical antibiotics and corticosteroids without any evident improvement. She presented with a pink-yellow infiltration in the inferior conjunctiva of both eyes. Conjunctival biopsy under optical microscopy revealed amyloid deposit, confirmed by Congo red staining. Mucosal biopsy from esophagus and rectus confirmed amyloidosis by Congo red stain. Immunohistochemistry of bone marrow biopsy showed an increased number of plasma cells and an over-expression of light chain kappa subunit. She was treated with corticosteroids and lubrication with an improvement of symptoms. Ocular lesions remained stable after a follow-up of 3 years.
Conjunctival amyloidosis is a rare entity that may be overlooked, and should be differentiated from chronic conjunctivitis and conjunctival malignancies. Although it presents most frequently as a local process, a systemic involvement should always be ruled out.
Amyloidosis is a rare group of disorders characterized by the deposition of insoluble fibrillar proteins in a β-pleated sheet configuration, known as amyloid, within the extracellular and perivascular space, as the consequence of a wrong folding process of normally soluble proteins, and may affect virtually any organ or tissue of the body [1–5].
Amyloidosis disorders are classified into three major forms: local, systemic, and hereditary systemic amyloidosis . The acquired forms may be primary (immunologic) and secondary (reactive) . In primary amyloidosis (AL) deposits contain immunoglobulin light chains, usually lambda and kappa monoclonal types, resulting from the abnormal production by plasmocytes in the bone marrow [2, 6]. Secondary amyloidosis (AA) is formed from serum protein A, an acute phase reactant protein that is synthesized in response to longstanding inflammation . In hereditary amyloidosis protein deposits are constituted by a mutant form of the transport protein transthyretin .
Ocular amyloidosis occurs most frequently as the local deposition of amyloid in the same place where it originates or, rarely, may be part of a systemic disorder [3, 9]. Amyloid may accumulate in the eyelid, conjunctiva, cornea, vitreous, or anterior orbit [3, 10].
Conjunctival amyloidosis is one of the most common forms of ocular involvement, mostly occurring as a local deposition of amyloid and rarely in association with systemic involvement [3, 10–15]. Due to the rarity of conjunctival amyloidosis, its diagnosis can often be overlooked or confused with other conditions that may affect the conjunctiva. It is more commonly observed in middle-aged adult patients, presenting as an inflammatory or malignant conjunctival entity [3, 11]. Besides, conjunctival malignant lesions can lead to amyloidosis and they should be ruled out [3, 12].
The purpose of our study is to report a new case of systemic amyloidosis with bilateral conjunctival involvement.
A 66-year-old Caucasian woman complaining of conjunctival hemorrhage and chemosis in both eyes for the last five years had been discontinuously treated with topical antibiotics and corticosteroids without any evident improvement.
The patient was treated with topical lubrication and the ocular lesions of both eyes remained stable after a follow-up of 3 years. She continues with periodical clinical controls to assess the eventual manifestation and progression of the systemic disease.
Conjunctival amyloidosis, predominantly affecting middle-aged adults, usually begins at the fornices, spreading to the bulbar and palpebral conjunctiva . This progression appears to affect more deeply the palpebral than the bulbar conjunctiva [3, 16]. In our patient, a bilateral diffuse pink-yellow infiltration with hemorrhagic areas was found throughout the lower bulbar conjunctiva without affecting the palpebral function and position, in contrast with the findings of Demirci et al  that observed a unilateral involvement in all of their six cases.
Associated spontaneous conjunctival hemorrhages, as observed in our patient, are a common finding that may be explained by the fact that amyloid infiltration of vessel walls induces rigidity and disruption of conjunctival vessels . A complete systemic evaluation to discard a primary systemic form of the disease is recommended  as conjunctival amyloidosis might be an early manifestation of systemic amyloidosis . In our case, the initial presentation of conjuctival amyloidosis led to the systemic findings that were asymptomatic. Only five cases have been reported as systemic amyloidosis with conjunctival involvement [3, 12–15].
Even though the condition may be clinically suspected, a tissue biopsy of the involved organ should be taken to confirm the diagnosis. In systemic disease the sampling can be performed directly in the organ or tissue affected, or in a clinically uninvolved site such as subcutaneous fat, minor salivary glands or rectal mucosa [1, 3]. Furthermore, testing for monoclonal protein population should be determined by serum and urine protein electrophoresis and immunofixation . In our patient, immunofixation of blood samples only revealed polyclonal hypergammaglobulinemy, and rectal and esophageal mucosal biopsies confirmed the diagnosis of systemic amyloidosis. In addition, immunohistochemical studies of bone marrow biopsies showed an increased population of plasma cells with the amyloidogenic overexpression of the subunit kappa.
There is still no consensus on the management of conjunctival amyloidosis and none of the available treatments are radical. Some authors recommend conservative treatment using lubricants and topical anti-inflammatories . Others believe that a more aggressive treatment should be done in order to prevent progression or recurrence . Cryotherapy,  radiotherapy,  surgical debulking,  and mucous membrane graft implantation,  are among the techniques that could be used. A conservative topical treatment was offered to our patient, as lesions remained stable over time and the patient referred no major ocular complaints.
Conjunctival amyloidosis is a rare entity that may be overlooked and should be differentiated from chronic conjunctivitis and conjunctival malignancies. Although commonly a local process, a systemic involvement should always be ruled out.
Written informed consent was obtained from the patient for publication of this Case report and any of the accompanying images. A copy of the written consent is available for review by the Editors of BMC Ophthalmology.
The authors are grateful to Dr. Ana V. Sanchez and Dr. Ana B. de Diller from the Department of Pathology, Hospital Privado Centro Medico de Cordoba, Argentina, for their invaluable assistance concerning bone marrow biopsy analysis and imaging.
- Goveric PD. An overview of amiloidosis. UpToDate® Wolters Kluwer Health. 2013; http://www.uptodate.com/contents/an-overview-of-amyloidosis
- Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, et al. Amyloid: Toward terminology clarification. Report from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid. 2005;12:1–4.View ArticlePubMedGoogle Scholar
- Leibovitch I, Selva D, Goldberg RA, Sullivan TJ, Saeed P, Davis G, et al. Periocular and orbital amyloidosis: clinical characteristics, management, and outcome. Ophthalmology. 2006;113:1657–64.View ArticlePubMedGoogle Scholar
- Demirci H, Shields CL, Eagle Jr RC, Shields JA. Conjuctival amyloidosis: report of six cases and review of the literature. Surv Ophthalmol. 2006;51:419–33.View ArticlePubMedGoogle Scholar
- Westermark GT, Fändrich M, Westermark P. AA amyloidosis: pathogenesis and targeted therapy. Annu Rev Pathol. 2015;10:321–44.View ArticlePubMedGoogle Scholar
- Glenner GG, Terry W, Harada M, Isersky C, Page D. Amyloid fibril proteins: proof of homology with immunoglobulin light chains by sequence analyses. Science. 1971;172:1150–1.View ArticlePubMedGoogle Scholar
- Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007;356:2361–71.View ArticlePubMedGoogle Scholar
- Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35:E2403–12.View ArticlePubMedGoogle Scholar
- Al-Nuaimi D, Bhatt PR, Steeples L, Irion L, Bonshek R, Leatherbarrow B. Amyloidosis of the orbit and adnexae. Orbit. 2012;31:287–98.View ArticlePubMedGoogle Scholar
- Aryasit O, Preechawai P, Kayasut K. Clinical presentation, treatment, and prognosis of periocular and orbital amyloidosis in a university-based referral center. Clin Ophthalmol. 2013;7:801–5.View ArticlePubMedPubMed CentralGoogle Scholar
- Ray M, Tan AW, Thamboo TP. Atypical presentation of primary conjuctival amiloidosis. Can J Ophthalmol. 2012;47:e2–4.View ArticlePubMedGoogle Scholar
- Abdallah AO, Westfall C, Brown H, Muzaffar J, Atrash S, Nair B. Unilateral conjunctival AL kappa amyloidosis with trace evidence of systemic amyloidosis. Am J Case Rep. 2012;13:102–5.View ArticlePubMedPubMed CentralGoogle Scholar
- Purcell Jr JJ, Birkenkamp R, Tsai CC, Riner RN. Conjunctival involvement in primary systemic nonfamilial amyloidosis. Am J Ophthalmol. 1983;95:845–7.View ArticlePubMedGoogle Scholar
- Iijima S. Primary systemic amyloidosis: a unique case complaining of diffuse eyelid swelling and conjunctival involvement. J Dermatol. 1992;19:113–8.View ArticlePubMedGoogle Scholar
- Shields JA, Eagle RC, Shields CL, Green M, Singh AD. Systemic amyloidosis presenting as a mass of the conjunctival semilunar fold. Am J Ophthalmol. 2000;130:523–5.View ArticlePubMedGoogle Scholar
- Rodrigues G, Sanghvi V, Lala M. A rare cause of unilateral upper and lower eyelid swelling: isolated conjuctival amyloidosis. Korean J Ophthalmol. 2001;15:38–40.View ArticlePubMedGoogle Scholar
- Patrinely JR, Koch DD. Surgical management of advanced ocular adnexal amyloidosis. Arch Ophthalmol. 1992;110:882–5.View ArticlePubMedGoogle Scholar
- Fraunfelder FW. Liquid nitrogen cryotherapy for conjunctival amyloidosis. Arch Ophthalmol. 2009;127:645–8.View ArticlePubMedGoogle Scholar
- Khaira M, Mutamba A, Meligonis G, Rose GE, Plowman PN, O´Donnell H. The use of radiotherapy for the treatment of localized orbital amyloidosis. Orbit. 2008;27:432–7.View ArticlePubMedGoogle Scholar
- Murdoch IE, Sullivan TJ, Moseley I, Hawkins PN, Pepys MB, Tan SY, et al. Primary localized amyloidosis of the orbit. Br J Ophthalmol. 1996;80:1083–6.View ArticlePubMedPubMed CentralGoogle Scholar
- Seider N, Beiran I, Kaltreider SA. Advanced localized primary conjunctival amyloidosis: surgical rehabilitation using mucous membrane graft implantation. Isr Med Assoc J. 2006;8:439–40.PubMedGoogle Scholar
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