Acute Ocular Complications after Recently Diagnosed Goodpastureʼs Syndrome – An Unusual Case of Hypertensive Retinopathy

Introduction

Ernest Goodpasture first identified Goodpastureʼs syndrome (GS) in 1919. It is a rare disease with an estimated incidence of about 0.5 – 1 case per million per year. GS most frequently occurs in two age ranges, 20 – 30 years and 60 – 70 years, and typically includes the following triad: acute renal failure, pulmonary hemorrhage, and presence of anti-glomerular basement membrane (anti-GBM) antibodies. Although the overall incidence is relatively low, GS is the cause of approximately one-fifth of all cases of acute renal failure with rapidly progressive glomerulonephritis. If accompanied by pulmonary hemorrhage or secondary malignant hypertension, the disease may be life-threatening [1].

A deeper understanding of GS was gained after the discovery of the anti-GBM antibodies binding reactive epitopes in the basement membranes of the kidneys and lungs, causing activation of the complement cascade, lastly resulting in tissue damage. These antigens are found in other specialized basement membranes, including Bruchʼs membrane, but clinically only the glomerular and alveolar basement membranes are usually affected. The reason for this seems to be the greater expression and accessibility of epitopes of the NC1 domain of the alpha 3 chain of type IV collagen units in these tissues [2], [3].

The exact cause of GS is still unknown. Genetics with an increased prevalence of HLA-DR15 and HLA-DRB1 and also certain behavioral and environmental factors (e.g., exposure to metallic dust, tobacco smoke, as well as lymphocyte depletion therapy, e.g., alemtuzumab) are thought to increase the risk [4].

GS symptoms can develop gradually, or rapidly in as little as a few days. Sixty to eighty percent of patients have clinical manifestation of both pulmonary and renal disease, 20 – 40% have renal disease alone, and less than 10% develop only lung disease. Some cases have been reported to develop autoimmune inner ear disease (AIED), presenting with sudden hearing loss [5], [6].

A kidney biopsy delivers a definitive diagnosis. Serologic assays for anti-GBM antibodies are important for initial diagnosis and monitoring of the disease treatment. The therapy involves rapid removal of circulating antibodies, primarily by plasmapheresis, as well as immunosuppression (e.g., corticosteroids and cyclophosphamide) to reduce the new production of antibodies. Currently, a 5-year survival of 80% can be reached with this treatment [4].

While systematic clinical data is missing about GS, numerous case reports and small case series have been published. However, only a few address or include potential ophthalmic manifestations of the syndrome [7], [8], [9], [10], [11], [12], [13], [14], [15].

Overall, there are two potential pathophysiological pathways by which GS can lead to ocular symptoms. On the one hand, GS involves anti-basement membrane auto-antibodies, which could lead to primary changes to eye structures due to immunoglobulin deposition in the basement membranes. On the other hand, GS can cause secondary complications, such as severe arterial hypertension, which may lead to vascular and structural changes in the ocular tissue [10].

In the following description, ocular findings in a young patient with GS are carefully described.

Publikationsverlauf

Eingereicht: 17. Oktober 2022

Angenommen: 22. Januar 2023

Artikel online veröffentlicht:
25. April 2023

• References

• 1 Cui Z, Zhao MH. Advances in human antiglomerular basement membrane disease. Nat Rev Nephrol 2011; 7: 697-705
• 2 Ohlsson S, Herlitz H, Lundberg S. et al. Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease. Am J Kidney Dis 2014; 63: 289-293
• 3 Kluth DC. Anti-Glomerular Basement Membrane Disease. J Am Soc Nephrol 1999; DOI: 10.1681/ASN.V10112446.
• 4 Greco A, Rizzo MI, De Virgilio A. et al. Goodpastureʼs syndrome: a clinical update. Autoimmun Rev 2015; 14: 246-253 DOI: 10.1016/j.autrev.2014.11.006.
• 5 Srivastava A, Rao GK, Segal PE. et al. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol 2013; 32: 1317-1322
• 6 Bovo R, Ciorba A, Martini A. Vertigo and autoimmunity. Eur Arch Otorhinolaryngol 2010; 267: 13-19
• 7 Lommatzsch C, Lommatzsch A, Heinz C. et al. Goodpasture-Syndrom: Okuläre Manifestation bei einem jungen Mann. Ophthalmologe 2018; 115: 761-764 DOI: 10.1007/s00347-017-0612-x.
• 8 Szela S, Tyszka A, Buss E. et al. [Case of Goodpastureʼs syndrome with ocular and skin manifestations]. Wiadomosci Lek Wars Pol 1960 1980; 33: 1669-1672
• 9 Köhler U. Ungewöhnlicher Verlauf eines Goodpasture-Syndroms. Klin Monbl Augenheilkd 1988; 192: 354-357 DOI: 10.1055/s-2008-1050125.
• 10 Jampol LM, Lahav M, Albert DM. et al. Ocular clinical findings and basement membrane changes in Goodpastureʼs syndrome. Am J Ophthalmol 1975; 79: 452-463 DOI: 10.1016/0002-9394(75)90622-4.
• 11 Nieuwhof CMG, de Heer F, de Leeuw P. et al. Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. Kidney Int 1997; 51: 1596-1601 DOI: 10.1038/ki.1997.219.
• 12 Rowe PA, Mansfield DC, Dutton GN. Ophthalmic features of fourteen cases of Goodpastureʼs syndrome. Nephron 1994; 68: 52-56 DOI: 10.1159/000188087.
• 13 Hoscheit AM, Austin JK, Jones WL. Nonrhegmatogenous retinal detachment in Goodpastureʼs syndrome: a case report and discussion of the clinicopathologic entity. J Am Optom Assoc 1993; 64: 563-567
• 14 Proskey AJ, Weatherbee L, Easterling RE. et al. Goodpastureʼs syndrome. A report of five cases and review of the literature. Am J Med 1970; 48: 162-173 DOI: 10.1016/0002-9343(70)90112-9.
• 15 Benoit FL, Rulon DB, Theil GB. et al. Goodpastureʼs Syndrome: A Clinicopathologic Entity. Am J Med 1964; 37: 424-444 DOI: 10.1016/0002-9343(64)90199-8.
• 16 Schoenenberger RA, Haefeli WA, Schifferli J. Hrsg. Internistische Notfälle: Sicher durch die Akutsituation und die nachfolgenden 48 Stunden. 8. Aufl.. Stuttgart: Thieme; 2008. Zugriff am 23. September 2022 unter: https://www.buchfreund.de/de/suche/ergebnisse?stichwort=3-13-510608-X
• 17 Seeman T, Hamdani G, Mitsnefes M. Hypertensive crisis in children and adolescents. Pediatr Nephrol Berl Ger 2019; 34: 2523-2537 DOI: 10.1007/s00467-018-4092-2.
• 18 van den Born BH, Lip GYH, Brguljan-Hitij J. et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother 2019; 5: 37-46 DOI: 10.1093/ehjcvp/pvy032.
• 19 American Academy of Ophthalmology. Hypertensive retinopathy. Accessed March 13, 2022 at: https://www.aao.org/image/hypertensive-retinopathy-3
• 20 Jordan J, Kurschat C, Reuter H. Arterial Hypertension. Dtsch Arztebl Int 2018; 115: 557-568 DOI: 10.3238/arztebl.2018.0557.
• 21 Muiesan ML, Salvetti M, Amadoro V. et al. An update on hypertensive emergencies and urgencies. J Cardiovasc Med (Hagerstown) 2015; 16: 372-382 DOI: 10.2459/JCM.0000000000000223.