AA amyloidosis as a multidisciplinary problem - report of three cases of rare diseases, complicated by systemic AA amyloidosis

Introduction: АА amyloid precursor is serum amyloid A protein, produced in response to the cytokine stimulation. The broad spectrum of the diseases with quite different etiology and pathogenesis may be eventually compicated by AA amyloidosis, in some cases these are rare diseases, presenting difficulties for diagnostics. Case presentation: we present three cases of systemic AA amyloidosis, illustrating the difficulties in diagnostics of the underlying diseases. AA amyloidosis complicated prolonged chronic inflammation in patients with Castleman’s disease, sclerosing angiomatoid nodular transformation of spleen (SANT), and cystic fibrosis. In all cases the disease had a prolonged course with persistent chronic inflammation, presenting with non-specific clinical features and highly elevated C-reactive protein level. AA amyloidosis diagnostics based on the gradual development of nephrotic syndrome with impaired kidney function was confirmed by histology. End stage of renal disease demanded hemodialysis, however, surgical removal of the source of inflammation and absence of other organs dysfunction gives an opportunity to offer kidney transplantation. Conclusions: nephrotic syndrome and impaired kidney function in patients with signs and symptoms of chronic inflammation, regardless of its known or unknown origin, provide the high suspicion index for AA amyloidosis. Pathology confirmation is crucial; however even in the absence of timely pathology diagnostics clinical judgment in some cases gives a guidance for work-up and treatment. Different etiology of chronic inflammatory conditions, leading to AA amyloidosis, demands multidisciplinary approach. Rarity of the described conditions leads to the substantial difficulties for diagnostics; therefore only collaboration between the representatives of different specialties ensures adequate diagnostics and successful treatment.

почки, болезнь Кастлемана, склерозирующая ангиоматоидная нодулярная трансформация селезенки, муковисцидоз, АА amyloidosis, kidneys, Castleman’s disease, sclerosing angiomatoid nodular transformation, cystic fibrosis

1. Sipe J.D., Benson M.D., Buxbaum J.N., Ikeda S., Merlini G., Saraiva M.J., Westermark P. Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid. 2014; 21(4): 221-224. doi: 10.3109/13506129.2014.964858

2. Said S.M., Sethi S., Valeri A.M., Leung N., Cornell L.D., Fidler M.E., Herrera Hernandez L., Vrana J.A., Theis J.D., Quint P.S., Dogan A., Nasr S.H. Renal amyloidosis: origin and clinicopatholpgic correlations of 474 recent cases. Clin J Am soc Nephrol. 2013;8: 1515-1523

3. Picken M.M., Dogan A. Amyloidosis of the Kidney, the Lower Urinary and Genital Tract IMale and female) and the Breast. In Amyloid and Related Disorders. Ed Picken M.M., Herrera G.A., Dogan A. Humana Press (Springer) 2015: 369-390

4. Lachmann H.J., Goodman H.J.B., Gilbertson A.J., Gallimore J.R., Sabin S.A., Gillmore J.D., Hawkins P.N. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007;356: 2361-2371

5. Obici L., Merlini G. AA amyloidosis: Basic knowledge, unmet needs and future treatments. Swiss medical weekly. 2012;31: 142. DOI: 10.4414/smw.2012.13580

6. Ombrello A.K., Aksentijevich I. AA Amyloidosis. In Amyloid and Related Disorders. Ed Picken M.M., Herrera G.A., Dogan A. Humana Press (Springer) 2015: 31-54

7. Castleman B., Iverson L., Menendez V.P. Localized mediastinal lymphnode hyperplasia resembling thymoma. Cancer. 1956;(4):822-830

8. Munshi N., Mehra M., van de Velde H., Desai A., Potluri R., Vermeulen J. Use of a claims database to characterize and estimate the incidence rate for Castleman disease. Leuk Lymphoma. 2015;56: 1252-1260

9. Cronin D.M., Warnke R.A. Castleman disease: an update on classification and the spectrum of associated lesions. Adv Anat Pathol. 2009;16: 236-246

10. Lachmann H.J., Gilbertson J.A., Gillmore J.D., Hawkins P.N., Pepys M.B. Unicentric Castleman's disease complicated by systemic AA amyloidosis: a curable disease. Q J Med. 2002; 95 (4): 211-218

11. El Karoui K., Vuiblet V., Dion D. et al. Renal involvement in Castleman disease. Nephrol Dial Transplant. 2011; 26(2): 599-609

12. Gaduputi V., Tariq H., Badipatla K., Ihimoyan A. Systemic Reactive Amyloidosis Associated with Castleman's Disease. Case Rep Gastroenterol. 2013;7(3): 476-481. doi: 10.1159/00035682

13. Curioni S., D’Amico M., Quartagano R., Martino S., Dell’Antonio G., Cusi D. Castleman's disease with nephrotic syndrome, amyloidosis and autoimmune manifestations. Nephrol Dyal Transplant. 2001;16(7): 1475-1478

14. Martel M., Cheuk W., Lombardi L., Lifschitz-Mercer B., Chan J.K., Rosai J. Sclerosing angiomatoid nodular transformation (SANT): report of 25 cases of a distinctive benign splenic lesion. Am J Surg Pathol. 2004; 28: 1268-1279

15. Wang T-B., Hu B-G., Liu D-W., Gao Z.H., Shi H.P., Dong W.G. Sclerosing angiomatoid nodular transformation of the spleen: A case report and literature review. Oncology Letters. 2016;12: 928-932

16. Nagai Y., Satoh D., Matsukawa H., Shiozaki S. Sclerosing angiomatoid nodular transformation of the spleen presenting rapid growth after adrenalectomy: Report of a case. International Journal of Surgery Case Reports. 2017;30: 108-111

17. Önder S., Kosemehmetoglu K., Himmetoglu C., Firat P., Uner A. Sclerosing angiomatoid nodular transformation (SANT) of spleen: a case report describing cytology, histology, immunoprofile and differential diagnosis. Cytology. 2012;23:129-132

18. Kashiwagi S., Kumasaka T., Bunsei N., Fukumura Y., Yamasaki S., Abe K. Detection of Epstein-Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen. Virchows Arch. 2008; 453:275-282

19. Said S.M., Leung N., Sethi S., Cornell L.D., Fidler M.E., Grande J.P., Herrmann S., Tefferi A., D'Agati V.D., Nasr S.H. Myeloproliferative neoplasms cause glomerulopathy. Kidney International. 2011;80: 753-759

20. Jhaveri K.D., Shah H.H., Calderon K., Campenot ES, Radhakrishnan J. Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney International. 2013;84: 34-44

21. Pallante A.J., Leung N., Kyle R.A., Tefferi A., Russell S.J., Habermann T.M., Lacy M.Q., Hayman S.R., Al-Kali A., Reeder C., Dispenzieri A., Gertz M.A., Buadi F.K., Hook C.C., Dingli D., Pardanani A. Concomitant Myeloproliferative Disorders and Amyloidosis. Blood. 2016;128: 54-80

22. Kim H.H., Hur Y.H., Koh Y.S., Kim J.C., Kim H.J., Kim J.W. Sclerosing angiomatoid nodular transformation of the spleen related to IgG4-associated disease: report of a case, Surg. Today 2013;43: 930-936

23. Zakharova E.V., Shutov E.V., Vorobyova O.A., Nikitin E.A. AA amyloidosis in a patient with essential thrombocythemia and sclerosing angiomatoid nodular transformation of the spleen. J Onco-Nephrol. 2017;1(3): 13-17. DOI: 10.5301/jo-n.5000028

24. O'Sullivan B.P., Freedman S.D. Cystic fibrosis. Lancet. 2009;373(9678): 1891-904 doi:10.1016/s0140-6736(09)60327-5. PMID 19403164.

25. Hodson M., Geddes D., Bush A. Eds. Cystic fibrosis. 2012 (3rd ed.). London, Hodder Arnold. 486 pages. ISBN 978-1-4441-1369-3

26. Mitchell R.S., Kumar V., Robbins S.L., Abbas A.K., Fausto N. ROBBINS Basic Pathology. 2007. Saunders/Elsevier. 946 pages. ISBN 1-4160-2973-7.

27. Mc Laughlin A.M., Crotty T.B., Egan J.J., Watson A.J., Gallagher C.G. Amyloidosis in cystic fibrosis: a case series. J Cyst Fibros. 2006;5:59-61

28. Gottlieb J., Ballmann M., VonMallinckrodt C., Staab D., Smaczny C., Simon A., Welte T., Wagner T.O. Lung transplantation in cystic fibrosis - a position paper. Pneumologie. 2009;63(8):451-460

29. Braun A.T., Merlo C.A. Cystic fibrosis lung transplantation. Current Opinion in Pulmonary Medicine. 2011;17(6): 467-472

30. Kaplan B., Qazi Y., Wellen J.R. Strategies for the management of adverse events associated with mTOR inhibitors. Transplantation Reviews. 2014; 28: 126-133