A Case of Seronegative Pulmonary-renal Syndrome: Diagnostic and Therapeutic Challenge
Keywords:pulmonary-renal syndrome, seronegative ANCA antibody, seronegative anti-GBM antibody, plasmapheresis, a double-seronegative PRS
BACKGROUND: Pulmonary renal syndrome (PRS) is not a single entity but is caused by varied etiologies, including anti-neutrophil cytoplasmic antibody (ANCA), associated small vessel vasculitis (such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss vasculitis), Goodpasture’s syndrome, systemic lupus erythematosus, Henoch-Schonlein purpura, cryoglobulinemia, and rare causes such as druginduced vasculitis and subacute endocarditis.
CASE REPORT: We report a case of a 51-year-old man who was referred to our hospital with a 2-month history of breathing difficulties, mild hemoptysis, and deteriorated renal function with a serum creatinine of 269 μmol/L. Serological testing was negative for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody, and also all cultures, including blood and urine, remained negative. In the renal biopsy, not linear deposition of IgG along the GBM and crescents at varying stages with extracapillary glomerulonephritis emphasizes the possibility of a double-seronegative pulmonary renal syndrome. Regarding therapeutic dilemmas, on the 3rd day of hospitalization, we initiated immunosuppression with cyclophosphamide and corticosteroids as well as plasma exchange (5 treatments). Under immunosuppressive therapy and plasma exchange, the patient’s status continually improved; there was no pulmonary bleeding, but the serum creatinine remained high and renal function remained in stage 4 chronic kidney disease. Four weeks later, he was hospitalized again, and we faced a new therapeutic dilemma because of the rapid relapse during immunosuppressive therapy and renal function deterioration that required hemodialysis treatment. Despite repeatedly negative results for anti-GBM and ANCA, initial immunosuppressive therapy with plasma exchange (9 treatments) was included again. The patient was discharged 30 days after admission in a stable general condition, with the maintenance immunosuppressive therapy with mycophenolate mofetil and hemodialysis 3 times/week. After 24 months, we have received information from the hemodialysis center that he is on regular hemodialysis and that he is in good condition.
CONCLUSION: We think that in this atypical case, intensive plasma exchange and immunosuppressive therapy are crucial in the early stage and maintenance therapy is necessary for vasculitis in remission. This reported case has important clinical implications because pulmonary-renal syndrome with negative ANCAs and anti-GBM antibodies is extremely rare and no treatment recommendations have been established yet.
Plum Analytics Artifact Widget Block
Papiris SA, Manali ED, Kalomenidis I, Kapotsis GE, Karakatsani A, Roussos C. Bench-to-bedside review: Pulmonary-renal syndromes-an update for the intensivist. Crit Care. 2007;11(3):213. https://doi.org/10.1186/cc5778 PMid:17493292
Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syndrome: A 4-year, single-center experience. Am J Kidney Dis. 2002;39:42- 7. https://doi.org/10.1053/ajkd.2002.29876 PMid:11774100 3. Geetha D, Jefferson JA. ANCA-associated vasculitis: Core curriculum 2020. Am J Kidney Dis. 2020;75(1):124-37. https://doi.org/10.1053/j.ajkd.2019.04.031 PMid:31358311
Pusey CD. Anti-glomerular basement membrane disease. Kidney Int. 2003;64(4):1535-50. https://doi.org/10.1046/j.1523-1755.2003.00241.x
KDIGO Clinical Practice Guideline for Glomerulonephritis. Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis. Kidney Int Suppl. 2012;2:233-42. https://doi.org/10.1038/kisup.2012.26
West SC, Arulkumaran N, Ind PW, Pusey CD. Pulmonaryrenal syndrome: A life threatening but treatable condition. Postgrad. 2013;89(1051):274-83. https://doi.org/10.1136/ postgradmedj-2012-131416 PMid:23349383
McAdoo SP, Tanna A, Hrušková Z, Holm L, Weiner M, Arulkumaran N, et al. Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients. Kidney Int. 2017;92(3):693-702. https://doi.org/10.1016/j.kint.2017.03.014 PMid:28506760
Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD atlas of renal pathology: Anti-glomerular basement membrane antibodymediated glomerulonephritis. Am J Kidney Dis. 2016;68(5):e29- 30. https://doi.org/10.1053/j.ajkd.2016.09.003
Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD atlas of renal pathology: Pauci-immune necrotizing crescentic glomerulonephritis. Am J Kidney Dis. 2016;68(5):31-2. https://doi.org/10.1053/j.ajkd.2016.09.002
Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med. 2004;25(3):583-92. https://doi.org/10.1016/j.ccm.2004.04.007 PMid:15331194
Li J, Li C, Li J. Thoracic manifestation of Wegener’s granulomatosis: Computed tomography findings and analysis of misdiagnosis. Exp Ther Med. 2018;16(1):413-9. https://doi.org/10.3892/etm.2018.6154 PMid:29896268
Chen M, Yu F, Wang SX, Zou WZ, Zhao MH, Wang HY. Antineutrophil cytoplasmic autoantibody-negative pauciimmune crescentic glomerulonephritis. J Am Soc Nephrol 2007;18(2):599-605. https://doi.org/10.1681/asn.2006091021 PMid:17215440
Adapa S, Madhav Konala V, Hou J, Naramala S, Agrawal N, Dhingra H, et al. Seronegative atypical anti-glomerular basement membrane crescentic glomerulonephritis. Ann Transl Med. 2019;7(11):246. https://doi.org/10.21037/atm.2019.04.60 PMid:31317016
Salama AD, Dougan T, Levy JB, Cook HT, Morgan SH, Naudeer S, et al. Goodpasture’s disease in the absence of circulating anti-glomerular basement membrane antibodies as detected by standard techniques. Am J Kidney Dis. 2002;39(6):1162-7. https://doi.org/10.1053/ajkd.2002.33385 PMid:12046026
Rovin BH, Caster DJ, Cattran DC, Gibson KL, Hogan JJ, Moeller MJ, et al. Management and treatment of glomerular diseases (part 2): Conclusions from a kidney disease: Improving global outcomes (KDIGO) controversies conference. Kidney Int. 2019;95(2):281-95. https://doi.org/10.36485/1561-6274-2020-24-2-22-41 PMid:30665569
Yamaguchi H, Shirakami A, Haku T, Taoka T, Nakanishi Y, Inai T, et al. Pulmonary-renal syndrome with negative ANCAs and anti-GBM antibody. Case Rep Nephrol. 2013;2013:434531. https://doi.org/10.1155/2013/434531
Fröhlich-Gildhoff M, Jabs WJ, Berhold C, Kuhlmann MK, Ketterer U, Kische S, et al. A rare clinical course of seronegative pulmonary-renal syndrome. Case Rep Crit Care. 2016;2016:4893496. https://doi.org/10.1155/2016/4893496
How to Cite
Copyright (c) 2021 Shkelqim Muharremi, Aleksandar Poposki, Vangelka Kovaceska, Liljana Tozija, Gordana Petrusevska, Biljana Gerasimovska, Blerim Bexheti, Nikola Gjorgjievski, Zoran Janevski, Muhamed Saidi, Adrijana Spasovska, Bojana Poposka, Gjulsen Selim (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All rights reserved.