Self limited membranous glomerulonephritis due to syphilis

Accepted Article SELF LIMITED MEMBRANOUS GLOMERULONEPHRITIS DUE TO SYPHILIS SELF LIMITED MEMBRANOUS GLOMERULONEPHRITIS DUE TO SYPHILIS Ana R. Fernandes1 [email protected] Francisco Gouveia2 [email protected] Marcio S. R. Viegas1 [email protected] Sofia S. Coelho1 [email protected] Elsa Q. Soares1 [email protected] Ana S. Natário1 [email protected] José C. Barreto1 [email protected] José M. Vinhas [email protected] 1 Centro Hospitalar de Setúbal 2 Centro Hospitalar Barreiro Montijo Corresponding author: Ana R. Fernandes Centro Hospitalar de Setúbal – Departamento de Nefrologia R. Camilo Castelo Branco, 2910-446 Setúbal, Portugal Key words: Syphilis, membranous glomerulonephritis, nephrotic syndrome This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jdv.14329 This article is protected by copyright. All rights reserved. Accepted Article Editor, Syphilis is known as “the great mimic” owing to the wide range of clinical presentations. Primary syphilis usually presents as a highly contagious ulcerated lesion that appears 9-90 days after infection (1). Secondary syphilis manifests after hematogenous and lymphatic dissemination. We report a case of secondary syphilis manifested by auto-limited nephrotic syndrome. A 29-year-old woman with small erythematous papules in the trunk and upper limbs, lower limb edema and inguinal adenopathy was admitted at our Hospital. From the lab work done we highlight hypoalbuminemia (1.1 g/dL) and hypercholesterolemia (total cholesterol 363 mg/dl, LDL 252 mg/dl, triglycerides 305 mg/dl). Urine sediment showed 10 erythrocytes per field, hyaline casts and the spot urine protein-to-creatinine ratio was 5.3 gr/gr. Anticardiolipin antibodies was Ig M 65 U/mL and Ig G 21 U/mL and β2-glycoprotein was negative, further auto-immunity test and tests for HBsAg, anti-HCV and HIV antibodies were negative. To aid the diagnosis we did a kidney biopsy before every serological result being available, the histological lesions made the diagnosis of membranous glomerulopathy- Stage I (Figure 1). By this time we got the result of VDRL serology test, showing a titre of 1/64. Treponema pallidum particle agglutination assay (TPHA) title was 1/2560. We repeated the proteinuria measurement and it was negative. The clinical manifestations vanished, however we later administered 2 400 000 U of intramuscularly penicillin to treatment of the disease. Renal manifestations of secondary syphilis are known since the 18th century (2). Renal manifestations of syphilis can range from mild transient proteinuria to frank nephrosis associated with minimal change disease, membranous glomerulopathy or even diffuse proliferative glomerulonephritis or rapidly progressive crescentic glomerulonephritis. Renal gumma and amyloid are also reported with late syphilis (3). The most frequent histological lesion is membranous nephropathy. Membranous glomerulonephritis from syphilis is the result of antitreponemal antibody (Ig G) or immune complex deposition in the This article is protected by copyright. All rights reserved. Accepted Article subepithelial layer of the glomerular basement membrane (4). The deposition of these immune complexes results in complement mediated podocyte injury and proteinuria (4). It is difficult to establish a true causal relationship between syphilis and renal disease. Pointer to the diagnosis include history of recent infection, coexistence of late primary or secondary syphilis with nephropathy, a positive serological test, spontaneous remission or rapid recovery following antisyphilitic therapy and the absence of other causes of renal disease (5). The patient of the case reported fulfilled all the criteria above. To our Knowledge this is the second case of subclinical syphilis and membranous glomerulonephritis with a spontaneous remission of the proteinuria. Satoskar et al (6) reported a similar case but due to the initial diagnosis of lupus membranous glomerulonephritis they did an empirical treatment with corticosteroids and mycophenolate mofetil. They attributed the remission of the proteinuria to this medication. In the case we report the patient had not done any immunosuppressive treatment and proteinuria remited before infection treatment. This spontaneous remission is characteristic of secondary syphilis manifestations (7), though the pathophysiological explanation to this finding was not found. Syphilis is an emerging disease; global statistics show about 10 000 new reports every year (8). In Europe the incidence of the disease has been increasing (9) particularly in men who have sex with men. In Portugal, until 2013 primary syphilis was an obligatory notification disease and between 2009 and 2012 there was an increase of its incidence. In 2009 it was reported 150 cases, in 2010 - 179 cases, in 2011 -159 cases and 267 new cases in 2012 (10). In the 70’s and 80’s there were some cases describing renal manifestations of syphilis but nowadays they are rare. The number of cases of syphilis is rising, so it may re-emerge and clinical suspicion to diagnosis is essential to adequate treatment of the disease. This article is protected by copyright. All rights reserved. Accepted Article REFERENCES 1. Goh BT. Syphilis adults. Sex Transm Infect 2005;81:6 448-452 2 Hunte W, al-Ghraoui F, Cohen RJ. Secondary syphilis and the nephrotic syndrome. J Am Soc Nephrol. 1993 Jan;3(7):1351-5. 3 Hannawi B, Raghavan R. Syphilis and kidney disease: a case report and review of literature. Nephrology Research and Reviews 2012; 4(2): 45 – 47 4 Viecelli AK, Wong DD, McLean-Tooke AP, Chakera A. Spiralling into the nephrotic syndrome. Med J Aust. 2014 Jun 16;200(11):673-4 5 Hunte W, al-Ghraoui F, Cohen RJ. Secondary syphilis and the nephrotic syndrome. J Am Soc Nephrol. 1993 Jan;3(7):1351-5. 6 Satoskar AA, Kovach P, O'Reilly K, Nadasdy T. An uncommon cause of membranous glomerulonephritis. Am J Kidney Dis. 2010 Feb;55(2):386-90 7 Canney M, Liu E, Vonthethoff L, Weatherall C, Ong S. Nephrotic syndrome and hepatitis due to acquired syphilis: an uncommon presentation of a re-emerging disease. NDT Plus. 2011 Feb;4(1):67-70. 8. Tong ML, Lin LR, Liu GL, Zhang HL, Zeng YL, Zheng WH, et al. Factors associated with serological cure and the serofast state of HIV-negative patients with primary, secondary, latent, and tertiary syphilis. PLoS One. 2013;8:e70102. 9. ECDC (2013) - Surveillance Report: Annual epidemiological report – Reporting on 2011 surveillance data and 2012 epidemic intelligence data. [consultado 2015 jan 12]. Disponível em: http://www.ecdc.europa.eu/en/publications/Publications/AnnualEpidemiological-Report-2013.pdf. 10. Direção-Geral da Saúde. Doenças de declaração obrigatória 2009-2012 – Volume I. [consultado 2015 jan 12]. Disponível em: http://www.google.pt/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CC MQFjAB&url=http%3A%2F%2Fwww.dgs.pt%2Fportalda-estatistica-dasaude%2Fpublicacoes-estatisticas-146417-pdf.aspx%3Fv%3D11736b14-73e64b34-a8e8- This article is protected by copyright. All rights reserved. Accepted Article d22502108547&ei=hM7HVJ2qMpaZsQT2ooCoCQ&usg=AFQjCNErfKOuiE2ON 9cHlJcUr8BoIBgZw&bvm=bv.84349003,d.cWc. Image 1A: Methamine Silver stained paraffin embedded section. The glomerulus looks unremarkable (original magnification 400x) B: Staining pattern for Imunoglobulin G – Direct immunofluorescence shows moderate granular staining for IgG along the glomerular capillary wall (frozen section original magnification x 400) C: Staining pattern for C1q – Direct immunofluorescence shows moderate granular staining for C1q along the glomerular capillary wall (frozen section original magnification x 400) This article is protected by copyright. All rights reserved.