Membranous nephropathy related to secondary syphilis

Anton Pampols, Paula; Espejo-Herrera, Nadia; Coloma, Ana

doi:10.1016/j.medcle.2021.01.018

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We report a clinical case of MN secondary to syphilis which, although a rare infection, has seen an increase in its incidence and complications during the last decade.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>The case involved a 23-year-old Caucasian male, tobacco, and cannabis smoker, with bronchial hyperresponsiveness and recurrent pharyngotonsillitis in childhood.The patient went to the emergency department for a 10-day history of arthralgias without arthritis and oedema. Two months earlier, he had presented with a dry cough, odynophagia, dysthermia without thermometer fever and generalized erythematous macular lesions that did not disappear under diascopy, including the palms and soles, but not affecting the mucous membranes, self-limiting within 15 days. He denied macroscopic hematuria; he also reported taking non-steroidal anti-inflammatory drugs and paracetamol. He denied alcohol consumption and reported unsafe sex 2 months earlier.Physical examination revealed pharyngo-tonsillar erythema, occipital lymphadenopathy, and generalized oedema. There were no lesions on the skin or mucous membranes and no signs of arthritis. The rest of the examination was normal.The CBC showed a proteinuria of 8g/d with hypoalbuminemia (18g/l), hypercholesterolaemia (7.17mmol/l), decreased antithrombin-III (67int.u./dl), creatinine of 73μmol/l, C-reactive protein 15.5mg/l and a pattern of dissociated cholestasis and mild cytolysis. Urinary sediment with mild intermittent hematuria. The immunological study showed polyclonal hypergammaglobulinemia with positive cryoglobulins not characterized by low cryocrit, with negative rheumatoid factor. Complement, antinuclear antibody, anti-neutrophil cytoplasmic antibody and antiPLA2R were negative. Negative serology for hepatitis B, C and human immunodeficiency virus, positive Epstein–Barr virus (both IgM and IgG) and positive syphilis serologies (reagin and non-reagin tests).A renal biopsy showed 31 glomeruli without significant histological findings, with hematoxylin–eosin, PAS and methenamine silver staining. Immunofluorescence showed IgG+++, C1q++, C3+/−, Kappa and Lambda+++ deposits with diffuse and generalized intramembranous granular parietal pattern. PLA2R staining was negative.It was diagnosed as MN secondary to syphilis, initiating treatment with a single dose of intramuscular benzathine penicillin (2,4 MIU), together with treatment for NS (prophylactic, lipid-lowering and diuretic heparin) and antiproteinuric therapy with angiotensin-converting enzyme inhibitor. One month after treatment the patient achieved complete remission of NS.The rare association between NS and secondary syphilis has been known for more than 100 years.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> In 1935 Herrmann and Marr reported an incidence of NS of 0.28% in a series of 1040 patients with syphilis.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Subsequently, thanks to antibiotic treatment and the use of condoms, the incidence of infection and the number of association cases decreased, with a current spike in reported cases.Although other types of nephropathies associated with syphilis (minimal change, postinfectious, …) have been reported, the most common is MN. The subepithelial deposition of syphilis antigen–antibody complexes has been postulated as the pathophysiological mechanism of kidney involvement.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> Histologically, it may develop with optically normal glomeruli, as in this case, raising the differential diagnosis with minimal change nephropathy. The most decisive findings are provided by immunofluorescence, showing abundant subepithelial deposits with a prevalence of IgG, usually along with positive C1q.Syphilis is a sexually transmitted disease caused by the Treponema pallidum spirochete. The most common lesion in secondary syphilis is a 1–2cm macular erythema, painless, affecting the palms, soles, and even mucous membranes. In addition, it can be accompanied by lymphadenopathy, hepatosplenomegaly, hepatitis, gastrointestinal symptoms, and renal involvement with NS, as in the case at hand, among others.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>Treatment of syphilis-associated MN is based on specific treatment of the infection with intramuscular benzathine penicillin, resulting in rapid clinical and laboratory improvements and a high percentage of complete nephropathy remission.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>Therefore, the possibility of underlying syphilis must be considered in the study of MN, making it a diagnostic challenge in the face of the increasing prevalence of syphilis disease and its secondary symptoms.FundingNo funding has been received for the preparation of this paper." 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Hook" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(16)32411-4" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2017" "volumen" => "389" "paginaInicial" => "1550" "paginaFinal" => "1557" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27993382" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute syphilitic nephrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Robins" 1 => "A. Ladd" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "AM J Med" "fecha" => "1962" "volumen" => "1962" "paginaInicial" => "817" "paginaFinal" => "821" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The nephrotic syndrome associated with secondary syphilis. An immune deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Braunstein" 1 => "E. Lewis" 2 => "E.G. Galvanek" 3 => "A. Hamilton" 4 => "W. Bell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0002-9343(70)90016-1" "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1970" "volumen" => "48" "paginaInicial" => "643" "paginaFinal" => "648" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4912935" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Gamble" 1 => "J. Reardan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM197502272920903" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1975" "volumen" => "292" "paginaInicial" => "449" "paginaFinal" => "454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1089888" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Syphilis: a reversible cause of nephrotic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.L. Handoko" 1 => "M. Duijvestein" 2 => "C.G. Scheepstra" 3 => "C.W.H. de Fijter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2013" "paginaInicial" => "2012" "paginaFinal" => "2014" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015700000012/v1_202112201710/S2387020621006434/v1_202112201710/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015700000012/v1_202112201710/S2387020621006434/v1_202112201710/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621006434?idApp=UINPBA00004N"]

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Vol. 157. Issue 12.

Pages 596-597 (December 2021)

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