syphilis is a sexually transmitted disease caused by infection with the bacterium treponema pallidum whose diagnosis remains elusive .
the introduction of penicillin approximately 60 years ago along with public health improvements led to a decline in syphilis infection rates.1 however , after the rise of acquired immunodeficiency syndrome , the incidence of reported cases of syphilis increased.2 moreover , in south korea , the number of reported cases of syphilis gradually increased from 134 to 1,548 between 2002 and 2008.3 syphilis is clinically subdivided into three stages : primary , secondary , and tertiary .
secondary syphilis can spread to the stomach , kidney , liver , joints , and eyes .
the first two cases of gastric syphilis ( gs ) were reported in 1834 by andral,4 and the first histopathologically confirmed case of gs was reported by graham at 1922 in a patient whose tissues had been surgically removed.4 subsequently , additional studies have described a high incidence of gs diagnoses based on clinical , serological , and radiological evidences.1 moreover , kidney involvement due to syphilis has been reported during secondary , latent , and tertiary syphilis.5 although a number of nephritic syndrome case reports associated with secondary syphilis have previously been published , it is considered a rare presentation.6 furthermore , some cases of syphilis - related nephropathy were reported in the 1940s and 1950s , but relatively little has been published in more recent times . in addition , the co - occurrence of gs and nephrotic syndrome in the same patient is extremely rare . here
we report a particular case of gs presenting with concomitant membranous glomerulonephritis ( mgn ) .
as cases such as this represent a diagnostic challenge , this report provides information on the typical features of gs that might be helpful for raising awareness of this rare disease entity among clinicians , facilitating its earlier diagnosis and appropriate therapy .
a 34-year - old unmarried man presented to our hospital on february 28 , 2011 with nocturnal epigastric pain and mild febrile sensation lasting 3 weeks .
physical examination on admission revealed a blood pressure of 110/70 mm hg , heart rate of 82 beats per minute , respiration rate of 14 breaths per minute , body temperature of 36.8 , and 1 + pitting edema below the knee .
he did not have any important personal , family , hospitalization , surgery , or other diseases history .
multiple ulcers and erosions , extending from the cardia to the pylorus , were observed on upper endoscopy ( fig .
1 ) . the gastric mucosa was thickened and friable , and associated with the ulcer lesions .
histologically , the biopsied tissue revealed gastric ulcer and diffuse active gastritis with dense plasma cell infiltration , as well as variable numbers of lymphocytes and neutrophils .
although no endarteritis or endophlebitis were observed , owing to the superficial nature of biopsied tissue , silver staining was performed because of the suspicion of gs .
numerous spirochetes were detected within the lamina propria and between epithelial cells , confirming the diagnosis of gs .
in addition , some helicobacter organisms were also identified in the superficial mucus layer ( fig .
2 ) . laboratory investigations revealed normal hemoglobin , hematocrit , white blood cell count , and liver function .
the speckled and skeleton patterns of antinuclear antibodies were detected at a titer of 1:80 and 1:320 , respectively .
. the venereal diseases research laboratory ( vdrl ) syphilis serology test was positive , with a titer of 1:256 , and the fluorescent treponemal antibody absorption ( fta - abs ) and t. pallidum latex agglutination tests were also positive .
urinalysis revealed 3 + protein without blood or red blood cells , and a 24-hour urine collection revealed 11.3 g of protein .
laboratory data showed blood urea nitrogen , creatinine , and albumin values of 19 mg / dl , 1.2 mg / dl , and 1.8 g / dl , respectively .
serum total cholesterol and triglycerides were elevated , with values of 301 mg / dl and 202 mg / dl , respectively . at this stage , we suspected nephrotic syndrome secondary to syphilis , and a diagnostic kidney biopsy was performed .
the renal biopsy revealed slight thickening of glomerular capillary walls with segmental subepithelial ' pores ' on tangentially cut sections on silver staining , but the mesangium was not expanded .
weak granular immunoglobulin g ( igg ) and c3 staining along the glomerular capillary walls was observed on immunofluorescence microscopy .
electron microscopy ( em ) could not be performed because the em sample did not include the glomerulus ( fig .
correlation of clinical and serological findings with gastroscopy and renal biopsy results was consistent with gs and mgn secondary to syphilis .
the patient was treated with 2.4 million units of penicillin g benzathine , leading to resolution of his clinical symptoms , including epigastric pain , skin rash , and generalized edema .
the proteinuria also improved , with a reduction in the 24-hour urine protein values from 11.3 to 0.7 g after penicillin g treatment .
although gs patients generally experience epigastric pain , anorexia , early satiety , nausea , vomiting , and weight loss,7,8 these symptoms rarely contribute to gs diagnosis.1 a systematic review published in 2010 showed that the majority of patients with gs had no clinical history ( 87% ) or physical examination results ( 56% ) compatible with syphilis .
moreover , as no clear diagnostic criteria exist , establishing relevant associations between the medical , sexual history , and physical examination is important for diagnosis .
moreover , as symptoms are nonspecific , a high degree of diagnostic suspicion is especially required . as gastric involvement
is usually seen after secondary syphilis when the spirochetes spread via the circulation , after considering the timing of past intercourse in our patient history , we estimated that he had secondary stage syphilis .
most patients show more than one lesion type , including multiple ulcerations ( 48% ) , nodular mucosa ( 26% ) , erosions ( 24% ) , large ulcers ( 24% ) , thickened folds ( 17% ) , narrowing and rigidity ( 17% ) , and mass lesions ( 2%).1 hypertrophy of the rugae at the antral and prepyloric regions is a common endoscopic finding . moreover
, rugal hypertrophy and poor distensibility may lead to misdiagnosis of scirrhous carcinoma or lymphoma.9 a reddish purple stomach color is thought to be characteristic of gs by some authors.10 in our case , upper endoscopy revealed multiple irregular , shallow ulcers covered with whitish exudates and a central depression ranging from 0.5 to 2 cm in diameter in the antrum , body , and cardia , abruptly ending at the pyloric level .
complications including gastric hemorrhage , perforation , and gastric outlet obstruction have also been reported , but are less common.11 spirochetes detection on silver staining is difficult in a background of elastic and reticulum fibers . nevertheless , a positive finding of mucosal spirochetes on silver staining is considered an important diagnostic tool for gs . in our case ,
histopathological analysis findings compatible with endovasculitis include arterial wall and submucosal layer thickening , perivascular cell infiltrate , diffuse lymphocytes , and plasmocytes infiltrate .
although vasculitis , manifested by endarteritis or endophlebitis , is a typical finding in other sites , it is rarely observed in gastric samples , probably because endoscopic biopsies do not reach the submucosal layer .
the nephrotic syndrome that occurs in patients with syphilis is the most common clinical sign that occurs in 0.3% of patients with syphilis,12 and results from the growth of syphilis bacteria in the kidney .
the mechanism of renal injury associated with syphilis involves an immune complex - mediated glomerulonephropathy , with mgn being the most common .
however , in korea , only one case of concurrent gs and nephrotic syndrome was reported by kwon et al.13 in 2004 . in our case ,
the patient was diagnosed by using serology , gastroscopy , and renal biopsy , and his clinical symptoms and laboratory findings completely improved after penicillin treatment .
even though gs and mgn caused by syphilis are rare , it is important to emphasize this particular case owing to its diagnostic difficulty .
furthermore , as syphilis prevalence has seen a recent increase , it is likely that more patients will present to the clinic .
thus , recognition of the clinical picture of syphilis and its gastric and renal complications is important . by providing information on the typical features of gs ,
this case report will help to raise awareness of this rare disease entity among clinicians , resulting in earlier diagnosis and appropriate therapy .
 syphilis is a chronic systemic infectious disease caused by the bacterium treponema pallidum . gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis , but the co - occurrence of these two complications in the same patient is extremely rare 
 . 
 thus , because of their nonspecific presentation , suspicion of gastric syphilis ( gs ) and nephrotic syndrome is essential for diagnosis . 
 patients should be investigated thoroughly and a diagnosis made based on clinical , endoscopic , and histological findings , in order to initiate appropriate therapy . 
 we report of a 34-year - old male patient with a history of epigastric pain and a diagnosis of gs and syphilis - associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy , who was treated successfully with penicillin g benzathine . 
 this case report provides information on the typical features of gs that should help raise awareness of this rare disease entity among clinicians , resulting in earlier diagnosis and administration of appropriate therapy . 
INTRODUCTION
CASE REPORT
DISCUSSION