Syphilis masquerading as focal segmental glomerulosclerosis

Introduction

Syphilis is the “great imitator”, presenting with single organ or multi-system disease. Renal manifestations of syphilis are well described but rare. Secondary and late syphilis have been associated with nephrotic syndrome, with biopsy revealing membranous,^1–5 minimal change ⁶ or rapidly progressive glomerulonephritis. ⁷ Tertiary syphilis can cause renal gummas. ⁸

Syphilis serology is often included as part of a general medical screen but positive serology may be viewed as incidental and not attributed to the presenting condition. We report a case of positive syphilis serology in a Burmese gentleman presenting with nephrotic syndrome.

Case report

A 54-year-old Burmese gentleman was referred to the genitourinary clinic with a swollen penis and scrotum, and positive syphilis serology: enzyme immunoassay (EIA) positive, Treponema pallidum particle agglutination assay (TPPA) positive and rapid plasma reagin negative. He described bilateral leg oedema along with penile and scrotal swelling which had developed over six weeks. He last had sexual intercourse with his wife one year ago and had had no other sexual partners for the last 20 years. He could not recall genital ulcers or rashes and had not previously been treated for syphilis. His past medical history included vertigo and arthritis and his drug history included amitriptyline and co-codamol. On examination, he had bilateral lower limb oedema to the groin with penile and scrotal oedema. Cardiovascular and neurological examinations were normal and he was normotensive. There were no genital ulcers or features of secondary syphilis. Urethral swab for a Gram-stained smear revealed a dry slide. Urine dipstick showed 3+ protein but was negative for glucose, blood, nitrites and leucocytes.

The gentleman was referred to the renal physicians. Repeat syphilis serology confirmed the initial result. Other significant results included creatinine 132 µmol/L and albumin 15 g/L. A further renal screen revealed negative hepatitis B, hepatitis C and HIV serology, negative serum electrophoresis with no paraprotein and negative vasculitic screen including lupus serology. Urine protein:creatinine ratio (UPCR) was 1108 mg protein/mmol creatinine. Renal biopsy showed focal segmental glomerulosclerosis (FSGS; Figures 1–3) with IgM decorating the mesangial regions and segmental lesions. Glomerular tip lesions were present. Polymerase chain reaction (PCR) for T. pallidum was negative on the biopsy. OPEN IN VIEWER

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Figure 2.

Haematoxylin and eosin stain highlights the segmental region of sclerosis.

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Figure 3.

Silver stain confirms an absence of spikes.

Causes of FSGS such as HIV, drugs, malignancy and haemodynamic factors were excluded as a cause of secondary FSGS. He was treated for late syphilis with doxycycline 200 mg twice a day for 28 days, having declined injections. The regimen was chosen so to provide antimicrobial cover for asymptomatic neurosyphilis (as lumbar punctures are not routinely performed in our centre), given the suspicion of a causal relationship between the FSGS and syphilis. Steroids were not used as treatment of the FSGS was felt to be treatment of the possible underlying cause.

Having only had treatment with doxycycline, in the context of untreated FSGS, a drop in proteinuria with urine PCR falling to 254 mg protein/mmol creatinine and normalisation of the serum albumin was noted. He was commenced on irbesartan with further improvement in his proteinuria. On review at three months, he had normal renal function, no oedema nor proteinuria and consequently a convalescent biopsy was not performed. His wife’s syphilis serology was negative.

Over two years since his initial presentation, our patient has represented with nephrotic syndrome. The cause of the nephrotic syndrome remains unclear, with no new positive results. His syphilis serology has remained unchanged. He has been started on steroids and accepting injections, he is now in the process of being retreated with 17 days of procaine penicillin 1.8 MU intramuscularly plus probenecid 500 mg four times a day.

Discussion

FSGS is a cause of nephrotic syndrome, and can be divided into primary and secondary types. Causes of secondary FSGS include drugs, viral and haemodynamic factors with a genetic predisposition also isolated. ⁹ It is likely acute asymptomatic infection with parvovirus can cause FSGS, although not tested in our case. ¹⁰ In relation to sexually transmitted infections, FSGS is most commonly seen in HIV associated nephropathy (HIVAN). ¹¹

In terms of syphilis, renal presentations, although rare, are more commonly a manifestation of secondary disease. Proteinuria in the context of secondary syphilis may be common and often be undiagnosed. In one old study of patients with secondary syphilis, proteinuria and frank nephrotic syndrome was found in 7% and 0.3% of patients’, respectively. ¹² Membranous glomerulonephritis is the commonest histological finding associated with syphilis^1–5 but case reports describe associations with minimal change ⁶ and rapidly progressive glomerulonephritis. ⁷ Anti-treponemal antibodies within glomerular immune complex deposits have been demonstrated in some reports, offering an aetiology to syphilitic glomerulonephritis. ¹³

In our case, late ‘latent’ syphilis was diagnosed from the patient’s syphilis serology, sexual history and absence of signs consistent with primary, secondary or tertiary syphilis. On his first presentation, the nephrotic syndrome improved rapidly with anti-treponemicidal medication. It was therefore hypothesised that syphilis was a cause of secondary FSGS, as spontaneous remissions are rare in the absence of other specific treatment including steroids. It is unclear why FSGS would present in late, serologically latent, syphilis but other specific causes of FSGS were excluded. Representing over two years later, we feel he warrants first line treatment for late syphilis in case of treatment failure.^14,15

Conclusion

Syphilis serology continues to be performed by clinicians to investigate multiple presenting complaints. From his initial presentation, this case suggests a possible therapeutic diagnosis of syphilitic renal disease. Syphilis is the “great imitator” and most importantly, the case serves to remind clinicians not to dismiss positive syphilis serology.