Syphilis-related rapidly progressive glomerulonephritis: a case presentation.

BACKGROUND: Syphilis is a multisystemic infection that causes a wide variety of symptoms and thus has been dubbed one of the great medical mimickers. Due to recent global re-emergence of syphilis, it has become important to recognize its various presentations. Relative to the kidney, syphilitic infections generally present themselves with nephrotic range proteinuria, and are most often associated with pathological features of a membranous glomerulonephritis with subepithelial immune complex deposition. However, other rare renal presentations have been reported. One of these includes a rapidly progressive glomerulonephritis picture. All described cases have been successfully resolved with the treatment of the underlying syphilis infection. CASE PRESENTATION: The patient was an elderly woman of Caribbean descent who presented with lower extremity weakness, anasarca and proteinuria, hematuria with progressive renal failure. On kidney biopsy, she was found to have a pauci-immune crescentic glomerulonephritis pattern and a concomitant acute tubulointerstitial nephritis. She had a positive Treponema pallidum particle agglutination test and a negative syphilis rapid plasma reagin test with clinical evidence of polyneuropathy suggestive chronic syphilis infection. CONCLUSION AND DISCUSSION: It is important in the context of pauci-immune crescentic glomerulonephritis to explore all differential diagnoses. Given the positive syphilis serologies, clinical context and presence of tubulointerstitial nephritis, she was determined to have syphilitic glomerulonephritis that resolved with a course of both penicillin and steroids.

Resolution of syphilis-related rapidly progressive glomerulonephritis with penicillin therapy: Case report
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Renal manifestations of syphilis are variable, with membranous nephropathy being the most commonly described lesion. Rapidly progressive glomerulonephritis (RPGN) is rare and there is only one case report in the literature describing syphilis-associated crescentic glomerulonephritis. We report a rare case of RPGN secondary to latent syphilis, which resolved with penicillin treatment in the absence of immunosuppressive therapy. A 28-year-old Black male with a history of HIV was evaluated for severe acute kidney injury, nephrotic-range proteinuria, and active urine sediment. Serologies for glomerulonephritis were negative. Rapid plasma reagin and treponema pallidum particle agglutination assay were reactive, confirming syphilis diagnosis. Kidney biopsy revealed focal and segmental necrotizing and crescentic lesion. Patient received weekly benzathine penicillin (PCN) for 3 weeks, and renal function improved to baseline. This dramatic improvement happened with PCN alone, a finding which has not been previously reported. We recommend that syphilis be considered in the differential diagnosis of all patients with proteinuria or suspected glomerulonephritis.

Characteristics of Persons With Repeat Syphilis-Idaho, 2011 to 2015.

During 2011 through 2015 in Idaho, 14 (7%) of 193 persons with early syphilis had repeat syphilis. Persons with repeat infections were more likely to have had secondary or early latent syphilis (P = 0.037) and be infected with human immunodeficiency virus (P < 0.001) compared with those having 1 infection.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Acute syphilitic posterior placoid chorioretinitis in late latent syphilis.

Diverse manifestations of ocular syphilis may involve any structure in the eye, at any stage of the disease. Posterior uveitis in the form of posterior placoid chorioretinitis has been described in secondary- and tertiary-acquired syphilis. In this case report, we present a 47-year-old man with late latent syphilitic infection and fundoscopic, as well as angiographic findings consistent with acute syphilitic posterior placoid chorioretinitis. To our knowledge this form of patchy multifocal choroiditis has never been described in the latent stage of the disease.

Multimodal Imaging of Atypical Acute Syphilitic Posterior Placoid Chorioretinitis Mimicking a White Dot Syndrome.

As rates of infectious syphilis continue to rise in the U.S., it is important to be familiar with known manifestations of ocular syphilis as well as report presentations not previously described in the literature. Here, the authors report a case of a 49-year-old myopic woman presenting with bilateral white dots characteristic of a white dot syndrome; these white dots were not evident on slit-lamp examination and became obvious on fundus autofluorescence. She tested positive and was successfully treated for syphilis. This case demonstrates that ocular syphilis can present with white dots and should be on the differential diagnosis of white dot syndromes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e52-e55.].

The outcome of treatment of early latent syphilis and syphilis with undetermined duration in HIV-infected and HIV-uninfected patients.

The aim of the study was to compare the outcome of syphilis treatment in HIV-infected and -uninfected patients. An observational study on patients diagnosed with early syphilis in three genitourinary clinics in the UK between January 2003 and June 2005 was conducted. Failure of the initial Venereal Disease Research Laboratory (test) (VDRL) titre to decrease four-fold within 12 months in the absence of history of re-infection was considered as treatment failure. During the study period, 190 HIV-uninfected and 129 HIV-infected patients were diagnosed, and 161 (84%) HIV-uninfected and 100 (77.5%) HIV-positive patients with diagnosis of syphilis who had 24 months follow-up syphilis serology results were included in the study (P = 0.10). There were 381 and 508 follow-up episodes for HIV-infected and -uninfected patients, respectively, within 24 months. One HIV-infected patient was diagnosed with neuro-syphilis. After 12 months, 102 (63%) HIV-uninfected and 76 (70%) HIV-infected patients were treated (P = 0.04). On Cox proportional hazard model, successful treatment after 12 months was associated with having VDRL titre more than 1:6 (hazard ratio [HR] 1.011; 95% confidence interval [CI], 1.004-1.019; P = 0.002). Those with negative immunoglobulin M enzyme immunoassay were less likely to have been successfully treated after 12 months (HR 0.676 [95% CI 0.518-0.883]; P = 0.004). HIV sero-status, age, sex group and treatment regimen were not associated with success of treatment. In conclusion, HIV sero-status did not play a role in the outcome of syphilis treatment. Treatment failure in a proportion of HIV-infected patients is due to a slower decline in VDRL titre rather than lack of response to treatment.

Lumbar puncture for evaluation of latent syphilis in hospitalized patients. High prevalence of cerebrospinal fluid abnormalities unrelated to syphilis.

OBJECTIVE: To determine the prevalence of abnormal neurologic findings and cerebrospinal fluid abnormalities in hospitalized patients with serologic evidence of latent syphilis. DESIGN: Cross-sectional survey. METHODS: Consecutively admitted hospital inpatients from an inner-city population were screened for serologic evidence of syphilis with reactive plasma reagin and confirmatory fluorescent treponemal antibody absorption assays. In those with reactive tests, such clinical findings as a history of treatment for syphilis, neurologic abnormalities, presence of human immunodeficiency virus infection, and rapid plasma reagin titer were correlated with cerebrospinal fluid white blood cell count, protein level, and VDRL result. RESULTS: Of 490 consecutive patients, 52 (11%) had serologic evidence of syphilis. Forty-three (83%) of these underwent lumbar puncture. Of the 43, 31 (72%) were seronegative for human immunodeficiency virus and 12 (28%) were seropositive. No patient had a reactive cerebrospinal fluid VDRL test. Cerebrospinal fluid abnormalities were seen in 32% of human immunodeficiency virus-seronegative patients and in 67% of human immunodeficiency virus-seropositive patients. Cerebrospinal fluid abnormalities were not predicted by history of treatment for syphilis, abnormal neurologic findings, or an elevated rapid plasma reagin titer. Cerebrospinal fluid IgG indexes in patients with elevated cerebrospinal fluid protein levels suggested that the protein abnormalities were not caused by local antibody production. Nonreactive cerebrospinal fluid fluorescent treponemal antibody absorption tests suggest that the cerebrospinal fluid abnormalities were not the result of neurosyphilis. CONCLUSIONS: There was a high prevalence of cerebrospinal fluid abnormalities in hospitalized patients with latent syphilis detected by routine screening. Because of the nonspecificity of the cerebrospinal fluid findings, routine lumbar puncture for such patients appears to contribute little to the treatment of latent syphilis.

Syphilitic hepatitis uncommon presentation of an old scourge.

BACKGROUND: Giant cell hepatitis is a rare entity in adults, accounting for 0.1% to 0.25% of liver disease in adults. Postinfantile giant cell hepatitis is often characterized by multinucleated giant cells on liver biopsy and a fulminant hepatitis. CASE REPORT: An active duty 36-year-old African-American male deployed to Kabul, Afghanistan, presented with jaundice 2 weeks after starting a testosterone analogue. He discontinued the supplement, but his jaundice persisted with up-trending bilirubin. Serologic testing was negative for hepatitis A, B, C, and E; cytomegalovirus; Epstein-Barr virus; herpes simplex virus; and human immunodeficiency virus. Evaluation for autoimmune hepatitis was negative. Magnetic resonance cholangiopancreatography was negative for obstruction. Liver biopsy revealed giant cell transformation of numerous hepatocytes and cholestatic hepatitis. Rapid plasma reagin was positive without physical findings. Treponema pallidum hemagglutination assays confirmed the diagnosis of latent syphilis. He was started on penicillin treatment with rapid improvement of bilirubin, creatinine, and hepatic synthetic function, all of which eventually normalized. CONCLUSION: Postinfantile giant cell hepatitis is a severe form of hepatitis that has several different potential etiologies, 2 of which were present in this patient: androgenic supplements and infection. This case highlights syphilis as an unusual but treatable cause of giant cell hepatitis. Testing for syphilis should be considered in any persistent liver injury.

Tonic pupils in neurosyphilis.

Of 60 patients with tonic pupils, 29 had serologic tests for syphilis. Five patients had positive blood serology and confirmatory tests; four had other manifestations of neurosyphilis and positive CSF serology. All seropositive patients had bilateral tonic pupils with light-near dissociation and denervation hypersensitivity. Of the 10 tonic pupils, only 1 was miotic and 1 dilated. Although tonic pupils tend to become small and bilateral, they should be distinguished readily from Argyll Robertson pupils, which react briskly, not tonically, to near stimuli. Patients with bilateral tonic pupils should have serologic tests for syphilis.

Rapidly progressive glomerulonephritis in a patient with syphilis. Identification of antitreponemal antibody and treponemal antigen in renal tissue.

A 37-year-old man presented with biopsy-proved rapidly progressive glomerulonephritis and a strongly positive fluorescent treponemal antibody result. The patient was treated with hemodialysis, plasmapheresis, methylprednisolone, and penicillin, with rapid improvement and stabilization of renal function. Antibody was eluted from the frozen renal tissue and demonstrated a strongly positive reaction to the treponemal antigen when used in the fluorescent treponemal antibody test. In addition, when specific rabbit antitreponemal antiserum was applied to the frozen renal sections, there was a strongly positive reaction. Although syphilis has been associated with membranous glomerulopathy and post-infectious glomerulonephritis, this appears to be the first case of latent syphilis in which rapidly progressive glomerulonephritis has been identified. The presence within the glomeruli of treponemal antigen and antitreponemal antibody supports the association of these two entities.

Prevalence of neurosyphilis in human immunodeficiency virus-infected patients with latent syphilis.

PURPOSE: A prospective study was done to determine the prevalence of confirmed neurosyphilis (cerebrospinal fluid [CSF] Venereal Disease Research Laboratory [VDRL]-reactive) in human immunodeficiency virus (HIV)-infected patients with latent syphilis (reactive serum rapid plasma reagin [RPR] and microhemagglutination-Treponema pallidum [MHA-TP]). PATIENTS AND METHODS: All HIV-infected patients seen for their first visit at the Los Angeles County/University of Southern California Medical Center AIDS Clinic from June through December 1990 were screened for latent syphilis. Those with reactive serum RPRs and MHA-TPs who had not received recent (within 6 months) therapy for syphilis were offered diagnostic CSF sampling. RESULTS: A total of 312 patients were screened, of whom 71 (22.8%) had reactive serum RPRs and MHA-TPs. Thirty-three of these patients (47%) had diagnostic CSF sampling (26 refused lumbar puncture or were lost to follow-up; 12 had had recent therapy for syphilis and thus did not have CSF sampling). Among the 33 patients who had CSF sampling, 20 (60.6%) had normal CSF profiles (white blood cell count less than 8/mm3; protein less than 0.60 g/L; glucose greater than 2.8 mmol/L) and nonreactive CSF VDRLs. Ten of the 33 patients (30.3%) had abnormal CSF profiles and nonreactive CSF VDRLs, and three of 33 (9.1%) had reactive CSF VDRLs. CONCLUSIONS: Asymptomatic neurosyphilis was found in 9.1% of our patient population undergoing CSF sampling, giving a 1.0% prevalence of CSF VDRL-reactive neurosyphilis in the population we screened. The abnormal CSF findings may have been due to either nonreactive CSF VDRL neurosyphilis, central nervous system infection with HIV, or infection with some unrecognized agent.

Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost-effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients.

Syphilitic neuroretinitis.

Four patients (three men, 32, 43, and 53 years old, and one 37-year-old woman) with syphilitic neuroretinitis had cerebrospinal fluid evidence of neurosyphilis. Therapy failed in one patient given penicillin G benzathine intramuscularly and it may have failed in a second patient. Another treatment failure occurred in a patient given tetracycline orally. Intramuscular penicillin G benzathine or intramuscular penicillin G procaine in doses of less than 2.4 million units/day does not produce spirocheticidal drug levels in the cerebrospinal fluid. All four patients improved after high-dose treatment with aqueous penicillin G.

Syphilitic retinal detachment and uveal effusion.

A 32-year-old man developed a recurrent nonrhegmatogenous retinal detachment, uveal effusion, and visual loss as a result of latent secondary syphilis. Treponemes were found in the subretinal fluid and the Treponema pallidum hemagglutination test demonstrated substantially higher titers in the subretinal fluid than in the serum (1: 2,569 vs 1: 16). Despite scleral dissection and a scleral implant and treatment with penicillin, the patient's visual loss persisted and the last examination showed a thickened choroid, a flat nonrhegmatogenous retinal detachment, and reaccumulation of subretinal fluid.

Otologic manifestations of AIDS: the otosyphilis connection.

Five cases of otosyphilis presenting in patients with HIV infection are discussed. The group is representative of the known stages of the disease, from asymptomatic carrier to the fully expressed immunodeficiency syndrome, and it is of relevance because otosyphilis appears to have developed at an accelerated rate from the primary infection. Four patients had been treated with penicillin 2 to 5 years previously and had a positive fluorescent treponemal antibody absorption (FTA-ABS) test. The fifth had concurrent neurosyphilis and was VDRL-test (Venereal Disease Research Laboratory) negative 2 years prior to the onset of symptoms. In all five patients, syphilis was in the latent stage. It is proposed that it is during this phase of the disease that HIV may alter its course and hasten the development of otosyphilis. It is also suggested that otosyphilis can present at any stage of HIV infection and should be considered in seropositive patients presenting with otologic complaints.

Testing for syphilis.

Syphilis remains an important public health problem of growing proportions despite effective means of prevention and therapy. Clinical staging is difficult. The diagnosis is complicated by the lack of an easy culture method. History, clinical findings, and the detection of spirochetes in tissue serve as the basis for diagnosis. Simple nontreponemal tests are available for screening, and more difficult treponemal tests are used for confirmation. False-positive test results are more common with the reaginic tests but are also seen with the specific antitreponemal tests. The diagnosis of central nervous system syphilis is imprecise and is of particular importance in HIV-positive individuals. HIV infection has complicated the diagnosis of syphilis with serologic testing, although the current tests are generally adequate. Follow-up testing after treatment is used to confirm a therapeutic response. New diagnostic tests, including monoclonal antibody staining and the polymerase chain reaction, may ultimately assist in the diagnosis of this ancient disease that still has major health implications in the modern world.