Luetic (syphilitic) hepatitis: the great imitator persists in the 21st century
- Daniel Mullally ,
- Sreelakshmi Kotha ,
- Mandour Omar Mandour and
- Philip Berry
- Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Correspondence to Dr Sreelakshmi Kotha; sreelakshmi_kotha@yahoo.com
Abstract
A male patient in his 20s was referred to the hepatology team with jaundice, pruritus and drenching night sweats. Investigations revealed an acute hepatitis with negative autoimmune and viral serology. Liver biopsy demonstrated severe pan-lobular hepatitis, and an extended diagnostic screen included a positive treponemal antibody test, with an RPR titre of 64, indicating active syphilis infection. He was treated with 2.4 million units of intramuscular benzathine penicillin as a single dose which led to complete resolution of the abnormal liver tests and symptoms. Diagnostic and management challenges, including the role of good history taking, appropriate investigations and role of multidisciplinary team, are discussed.
Background
Syphilis is caused by Treponema pallidum and can be transmitted sexually or vertically. It is a major public health issue worldwide, and it is estimated there are 6.3 million new cases every year.1 Syphilis can affect multiple organ systems and is known as the great imitator as it can be confused with numerous other infectious causes. Syphilitic hepatitis is rare with an incidence ranging from 0.25% to 38%.2 The liver can be involved at any stage, syphilitic hepatitis being more common in homosexual men or patients with HIV. Clinicians need to maintain a high index of suspicion to diagnose this condition.
Case presentation
A male patient in his 20s with no medical history presented with jaundice, pruritus, drenching night sweats and fatigue with pale stools and dark urine for 1 week. He reported a weight loss of 4 kg over 5 months. There was no recent travel history. He reported one regular female sexual partner and denied excess alcohol intake, over-the-counter medication or use of recreational drugs. On examination, the abdomen was non-tender without organomegaly. His tonsils were enlarged, and there were palpable submandibular and axillary lymph nodes. Neurological assessment was normal with no evidence of hepatic encephalopathy.
Investigations
Blood tests revealed acute hepatitis: alanine amino transferase (ALT) 2595 (10–130 U/L), total bilirubin 155 (3–20 µmol/L), conjugated bilirubin 125 (0–14 µmol/L), alkaline phosphatase 339 (35–130 U/L), gamma glutamyl transferase 96 (10–48 U/L), aspartate amino transferase 1386 (5–40 U/L), INR 1.3 (1.0–1.2), ferritin 862 µg/L (25–275 µg/L), C reactive protein 8 (<3) and paracetamol level 4 mg/L. Full blood count and renal profile were unremarkable. Virological and autoimmune screens are shown in tables 1 and 2.
Virological screen
Virological screen
Autoimmune screen
| Immunoglobulin G | 15.3 (6.0–16.0 g/L) |
| Smooth muscle antibody | Negative |
| Gastric parietal cell antibody | Negative |
| Mitochondrial antibody | Negative |
| Liver/kidney microsomal antibody | Negative |
| Anti-LC1/LKM | Negative |
| M2 | Negative |
| Anti-SLA | Negative |
Differential diagnosis
Due to PET scan findings, consideration of an early lymphoproliferative disease remained the leading differential. Hepatitic liver function tests raised the possibility of autoimmune hepatitis. However, a predominant lymphocytic infiltrate in the biopsy made autoimmune hepatitis unlikely (absence of plasma-cell infiltrate), so a treponemal antibody test was carried out with the patient’s consent. This was positive, with an RPR titre of 64, indicating active infection. The patient denied previous rashes, genital lesions or symptoms of sexually transmitted infection and reiterated; he was monogamous with a female sexual partner on repeated questioning. His case was discussed with the infectious disease and genitourinary medicine (GUM) teams, and plans for a lymph-node biopsy were put on hold to see if there was response to treatment for syphilis.
Treatment
The patient received 2.4 million units of intramuscular benzathine penicillin and was monitored as an outpatient. Psychological support was offered, and counselling was provided through the genitourinary medicine (GUM) team. The GUM team undertook partner notification and contact tracing. These details are not available due to confidentiality.
Outcome and follow-up
Liver function tests improved dramatically, with resolution of coagulopathy after 24 hours and reduction of ALT by 30% at 48 hours (figure 2). Blood tests following discharge showed continued improvement, while review by GUM services confirmed treatment response with corresponding decremental RPR titres. Further review of the liver biopsy found no immunohistochemical or morphological evidence of spirochetes in the hepatic tissue.
Trend of ALT and bilirubin pretreatment and post-treatment showing rapid improvement.
Discussion
Syphilitic hepatitis is relatively rare and presents a diagnostic challenge due to multisystem involvement, overlapping stages and under recognition. There is a small body of evidence in the literature documenting its occurrence. Syphilis has frequently been labelled ‘The Great Imitator’ with secondary infections often manifesting with non-specific signs and symptomatology.3 4 In a recent systematic review of 97 syphilitic hepatitis cases with documented signs, only 30.9% displayed lymphadenopathy; a rash was observed in 77.9%, while vague features of fatigue, anorexia, fever and weight loss were the next most frequent symptoms.5 Huang et al noted that, of 99 of their 144-patient sample with available liver biochemistry, a cholestatic picture was overwhelmingly displayed. Of 28 cases that had immunohistochemical or Warthin-Starry staining, spirochetes were identified in only 19. The predominant feature of biopsy was non-specific inflammatory cell inflammation in the portal or hepatic lobular areas, which was seen in 87.2% of cases. As syphilis is largely diagnosed and managed in an outpatient GUM setting, there is poor documentation of radiological features of secondary infection; however, a systematic review identified only 36 cases of bony involvement in the English language literature over 50 years.5
Clinical symptoms are non-specific and include fatigue, malaise, weight loss, sore throat, arthralgia and lymphadenopathy. The classic maculopapular rash is not seen routinely. Liver involvement can occur at any stage of liver disease. Histopathology of liver samples is non-specific with mixed lymphoplasmacytic infiltrate, and false negative result for spirochete staining is common. There are no clear diagnostic criteria for syphilitic hepatitis. Mullick et al proposed a reasonable diagnosis could be made with abnormal liver enzyme levels in a cholestatic pattern, serological evidence for syphilis, exclusion of other causes of liver diseases and normalisation of liver enzymes following antimicrobial therapy.6 Our patient fulfilled all these criteria. Fulminant hepatitis requiring liver transplantation is rare.
This case emphasises the challenges associated with diagnosis of syphilitic hepatitis and the importance of maintaining a high index of suspicion in seronegative hepatitis.
Learning points
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Syphilitic hepatitis presents a diagnostic clinical challenge due to non-specific signs and symptoms.
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It is important to keep an open mind about differentials in seronegative hepatitis.
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Treponemal screening should be considered in individuals at risk of sexually transmitted disease with abnormal liver enzymes.
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Syphilitic hepatitis is treatable with a single dose of antibiotic, so the opportunity to diagnose and treat this condition should not be lost.
Ethics statements
Patient consent for publication
Footnotes
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Contributors DM: management and writing case. SK: management and writing case. MOM: management and writing case. PB: management and writing case. DM, SK, MOM and PB: final approval of the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.
References
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