Clinical Case Summary

Background: Syphilis is a chronic systemic infection caused by the spirochete Treponema pallidum, often referred to as "the great imitator" due to its ability to affect nearly any organ. Syphilitic hepatitis, or "luetic jaundice," is a rare manifestation, indicating spirochete dissemination to the liver.
Case Report: A 26-year-old female was admitted to the hospital with fever (39.5 °C), fatigue, sweating, tremor, dark urine, pale stools, and significant weight loss (15 kg over two months). She also reported lower extremity muscle and joint pain, cough and slowing of speech. On examination, she had icteric skin, a generalized maculopapular rash, and enlarged cervical lymph nodes. No history of alcohol or drug use was noted.
Laboratory tests revealed elevated levels of both cytolytic and cholestatic liver enzymes, along with increased bilirubin an elevated C-reactive protein.
Abdominal ultrasound and contrast CT showed hepatomegaly, hilar and retroperitoneal lymphadenopathy and splenomegaly.
Viral hepatitis markers (HBsAg, HBV PCR, HCVAb, HCV PCR, anti-HAV IgM, anti-HEV IgM) and antibodies for CMV, EBV, HIV, HSV-1,2 were negative. Wright-Hedelson test for brucellosis and serological markers for autoimmune hepatitis were negative while IgG and cerulopasmin levels were within normal range. Given systemic findings and history, syphilis was considered. Serologic tests were positive for Treponema pallidum (ELISA, TPHA, MRP). Liver biopsy revealed mild active hepatitis. The diagnosis of ^secondary syphilitic hepatitis was made. The patient was started on antimicrobial therapy. During follow-up, liver function tests normalized, and systemic symptoms resolved.
Conclusion: This case underscores the importance of considering syphilis in the differential diagnosis of unexplained hepatitis. Although rare, syphilitic hepatitis should be considered in patients with liver enzyme elevations and nonspecific symptoms, particularly when no clear alternative diagnosis is found.

References

1) Malvar G, Cardona D, Pezhouh MK, Adeyi OA, Chatterjee D, Deisch JK, Lamps LW, Misdraji J, Stueck AE, Voltaggio L, Gonzalez RS. Hepatic Secondary Syphilis Can Cause a Variety of Histologic Patterns and May Be Negative for Treponeme Immunohistochemistry. Am J Surg Pathol. 2022 Apr 1;46(4):567-575. doi: 10.1097/PAS.0000000000001848. PMID: 34864775.
2)Supronowicz Ł, Rogalska M. Syphilitic hepatitis. Clin Exp Hepatol. 2024 Mar;10(1):9-13. doi: 10.5114/ceh.2024.136235. Epub 2024 Mar 12. PMID: 38765910; PMCID: PMC11100338.
3)Al Dallal HA, Narayanan S, Alley HF, Eiswerth MJ, Arnold FW, Martin BA, Shandiz AE. Case Report: Syphilitic Hepatitis-A Rare and Underrecognized Etiology of Liver Disease With Potential for Misdiagnosis. Front Med (Lausanne). 2021 Nov 29;8:789250. doi: 10.3389/fmed.2021.789250. PMID: 34912834; PMCID: PMC8666961.
Figure 1: Histological images of the liver biopsy
Figure 2: Abdominal CT images
Figure 3: Images of maculopapular rash

Clinical Case Summary

A 64-year-old male patient presented with acute epigastric pain over 7 days, worsening after meals, nausea, vomiting 2 times without signs of bleeding, diarrhea 5-6 times/day, high blood pressure 180/100 mmHg. He had a 6-year history of recurrent epigastric pain, after multiple EGDSs was diagnosed as gastric ulcer and atrophic gastritis. The patient had undergone HP eradication and received standard anti-ulcer therapy several times, with no clinical improvement. On physical examination, the patient appeared pale. The abdomen was soft, without pain, guarding or rebound tenderness. The patient's medical history was significant for arterial hypertension. Lab abnormalities included WBC 16.32-10x10⁹/L, ESR 94mm/sec, CRP at 184.3 mg/L, FBG 767 mg, Total protein 50.9 g/L, CREA 147 mmol/L, Urea 13.42 mmol/L, Na 129 mmol/L. Intestinal infections were negative. New EGDS revealed an ulcerative lesion with 0.8cm diameter, in the region from antrum to greater curvature, covered with fibrin. Colonoscopy was normal. Duplex ultrasound revealed a 70% stenosis of the celiac trunk and superior mesenteric artery, with atherosclerotic wall deformation and intima-media thickening. A thrombosis was detected in the region of the aortic bifurcation. CT angiography revealed up to 70% stenosis of the suprarenal abdominal aorta, no contrast enhancement was observed in the origins of the celiac trunk, superior mesenteric artery, left renal artery (left kidney appeared atrophic), total occlusion of bilateral common, external, and internal iliac arteries.
Conclusion: Gastric ulcers are mostly associated with HP. However, in rare cases, underlying vascular pathology may be critical in their pathogenesis. This case highlights an overlooked cause of gastric ulcers, particularly in patients with atherosclerotic risk factors. In patients with persistent symptoms despite medical therapy ischemic ulceration should be included in the differential diagnosis.

Clinical Case Summary

A 30-year-old-female presented with a one-week history of jaundice and pedal edema. Initial laboratory investigations revealed elevated liver enzymes and total bilirubin of 37.90 mg/dL. Over the following three months her condition worsened, a transjugular liver biopsy revealed 50% necrosis, indicative of severe liver injury for which she underwent a Liver transplant. On POD 7 she developed severe thrombocytopenia (8000/μL) and neutropenia (858/μL), along with elevated LFTs (AST=473 IU/L, ALT=992 IU/L), challenging the post-operative management. Some differentials were Acute transplant rejection, CMV, infection, drug induced hepatotoxicity etc. CMV PCR testing was ordered which revealed a positive result, prompting antiviral therapy. Due to persistent pancytopenia a bone marrow biopsy was performed confirming the presence of hemophagocytosis, leading to a diagnosis of Hemophagocytic Lymphohistiocytosis. Diagnosis was supported by other Lab values (platlets=8000/μL, neutrophils=858/μL, LFTs; AST=473 IU/L, ALT=992 IU/L, fibrinogen=508 mg/dl and ferritin=2269 Ng/ml).
Appropriate treatment with high-dose steroids and etoposide was initiated promptly adhering to the HLH-2004 protocol [1], however the patients condition continued to worsen. On POD 16 she eventually succumbed to multi-organ failure due to mucormycosis and septic shock.
The incidence of HLH in liver transplant patients is not well documented, only forty-one previous post-LT HLH cases have been reported in present literature, out of which only 5 were initially diagnosed with acute liver failure [2,3] ,This case adds to the existing literature on HLH and highlights the importance of including HLH as a differential diagnosis in immunocompromised patients, especially in post-liver transplant cases, due to its severe outcomes. Integrating novel diagnostic tools like the HScore may enhance the ability to diagnose HLH in complex clinical situations [4], although they cannot replace astute clinical judgment.

References

1. Henter J, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb 25;48(2):124–31.
2. Chesner J, Schiano TD, Fiel MI, Crismale JF. Hemophagocytic lymphohistiocytosis occurring after liver transplantation: A case series and review of the literature. Clin Transplant. 2021 Aug 8;35(8).
3. Iseda N, Yoshizumi T, Toshima T, Morinaga A, Tomiyama T, Takahashi J, et al. Hemophagocytic syndrome after living donor liver transplantation: a case report with a review of the literature. Surg Case Rep. 2018 Dec 29;4(1):101.
4. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome. Arthritis & Rheumatology. 2014 Sep 26;66(9):2613–20.