Clinics in diagnostic imaging (219)
2024; Medknow; Volume: 65; Issue: 4 Linguagem: Inglês
10.4103/singaporemedj.smj-2022-121
ISSN2737-5935
AutoresJ. Kenneth Chong, Chung Yau Nah, Hsien Min Low,
Tópico(s)Diagnosis and treatment of tuberculosis
ResumoCASE PRESENTATION A 74-year-old man presented with a 2-month history of painless obstructive jaundice associated with loss of weight and appetite. Of note, the patient was admitted 1 month ago for excision of a penile foreskin lesion, for which the histology revealed dense inflammatory infiltrate with a predominant lymphocytic response and negative for malignancy. The patient was also found to be positive for syphilis antibody (both rapid plasma reagin and Treponema pallidum haemagglutination assay), but negative for human immunodeficiency virus (HIV). Further probing revealed that the patient's last sexual intercourse was 2 years ago, and it was unprotected vaginal sexual intercourse with his partner of 2 years' duration. On examination, there was scleral icterus, as well as an erythematous papulosquamous eruption involving the limbs, including the palms and soles. There was no hepatosplenomegaly or peripheral stigmata of chronic liver disease. Blood investigations revealed deranged liver function tests with a predominantly cholestatic picture and a significantly raised carbohydrate antigen 19-9 of >10,000. Magnetic resonance imaging (MRI) of the abdomen was performed [Figure 1]. What do the images show? What is the diagnosis?Figure 1: (a) & (b) MR images and (c) magnetic resonance cholangiopancreatography-maximum intensity projection image of the abdomen.IMAGE INTERPRETATION Axial T2-weighted (T2-W) fat-saturated sequence [Figure 1a] shows mildly dilated bile ducts in the periphery of the liver (arrows). Axial postcontrast T1-W delayed phase image [Figure 1b] shows mild periductal enhancement and dilated bile ducts (arrows). Maximum intensity projection (MIP) image from the magnetic resonance cholangiopancreatography (MRCP) study [Figure 1c] demonstrates dilated bile ducts in the periphery of the liver (arrows), with a beaded appearance of the intrahepatic bile ducts due to multifocal strictures. No extrahepatic biliary dilatation, discrete mass or dominant stricture is detected to suggest an underlying malignancy. Imaging features are those of sclerosing cholangitis. DIAGNOSIS Sclerosing cholangitis due to secondary syphilis. CLINICAL COURSE The patient received one dose of intramuscular benzathine penicillin 2.4 mU per week over 3 weeks. On subsequent outpatient review, the patient reported improvement in clinical signs and symptoms; also, there was resolution of the deranged liver function tests over a period of 4 months. The MRI performed 1 month after institution of antibiotic therapy demonstrated improvement in the degree of biliary dilatation, and a scan performed 4 months later showed resolution of these findings [Figure 2]. Further investigations for other potential causes of cholestatic hepatitis (including hepatitis A, B and E as well as antimitochondrial antibody and thyroid function tests) were also negative. Hence, the patient was discharged.]Figure 2: Posttreatment MR images. (a) MR cholangiopancreatography-maximum intensity projection (MRCP-MIP) performed 1 month posttreatment shows improvement in the degree of biliary dilatation, which is now predominantly seen in the proximal intrahepatic biliary tree (arrows). (b) MRCP-MIP performed 4 months posttreatment shows resolution of the previously described changes with a normal-appearing biliary tree with smooth, nondilated and nonbeaded bile ducts. CHD: common hepatic duct, L IHD: left intrahepatic duct, R IHD: right intrahepatic ductDISCUSSION Syphilis is a sexually transmitted infection caused by the spirochaete T. pallidum, with varied clinical manifestations. Its natural course is to progress from primary to secondary, and finally to tertiary syphilis if left untreated. It has been termed 'the great imitator' due to its ability to involve multiple organs with variable clinical presentation.[1,2] Patients with primary syphilis typically present with a solitary painless chancre at the site of inoculation, with or without localised painless adenopathy, often within the first 3 months after exposure. Secondary syphilis is a manifestation of bacterial dissemination and often presents 2 weeks to 6 months after exposure, with a diffuse symmetric maculopapular rash, often involving the palms or soles, with varied systemic involvement.[1] Early neurosyphilis develops in up to 60% of cases with neurological symptoms such as cranial nerve palsies, meningitis, altered mental status or changes in memory.[1] Without treatment, up to 40% of patients diagnosed with syphilis will eventually progress to tertiary syphilis with irreversible damage to the involved organ in subsequent years.[1] Hepatobiliary involvement in syphilis is not common, with only two other known reported cases of secondary syphilis with sclerosing cholangitis and 144 cases of syphilitic hepatitis reported in a systematic review by Huang et al.[2,3,4,] Syphilitic hepatitis has a similar clinical presentation — a characteristic rash and deranged liver function tests with a predominantly cholestatic picture. Histopathological features include inflammatory cell infiltration of portal areas or hepatic lobules, hepatocellular necrosis and cholestasis.[2] It is possible that a subset of patients diagnosed with syphilitic hepatitis may actually have imaging features of sclerosing cholangitis, but were treated empirically without any imaging performed beforehand. Screening for underlying HIV is important in this group of patients, as early diagnosis of HIV will enable prompt commencement of antiretroviral therapy. Furthermore, HIV cholangiopathy can also have a similar clinical presentation and resembles sclerosing cholangitis radiologically. In our patient, the penile lesion that was excised 1 month ago could have represented the primary syphilitic chancre, although a history of last unprotected sexual intercourse 2 years ago is atypical. Subsequent presentation with a typical palmoplantar rash, lymphadenopathy as well as a positive syphilis antibody is suggestive of secondary syphilis. This led to a working diagnosis of hepatobiliary involvement, given the presence of deranged liver function tests of a predominantly cholestatic picture and the abnormal MRI findings of a beaded appearance of the intrahepatic biliary tree and mild periductal enhancement on contrast-enhanced sequences. Serology for other causes of hepatitis (including HIV, hepatitis A, B and E, as well as antimitochondrial antibody and thyroid function tests) was negative, and imaging did not reveal any suspicious mass or dominant stricture to suggest underlying malignancy. Subsequent follow-up after treatment with intramuscular penicillin for syphilis also demonstrated resolution of the MRI findings as well as normalisation of the CA19-9 levels and liver enzymes, indicative of syphilis as the underlying cause of sclerosing cholangitis. Liver biopsy was, therefore, not necessary for diagnosis in this case. Sclerosing cholangitis is a spectrum of variably progressive cholestatic disease of the intrahepatic and/or extrahepatic biliary system, and it is characterised by patchy inflammation, fibrosis and formation of bile duct strictures. It may be primary (i.e. idiopathic) or secondary to other causes such as infection (as in our case), ischaemia and autoimmune conditions. Therefore, early recognition of potential underlying causes is important, as they may respond favourably to institution of early treatment.[5] As mentioned, sclerosing cholangitis associated with secondary syphilis is not commonly encountered in clinical practice. Below, we describe the imaging features of sclerosing cholangitis and the common entities associated with it. Imaging features of sclerosing cholangitis The preferred diagnostic imaging is MRI, given its noninvasive nature, lack of radiation and potential for contemporaneous MR elastography for evaluation of associated hepatic fibrosis.[6] Classical imaging findings in sclerosing cholangitis include multifocal strictures of the intrahepatic and extrahepatic bile ducts with intervening sites of dilated and normal ducts, giving rise to a 'beaded' appearance of the biliary tree. The pruned appearance of the biliary tree, also known as the 'tree-in-winter' appearance, develops as the disease progresses with obliteration of the smaller peripheral ducts.[5,7] The MRCP utilises heavily weighted T2 sequences to depict the fluid signal within the bile ducts and suppresses the surrounding signal arising from the liver and soft tissues. This generates detailed images of the biliary tree to help identify ductal pathologies. The MIP images from the MRCP are useful to give a global overview of the degree of bile duct dilatation. Primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is the most common disease entity associated with sclerosing cholangitis. It is an idiopathic condition that can occur by itself or in association with other conditions such as inflammatory bowel disease (IBD). The diagnosis requires the exclusion of secondary causes of sclerosing cholangitis. Primary sclerosing cholangitis is usually seen in male patients aged 30–40 years, with underlying IBD and deranged liver function tests, although the diagnosis of PSC may also precede that of IBD. The pathogenesis is not entirely clear, preventing the development of effective therapies, but may involve defects in mechanisms protecting against bile acid toxicity, with resultant chronic bile duct injury and concentric periductal fibrosis.[7] Disease course typically fluctuates, but liver disease progression to cirrhosis is inevitable in most patients due to inflammation and fibrosis, leading to cholestasis and parenchymal injury. Although PSC in its early stages may be mainly autoimmune mediated, cholestasis can become self-sustaining with bile acid toxicity leading to a cycle of progressive injury, with superimposed infection also contributing to disease progression. Portal hypertension may develop before impairment of liver function or cirrhosis is seen, due to biliary scarring leading to venous compression in the portal triads that is more marked than in other causes of chronic liver disease, such as viral hepatitis.[8] Liver transplantation is the only curative treatment option, although this is also fraught with a high frequency of acute cellular rejections and disease recurrence.[7] Cases with the previously described imaging features of sclerosing cholangitis are termed 'large duct PSC'. Figure 3 shows a case of typical PSC with beaded appearance of the intrahepatic biliary tree due to multifocal strictures and periductal enhancement. Those with clinical, biochemical and histological abnormalities suggestive of PSC but normal cholangiograms are known as 'small duct PSC'.[9,10] A liver biopsy is recommended for such cases to demonstrate the histological findings compatible with PSC, which include periductal fibrosis, fibro-obliterative cholangitis, periductal inflammation, ductopenia and variable amounts of portal inflammation.[6] The MR images of patients with small duct PSC will show normal-calibre biliary tree, but may demonstrate arterial or delayed phase peribiliary enhancement. Arterial phase peribiliary enhancement may reflect active inflammation and is associated with a poorer prognosis, while delayed enhancement is probably due to chronic/fibrotic biliary change.[11,12] There may also be heterogeneous hepatic parenchymal signal intensity on T2-W images, with heterogeneous delayed enhancement on postcontrast T1-W sequences, probably related to underlying periductal inflammation and subsequently fibrosis, which can involve the adjacent vessels and cause perfusion abnormalities.[11]Figure 3: Typical primary sclerosing cholangitis. (a) Axial T2-W fat-saturated sequence and (b) coronal T2-W sequence show mildly dilated bile ducts in the periphery of the liver (arrows). (c) Axial postcontrast T1-W delayed phase sequence shows mild periductal enhancement and duct dilatation (arrows). (d) MR cholangiopancreatography-maximum intensity projection shows dilated bile ducts with a beaded appearance due to multifocal strictures. The disease is worse in the left lobe of the liver with more markedly dilated bile ducts (arrow).A review of existing literature shows that approximately 25% of patients with small duct PSC go on to develop large duct PSC.[9,10,11] Small duct PSC appears to run a more benign course as compared to large duct PSC, with fewer patients developing chronic hepatic failure leading to death or liver transplantation and longer time to transplantation.[6,9,10] Another main cause for mortality in PSC is development of cholangiocarcinoma, and studies suggest that there is also a lower malignancy potential in small duct PSC, with only one known case of small duct PSC being diagnosed with cholangiocarcinoma at the same time as the development of large duct PSC.[9] Indeed, a review by Chapman and Williamson[13] demonstrated the association between a dominant stricture and a worse prognosis with an increased risk of cholangiocarcinoma. The dominant stricture may represent the early presentation of cholangiocarcinoma or it may be a benign stricture, which with repeated bouts of infection and inflammation due to biliary obstruction, may eventually develop malignant change.[13] Treatment of superimposed infection and dilatation of dominant strictures are, therefore, likely to be effective treatment approaches in delaying disease progression.[8] Cholangiocarcinoma in PSC usually manifests as intrahepatic mass-forming or perihilar periductal-infiltrating type. Small mass-forming cholangiocarcinoma is often difficult to detect due to the heterogeneous appearance and enhancement of the diseased liver. Periductal infiltrating cholangiocarcinoma grows along the bile duct and often results in focal concentric wall thickening of the involved duct. As the tumour grows, there is progressive narrowing of the bile duct with resultant upstream biliary dilatation. Early diagnosis in this instance is challenging due to pre-existing bile duct wall thickening and biliary strictures. Figure 4 demonstrates a case of periductal infiltrating cholangiocarcinoma in a patient with known PSC, with resultant disproportionate dilatation of the upstream biliary tree. Prognosis is often poor due to advanced tumour stage at the time of diagnosis and underlying liver disease limiting treatment options.[14]Figure 4: Primary sclerosing cholangitis complicated by cholangiocarcinoma. (a) Axial T2-W fat-saturated sequence shows a mass-like periductal infiltrating lesion along the segment 2 and 3 bile ducts that appears to encase the segmental portal vein as well as extend into the ligamentum teres (arrows). There is also disproportionate dilatation of the upstream biliary tree in the left lobe (arrowheads). (b) Magnetic resonance cholangiopancreatography-maximum intensity projection shows background dilated bile ducts with a beaded appearance due to multifocal strictures. (c) Cholangiopancreatography shows dilated bile ducts with a beaded appearance, worse in segments 2 and 3, with a dominant stricture just distal to the bifurcation of the left hepatic duct (arrow).Patients with PSC should, therefore, undergo regular clinical, biochemical and imaging surveillance for disease progression and hepatobiliary malignancy. This would include clinical review, serum liver function tests and coagulation profile, as well as ultrasound or MRI with or without elastography to evaluate the development of cirrhosis. Imaging interval may need to be shortened (e.g. six monthly) in the presence of cirrhosis to allow for early detection of malignancy and, therefore, possible curative treatment.[6] IgG4-associated sclerosing cholangitis The main differential diagnosis for sclerosing cholangitis is immunoglobulin G4 (IgG4)-associated sclerosing cholangitis, which is a separate entity with an elevated IgG4 and is often seen in association with other IgG4-related conditions such as retroperitoneal fibrosis, pancreatitis and dacryoadenitis.[7,15]Figure 5 shows the MR images of a patient with known IgG4-associated sclerosing cholangitis demonstrating similar imaging features. Figure 6 shows some other manifestations of IgG4 disease in a different patient with involvement of the lacrimal glands [Figure 6a], submandibular glands [Figure 6b] and pancreas [Figure 6c]. Determination of serum IgG4 levels is, therefore, suggested in every adult patient with imaging features of sclerosing cholangitis.[6] It is categorised into four types based on the stricture regions, with type 1 involving the lower part of the common bile duct (CBD), type 2 diffusely involving the intrahepatic and extrahepatic biliary tree, type 3 involving the hilum and distal CBD, and type 4 involving only the hilum.[15] Biliary strictures and thickening can involve any portion of the biliary tree, but the CBD is most commonly affected. Diagnosis is based on two or more main manifestations (including elevated serum IgG4, suggestive pancreatic imaging findings and other organ involvement) combined with a significant response to corticosteroid treatment. Bile duct or ampullary biopsies often show dense infiltration of IgG4-positive plasma cells with extensive fibrosis in the bile duct.[7,15] Imaging findings, especially for type 2 IgG4-associated sclerosing cholangitis, are similar to those of other causes of sclerosing cholangitis, with possible marked localised or multifocal bile duct thickening and enhancement that may be mistaken for cholangiocarcinoma. Awareness and clinical suspicion of underlying IgG4-associated sclerosing cholangitis and distinction from PSC are important, given the often dramatic response to corticosteroid therapy.Figure 5: Immunoglobulin G4 cholangitis. (a) Axial postcontrast T1-W delayed phase sequence shows mild periductal enhancement (arrows). (b) MR cholangiopancreatography-maximum intensity projection shows dilated bile ducts with a beaded appearance due to multifocal strictures predominantly involving the right lobe of the liver (arrows).Figure 6: Immunoglobulin G4 manifestations. (a) Coronal contrast-enhanced CT image of the orbits shows bilateral symmetrical enlargement of the lacrimal glands, suggestive of dacryoadenitis (arrows). (b) Coronal contrast-enhanced CT image of the neck shows bilateral symmetrical, marked enlargement of the submandibular glands (arrows). The lower border of the submandibular glands extends below the inferior border of the mandible. (c) Axial contrast-enhanced CT image of the abdomen shows enlargement of the pancreatic tail with a peripancreatic rim of low attenuation soft tissue thickening (arrows), which has been described as a 'halo sign'.In summary, sclerosing cholangitis may be primary (idiopathic) or due to other causes such as secondary syphilis, as in our case. Imaging is often unable to differentiate between the primary and secondary forms of sclerosing cholangitis. Clinical history and biochemical markers are often more helpful in the identification of a secondary cause. Imaging is required in cases of PSC to evaluate the presence of a dominant stricture and to perform surveillance for the early detection of cirrhosis and cholangiocarcinoma. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. SMC CATEGORY 3B CME PROGRAMME Online Quiz: https://www.sma.org.sg/cme-programme Deadline for submission: 6 pm, 22 May 2024
Referência(s)