Secondary Sclerosing Cholangitis in a Critically Ill Burn Patient: A Case Report and Review of the Literature

ABSTRACT

A 17‐year‐old with 80% total body burns developed secondary sclerosing cholangitis (SSC) 3 months post‐injury. This rare liver complication, confirmed by imaging, highlights the need to consider SSC in burn patients presenting with cholestatic liver dysfunction. Early recognition is crucial for timely management and improved outcomes.

1. Introduction

Secondary sclerosing cholangitis (SSC) is a long‐term cholestatic biliary disease that may occur after several types of damage to the biliary system. Its symptoms are similar to those of primary sclerosing cholangitis (PSC). Contrary to PSC, which is idiopathic and immune‐mediated, SSC has discernible secondary causes, such as infection, ischemia, or biliary obstruction [1]. Secondary sclerosing cholangitis in critically ill patients (SSC‐CIP) is a unique subtype initially characterized by Schmitt et al. in 1997 [2, 3]. Patients without previous hepatobiliary illness may acquire SSC‐CIP following extended intensive‐care therapy for significant surgery, trauma, sepsis, or burns [1, 3]. This case report illustrates an uncommon occurrence of SSC‐CIP after significant burn damage and serves as a foundation to examine its pathogenesis, diagnostic difficulties, and prognosis in critically ill patients.

SSC‐CIP affects patients without prior hepatobiliary disease and develops after intensive care unit (ICU) treatment for various underlying conditions, including major surgery, sepsis, trauma, and burns [1, 3]. Consideration of SSC‐CIP is crucial in the differential diagnosis of cholestasis in ICU patients when cholestasis persists beyond the successful management of the underlying disease [3]. This report presents a rare case of SSC‐CIP following severe burn injury and aims to discuss the underlying pathophysiology, diagnostic considerations, and prognostic implications associated with this condition.

2. Case History/Examination

In April 2023, a 17‐year‐old boy with no major health problems suffered severe third‐degree burns that covered 80% of his body when his garments caught fire during a BBQ mishap that used gasoline. Upon entering the critical care unit (ICU), he was intubated and brought back to life right away. During his first stay in the ICU, he had many surgeries, such as burn debridement and autogenous split‐thickness skin grafting (STSG) utilizing grafts taken from the scalp and right upper back and meshed using the Meek method (1:6 ratio). During surgery, he needed numerous transfusions of packed red blood cells and fresh frozen plasma.

The ICU stay was made more difficult by severe hypotension (systolic blood pressure < 70 mmHg) caused by septic shock, with blood cultures showing Klebsiella, Acinetobacter, Providencia, Fusarium, and Enterococcus faecalis . He had vasopressor support and a mix of intravenous antibiotics (Colistin and Vancomycin). A tracheostomy was done so that the patient could breathe for a long time. After more than 4 months of mechanical breathing, the patient's health slowly became better, and he was able to stop using the ventilator.

About 3 months after the first injury, while he was still in the ICU recovery phase, his skin and sclera became yellow, his urine became black, his feces became clay‐colored, and he had itchy skin. Tests in the lab showed that the total bilirubin (11 mg/dL; direct 10 mg/dL) and cholestatic liver enzymes were quite high. Abdominal ultrasonography indicated hepatomegaly without focal lesions, necessitating further imaging by magnetic resonance cholangiopancreatography (MRCP), which revealed several intrahepatic bilomas and little ductal dilatation, consistent with secondary sclerosing cholangitis.

He began taking oral ursodeoxycholic acid (250 mg twice a day) and drinking enough water. There was a gradual improvement in clinical and biochemical indicators, and once he was stable, he was sent to a rehabilitation program where he would continue to get medical treatment and have frequent checkups.

The signs of SSC appeared around 3 months after the first burn injury, while the patient was still recovering in the ICU. The next incident of ascending cholangitis happened several weeks after discharge, during an outpatient follow‐up.

3. Differential Diagnosis, Investigations, and Treatment

Ultrasonography identified hepatomegaly without focal findings, leading to further investigation with magnetic resonance cholangiopancreatography (MRCP). MRCP confirmed intrahepatic biliary irregularities and bilomas consistent with SSC‐CIP (details already described in the Case Presentation; see Figure 1). Based on clinical, biochemical, and imaging findings, the patient was diagnosed with SSC secondary to burns. He was prescribed oral ursodeoxycholic acid at a dosage of 250 mg twice daily, along with adequate hydration. This regimen notably improved his skin color and bilirubin levels. He was discharged with a prescription for oral ursodeoxycholic acid and advised to participate in a rehabilitation program.

FIGURE 1.

T2‐weighted magnetic resonance cholangiopancreatography (MRCP) images. (A) axial view, (B) coronal view, showing multiple intrahepatic biliary duct dilations and strictures with no significant extrahepatic bile duct involvement, in addition to fluid processes mainly in the right lobe, suggestive of bilomas and abscesses.

Unfortunately, the patient's yellowish discoloration worsened, along with fever and abdominal discomfort, primarily in the right upper quadrant, while in rehabilitation. His total bilirubin levels had risen to 15 mg/dL, with 10 mg/dL representing the direct bilirubin fraction, along with elevated inflammatory markers. He was admitted to the hospital after being diagnosed with ascending cholangitis as a complication of his underlying condition.

Upon admission, the patient received broad‐spectrum antibiotics and adequate IV hydration. His clinical condition improved significantly, and his bilirubin levels dropped noticeably. After a five‐day stay at the hospital, the patient showed satisfactory progress and was discharged.

4. Conclusion and Results (Outcome and Follow‐Up)

Following discharge, the patient actively participated in a rigorous rehabilitation program. During follow‐up outpatient assessments, it was discovered that he relied on a wheelchair and required assistance with daily activities. However, there was marked improvement in his overall condition, and no complications or adverse events were reported during this timeframe.

SSC‐CIP is a rapidly advancing condition that is often underdiagnosed. There is no single cause for the disease, but rather several causes combined, including ischemia of the biliary system, treatment received during an ICU stay, and bile toxicity. Its underdiagnosis stems from the fact that it manifests primarily as cholestasis, which has a wide differential diagnosis. Diagnosis typically relies on MRCP or ERCP. Despite any initial clinical and biochemical improvement, the disease persists and progresses, leading inevitably to liver cirrhosis, necessitating liver transplantation for the patient.

5. Discussion

Our patient, a previously healthy 17‐year‐old male with extensive third‐degree burns covering 80% of his total body surface area, underwent a protracted ICU admission complicated by sepsis, multiorgan dysfunction, and the administration of vasopressors, clinical features characteristic of secondary sclerosing cholangitis in critically ill patients (SSC‐CIP) [1, 3, 4]. The persistent hypotension and vasopressor medication likely induced ischemic cholangiopathy, given that the intrahepatic bile ducts rely only on branches of the hepatic artery, making them particularly vulnerable to hypoperfusion [3, 5, 6, 7]. Moreover, bile toxicity and systemic inflammation resulting from significant burns may have exacerbated cholangiocytic injury, consistent with the dual pathogenic pathways of ischemia and toxic bile‐mediated damage outlined in SSC‐CIP [3, 5, 8]. MRCP was the best test for this patient because it was non‐invasive and showed problems with the intrahepatic ducts and biliary casts without the hazards of ERCP in a patient with weak blood flow [3, 7]. Our patient's survival without liver transplantation, in contrast to previously documented SSC‐CIP instances reported in Table 1, may likely be ascribed to early detection, the swift commencement of ursodeoxycholic acid treatment, and meticulous long‐term monitoring [7, 8, 11, 12]. These data emphasize the need to sustain a heightened index of suspicion for SSC‐CIP in critically ill burn patients exhibiting chronic cholestasis, as early detection and supportive care may substantially enhance outcomes [3, 5, 7, 12].

TABLE 1.

Cases of secondary sclerosing cholangitis following burn injuries published in Pubmed between 2002 and 2024.

Parameter/reference	Year	Age (years)	Sex	BSA burned	ICU stay (days)	Mechanical ventilation	Total bilirubin (mg/dl) a	ALP (IU/L) a	GGT (IU/L) a	Diagnosis modality	Time to SSC‐CIP diagnosis (days)	UDCA treatment	Alive	Liver transplantation	Cause of death
Engler et al. [9].	2002	16	Male	44%	—	Yes	2	1637	428	ERCP and biopsy	No	Yes	Yes	Listed	—
Engler et al. [9].	2002	60	Male	33%	—	Yes	31	2989	858	ERCP and biopsy	No	Yes	No	—	Septic shock
Engler et al. [9].	2002	59	Female	34%	—	Yes	1.5	419	45	ERCP and biopsy	No	Yes	No	—	Hepatic coma
Engler et al. [9].	2002	47	Female	45%	—	Yes	8	1905	359	ERCP and biopsy	No	Yes	Yes	—	—
Engler et al. [9].	2002	55	Male	24%	—	Yes	3.2	1094	430	ERCP and biopsy	No	Yes	No	Yes	Right heart failure
Benninger et al. [4].	2004	56	Female	34%	58	Yes	No	No	No	ERCP	130	Yes	No	—	Liver insufficiency
Esposito et al. [10].	2008	16	Male	—	15	Yes	2.2	1677	396	Biopsy	Variable	No	Yes	Yes	—
Al benna et al. [11].	2010	22	Male	44%	13	Yes	12.1	1497	1633	ERCP	No	Yes	Yes	Listed	—
Ben‐Ari et al. [8].	2015	18	Male	95%	153	Yes	17.9	2009	4573	MRCP and liver biopsy	106	Yes	Yes	Yes	—
Ben‐Ari et al. [8].	2015	50	Male	35%	76	Yes	4.15	3032	5678	ERCP	53	Yes	Yes	—	—
Ben‐Ari et al. [8].	2015	28	Male	90%	192	Yes	40.7	2772	4890	MRCP and liver biopsy	42	Yes	No	Listed	Septic shock
Ben‐Ari et al. [8].	2015	56	Male	50%	96	Yes	16.4	2123	1040	MRCP and liver biopsy	33	Yes	No	—	Septic shock
Leonhardt et al. [7].	2015	18	Male	—	82	Yes	6	No	630	Biopsy	No	No	No	—	Septic shock
Our case	2024	17	Male	80%	120	Yes	11	—	—	MRCP	90	Yes	Yes	—	—

Abbreviations: ALP, alkaline phosphatase; BSA, body surface area; ERCP, endoscopic retrograde cholangiopancreatography; GGT, gamma‐glutamyl transferase; ICU, intensive care unit; MRCP, magnetic resonance pancreatography; SSC‐CIP, secondary sclerosing cholangitis in critically‐ill patients; UDCA, ursodeoxycholic acid.

^a Levels at time of diagnosis.

It is not one but multiple concomitant processes that are speculated to go hand in hand in the causation of the structural changes seen in SSC‐CIP. It is also becoming increasingly plausible to believe that all these processes culminate in mediating damage primarily through two mechanisms called ischemic cholangiopathy and toxic bile [3, 5]. Hypotension, the use of vasopressor therapy, microcirculatory changes, and mechanical ventilation are consistently implicated in SSC, contributing to ischemic cholangiopathy [5]. Unlike the duality of blood supply to the liver and common bile duct, the intrahepatic biliary system solely relies on branches of the hepatic artery for blood supply, rendering it vulnerable to ischemia in cases of hypoperfusion [6]. Consequently, the intrahepatic bile ducts are more prone to involvement in this disease compared to other parts of the biliary system [3, 4, 7, 8].

Based on findings from multiple reports, it was consistently prevalent that patients experienced a period of severe hemodynamic instability due to both sepsis and fluid losses [4, 7, 8, 9, 13]. Silke Leonhardt also noted that the occurrence of hypotensive episodes later in the disease course correlated with delayed signs of cholestasis in patients, further supporting the association [5]. In efforts to control the compromise in blood flow, almost all reported individuals received inotropic vasopressors, which, despite their effectiveness in restoring the intravascular pool, are known to do so by preferentially constricting the arteries of the splanchnic circulation [14]. In addition to vasopressor therapy, all patients with SSC‐CIP received mechanical ventilation as part of their management, with specific settings including high positive end‐expiratory pressure (PEEP) higher than 10 mmHg in most patients, low tidal volume, and prone positioning. These settings collectively reduce both cardiac output and hepatic blood flow, reasonably contributing to biliary system hypoperfusion [3, 5, 15].

Deriving from previous experimental models, it was found that the smaller the feeding artery is, the more damage it causes in cases of occlusion, emphasizing the role of microcirculatory disturbances in the development of SSC‐CIP [16]. Red blood cell aggregation from blood products, increased blood viscosity from the direct effect of burn injury, hemoconcentration, or the administration of colloidal solutions, are the elements most implicated [5]. Since all available reports describe at least one of these factors, their contribution to the disease process is appreciable.

The severe injuries associated with the development of SSC‐CIP are mirrored by a heightened generalized inflammatory response. The generalized systemic inflammation seen in burn patients, coupled with ischemia, leads to the emergence of the toxic bile effect, characterized by the destruction of the biliary epithelium through the detergent effects of bile [3, 5]. The hepatobiliary transport system normally emulsifies bile through hepatocytic phospholipid secretion, and the biliary epithelium is furthermore protected through biliary bicarbonate secretion, forming an alkaline barrier protecting the cholangiocytes. It is highly plausible that ischemia and inflammatory cytokines exert deleterious effects on this transport system [3, 5].

Several other factors were studied in their contribution to the development of SSC‐CIP, but were dismissed due to inconsistency or an implausible connection. These factors include total parenteral nutrition (TPN), the use of antibiotics, and the duration of stay in the ICU [5].

In addition to the aforementioned effects of ischemia and systemic inflammation on the biliary system, these factors also facilitate bacterial colonization by compromising the gut barrier, giving way to bacterial cholangiopathy. While bacterial cholangitis alone has a favorable prognosis, in the context of SSC‐CIP, with its obliterative changes and loss of normal biliary flow necessary for a favorable outcome, it exacerbates the destruction of biliary ducts, giving the disease the progressive nature that is consistent among all reported cases of SSC‐CIP to date [3, 7].

In the early stages of SSC, clinical signs and symptoms are infrequent, and cholestasis is primarily evidenced by abnormal liver function tests. SSC‐CIP presents a cholestatic pattern, characterized by a sequential increase in biomarkers [1]. An early indicator of SSC‐CIP is the rapid elevation of γ‐glutamyltransferase (GGT), peaking around 7–9 days after the primary insult, followed by an increase in alkaline phosphatase (ALP) a few days later. Bilirubin exhibits the slowest rise, taking around 20 days. Notably, GGT elevation is the most pronounced, peaking at approximately 20–50 times the upper limit of normal (ULN), while ALP and bilirubin reach a maximum of 15 times the ULN. In contrast, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) show a moderate increase, up to three times the ULN [3]. Intriguingly, bilirubin levels may spontaneously decrease after 2–6 months, even as SSC‐CIP continues to progress [4]. A study revealed a significant rise in cholesterol levels in SSC‐CIP patients, reaching around 2.5 times the ULN, distinguishing it from PSC, where hypercholesterolemia is uncommon [3]. As the condition advances, the predominant manifestations become jaundice, pruritus, and abdominal discomfort confined to the right upper quadrant [1].

Diagnosing SSC‐CIP poses several challenges for several reasons: it is an underdiagnosed entity, remains asymptomatic in its early stages with only cholestasis as a presenting feature, has a wide range of differential diagnoses for ICU patients with cholestasis, and only a small percentage of them have SSC‐CIP. In addition, high mortality rates during ICU stays often impede timely diagnosis, and the only diagnostic tests available are either MRCP or endoscopic retrograde cholangiopancreatography (ERCP) [3].

Sepsis‐induced cholestasis, drug‐induced liver injury, TPN, and choledocholithiasis are among the several conditions that can cause cholestasis in an ICU patient [17, 18]. The primary distinguishing feature in SSC‐CIP is the persistence of cholestasis even after achieving clinical recovery, pointing towards enduring anatomical damage rather than a transient functional impairment. This implies that despite improvement in clinical symptoms, there may be irreversible harm to the bile ducts or liver tissue [3].

Abdominal US is typically the initial diagnostic imaging for patients diagnosed with cholestasis. It is useful in excluding other causes of cholestasis, although normal results do not rule out SSC. MRCP is the recommended non‐invasive diagnostic modality for accurately diagnosing SSC‐CIP following US [3]. In the early stages of the disease, the common initial findings are multiple ribbon‐like intraductal filling defects known as biliary casts. Subsequently, infections may occur, leading to the development of multiple hepatic abscesses. As the disease progresses, findings include multiple irregular strictures, dilations, beading, and wall thickening. Crucially, the distal common bile duct remains intact at every stage, forming a “pruned tree” appearance, as described by Leonhardt et al. Moreover, features of cirrhosis develop approximately within 6 months of diagnosis in most patients. Generally, the final diagnosis of SSC‐CIP is made after 2–3 months of initial signs of cholestasis [7]. Considering that ERCP could not prevent the progression of the disease, MRCP is a better choice than ERCP to diagnose SSC‐CIP because it is a non‐invasive procedure, and ERCP should be avoided in critically ill patients [8]. Microbiological analysis performed on bile samples collected while performing ERCP is imperative, given that it has a success rate of 98% at distinguishing the pathogen in patients and allows for targeted microbial therapy [3].

The differential diagnosis relies on radiographic findings, encompassing PSC and various forms of SSC. In order to distinguish SSC‐CIP from other types of sclerosing cholangitis and to help identify the main insult, the clinical history is crucial. Radiological features suggestive of SSC‐CIP include biliary casts and preservation of extrahepatic bile ducts [7].

Liver biopsy has no significant diagnostic value, given the fact that its features are not specific for chronic biliary obstruction; only about one‐third of patients may exhibit biopsy findings indicative of SSC‐CIP [3]. Within the first 3 months, the findings are variable but often suggest a pattern of biliary obstruction. However, during the subsequent 8 months, liver fibrosis and progressive loss of intrahepatic bile ducts became apparent on biopsy. Liver cirrhosis is the ultimate sequel of the disease, occurring within 14–17 months [1].

Despite the nonspecific presentation of the disease, it has a dramatic course with mortality rates reaching up to 50% during ICU stay. Renal failure and higher MELD scores are associated with higher mortality rates [3]. The reason for ICU admission also influences mortality; for instance, trauma and burns in previously healthy individuals are associated with better outcomes [12].

Patients with SSC‐CIP may experience substantial weight loss with an average loss of 18 kg within the first year of diagnosis [7]. They frequently suffer from recurrent bacterial cholangitis resulting from bile duct destruction. In addition, the efficacy of antibiotic treatment is reduced due to biliary stenosis and diminished bile flow. Biliary sepsis significantly contributes to the overall mortality in these patients [7, 13].

The progression to liver cirrhosis in SSC‐CIP often occurs rapidly, typically within weeks to months. This swift advancement is linked to elevated mortality rates. The median survival without a liver transplant ranges from 13 months to 44 months. These outcomes sharply contrast with the average median survival in PSC and other forms of SSC, which can reach up to 89 and 72 months, respectively, without a liver transplant. The average one‐year survival is 55%, decreasing to only 14% after 6 years [3]. In addition, cholangiocarcinoma is not reported in any patient with SSC‐CIP. This could be due to the brief follow‐up in the current studies and the short life expectancy of patients [3]. Hepatic failure, which affects roughly 36% of patients, is the main cause of death in these cases. Of the 60% of patients that survive, about 40% develop biliary cirrhosis and stay in stable condition; the other 20% develop end‐stage liver disease that necessitates liver transplantation [3].

A total of 13 cases of secondary sclerosing cholangitis following burn injuries were published in PubMed between 2002 and 2024 (Table 1). The cases vary in terms of age, BSA burned, duration of ICU stay, and severity of burns. The table highlights the complexity and variability in outcomes among different burn patients, influenced by these factors. Analyzing the cases of secondary sclerosing cholangitis reveals a varied demographic profile and clinical course. Among the cases provided, there is a slight male predominance, with a female‐to‐male ratio of 3:2. The patients' ages range from 18 to 56 years, with a mean age of approximately 38 years. The duration of ICU stay varies significantly, ranging from 15 to 192 days, with an average duration of approximately 109 days. Similarities among the cases include the occurrence of septic episodes in all cases and the requirement for mechanical ventilation in most cases. Differences include the extent of burns, with varying percentages and degrees, and the outcomes, including mortality and the need for liver transplantation. These findings highlight the heterogeneity of secondary sclerosing cholangitis presentations and underscore the importance of individualized treatment approaches tailored to each patient's unique clinical profile.

Author Contributions

Amanda N. Siniora: resources, writing – original draft. Omar Marouf: writing – original draft. Rasha R. Arekat: resources. Fatima A. Abuhilal: methodology. Mohammad I. Salah: resources. Mohammed AbuBaha: visualization. Hossam Salameh: visualization, writing – review and editing. Hatem M. Taha: project administration.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.

Conflicts of Interest

The authors declare no conflicts of interest.

Siniora A. N., Marouf O., Arekat R. R., et al., “Secondary Sclerosing Cholangitis in a Critically Ill Burn Patient: A Case Report and Review of the Literature,” Clinical Case Reports 13, no. 12 (2025): e71549, 10.1002/ccr3.71549.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.