Fatal Acute Intestinal Obstruction with Hemophagocytic Lymphohistiocytosis and Multiple Organ Failure in Adult-Onset Still’s Disease: A Rare Case Report

Introduction

Adult-onset Still’s disease (AOSD) is an uncommon systemic autoimmune inflammatory condition with an unknown cause, thought to result from a complex interplay of genetic predispositions and environmental influences.¹ AOSD was initially characterized by Eric Bywaters in 1970 as an inflammatory condition primarily affecting young adults.² It is typically marked by a triad of spiking fever, arthritis, and a salmon-colored skin rash. It closely parallels childhood-onset Still’s disease, often referred to as systemic juvenile idiopathic arthritis, which was first documented by George Still in 1897.³

Although the precise pathogenic mechanisms underlying AOSD remain unclear, various factors have been proposed to contribute to its etiology. These factors include genetic predispositions such as associations with human leukocyte antigen (HLA) DRB11201, DRB11501, B35, DR2, and DR5; infections caused by viral and bacterial pathogens; and dysregulation of the immune system.^4–7 Several cytokines, including interleukin (IL)-18, IL-1, and IL-6, play critical roles in the pathophysiology of AOSD.⁸ Serious complications occur in approximately 15% of patients, including hemophagocytic lymphohistiocytosis (HLH), also referred to as macrophage activation syndrome (MAS), and disseminated intravascular coagulation (DIC), both of which are associated with high mortality rates.^8,9 AOSD primarily affects the joints and is commonly associated with systemic inflammation; however, gastrointestinal (GI) involvement is rare. Cases of concurrent acute intestinal obstruction and HLH are particularly uncommon.

Human cytomegalovirus (CMV) is a ubiquitous double-stranded DNA virus in the β-herpesvirus subfamily.¹⁰ Following initial infection, it establishes latency in poorly differentiated myeloid precursors and can later reactivate, causing recurrences.¹¹ In immunocompromised patients, CMV infection may lead to severe, life-threatening diseases such as retinitis, encephalitis, pneumonitis, hepatitis, colitis, and radiculopathy, with clinical severity correlating to the degree of immunosuppression.^12,13

Acute intestinal pseudo-obstruction is defined by a functional blockage of the intestine in the absence of any mechanical cause. It is a relatively rare condition affecting approximately 100 out of every 100,000 hospitalized patients.¹⁴ These complications may result from various conditions, including cardiovascular diseases, neurological disorders (such as myasthenia gravis), inflammatory conditions (such as acute pancreatitis), sepsis, electrolyte imbalances, and endocrinopathies (such as hypothyroidism).^15,16 The mortality rate for acute intestinal pseudo-obstruction is 30%, rising to 45% in 10–20% of patients who develop ischemia and perforation of the colon.¹⁴

Here, we present a rare case of AOSD complicated by concurrent acute intestinal obstruction and HLH, which ultimately led to multiorgan failure and death. Our present findings reveal that it is critical to raise awareness about these rare complications, ensure timely diagnosis, and provide prompt treatment in the early stages.

Case Presentation

A 68-year-old man arrived at the Emergency Department of The First Affiliated Hospital of Zhejiang University School of Medicine, China, presenting with symptoms of severe abdominal pain, abdominal distension, nausea, vomiting, a decreased appetite, and increased stool frequency (5–8 times daily with loose stools) for the past 3 days. The patient had a one-month history of AOSD, previously manifesting as high fever, polyarthritis, a non-pruritic maculopapular erythematous chest rash, leukocytosis, and elevated ferritin levels (Table 1). A positron emission tomography scan with fluorodeoxyglucose (18F-FDG) revealed mild FDG uptake in multiple small lymph nodes, a diffusely swollen spleen with mildly increased FDG metabolism, and diffuse FDG uptake in the bone marrow, including the spine, pelvis, and sternum (Figure 1A). Subsequent bone marrow cytology showed no abnormalities in the proportion or morphology of mature lymphocytes; however, the proportion of plasma cells was elevated (Figure 1B). Despite treatment with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclosporine, the symptoms of the patient showed only slight improvement.

Table 1 Clinical Characteristics of the Patient

Figure 1 Imaging findings from radiologic and bone marrow examinations of the patient during the hospital stay. (A) Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging revealed mild FDG uptake in multiple small lymph nodes, a diffusely swollen spleen with mildly increased FDG metabolism compared to the liver, and diffuse FDG uptake in the bone marrow, including the spine, pelvis, and sternum. (B) Bone marrow cytology revealed no abnormalities in the proportion or morphology of mature lymphocytes. However, the proportion of plasma cells was elevated. (C) Bone marrow cytology revealed a reduced proportion of mature lymphocytes with no observable morphological abnormalities. Monocytoid reticular cells accounted for 5% of the cell population, while phagocytic reticular cells, identified by their engulfment of erythrocytes and platelets, constituted 2% of the cell population. (D) Abdominal computed tomography (CT) with contrast enhancement revealed marked edema and thickening of the colonic and rectal walls, with a maximum wall thickness of 1.7 cm. Abdominal and pelvic effusion, along with significant ascites, was evident. (E) Abdominal CT with contrast enhancement showed pronounced edema and thickening of the colonic and rectal walls, with a maximum thickness of 2.6 cm. Abdominal and pelvic effusion, accompanied by substantial ascites, was observed. The splenic artery and superior mesenteric artery were notably slender.

Three days prior to admission, his abdominal symptoms had worsened progressively, prompting his visit to the emergency department. He was admitted to the rheumatology department with a provisional diagnosis of AOSD.^17,18 At the time of AOSD diagnosis, malignancies and other rheumatic diseases were systematically excluded through appropriate testing. He had no history of hypertension, diabetes, heart disease, kidney disease, or other chronic conditions. The patient denied any personal or family history of chronic inflammatory bowel disease or prior abdominal surgery. Additionally, he and his family denied a history of hepatitis, tuberculosis, influenza, or other infectious diseases.

Initial Evaluations and Imaging Findings

On admission, the patient appeared acutely ill, presenting with abdominal distension, tenderness, and reduced bowel sounds. His vital signs were as follows: temperature, 36.8°C; pulse, 89 beats per minute; respiratory rate, 18 breaths per minute; and blood pressure, 131/98 mmHg. Laboratory test results showed leukocytosis (white blood cell count: 16.56 × 10⁹/L, neutrophils: 87.9%, and lymphocytes: 6.9%); hemoglobin levels, 129 g/L; platelet count, 246 × 10⁹/L; C-reactive protein levels, 9.22 mg/L; and erythrocyte sedimentation rate, 8 mm/h, suggesting an inflammatory response. Liver and kidney function test results were within normal limits (albumin 35.9 g/L, alanine aminotransferase (ALT) 7 U/L, aspartate aminotransferase (AST) 12 U/L, creatinine 90 μmol/L, and urea 8.38 mmol/L). Serum ferritin levels were markedly elevated (5672.2 ng/mL), and CMV DNA was detected (5.13 × 10² IU/mL). Echocardiography showed impaired left ventricular diastolic function but normal systolic function (ejection fraction: 55%). The cyclosporine trough concentration was 63.30 ng/mL (within normal range). Stool bacterial culture and identification revealed normal gut flora. The clinical indicators of the patient during hospitalization are presented in Table 1.

An abdominal computed tomography (CT) scan with contrast enhancement performed on the second day of admission revealed significant thickening and dilation of the entire colon, with wall thickness measuring up to 1.7 cm, accompanied by abdominal and pelvic effusions (Figure 1D). The thickened bowel segments exhibited marked proximal dilation, indicating acute intestinal obstruction without any evidence of perforation.

Management and Clinical Course

Given the severity of the condition and suspected acute intestinal obstruction, consultations were sought with gastroenterology and surgery teams. Initial management included methylprednisolone, cefoperazone-sulbactam, bowel rest, nasogastric decompression, intravenous fluids, parenteral nutrition, and somatostatin infusion (3 mg q12 h via continuous pump). Antiviral therapy with ganciclovir was initiated for CMV infection. Despite these interventions, the clinical response was minimal.

On the fourth day of admission, the patient experienced worsening abdominal pain, primarily epigastric and paroxysmal in nature, along with several episodes of green, watery diarrhea. Examination revealed abdominal tenderness without rebound tenderness and hyper-resonance on percussion. Over the next few hours, he developed signs of septic shock, including profound hypotension (blood pressure, 60/40 mmHg) requiring vasopressors.

Repeat laboratory test results revealed worsening metabolic acidosis (pH 7.18, BE −21.4 mmol/L), hyperlactatemia (8.4 mmol/L), thrombocytopenia (platelet count 12 × 10⁹/L), and rapid elevation of liver enzymes (ALT 4011 U/L and AST 17,054 U/L). Blood cultures were collected, and subsequent results were negative (Table 1). Repeat CT showed further thickening of the colonic wall (up to 2.6 cm), worsening ascites, and pleural effusion (Figure 1E).

Given the limited effectiveness of conventional treatments, the complexity of the condition of the patient, and its rapid deterioration, a multidisciplinary team (MDT) approach to diagnosis and treatment was adopted. Radiology experts reviewed consecutive imaging studies and identified a diffuse colonic edema and blood vessel irregularities (narrowing of splenic and superior mesenteric arteries), raising suspicions of systemic vasculitis or thrombotic complications. However, given the enhancement of the intestinal mucosa, gastroenterologists and surgeons unanimously agreed that there were no radiological signs of perforation or mesenteric ischemia, and thus no indication for surgical intervention. They considered the significant colonic edema to be related to inflammation caused by AOSD. Hematology experts expressed concerns about HLH/MAS due to the rapid clinical deterioration, elevated ferritin levels, and cytopenia.

Further tests confirmed MAS, indicated by natural killer (NK) cell activity of <15%, a soluble CD25 level of 3623.15 pg/mL, and evidence of hemophagocytosis observed via bone marrow cytology (Figure 1C).¹⁹ The results of screening blood via next-generation sequencing²⁰ for bloodstream infection were negative.

Clinical Outcomes

Despite aggressive management, including high-dose methylprednisolone (40 mg q12h), carbapenem antibiotics (imipenem-cilastatin 0.5 g q6h), plasma transfusion, hepatoprotective therapy, and continuous renal replacement therapy (CRRT), the condition of the patient deteriorated rapidly. He developed refractory shock, severe metabolic acidosis, and multiple organ failure. Respiratory function worsened with declining oxygenation indices. Although a higher dose of methylprednisolone, further use of the IL-6 inhibitor, and invasive mechanical ventilation were recommended, his family declined these interventions, opting only for high-flow nasal oxygen therapy.

On the sixth day of admission, the family decided to discontinue treatment, and the patient was discharged against medical advice. He passed away shortly after leaving the hospital.

Discussion

AOSD is a disease defined by uncontrolled inflammation, leading to the activation of a cytokine storm.²¹ Abdominal pain is a common manifestation among the many systemic symptoms of AOSD, with its reported frequency ranging widely between 1% and 48%.²²

We managed an elderly male patient with a rare presentation of AOSD, complicated by acute intestinal pseudo-obstruction, hemophagocytic syndrome, refractory shock, and multiple organ failure. Following the onset of acute intestinal pseudo-obstruction and hemophagocytic syndrome, the patient rapidly developed severe shock and multiple organ failure, ultimately resulting in his death.

Ogilvie syndrome, first described in 1948 by William Heneage Ogilvie, is an acute condition characterized by intestinal pseudo-obstruction. An imbalance between sympathetic and parasympathetic nerve activity is believed to contribute to its development, providing potential insights into its pathogenesis.²³ Several pathogenic mechanisms, such as interstitial cells of Cajal dysfunction, abnormalities in the enteric nervous system, and disruptions in autonomic balance, may contribute to the development of acute intestinal pseudo-obstruction.¹⁴ In critically ill patients, conditions such as severe sepsis, shock, and postoperative states are linked to an elevated risk of developing intestinal pseudo-obstruction, likely mediated by cytokine activity.^14,24 Acute colonic pseudo-obstruction has been associated with several viral infections, including herpes zoster, cytomegalovirus (CMV), and severe dengue.^25–28 In immunocompromised patients with AOSD who develop intestinal inflammation, these viral infections should be considered as potential etiologies. Our patient initially tested negative for CMV DNA upon admission, but a subsequent test was positive, suggesting CMV reactivation. Antiviral therapy was initiated immediately, and follow-up NGS testing no longer detected CMV infection. Thus, the likelihood of CMV-induced colitis in this patient was considered low, although it could not be entirely excluded, as diagnosis typically relies on biopsy. Colonic mucosal biopsies stained with hematoxylin and eosin may reveal characteristic “owl eye” inclusion bodies, which are highly specific for CMV. Notably, immunohistochemistry, which has higher sensitivity, is the gold standard for diagnosing CMV colitis.^26,29 In this case, an endoscopic biopsy was not performed due to the patient’s rapid clinical deterioration and the family’s refusal of further diagnostic and therapeutic interventions, which represents a limitation of this study.

Only a small number of cases involving AOSD complicated by pseudo-obstruction have been documented in the literature.^30–33 Additionally, a recent case report highlighted duodenojejunal inflammation as a cause of chronic vomiting,³⁴ suggesting the need for further investigation into gastrointestinal involvement in AOSD. Cytokines play a role in the autonomic regulation of both sympathetic and parasympathetic nerves, and hypercytokinemia in patients with acute conditions may lead to intestinal pseudo-obstruction via alterations in autonomic nerve responses.³⁵ Previous studies have indicated that AOSD may impact sympathetic bowel tone and disrupt the autonomic enteric nervous system, resulting in colonic distension.³³ However, AOSD is marked by elevated levels of pro-inflammatory cytokines, including IL-18, IL-1, IL-6, interferon (IFN)-α, and IFN-γ, which are crucial in the pathophysiology of the disease.⁸ Notably, IL-18 levels that are particularly elevated in patients with AOSD³⁶ may contribute as well. Given that Crohn’s disease is also associated with elevated IL-18 levels and abdominal symptoms, shared mechanisms may underlie these conditions, including mucosal inflammation and disruption of the intestinal barrier, potentially contributing to gastrointestinal complications in AOSD.³⁷ Further, AOSD can cause multiple enteric adenopathies, potentially exacerbating bowel motility impairment.³⁸ Amyloidosis should be considered a potential differential diagnosis in cases of intestinal pseudo-obstruction in patients with AOSD.^31,39 AOSD can lead to intestinal pseudo-obstruction in both acute and chronic stages, particularly when amyloidosis is a complicating factor.

Pseudo-obstruction can occur as a complication of several diseases, particularly acute conditions.¹⁴ After ruling out mechanical obstruction, it is crucial to assess the possibility of ischemia and perforation, as these complications may require surgical intervention.⁴⁰ Our patient experienced rapid clinical deterioration and severe shock; hence, we immediately considered these possibilities. However, contrast-enhanced abdominal CT revealed no evidence of intestinal blood flow obstruction or mechanical blockage, thereby excluding the possibility of bowel necrosis or perforation. The significant colonic wall thickening observed in this patient, reaching up to 2.6 cm as measured via CT imaging, indicated a severe inflammatory process affecting the gastrointestinal tract, which is very rare in AOSD. Through the MDT approach, it was determined that the intestinal obstruction could be related to diffuse vasculitis, a common complication of AOSD. Based on this diagnosis, we modified the treatment direction and implemented a conservative management strategy. This included anti-shock therapy, administration of methylprednisolone, fasting, gastrointestinal decompression, and comprehensive measures such as CRRT.

In retrospect, earlier and more aggressive immunosuppressive therapy may have improved the outcome for our patient. The presence of hemophagocytic activity in the bone marrow biopsy confirmed the diagnosis of HLH,⁴¹ but the critical condition of the patient precluded any meaningful therapeutic response. The most severe complication of AOSD is secondary HLH, which has an estimated prevalence of 10–15% and is associated with a high mortality rate.⁴² HLH is a systemic immune hyperactivation syndrome. When HLH is associated with a rheumatologic disorder, it is referred to as MAS. Although the precise pathogenic pathways remain unclear, reduced NK cell activity, elevated soluble interleukin-2 receptor levels, and excessive cytokine production are thought to play a role in the pathogenesis of both AOSD and MAS.^22,43 Due to its complexity, HLH/MAS is often difficult to differentiate from sepsis and other conditions causing systemic inflammation. MAS can progress to multiple organ failure and, ultimately, result in a fatal outcome.⁴⁴ Consequently, we initially administered aggressive antimicrobial therapy and corticosteroids.

The various treatment approaches for AOSD are tailored to the clinical presentation. NSAIDs and glucocorticoids are typically employed. In cases of HLH/MAS, hyperferritinemia, or liver involvement, IL-1 inhibitors, IL-6 receptor inhibitors such as tocilizumab, and JAK inhibitors like tofacitinib and baricitinib have proven effective.^19,45–48 Intravenous immunoglobulins, administered at doses ranging from 0.4 g/kg to 2 g/kg of body weight for 2–5 days per month, have shown potential efficacy.⁴⁹ Additionally, abatacept has been utilized in some cases of AOSD,⁵⁰ and the IL-17 inhibitor is still under preliminary investigation.⁴⁴ In the present case, the patient’s family declined further treatment, which precluded the escalation of methylprednisolone and the continued use of IL-6 inhibitors.

Management of AOSD, especially when complicated by HLH and gastrointestinal involvement, remains a challenge. This case serves as a reminder that HLH should be considered in AOSD patients who present with systemic inflammation, multiple organ dysfunction, and rapid clinical deterioration. Early identification of HLH and timely initiation of appropriate treatment protocols, such as etoposide-based regimens or biologic therapies targeting cytokines such as IL-1 or IL-6, may improve outcomes in similar cases.⁴⁸ The timing and selection of empiric immunosuppressive therapy remain significant challenges in the management of suspected HLH/MAS, particularly in patients who are critically ill, due to the persistent concern for underlying infections. These decisions rely heavily on individual patient factors and clinician expertise. In the present case, despite intensive treatment, the condition of the patient deteriorated rapidly, culminating in multiple organ failure shortly after admission to the intensive care unit. This case underscores the critical importance of early recognition and timely intervention in such scenarios. The swift progression of the clinical course of the disease also highlights the necessity for further research into the underlying pathophysiology of these severe complications associated with AOSD.

Conclusion

In summary, the present case highlights the rare yet severe complication of acute intestinal obstruction and HLH in patients with AOSD. Clinicians should maintain a high index of suspicion when encountering patients with AOSD presenting with gastrointestinal symptoms or systemic decline. A prompt diagnosis and timely, aggressive treatment is essential for improving outcomes in patients experiencing such complex and life-threatening manifestations of AOSD.