Dengue fever (DF) is a mosquito-borne viral infection caused by the dengue virus (DENV) and transmitted primarily by Aedes mosquitoes. Under the 2009 World Health Organization (WHO) classification, DF is categorized as dengue with or without warning signs and severe dengue, the latter defined by plasma leakage, major bleeding, or severe organ involvement such as hepatitis, central nervous system dysfunction, cardiac impairment, or acute kidney injury (1). While most infections are self-limited, DF can present atypically, particularly in older adults or those with comorbidities.

In 2011, the WHO introduced the concept of Expanded Dengue Syndrome (EDS) to encompass multi-organ involvement beyond classical dengue manifestations, including neurologic, gastrointestinal, renal, respiratory, and cardiovascular complications (2). These atypical presentations often pose diagnostic challenges and may mimic other acute illnesses.

Acute pancreatitis (AP) is an uncommon but recognized complication of DF. Although gallstones, alcohol, and hypertriglyceridemia account for most AP cases in the general population, infectious etiologies contribute up to 10% (3). Dengue-associated AP is rare, with reported incidence ranging from 0.8 to 7% (4), and mechanisms proposed include direct viral injury, immune-mediated inflammation, and ischemia related to severe plasma leakage or shock (5).

Cardiac involvement is another notable complication of DF. Reported manifestations range from asymptomatic electrocardiographic changes to myocarditis and pericardial effusion. Pericardial effusion, in particular, is increasingly recognized as a marker of severe dengue and is thought to reflect cytokine-mediated endothelial dysfunction and increased vascular permeability (6). Although usually self-limiting, its presence warrants close monitoring.

We report two elderly patients with DF complicated by both AP and pericardial effusion, one of whom died despite intensive management. These cases underscore the importance of recognizing atypical and severe dengue manifestations—especially in high-risk populations—and highlight the need for early diagnosis and tailored supportive care to improve outcomes.

These two cases illustrate the diagnostic and clinical challenges of severe dengue complicated by AP and pericardial effusion—an uncommon but clinically important constellation of findings. Although AP has been reported in up to 7.7% of DF cases (7), most published patients are younger adults (8), typically presenting with epigastric pain during the febrile or critical phase (9). In contrast, both of our patients were women in their eighties who presented with nonspecific features, highlighting that elderly individuals may manifest severe dengue or EDS atypically, often without classical abdominal pain or warning signs. This observation is consistent with studies showing that older adults have blunted febrile responses, fewer mucocutaneous findings, and a higher risk of severe disease and organ dysfunction.

In this context, early dengue infection may mimic or coexist with other infectious processes, particularly in elderly patients who often present atypically. In Case 1, an initial diagnosis of urinary tract infection was reasonable; however, the rapid progression to severe thrombocytopenia, metabolic acidosis, shock, and radiographic evidence of plasma leakage was disproportionate to an isolated bacterial infection and prompted reconsideration of the diagnosis. Clinicians should suspect dengue in patients with acute febrile illness who develop unexplained thrombocytopenia or serosal effusions, even when an alternative diagnosis has been established. Although dengue is a viral illness, empiric antibiotic therapy may be appropriate in severe dengue when bacterial coinfection or sepsis cannot be confidently excluded, particularly in elderly patients with shock or positive cultures (10). Antibiotic use should be reassessed and de-escalated once bacterial infection is excluded.

The pathophysiology of dengue-associated AP is likely multifactorial, involving direct viral invasion of pancreatic tissue, pancreatic ductal obstruction from inflammatory edema, and immune-mediated injury (3). These mechanisms may converge in older adults with diabetes or hypertension, whose pancreatic microvasculature and immune response are already compromised, thereby increasing susceptibility to organ-specific injury. Furthermore, severe dengue is often driven by antibody-dependent enhancement (ADE), where pre-existing heterologous antibodies from a primary infection facilitate viral entry into host cells during a secondary infection (11). This process leads to an amplified immune response, increased viral load, and massive cytokine release, which contribute to severe plasma leakage and multiorgan dysfunction. Given that both patients were infected with DENV-2, a serotype frequently implicated in severe disease, ADE may have played a significant role in their rapid clinical deterioration. Importantly, AP may mimic other critical-phase complications of DF—such as hepatitis, shock, or gallbladder edema—making timely diagnosis difficult when abdominal pain is absent or overshadowed by systemic instability.

Management of dengue-related AP remains largely supportive. Fluid therapy must balance the need for pancreatic perfusion with the risk of worsening plasma leakage in severe DF. Invasive procedures are rarely indicated unless complications such as necrosis, pseudocysts, or abscess occur (12). Patient 1’s prolonged enzyme elevation raised concern for such sequelae (13), although follow-up imaging excluded these complications. Her favorable recovery after conservative management reinforces that early recognition and careful hemodynamic titration are crucial in preventing progression. Managing fluid resuscitation in octogenarians with severe dengue is particularly challenging. While aggressive crystalloid administration is standard for treating DSS (14), elderly patients with pre-existing diabetes, hypertension, and coronary artery disease have reduced cardiac compliance and impaired renal compensation. In these cases, excessive fluid may exacerbate third-space losses, such as the pleural and pericardial effusions observed in our patients, potentially leading to acute heart failure or respiratory distress (14). Therefore, fluid management in this population should emphasize a judicious, titratable strategy guided by frequent reassessment rather than standard weight-based boluses.

Cardiac involvement represents another key dimension of severe dengue. Pericardial effusion is reported in up to 7.4% of hospitalized dengue patients, generally reflecting cytokine-mediated capillary leakage rather than primary cardiac disease (15). While most effusions are mild and self-limited, rare cases may deteriorate into tamponade (16), which can be difficult to distinguish from DSS given similar presentations of hypotension and respiratory distress. In both of our cases, pericardial effusion was part of widespread third-spacing rather than isolated cardiac inflammation. These findings underscore the importance of routine point-of-care ultrasonography in elderly DF patients with hemodynamic instability, as early identification of pericardial fluid can guide timely interventions and prevent misattribution to septic or dengue shock alone.

Patient 2 also highlights a relevant diagnostic pitfall: recent COVID-19 vaccination. Post-vaccination symptoms—fever, myalgia, malaise—overlap with early dengue manifestations, potentially delaying recognition of plasma leakage. Additionally, although rare, AP has been reported following vaccination (17), which may further obscure the etiology of abdominal symptoms. In endemic regions or during outbreaks, clinicians should maintain a high index of suspicion for DF even when symptoms appear temporally associated with vaccination.

Collectively, these cases emphasize that elderly patients with comorbidities represent a uniquely vulnerable population, likely to develop atypical and severe manifestations of severe dengue, characterized here as EDS involving AP and pericardial effusion. The overlap of systemic deterioration, bacterial coinfection, and metabolic derangements further complicates early diagnosis and timely management.

These two cases highlight an uncommon but clinically significant presentation of DF—AP accompanied by pericardial effusion—in elderly patients with metabolic and cardiovascular comorbidities. Their atypical symptoms, delayed recognition, and rapid clinical deterioration demonstrate the need for heightened vigilance when evaluating older adults with nonspecific systemic complaints in dengue-endemic regions.

The novelty of this report lies in illustrating how dengue-associated AP and cardiac serositis can mimic other acute illnesses, coexist with bacterial coinfection, and present without typical abdominal pain, particularly in older adults. Early use of point-of-care ultrasound, careful interpretation of pancreatic enzyme elevation, and close hemodynamic monitoring are essential to differentiate dengue-related organ involvement from other comorbid conditions.

Future work should focus on identifying risk factors for dengue-associated AP in the elderly, clarifying the mechanisms underlying pancreatic and cardiac involvement, and developing diagnostic algorithms that integrate clinical, laboratory, and imaging findings to improve early recognition of these rare but serious complications.