It must be mono: An atypical case of splenic rupture

Abstract

Splenic rupture is a rare but life-threatening complication of infectious mononucleosis, typically associated with Epstein–Barr virus. Early diagnosis of infectious mononucleosis is essential for appropriate management but may be delayed by false-negative early testing and atypical presentations. We report an atypical case of infectious mononucleosis in a 17-year-old male who presented with an acute abdomen secondary to atraumatic splenic rupture confirmed on CT. Initial mononucleosis testing was negative, delaying diagnosis, but repeat testing and subsequent laboratory findings strongly supported the diagnosis of infectious mononucleosis. Despite initial conservative management, worsening symptoms and progression of the splenic hematoma necessitated partial splenectomy. This case highlights the importance of maintaining a high index of suspicion for infectious mononucleosis in young patients with atraumatic splenic rupture despite negative initial testing, as early diagnosis may help guide appropriate management.

Introduction

Infectious mononucleosis (IM), most commonly caused by Epstein–Barr virus (EBV), is generally a self-limited illness affecting adolescents and young adults. ¹ Although most patients present with fever, pharyngitis, and lymphadenopathy, rare complications can occur, including splenomegaly and atraumatic splenic rupture (SR), which is reported in approximately 0.1%–0.5% of cases and may be life-threatening.^2,3 SR most commonly occurs within the first 2–3 weeks of illness and, in rare cases, may precede the clinical manifestations of IM, creating diagnostic challenges.^4,5 These challenges may be compounded by false-negative heterophile antibody testing early in the disease course. ⁶ We present a case of delayed diagnosis of IM due to a false-negative Monospot test, complicated by the need for partial splenectomy.

Case presentation

A 17-year-old male with a past medical history of irritable bowel syndrome, major depressive disorder, attention-deficit/hyperactivity disorder, cannabis use, post-traumatic stress disorder, and generalized anxiety disorder presented with a lump behind his left ear, fatigue, and sore throat shortly after hospital discharge. He was accompanied by his mother.

Five days prior to presentation, the patient had been hospitalized at Penn State Hershey Medical Center (Hershey, PA, USA, in July 2024) for acute left upper quadrant (LUQ) abdominal pain associated with nausea, vomiting, and diarrhea (Figure 1). Computed Tomography (CT) imaging revealed mild-to-moderate hemoperitoneum with clot formation near an enlarged spleen measuring up to 16.9 cm (Figure 2), consistent with spontaneous SR. Notably, prior imaging had shown a normal spleen. Laboratory evaluation revealed mild transaminitis, anemia, leukocytosis, and lactic acidosis with an elevated anion gap. Coagulation studies showed mildly elevated prothrombin time (PT) and international normalized ratio (INR), though coagulation factors and fibrinogen were within normal limits (Table 1). Initial infectious workup, including heterophile antibody (Monospot) and cytomegalovirus testing, was negative (Table 1). Given that the hematoma was confined within the splenic capsule, no active extravasation was noted on CT, the patient remained hemodynamically stable, there was no history of traumatic injury, and hemoglobin remained stable (Table 1), conservative management was pursued. The patient was managed with observation, antibiotics, serial hemoglobin monitoring, and analgesia and was subsequently discharged with outpatient follow-up. Of note, the patient had an allergic reaction manifested as a rash during hospitalization and was managed with diphenhydramine (Benadryl).

Figure 1.

Flowsheet of clinical events.

Figure 2.

CT scan of the abdomen at first hospital presentation showing hemoperitoneum (red arrow) and subscapular splenic hematoma (blue arrow) with sentinel clot.

Table 1.

Key laboratory findings.

Parameter	First hospitalization	Second hospitalization	Third hospitalization	Reference range
Hemoglobin (g/dL)	12.2 =>9.1 =>8.7=>9.6	12.5=>12.6	13.5=>13.4	Reference 13.5–17.5
WBC (K/µL)	15.1	7.64	9.5	4.5–13.5
Platelet count (K/µL)	249	253	254	150–350
PT (s)/INR	15/1.2	14.3/1.1
PTT (s)	30	33
ALT/AST (U/L)	81/61	24/16	7/13	0–41/0–40
Monospot	Negative			Negative
Urine toxicology	Positive for cannabinoid
Fibrinogen (mg/dL)	Normal (275)			208–435
Factors X, II, V, VII (%)	Normal (64, 74, 86, 69)			50–150
CMV	Nonreactive			Nonreactive

CMV: cytomegalovirus; INR: international normalized ratio; PT: prothrombin time; PTT: Partial thromboplastin time; WBC: white blood cell count; ALT/AST: Alanine aminotransferase/Aspartate aminotransferase.

Note. After first hospitalization and prior to the second, a repeat Monospot test was done outpatient and came back positive.

At clinic evaluation, physical examination revealed left postauricular and cervical lymphadenopathy. Given persistent symptoms and high clinical suspicion for IM, repeat Monospot testing was performed and returned positive, supporting IM. The patient was advised to receive supportive care and to avoid nonsteroidal anti-inflammatory drugs and contact sports. Some add-on laboratory tests eventually became available after the positive repeat Monospot test, showing positive V Capsid IgM, negative EBV nuclear antibody, and equivocal V Capsid IgG (Table 2). Hence, the diagnosis of IM was ultimately supported by both repeat heterophile antibody testing and EBV-specific serology.

Table 2.

EBV specific serology labs that were added to patient’s blood sample at first hospitalization. Labs resulted after the first repeat Monospot.

Parameter	Actual value	Reference value
EBNA	Negative	Negative
V Capsid IgG	Equivocal	Negative
V Capsid IgM	Positive	Negative

EBNA: Epstein–Barr virus nuclear antibody; EBV: Epstein–Barr virus.

Three weeks after his initial clinic presentation, the patient was readmitted with persistent LUQ abdominal pain. Repeat imaging demonstrated progression of the subcapsular splenic hematoma to 6.6 cm. Although the hematoma was noted to be evolving, there was no evidence of rebleeding on CT, the patient was stable, and hemoglobin remained stable (Table 1). He was again managed conservatively and discharged with Pediatric General Surgery follow-up. Six weeks later, he continued to report activity-limiting abdominal pain at outpatient follow-up with Pediatric General Surgery. Although elective surgery was under consideration, he returned to the emergency department 1 week later with worsening symptoms. CT imaging demonstrated further enlargement of the evolving hematoma to 10.6 cm over a 7-week period. Given persistent symptoms and progressive splenic enlargement despite conservative management, the patient was admitted and underwent partial splenectomy the following day.

Postoperatively, he recovered well and continued outpatient follow-up. Over the next 2 years, he had multiple emergency department visits for acute abdominal pain at various sites; none required admission. Several CT scans obtained during these visits demonstrated stable persistent splenomegaly, with the most recent study obtained 23 months after diagnosis. Although the imaging itself was unavailable for review, the radiology report confirmed stable mild splenomegaly. At nearly 2 years of follow-up, he remained clinically stable and was doing well.

The reporting of this study conforms to the CARE guidelines. ⁷ Written informed consent was obtained from the legally authorized representative of the minor subject (17 years old). In this case, the representative was the patient’s grandmother, who accompanied the patient during one of his follow-up office visits.

Discussion

This case describes an atypical presentation of IM, where SR occurred prior to the typical initial symptoms. SR is thought to result from lymphocytic infiltration causing splenomegaly and capsular thinning, predisposing the spleen to rupture even without trauma.^1,8

The initial absence of classic IM features such as pharyngitis or lymphadenopathy made diagnosis challenging. His initial presentation with an acute abdomen and SR, though atypical, has been described in previous case reports. ⁴ In hemodynamically stable patients, SR in IM is usually managed conservatively with observation and serial imaging,^4,9 though worsening hematoma may require surgery. The patient required partial splenectomy, which is less common but has been reported in prior cases. ⁹ A systematic review of 85 IM-related SR cases reported abdominal pain in 88%, non-operative management in 32%, splenectomy in 67%, and 9% mortality. ⁴

Notably, in this case, the initial negative Monospot contributed to diagnostic uncertainty. However, false-negative heterophile antibody results are a well-recognized limitation of early testing for IM, particularly during the first week of illness, when test sensitivity is substantially reduced. ⁶ EBV-specific testing may also be inconclusive early, delaying diagnosis. ⁶ Repeating testing is therefore important when suspicion remains high. While earlier confirmation may facilitate appropriate counseling and reduce diagnostic uncertainty, delayed diagnosis in this case was largely attributable to the established limitations of early serologic testing rather than a failure to recognize the disease. ⁶ Given the unclear etiology of SR in the patient, there was concern for hematologic or oncologic causes, prompting planned hematology-oncology follow-up and additional investigations (e.g., fibrinogen and clotting factors).

Early IM diagnosis helps prevent complications such as airway obstruction, splenomegaly-related events, inappropriate antibiotic use, and hepatitis. SR remains the most serious preventable complication. Prompt diagnosis enables counseling to avoid contact sports for 3–8 weeks from symptom onset, the mainstay of prevention, ⁶ and the early use of corticosteroids to avoid airway compromise. ¹⁰ The patient received antibiotics, which resulted in an allergic reaction requiring treatment with diphenhydramine (Benadryl). The antibiotic therapy was unnecessary, as the patient’s illness was ultimately due to IM. Earlier recognition of mononucleosis might have reduced unnecessary antibiotic exposure and, consequently, the allergic reaction. Early diagnosis may not have prevented SR in this case because, at his first contact with a clinical setting (hospital), the patient had already sustained SR, which also happened to be the first presenting feature. Therefore, even if IM had been diagnosed at that time, it would not have prevented this complication. However, delayed recognition has reportedly led to preventable complications, such as in a case reported by Owies et al., where initial misdiagnosis preceded SR and unnecessary antibiotic use. ¹¹

Some differential diagnoses that were considered included connective tissue disease, hematologic malignancy such as lymphoma, and coagulopathy. Given the normal fibrinogen level, connective tissue disease was deemed unlikely. Coagulation factors (FX, II, V, VII), platelet count and morphology, as well as PT/INR and PTT, were overall unremarkable. This made coagulopathy less likely. The patient was already scheduled to follow up with Hematology/Oncology to evaluate hematologic malignancy. This plan was eventually aborted following the diagnosis of IM, which was ultimately supported by both positive repeat heterophile antibody testing and the EBV-specific serology results.

This case adds to the available reports of atypical IM, highlighting the need for high clinical suspicion. Early confirmation, including repeat testing when needed, can prevent unnecessary management and reduce complications.

Conclusion

This case contributes to the growing literature demonstrating that SR may be the initial manifestation of IM, even in the absence of classic symptoms despite initially negative diagnostic testing. In accordance with previous reports, it highlights the limitations of early Monospot testing and the importance of repeat evaluation when clinical suspicion remains high. Although atraumatic SR remains a rare complication of IM, its potentially life-threatening nature warrants consideration in young patients presenting with acute abdominal pain and splenic injury. As such, prompt and accurate diagnosis is crucial to avoid unnecessary investigations and inappropriate management.