Spontaneous Rupture of the Spleen Due to Infectious Mononucleosis
DAVID R. FARLEY, M.D., Department ofSurgery; SCOTT P. ZIETLOW, M.D., MICHAEL P. BANNON, M.D., MICHAEL B. FARNELL, M.D., Division of Gastroenterologic and General Surgery and Emergency Room Surgical Service Spontaneous splenic rupture is an extremely rare but life-threatening complication of infectious mononucleosis in young adults. Although splenectomy remains effective treatment, reports of successful nonoperative management have challenged the time-honored approach of emergent laparotomy. On retrospective analysis of our institutional experience with 8,116 patients who had this disease during a 40-year period, we found 5 substantiated cases of atraumatic splenic rupture due to infectious mononucleosis. Four additional cases of suspected splenic rupture were noted. All nine patients were hospitalized and treated (seven underwent splenectomy and two were treated with supportive measures only), and they remain alive and well. In patients with infectious mononucleosis suspected of having rupture of the spleen, a rapid but thorough assessment and prompt implementation of appropriate management should minimize the associated morbidity and mortality. On the basis of review of the medical literature and careful scrutiny of our own experience, we.advocate emergent splenectomy for spontaneous splenic rupture in patients with infectious mononucleosis.
Spontaneous rupture of the enlarged spleen in infectious mononucleosis (1M) is well documented in the medical literature but remains an exceedingly rare clinical entity. Although splenectomy is a time-honored and effective treatment for both traumatic and spontaneous splenic rupture, it is no longer the only therapeutic option available. Reports of successful nonoperative management'? or splenorrhaphy' in patients with 1M who have splenic rupture have challenged the invariable use of splenectomy for nontraumatic splenic injury of a diseased spleen.>!? In this study, we analyzed our institutional experience with spontaneous splenic rupture due to 1M and compared and contrasted our findings with those previously published in the medical literature. Our objective was to determine the optimal treatment for these patients.
noses of 1M and splenic injury or rupture were identified and reviewed. All cases of splenic injury were excluded except those in which a temporal relationship of spontaneous (atraumatic) splenic rupture followed the diagnosis of 1M. In accordance with the strict criteria established by Orloff and Peskin" and subsequently modified by Rutkow'? (Table 1), five definite cases of spontaneous splenic rupture were identified along with four cases highly suggestive of such an injury. Data were obtained about patient symptoms, physical and serologic findings, diagnostic evaluation, operative management, hospitalization, and subsequent morbidity and mortality. All patients had recently (in 1991) undergone a physical examination or had been contacted by telephone to provide long-term follow-up data.
PATIENTS AND METHODS Through a computerized search of the medical records of all patients registered at the Mayo Clinic, those with the diag-
RESULTS Definite Cases.-Five well-substantiated cases (with serologic and physical evidence) of 1M and subsequent atraumatic splenic rupture were identified (Table 2). Less than 24 hours before admission, all five patients had the acute onset of upper abdominal pain, with localization to
Address reprint requests to Dr. S. P. Zietlow, Department of Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:846-853,1992
846
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
Mayo Clin Proc, September 1992, Vol 67
Table I.-Criteria for Definite Spontaneous Splenic Rupture in Patients With Infectious Mononucleosis (1M) 1. 2. 3. 4.
No history of recent trauma Hematologic and serologic evidence of 1M Recent clinical symptoms of 1M Histologic splenic evidence consistent with 1M
Data from Rutkow.'?
the left upper quadrant. Three patients had referred pain in the left shoulder that was worsened by inspiration (Kehr's sign). Assessment in the emergency department revealed abdominal tenderness, abnormal vital signs, and anemia in all five patients. In addition, all patients had mildly increased results of liver function studies (Table 3). Splenectomy was performed in all five patients, in two of whom initial attempts at nonoperative management had failed. One patient (case 1) became hemodynamically unstable 24 hours after admission, and the serum hemoglobin concentration decreased from 11.3 to 9.3 g/dl. On the seventh day of hospitalization, another patient (case 3) had sudden recurrent pain in the left upper quadrant of the abdomen that immediately preceded a syncopal episode. Laparotomy revealed free intraperitoneal blood and multiple subcapsular splenic hematomas associated with active bleeding from a single capsular tear in all five patients. Each patient underwent complete splenectomy. Pathologic and histologic evaluation consistently disclosed splenomegaly in conjunction with lymphoid hyperplasia and a diffuse mononuclear infiltrate, often involving both the red and the white pulp. Subcapsular hematomas with capsular tears that
ranged from 1 to 4 em in depth and up to 8 em in length were detected. Suggestive Cases.-Although the preceding five cases were relatively straightforward and all patients fared well after splenectomy, four similar patients had complicated cases and received varied management. On the basis of the previously described strict criteria (Table 1), each case could not technically be substantiated as spontaneous splenic rupture attributable to 1M, but such a diagnosis was extremely likely. The details of these four cases are summarized in the following material. Case 6 (1958).-One month after 1M was diagnosed, a 17-year-old boy was admitted to his local hospital because of fever, malaise, and weight loss (9 kg). While hospitalized, the patient had acute pain in the left upper quadrant of the abdomen, palpable tenderness, and orthostatic hypotension coincident with Kehr's sign. Splenomegaly was noted. Serum hemoglobin concentrations decreased from 15.5 to 12.4 gldl overnight. The patient received two units of whole blood and was observed closely. He subsequently had an uneventful recovery. On referral to our institution several weeks later, findings were unremarkable except for palpable splenomegaly. The patient remains alive and well. Case 7 (1963).-Two months after 1M was diagnosed, a 17-year-old boy came to our emergency department because of dyspnea and acute onset of pain in the left shoulder. The serum hemoglobin concentration was 11.8 g/dl (2 months previously, it had been 14.6 g/dl). He was hospitalized and observed for 1 week. Despite massive splenomegaly, he recovered with supportive measures only. At follow-up examinations at 6 and 18 months, the patient remained easily
Table 2.-overview of Mayo Patients With Infectious Mononucleosis and Spontaneous Splenic Rupture* Case
Age (yr) and sex
847
Vital signs] Manifestationst
Temp
HR
BP
RR
Hb
Interval from ER to OR
1 (1966)
17F
LUQ pain and tenderness, Kehr's sign, splenomegaly
39.1
96
100/60
22
11.3
24h
2 (1975)
33M
LUQ pain and tenderness, splenomegaly
37.7
120
118/60
16
11.3
4h
3 (1987)
28M
LUQ pain and tenderness, Kehr's sign, splenomegaly, chest pain
38.5
88
120/66
20
12.8
4 (1990)
16 F
LUQ pain and tenderness, Kehr's sign, chest pain
37.1
100
94/64
20
7.8
6h
5 (1991)
IBM
LUQ pain and tenderness
36.9
108
90/53
16
9.7
1h
7 days
*BP = blood pressure (mm Hg); ER = emergency room (department); Hb = hemoglobin (g/dl); HR = heart rate (beats/min); LUQ = left upper quadrant of the abdomen; OR = operating room; RR = respiratory rate (breaths/ min); temp = body temperature (Qq. t As noted on assessment in the emergency department.
848
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
Table 3.-Results of Liver Function Tests at Time of Initial Assessment of Five Mayo Patients With Infectious Mononucleosis and Spontaneous Splenic Rupture* Alkphos
AST
Case
(UIL)
(UIL)
Bilirubin (mg/dl) Direct Total
Normal range
98-251
12-31
0.0-0.3
0.1-1.1
0.6 0.1 0.1 0.3 0.0
1.5 3.2 0.7 1.8 1.0
0.2
1.6
*Alk
1
63
2 3 4 5
264
317
179 58 89 129 120
Mean
197
115
phos ferase.
166 176
= alkaline
phosphatase; AST
= aspartate aminotrans-
fatigued. Serologic analysis confirmed the presence of persistent leukopenia (leukocyte count, 3.6 X 103/mm3; normal, 4.1 to 10.9 x 103/mm3) and thrombocytopenia (platelet count, 36 X 103/mm3 ; normal, 184 to 370 X 103/mm3) . Splenectomy, performed electively in 1964, revealed congestive splenomegaly and an old splenic infarct (4 by 2 by 1 em). Postoperatively, the patient's energy level and blood cell counts improved (leukocytes, 9.7 X 103/mm3 ; platelets 407 X 103/mm3; hemoglobin, 14.7 g/dl), and he remains alive and well. Case 8 (1975).- Two months after 1M was diagnosed and several weeks after its apparent resolution in a Zl-yearold woman, an asymptomatic left-sided abdominal mass was noted by the husband of this patient. No history of trauma, abdominal pain or tenderness, or dyspnea was elieited. Current symptoms included fatigue and fullness in the left upper quadrant of the abdomen; diagnostic evaluation identified an obscure abdominal mass in the left upper quadrant and possible involvement of the left kidney. Exploratory laparotomy and subsequent splenectomy revealed a 3,185-g spleen, of which 2,667 g was due to a contained intrasplenic hematoma. Recovery was uneventful, and she remains alive and well. Case 9 (1985).-Two weeks after the onset of fever, malaise, and an infection of the upper respiratory tract, a 19year-old man experienced acute pain in the upper abdominal area and the left side of the chest while at rest. On initial assessment in our emergency department, he had tenderness in the left upper quadrant of the abdomen and stable vital signs: temperature, 38.8°C; heart rate, 100 beats/min; respiratory rate, 16 breaths/min; and blood pressure, 130/60 mm Hg. The serum hemoglobin concentration was 10.5 g/dl. An abdominal computed tomographic scan disclosed a large subcapsular splenic hematoma but no evidence of free intraperitoneal fluid (Fig. 1). Because of a positive mononucleo-
Mayo CIiD Proc, September 1992,Vol 67
sis spot slide test and the current hemodynamic stability, the patient was cautiously observed. A repeated computed tomographic examination 6 days later (Fig. 2) revealed a left-sided thoracic pleural effusion and no change in the size of the splenic hematoma. Recovery was uneventful, and the patient was dismissed at 1 week. Ultrasonography at 1month follow-up showed complete resolution of both the pleural effusion and the subcapsular hematoma. The patient remains alive and well.
DISCUSSION Spontaneous rupture of the spleen is the most common cause of death in patients with IM.20 This exceedingly rare complication is well documented in the medical literature (Table 4). The incidence, initial manifestations, diagnostic evaluation, and subsequent medical and surgical management merit discussion to help physicians minimize the morbidity and mortality from this unusual but serious condition. Definition.-Based on Rutkow's'? criteria, the diagnosis of spontaneous splenic rupture associated with 1M requires historical, physical, serologic, and histologic evidence. Because of the current availability of high-resolution computed tomography and magnetic resonance imaging and the selected use of nonoperative management or splenic salvage operations, obtaining histologic evidence is no longer possible or necessary in every case. Therefore, the criteria should be amended to include either radiographic or histologic verification along with the appropriate historical, physical, and serologic findings.
Fig. 1 (case 9). Abdominal computed tomographic scan, demonstrating splenic subcapsular hematoma on day of admission of 19year-old man who had a positive mononucleosis spot slide test. (See text for further details.)
Mayo Clio Proc, September 1992, Vol 67
Fig. 2 (case 9). Follow-up abdominal computed tomographic scan 6 days after initial scan shown in Figure 1, depicting stable subcapsular splenic hematoma.
Cause.-Common in teenagers and young adults, 1M is caused by the Epstein-Barr virus. Typically, this acute viral infection causes a transient but diffuse lymphoproliferative response. Although 1M is usually a benign and self-limited illness of 1 to 4 weeks' duration, serious complications can occur in up to 5% of patients," Incidence-s- The incidence of nontraumatic spontaneous splenic rupture is low; worldwide, however, 1M is second only to malaria in causing this rare complication." Lai 26 estimated the incidence of spontaneous splenic rupture to be 0.5% of all cases ofIM. This estimation exceeds the findings reported by Rawsthorne and associates'v-s-I case during 14 years in a city of 440,000 persons. Similarly, Lee and colleagues" found only 2 cases during a 13-year period in a city of 600,000 population. Springate and Adelson" reported only 1 such case among 25,000 autopsies surveyed in Cleveland, Ohio, in 1966. In the United States, a reasonable estimate is that 0:1% of all patients with 1M sustain spontaneous splenic rupture. 29 Our finding of at least 5 cases of spontaneous splenic rupture among 8,116 patients diagnosed with 1M at the Mayo Clinic during a 40-year period lends credence to such an approximation. In the United States, 1M is commonplace: at least 25 to 50 cases per 100,000 persons are diagnosed annually." If the estimate of spontaneous splenic rupture in 0.1% of cases of 1M is applied, approximately 50 to 100 cases of spontaneous rupture of the spleen in patients with 1M might occur yearly in the United States. Therefore, spontaneous rupture of the spleen associated with 1M is likely underreported." Similarly, accurate nationwide assessment of complications and rare fatalities from 1M is difficult. Penman" estimated the overall collective mortality from 1M to be I in 3,000 cases. Finch" estimated that the 1M-associated mor-
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
849
tality was 0.1 % and that many deaths were due to splenic rupture. Wechsler and associates," however, found no deaths in a series of 556 cases of 1M. In England and Wales between 1962 and 1972, a mean of eight patients died of 1M each year,? In a survey that encompassed 10 years, the Centers for Disease Control in Atlanta, Georgia, reported 200 deaths from IM. 25 Although splenic rupture due to 1M is likely underreported in the medical literature, the exact frequency of occurrence and any subsequent morbidity and mortality remain unknown. Initial Manifestations.-IM has no gender preponderance, but 80% of all splenic injuries occur in young men as a result of involvement in contact sports.V Although 1M is reportedly more common in male than in female subjects," no clear-cut gender preference was noted in a review of the literature on spontaneous (atraumatic) splenic rupture. Eighty percent of the patients with 1M are younger than 25 years of age,? Although spontaneous splenic rupture complicates 1M in a similar age-group, cases reported in the literature have occurred in patients from 14 to 72 years of age. 9,20 Complaints of fever, sore throat, headache, malaise, and fatigue are well documented in patients with IM.19,25,34 Abdominal pain, an infrequent complaint among patients with 1M, has been noted in more than 90% of those in whom splenic hemorrhage develops." Pain referred to the left shoulder because of diaphragmatic irritation caused by the presence of free intraperitoneal blood (Kehr's sign) is present in more than 50% of patients with splenic rupture. 18,19 Our group of patients with pathologically proven splenic rupture uniformly had pain and tenderness in the left upper quadrant of the abdomen, and most patients had chest or shoulder pain that intensified during inspiration. Physical Examination.-A brief medical history and a thorough examination are imperative and will likely provide the crucial information to prompt the examining physician to consider spontaneous rupture of the spleen in the differential diagnosis. Although upper abdominal pain is characteristic, the spectrum of symptoms in these patients is broad. The first symptoms of acute spontaneous splenic rupture have been followed by death in as brief a period as 20 minutes when emergent treatment was not administered." Some patients, however, may remain asymptomatic if the rupture is contained (note our case 8 summarized previously in Results). Most patients have manifestations somewhere between these two extremes and therefore require a rapid but thorough assessment. Following the Advanced Trauma Life Support" protocol (despite the absence of a traumatic insult) ensures prompt hemodynamic stabilization in those few patients who have hemorrhagic shock. Because the heart rate is rarely more than 100 beats/min in "routine" 1M, tachycardia should alert
850
SPLENIC RUPTIJRE IN INFECTIOUS MONONUCLEOSIS
Table 4.-Historical Documentation of Spontaneous Splenic Rupture*
Mayo CIiD Proc, September 1992, Vol 67
the patient's manifestations, additional studies may be warranted-for example, serum pregnancy test (in female patients), serum amylase, arterial blood gas analysis, and blood Year Event cultures. 1861 Rokitansky" described spontaneous rupture of the After examination of a peripheral blood smear, which spleen in a patient with leukemia may demonstrate atypical lymphocytes, the diagnosis of 1M 1874 Atkinson" reported splenic rupture without a known can be confirmed by an increased heterophil antibody titer cause or, more accurately and rapidly, by the mononucleosis spot 1922 Friesleben" described spontaneous rupture of the spleen slide test (in which a drop of serum is mixed with equine that, in retrospect, was likely due to 1M erythrocytes stabilized by formaldehyde)." 1932 Attlee" reported a likely case of spontaneous splenic Common laboratory findings include anemia and rupture from 1Min a 23-year-old woman with leukocytosis with a preponderance of lymphocytes." ScruVincent's angina tiny of patients with 1M reveals at least minor abnormal 1941 King" first substantiated spontaneous splenic rupture in results of liver function studies in 86%.3 In patients who a patient with proven 1M have abdominal pain, liver enzyme levels can fluctuate se1958 Orloff and Peskin" delineated four criteria for a definite verely.' All five of our patients who had definite spontanediagnosis of spontaneous splenic rupture ous splenic rupture had mildly increased results of liver 1978 In a review of the literature, Rutkow" found 18 bona function studies (Table 3). fide cases of nontraumatic, spontaneous splenic Plain films of the chest and abdomen frequently show a rupture attributable to 1M medially displaced gastric air bubble, an inferiorly displaced *IM =infectious mononucleosis. left kidney, and splenomegaly or an opacity in the left upper quadrant of the abdomen. Additional diagnostic studies are the attending physician to the possibility of splenic rupture." warranted in hemodynamically stable patients. Useful imagOnce the patient's condition is stabilized, the physician can ing modalities include abdominal ultrasonography, [99rnTc]sulfur colloid scanning, and abdominal computed perform a more detailed analysis. If thorough elicitation of the history fails to reveal a tomography. Although ultrasonography" and technetium classic prodrome of 2 to 3 weeks of fever, headache, sore scanning'? have proved successful, abdominal computed throat, and malaise or fatigue, the presence of cervical, axil- tomographic scanning remains the standard procedure for lary, or pelvic lymphadenopathy may suggest the diagnosis assessing the injured spleen.t':" The three patients who of 1M. Other important findings may include pharyngitis, underwent abdominal computed tomography in our study scleral icterus, and weight loss. Palpable splenomegaly, had findings correlating precisely with the pathologic however, is the most important diagnostic clue. Splenic en- changes noted intraoperatively. The availability of two largement, noted in 50% of patients with 1M, is universally high-resolution computed tomographic scanners adjacent to associated with spontaneous splenic rupture." A palpable our emergency trauma unit makes this technique our imagmass in the left upper quadrant of the abdomen and abdomi- ing modality of choice in hemodynamically stable patients. In hemodynamically unstable patients with a suspected nal tenderness with or without peritoneal irritation suggest the diagnosis of splenic rupture in most patients with a recent splenic injury, computed tomographic scanning with the history of 1M. Pain in the left side of the chest and in the inherent time constraints is not justified. Diagnostic peritoshoulder that is intensified during inspiration is usually in- neal lavage quickly and sensitively detects free intraperitodicative of free intraperitoneal blood in such a patient. neal blood and provides vital information on patients with Whatever the eventual management, we have found serial equivocal abdominal findings. Hemodynamically unstable examinations paramount to identifying a change in the con- patients with evidence of abdominal peritoneal irritation dition of the patient. Repeated deep palpation of an enlarged warrant direct transfer to the operative suite and subsequent spleen in a patient with 1M, however, is inadvisable. In at emergent laparotomy. Pathologic Changes in the Spleen.-The normal spleen least two instances, such repeated examinations have led directly to splenic rupture.v-" is characterized by the "rule of odds"-1 by 3 by 5 inches Diagnostic Evaluation.-In the emergency department, (2.5 by 7.6 by 12.7 cm) in size, weighing approximately 7 assessment of a young patient with acute abdominal pain ounces (198 g), and lying between ribs 9 and 11.46 In several days to weeks after a viral illness should include the contrast, the enlarged spleen that ruptures because of 1M following basic studies: complete blood cell count and often weighs in excess of 750 g.7,9,15 More than 50% of patients with 1M have palpable differential count, serum chemistries, urinalysis, and plain roentgenograms of the chest and abdomen. Depending on splenomegaly, and the normally sturdy splenic architecture
Mayo Clin Proc, September 1992, Vol 67
becomes fragile with the increase in size. 12,47 Although the mechanism for spontaneous rupture of the spleen in patients with 1M is unclear, approximately 2 weeks after the onset of 1M the enlarged spleen has shown capsular and trabecular infiltration with normal and atypical lymphocytes" (Fig, 3). The fibromuscular and vascular structures of the trabeculae and capsule can be so strikingly diminished by mononuclear infiltrates (with complete replacement in some areas) that a tear could occur with coughing, vomiting, or defecation. 7,8,lO,30,47,48 Subsequent pathologic evaluation typically reveals capsular tears up to 10 em long and several centimeters deep as the source for free intraperitoneal blood, Management.-A collective review of the English medical literature reveals the overwhelming current success of splenectomy in cases of spontaneous splenic rupture in 1M. Historically, however, such a successful outcome was not achieved. In a report by Smith and Custer" in 1946 of their experience with military personnel, three of six patients with spontaneous splenic rupture from 1M died, including two of five who had undergone emergent splenectomy. The postoperative mortality was related to pulmonary embolism in both patients. In a review published in 1978, Rutkow'? found no operative deaths when splenectomy was used to treat confirmed cases of spontaneous splenic rupture in patients with 1M. Numerous reports 5,8,I7,35,38 and our own experience with five additional patients substantiate the efficacy of timely splenectomy in this group of patients. Splenectomy, however, is not without associated morbidity. Whatever the indication for the procedure (for example, trauma, malignant lesion, or spontaneous rupture), almost a third of the patients sustain postoperative complications, including pulmonary atelectasis, subdiaphragmatic abscess, and pulmonary embolism." Although splenectomy remains the standard for treating spontaneous splenic rupture in patients with 1M, changing attitudes that favor splenic conservation (observation or splenorrhaphy) to preserve hematologic and immunologic competence, however, are well founded and deserve consideration. Apparently, carefully selected patients with 1M who have a contained splenic rupture can be managed nonoperatively.l-" Alberty? described successful management of two patients with histories suggestive of splenic rupture without laparotomy, recommending such an option only if patients remain hemodynamically stable and have no abdominal rigidity or rebound tenderness. A report from Canada'? reaffirmed such a nonoperative strategy and recommended repeated scintigraphic or sonographic examinations plus periodic withdrawal of peritoneal fluid during follow-up of such patients. Although we do not advocate this strategy, such management has been used effectively for
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
851
Fig. 3 (case 4). Histologic section of splenic tissue obtained after splenectomy, which was performedbecause of spontaneoussplenic rupture due to infectious mononucleosisin 16-year-oldgirl. Arrow identifies one of many "atypical" or large, reactive T lymphocytes (so-called imrnunoblasts). (Hematoxylin-eosin; x400.) monitoring of patients and has repeatedly obviated laparotomy in Canadian medical centers. Even though other case reports of successful nonoperative management have been published," several investigators'
DAVID R. FARLEY, M.D., Department ofSurgery; SCOTT P. ZIETLOW, M.D., MICHAEL P. BANNON, M.D., MICHAEL B. FARNELL, M.D., Division of Gastroenterologic and General Surgery and Emergency Room Surgical Service Spontaneous splenic rupture is an extremely rare but life-threatening complication of infectious mononucleosis in young adults. Although splenectomy remains effective treatment, reports of successful nonoperative management have challenged the time-honored approach of emergent laparotomy. On retrospective analysis of our institutional experience with 8,116 patients who had this disease during a 40-year period, we found 5 substantiated cases of atraumatic splenic rupture due to infectious mononucleosis. Four additional cases of suspected splenic rupture were noted. All nine patients were hospitalized and treated (seven underwent splenectomy and two were treated with supportive measures only), and they remain alive and well. In patients with infectious mononucleosis suspected of having rupture of the spleen, a rapid but thorough assessment and prompt implementation of appropriate management should minimize the associated morbidity and mortality. On the basis of review of the medical literature and careful scrutiny of our own experience, we.advocate emergent splenectomy for spontaneous splenic rupture in patients with infectious mononucleosis.
Spontaneous rupture of the enlarged spleen in infectious mononucleosis (1M) is well documented in the medical literature but remains an exceedingly rare clinical entity. Although splenectomy is a time-honored and effective treatment for both traumatic and spontaneous splenic rupture, it is no longer the only therapeutic option available. Reports of successful nonoperative management'? or splenorrhaphy' in patients with 1M who have splenic rupture have challenged the invariable use of splenectomy for nontraumatic splenic injury of a diseased spleen.>!? In this study, we analyzed our institutional experience with spontaneous splenic rupture due to 1M and compared and contrasted our findings with those previously published in the medical literature. Our objective was to determine the optimal treatment for these patients.
noses of 1M and splenic injury or rupture were identified and reviewed. All cases of splenic injury were excluded except those in which a temporal relationship of spontaneous (atraumatic) splenic rupture followed the diagnosis of 1M. In accordance with the strict criteria established by Orloff and Peskin" and subsequently modified by Rutkow'? (Table 1), five definite cases of spontaneous splenic rupture were identified along with four cases highly suggestive of such an injury. Data were obtained about patient symptoms, physical and serologic findings, diagnostic evaluation, operative management, hospitalization, and subsequent morbidity and mortality. All patients had recently (in 1991) undergone a physical examination or had been contacted by telephone to provide long-term follow-up data.
PATIENTS AND METHODS Through a computerized search of the medical records of all patients registered at the Mayo Clinic, those with the diag-
RESULTS Definite Cases.-Five well-substantiated cases (with serologic and physical evidence) of 1M and subsequent atraumatic splenic rupture were identified (Table 2). Less than 24 hours before admission, all five patients had the acute onset of upper abdominal pain, with localization to
Address reprint requests to Dr. S. P. Zietlow, Department of Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 67:846-853,1992
846
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
Mayo Clin Proc, September 1992, Vol 67
Table I.-Criteria for Definite Spontaneous Splenic Rupture in Patients With Infectious Mononucleosis (1M) 1. 2. 3. 4.
No history of recent trauma Hematologic and serologic evidence of 1M Recent clinical symptoms of 1M Histologic splenic evidence consistent with 1M
Data from Rutkow.'?
the left upper quadrant. Three patients had referred pain in the left shoulder that was worsened by inspiration (Kehr's sign). Assessment in the emergency department revealed abdominal tenderness, abnormal vital signs, and anemia in all five patients. In addition, all patients had mildly increased results of liver function studies (Table 3). Splenectomy was performed in all five patients, in two of whom initial attempts at nonoperative management had failed. One patient (case 1) became hemodynamically unstable 24 hours after admission, and the serum hemoglobin concentration decreased from 11.3 to 9.3 g/dl. On the seventh day of hospitalization, another patient (case 3) had sudden recurrent pain in the left upper quadrant of the abdomen that immediately preceded a syncopal episode. Laparotomy revealed free intraperitoneal blood and multiple subcapsular splenic hematomas associated with active bleeding from a single capsular tear in all five patients. Each patient underwent complete splenectomy. Pathologic and histologic evaluation consistently disclosed splenomegaly in conjunction with lymphoid hyperplasia and a diffuse mononuclear infiltrate, often involving both the red and the white pulp. Subcapsular hematomas with capsular tears that
ranged from 1 to 4 em in depth and up to 8 em in length were detected. Suggestive Cases.-Although the preceding five cases were relatively straightforward and all patients fared well after splenectomy, four similar patients had complicated cases and received varied management. On the basis of the previously described strict criteria (Table 1), each case could not technically be substantiated as spontaneous splenic rupture attributable to 1M, but such a diagnosis was extremely likely. The details of these four cases are summarized in the following material. Case 6 (1958).-One month after 1M was diagnosed, a 17-year-old boy was admitted to his local hospital because of fever, malaise, and weight loss (9 kg). While hospitalized, the patient had acute pain in the left upper quadrant of the abdomen, palpable tenderness, and orthostatic hypotension coincident with Kehr's sign. Splenomegaly was noted. Serum hemoglobin concentrations decreased from 15.5 to 12.4 gldl overnight. The patient received two units of whole blood and was observed closely. He subsequently had an uneventful recovery. On referral to our institution several weeks later, findings were unremarkable except for palpable splenomegaly. The patient remains alive and well. Case 7 (1963).-Two months after 1M was diagnosed, a 17-year-old boy came to our emergency department because of dyspnea and acute onset of pain in the left shoulder. The serum hemoglobin concentration was 11.8 g/dl (2 months previously, it had been 14.6 g/dl). He was hospitalized and observed for 1 week. Despite massive splenomegaly, he recovered with supportive measures only. At follow-up examinations at 6 and 18 months, the patient remained easily
Table 2.-overview of Mayo Patients With Infectious Mononucleosis and Spontaneous Splenic Rupture* Case
Age (yr) and sex
847
Vital signs] Manifestationst
Temp
HR
BP
RR
Hb
Interval from ER to OR
1 (1966)
17F
LUQ pain and tenderness, Kehr's sign, splenomegaly
39.1
96
100/60
22
11.3
24h
2 (1975)
33M
LUQ pain and tenderness, splenomegaly
37.7
120
118/60
16
11.3
4h
3 (1987)
28M
LUQ pain and tenderness, Kehr's sign, splenomegaly, chest pain
38.5
88
120/66
20
12.8
4 (1990)
16 F
LUQ pain and tenderness, Kehr's sign, chest pain
37.1
100
94/64
20
7.8
6h
5 (1991)
IBM
LUQ pain and tenderness
36.9
108
90/53
16
9.7
1h
7 days
*BP = blood pressure (mm Hg); ER = emergency room (department); Hb = hemoglobin (g/dl); HR = heart rate (beats/min); LUQ = left upper quadrant of the abdomen; OR = operating room; RR = respiratory rate (breaths/ min); temp = body temperature (Qq. t As noted on assessment in the emergency department.
848
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
Table 3.-Results of Liver Function Tests at Time of Initial Assessment of Five Mayo Patients With Infectious Mononucleosis and Spontaneous Splenic Rupture* Alkphos
AST
Case
(UIL)
(UIL)
Bilirubin (mg/dl) Direct Total
Normal range
98-251
12-31
0.0-0.3
0.1-1.1
0.6 0.1 0.1 0.3 0.0
1.5 3.2 0.7 1.8 1.0
0.2
1.6
*Alk
1
63
2 3 4 5
264
317
179 58 89 129 120
Mean
197
115
phos ferase.
166 176
= alkaline
phosphatase; AST
= aspartate aminotrans-
fatigued. Serologic analysis confirmed the presence of persistent leukopenia (leukocyte count, 3.6 X 103/mm3; normal, 4.1 to 10.9 x 103/mm3) and thrombocytopenia (platelet count, 36 X 103/mm3 ; normal, 184 to 370 X 103/mm3) . Splenectomy, performed electively in 1964, revealed congestive splenomegaly and an old splenic infarct (4 by 2 by 1 em). Postoperatively, the patient's energy level and blood cell counts improved (leukocytes, 9.7 X 103/mm3 ; platelets 407 X 103/mm3; hemoglobin, 14.7 g/dl), and he remains alive and well. Case 8 (1975).- Two months after 1M was diagnosed and several weeks after its apparent resolution in a Zl-yearold woman, an asymptomatic left-sided abdominal mass was noted by the husband of this patient. No history of trauma, abdominal pain or tenderness, or dyspnea was elieited. Current symptoms included fatigue and fullness in the left upper quadrant of the abdomen; diagnostic evaluation identified an obscure abdominal mass in the left upper quadrant and possible involvement of the left kidney. Exploratory laparotomy and subsequent splenectomy revealed a 3,185-g spleen, of which 2,667 g was due to a contained intrasplenic hematoma. Recovery was uneventful, and she remains alive and well. Case 9 (1985).-Two weeks after the onset of fever, malaise, and an infection of the upper respiratory tract, a 19year-old man experienced acute pain in the upper abdominal area and the left side of the chest while at rest. On initial assessment in our emergency department, he had tenderness in the left upper quadrant of the abdomen and stable vital signs: temperature, 38.8°C; heart rate, 100 beats/min; respiratory rate, 16 breaths/min; and blood pressure, 130/60 mm Hg. The serum hemoglobin concentration was 10.5 g/dl. An abdominal computed tomographic scan disclosed a large subcapsular splenic hematoma but no evidence of free intraperitoneal fluid (Fig. 1). Because of a positive mononucleo-
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sis spot slide test and the current hemodynamic stability, the patient was cautiously observed. A repeated computed tomographic examination 6 days later (Fig. 2) revealed a left-sided thoracic pleural effusion and no change in the size of the splenic hematoma. Recovery was uneventful, and the patient was dismissed at 1 week. Ultrasonography at 1month follow-up showed complete resolution of both the pleural effusion and the subcapsular hematoma. The patient remains alive and well.
DISCUSSION Spontaneous rupture of the spleen is the most common cause of death in patients with IM.20 This exceedingly rare complication is well documented in the medical literature (Table 4). The incidence, initial manifestations, diagnostic evaluation, and subsequent medical and surgical management merit discussion to help physicians minimize the morbidity and mortality from this unusual but serious condition. Definition.-Based on Rutkow's'? criteria, the diagnosis of spontaneous splenic rupture associated with 1M requires historical, physical, serologic, and histologic evidence. Because of the current availability of high-resolution computed tomography and magnetic resonance imaging and the selected use of nonoperative management or splenic salvage operations, obtaining histologic evidence is no longer possible or necessary in every case. Therefore, the criteria should be amended to include either radiographic or histologic verification along with the appropriate historical, physical, and serologic findings.
Fig. 1 (case 9). Abdominal computed tomographic scan, demonstrating splenic subcapsular hematoma on day of admission of 19year-old man who had a positive mononucleosis spot slide test. (See text for further details.)
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Fig. 2 (case 9). Follow-up abdominal computed tomographic scan 6 days after initial scan shown in Figure 1, depicting stable subcapsular splenic hematoma.
Cause.-Common in teenagers and young adults, 1M is caused by the Epstein-Barr virus. Typically, this acute viral infection causes a transient but diffuse lymphoproliferative response. Although 1M is usually a benign and self-limited illness of 1 to 4 weeks' duration, serious complications can occur in up to 5% of patients," Incidence-s- The incidence of nontraumatic spontaneous splenic rupture is low; worldwide, however, 1M is second only to malaria in causing this rare complication." Lai 26 estimated the incidence of spontaneous splenic rupture to be 0.5% of all cases ofIM. This estimation exceeds the findings reported by Rawsthorne and associates'v-s-I case during 14 years in a city of 440,000 persons. Similarly, Lee and colleagues" found only 2 cases during a 13-year period in a city of 600,000 population. Springate and Adelson" reported only 1 such case among 25,000 autopsies surveyed in Cleveland, Ohio, in 1966. In the United States, a reasonable estimate is that 0:1% of all patients with 1M sustain spontaneous splenic rupture. 29 Our finding of at least 5 cases of spontaneous splenic rupture among 8,116 patients diagnosed with 1M at the Mayo Clinic during a 40-year period lends credence to such an approximation. In the United States, 1M is commonplace: at least 25 to 50 cases per 100,000 persons are diagnosed annually." If the estimate of spontaneous splenic rupture in 0.1% of cases of 1M is applied, approximately 50 to 100 cases of spontaneous rupture of the spleen in patients with 1M might occur yearly in the United States. Therefore, spontaneous rupture of the spleen associated with 1M is likely underreported." Similarly, accurate nationwide assessment of complications and rare fatalities from 1M is difficult. Penman" estimated the overall collective mortality from 1M to be I in 3,000 cases. Finch" estimated that the 1M-associated mor-
SPLENIC RUPTURE IN INFECTIOUS MONONUCLEOSIS
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tality was 0.1 % and that many deaths were due to splenic rupture. Wechsler and associates," however, found no deaths in a series of 556 cases of 1M. In England and Wales between 1962 and 1972, a mean of eight patients died of 1M each year,? In a survey that encompassed 10 years, the Centers for Disease Control in Atlanta, Georgia, reported 200 deaths from IM. 25 Although splenic rupture due to 1M is likely underreported in the medical literature, the exact frequency of occurrence and any subsequent morbidity and mortality remain unknown. Initial Manifestations.-IM has no gender preponderance, but 80% of all splenic injuries occur in young men as a result of involvement in contact sports.V Although 1M is reportedly more common in male than in female subjects," no clear-cut gender preference was noted in a review of the literature on spontaneous (atraumatic) splenic rupture. Eighty percent of the patients with 1M are younger than 25 years of age,? Although spontaneous splenic rupture complicates 1M in a similar age-group, cases reported in the literature have occurred in patients from 14 to 72 years of age. 9,20 Complaints of fever, sore throat, headache, malaise, and fatigue are well documented in patients with IM.19,25,34 Abdominal pain, an infrequent complaint among patients with 1M, has been noted in more than 90% of those in whom splenic hemorrhage develops." Pain referred to the left shoulder because of diaphragmatic irritation caused by the presence of free intraperitoneal blood (Kehr's sign) is present in more than 50% of patients with splenic rupture. 18,19 Our group of patients with pathologically proven splenic rupture uniformly had pain and tenderness in the left upper quadrant of the abdomen, and most patients had chest or shoulder pain that intensified during inspiration. Physical Examination.-A brief medical history and a thorough examination are imperative and will likely provide the crucial information to prompt the examining physician to consider spontaneous rupture of the spleen in the differential diagnosis. Although upper abdominal pain is characteristic, the spectrum of symptoms in these patients is broad. The first symptoms of acute spontaneous splenic rupture have been followed by death in as brief a period as 20 minutes when emergent treatment was not administered." Some patients, however, may remain asymptomatic if the rupture is contained (note our case 8 summarized previously in Results). Most patients have manifestations somewhere between these two extremes and therefore require a rapid but thorough assessment. Following the Advanced Trauma Life Support" protocol (despite the absence of a traumatic insult) ensures prompt hemodynamic stabilization in those few patients who have hemorrhagic shock. Because the heart rate is rarely more than 100 beats/min in "routine" 1M, tachycardia should alert
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SPLENIC RUPTIJRE IN INFECTIOUS MONONUCLEOSIS
Table 4.-Historical Documentation of Spontaneous Splenic Rupture*
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the patient's manifestations, additional studies may be warranted-for example, serum pregnancy test (in female patients), serum amylase, arterial blood gas analysis, and blood Year Event cultures. 1861 Rokitansky" described spontaneous rupture of the After examination of a peripheral blood smear, which spleen in a patient with leukemia may demonstrate atypical lymphocytes, the diagnosis of 1M 1874 Atkinson" reported splenic rupture without a known can be confirmed by an increased heterophil antibody titer cause or, more accurately and rapidly, by the mononucleosis spot 1922 Friesleben" described spontaneous rupture of the spleen slide test (in which a drop of serum is mixed with equine that, in retrospect, was likely due to 1M erythrocytes stabilized by formaldehyde)." 1932 Attlee" reported a likely case of spontaneous splenic Common laboratory findings include anemia and rupture from 1Min a 23-year-old woman with leukocytosis with a preponderance of lymphocytes." ScruVincent's angina tiny of patients with 1M reveals at least minor abnormal 1941 King" first substantiated spontaneous splenic rupture in results of liver function studies in 86%.3 In patients who a patient with proven 1M have abdominal pain, liver enzyme levels can fluctuate se1958 Orloff and Peskin" delineated four criteria for a definite verely.' All five of our patients who had definite spontanediagnosis of spontaneous splenic rupture ous splenic rupture had mildly increased results of liver 1978 In a review of the literature, Rutkow" found 18 bona function studies (Table 3). fide cases of nontraumatic, spontaneous splenic Plain films of the chest and abdomen frequently show a rupture attributable to 1M medially displaced gastric air bubble, an inferiorly displaced *IM =infectious mononucleosis. left kidney, and splenomegaly or an opacity in the left upper quadrant of the abdomen. Additional diagnostic studies are the attending physician to the possibility of splenic rupture." warranted in hemodynamically stable patients. Useful imagOnce the patient's condition is stabilized, the physician can ing modalities include abdominal ultrasonography, [99rnTc]sulfur colloid scanning, and abdominal computed perform a more detailed analysis. If thorough elicitation of the history fails to reveal a tomography. Although ultrasonography" and technetium classic prodrome of 2 to 3 weeks of fever, headache, sore scanning'? have proved successful, abdominal computed throat, and malaise or fatigue, the presence of cervical, axil- tomographic scanning remains the standard procedure for lary, or pelvic lymphadenopathy may suggest the diagnosis assessing the injured spleen.t':" The three patients who of 1M. Other important findings may include pharyngitis, underwent abdominal computed tomography in our study scleral icterus, and weight loss. Palpable splenomegaly, had findings correlating precisely with the pathologic however, is the most important diagnostic clue. Splenic en- changes noted intraoperatively. The availability of two largement, noted in 50% of patients with 1M, is universally high-resolution computed tomographic scanners adjacent to associated with spontaneous splenic rupture." A palpable our emergency trauma unit makes this technique our imagmass in the left upper quadrant of the abdomen and abdomi- ing modality of choice in hemodynamically stable patients. In hemodynamically unstable patients with a suspected nal tenderness with or without peritoneal irritation suggest the diagnosis of splenic rupture in most patients with a recent splenic injury, computed tomographic scanning with the history of 1M. Pain in the left side of the chest and in the inherent time constraints is not justified. Diagnostic peritoshoulder that is intensified during inspiration is usually in- neal lavage quickly and sensitively detects free intraperitodicative of free intraperitoneal blood in such a patient. neal blood and provides vital information on patients with Whatever the eventual management, we have found serial equivocal abdominal findings. Hemodynamically unstable examinations paramount to identifying a change in the con- patients with evidence of abdominal peritoneal irritation dition of the patient. Repeated deep palpation of an enlarged warrant direct transfer to the operative suite and subsequent spleen in a patient with 1M, however, is inadvisable. In at emergent laparotomy. Pathologic Changes in the Spleen.-The normal spleen least two instances, such repeated examinations have led directly to splenic rupture.v-" is characterized by the "rule of odds"-1 by 3 by 5 inches Diagnostic Evaluation.-In the emergency department, (2.5 by 7.6 by 12.7 cm) in size, weighing approximately 7 assessment of a young patient with acute abdominal pain ounces (198 g), and lying between ribs 9 and 11.46 In several days to weeks after a viral illness should include the contrast, the enlarged spleen that ruptures because of 1M following basic studies: complete blood cell count and often weighs in excess of 750 g.7,9,15 More than 50% of patients with 1M have palpable differential count, serum chemistries, urinalysis, and plain roentgenograms of the chest and abdomen. Depending on splenomegaly, and the normally sturdy splenic architecture
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becomes fragile with the increase in size. 12,47 Although the mechanism for spontaneous rupture of the spleen in patients with 1M is unclear, approximately 2 weeks after the onset of 1M the enlarged spleen has shown capsular and trabecular infiltration with normal and atypical lymphocytes" (Fig, 3). The fibromuscular and vascular structures of the trabeculae and capsule can be so strikingly diminished by mononuclear infiltrates (with complete replacement in some areas) that a tear could occur with coughing, vomiting, or defecation. 7,8,lO,30,47,48 Subsequent pathologic evaluation typically reveals capsular tears up to 10 em long and several centimeters deep as the source for free intraperitoneal blood, Management.-A collective review of the English medical literature reveals the overwhelming current success of splenectomy in cases of spontaneous splenic rupture in 1M. Historically, however, such a successful outcome was not achieved. In a report by Smith and Custer" in 1946 of their experience with military personnel, three of six patients with spontaneous splenic rupture from 1M died, including two of five who had undergone emergent splenectomy. The postoperative mortality was related to pulmonary embolism in both patients. In a review published in 1978, Rutkow'? found no operative deaths when splenectomy was used to treat confirmed cases of spontaneous splenic rupture in patients with 1M. Numerous reports 5,8,I7,35,38 and our own experience with five additional patients substantiate the efficacy of timely splenectomy in this group of patients. Splenectomy, however, is not without associated morbidity. Whatever the indication for the procedure (for example, trauma, malignant lesion, or spontaneous rupture), almost a third of the patients sustain postoperative complications, including pulmonary atelectasis, subdiaphragmatic abscess, and pulmonary embolism." Although splenectomy remains the standard for treating spontaneous splenic rupture in patients with 1M, changing attitudes that favor splenic conservation (observation or splenorrhaphy) to preserve hematologic and immunologic competence, however, are well founded and deserve consideration. Apparently, carefully selected patients with 1M who have a contained splenic rupture can be managed nonoperatively.l-" Alberty? described successful management of two patients with histories suggestive of splenic rupture without laparotomy, recommending such an option only if patients remain hemodynamically stable and have no abdominal rigidity or rebound tenderness. A report from Canada'? reaffirmed such a nonoperative strategy and recommended repeated scintigraphic or sonographic examinations plus periodic withdrawal of peritoneal fluid during follow-up of such patients. Although we do not advocate this strategy, such management has been used effectively for
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Fig. 3 (case 4). Histologic section of splenic tissue obtained after splenectomy, which was performedbecause of spontaneoussplenic rupture due to infectious mononucleosisin 16-year-oldgirl. Arrow identifies one of many "atypical" or large, reactive T lymphocytes (so-called imrnunoblasts). (Hematoxylin-eosin; x400.) monitoring of patients and has repeatedly obviated laparotomy in Canadian medical centers. Even though other case reports of successful nonoperative management have been published," several investigators'
