Open Forum Infectious Diseases ID CASES or recent travel. Family history was remarkable for thyroid dis- Splenic Infarction: An ease in her mother and brother, but negative for thrombophilic Under-recognized Complication of disease. The physical exam was significant for temperature of Infectious Mononucleosis? 38.1°C, submandibular lymphadenopathy, and abdominal ten- 1 1 2 2,a 1,2,a derness at the left upper quadrant. Blood test results are shown Yan Li, Ann George, Sami Arnaout, Jennifer P. Wang, and George M. Abraham 1 2 in Table 1. Contrast computed tomography (CT) imaging of Saint Vincent Hospital, Worcester, Massachusetts; University of Massachusetts Medical School, Worcester, Massachusetts the abdomen and pelvis showed splenomegaly of 16.3 cm and multiple wedge-shaped hypodensities throughout the spleen Splenic infarction is a rare complication of infectious mono- consistent with infarcts (Figure 1), neither of which was pres- nucleosis. We describe 3 cases of splenic infarction attributed ent on an imaging study 1 year before. Blood cultures and tran- to infectious mononucleosis that we encountered within a sthoracic echocardiogram were negative. Babesia polymerase 2-month period. We underscore the awareness of this poten- chain reaction and Lyme antibody screen were negative. The tial complication of infectious mononucleosis and discuss the patient was diagnosed with IM complicated by splenic infarc- differential diagnosis of splenic infarction, including infectious tion. She received supportive care and was discharged on the etiologies. While symptomatic management is usually sufficient fourth hospital day with instructions to avoid contact sports. for infectious mononucleosis-associated splenic infarction, Approximately 2 months later, she was reassessed for Crohn’s close monitoring for other complications, including splenic disease, at which time MR enterography showed resolving sple- rupture, is mandated. Keywords. Epstein-Barr virus; infectious mononucleosis; nomegaly of 11.9 cm with a decrease in the size and extent of splenic infarction. splenic infarcts. CASE 2 A 20-year-old man with no significant past medical history While infectious mononucleosis (IM) usually represents a presented with 5 days of neck swelling, soreness, and hives benign clinical process, serious complications can occur. Scant and 1 day of left upper quadrant abdominal pain associated data on the incidence of splenic infarction as a complication with nausea. Review of systems was otherwise negative. He of IM exist, with the majority of the literature being individual reported no significant sick contacts, travel, outdoor activities, case reports. We report a cluster of 3 cases of IM complicated by or trauma. Family history was remarkable for stroke and deep splenic infarction that we saw over a 2-month period. We aim vein thrombosis in his 2 maternal aunts, with no other history to raise awareness of this potentially under-recognized clinical of thrombophilic diseases. Physical examination revealed a problem. well-nourished male with resolving hives present on his face CASE 1 and back. The abdomen was soft with mild tenderness with- A 24-year-old female with Crohn’s disease, Hashimoto thyroid- out rebound or guarding over the left upper quadrant. The itis, and sacroiliitis presented in late summer with a 1-week his- remainder of the exam was unremarkable. Laboratory find- tory of increasingly severe left-sided abdominal pain associated ings, including hypercoagulable workup, are shown in Table 1. with fever, nausea, loose stools, and fatigue. Review of systems CT scan of the abdomen and pelvis revealed hepatospleno- was otherwise negative. She reported no sick contacts, tick bites, megaly, multiple hypodensities suggesting splenic infarct, and borderline enlarged portal hepatic and periaortic lymph nodes. Given that no evidence of thrombophilic disease was Received 2 February 2018; editorial decision 8 February 2018; accepted 14 February 2018. found, the diagnosis of IM complicated by splenic infarction Equal contribution Correspondence: G. M. Abraham, MD, MPH, FACP, FIDSA, Department of Medicine, Saint was made. The patient was managed conservatively with sup- Vincent Hospital, University of Massachusetts Medical School, Saint Vincent Hospital, 123 portive treatment, including intravenous fluids, analgesics, Summer Street, Suite 385, Worcester, MA 01608-1320 (george.abraham@stvincenthospital. com). and antihistamines. Open Forum Infectious Diseases © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases CASE 3 Society of America. This is an Open Access article distributed under the terms of the Creative A 27-year-old man with no significant prior medical history Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any presented to the emergency department with complaints of left medium, provided the original work is not altered or transformed in any way, and that the work upper quadrant abdominal pain for 1 week. He also had fever, is properly cited. For commercial re-use, please contact email@example.com DOI: 10.1093/ofid/ofy041 chills, nausea, night sweats, and a sore throat. He denied recent ID CASE • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/3/ofy041/4868608 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Table 1. Laboratory Studies Case 1 Case 2 Case 3 Normal Range WBC 13.3 7.4 13.7 3.9–11.0 × 1000/μL Lymphocytes 44 1.3 6.0 0.7–4.5 × 1000/μL Reactive/atypical lymphocytes 8 49 20 0–6% HgB 11.9 14.7 13.3 12.5–17.0 g/dL Platelets 236 115 323 150–450 × 1000/μL AST 36 100 156 0–55 U/L ALT 20 86 379 0–44 U/L APTT 25.5 27.1 29.7 25.0–35.0 s PT 12.1 11 11.3 9.1–12.0 s INR 1.1 1.1 1.1 2.0–3.5 Heterophile, mononucleosis screen Positive Positive Positive Negative Epstein-Barr virus (VCA) antibody IgG 36.8 (positive) — — <18.0 Epstein-Barr virus (VCA) antibody IgM >160.0 (positive) — — <36.0 Epstein-Barr virus nuclear antigen antibody Negative — — <18.0 Lupus anticoagulant (dilute Russell’s viper venom time) — 58 47.6 0–47 s β-2 Glycoprotein IgM, IgG Negative Negative — <20 SU Anticardiolipin IgM 16 (indeterminate) Negative 15 (indeterminate) <10 U/mL Anticardiolipin IgG Negative Negative Negative <11 U/mL Phosphatidylserine IgM 29 (equivocal) — — <25 U/mL Phosphatidylserine IgG Negative — — <10 U/mL Protein C activity — 86 68 73%–180% Activated protein C resistance — 2.5 — 2.0–3.5 Free protein S — 78 — 57%–157% Total protein S — 73 — 60%–150% Functional protein S — — 63 63%–140% Antithrombin III activity — 116 93 75%–135% Factor V Leiden mutation — Negative Negative Negative Prothrombin gene mutation — Negative Negative Negative —, not done. Abbreviations: ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; HgB, hemoglobin; IgA, immunoglobulin A; IgG, immunoglobulin G; INR, international normalized ratio; PT, prothrombin time; SU, standard units; VCA, viral capsid antigen; WBC, white blood count. travel, tick bites, or sick contacts. Physical examination was department with analgesics. He was advised to avoid contact remarkable for tachycardia, abdominal tenderness over the left sports, physical strain, hepatotoxic medications, and to return upper quadrant, and mild splenomegaly. Blood work showed in several days for reevaluation. He returned 2 days later with a positive heterophile antibody test, leukocytosis with 23% worsening left upper quadrant abdominal pain and a new atypical lymphocytes, and transaminitis with AST 279 U/L and nonpruritic rash over the low back and lower extremities. He ALT 501 U/L. The patient was discharged from the emergency denied fever. A CT scan of abdomen and pelvis showed mod- erate splenomegaly with multiple peripheral wedge-shaped hypodensities consistent with splenic infarcts. During the hos- pitalization, laboratory studies and hypercoagulable workup, shown in Table 1, were notable only for a weakly positive anti- cardiolipin IgM antibody, lupus anticoagulant, and slightly reduced protein C activity; thus his splenic infarction was con- sidered to be a complication of IM. The patient admitted to occasional intravenous drug use, most recently 3 months prior to presentation. Following clinical improvement with symp- tomatic treatment, he was discharged but lost to follow-up without completion of an infectious endocarditis workup, a preliminary workup having been unrevealing. DISCUSSION Figure 1. Contrast-enhanced abdominal computed tomography revealed spleno- megaly with multiple wedge-shaped hypodensities throughout the spleen consist- The clinical course of IM is typically characterized by nonspecific ent with infarcts. Representative axial and coronal images from the patient in Case 1 are shown. symptoms including fever, sore throat, and lymphadenopathy 2 • OFID • ID CASE Downloaded from https://academic.oup.com/ofid/article-abstract/5/3/ofy041/4868608 by Ed 'DeepDyve' Gillespie user on 16 March 2018 followed by spontaneous recovery. Although splenic infarct is transient prothrombotic factors tend to disappear in 1–4 years reported to be an infrequent complication of IM, quite remark- . Third, an increased level of circulating immune complexes ably, we saw 3 such cases in Worcester, Massachusetts, within due to B cell proliferation, promoting leukocyte aggregation a 2-month period. The readily available radiological tools, and adhesiveness, has been associated with splenic infarction including CT scan, ultrasonography, and magnetic resonance with EBV . imaging, contribute significantly in uncovering this potentially Splenic infarction complicates infections besides EBV, and under-recognized serious complication of IM. We emphasize examples are listed in Table 2. Infectious endocarditis can result a heightened awareness for evaluating for infectious causes of in septic emboli to the spleen . At least 11 cases of cytomeg- splenic infarct, particularly given the high prevalence of IM. alovirus-associated splenic infarction in immunocompetent Epstein-Barr virus (EBV) represents the most common cause of patients have been reported, and, as with EBV, inadequate blood infectious mononucleosis. A total of 23 cases of splenic infarc- supply and transient production of antiphospholipid antibodies tion during acute IM due to EBV infection are reported in the are postulated as contributors to infarct . Other infections medical literature published between 1961 and 2017 [1–4], 20 associated with splenic infarct include malaria and babesi- of which are summarized by Heo et al. . Our cases are sim- osis, which are recognized causes of splenic disease. Forty- ilar to these in terms of the median age of 23.5 years (range, four cases of malaria associated with splenic infarcts, many of 7–57 years; available in 18 cases), mostly occurring in otherwise which involved splenomegaly, were recently reviewed . To healthy people without underlying disease, time of symptom date, 4 cases of babesiosis complicated by splenic infarct have onset to diagnosis of infarction of 5 days (range, 1–25 days), been published, for which the mechanism of infarct remains presence of splenomegaly, and good clinical outcome . undefined [12–14]. Malaria and babesia can be associated with Several mechanisms are proposed for the pathogenesis of splenic infarcts even during low parasitemia. A small number of splenic infarction during IM. First, arterial blood supply may cases of splenic infarction have been associated with parvovirus be insufficient for the increased demand of the hypercellular B19 infection, and very few published reports are available on spleen during acute IM, resulting in local infarct. Second, the brucella-associated splenic infarct in the absence of infectious presence of a transient hypercoagulable state during IM has endocarditis. Isolated reports have been made with murine been proposed. Transient elevated antiphospholipid antibod- typhus as well. Again, under such circumstances, the reason ies , lupus anticoagulant , and factor VIII  have been for infarct is obscure. With regards to noninfectious etiologies, documented during the acute stage of IM when complicated splenic infarction occurs with myeloproliferative disorders, by splenic infarction. Notably, anticardiolipin antibodies have in the presence of thromboembolic or hypercoagulable states been detected in 30%–62% of patients with IM with EBV, with including malignancy and antiphospholipid syndrome, and the majority bearing no known clinical significance; such with splenomegaly. Such conditions (adapted from Hunt et al. ) are listed in Table 2. Table 2. Conditions Associated With Splenic Infarct CONCLUSION Infections IM is a very common condition, whereas splenic infarction Infective endocarditis/septic emboli occurs relatively infrequently. Splenic infarction may mani- Epstein-Barr virus fest as left upper quadrant abdominal pain during IM. When Cytomegalovirus splenic infarct is observed on imaging studies, infectious etiol- Malaria (Plasmodium vivax, Plasmodium falciparum) ogies including EBV should be considered. While symptomatic Babesiosis (Babesia microti) Parvovirus B19 management is usually sufficient for IM-associated splenic Brucellosis (Brucella melitensis) infarction, close monitoring for other complications, including Murine typhus (Rickettsia typhi) splenic rupture, is mandated. Noninfectious conditions Myeloid disorders Note Myeloproliferative neoplasm Potential coni fl cts of interest. e a Th uthors declared no potential con- Myelodysplastic syndrome flicts of interest with respect to authorship and publication of this article. Acute leukemia All authors have submitted the ICMJE Form for Disclosure of Potential Thromboembolic events Conflicts of Interest. Conflicts that the editors consider relevant to the con- Cardioembolic tent of the manuscript have been disclosed. Hypercoagulable states: antiphospholipid syndrome, malignancy Lymphoma References Hemoglobinopathy 1. Heo DH, Baek DY, Oh SM, et al. Splenic infarction associated with acute infec- tious mononucleosis due to Epstein-Barr virus infection. J Med Virol 2017; Conditions with marked splenomegaly 89:332–6. Trauma 2. Naviglio S, Abate MV, Chinello M, Ventura A. Splenic infarction in acute infec- Wandering spleen tious mononucleosis. J Emerg Med 2016; 50:e11–3. ID CASE • OFID • 3 Downloaded from https://academic.oup.com/ofid/article-abstract/5/3/ofy041/4868608 by Ed 'DeepDyve' Gillespie user on 16 March 2018 3. Suzuki Y, Kakisaka K, Kuroda H, et al. Splenic infarction associated with acute 9. Ting W, Silverman NA, Arzouman DA, Levitsky S. Splenic septic emboli in endo- infectious mononucleosis. Korean J Intern Med 2018; 33:451–2. carditis. Circulation 1990; 82:IV105–9. 4. Noor M, Sadough M, Chan S, Singh G. Splenic infarct in a patient with infectious 10. Justo D, Finn T, Atzmony L, et al. Thrombosis associated with acute cytomegalo- mononucleosis: a rare presentation. J Community Hosp Intern Med Perspect virus infection: a meta-analysis. Eur J Intern Med 2011; 22:195–9. 2017; 7:248–50. 11. Norman FF, Rojas-Marcos J, Hermida-Donate JM, et al. Splenic infarction and 5. van Hal S, Senanayake S, Hardiman R. Splenic infarction due to transient antiphospholipid antibodies induced by acute Epstein-Barr virus infection. J Clin malaria. Trans R Soc Trop Med Hyg 2014; 108:455–60. Virol 2005; 32:245–7. 12. Florescu D, Sordillo PP, Glyptis A, et al. Splenic infarction in human babesiosis: 6. Machado C, Melo Salgado J, Monjardino L. The unexpected finding of a splenic two cases and discussion. Clin Infect Dis 2008; 46:e8–11. infarction in a patient with infectious mononucleosis due to Epstein-Barr virus. 13. Al Zoubi M, Kwak T, Patel J, et al. Atypical challenging and first case report of BMJ Case Rep 2015; 2015. doi: 10.1136/bcr-2015-212428. 7. Ben-Chetrit E, Wiener-Well Y, Fadeela A, Wolf DG. Antiphospholipid antibodies babesiosis in Ecuador. IDCases 2016; 4:15–7. during infectious mononucleosis and their long term clinical significance. J Clin 14. Wong D. Babesia parasitemia causing splenic infarction: a review of the literature. Virol 2013; 56:312–5. J Case Rep Intern Med 2016; 3:78–81. 8. Gavriilaki E, Sabanis N, Paschou E, et al. Splenic infarction as a rare complication 15. Hunt DP, Thabet A, Rosenberg ES. Case records of the massachusetts general of infectious mononucleosis due to Epstein-Barr virus infection in a patient with hospital. case 29-2010. a 29-year-old woman with fever and abdominal pain. N no significant comorbidity: case report and review of the literature. Scand J Infect Dis 2013; 45:888–90. Engl J Med 2010; 363:1266–74. 4 • OFID • ID CASE Downloaded from https://academic.oup.com/ofid/article-abstract/5/3/ofy041/4868608 by Ed 'DeepDyve' Gillespie user on 16 March 2018
Open Forum Infectious Diseases – Oxford University Press
Published: Mar 1, 2018
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