PEDIATRICS Vol. 119 No. 1 January 2007, pp. e292-e295 (doi:10.1542/peds.2006-1340)
EXPERIENCE & REASON |
Mycoplasma pneumoniae, Splenic Infarct, and Transient Antiphospholipid Antibodies: A New Association?
a Divisions of Hematology
b Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
c Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
ABSTRACT
We report 2 children with Mycoplasma pneumoniae pulmonary infection with splenic infarcts and transient antiphospholipid antibodies. This association has not been reported previously.
Key Words: pediatrics • anti-ß2-glycoprotein antibody • anticardiolipin antibody
Abbreviations: PCR, polymerase chain reaction • Ig, immunoglobulin • CT, computed tomography • APS, antiphospholipid antibody syndrome
We report 2 children with Mycoplasma pneumoniae pulmonary infection complicated by the development of splenic infarction and transient antiphospholipid antibodies. Splenic infarction may occur in patients with antiphospholipid antibodies, but this is the first report of an association with M pneumoniae infection.1–7
CASE REPORTS
Case 1.
This previously healthy 13-year-old girl presented with a 10-day history of fever, cough, and emesis. A left lower-lobe pneumonia, detected on chest radiograph, prompted treatment with oral azithromycin. Her respiratory symptoms worsened, and she was hospitalized 2 days later to receive intravenous antibiotics. On admission, she had cold agglutination of red cells, M pneumoniae was detected in her sputum by polymerase chain reaction (PCR), and M pneumoniae immunoglobulin M (IgM) was detected in her serum.
Over the next few days she had worsening respiratory distress, progressive hypoxia, and persistent left upper-quadrant abdominal pain. Because of her worsening respiratory status and unexplained abdominal pain, contrast-enhanced computed tomography (CT) of her chest and abdomen was performed and demonstrated a left lower-lobe infiltrate with a pleural effusion and hypodense lesions in the spleen that were suggestive of splenic infarction. No valvular vegetations or thrombi were detected by transthoracic echocardiogram.
The splenic infarct prompted a laboratory evaluation for thrombophilia, which revealed an elevated D-dimer, a lupus anticoagulant, and elevated anticardiolipin and ß2-glycoprotein antibodies (Table 1). Other causes of a hypercoagulable state, including thrombocytosis, factor V Leiden mutation, prothrombin mutation, low antithrombin activity, low protein S total or free, low protein C activity, high lipoprotein (a), or high homocysteine, were not identified.
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The girl was treated with doxycycline for M pneumoniae and vancomycin and cefotaxime for possible bacterial coinfection; her respiratory symptoms improved. She received therapeutic anticoagulation with low molecular weight heparin (enoxaparin, 1 mg/kg every 12 hours) for 3 months followed by 81 mg of aspirin daily until her lupus anticoagulant resolved.
Case 2.
This previously healthy 10-year-old boy presented with a 10-day history of cough and fever. He was treated with oral cephalexin for 5 days without improvement. A chest radiograph revealed a left lower-lobe infiltrate with a small effusion. His respiratory symptoms worsened, prompting hospitalization to receive intravenous antibiotics. On the fourth day of hospitalization, a thoracostomy tube was placed to drain an increasing left-sided pleural effusion. Despite drainage of 300 mL of pleural fluid, his respiratory status deteriorated, necessitating mechanical ventilation. The M pneumoniae genome was detected in his sputum by PCR (serologic testing for M pneumoniae was not obtained). No valvular vegetations or thrombi were detected by transthoracic echocardiogram.
The boy was treated with azithromycin for M pneumoniae and vancomycin and cefotaxime for possible bacterial coinfection. His condition slowly improved, and he was extubated after 10 days. After extubation he complained of significant left upper-quadrant abdominal pain. An abdominal CT demonstrated splenic infarcts with wedge-shaped lesions (Fig 1).
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Laboratory evaluation for thrombophilia revealed an elevated D-dimer, a lupus anticoagulant, and elevated anticardiolipin and ß2-glycoprotein antibodies (Table 1). His lipoprotein (a) was also elevated (75 mg/dL [upper limit of normal: 30 mg/dL]). Other causes of a hypercoagulable state including thrombocytosis, factor V Leiden mutation, prothrombin mutation, low antithrombin activity, low protein S total or free, low protein C activity, or high homocysteine were not identified. He received a 3-month course of therapeutic anticoagulation with low molecular weight heparin (enoxaparin, 1 mg/kg every 12 hours).
LABORATORY METHODS
Amplification targeting 16-subunit ribosomal DNA was performed to detect M pneumoniae as described previously.8,9 Briefly, seminested PCR with 40 and 15 cycles for amplification and reamplification, respectively, was used. All amplifications included 2'-deoxyuridine 5'-triphosphate instead of 2'-deoxythymidine 5'-triphosphate and uracil-DNA-glycosylase (UNG; Epicenter Technologies, Madison, WI) to prevent carryover contaminations from previous amplifications. The enzyme-linked immunosorbent assay was used for serologic testing for M pneumoniae (ARUP Laboratories, Salt Lake City, UT).
DISCUSSION
M pneumoniae is the etiologic agent responsible for 15% to 20% of cases of community-acquired pneumonia. Up to 25% of patients may experience extrapulmonary complications including rash, arthralgias, septic arthritis, pericarditis, myocarditis, cold-agglutinin hemolytic anemia, glomerulonephritis, rhabdomyolysis, priapism, encephalitis, cerebellar syndrome, cranial nerve palsies, and aseptic meningitis.10 Several of these extrapulmonary manifestations are related to autoimmune processes.10 Cold-agglutinin hemolytic anemia is the result of IgM autoantibodies directed against red blood cells. Patients with central nervous system complications often demonstrate antibodies to glucocerebrosidase, a component of myelin.10 Antiphospholipid antibodies have been detected in patients with M pneumoniae, although these antibodies are rarely associated with thrombotic events.11
We have reported 2 patients with pulmonary M pneumoniae infection complicated by splenic infarction. The similarity of these 2 cases is striking. Evaluation for thrombophilia revealed a lupus anticoagulant and elevated anticardiolipin and ß2-glycoprotein antibodies. Endocarditis as a source of the splenic infarcts was excluded by transthoracic echocardiography, and neither patient experienced a hypotensive episode that may have explained the infarct.
The clinical presentation of a splenic infarct can be vague, and symptoms may include nausea and left upper-quadrant abdominal pain. This relatively rare event can be diagnosed by CT; depending on the age of the infarct, the appearance varies from a mottled echo texture to a peripheral wedge-shaped lesion.12 The most common etiology of splenic infarction is cardiac embolism.13,14 Mechanical causes of infarction include splenic torsion, aortic dissection, portal hypertension, and trauma. Infarction may also develop secondary to systemic conditions including disseminated intravascular coagulopathy, hematologic malignancy, collagen vascular disease, sickle cell disease, vasculitis, thrombocytosis, metabolic infiltrative disorders, and infection. There have been case reports of splenic infarct in patients with antiphospholipid antibodies.1–7
Antiphospholipid antibodies are a heterogeneous group of IgM and IgG antibodies directed against plasma proteins bound to anionic, often phospholipid, surfaces. The term antiphospholipid antibody syndrome (APS) is used to describe patients who experience recurrent fetal loss or thrombosis in the setting of a persistent lupus anticoagulant or anticardiolipin antibodies. The mechanism by which these antibodies contribute to thrombosis is not well understood. Among patients who have a lupus anticoagulant and/or anti-ß2-glycoprotein antibodies, thrombosis is more common in those with IgG than in those with IgM antibodies and more common in those with high-titer antibodies.15,16
The presence of antiphospholipid antibodies is not always associated with a pathologic state. A lupus anticoagulant is not uncommon in healthy children who undergo routine preoperative coagulation screening and are found to have a prolonged partial thromboplastin time that does not correct when mixed with normal plasma. In this setting, antiphospholipid antibodies are transient, thought to be induced by a recent viral infection, and do not lead to clinical complications.17,18
Antiphospholipid antibodies are well documented in the setting of many infections including M pneumoniae without thrombotic complications.11,19 There have been isolated reports of patients with viral infections (hepatitis C virus, Epstein-Barr virus, and varicella zoster virus), transient antiphospholipid antibodies, and thrombotic complications. van Hal et al1 described a patient with Epstein-Barr virus infection who developed a splenic infarction in the setting of transient antiphospholipid antibodies. Rarely, infections induce a true APS with molecular mimicry as the proposed mechanism.19 Although this complication occurs more frequently in viral infections, APS has been reported after pulmonary infection with M pneumoniae.20
Our 2 patients had M pneumoniae pulmonary infections and transient antiphospholipid antibodies and developed splenic infarcts. This association has not been reported previously. The interplay between infection and transient antiphospholipid antibodies is poorly understood. We hypothesize that the antiphospholipid antibodies induced by the M pneumoniae infection resulted in a transient hypercoagulable state. In addition, both patients had left lower-lobe pulmonary infiltrates, which may have resulted in local inflammation that contributed to these thrombotic events.
Both patients received anticoagulation therapy while they continued to have positive antiphospholipid antibodies. Neither patient experienced further thrombotic or hemorrhagic complications. No data exist that define the indication, duration, or type of treatment for splenic infarction. Treatment will vary on the basis of the etiology of the infarct. Treatment options described in the literature include observation with symptomatic therapy, anticoagulation therapy, or splenectomy for severe cases.21–23 The potential complications of a splenic infarct include pseudocyst formation, abscess, hemorrhage, subcapsular hematoma, or splenic rupture.21,22,24,25
CONCLUSIONS
Patients who develop unusual thrombotic complications coincident with acute infection should be tested for the presence of antiphospholipid antibodies. The complex relationship between antiphospholipid antibodies, thrombosis, and infection requires additional study.25
ACKNOWLEDGMENTS
We thank Jeffrey M. Bergelson, MD, for thoughtful review of the manuscript.
FOOTNOTES
Accepted Aug 2, 2006.
Address correspondence to Char M. Witmer, MD, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, 4th Floor, Wood Building, Philadelphia, PA 19104. E-mail: witmer{at}email.chop.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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