Lupus (2015) 24, 109–110 http://lup.sagepub.com
LETTER TO THE EDITOR Splenic infarction due to disseminated primary CMV infection Case report Sir, A 36-year-old female with a 14-year history of systemic lupus erythematosus (SLE) managed with azathioprine 50 mg three times a day (tds) and hydroxychloroquine 400 mg once a day (od) presented with seven days of fevers, rigors, back pain, abdominal pain, and vomiting. On examination she was febrile 38 C, blood pressure (BP) 96/55 mmHg, pulse rate (PR) 88 beats per minute (bpm), and had severe tenderness over her left upper quadrant but no signs of peritonism. Investigations revealed pancytopenia (haemoglobin (Hb) 102 g/l, white cell count (WCC) 1.5, platelets (Plt) 101, neutrophils (Neut) 0.98, lymphocytes (lymph) 0.42), normal liver function tests, and C-reactive protein (CRP) 168. Splenomegaly and two wedge-shaped splenic infarcts were demonstrated on computed tomography (CT). Echocardiogram was normal. Blood cultures were negative. Treatment with broad-spectrum antibiotics produced no improvement. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) immunoglobulin (Ig)M and IgG were negative eight days after the start of fever. Complement levels were C3 1.56 g/l and C4 0.39 g/l. Anti-doublestranded DNA (anti-dsDNA) titre was 1. The lupus anticoagulant screen and anticardiolipin antibodies were negative. Clinical deterioration occurred with ongoing fevers, bilateral pulmonary consolidation with associated respiratory compromise, enlarging hepatosplenomegaly and progressive bone marrow failure including thrombocytopenia (platelet nadir 44 109/l). The international normalized ratio (INR) increased to 1.7 and prothrombin time increased to 19 seconds. Liver function tests were only marginally deranged (alkaline phosphatase (ALP) 108 U/l, gamma-glutamyl transpeptidase (GGT) 69 U/l, alanine aminotransferase (ALT) 38 U/l, aspartate aminotransferase (AST) 113 U/l, bilirubin 19 mmol/l). The main differential diagnoses considered were SLE flare vs infection. CMV
polymerase chain reaction (PCR) requested on the third day of admission (10th day of symptoms) was not processed until three days later and was positive (1.9 103 copies/ml). Intravenous ganciclovir was started, intensive care admission was narrowly avoided, and clinical improvement occurred within 48 hours. Subsequent CMV seroconversion occurred. Anticoagulation was not commenced due to the coagulopathic picture.
Discussion Infections are a primary cause of death in 37% of patients with SLE.1,2 Thrombosis occurs in 6.4% of patients hospitalized with CMV.3 Deep venous thrombosis/pulmonary embolism is the most common thrombosis site, occurring in 53.6%, followed by splanchnic vein (25.8%), splenic infarction (12.4%), and other sites (8.2%).4 Splenic infarction is more common in immunocompetent patients than in immunocompromised patients. There is increased mortality with acute CMV infection and thrombosis compared to acute CMV infection alone (22.2% vs 3.1%).3 Splenic infarction in SLE is described in association with anticardiolipin antibodies, and with the lupus anticoagulant.5 There are no previous reports of splenic infarction in a patient with SLE and CMV. This case highlights an atypical presentation of primary CMV infection with relatively light immune suppression, with the unusual features that the initial liver function tests were normal, and during disseminated disease were still only mildly deranged, CMV serology was negative, and splenic infarction occurred. There is significant overlap in the clinical presentation of an SLE flare and acute CMV infection.6 Consideration of viral infection should occur prior to increasing immune suppression. Splenic infarction in a patient with other symptoms of infection should lead the clinician to test for acute CMV infection. PCR should be ordered as well as serology as immune-compromised patients may demonstrate delayed seroconversion.
Funding Correspondence to: Jennifer Broom, Department of Medicine, Nambour General Hospital, PO Box 547, Nambour QLD 5470, Australia. Email: [email protected] Received 7 January 2014; accepted 4 August 2014
This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 15, 2015
10.1177/0961203314548885
Letter to the Editor J Broom
110
Conflict of interest statement The authors have no conflicts of interest to declare.
References 1 Fei Y, Shi X, Gan F, et al. Death causes and pathogens analysis of systemic lupus erythematosus during the past 26 years. Clin Rheumatol 2014; 33: 57–63. 2 Cohen MG, Li EK. Mortality in systemic lupus erythematosus: Active disease is the most important factor. Aust N Z J Med 1992; 22: 5–8. 3 Atzmony L, Halutz O, Avidor B, et al. Incidence of cytomegalovirus-associated thrombosis and its risk factors: A case-control study. Thromb Res 2010; 126: e439–e443.
4 Justo D, Finn T, Atzmony L, Guy N, Steinvil A. Thrombosis associated with acute cytomegalovirus infection: A meta-analysis. Eur J Intern Med 2011; 22: 195–199. 5 Fishman D, Isenberg DA. Splenic involvement in rheumatic diseases. Semin Arthritis Rheum 1997; 27: 141–155. 6 Ramos-Casals M, Cuadrado MJ, Alba P, et al. Acute viral infections in patients with systemic lupus erythematosus: Description of 23 cases and review of the literature. Medicine (Baltimore) 2008; 87: 311–318.
J Broom Infection Management Service, Department of Medicine, Nambour General Hospital, Queensland, Australia, and The University of Queensland
Lupus Downloaded from lup.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 15, 2015
LETTER TO THE EDITOR Splenic infarction due to disseminated primary CMV infection Case report Sir, A 36-year-old female with a 14-year history of systemic lupus erythematosus (SLE) managed with azathioprine 50 mg three times a day (tds) and hydroxychloroquine 400 mg once a day (od) presented with seven days of fevers, rigors, back pain, abdominal pain, and vomiting. On examination she was febrile 38 C, blood pressure (BP) 96/55 mmHg, pulse rate (PR) 88 beats per minute (bpm), and had severe tenderness over her left upper quadrant but no signs of peritonism. Investigations revealed pancytopenia (haemoglobin (Hb) 102 g/l, white cell count (WCC) 1.5, platelets (Plt) 101, neutrophils (Neut) 0.98, lymphocytes (lymph) 0.42), normal liver function tests, and C-reactive protein (CRP) 168. Splenomegaly and two wedge-shaped splenic infarcts were demonstrated on computed tomography (CT). Echocardiogram was normal. Blood cultures were negative. Treatment with broad-spectrum antibiotics produced no improvement. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) immunoglobulin (Ig)M and IgG were negative eight days after the start of fever. Complement levels were C3 1.56 g/l and C4 0.39 g/l. Anti-doublestranded DNA (anti-dsDNA) titre was 1. The lupus anticoagulant screen and anticardiolipin antibodies were negative. Clinical deterioration occurred with ongoing fevers, bilateral pulmonary consolidation with associated respiratory compromise, enlarging hepatosplenomegaly and progressive bone marrow failure including thrombocytopenia (platelet nadir 44 109/l). The international normalized ratio (INR) increased to 1.7 and prothrombin time increased to 19 seconds. Liver function tests were only marginally deranged (alkaline phosphatase (ALP) 108 U/l, gamma-glutamyl transpeptidase (GGT) 69 U/l, alanine aminotransferase (ALT) 38 U/l, aspartate aminotransferase (AST) 113 U/l, bilirubin 19 mmol/l). The main differential diagnoses considered were SLE flare vs infection. CMV
polymerase chain reaction (PCR) requested on the third day of admission (10th day of symptoms) was not processed until three days later and was positive (1.9 103 copies/ml). Intravenous ganciclovir was started, intensive care admission was narrowly avoided, and clinical improvement occurred within 48 hours. Subsequent CMV seroconversion occurred. Anticoagulation was not commenced due to the coagulopathic picture.
Discussion Infections are a primary cause of death in 37% of patients with SLE.1,2 Thrombosis occurs in 6.4% of patients hospitalized with CMV.3 Deep venous thrombosis/pulmonary embolism is the most common thrombosis site, occurring in 53.6%, followed by splanchnic vein (25.8%), splenic infarction (12.4%), and other sites (8.2%).4 Splenic infarction is more common in immunocompetent patients than in immunocompromised patients. There is increased mortality with acute CMV infection and thrombosis compared to acute CMV infection alone (22.2% vs 3.1%).3 Splenic infarction in SLE is described in association with anticardiolipin antibodies, and with the lupus anticoagulant.5 There are no previous reports of splenic infarction in a patient with SLE and CMV. This case highlights an atypical presentation of primary CMV infection with relatively light immune suppression, with the unusual features that the initial liver function tests were normal, and during disseminated disease were still only mildly deranged, CMV serology was negative, and splenic infarction occurred. There is significant overlap in the clinical presentation of an SLE flare and acute CMV infection.6 Consideration of viral infection should occur prior to increasing immune suppression. Splenic infarction in a patient with other symptoms of infection should lead the clinician to test for acute CMV infection. PCR should be ordered as well as serology as immune-compromised patients may demonstrate delayed seroconversion.
Funding Correspondence to: Jennifer Broom, Department of Medicine, Nambour General Hospital, PO Box 547, Nambour QLD 5470, Australia. Email: [email protected] Received 7 January 2014; accepted 4 August 2014
This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 15, 2015
10.1177/0961203314548885
Letter to the Editor J Broom
110
Conflict of interest statement The authors have no conflicts of interest to declare.
References 1 Fei Y, Shi X, Gan F, et al. Death causes and pathogens analysis of systemic lupus erythematosus during the past 26 years. Clin Rheumatol 2014; 33: 57–63. 2 Cohen MG, Li EK. Mortality in systemic lupus erythematosus: Active disease is the most important factor. Aust N Z J Med 1992; 22: 5–8. 3 Atzmony L, Halutz O, Avidor B, et al. Incidence of cytomegalovirus-associated thrombosis and its risk factors: A case-control study. Thromb Res 2010; 126: e439–e443.
4 Justo D, Finn T, Atzmony L, Guy N, Steinvil A. Thrombosis associated with acute cytomegalovirus infection: A meta-analysis. Eur J Intern Med 2011; 22: 195–199. 5 Fishman D, Isenberg DA. Splenic involvement in rheumatic diseases. Semin Arthritis Rheum 1997; 27: 141–155. 6 Ramos-Casals M, Cuadrado MJ, Alba P, et al. Acute viral infections in patients with systemic lupus erythematosus: Description of 23 cases and review of the literature. Medicine (Baltimore) 2008; 87: 311–318.
J Broom Infection Management Service, Department of Medicine, Nambour General Hospital, Queensland, Australia, and The University of Queensland
Lupus Downloaded from lup.sagepub.com at SUNY HEALTH SCIENCE CENTER on April 15, 2015
