JNI-475908; No of Pages 3 Journal of Neuroimmunology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Neuroimmunology journal homepage: www.elsevier.com/locate/jneuroim
Short communication
Splenic rupture associated with primary CMV infection, AMSAN, and IVIG☆ Adam de Havenon a,⁎, Gary Davis b,1, Robert Hoesch c,1 a b c
University of Washington, Department of Neurology, 2407 Federal Ave E, Seattle, WA 98102, USA University of Utah, Department of Pharmacy, 75 North Medical Drive, Salt Lake City, UT 84132, USA University of Utah, Department of Neurology, USA
a r t i c l e
i n f o
Article history: Received 7 November 2013 Accepted 4 May 2014 Available online xxxx Keywords: Guillain–Barré syndrome Intravenous immunoglobulin Cytomegalovirus Splenic rupture Hemolysis AMSAN
a b s t r a c t Splenic rupture is a rare complication of primary cytomegalovirus infection, but has not been reported after administration of intravenous immunoglobulin or in the setting of the Guillain–Barré syndrome and its many variants, which often lead to treatment with intravenous immunoglobulin. There is strong evidence that intravenous immunoglobulin causes sequestration of erythrocytes in the spleen and extravascular hemolytic anemia. This may result in a two-hit scenario that clinicians should be aware of, where a patient who is at risk for splenic rupture due to primary cytomegalovirus infection receives intravenous immunoglobulin as treatment for the cytomegalovirus-associated Guillain–Barré syndrome, further increasing their risk of rupture. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Primary cytomegalovirus (CMV) infection is the most common viral prodrome of the acute inflammatory neuropathy Guillain–Barré syndrome (GBS) (Jacobs et al., 1998). While primary CMV infection has been linked to splenic rupture (Alliot et al., 2001), it has not been reported in a patient after receiving intravenous immunoglobulin (IVIG) or in the setting of GBS and its many variants, which often lead to treatment with IVIG. However, there is strong evidence that IVIG causes sequestration of erythrocytes in the extravascular reticuloendothelial system, specifically the spleen, and can lead to extravascular hemolytic anemia (Nakamura et al., 1986; Pierce and Jain, 2003). This combination may result in a two-hit scenario, where a patient who is at risk for splenic rupture due to primary CMV infection receives IVIG as treatment for CMV-associated GBS, further increasing their risk of splenic rupture.
2. Case description We report an otherwise healthy 28 year-old male who presented with bilateral lower extremity paresthesias that began distally and, ☆ All authors contributed to the authorship and editing of the manuscript. We report no financial support or conflicts of interest. ⁎ Corresponding author. Tel.: +1 801 554 9439; fax: +1 206 744 7321. E-mail addresses: [email protected] (A. de Havenon), [email protected] (G. Davis), [email protected] (R. Hoesch). 1 Tel.: +1 801 581 7200; fax: +1 801 585 7575.
over the course of 5 days, spread to the level of his thighs accompanied by a mild ascending weakness. The patient had an upper respiratory tract infection 3–4 days prior to the onset of symptoms. He was admitted to an outside hospital where his exam was notable for symmetric 4/5 weakness in the lower extremities, areflexia at the knee and ankle, and sensory loss to the level of the knees. GBS was suspected and analysis of his cerebrospinal fluid revealed 3 white blood cells with an elevated protein of 62. Two nerve conduction studies, one at admission and one 5 days later, were consistent with the acute motor sensory axonal neuropathy (AMSAN) variant of GBS. He received a 66 gm dose of Carimune® IVIG. That afternoon he developed severe bradycardia and presyncope, at which point he was transferred to our institution. On admission to our neurocritical care unit, his WBC count was 4.17 K/μL with 37% lymphocytes, 32% of which were atypical. A peripheral smear showed reactive lymphocyte changes. He had a mild elevation in creatinine (1.3 mg/dL) and liver enzymes (AST 92 units/L and ALT 102 units/L). He received a second dose of IVIG, 65 gm of Privigen®, to equal a total dose of 2 gm/kg. Overnight he developed abdominal pain and the following morning his hemoglobin had fallen from normal range to 4.4 g/dL. A CT of the abdomen and pelvis revealed splenomegaly and splenic capsular rupture. An emergent splenectomy was performed. His blood type was A positive and he was transfused 10 units of packed red blood cells, after which his hemoglobin normalized. A hepatitis panel, Epstein–Barr virus (EBV) serum antibodies, and EBV PCR were normal. CMV IgG and IgM antibodies were highly elevated in the serum as was a quantitative CMV PCR, which initially measured 7490 copies/mL and, a week later, 14,400 copies/mL. Campylobacter
http://dx.doi.org/10.1016/j.jneuroim.2014.05.004 0165-5728/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
2
A. de Havenon et al. / Journal of Neuroimmunology xxx (2014) xxx–xxx
jejuni IgG antibody was negative. The bilirubin level 48 h after the splenic rupture was elevated at 1.7 mg/dL and haptoglobin was undetectable. His LDH the day of splenic rupture was elevated at 614 units/L in the morning and 1179 units/L by the evening. A repeat peripheral smear on the day of splenic rupture did not show microscopic evidence of hemolysis. The patient recovered well after the splenectomy and his only residual symptom from the AMSAN is a mild increase in fatigability. 3. Discussion Primary CMV infection in the immunocompetent adult is usually asymptomatic and more than 80% of adults have serologic evidence of prior infection. A small percentage of healthy patients will develop a mild Epstein–Barr virus-like mononucleosis and should not have reactivation unless their immune system is compromised. Symptoms include malaise, fever, lymphadenopathy, upper respiratory tract irritation, myalgia, and a nonspecific erythematous skin rash. Laboratory abnormalities are common, including lymphocytosis, atypical lymphocyte morphology, mild elevation in liver enzymes, and thrombocytopenia (Kano and Shiohara, 2000). Serologic diagnosis of acute CMV infection can be made either through ELISA antibody testing or DNA PCR sequencing. In most patients IgG is negative at time of diagnosis while IgM will be positive, although they may both be positive. More importantly, if a serum PCR viral load is greater than 400 copies/mL, it is highly suggestive of acute infection. The PCR will return to normal in several months and should remain negative thereafter (Görzer et al., 2010). AMSAN in our patient may have resulted from primary CMV infection, which is the most common viral prodrome of GBS, occurring in up 13% of cases, with an incidence of CMV-GBS between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (Jacobs et al., 1998; Orlikowski et al., 2011). There are only 7 case reports of splenic rupture in patients with primary CMV infection (Alliot et al., 2001; Amathieu et al., 2007; Maillard et al., 2007). In these reports, 5/7 were male and the average age was 27 years; 6 were healthy, 1 had malaria (a more common cause for splenic rupture) and the other CREST. There is no pathophysiologic basis for why certain patients would suffer splenic rupture during primary CMV infection. Splenic rupture has not been reported after IVIG administration, but the sequestration of erythrocytes in the spleen after IVIG is extensively documented, both in vivo and in vitro. The mechanism of erythrocyte sequestration is thought to be passive acquisition of A/B isohemagglutinins from the IVIG product, which coat erythrocytes with antibody, binding them to splenic macrophages via the Fc receptor. In severe cases, this can lead to hemolytic anemia (Padmore, 2012). The primary risk factor for IVIG-mediated erythrocyte sequestration is blood type A+. Among 30 patients with hemolytic anemia after IVIG, 22 were type A+ and 4 A (Kahwaji et al., 2009; Wilson et al., 1997). Hemolysis is observed as soon as 12 h after the first dose (Shakouri and Bahna, 2012). Of 33 reported cases of hemolysis, Gamunex® was causative in 26, Gammagard® in 5, and Privigen® in 2. Other risk factors include female sex, neurologic indication for IVIG, cumulative dose of at least 2 g/kg, and underlying inflammatory state. Anti-A titers N1:16 are more likely to cause clinically significant hemolysis. While anti-A titers vary depending on the batch of IVIG, among the 5 most common IVIG preparations only Privigen and Gammagard exceeded a titer of 1:64 in published literature (Kahwaji et al., 2009; Shakouri and Bahna, 2012; Daw et al., 2008). Common laboratory findings of IVIG-mediated erythrocyte sequestration include elevated LDH, total bilirubin, and a decrease in haptoglobin. In the only case series where peripheral smears were recorded, 2/5 had evidence of hemolysis (Kahwaji et al., 2009). 4. Conclusion Splenic rupture in our patient was a double-hit side effect, which is demonstrative of the pathophysiology of primary CMV infection and the pharmacological and serological effects of IVIG. Splenic rupture is a
rare complication of primary CMV infection, having been reported in only 7 patients, but it has not been reported after receiving IVIG or in the setting of an acute inflammatory neuropathy like GBS or AMSAN. The etiology of our patient's splenic rupture was likely due mainly to primary CMV infection. He had many of the secondary serologic markers of CMV infection previously mentioned and highly elevated viral titers. However, based on the robust evidence for splenic erythrocyte sequestration and congestion after IVIG administration, it may have played a secondary role in the mechanism of his splenic rupture. When the sequestration is severe it results in serologic evidence of hemolytic anemia, which was evident in our patient, including an elevation of LDH and bilirubin with a low haptoglobin, as well as a slight drop in his hemoglobin prior to the rupture. His peripheral smear did not show morphology consistent with hemolysis, but abnormal findings on peripheral smear were present in less than half of patients in one case series of IVIG-associated hemolysis (Kahwaji et al., 2009) and the extravascular hemolysis of the spleen does not always result in abnormal erythrocyte morphology (Lipka et al., 2012). Furthermore, at our institution, the patient received Privigen®, one of the IVIG formulations documented to cause hemolytic reactions and have elevated anti-A titers. When a patient presents with an acute inflammatory neuropathy, such as GBS or AMSAN, and will receive IVIG treatment, the physician should screen for clinical symptoms or serologic abnormalities that would suggest the prodrome of a primary CMV infection. If present, it is reasonable to administer a formulation of IVIG that has not been shown to cause clinically significant hemolysis, such as Carimune®, Flebogamma®, or Octagam®, and the IVIG can be cross-matched to the patient. The pharmacist can also call the manufacturer to ensure that the anti-A titer is b1:16 in the batch that is being used. These patients will need closer monitoring of their blood counts, markers of hemolysis, and abdominal exam. CMV serology should be sent when there is suspicion of infection. This more aggressive monitoring may lead to ultrasound or CT imaging of the abdomen and advance warning of possible splenic rupture. Finally, if an IVIG-associated hemolytic reaction or splenic rupture does occur, to avoid exacerbating the hemolytic process only type O blood should be transfused until consulting with a hematologist (Padmore, 2012).
References Alliot, C., Beets, C., et al., 2001. Spontaneous splenic rupture associated with CMV infection: report of a case and review. Scand. J. Infect. Dis. 33 (11), 875. Amathieu, R., Tual, L., et al., 2007. Splenic rupture associated with CMV infection: case report and review. Ann. Fr. Anesth. Reanim. 26 (7–8), 674–676. http://dx.doi.org/10. 1016/j.annfar.2007.03.037. Daw, Z., Padmore, R., et al., 2008. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion (Paris) 48 (8), 1598–1601. http://dx.doi.org/10.1111/j.1537-2995.2008. 01721.x. Görzer, I., Kerschner, H., et al., 2010. Human cytomegalovirus (HCMV) genotype populations in immunocompetent individuals during primary HCMV infection. J. Clin. Virol. 48 (2), 100–103. http://dx.doi.org/10.1016/j.jcv.2010. 03.005. Jacobs, B.C., Rothbarth, P.H., et al., 1998. The spectrum of antecedent infections in Guillain–Barré syndrome: a case–control study. Neurology 51 (4), 1110–1115. Kahwaji, J., Barker, E., et al., 2009. Acute hemolysis after high-dose intravenous immunoglobulin therapy in highly HLA sensitized patients. Clin. J. Am. Soc. Nephrol. 4 (12), 1993–1997. http://dx.doi.org/10.2215/CJN.04540709. Kano, Y., Shiohara, T., 2000. Current understanding of cytomegalovirus infection in immunocompetent individuals. J. Dermatol. Sci. 22 (3), 196–204. http://dx.doi.org/10. 1016/S0923-1811(99)00085-7. Lipka, S., Singh, J., et al., 2012. Extravascular hemolysis mimicking severe obstructive jaundice. Transfus. Clin. Biol. 19 (6), 366–367. http://dx.doi.org/10.1016/j.tracli. 2012.06.005. Maillard, N., Koenig, M., et al., 2007. Spontaneous splenic rupture in primary cytomegalovirus infection. Presse Méd. Paris Fr. 1983 36 (6 Pt 1), 874–877. http://dx.doi.org/10. 1016/j.lpm.2007.02.014. Nakamura, S., Yoshida, T., et al., 1986. Hemolysis due to high-dose intravenous gammaglobulin treatment for patients with idiopathic thrombocytopenic purpura. Acta Haematol. 76 (2–3), 115–118.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
A. de Havenon et al. / Journal of Neuroimmunology xxx (2014) xxx–xxx Orlikowski, D., Porcher, R., et al., 2011. Guillain–Barré syndrome following primary cytomegalovirus infection: a prospective cohort study. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 52 (7), 837–844. http://dx.doi.org/10.1093/cid/cir074. Padmore, R.F., 2012. Hemolysis upon intravenous immunoglobulin transfusion. Transfus. Apher. Sci. 46 (1), 93–96. http://dx.doi.org/10.1016/j.transci.2011.11.004. Pierce, L.R., Jain, N., 2003. Risks associated with the use of intravenous immunoglobulin. Transfus. Med. Rev. 17 (4), 241–251. http://dx.doi.org/10.1016/S0887-7963(03) 00038-5.
3
Shakouri, A.A., Bahna, S.L., 2012. Acute hemolysis secondary to high-dose intravenous immunoglobulin in a patient with Stevens–Johnson syndrome. Ann. Allergy Asthma Immunol. 108 (6), 463–464. http://dx.doi.org/10.1016/j.anai.2012.04. 013. Wilson, J.R., Bhoopalam, H., et al., 1997. Hemolytic anemia associated with intravenous immunoglobulin. Muscle Nerve 20 (9), 1142–1145.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
Contents lists available at ScienceDirect
Journal of Neuroimmunology journal homepage: www.elsevier.com/locate/jneuroim
Short communication
Splenic rupture associated with primary CMV infection, AMSAN, and IVIG☆ Adam de Havenon a,⁎, Gary Davis b,1, Robert Hoesch c,1 a b c
University of Washington, Department of Neurology, 2407 Federal Ave E, Seattle, WA 98102, USA University of Utah, Department of Pharmacy, 75 North Medical Drive, Salt Lake City, UT 84132, USA University of Utah, Department of Neurology, USA
a r t i c l e
i n f o
Article history: Received 7 November 2013 Accepted 4 May 2014 Available online xxxx Keywords: Guillain–Barré syndrome Intravenous immunoglobulin Cytomegalovirus Splenic rupture Hemolysis AMSAN
a b s t r a c t Splenic rupture is a rare complication of primary cytomegalovirus infection, but has not been reported after administration of intravenous immunoglobulin or in the setting of the Guillain–Barré syndrome and its many variants, which often lead to treatment with intravenous immunoglobulin. There is strong evidence that intravenous immunoglobulin causes sequestration of erythrocytes in the spleen and extravascular hemolytic anemia. This may result in a two-hit scenario that clinicians should be aware of, where a patient who is at risk for splenic rupture due to primary cytomegalovirus infection receives intravenous immunoglobulin as treatment for the cytomegalovirus-associated Guillain–Barré syndrome, further increasing their risk of rupture. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Primary cytomegalovirus (CMV) infection is the most common viral prodrome of the acute inflammatory neuropathy Guillain–Barré syndrome (GBS) (Jacobs et al., 1998). While primary CMV infection has been linked to splenic rupture (Alliot et al., 2001), it has not been reported in a patient after receiving intravenous immunoglobulin (IVIG) or in the setting of GBS and its many variants, which often lead to treatment with IVIG. However, there is strong evidence that IVIG causes sequestration of erythrocytes in the extravascular reticuloendothelial system, specifically the spleen, and can lead to extravascular hemolytic anemia (Nakamura et al., 1986; Pierce and Jain, 2003). This combination may result in a two-hit scenario, where a patient who is at risk for splenic rupture due to primary CMV infection receives IVIG as treatment for CMV-associated GBS, further increasing their risk of splenic rupture.
2. Case description We report an otherwise healthy 28 year-old male who presented with bilateral lower extremity paresthesias that began distally and, ☆ All authors contributed to the authorship and editing of the manuscript. We report no financial support or conflicts of interest. ⁎ Corresponding author. Tel.: +1 801 554 9439; fax: +1 206 744 7321. E-mail addresses: [email protected] (A. de Havenon), [email protected] (G. Davis), [email protected] (R. Hoesch). 1 Tel.: +1 801 581 7200; fax: +1 801 585 7575.
over the course of 5 days, spread to the level of his thighs accompanied by a mild ascending weakness. The patient had an upper respiratory tract infection 3–4 days prior to the onset of symptoms. He was admitted to an outside hospital where his exam was notable for symmetric 4/5 weakness in the lower extremities, areflexia at the knee and ankle, and sensory loss to the level of the knees. GBS was suspected and analysis of his cerebrospinal fluid revealed 3 white blood cells with an elevated protein of 62. Two nerve conduction studies, one at admission and one 5 days later, were consistent with the acute motor sensory axonal neuropathy (AMSAN) variant of GBS. He received a 66 gm dose of Carimune® IVIG. That afternoon he developed severe bradycardia and presyncope, at which point he was transferred to our institution. On admission to our neurocritical care unit, his WBC count was 4.17 K/μL with 37% lymphocytes, 32% of which were atypical. A peripheral smear showed reactive lymphocyte changes. He had a mild elevation in creatinine (1.3 mg/dL) and liver enzymes (AST 92 units/L and ALT 102 units/L). He received a second dose of IVIG, 65 gm of Privigen®, to equal a total dose of 2 gm/kg. Overnight he developed abdominal pain and the following morning his hemoglobin had fallen from normal range to 4.4 g/dL. A CT of the abdomen and pelvis revealed splenomegaly and splenic capsular rupture. An emergent splenectomy was performed. His blood type was A positive and he was transfused 10 units of packed red blood cells, after which his hemoglobin normalized. A hepatitis panel, Epstein–Barr virus (EBV) serum antibodies, and EBV PCR were normal. CMV IgG and IgM antibodies were highly elevated in the serum as was a quantitative CMV PCR, which initially measured 7490 copies/mL and, a week later, 14,400 copies/mL. Campylobacter
http://dx.doi.org/10.1016/j.jneuroim.2014.05.004 0165-5728/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
2
A. de Havenon et al. / Journal of Neuroimmunology xxx (2014) xxx–xxx
jejuni IgG antibody was negative. The bilirubin level 48 h after the splenic rupture was elevated at 1.7 mg/dL and haptoglobin was undetectable. His LDH the day of splenic rupture was elevated at 614 units/L in the morning and 1179 units/L by the evening. A repeat peripheral smear on the day of splenic rupture did not show microscopic evidence of hemolysis. The patient recovered well after the splenectomy and his only residual symptom from the AMSAN is a mild increase in fatigability. 3. Discussion Primary CMV infection in the immunocompetent adult is usually asymptomatic and more than 80% of adults have serologic evidence of prior infection. A small percentage of healthy patients will develop a mild Epstein–Barr virus-like mononucleosis and should not have reactivation unless their immune system is compromised. Symptoms include malaise, fever, lymphadenopathy, upper respiratory tract irritation, myalgia, and a nonspecific erythematous skin rash. Laboratory abnormalities are common, including lymphocytosis, atypical lymphocyte morphology, mild elevation in liver enzymes, and thrombocytopenia (Kano and Shiohara, 2000). Serologic diagnosis of acute CMV infection can be made either through ELISA antibody testing or DNA PCR sequencing. In most patients IgG is negative at time of diagnosis while IgM will be positive, although they may both be positive. More importantly, if a serum PCR viral load is greater than 400 copies/mL, it is highly suggestive of acute infection. The PCR will return to normal in several months and should remain negative thereafter (Görzer et al., 2010). AMSAN in our patient may have resulted from primary CMV infection, which is the most common viral prodrome of GBS, occurring in up 13% of cases, with an incidence of CMV-GBS between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (Jacobs et al., 1998; Orlikowski et al., 2011). There are only 7 case reports of splenic rupture in patients with primary CMV infection (Alliot et al., 2001; Amathieu et al., 2007; Maillard et al., 2007). In these reports, 5/7 were male and the average age was 27 years; 6 were healthy, 1 had malaria (a more common cause for splenic rupture) and the other CREST. There is no pathophysiologic basis for why certain patients would suffer splenic rupture during primary CMV infection. Splenic rupture has not been reported after IVIG administration, but the sequestration of erythrocytes in the spleen after IVIG is extensively documented, both in vivo and in vitro. The mechanism of erythrocyte sequestration is thought to be passive acquisition of A/B isohemagglutinins from the IVIG product, which coat erythrocytes with antibody, binding them to splenic macrophages via the Fc receptor. In severe cases, this can lead to hemolytic anemia (Padmore, 2012). The primary risk factor for IVIG-mediated erythrocyte sequestration is blood type A+. Among 30 patients with hemolytic anemia after IVIG, 22 were type A+ and 4 A (Kahwaji et al., 2009; Wilson et al., 1997). Hemolysis is observed as soon as 12 h after the first dose (Shakouri and Bahna, 2012). Of 33 reported cases of hemolysis, Gamunex® was causative in 26, Gammagard® in 5, and Privigen® in 2. Other risk factors include female sex, neurologic indication for IVIG, cumulative dose of at least 2 g/kg, and underlying inflammatory state. Anti-A titers N1:16 are more likely to cause clinically significant hemolysis. While anti-A titers vary depending on the batch of IVIG, among the 5 most common IVIG preparations only Privigen and Gammagard exceeded a titer of 1:64 in published literature (Kahwaji et al., 2009; Shakouri and Bahna, 2012; Daw et al., 2008). Common laboratory findings of IVIG-mediated erythrocyte sequestration include elevated LDH, total bilirubin, and a decrease in haptoglobin. In the only case series where peripheral smears were recorded, 2/5 had evidence of hemolysis (Kahwaji et al., 2009). 4. Conclusion Splenic rupture in our patient was a double-hit side effect, which is demonstrative of the pathophysiology of primary CMV infection and the pharmacological and serological effects of IVIG. Splenic rupture is a
rare complication of primary CMV infection, having been reported in only 7 patients, but it has not been reported after receiving IVIG or in the setting of an acute inflammatory neuropathy like GBS or AMSAN. The etiology of our patient's splenic rupture was likely due mainly to primary CMV infection. He had many of the secondary serologic markers of CMV infection previously mentioned and highly elevated viral titers. However, based on the robust evidence for splenic erythrocyte sequestration and congestion after IVIG administration, it may have played a secondary role in the mechanism of his splenic rupture. When the sequestration is severe it results in serologic evidence of hemolytic anemia, which was evident in our patient, including an elevation of LDH and bilirubin with a low haptoglobin, as well as a slight drop in his hemoglobin prior to the rupture. His peripheral smear did not show morphology consistent with hemolysis, but abnormal findings on peripheral smear were present in less than half of patients in one case series of IVIG-associated hemolysis (Kahwaji et al., 2009) and the extravascular hemolysis of the spleen does not always result in abnormal erythrocyte morphology (Lipka et al., 2012). Furthermore, at our institution, the patient received Privigen®, one of the IVIG formulations documented to cause hemolytic reactions and have elevated anti-A titers. When a patient presents with an acute inflammatory neuropathy, such as GBS or AMSAN, and will receive IVIG treatment, the physician should screen for clinical symptoms or serologic abnormalities that would suggest the prodrome of a primary CMV infection. If present, it is reasonable to administer a formulation of IVIG that has not been shown to cause clinically significant hemolysis, such as Carimune®, Flebogamma®, or Octagam®, and the IVIG can be cross-matched to the patient. The pharmacist can also call the manufacturer to ensure that the anti-A titer is b1:16 in the batch that is being used. These patients will need closer monitoring of their blood counts, markers of hemolysis, and abdominal exam. CMV serology should be sent when there is suspicion of infection. This more aggressive monitoring may lead to ultrasound or CT imaging of the abdomen and advance warning of possible splenic rupture. Finally, if an IVIG-associated hemolytic reaction or splenic rupture does occur, to avoid exacerbating the hemolytic process only type O blood should be transfused until consulting with a hematologist (Padmore, 2012).
References Alliot, C., Beets, C., et al., 2001. Spontaneous splenic rupture associated with CMV infection: report of a case and review. Scand. J. Infect. Dis. 33 (11), 875. Amathieu, R., Tual, L., et al., 2007. Splenic rupture associated with CMV infection: case report and review. Ann. Fr. Anesth. Reanim. 26 (7–8), 674–676. http://dx.doi.org/10. 1016/j.annfar.2007.03.037. Daw, Z., Padmore, R., et al., 2008. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion (Paris) 48 (8), 1598–1601. http://dx.doi.org/10.1111/j.1537-2995.2008. 01721.x. Görzer, I., Kerschner, H., et al., 2010. Human cytomegalovirus (HCMV) genotype populations in immunocompetent individuals during primary HCMV infection. J. Clin. Virol. 48 (2), 100–103. http://dx.doi.org/10.1016/j.jcv.2010. 03.005. Jacobs, B.C., Rothbarth, P.H., et al., 1998. The spectrum of antecedent infections in Guillain–Barré syndrome: a case–control study. Neurology 51 (4), 1110–1115. Kahwaji, J., Barker, E., et al., 2009. Acute hemolysis after high-dose intravenous immunoglobulin therapy in highly HLA sensitized patients. Clin. J. Am. Soc. Nephrol. 4 (12), 1993–1997. http://dx.doi.org/10.2215/CJN.04540709. Kano, Y., Shiohara, T., 2000. Current understanding of cytomegalovirus infection in immunocompetent individuals. J. Dermatol. Sci. 22 (3), 196–204. http://dx.doi.org/10. 1016/S0923-1811(99)00085-7. Lipka, S., Singh, J., et al., 2012. Extravascular hemolysis mimicking severe obstructive jaundice. Transfus. Clin. Biol. 19 (6), 366–367. http://dx.doi.org/10.1016/j.tracli. 2012.06.005. Maillard, N., Koenig, M., et al., 2007. Spontaneous splenic rupture in primary cytomegalovirus infection. Presse Méd. Paris Fr. 1983 36 (6 Pt 1), 874–877. http://dx.doi.org/10. 1016/j.lpm.2007.02.014. Nakamura, S., Yoshida, T., et al., 1986. Hemolysis due to high-dose intravenous gammaglobulin treatment for patients with idiopathic thrombocytopenic purpura. Acta Haematol. 76 (2–3), 115–118.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
A. de Havenon et al. / Journal of Neuroimmunology xxx (2014) xxx–xxx Orlikowski, D., Porcher, R., et al., 2011. Guillain–Barré syndrome following primary cytomegalovirus infection: a prospective cohort study. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 52 (7), 837–844. http://dx.doi.org/10.1093/cid/cir074. Padmore, R.F., 2012. Hemolysis upon intravenous immunoglobulin transfusion. Transfus. Apher. Sci. 46 (1), 93–96. http://dx.doi.org/10.1016/j.transci.2011.11.004. Pierce, L.R., Jain, N., 2003. Risks associated with the use of intravenous immunoglobulin. Transfus. Med. Rev. 17 (4), 241–251. http://dx.doi.org/10.1016/S0887-7963(03) 00038-5.
3
Shakouri, A.A., Bahna, S.L., 2012. Acute hemolysis secondary to high-dose intravenous immunoglobulin in a patient with Stevens–Johnson syndrome. Ann. Allergy Asthma Immunol. 108 (6), 463–464. http://dx.doi.org/10.1016/j.anai.2012.04. 013. Wilson, J.R., Bhoopalam, H., et al., 1997. Hemolytic anemia associated with intravenous immunoglobulin. Muscle Nerve 20 (9), 1142–1145.
Please cite this article as: de Havenon, A., et al., Splenic rupture associated with primary CMV infection, AMSAN, and IVIG, J. Neuroimmunol. (2014), http://dx.doi.org/10.1016/j.jneuroim.2014.05.004
