- Email: [email protected]
Systemic lupus erythematosus following meningococcal vaccination
YAJEM-57023; No of Pages 2 American Journal of Emergency Medicine xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Systemic lupus erythematosus following meningococcal vaccination☆ Alexandria D. Holmes, BS a, Osman Z. Abbasi, DO b, Jeanne L. Jacoby, MD a,b,⁎ a b
University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, United States Department of Emergency Medicine, Lehigh Valley Health Network, 1240 South Cedar Crest Boulevard, Allentown, PA 18103, United States
a r t i c l e
i n f o
Article history: Received 11 September 2017 Accepted 7 October 2017 Available online xxxx Keywords: Systemic lupus erythematosus Meningococcal vaccine Vaccination Autoimmune diseases
1. Case report A previously healthy, 17-year-old Asian female presented to our emergency department 15 days after receiving the Menveo® (Meningococcal groups A, C, Y and W-135, oligosaccharide diphtheria CRM197 conjugate) vaccine. The evening after she received the vaccination, she began to feel ill and subsequently experienced 14 days of fever and fatigue; 5 days prior to the ED visit she developed a progressive, erythematous, non-pruritic, non-painful facial rash. She received 2 days of cefadroxil prior to presentation; there was no improvement in her symptoms. Review of systems was positive only for mild right-sided neck pain. The patient was of Chinese descent and had immigrated to the United States as a young child. Her immunizations were up to date; she had no history of vaccine reactions, allergic reactions, recent travel, known sick contacts, animal exposure, or significant outdoor activity. She did not take any medications regularly. Initial vital signs included a blood pressure of 110/61 mmHg, heart rate of 102 bpm, respiratory rate of 20, an oxygen saturation of 97% and a temporal temperature of 102.4 °F (39.1 °C). She was an illappearing female with a non-blanching, erythematous maculopapular facial rash, including the right periorbital region and bilateral upper cheeks, with extension to the right ear. The rash was associated with mild right periorbital swelling, as well as perioral dermatitis and dry, chapped lips. She had a painless ulceration of the hard palate. Her first, second, and third fingertips revealed non-painful, purpuric lesions ☆ The authors have no outside support information, conflicts or financial interest to disclose and this work has not been presented elsewhere. ⁎ Corresponding author at: Emergency Medicine Research, 2545 Schoenersville Road, 5th Floor, South Wing, Bethlehem, PA 18017, United States. E-mail address: [email protected] (J.L. Jacoby).
bilaterally. Neck exam was significant for palpable right posterior cervical chain lymphadenopathy without meningismus. The remainder of her exam was unremarkable. CBC revealed pancytopenia. The WBC was 2.8 (neutrophils 48% with 13% bands; there were 35% lymphocytes and 4% monocytes); the hgb was 10.2 and the platelets were 48,000. The d-dimer and erythrocyte sedimentation rate (ESR) were elevated at 1.38 and 40, respectively. Urinalysis showed protein, blood, and leukocytes. All other initial labs were unremarkable. EKG and CXR were normal. CT of the head and neck revealed diffuse bilateral lymphadenopathy. The patient was admitted to the Medical ICU. Despite empiric antibiotic therapy, her CBC on Day 2 demonstrated worsening pancytopenia, with WBC 1.7. Prednisone was started and her pancytopenia began to resolve. All cultures were negative and antibiotics were discontinued on Day 5. On Day 7 she was started on the immunosuppressant mycophenolate (CellCept®); her fever and rash improved. Serological testing was positive for SLE (ANA titer of 1:320 and anti-double-stranded DNA titer of 1:640). She was discharged on Day 9 with prednisone and mycophenolate and plaquenil. She was doing well at one-month follow up. 2. Discussion Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with a myriad of non-specific presenting symptoms that can affect nearly any organ system. According to most recent data, the incidence of SLE in the US is 5.1 per 100,000 people per year [1]. The pathogenesis of SLE is not clearly understood, but research shows it involves complex immune dysfunction, specifically, the production of autoantibodies against the body's connective tissues. Many factors have been proven to increase the risk for developing SLE, including genetic predisposition, family history, female gender, and racial background; compared with the white non-Hispanic population, SLE develops 3–4 times more frequently and is often more severe in African Americans, Asian Americans, and Hispanic patients [2] [3] [4]. Recently, there has been increasing speculation that immunizations could play a role in unmasking SLE and other autoimmune diseases [5]. It has been reported that certain vaccines have the ability to trigger a relapse or flare of preexisting autoimmune disease [6]. The issue of whether vaccination has a role in the initial presentation of an autoimmune disease such as SLE is controversial [5] [7]. Although there have been several case reports demonstrating a temporal relationship between recent vaccination and the development of SLE [7] [8] [9], this association cannot establish causality. To our knowledge, there has never been a case published on acute presentation of SLE in association with
https://doi.org/10.1016/j.ajem.2017.10.020 0735-6757/© 2017 Published by Elsevier Inc.
Please cite this article as: Holmes AD, et al, Systemic lupus erythematosus following meningococcal vaccination, American Journal of Emergency Medicine (2017), https://doi.org/10.1016/j.ajem.2017.10.020
2
A.D. Holmes et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx
the meningococcal vaccination. In our case, the extreme proximity of the vaccination to the clinical symptoms, and the pathognomonic serologic findings argues in favor of a cause and effect relationship between the vaccine and classical SLE. Recent research has suggested that vaccinations significantly increase the risk of SLE [8] [10]; however it is unclear whether the vaccination merely unmasks a latent immunologic condition or is truly the cause of the disease. In addition, the association between vaccination and autoimmune disease may be a manifestation of a yet unrecognized third factor. More research is necessary to delineate the causal relationship, if any, between vaccinations and SLE. Our case highlights the importance of inquiring about recent vaccinations in any patient presenting with the unexplained onset of symptoms typical of autoimmune disease. References [1] Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006 May 2;15(5):308–18. [2] Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003 Jul;56(7):481–90.
[3] Kuo C-F, Grainge MJ, Valdes AM, See L-C, Luo S-F, K-H Yu, et al. Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Intern Med 2015 Sep 1;175(9):1518. [4] Lupus Manzi S. Update: perspective and clinical pearls. Cleve Clin J Med 2009 Feb 1; 76(2):137–42. [5] Chen RT, Pless R, Destefano F. Epidemiology of autoimmune reactions induced by vaccination. J Autoimmun 2001 May;16(3):309–18. [6] Bijl M, Agmon-Levin N, Dayer J-M, Israeli E, Gatto M, Shoenfeld Y. Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefitrisk assessment. Autoimmun Rev 2012 Jun;11(8):572–6. [7] Agmon-Levin N, Zafrir Y, Paz Z, Shilton T, Zandman-Goddard G, Shoenfeld Y. Ten cases of systemic lupus erythematosus related to hepatitis B vaccine. In: Shoenfeld Y, editor. Lupus. London, England: SAGE Publications Sage UK; 2009 Nov 30. p. 1192–7. [8] Older SA, Battafarano DF, Enzenauer RJ, Krieg AM. Can immunization precipitate connective tissue disease? Report of five cases of systemic lupus erythematosus and review of the literature. Semin Arthritis Rheum 1999 Dec;29(3):131–9. [9] Kikuchi S, Sato M, Otaka Y, Takahashi Y, Watanabe T, Goda F. Case report; a case of systemic lupus erythematosus complicated with limbic encephalitis after vaccination for influenza virus. Nippon Naika Gakkai Zasshi 2012 Oct 10;101(10):2952–4. [10] Wang B, Shao X, Wang D, Xu D, Zhang J-A. Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: a systematic review and meta-analysis. Autoimmun Rev 2017 Jul;16(7):756–65.
Please cite this article as: Holmes AD, et al, Systemic lupus erythematosus following meningococcal vaccination, American Journal of Emergency Medicine (2017), https://doi.org/10.1016/j.ajem.2017.10.020
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Systemic lupus erythematosus following meningococcal vaccination☆ Alexandria D. Holmes, BS a, Osman Z. Abbasi, DO b, Jeanne L. Jacoby, MD a,b,⁎ a b
University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, United States Department of Emergency Medicine, Lehigh Valley Health Network, 1240 South Cedar Crest Boulevard, Allentown, PA 18103, United States
a r t i c l e
i n f o
Article history: Received 11 September 2017 Accepted 7 October 2017 Available online xxxx Keywords: Systemic lupus erythematosus Meningococcal vaccine Vaccination Autoimmune diseases
1. Case report A previously healthy, 17-year-old Asian female presented to our emergency department 15 days after receiving the Menveo® (Meningococcal groups A, C, Y and W-135, oligosaccharide diphtheria CRM197 conjugate) vaccine. The evening after she received the vaccination, she began to feel ill and subsequently experienced 14 days of fever and fatigue; 5 days prior to the ED visit she developed a progressive, erythematous, non-pruritic, non-painful facial rash. She received 2 days of cefadroxil prior to presentation; there was no improvement in her symptoms. Review of systems was positive only for mild right-sided neck pain. The patient was of Chinese descent and had immigrated to the United States as a young child. Her immunizations were up to date; she had no history of vaccine reactions, allergic reactions, recent travel, known sick contacts, animal exposure, or significant outdoor activity. She did not take any medications regularly. Initial vital signs included a blood pressure of 110/61 mmHg, heart rate of 102 bpm, respiratory rate of 20, an oxygen saturation of 97% and a temporal temperature of 102.4 °F (39.1 °C). She was an illappearing female with a non-blanching, erythematous maculopapular facial rash, including the right periorbital region and bilateral upper cheeks, with extension to the right ear. The rash was associated with mild right periorbital swelling, as well as perioral dermatitis and dry, chapped lips. She had a painless ulceration of the hard palate. Her first, second, and third fingertips revealed non-painful, purpuric lesions ☆ The authors have no outside support information, conflicts or financial interest to disclose and this work has not been presented elsewhere. ⁎ Corresponding author at: Emergency Medicine Research, 2545 Schoenersville Road, 5th Floor, South Wing, Bethlehem, PA 18017, United States. E-mail address: [email protected] (J.L. Jacoby).
bilaterally. Neck exam was significant for palpable right posterior cervical chain lymphadenopathy without meningismus. The remainder of her exam was unremarkable. CBC revealed pancytopenia. The WBC was 2.8 (neutrophils 48% with 13% bands; there were 35% lymphocytes and 4% monocytes); the hgb was 10.2 and the platelets were 48,000. The d-dimer and erythrocyte sedimentation rate (ESR) were elevated at 1.38 and 40, respectively. Urinalysis showed protein, blood, and leukocytes. All other initial labs were unremarkable. EKG and CXR were normal. CT of the head and neck revealed diffuse bilateral lymphadenopathy. The patient was admitted to the Medical ICU. Despite empiric antibiotic therapy, her CBC on Day 2 demonstrated worsening pancytopenia, with WBC 1.7. Prednisone was started and her pancytopenia began to resolve. All cultures were negative and antibiotics were discontinued on Day 5. On Day 7 she was started on the immunosuppressant mycophenolate (CellCept®); her fever and rash improved. Serological testing was positive for SLE (ANA titer of 1:320 and anti-double-stranded DNA titer of 1:640). She was discharged on Day 9 with prednisone and mycophenolate and plaquenil. She was doing well at one-month follow up. 2. Discussion Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with a myriad of non-specific presenting symptoms that can affect nearly any organ system. According to most recent data, the incidence of SLE in the US is 5.1 per 100,000 people per year [1]. The pathogenesis of SLE is not clearly understood, but research shows it involves complex immune dysfunction, specifically, the production of autoantibodies against the body's connective tissues. Many factors have been proven to increase the risk for developing SLE, including genetic predisposition, family history, female gender, and racial background; compared with the white non-Hispanic population, SLE develops 3–4 times more frequently and is often more severe in African Americans, Asian Americans, and Hispanic patients [2] [3] [4]. Recently, there has been increasing speculation that immunizations could play a role in unmasking SLE and other autoimmune diseases [5]. It has been reported that certain vaccines have the ability to trigger a relapse or flare of preexisting autoimmune disease [6]. The issue of whether vaccination has a role in the initial presentation of an autoimmune disease such as SLE is controversial [5] [7]. Although there have been several case reports demonstrating a temporal relationship between recent vaccination and the development of SLE [7] [8] [9], this association cannot establish causality. To our knowledge, there has never been a case published on acute presentation of SLE in association with
https://doi.org/10.1016/j.ajem.2017.10.020 0735-6757/© 2017 Published by Elsevier Inc.
Please cite this article as: Holmes AD, et al, Systemic lupus erythematosus following meningococcal vaccination, American Journal of Emergency Medicine (2017), https://doi.org/10.1016/j.ajem.2017.10.020
2
A.D. Holmes et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx
the meningococcal vaccination. In our case, the extreme proximity of the vaccination to the clinical symptoms, and the pathognomonic serologic findings argues in favor of a cause and effect relationship between the vaccine and classical SLE. Recent research has suggested that vaccinations significantly increase the risk of SLE [8] [10]; however it is unclear whether the vaccination merely unmasks a latent immunologic condition or is truly the cause of the disease. In addition, the association between vaccination and autoimmune disease may be a manifestation of a yet unrecognized third factor. More research is necessary to delineate the causal relationship, if any, between vaccinations and SLE. Our case highlights the importance of inquiring about recent vaccinations in any patient presenting with the unexplained onset of symptoms typical of autoimmune disease. References [1] Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006 May 2;15(5):308–18. [2] Mok CC, Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol 2003 Jul;56(7):481–90.
[3] Kuo C-F, Grainge MJ, Valdes AM, See L-C, Luo S-F, K-H Yu, et al. Familial aggregation of systemic lupus erythematosus and coaggregation of autoimmune diseases in affected families. JAMA Intern Med 2015 Sep 1;175(9):1518. [4] Lupus Manzi S. Update: perspective and clinical pearls. Cleve Clin J Med 2009 Feb 1; 76(2):137–42. [5] Chen RT, Pless R, Destefano F. Epidemiology of autoimmune reactions induced by vaccination. J Autoimmun 2001 May;16(3):309–18. [6] Bijl M, Agmon-Levin N, Dayer J-M, Israeli E, Gatto M, Shoenfeld Y. Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefitrisk assessment. Autoimmun Rev 2012 Jun;11(8):572–6. [7] Agmon-Levin N, Zafrir Y, Paz Z, Shilton T, Zandman-Goddard G, Shoenfeld Y. Ten cases of systemic lupus erythematosus related to hepatitis B vaccine. In: Shoenfeld Y, editor. Lupus. London, England: SAGE Publications Sage UK; 2009 Nov 30. p. 1192–7. [8] Older SA, Battafarano DF, Enzenauer RJ, Krieg AM. Can immunization precipitate connective tissue disease? Report of five cases of systemic lupus erythematosus and review of the literature. Semin Arthritis Rheum 1999 Dec;29(3):131–9. [9] Kikuchi S, Sato M, Otaka Y, Takahashi Y, Watanabe T, Goda F. Case report; a case of systemic lupus erythematosus complicated with limbic encephalitis after vaccination for influenza virus. Nippon Naika Gakkai Zasshi 2012 Oct 10;101(10):2952–4. [10] Wang B, Shao X, Wang D, Xu D, Zhang J-A. Vaccinations and risk of systemic lupus erythematosus and rheumatoid arthritis: a systematic review and meta-analysis. Autoimmun Rev 2017 Jul;16(7):756–65.
Please cite this article as: Holmes AD, et al, Systemic lupus erythematosus following meningococcal vaccination, American Journal of Emergency Medicine (2017), https://doi.org/10.1016/j.ajem.2017.10.020