148
Letters / Ann Allergy Asthma Immunol 115 (2015) 147e162
Table 1 UAS7-guided determination of dosing interval for each patient Patient number
Baseline UAS7
On-relapse equivalent daily prednisone dose (mg/d)
UAS7 score 4 wk after first OMZ dose
UAS7 score at 6-mo end point
Calculated optimal dosing interval (d)
1 2 3 4 5 6 7 8 Mean SD Pa
34 37 37 31 36 35 42 25 34.6 4.98 d
5 35 7 50 10 13 75 0 24.4 26.5 d
0 0 3 21 0 2 0 5 3.9 7.16 >.00007
0 0 5 6 0 0 0 0 1.4 2.56 >.000001
69 49 34 28 84 35 suspended 30 47.0 21.73 d
Abbreviations: OMZ, omalizumab; UAS7, 7-day Urticaria Activity Score. a Comparing UAS7 scores at baseline vs 4-week and baseline vs 6-month end point.
symptom control, and therefore delaying the dose should be attempted. We could not find any difference in baseline features that could be predictive of suspension or tapering tolerance in patients owing to the small number of observations. Nevertheless, it should be kept in mind that in a larger cohort a small percentage of patients (8%) who became unresponsive to treatment, with no clear biological explanation, was identified9; whether this could affect the safety of long-term maintenance strategies and to what extent have yet to be elucidated. Acknowledgments The authors thank Paul Bowerbank for his help in reviewing this report. Chiara Tontini, MD Lucia Marinangeli, MD Miriam Cognigni, MD Maria Beatrice Bilò, MD Leonardo Antonicelli, MD Department of Internal Medicine, Allergy Unit Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Italy [email protected]
References [1] Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924e935. [2] Ferrer M, Gamboa P, Sanz ML, et al. Omalizumab is effective in nonautoimmune urticaria. J Allergy Clin Immunol. 2011;127:1300e1302. [3] Saini S, Rosen KE, Hsieh HJ, et al. A randomized, placebo-controlled, doseranging study of single-dose omalizumab in patients with H1-antihistamineerefractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011; 128:567e573. [4] Zuberbier T, Aberer W, Asero R, et al. Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2014; 69:1e29. [5] European Public Assessment Report (EPAR) for Xolair 2014. http://www.ema. europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/ 000606/WC500057298.pdf. Accessed April 4, 2015. [6] Romano C, Sellitto A, De Fans U, et al. Maintenance of remission with low-dose omalizumab in long-lasting, refractory chronic urticaria. Ann Allergy Asthma Immunol. 2010;104:95e96. [7] Silva PM, Costa AC, Mendes A, Barbosa MP. Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria. Allergol Immunopathol (Madr). 2015;43:168e173. [8] Uysal P, Eller E, Mortz CG, Bindslev-Jensen C. An algorithm for treating chronic urticaria with omalizumab: dose interval should be individualized. J Allergy Clin Immunol. 2014;133:914e915. [9] Sussman G, Hébert J, Barron C, et al. Real-life experiences with omalizumab for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2014;112: 170e174.
Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy Enteroviruses (EVs) are the most common circulating viruses and cause of viral meningoencephalitis in the United States. In the general population, enteroviral infection is usually a self-limited disease. However, in patients with humoral immunodeficiency, infections can be fatal. The present case is that of a woman with Evans syndrome treated with splenectomy and rituximab who developed hypogammaglobulinemia and, despite antibody replacement, a fatal Coxsackie B3 virus meningoencephalitis. Enteroviruses are positive-sense single-stranded RNA viruses with a capsid composed of 4 structural proteins (VP1eVP4).1,2 Although EV meningoencephalitis (EM) is typically self-limited, in patients with humoral immunodeficiency, chronic EM has been reported often with fatal outcome.3,4 The use of intravenous Disclosures: Authors have nothing to disclose.
immunoglobulin (IVIG) has dramatically decreased the incidence of chronic EM in congenital agammaglobulinemic conditions. Unfortunately, there are limited pharmaceutical treatment options available once chronic EM develops, all with varying degrees of success, including pleconaril (a picornavirus capsid protein inhibitor), high-dose IVIG, intrathecal immunoglobulin, and use of immunoglobulin preparations selected to contain high titers of enteroviral antibody. A 28-year-old white woman presented to the University of Virginia Hospital. At 15 years of age, she was diagnosed with Evans syndrome (autoimmune hemolytic anemia) and idiopathic thrombocytopenic purpura.5 Workup at that time was negative for immunodeficiency (Table 1). She was initially treated with danazol and corticosteroids. Then, she received high-dose (1 mg/kg) IVIG and a total of 8 doses of 375 mg/m2 of rituximab during a 10-month
Letters / Ann Allergy Asthma Immunol 115 (2015) 147e162 Table 1 (continued )
Table 1 Laboratory results before and after rituximab treatment Time point 15 y of age Diagnosed with Evans syndrome
Time point 28 y of age CSF results (LP 4)
antinuclear antibody negative
IgG 1,140 mg/dL (700e1,450 mg/dL) IgA 256 mg/dL (70e370 mg/dL) IgM 172 mg/dL (30e210 mg/dL) IgE 124 IU/mL (10e130 IU/mL) HIV-1 and -2 IgG negative
27 y of age CSF results (LP 1)1
28 y of age Diagnosed with hypogammaglobulinemia
fluid colorless and clear WBC count 118 mL (55% lymphocytes) RBC count 2/mL protein 87 mg/dL (15e40 mg/dL) glucose 41 mg/dL (40e70 mg/dL) oligoclonal bands not detected IgG 259 mg/dL (700e1,450 mg/dL) IgA 38.9 mg/dL (70e370 mg/dL) IgM
Letters / Ann Allergy Asthma Immunol 115 (2015) 147e162
Table 1 UAS7-guided determination of dosing interval for each patient Patient number
Baseline UAS7
On-relapse equivalent daily prednisone dose (mg/d)
UAS7 score 4 wk after first OMZ dose
UAS7 score at 6-mo end point
Calculated optimal dosing interval (d)
1 2 3 4 5 6 7 8 Mean SD Pa
34 37 37 31 36 35 42 25 34.6 4.98 d
5 35 7 50 10 13 75 0 24.4 26.5 d
0 0 3 21 0 2 0 5 3.9 7.16 >.00007
0 0 5 6 0 0 0 0 1.4 2.56 >.000001
69 49 34 28 84 35 suspended 30 47.0 21.73 d
Abbreviations: OMZ, omalizumab; UAS7, 7-day Urticaria Activity Score. a Comparing UAS7 scores at baseline vs 4-week and baseline vs 6-month end point.
symptom control, and therefore delaying the dose should be attempted. We could not find any difference in baseline features that could be predictive of suspension or tapering tolerance in patients owing to the small number of observations. Nevertheless, it should be kept in mind that in a larger cohort a small percentage of patients (8%) who became unresponsive to treatment, with no clear biological explanation, was identified9; whether this could affect the safety of long-term maintenance strategies and to what extent have yet to be elucidated. Acknowledgments The authors thank Paul Bowerbank for his help in reviewing this report. Chiara Tontini, MD Lucia Marinangeli, MD Miriam Cognigni, MD Maria Beatrice Bilò, MD Leonardo Antonicelli, MD Department of Internal Medicine, Allergy Unit Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Italy [email protected]
References [1] Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924e935. [2] Ferrer M, Gamboa P, Sanz ML, et al. Omalizumab is effective in nonautoimmune urticaria. J Allergy Clin Immunol. 2011;127:1300e1302. [3] Saini S, Rosen KE, Hsieh HJ, et al. A randomized, placebo-controlled, doseranging study of single-dose omalizumab in patients with H1-antihistamineerefractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011; 128:567e573. [4] Zuberbier T, Aberer W, Asero R, et al. Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2014; 69:1e29. [5] European Public Assessment Report (EPAR) for Xolair 2014. http://www.ema. europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/ 000606/WC500057298.pdf. Accessed April 4, 2015. [6] Romano C, Sellitto A, De Fans U, et al. Maintenance of remission with low-dose omalizumab in long-lasting, refractory chronic urticaria. Ann Allergy Asthma Immunol. 2010;104:95e96. [7] Silva PM, Costa AC, Mendes A, Barbosa MP. Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria. Allergol Immunopathol (Madr). 2015;43:168e173. [8] Uysal P, Eller E, Mortz CG, Bindslev-Jensen C. An algorithm for treating chronic urticaria with omalizumab: dose interval should be individualized. J Allergy Clin Immunol. 2014;133:914e915. [9] Sussman G, Hébert J, Barron C, et al. Real-life experiences with omalizumab for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2014;112: 170e174.
Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy Enteroviruses (EVs) are the most common circulating viruses and cause of viral meningoencephalitis in the United States. In the general population, enteroviral infection is usually a self-limited disease. However, in patients with humoral immunodeficiency, infections can be fatal. The present case is that of a woman with Evans syndrome treated with splenectomy and rituximab who developed hypogammaglobulinemia and, despite antibody replacement, a fatal Coxsackie B3 virus meningoencephalitis. Enteroviruses are positive-sense single-stranded RNA viruses with a capsid composed of 4 structural proteins (VP1eVP4).1,2 Although EV meningoencephalitis (EM) is typically self-limited, in patients with humoral immunodeficiency, chronic EM has been reported often with fatal outcome.3,4 The use of intravenous Disclosures: Authors have nothing to disclose.
immunoglobulin (IVIG) has dramatically decreased the incidence of chronic EM in congenital agammaglobulinemic conditions. Unfortunately, there are limited pharmaceutical treatment options available once chronic EM develops, all with varying degrees of success, including pleconaril (a picornavirus capsid protein inhibitor), high-dose IVIG, intrathecal immunoglobulin, and use of immunoglobulin preparations selected to contain high titers of enteroviral antibody. A 28-year-old white woman presented to the University of Virginia Hospital. At 15 years of age, she was diagnosed with Evans syndrome (autoimmune hemolytic anemia) and idiopathic thrombocytopenic purpura.5 Workup at that time was negative for immunodeficiency (Table 1). She was initially treated with danazol and corticosteroids. Then, she received high-dose (1 mg/kg) IVIG and a total of 8 doses of 375 mg/m2 of rituximab during a 10-month
Letters / Ann Allergy Asthma Immunol 115 (2015) 147e162 Table 1 (continued )
Table 1 Laboratory results before and after rituximab treatment Time point 15 y of age Diagnosed with Evans syndrome
Time point 28 y of age CSF results (LP 4)
antinuclear antibody negative
IgG 1,140 mg/dL (700e1,450 mg/dL) IgA 256 mg/dL (70e370 mg/dL) IgM 172 mg/dL (30e210 mg/dL) IgE 124 IU/mL (10e130 IU/mL) HIV-1 and -2 IgG negative
27 y of age CSF results (LP 1)1
28 y of age Diagnosed with hypogammaglobulinemia
fluid colorless and clear WBC count 118 mL (55% lymphocytes) RBC count 2/mL protein 87 mg/dL (15e40 mg/dL) glucose 41 mg/dL (40e70 mg/dL) oligoclonal bands not detected IgG 259 mg/dL (700e1,450 mg/dL) IgA 38.9 mg/dL (70e370 mg/dL) IgM
