Subcutaneous Veltuzumab in Refractory Pemphigus
Case Report/Case Series Research
2. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5 (175):175ra30. doi:10.1126/scitranslmed.3005166.
7. Liebman HA, Saleh MN, Bussel JB, et al. Low-dose anti-CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study. Br J Haematol. 2013;162(5):693-701.
11. Ohyama B, Nishifuji K, Chan PT, et al. Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2–based swapped molecules. J Invest Dermatol. 2012;132(4):1158-1168.
3. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355(17):1772-1779.
8. Tahir H, Rohrer J, Bhatia A, Wegener WA, Isenberg DA. Humanized anti-CD20 monoclonal antibody in the treatment of severe resistant systemic lupus erythematosus in a patient with antibodies against rituximab. Rheumatology (Oxford). 2005;44(4):561-562.
12. Schroder C, Azimzadeh AM, Wu G, Price JO, Atkinson JB, Pierson RN. Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transpl Immunol. 2003;12(1): 19-28.
4. Lunardon L, Payne AS. Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus. J Allergy Clin Immunol. 2012;130 (3):800-803. 5. Goldenberg DM, Rossi EA, Stein R, et al. Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody. Blood. 2009;113(5):1062-1070. 6. Negrea GO, Elstrom R, Allen SL, et al. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma. Haematologica. 2011;96(4):567-573.
9. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043-1046. 10. Cheng SW, Kobayashi M, Kinoshita-Kuroda K, Tanikawa A, Amagai M, Nishikawa T. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol. 2002;147(2): 261-265.
13. Mao CP, Brovarney MR, Dabbagh K, Birnböck HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013;8(11):e80533. doi:10.1371/journal.pone .0080533. 14. Horváth B, Huizinga J, Pas HH, Mulder AB, Jonkman MF. Low-dose rituximab is effective in pemphigus. Br J Dermatol. 2012;166(2):405-412.
NOTABLE NOTES
White Shadows in a Dark Land Rina M. Allawh, BS; Scott A. Norton, MD
The documentary In the Shadow of the Sun captures Josephat Torner, an advocate for Tanzania’s albino community, stating “It’s my dream in my life that people with albinism are respected and given all rights which other human beings are being given.”1 Since 2000, nearly 200 albinos in East Africa have been killed and dozens more mutilated by the intentional severing of limbs.2 Recent efforts from local and international albino advocacy organizations, along with the United Nations, have increased protections for albinos in East Africa and have promoted education, locally and globally, about the plight of albinos. Albinism encompasses several inherited disorders of melanin biosynthesis characterized by various degrees of incomplete pigmentation of hair, skin, and eyes. Clinical manifestations and classification are based on the genes affected; OCA2 is the most common form in subSaharan Africans (OMIM 20320).3 In the United States, approximately 1 in 20 000 individuals have albinism, but the condition is 5 times more common in East Africa.1 The award-winning documentary, In the Shadow of the Sun, uncovers the social rejection, dehumanization, discrimination, and violence facing Tanzania’s albinos through the stories of 45-year-old Josephat Torner and Vedastus Zangule, a school child.1 Filmed over 6 years, In the Shadow of the Sun is an 84-minute, small-budget film directed by British filmmaker Harry Freeland and produced by Inroads Films. It premiered at the International Documentary Film Festival in Amsterdam in November 2012 and then was shown at 50 festivals in 28 countries, including Tanzania.1 With a passion for East African culture, Freeland traveled to Ukerewe, an island in Lake Victoria, where he met the force behind the film, Josephat, at a protest confronting the superstitions and myths about albinism.1 Persecution against albinos within Tanzanian society arises
jamadermatology.com
from an ancient spiritual belief, reinforced by traditional healers, that blood and body parts of albinos enhance the ability of potions, charms, and ritual practices to confer magical powers, prosperity, and good health to a believer.1,2 Are traditional healers the only perpetrators? Freeland’s interview with local fishermen reveals that anti-albino barbarism is a business, perhaps originally based on deep-rooted superstitions, but now fueled by poverty, involving “people with money and power.”1 By merging distressing footage with present-day interviews, Freeland reveals that traditional healers and community entrepreneurs are involved in these murders.1 Despite unpredictable dangers, Josephat and Vedastsus are determined to overcome personal obstacles, thereby providing a sense of accomplishment and hope to albinos in East Africa. No longer hidden in the shadows, the voices of Josephat, Vedastus, and others experiencing discrimination are now heard worldwide. As a result of the global success of the documentary (which is available on DVD in England and Ireland and for downloading on movieler.com), Freeland has founded a frontline nonprofit organization, Standing Voice, that advances human rights for people with albinism in East Africa.1 Author Affiliations: George Washington University School of Medicine, Washington, DC (Allawh); Department of Dermatology, Children’s National Medical Center, Washington, DC (Norton). Corresponding Author: Scott A. Norton, MD, Department of Dermatology, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC 20010 ([email protected]). 1. Freeland H, director. Torner J, Zangul V, narrators. In the Shadow of the Sun [motion picture]. San Diego, CA: Dogwoof; 2012. 2. Cruz-Inigo AE, Ladizinski B, Sethi A. Albinism in Africa: stigma, slaughter, and awareness campaigns. Dermatol Clin. 2011;29(1):79-87. 3. Kelly AP, Taylor S. Dermatology for Skin of Color. New York, NY: McGraw-Hill Medical; 2009:325.
JAMA Dermatology December 2014 Volume 150, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Florida International University Medical Library User on 05/24/2015
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Case Report/Case Series Research
2. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5 (175):175ra30. doi:10.1126/scitranslmed.3005166.
7. Liebman HA, Saleh MN, Bussel JB, et al. Low-dose anti-CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study. Br J Haematol. 2013;162(5):693-701.
11. Ohyama B, Nishifuji K, Chan PT, et al. Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2–based swapped molecules. J Invest Dermatol. 2012;132(4):1158-1168.
3. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355(17):1772-1779.
8. Tahir H, Rohrer J, Bhatia A, Wegener WA, Isenberg DA. Humanized anti-CD20 monoclonal antibody in the treatment of severe resistant systemic lupus erythematosus in a patient with antibodies against rituximab. Rheumatology (Oxford). 2005;44(4):561-562.
12. Schroder C, Azimzadeh AM, Wu G, Price JO, Atkinson JB, Pierson RN. Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transpl Immunol. 2003;12(1): 19-28.
4. Lunardon L, Payne AS. Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus. J Allergy Clin Immunol. 2012;130 (3):800-803. 5. Goldenberg DM, Rossi EA, Stein R, et al. Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody. Blood. 2009;113(5):1062-1070. 6. Negrea GO, Elstrom R, Allen SL, et al. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma. Haematologica. 2011;96(4):567-573.
9. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043-1046. 10. Cheng SW, Kobayashi M, Kinoshita-Kuroda K, Tanikawa A, Amagai M, Nishikawa T. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol. 2002;147(2): 261-265.
13. Mao CP, Brovarney MR, Dabbagh K, Birnböck HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013;8(11):e80533. doi:10.1371/journal.pone .0080533. 14. Horváth B, Huizinga J, Pas HH, Mulder AB, Jonkman MF. Low-dose rituximab is effective in pemphigus. Br J Dermatol. 2012;166(2):405-412.
NOTABLE NOTES
White Shadows in a Dark Land Rina M. Allawh, BS; Scott A. Norton, MD
The documentary In the Shadow of the Sun captures Josephat Torner, an advocate for Tanzania’s albino community, stating “It’s my dream in my life that people with albinism are respected and given all rights which other human beings are being given.”1 Since 2000, nearly 200 albinos in East Africa have been killed and dozens more mutilated by the intentional severing of limbs.2 Recent efforts from local and international albino advocacy organizations, along with the United Nations, have increased protections for albinos in East Africa and have promoted education, locally and globally, about the plight of albinos. Albinism encompasses several inherited disorders of melanin biosynthesis characterized by various degrees of incomplete pigmentation of hair, skin, and eyes. Clinical manifestations and classification are based on the genes affected; OCA2 is the most common form in subSaharan Africans (OMIM 20320).3 In the United States, approximately 1 in 20 000 individuals have albinism, but the condition is 5 times more common in East Africa.1 The award-winning documentary, In the Shadow of the Sun, uncovers the social rejection, dehumanization, discrimination, and violence facing Tanzania’s albinos through the stories of 45-year-old Josephat Torner and Vedastus Zangule, a school child.1 Filmed over 6 years, In the Shadow of the Sun is an 84-minute, small-budget film directed by British filmmaker Harry Freeland and produced by Inroads Films. It premiered at the International Documentary Film Festival in Amsterdam in November 2012 and then was shown at 50 festivals in 28 countries, including Tanzania.1 With a passion for East African culture, Freeland traveled to Ukerewe, an island in Lake Victoria, where he met the force behind the film, Josephat, at a protest confronting the superstitions and myths about albinism.1 Persecution against albinos within Tanzanian society arises
jamadermatology.com
from an ancient spiritual belief, reinforced by traditional healers, that blood and body parts of albinos enhance the ability of potions, charms, and ritual practices to confer magical powers, prosperity, and good health to a believer.1,2 Are traditional healers the only perpetrators? Freeland’s interview with local fishermen reveals that anti-albino barbarism is a business, perhaps originally based on deep-rooted superstitions, but now fueled by poverty, involving “people with money and power.”1 By merging distressing footage with present-day interviews, Freeland reveals that traditional healers and community entrepreneurs are involved in these murders.1 Despite unpredictable dangers, Josephat and Vedastsus are determined to overcome personal obstacles, thereby providing a sense of accomplishment and hope to albinos in East Africa. No longer hidden in the shadows, the voices of Josephat, Vedastus, and others experiencing discrimination are now heard worldwide. As a result of the global success of the documentary (which is available on DVD in England and Ireland and for downloading on movieler.com), Freeland has founded a frontline nonprofit organization, Standing Voice, that advances human rights for people with albinism in East Africa.1 Author Affiliations: George Washington University School of Medicine, Washington, DC (Allawh); Department of Dermatology, Children’s National Medical Center, Washington, DC (Norton). Corresponding Author: Scott A. Norton, MD, Department of Dermatology, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC 20010 ([email protected]). 1. Freeland H, director. Torner J, Zangul V, narrators. In the Shadow of the Sun [motion picture]. San Diego, CA: Dogwoof; 2012. 2. Cruz-Inigo AE, Ladizinski B, Sethi A. Albinism in Africa: stigma, slaughter, and awareness campaigns. Dermatol Clin. 2011;29(1):79-87. 3. Kelly AP, Taylor S. Dermatology for Skin of Color. New York, NY: McGraw-Hill Medical; 2009:325.
JAMA Dermatology December 2014 Volume 150, Number 12
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Florida International University Medical Library User on 05/24/2015
1335
