Annals of Oncology 14:1792, 2003
© 2003 European Society for Medical Oncology
Letters to the Editor |
Delayed-type hypersensitivity reaction or serum sickness after rituximab treatment
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA
*E-mail: aahmed@umich.edu
We report a case of significant delayed cutaneous reaction and possible serum sickness associated with rituximab treatment.
The patient is a 23-year-old female with a long-standing diagnosis of lupus, on chronic steroids. Her recent pregnancy was complicated by autoimmune hemolytic anemia, which required high doses of steroids and periodic blood transfusions. During her pregnancy, she also had significant arthralgias, suggestive of her usual lupus flares.
Post-partum, she developed thrombocytopenia, with a platelet nadir of 4000 mm3, also thought to be autoimmune in nature, although not associated with usual lupus flare symptomatology. Additionally, her C-reactive protein and complement levels were normal. She received WinRho and her prednisone dose was doubled. Her platelet count improved only minimally, up to 24 000 mm3. She was then started on rituximab treatment and tolerated her first dose (22 May 2003) well, with only mild infusional toxicity.
Her platelet count was 37 000 mm3 when she received her second dose of rituximab on 30 May 2003. Approximately 24 h after receiving her second dose, she developed a fever to 38.3°C and chills. Approximately 48 h after the infusion, she developed a diffuse, pruritic, maculopapular rash with generalized edema, small apthous ulcers, diarrhea, and severe arthralgias and myalgias. She presented to the emergency room on 1 June 2003. On examination, her pulse was 119 b.p.m. and her blood pressure was 149/76. She was noted to have shotty axillary lymphadenopathy, as well as the rash. At that time, her platelet count was 24 000 mm3, her chemistries were within normal limits and she showed no proteinuria. She was given a steroid bolus with improvement in the rash. By 3 June 2003 her symptoms, including the rash, had improved significantly. Her platelet count was 62 000 mm3, with normal complement levels and chemistry panels. By 11 June 2003 her platelet count improved to 248 000 mm3, and all of her symptoms had completely resolved.
Rituximab is a human/murine monoclonal antibody targeted against the CD20 antigen on the surface of B lymphocytes. Most of the toxicities associated with rituximab occur at the time of infusion, and are often related to the number of circulating target cells, presumably secondary to cytokine release [1]. However, significant post-infusion syndromes have been reported, including Stevens–Johnson syndrome [2], serum sickness [3, 4] and vasculitis [5]. Typically, serum sickness develops 8–13 days after exposure to an antigen; therefore, whether this reaction developed as a result of the first or second dose is unknown. The underlying disease may play a role in the development of delayed or cutaneous reactions, as the two reported cases of serum sickness developed in patients with autoimmune polyneuropathy and autoimmune thrombocytopenia, while the vasculitis and Stevens–Johnson syndrome were seen in patients with chronic lymphocytic leukaemia and follicular non-Hodgkin’s lymphoma, respectively. Human anti-mouse (HAMA) and human anti-chimeric (HACA) antibody levels can be considered to determine whether the rituximab therapy is primarily responsible for the development of symptoms.
As the role for monoclonal antibodies expands, the possibility of such reactions needs to be more clearly elucidated in the context of clinical trials.
Acknowledgements
We thank Ms Donna Gschwend for manuscript preparation.
B. Hellerstedt & A. Ahmed*
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA (*E-mail: aahmed@umich.edu)
References
1. Winkler U, Jensen M, Manzke H et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999; 94: 2217–2224.
2. Lowndes S, Darby A, Mead G, Lister A. Stevens–Johnson syndrome after treatment with rituximab. Ann Oncol 2002; 13: 1948–1950.
3. D’Arcy CA, Mannik M. Serum sickness secondary to treatment with the murine-human chimeric antibody IDEC-C2B8 (rituximab). Arthritis Rheum 2001; 44: 1717–1718.[CrossRef][Medline]
4. Herishanu Y. Rituximab-induced serum sickness. Am J Hematol 2002; 70: 329.[Medline]
5. Dereure O, Navarro R, Rossi JF, Guilhou JJ. Rituximab-induced vasculitis. Dermatology 2001; 203: 83–84.[CrossRef][Web of Science][Medline]
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