The authors present three patients with severe GVHD not responding to treatment with steroids. The cohort of patients had developed grade II-IV GVHD after transplant and received treatment with high-dose steroids for a median of 7 days (range 7-10) in addition to mycophenolate mofetil for one day. The subjects were then started on infliximab with 3 weekly doses of 5 mg/kg. One patient (33%) experienced a partial resolution of diarrhea and minor improvement of skin rash. One other patient (33%) died with refractory GVHD. The authors concluded that infliximab is apparently an effective drug for the treatment of a GVHD, but can be more effective at doses of 5 mg/kg or higher and/or by administering it repeatedly every week.
JDD ARTICLE EVALUATION:
Tumor necrosis factor alpha (TNF-[alpha]) has been implicated in the pathophysiology of GVHD. Infliximab is a genetically constructed IgG1 murine-human chimeric antibody against TNF-[alpha]; it binds to the TNF-[alpha] receptors and also causes lysis of TNF-[alpha] precursor cells (1). The authors have reported a case of TNF-[alpha] blockage leading to partial resolution of diarrhea and improvement of rash, but the number of patients was so low that we should take this as anecdotal at best. The therapy was well tolerated, but with the death of one of the subjects, their attestations to the efficacy of the drug are to be taken guardedly. We agree with the authors that symptoms of GVHD were improved with TNF-[alpha] blockers, but survival may be unchanged. Perhaps higher doses or earlier initiation of therapy might be beneficial in the future for steroid-resistant GVHD. The importance of TNF in many diseases is evolving, and future trials and research is necessary for us to understand how TNF acts in different disorders.
This article has been included in our review because dermatologists are often consulted to evaluate transplant patients with skin eruptions. Early on in GVHD, the pathology is very non-specific with a mixed cell infiltrate and a clinical picture of mostly erythematous, edematous plaques. This is especially true for the pathology in the first three weeks; after this period, interface changes are better identified and a lymphocytic infiltrate usually prevails, both of which are essential for diagnosis of GVHD. It is essential for dermatologists to identify the cutaneous findings of GVHD and to know how to treat the disease. A colleague of mine once told me that consulting is our moment to shine and demonstrate to other services how essential it is to understand skin changes in the pathophysiology of disease. It is my belief that our role as consultants is necessary for our continuing integration into the medical community, and with that we must do it with pride and with the thoroughness and respect that our field deserves.
WASHINGTON WHISPERS APPEARS IN EACH ISSUE AND PROVIDES A SUMMARY AND CRITICAL EVALUATION OF THE LATEST DRUG TRIALS, STUDIES, AND REACTIONS AVAILABLE TO THE MEDICAL COMMUNITY, AS COLLATED FROM A WEALTH OF INDUSTRY SOURCES.
References:
1. Couriel DR, et al. Tumor necrosis factor alpha blockade for the treatment of steroid-refractory acute GVHD. Blood 2004 Apr; [E-pub ahead of print].
Yamane T. et al. Leukemia and Lymphoma 2003; 44(12):2095-7.
COPYRIGHT 2004 Journal of Drugs in Dermatology
COPYRIGHT 2004 Gale Group
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