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Skin Patch Test Shows Promise in Diagnosis
and Prevention of Abacavir Hypersensitivity
Abacavir
hypersensitivity syndrome (AHS) is a treatment-limiting and potentially
life-threatening adverse event occurring in 5-9% of those initiating
the antiretroviral agent abacavir (Ziagen). A cutaneous patch test
(PT) has shown promise in characterizing patients with true AHS
(Phillips et al. AIDS 15; 2002).
Genetic
factors such as HLA-B*5701 and associated alleles carried on the
57.1 ancestral haplotypes have been identified as strong risk factors
for AHS in Caucasians.
The
high numbers of CD8
cells found in the skin of patients with skin
rash and positive PT associated with AHS as well
as epidemiological studies associating an elevated CD8 count as
a risk factor for AHS, support a role for CD8 cells in the pathogenesis
of this disease.
TNF-α
levels were increased in response to abacavir in the whole blood
of AHS cases in vitro, and were attenuated by CD8 T-cell
depletion, suggesting an immunopathogenetic role of CD8 T cells
in AHS.
Further
testing was conducted to explore the durability of the PT, the association
of the PT with genetic testing and abacavir-specific lymphocyte
responses.
Seven
out of seven previously PT-positive cases showed positive PT at
24 h with all patients reporting local pruritus but no systemic
symptoms.
Abacavir-specific
IFN-γ production was seen in two out of seven cases (29%) but
no controls (P = 0.04). PT-positive and abacavir-tolerant
controls did not differ for abacavir-specific CD4 cell proliferation,
but CD8 T-cell proliferation was observed in five out of seven PT-positive
cases (71%), and only in one out of 11 of the abacavir-tolerant
controls (9%; P = 0.005).
Conclusions
In
conclusion, the authors write, “The abacavir PT shows durability
over time, suggesting that it may be useful when the history of
AHS is remote. CD8 proliferation in response to abacavir is a new
finding, which combined with the genetic findings implicates the
role of HLA-B*5701-restricted CD8 cells in the pathogenesis of AHS.”
“A
good correlation between patch, immunological and genetic testing
suggests that these tests may complement each other in the clinical
setting and enhance the ability to diagnose and prevent the occurrence
of AHS.”
British Columbia Centre for Excellence
in HIV/AIDS, Vancouver, University of British Columbia, Canada Royal
Liverpool and Broadgreen University Hospitals NHS Trust, University
of Liverpool, Liverpool, UK University Health Network dSunnybrook
and Women's College Health Sciences Centre, University of Toronto,
Toronto, Canada Centre for Clinical Immunology and Biomedical Statistics,
Royal Perth Hospital and Murdoch, Perth, Western Australia.
07/01/05
Reference
E
J Phillips and others. Clinical and immunogenetic correlates of
abacavir hypersensitivity. AIDS
19(9): 979-981. June 10, 2005.
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