Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving...
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Transcript of Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving...
Acceleration of Vitiligo and development of multiple Halo Naevi
in two patients treated with Adalimumab
Dr Thivi Maruthappu¹Dr Susie Morris¹
Dr Maria Leandro²Departments of Dermatology¹ and Rheumatology²
Ankylosing Spondylitis HLAB27+
Adalimumab 40mg sc alt. weeks
Stable vitiligo
Case 1 Case 2
3 months
hi
Ankylosing Spondylitis HLAB27+
Adalimumab 40mg sc alt. weeks
Stable vitiligo
3 months
Case 1 Case 2
No history of vitiligo/HN
6 months
Ankylosing Spondylitis HLAB27+
Adalimumab 40mg sc alt. weeks
Stable vitiligo
3 months
Case 1 Case 2
No history of vitiligo/HN
6 months
“Immune mediated skin lesions” and TNFα
Exarchou et al . Scand J Rheumatol 2009;38:328-331
Auto-Immunity
¹Ferraccoioli et al Ann. Rheum. Dis. 61(2002)358
²D’Auria P et al. J. Intern. Med. 2004:255:409-418
³Via C.S. J. Immunol. 67 (2001) 6821
Increased susceptibility to
infections¹
B Cell
Auto-antibodies and Vitiligo
Norris et al J. Invest Derm 783-787 1988
•Cause vs consequence•Anti-melanocyte antibodies in sera of NSV & HN patients•Autoantibody targets
•Tryosine Hydroxylase•Transcription factor SOX10•Melanin concentrating hormone receptor
•Sera incubated with melanocytes induces cell death by antibody dependent cell mediated toxicity
Auto-Immunity
¹Ferraccoioli et al Ann. Rheum. Dis. 61(2002)358
²D’Auria P et al. J. Intern. Med. 2004:255:409-418
³Via C.S. J. Immunol. 67 (2001) 6821
Increased susceptibility to
infections¹
Nucleosomes/ROS increased²
B Cell
Anti-TNF
AUTOANTIGENS
and ROS
Reactive Oxygen Species and Vitiligo
•Research confirms oxidative stress throughout the epidermis of patients with vitiligo•Elevated H2O2 inhibition of Tyrosinase•Low Catalase levels
•Schallreuter et al. J. Invest Dermatol 1999 93-96
H2O2
CATALASE
H2O +O2
Auto-Immunity
¹Ferraccoioli et al Ann. Rheum. Dis. 61(2002)358
²D’Auria P et al. J. Intern. Med. 2004:255:409-418
³Via C.S. J. Immunol. 67 (2001) 6821
Increased susceptibility to
infections¹
Inhibition of CTL that suppress
autoreactive B Cells
Nucleosomes (auto-antigens)
increased²
B Cell
Anti-TNFCTL
Anti-TNF
Autoreactive Cell
AUTOANTIGENS
and ROS
TNF and Vitiligo
↑ TNF in perilesional skin in NSV¹
Case reports of vitiligo improvement with infliximab²
¹Birol et al Int J. Derm 2006 992-993²Simon et al, Dermatology 2008 234-5
Deterioration of vitiligo
Other auto-immune skin diseases