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THIVI MARUTHAPPU Introduction:Anti-TNF drugs are widely prescribe by dermatologists as well as other specialists. With their use comes increasing awareness of potential adverse effects. Patient 1 had a 20 year history of stable vitiligo however 3 months after starting adalimumab for ankylosing spondylitis he developed rapid deterioration in his vitilgo which started to affect his face, hands and axillae in a symmetrical distribution. Adalimumab was stopped and he improved with potent topical steroids. Case 2 developed multiple halo naevi after commencing adalimumab. These were not dysplastic and he has remained on treatment. The potential pathophysiological mechanism for developing immune mediated dermatoses with anti-tnf treatment are discussed.Q1. Which of the following have not been described following use of anti-TNF drugs1. Irreversible alopecia areata2. Erythema elevatum diutunum3. Systemic lupus erythematosus.Q2. Which of the following is false1.vitilgo can be cured with with anti-TNF2. Vitiligo can improve with anti-TNF3.vitiligo can deteriorate with anti-TNF- Disclaimer- This PPT is loaded as student material "as is", from the VRF Vitiligo Master Class Barcelona November 2011; VRF does not endorse or otherwise approve it.
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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
