Transcript
Page 1: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 2: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

Ankylosing Spondylitis HLAB27+

Adalimumab 40mg sc alt. weeks

Stable vitiligo

Case 1 Case 2

3 months

Page 3: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab
Page 4: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

hi

Page 5: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab
Page 6: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

Ankylosing Spondylitis HLAB27+

Adalimumab 40mg sc alt. weeks

Stable vitiligo

3 months

Case 1 Case 2

No history of vitiligo/HN

6 months

Page 7: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab
Page 8: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

Ankylosing Spondylitis HLAB27+

Adalimumab 40mg sc alt. weeks

Stable vitiligo

3 months

Case 1 Case 2

No history of vitiligo/HN

6 months

Page 9: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

“Immune mediated skin lesions” and TNFα

Exarchou et al . Scand J Rheumatol 2009;38:328-331

Page 10: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 11: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 12: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 13: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 14: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 15: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab

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

Page 16: Title-deterioration of vitiligo and de novo onset of Halo Naevi in two patients receiving adalimumab