Pathogenesis of calciphylaxis: Hans Selye to nuclear factor κ-B

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Presentation transcript:

Pathogenesis of calciphylaxis: Hans Selye to nuclear factor κ-B Roger H. Weenig, MD, MPH Journal of the American Academy of Dermatology Volume 58, Issue 3, Pages 458-471 (March 2008) DOI: 10.1016/j.jaad.2007.12.006 Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 1 Photomicrographs of biopsy specimens taken from skin affected by calciphylaxis. A, Medial calcification and subintimal fibroplasia of pannicular arteriole. B, Thrombotic occlusion of numerous papillary dermal vessels. C, Pancutaneous ischemic (coagulative) necrosis. (A to C, Hematoxylin-eosin stain; original magnifications: A, ×80; B and C, ×100.) Journal of the American Academy of Dermatology 2008 58, 458-471DOI: (10.1016/j.jaad.2007.12.006) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 2 Photograph of clinical findings of calciphylaxis shows multiple areas of ischemic purpura, necrosis, and ulceration of thigh, hip, and abdomen. Journal of the American Academy of Dermatology 2008 58, 458-471DOI: (10.1016/j.jaad.2007.12.006) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 3 Photomicrograph of biopsy specimen taken from skin affected by calciphylaxis shows medial calcification and adjacent osteoid formation in pannicular arteriole. (Hematoxylin-eosin stain; original magnification: ×400.) Journal of the American Academy of Dermatology 2008 58, 458-471DOI: (10.1016/j.jaad.2007.12.006) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 4 A, Photomicrograph of biopsy specimen taken from skin affected by calciphylaxis shows arteriole with aluminum (Al) deposits associated with medial calcification. (Solochrome-azurine stain; original magnification: ×400.) B, Energy-dispersive microanalysis of arteriole confirms presence of Al. Other inorganic elements identified in analysis include carbon (C), oxygen (O), sodium (Na), phosphorus (P), chloride (Cl), and calcium (Ca). Titanium (Ti) represents grid material. Journal of the American Academy of Dermatology 2008 58, 458-471DOI: (10.1016/j.jaad.2007.12.006) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 5 Schematic illustration for proposed molecular pathogenesis of calciphylaxis. BMP, Bone morphogenic protein; Cbfa-1, core-binding factor α/runt-related transcription factor; ET, endothelin; IκB, nuclear factor κ-B (NFκB) inhibitor; IKKα/β/γ, NFκB inhibitor α, β, and γ complex; IL, interleukin; IL-1R, IL-1 receptor; MEKK, mitogen-activated kinase 1; MGP, matrix Gla protein; NIK, NFκB-inducing kinase; OPG, osteoprotegerin; PTH, parathyroid hormone; p50/p52, NFκB subunits 1/2; RANK, receptor activator of NFκB; RANKL, ligand of RANK; TNF, tumor necrosis factor; TNFR, TNF-α receptor; TRAF, TNF receptor-associated factor. Journal of the American Academy of Dermatology 2008 58, 458-471DOI: (10.1016/j.jaad.2007.12.006) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions