Orf-induced immunobullous disease: A distinct autoimmune blistering disorder  Kevin P. White, MD, Daniel C. Zedek, MD, Wain L. White, MD, Eric L. Simpson, MD, Eric Hester, MD, Lynne Morrison, MD, Zelmira Lazarova, MD, Debra Liu, MD, Alessandra Scagliarini, DVM, PhD, Stephen E. Kurtz, PhD, Clifton R. White, MD, Kim B. Yancey, MD, Andrew Blauvelt, MD  Journal of the American Academy of Dermatology  Volume 58, Issue 1, Pages 49-55 (January 2008) DOI: 10.1016/j.jaad.2007.08.029 Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 1 A, Targetoid palmar lesions at presentation. B, Small, tense vesicles and shallow erosions over distal aspect of tongue. C, Tense, noninflamed bullae and dusky, targetoid papule over inner aspect of left thigh. D, Medium-power view demonstrating subepidermal vesicular mixed dermatitis with eosinophils and neutrophils. (Hematoxylin-eosin stain; original magnification: ×100.) Journal of the American Academy of Dermatology 2008 58, 49-55DOI: (10.1016/j.jaad.2007.08.029) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 2 A, Yellowish, slightly verrucous, firm papule on distal aspect of thumb at site of orf infection. B, Shave biopsy specimen showing acanthosis. C, Higher power view showing vacuolization of spinous keratinocytes. (B and C, Hematoxylin-eosin stain; original magnifications: B, ×25; C, ×400.) Journal of the American Academy of Dermatology 2008 58, 49-55DOI: (10.1016/j.jaad.2007.08.029) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 3 A, Direct immunofluorescence microscopy of patient's perilesional skin showing linear deposits of IgG in epidermal basement membrane. B, Western blot studies of human keratinocyte extracts found that sera from patient 1 (lane 1) and patient 2 (lane 2) did not recognize any known (or common) antigens in this substrate. Serum from patient with bullous pemphigoid (BP) (lane 5) contained IgG that bound BP180 and BP230 antigens (bands circled). Other controls used were sera from patients with epidermolysis bullosa acquisita (EBA) (lane 3), anti-epiligrin cicatricial pemphigoid (lane 4), p200 pemphigoid (lane 6), and serum from healthy volunteer (lane 7). Rabbit polyclonal antiserum immunoblotted all subunits of laminin 5 (lane 8). C, Western blot studies of human dermal extract demonstrated that sera from patient 1 (lane 1) and patient 2 (lane 2) did not show specific or common reactivity to this substrate. Control-positive and -negative sera were used in same order as shown on B. D, Western blot studies of recombinant NC1 domain of collagen VII found that sera from patients 1 and 2 (and sera from controls [shown in same order as C ]) did not demonstrate specific reactivity to this substrate. Conversely, IgG from patient with EBA (positive control, lane 3) bound this 145-kd bacterial recombinant protein (band circled). Journal of the American Academy of Dermatology 2008 58, 49-55DOI: (10.1016/j.jaad.2007.08.029) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 4 A, Papules and vesicles on fifth digit extended onto back of hand and forearm in area that corresponded with site of grease burn a few days before. B, Forearm lesion showed scale crust, hypergranulosis, and intraepidermal vesiculation. There was also pseudocarcinomatous hyperplasia with epidermal pallor overlying perivascular and interstitial mixed inflammatory cell infiltrate. C, Higher magnification showed dense eosinophilic, intracytoplasmic inclusions consistent with parapoxvirus infection. D, Electron microscopy demonstrated laminated cylindric virions (200-300 nm in diameter) with homogeneous capsid and dense central cores, characteristic of parapoxvirus. (B and C, Hematoxylin-eosin stain; original magnifications: B, ×20; C, ×400.) Journal of the American Academy of Dermatology 2008 58, 49-55DOI: (10.1016/j.jaad.2007.08.029) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions

Fig 5 A, Widespread cutaneous and oral bullae appeared approximately 2 weeks after initial orf infection. B and C, Subepidermal blister with neutrophils and eosinophils. D, Immunoblot studies of dermal extracts revealed that patient's serum contained IgG that bound 68-kd polypeptide (lane 3), but not type VII collagen (290- and 145-kd bands identified by IgG from patient with epidermolysis bullosa acquisita, lane 2). Immunoblot performed in parallel with equivalent 1:40 dilution of serum from healthy volunteer (negative control) is shown in lane 1. (B and C, Hematoxylin-eosin stain; original magnifications: B, ×25; C, ×400.) Journal of the American Academy of Dermatology 2008 58, 49-55DOI: (10.1016/j.jaad.2007.08.029) Copyright © 2008 American Academy of Dermatology, Inc. Terms and Conditions