Matthew G. Fleming

Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the injection site was blunted. The lack of response due to MC deficiency was overcome by intradermal administration of a neutrophil chemoattractant, IL-8, or by reconstitution of the injection sites with neutrophils. These findings provide the first direct evidence to our knowledge that MCs play an essential role in neutrophil recruitment during subepidermal blister formation in experimental BP.

Techniques for a structural analysis of dermatoscopic imagery.

Techniques were developed for automated detection and characterization of dermatoscopic structures, including the pigment network and brown globules. These techniques incorporate algorithms for grayscale shape extraction based on differential geometry developed by Steger, a snake algorithm, and a modification of the region competition strategy of Zhu and Yuille. A novel approach was developed for global segmentation of pigmented lesions, based on stabilized inverse diffusion equations. Procedures for detection of air bubbles and hairs in dermatoscopic images are also reported.

Segmentation of dermatoscopic images by stabilized inverse diffusion equations

Several segmentation techniques were evaluated for their effectiveness in distinguishing lesion from background in dermatoscopic images of pigmented lesions (moles and melanomas). These included 5 techniques previously used for segmentation of pigmented lesions, and several new techniques based on stabilized inverse diffusion equations (SIDE) and Markov random fields (MRF). Novel multiresolution implementations of the SIDE and MRF algorithms were created for this work. Techniques based on the SIDE and MRF algorithms produced the most accurate segmentations.

A subepidermal bullous eruption associated with IgG autoantibodies to a 200 kd dermal antigen: The first case report from the United States

We describe an 81-year-old white man in whom a subepidermal bullous eruption developed that clinically resembled bullous pemphigoid. The eruption promptly responded to oral tetracycline and niacinamide and topical clobetasol. Histologic examination of perilesional skin revealed neutrophilic infiltration with formation of papillary microabscesses and subepidermal cleavage. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane zone. By indirect immunofluorescence, circulating IgG autoantibodies bound exclusively to the dermal side of salt-split normal human skin. Immunoblot analysis demonstrated that the patients autoantibodies reacted with a 200 kd dermal protein that was different from type VII collagen, the epidermolysis bullosa acquisita autoantigen. This patient represents the first confirmed case from the United States with a recently reported novel autoimmune subepidermal bullous disease associated with IgG autoantibodies to a 200 kd dermal antigen.

Analysis of the network pattern in dermatoscopic images

Procedures have been developed for automated analysis of the pigment network in dermatoscopic images. These procedures perform complete network segmentation as well as measurement of the width of network lines and the size and shape of network holes.

Novel technique for multiresolution color image segmentation

We describe a novel technique for color image segmentation. This technique includes three components: a color space transformation, Markov random field expectation-maximization (MRF-EM) segmentation, and a multiresolution implementation termed ‘‘narrow band.’’ The color space transformation, from RGB to LUV, contributes to a perceptually reasonable segmentation result. The MRF-EM algorithm enables unsupervised segmentation and enforces a region smoothness constraint. The narrow-band, multiresolution implementation confines fine resolution processing to a small fraction of the image, thereby achieving acceleration over traditional multiresolution schemes. Experimental results with medical and TV images demonstrate the efficacy of the proposed technique.

Pigmented lesion pathology: what you should expect from your pathologist, and what your pathologist should expect from you.

The first part of this review examines the reliability of histologic diagnosis in pigmented lesions, as measured by concordance studies and medicolegal analysis. It emphasizes the role of clinicians in maximizing that reliability, by providing adequate clinical descriptions, using appropriate biopsy technique, and critically interpreting pathology reports. It identifies those entities that are especially problematic, either because they cannot be reliably recognized by the histopathologist or because their histology is a poor guide to their biologic behavior. The second part of the review is a guide to some of the more difficult and controversial pigmented lesions, including dysplastic nevus, spitzoid nevi and melanomas, cellular blue nevus, animal-type melanoma, and deep penetrating nevus.

Image analysis in dermatopathology.

Background/aims: Image analysis in dermatopathology has been used for DNA ploidy analysis, morphometry, stereology, and quantitative immunohistochemistry. The object is to review image analysis in dermatopathology and evaluate these modalities and their application in pigmented lesion pathology, for elucidation of tumor behaviour and architecture and as an aid in tumor identification and prognostication.