Dédée F. Murrell

The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB

BACKGROUND Since publication in 2000 of the Second International Consensus Report on Diagnosis and Classification of Epidermolysis Bullosa, many advances have been made to our understanding of this group of diseases, both clinically and molecularly. At the same time, new epidermolysis bullosa (EB) subtypes have been described and similarities with some other diseases have been identified. OBJECTIVE We sought to arrive at a new consensus of the classification of EB subtypes. RESULTS We now present a revised classification system that takes into account the new advances, as well as encompassing other inherited diseases that should also be included within the EB spectrum, based on the presence of blistering and mechanical fragility. Current recommendations are made on the use of specific diagnostic tests, with updates on the findings known to occur within each of the major EB subtypes. Electronic links are also provided to informational and laboratory resources of particular benefit to clinicians and their patients. LIMITATIONS As more becomes known about this disease, future modifications may be needed. The classification system has been designed with sufficient flexibility for these modifications. CONCLUSION This revised classification system should assist clinicians in accurately diagnosing and subclassifying patients with EB.

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

Modulation of tendon healing by nitric oxide

Abstract. Nitric oxide (NO.) is a small, diffusible free radical that is generated from L-arginine by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in tendon healing. NO. synthase activity and immunoreactivity was absent in un-injured rat Achilles tendon. After surgical division there was a five-fold increase in NO. synthase activity and immunoreactivity within the healing tendon at day 7, with a return to near baseline levels at day 14. Inhibition of NO. synthase activity with oral administration of N-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in cross-sectional area (30% at day 7, p < 0.01, 50% at day 15, p < 0.001) and failure load (24% at day 7, p <0.01) of the healing Achilles tendon constructs. Rats fed the same regimen of the enantiomer of L-NAME, (D-NAME) had normal tendon healing. These results indicate that nitric oxide synthase is induced during tendon healing and inhibition of nitric oxide synthase inhibits this tendon healing.

Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts

Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies.

A radical proposal for the pathogenesis of scleroderma.

Because the etiology and pathogenesis of scleroderma are largely speculative, effective therapy is not available for this debilitating condition and its variants. This article reviews current concepts in the etiology and pathogenesis of scleroderma and suggests a unifying hypothesis involving the generation of free radicals. The role of specific free radical scavengers should be tested both in vitro and in clinical trials of patients with scleroderma.

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8-20 mm), with a 12-month follow-up.

Objective  To compare the efficacy and cosmetic outcome (CO) of photodynamic therapy with topical methyl aminolevulinate (MAL‐PDT) with simple excision surgery for superficial basal cell carcinoma (sBCC) over a 1‐year period.

Photodynamic therapy with topical methyl aminolaevulinate for 'difficult-to-treat' basal cell carcinoma

Background  Basal cell carcinoma (BCC) may be difficult to treat by conventional means, particularly if the lesions are large or located in the mid‐face (H‐zone). Photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL) may be a good noninvasive option for these patients.

Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa

Abstract:  Dystrophic epidermolysis bullosa (DEB) is inherited in both an autosomal dominant DEB and autosomal recessive manner RDEB, both of which result from mutations in the type VII collagen gene (COL7A1). To date, 324 pathogenic mutations have been detected within COL7A1 in different variants of DEB; many mutations are clustered in exon 73 (10.74%) which is close to the 39 amino acid interruption region. Dominant dystrophic epidermolysis bullosa usually involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice‐site mutations may underlie some cases. In recessive dystrophic epidermolysis bullosa, the mutations include nonsense, splice site, deletions or insertions, ‘silent’ glycine substitutions within the triple helix and non‐glycine missense mutations within the triple helix or non‐collagenous NC‐2 domain. The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes.

A prospective study of the use of cryosurgery for the treatment of actinic keratoses.

Background  Actinic keratoses are the most common actinic lesions on Caucasian skin. Cryosurgery with liquid nitrogen is commonly used to treat actinic keratoses, but there have been few studies examining the true rate of cure in everyday dermatologic practice.

Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome.

Klippel‐Feil syndrome (KFS) is a congenital disorder of spinal segmentation distinguished by the bony fusion of anterior/cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. Here we report mutations at the GDF6 gene locus in familial and sporadic cases of KFS including the recurrent missense mutation of an extremely conserved residue c.866T>C (p.Leu289Pro) in association with mirror movements and an inversion breakpoint downstream of the gene in association with carpal, tarsal, and vertebral fusions. GDF6 is expressed at the boundaries of the developing carpals, tarsals, and vertebrae and within the adult vertebral disc. GDF6 knockout mice are best distinguished by fusion of carpals and tarsals and GDF6 knockdown in Xenopus results in a high incidence of anterior axial defects consistent with a role for GDF6 in the etiology, diversity, and variability of KFS. Hum Mutat 0,1–11, 2008.