Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI).

BACKGROUND: There is a lack of validated standardized outcome measures for epidermolysis bullosa (EB) that can separate activity from damage. OBJECTIVE: We sought to develop and validate an instrument for inherited EB of all ages and subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores activity responsive to therapy separately from scarring. METHODS: The EBDASI was validated by comparing its reliability and validity against the Birmingham EB Severity (BEBS) score (partially validated with activity mixed with scarring), using the Physician Global Assessment (PGA) scale as a reference measurement. Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2 junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad hoc basis during routine patient clinic were also included. RESULTS: For interrater reliability, the overall total score intraclass correlation coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS 0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926 (0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation with PGA (ρ = 0.871) than BEBS with PGA (ρ = 0.852). Intraclass correlation coefficients scatterplots showed the EBDASI was better at distinguishing milder forms of EB, with better correlations at higher severity scores than the BEBS. LIMITATIONS: A limited number of patients were recruited for this study. An independent study will be required to demonstrate the responsiveness of the EBDASI. CONCLUSION: The EBDASI demonstrated excellent reliability and validity, as compared with 2 other outcome measures.

Diffuse melanosis cutis: a systematic review of the literature.

BACKGROUND: Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma characterized by a progressive blue-gray discoloration of the skin and mucous membranes. OBJECTIVE: To foster a better understanding of the clinical presentation, histological findings, and pathophysiology underlying DMC. METHODS: A systematic review of the literature was completed utilizing MEDLINE, CINAHL, Embase, and Google. Data were extracted using a protocol-driven spread sheet with all statistical analyses completed using SPSS. RESULTS: The review identified 68 original cases of DMC. The mean time from diagnosis of melanoma until development of DMC was 11.48 months (95% confidence interval [CI]: 0-48.16). The mean time to death following the onset of DMC was 4.43 months (95% CI: 0.00-11.11). Histological findings were relatively consistent demonstrating intracellular and extracellular melanin deposition in the dermis, with a pronounced perivascular distribution. The pathophysiological mechanisms underlying DMC could not be definitively elucidated; however, it is hypothesized that the melanin precursors, melanin, and melanosomes liberated by cytolytic metastatic melanoma deposits are phagocytosed by dermal histiocytes, manifesting clinically as diffuse melanosis. LIMITATIONS: The cross-sectional nature of case reports, paucity of cases of DMC, and heterogeneity in reporting limit any conclusions being drawn regarding the pathophysiology of DMC definitively. CONCLUSION: DMC heralds a poor prognosis for patients with metastatic melanoma and affected patients should be made aware of the implications of this condition on survival.

A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa.

BACKGROUND: Chronic wounds are a major source of morbidity and mortality in generalized severe recessive dystrophic epidermolysis bullosa (RDEB-GS). OBJECTIVE: This was a phase II double-blinded randomized controlled trial of intralesional allogeneic cultured fibroblasts in suspension solution versus suspension solution alone for wound healing in RDEB-GS. METHODS: Adult patients with RDEB-GS were screened for chronic ulcers and reduced collagen VII expression. Up to 6 pairs of symmetric wounds were measured and biopsied at baseline, then randomized to cultured allogeneic fibroblasts in a crystalloid suspension solution with 2% albumin or suspension solution alone. Ulcer size, collagen VII protein and messenger RNA expression, anchoring fibril numbers, morphology, and inflammatory markers were measured at 2 weeks and at 3, 6, and 12 months. RESULTS: All wounds healed significantly more rapidly with fibroblasts and vehicle injections, with an area decrease of 50% by 12 weeks, compared with noninjected wounds. Collagen VII expression increased to a similar degree in both study arms in wounds from 3 of 5 patients. LIMITATIONS: The number of patients with RDEB-GS who met inclusion criteria was a limitation, as was 1 trial center rather than multicenter. CONCLUSIONS: The injection of both allogeneic fibroblasts and suspension solution alone improved wound healing in chronic nonhealing RDEB-GS wounds independently of collagen VII regeneration. This may provide feasible therapy for wound healing in patients with RDEB-GS.

Results of a nationwide dermoscopy survey investigating the prevalence, advantages and disadvantages of dermoscopy use among Australian dermatologists.

BACKGROUND/OBJECTIVES: The primary objective of this survey was to assess the prevalence of use of dermoscopy by Australian dermatologists. The secondary objective was to understand the perceived advantages and disadvantages of dermoscopy use. METHODS: Invitation letters were sent to all 282 Australian dermatologists belonging to the Australasian College of Dermatology in 2008. The survey, investigating prevalence and perceptions of dermoscopy use, was completed either online or on paper. RESULTS: Ninety-nine of the 283 (35%) dermatologists completed the survey eligibly. A total of 98% of dermatologists reported using dermoscopy and 95% had received formal training. Only 2-3% found it not useful for the diagnosis of pigmented lesions, melanoma or atypical naevi, whereas 12% found it not useful for the diagnosis of non-pigmented tumours. Eighty-five percent found it improved diagnosis compared to naked eye examination; and 57% of dermatologists used baseline dermoscopy to follow up changes in lesions, of which 78% used some image capture device. CONCLUSIONS: In the sample of Australian dermatologists agreeing to be surveyed, there was a high prevalence rate of dermoscopy use. The factors supporting the use of dermoscopy are explored in this foundational database of dermoscopy use among Australian dermatologists.

Diffuse melanosis cutis in the setting of BRAF(V600E) metastatic melanoma.

CASE REPORT: A 79-year-old Caucasian male presented with a 1-week history of diffuse progressive blue-gray discoloration of the skin subsequently found to due to diffuse melanosis cutis (DMC) in the setting of metastatic melanoma. Mutation testing demonstrated BRAF(V600E) mutation status, an unexpected finding given his age. He died two weeks after presentation. DISCUSSION: As our understanding of the molecular subtypes of melanoma increases, in the future it may be possible to predict which melanoma patients have a predilection to developing DMC. Mutation testing of DMC patients should be considered as BRAF inhibitors, and other novel targeted therapies may improve the bleak prognosis associated with this unusual presentation of metastatic melanoma.

Development of a quality-of-life instrument for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life questionnaire.

IMPORTANCE: Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. OBJECTIVE: To develop a QOL instrument specific to autoimmune bullous disease (AIBD). DESIGN: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. SETTING: Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. MAIN OUTCOMES AND MEASURES: The development of an AIBD-specific QOL instrument. RESULTS: Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). CONCLUSIONS AND RELEVANCE: The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. CLINICAL TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12612000750886.

Diagnosis and clinical features of pemphigus vulgaris.

Autoimmune bullous diseases are associated with autoimmunity against structural components that maintain cell-cell and cell-matrix adhesion in the skin and mucous membranes. They include those where the skin blisters at the basement membrane zone and those where the skin blisters within the epidermis (pemphigus vulgaris, pemphigus foliaceus, and other subtypes of pemphigus). The variants of pemphigus are determined according to the level of intraepidermal split formation. There are 5 main variants of pemphigus: pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, drug-induced pemphigus, and paraneoplastic pemphigus. This review focuses only on pemphigus vulgaris.

Diagnosis and clinical features of pemphigus vulgaris.

Autoimmune bullous diseases are associated with autoimmunity against structural components that maintain cell-cell and cell-matrix adhesion in the skin and mucous membranes. They include those where the skin blisters at the basement membrane zone and those where the skin blisters within the epidermis (pemphigus vulgaris, pemphigus foliaceus, and other subtypes of pemphigus). The variants of pemphigus are determined according to the level of intraepidermal split formation. There are 5 main variants of pemphigus: pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, drug-induced pemphigus, and paraneoplastic pemphigus. This review focuses only on pemphigus vulgaris.

Treatment of skin cancers in epidermolysis bullosa.

Squamous cell carcinomas (SCCs) are highly aggressive in patients with epidermolysis bullosa (EB). Non-ultraviolet-related SCCs are the leading cause of death in patients with recessive dystrophic EB, particularly recessive dystrophic EB-generalized severe subtype (RDEB-GS). The mechanism of SCC development in patients with RDEB continues to be investigated and several theories have been reported in the literature.

Responsiveness of nonHerlitz junctional epidermolysis bullosa to topical gentian violet.

BACKGROUND: Gentian violet (GV), a mixture of crystal violet and methyl violet, a dye belonging to the di- and triaminophenylmethanes class and has been widely used for its bactericidal and fungicidal properties. To date, there have been no reports of long-term therapeutic use of GV in epidermolysis bullosa (EB). METHODS: Two brothers with nonHerlitz junctional epidermolysis bullosa (JEB) aged 12 and 14 tried topical GV to one lower leg with conventional silicone dressings and this was compared with leaving the other leg with silicone dressings alone, over 4 weeks. Wounds were photographed and measured using Visitrak analysis. Pain, ooze, and appearance were assessed using visual analog scales (VAS) scales and Quality of life using Dermatology Life Quality Index and QOLEB (2) tools. RESULTS: The side treated with dressings and GV reduced to 14.9 cm(2) (-20.74%) and to 9.5 cm(2) (-56.62%) for dressings alone in the older brother (EB-012) and to 4.2 cm(2) (+20%) and 12.5 cm(2) (-7%) for the younger brother (EB-011) in ulcer size, respectively. Both patients did complain of stinging on the sites treated within a few days. QOL measures and VAS scores did not show any significant change. CONCLUSIONS: GV may be considered to be a therapeutic option for ulcers in nH-JEB patients and potentially other EB subtypes. A formal randomized controlled trial and long-term safety study of GV in EB is recommended.

Seasonal onychomadesis in an elderly gentleman.

A 79-year-old man with a history of dementia and hypertension initially presented with a ten year history of Beau's lines and seasonal nail shedding of his fingernails only. He denied any exposure to heavy metals, unusual activities or food. He stated that the seasonal nail shedding had been occurring for the last 5-10 years. On examination, six out of ten fingernails had been affected. He had significant toenail dystrophy. Fungal cultures and PAS staining of the toenails were negative. Routine serum biochemistry and haematology results were normal. Serum arsenic, cadmium and lead levels were also normal. Vitamin B12, zinc, folate, iron studies, thyroid function studies and homocysteine levels were also normal. Rheumatoid factor and anti-cyclic citrullinated peptide antibody antibodies were negative. Bilateral hand X-ray showed osteoarthritic change and did not show any features of psoriatic arthropathy. We discuss the case of a 79-year-old man with seasonal nail shedding, curiously affecting his fingernails only.