John W. Frew

Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument

Background  Epidermolysis bullosa (EB) has a profound effect on quality of life (QOL); however, generic QOL assessments are poor indicators of the impact of EB.

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.

Paraneoplastic Pemphigus (Paraneoplastic Autoimmune Multiorgan Syndrome): Clinical Presentations and Pathogenesis

Paraneoplastic pemphigus is a rare condition with extremely high rates of mortality. Although its pathogenesis is incompletely understood, its pathologic findings have significant overlap with other autoimmune blistering diseases, such as pemphigus vulgaris, bullous pemphigoid, erythema multiforme and erosive lichen planus. A universally accepted consensus definition is needed to firmly define the condition. This would aid in identification of paraneoplastic pemphigus and the institution of timely and appropriate treatment to avoid rapid patient deterioration as well as recruitment for trials to further examine the pathogenesis and new therapeutic modalities. This article reviews the varied clinical presentations and pathologic characteristics pertaining to paraneoplastic pemphigus.

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.

Quality-of-Life Measurement in Blistering Diseases

Both congenital and acquired bullous dermatoses have the potential to impose a significant burden of disease, and the impact exerted on the quality of life (QOL) of patients is often multifaceted. The qualitative and quantitative studies reviewing QOL in patients with bullous dermatoses have all reported a significant decrease in QOL scores compared with the greater population using a range of patient-based measures. Formal evaluation of QOL in the setting of bullous dermatoses facilitates the assessment of disease severity and mapping of disease trajectory and can capture outcomes of therapeutic intervention relevant to the patient.

Current Management Strategies in Paraneoplastic Pemphigus (Paraneoplastic Autoimmune Multiorgan Syndrome)

Paraneoplastic pemphigus (PNP) or paraneoplastic autoimmune multiorgan syndrome (PAMS) is a life-threatening autoimmune blistering disease commonly associated with lymphoproliferative neoplasms. This article focuses on current management strategies in PNP/PAMS, and reported instances of their treatment successes and failures. Due to the rarity of the condition and the high rates of treatment failure, no randomized control trials exist to guide the evidence-based treatment of this condition; all evidence to date on the efficacy of therapeutic modalities has been gained from individual case reports, small case series, and expert recommendations.

The development and validation of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease

Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment.

Quality of Life Measurements in Epidermolysis Bullosa: Tools for Clinical Research and Patient Care

Quality of life (QOL) evaluation in epidermolysis bullosa (EB) has important applications in clinical management, patient advocacy, clinical research, and the development of new treatments. Several new quantitative and qualitative QOL measurement tools were developed recently, providing insight into the impact EB has on individuals and their family members. Selection of the most appropriate QOL tool for patients who have EB depends on not only the type of information required but also the general or specific cohort being examined. EB-specific quantitative tools possess the highest level of content validity and statistical accuracy. However, generic dermatologic tools may also be appropriate in some circumstances. Overall, QOL evaluation in EB is still a developing area of research that may help improve patient management and assess emerging treatment modalities for their efficacy in improving the QOL of patients with EB.

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.

Evidence-based treatments in pemphigus vulgaris and pemphigus foliaceus.

Treatment modalities in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are many and varied, although level 1 evidence supporting their use is limited. To date, only 2 systematic reviews exist to support the use of different treatment modalities to control this group of conditions. Overall, within the literature, the quality of trials comparing treatment modalities is poor. Cohort sizes are small, methodologies are varied, and standardized outcome measurements are lacking. The authors aim to present a comprehensive view of the level 1 evidence that exists for common treatment modalities used in PV and PF.