Evaluation and treatment of vitiligo

This thesis considers several aspects of vitiligo; it investigates (i) provoking factors of vitiligo, (ii) the prevalence of thyroid disease, (iii) the efficacy and safety of autologous punch- and cell suspension grafting and (iv) measurement properties of outcome measures for vitiligo. Chapter 2.1 is a retrospective cohort study and gives insight in the patient reported provoking factors of vitiligo including contact with chemicals. In Chapter 2.2 the role of 4-TBP as provoking factor for vitiligo was analysed in a patient with chemically induced contact vitiligo. In Chapter 3.1 current evidence of the prevalence of thyroid diseases in vitiligo is summarised and critically appraised in a systematic review. We found an increased prevalence and an increased risk of (autoimmune) thyroid disease in patients with vitiligo patients compared to non-vitiligo. In Chapter 4.1 the efficacy and safety of different punch depths and punch sizes in autologous punch grafting is compared in an observer blinded randomised controlled trial. We show that 1.5 mm superficial grafts are most beneficial and could be recommended to use in autologous punch grafting in patients with stable vitiligo and piebaldism. Chapter 4.2 determines the efficacy and safety of cellsuspension grafting with a cell harvesting divice (CST-CHD) in vitiligo and piebaldism. The CST-CHD method is found to be an effective, safe and relatively simple technique for CST that allows for the complete transplantation in the operation theatre. Chapter 5 presents the results of a systematic review on outcome measures for vitiligo using the COSMIN checklist. We found that current evidence is insufficient owing to a low number of studies with a poor methodological quality and unclear clinical relevance

Ablative 10,600 nm fractional laser for the treatment of scars

Background: Pathologic scars such as hypertrophic or atrophic scars can be highly disfiguring and could have major psychological impact. These scars remain a challenging problem as current available therapies often fail to improve them. Ablative fractional laser therapy (AFLT) is a new treatment modality and is expected to improve scars. The aim of this study is to assess the efficacy and safety of AFLT for the treatment of atrophic and hypertrophic scars. Methods: In a prospective single blinded randomized controlled split lesion trial twenty-one adult patients with hypertrophic or atrophic scars of 1 year or older and Fitzpatrick skin types I-IV were included. AFLT involved three sessions with an interval of 8 weeks. Blinded on-site evaluations were done at every treatment session and 2 months after the final treatment. Primary endpoints were the Physicians Global Assessment (0-3 categorical scale), the Patients Global Assessment (0-3 categorical scale) and the melanin- and erythema index. Secondary endpoints were the Clinical assessment of particular items of the scar (0-3 categorical scale) and adverse events. Results: Because of delay, the study is still running and preliminary results of one laser treatment of 15 patients were available for analysis and are presented in this paper. A significant difference of the PhGA was found between baseline and 8 weeks post treatment (p=0.025). No significant differences were found on the PGA and Clinical Assessment. Both hyperpigmented and hypopigmented scars showed an unfavorable increase of melanin index. In the intervention group the erythema index significantly increased 8 weeks post treatment (p=0.013). Adverse events reported by patients themselves showed 87% erythema, 40% burning, 40% edema, 47% vesicles, 60% crusting, 40% itching and 20% oozing. Five patients reported long lasting eythema, still present 8 weeks post treatment. The physician reported adverse events showed 31% hyperpigmentations and 46% erythema and no hypopigmenations and scar formations. Conclusion: Ablative 10,600 nm fractional laser therapy after one laser treatment is little efficacious and has a considerable risk of erythema and hyperpigmentation. However, no definitive conclusions about the efficacy of AFLT for the treatment of scars can be drawn as preliminary results of one treatment were analysed. The results after the second and third treatment are needed to draw these conclusions. In addition, AFLT is not as safe as expected as more and long term side effects were reported and objectified. Therefore, caution is urged when treating scars with AFLT. Future research of high quality is necessary to strengthen the evidence of the efficacy and safety of AFLT.

Laser and intense pulsed light therapy for the treatment of hypertrophic scars: a systematic review

Hypertrophic scars are difficult to improve and remain a therapeutic challenge. Several lasers and light sources have been evaluated in the past decades and have been shown to improve hypertrophic scars. However, a systematic review is not available. To assess current evidence of efficacy of all laser and intense pulsed light therapies used in the treatment of hypertrophic scars, we performed a systematic review searching electronic databases MEDLINE, EMBASE and CENTRAL. The quality of the controlled clinical trials was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Thirteen articles involving seven different lasers met the inclusion criteria. Most evidence was found for the pulsed dye laser (PDL) 585 nm (eight studies), followed by the PDL 595 nm (two studies), whereas limited evidence (one trial per laser) was available for the fractional nonablative laser 1540 nm, CO₂ laser 10,600 nm, low-level laser therapy, Nd:YAG laser 532 nm and Erbium:YAG laser 2940 nm. Treatment recommendations should be formulated with caution as current evidence is insufficient for comparing the efficacy of different laser therapies. The PDL 585 nm showed a low efficacy for the treatment of hypertrophic scars. With moderate efficacy, the PDL 595 nm is promising, although more research is necessary. Little evidence was found for the efficacy of other lasers. Future research, with a low risk of bias, well-defined scar characteristics, validated outcome measures, standardized measurement methods, follow-up periods of at least 6 months and well-defined laser settings, is neede

The prevalence of thyroid disease in patients with vitiligo: a systematic review

Background Thyroid disease has been suggested to be associated with vitiligo. However, the outcomes of prevalence studies on thyroid disease in vitiligo vary widely. Objectives To summarize and critically appraise current evidence of the prevalence of thyroid diseases in vitiligo. Methods A systematic review was performed searching the electronic databases OVID MEDLINE, OVID EMBASE and PubMed. Guidelines for the critical appraisal of studies on prevalence of a health problem were adapted to evaluate the methodological quality of the included studies. Results were analysed in a meta-analysis with a risk ratio (RR). Results Forty-eight studies published between 1968 and 2012 met the inclusion criteria. Most of the studies (50%) were of fair methodological quality, whereas 18 studies (38%) were of poor quality and six studies (12%) were of good quality. Thyroid disease, autoimmune thyroid disease and presence of thyroid-specific autoantibodies showed a mean prevalence of, respectively, 15.1%, 14.3% and 20.8% in patients with vitiligo and an RR of, respectively, 1.9, 2.5 and 5.2 (all statistically significant). This review shows an increased prevalence and an increased risk of (autoimmune) thyroid disease in patients with vitiligo compared with nonvitiligo. This risk seems to increase with age. Conclusions Clinicians should be aware of this increased risk in patients with vitiligo and should be attentive for symptoms of thyroid disease. To make recommendations on screening for thyroid disease in patients with vitiligo future research of good methodological quality, including differentiation of vitiligo types and the use of standardized outcome measures, is neede