Review of literature and clinical practice experience for the therapeutic management of Morgellons disease.

Morgellons disease (MD) is a rare and contentious health condition characterized by dermatological symptoms including slow-healing skin lesions 'attributed' to fibres emerging from or under the skin. Patients also report sensations of crawling, biting and infestation with inanimate objects. This review examines the aetiology, patient characteristics, epidemiology, historical context, correlation with Lyme disease, role of internet, impact on quality of life and treatment approaches for MD. Despite ongoing debate, MD is not officially recognized in medical classifications, with differing views on its aetiology. Some link MD to Lyme disease, while others view it as a variant of delusional infestation. The literature suggests both psychiatric and environmental factors may contribute. The manuscript explores the association with substance abuse, psychiatric comorbidities, infectious agents and the role of internet communities in shaping perceptions. MD's impact on quality of life is significant, yet often overlooked. Treatment approaches are varied due to limited evidence, with low-dose antipsychotics being considered effective, but patient beliefs may influence adherence. A patient-centred, multidisciplinary approach is emphasized, considering both the physical and psychological dimensions of MD. Addressing the controversies surrounding MD while focusing on patient well-being remains a critical challenge for healthcare professionals.

Lentigo maligna (melanoma): A systematic review and meta-analysis on surgical techniques and presurgical mapping by reflectance confocal microscopy.

Because of an increased risk of local recurrence following surgical treatment of lentigo maligna (melanoma) (LM/LMM), the optimal surgical technique is still a matter of debate. We aimed to evaluate the effect of different surgical techniques and reflectance confocal microscopy (RCM) on local recurrence and survival outcomes. We searched MEDLINE, Embase and PubMed databases through 20 May 2022. Randomized and observational studies with ≥10 lesions were eligible for inclusion. Bias assessment was performed using the Methodological Index for Non-Randomized Studies instrument. Meta-analysis was performed for local recurrence, as there were insufficient events for the other clinical outcomes. We included 41 studies with 5059 LM and 1271 LMM. Surgical techniques included wide local excision (WLE) (n = 1355), staged excision (n = 2442) and Mohs' micrographic surgery (MMS) (n = 2909). Six studies included RCM. The guideline-recommended margin was insufficient in 21.6%-44.6% of LM/LMM. Local recurrence rate was lowest for patients treated by MMS combined with immunohistochemistry (<1%; 95% CI, 0.3%-1.9%), and highest for WLE (13%; 95% CI, 7.2%-21.6%). The mean follow-up varied from 27 to 63 months depending on surgical technique with moderate to high heterogeneity for MMS and WLE. Handheld-RCM decreased both the rate of positive histological margins (p < 0.0001) and necessary surgical stages (p < 0.0001). The majority of regional (17/25) and distant (34/43) recurrences occurred in patients treated by WLE. Melanoma-associated mortality was low (1.5%; 32/2107), and more patients died due to unrelated causes (6.7%; 107/1608). This systematic review shows a clear reduction in local recurrences using microscopically controlled surgical techniques over WLE. The use of HH-RCM showed a trend in the reduction in incomplete resections and local recurrences even when used with WLE. Due to selection bias, heterogeneity, low prevalence of stage III/IV disease and limited survival data, it was not possible to determine the effect of the different surgical techniques on survival outcomes.

UV light set-ups for vitiligo photography, a comparative study on image quality and ease of use.

BACKGROUND: Ultraviolet (UV) light is an essential tool to assess the extent, spreading and staging of vitiligo. Different UV light set-ups are used for vitiligo photography, including the following: (i) hand-held Wood's lamps; (ii) soft boxes with UV lamps; (iii) UV flash attached to the camera; and (iv) high output UV flash. OBJECTIVE: Our objective was to compare UV light set-ups for vitiligo photography regarding image quality and ease of use. METHODS: Patients with vitiligo lesions with unclear borders were included. Two images were made with all four UV set-ups per patient, for a large and a small area. Image quality was scored separately by three blinded vitiligo experts on five criteria: overall quality, clearness of borders, contrast and sharpness and for larger areas the shadows. The two professional medical photographers were asked to score the ease of use for each set-up. RESULTS: A total of 88 photos were assessed from 11 patients. For larger areas, the frequency of a 'good' or 'very good' overall quality rating was 12.1% (Wood's), 6.1% (soft boxes), 15.2% (camera flash) and 78.8% (high output flash). For smaller areas, the score 'good' or 'very good' was given to 54.5%, 3%, 66.6% and 84.8% in the same order. For the shadow criteria, each set-up scored below 40% on a 'good' or 'very good' score. The high output flash was scored as most easy to use by the photographers. CONCLUSION: When comparing four different UV light set-ups for vitiligo photography, we concluded that the UV set-ups strongly influenced the quality scores of the obtained images. The high output flash scored best for both small and large areas and for ease of use. For small areas, Wood's lamp and camera flash were acceptable. All set-ups scored badly for shadows, and more research is needed to find the optimal exposure to avoid shadows.

The role of phototherapy in the surgical treatment of vitiligo: a systematic review.

Vitiligo is frequently treated with the combination of phototherapy and melanocyte transplantation. However, the additional benefit of phototherapy is unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The objective of this systematic review was to identify whether phototherapy improves the outcome of melanocyte transplantation in vitiligo. We searched and screened for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included all clinical studies investigating melanocyte transplantation combined with phototherapy. After screening and selection of abstracts and full-texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n = 19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy.

Interrater and intrarater agreement of confocal microscopy imaging in diagnosing and subtyping basal cell carcinoma.

BACKGROUND: Reflectance confocal microscopy (RCM) imaging can be used to diagnose and subtype basal cell carcinoma (BCC) but relies on individual morphologic pattern recognition that might vary among users. OBJECTIVES: We assessed the inter-rater and intrarater agreement of RCM in correctly diagnosing and subtyping BCC. METHODS: In this prospective study, we evaluated the inter-rater and intrarater agreement of RCM on BCC presence and subtype among three raters with varying experience who independently assessed static images of 48 RCM cases twice with four-week interval (T1 and T2). Histopathologic confirmation of presence and subtype of BCC from surgical excision specimen was defined as the reference standard. RESULTS: The inter-rater agreement of RCM for BCC presence showed an agreement of 82% at T1 and 84% at T2. The agreements for subtyping BCC were lower (52% for T1 and 47% for T2). The intrarater agreement of RCM for BCC presence showed an observed agreement that varied from 79% to 92%. The observed agreements for subtyping varied from 56% to 71%. CONCLUSIONS: In conclusion, our results show that RCM is reliable in correctly diagnosing BCC based on the assessment of static RCM images. RCM could potentially play an important role in BCC management if accurate subtyping will be achieved. Therefore, future clinical studies on reliability and specific RCM features for BCC subtypes are required.

Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown. OBJECTIVE: To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC. METHODS: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes. RESULTS: Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy. CONCLUSION: Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.

Autologous cell suspension grafting in segmental vitiligo and piebaldism: a randomized controlled trial comparing full surface and fractional CO2 laser recipient-site preparations.

BACKGROUND: Autologous noncultured cell suspension transplantation is an effective treatment for repigmentation in segmental vitiligo and piebaldism. Full surface laser ablation is frequently used to prepare the recipient site before cell suspension transplantation, even though the optimal laser settings and ablation depth are unknown. OBJECTIVES: To assess the efficacy and safety of less invasive recipient-site preparations. METHODS: In a randomized, observer-blinded, controlled trial we compared different recipient-site preparations before cell suspension transplantation in segmental vitiligo and piebaldism. In each patient, we randomly allocated three CO2 laser recipient-site preparations (209 and 144 µm full surface, and fractional) and a control (no treatment) to four depigmentations. After 6 months we assessed repigmentation and side-effects. RESULTS: We included 10 patients with vitiligo (n = 3) and piebaldism (n = 7). Compared with the control site, we found more repigmentation after full surface ablation at 209 µm (median 68·7%, P = 0·01) and 144 µm (median 58·3%, P = 0·007), but no repigmentation after fractional ablation (median 0·0%, P = 0·14). CONCLUSIONS: Superficial full surface ablation with a depth of 144 µm is an effective recipient-site preparation before cell suspension transplantation, while fractional CO2 laser is not.

One-stop-shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open-label, noninferiority, randomized controlled multicentre trial.

BACKGROUND: Routine punch biopsies are considered to be standard care for diagnosing and subtyping basal cell carcinoma (BCC) when clinically suspected. OBJECTIVES: We assessed the efficacy of a one-stop-shop concept using in vivo reflectance confocal microscopy (RCM) imaging as a diagnostic tool vs. standard care for surgical treatment in patients with clinically suspected BCC. METHODS: In this open-label, parallel-group, noninferiority, randomized controlled multicentre trial we enrolled patients with clinically suspected BCC at two tertiary referral centres in Amsterdam, the Netherlands. Patients were randomly assigned to the RCM one-stop-shop (diagnosing and subtyping using RCM followed by direct surgical excision) or standard care (planned excision based on the histological diagnosis and subtype of a punch biopsy). The primary outcome was the proportion of patients with tumour-free margins after surgical excision of BCC. RESULTS: Of the 95 patients included, 73 (77%) had a BCC histologically confirmed using a surgical excision specimen. All patients (40 of 40, 100%) in the one-stop-shop group had tumour-free margins. In the standard-care group tumour-free margins were found in all but two patients (31 of 33, 94%). The difference in the proportion of patients with tumour-free margins after BCC excision between the one-stop-shop group and the standard-care group was -0·06 (90% confidence interval -0·17-0·01), establishing noninferiority. CONCLUSIONS: The proposed new treatment strategy seems suitable in facilitating early diagnosis and direct treatment for patients with BCC, depending on factors such as availability of RCM, size and site of the lesion, patient preference and whether direct surgical excision is feasible.

Patients with lichen sclerosus experience moderate satisfaction with treatment and impairment of quality of life: results of a cross-sectional study.

BACKGROUND: Although they are considered relevant, little is known about satisfaction with treatment and health-related quality of life (HRQoL) among patients with lichen sclerosus (LS). OBJECTIVES: In a cross-sectional study, we aimed to examine (i) satisfaction with treatment, (ii) patient characteristics associated with satisfaction and (iii) HRQoL in Dutch patients with LS. METHODS: Members of the Dutch LS Patient Association (n = 750) were invited to complete a web-based survey. We measured satisfaction with treatment with a study-specific questionnaire, and HRQoL with the Skindex-29. We calculated domain scores for symptoms, emotions and functioning, and categorized scores into little, mildly, moderately or severely impaired HRQoL. We used a multiple linear regression analysis to examine whether patient characteristics were associated with treatment satisfaction. RESULTS: In total 303 patients (40·4%) were included. Patients under current treatment (n = 265, 87·5%) were moderately satisfied with their treatment. Patients rated 'treatment effectiveness' as most important, although 58 (22%) were dissatisfied with the effectiveness of their current treatment. More impairment on the HRQoL emotions domain and a higher degree of disease severity were both associated with lower satisfaction with treatment and explained in total 13·5% of the variance in treatment satisfaction. On all HRQoL domains, one-third of the patients (range 34·7-38·9%) reported severe impairment. CONCLUSIONS: Patients with LS are moderately satisfied with their treatment, and one-third of patients experience severe impairment of HRQoL. To improve dermatological care, we recommend enhancement of doctor-patient communication, information provision and organization, which may be more amenable to change than treatment effectiveness or safety.

Focal vitiligo: long-term follow-up of 52 cases.

BACKGROUND: Focal vitiligo is characterized by depigmented patches located in a small area without a typical segmental distribution. Focal vitiligo is classified as an undetermined type of vitiligo, and a more definitive diagnosis can be made when the lesions have not evolved into non-segmental or segmental vitiligo after a period of 1-2 years. However, the chance of progression is not known and may lead to treatment-indecision. OBJECTIVE: The objective was to study the characteristics of patients with focal vitiligo and possible predictors of progression. METHODS: We conducted a survey study in patients with initial diagnosis of focal vitiligo between January 2005 and June 2010. Focal vitiligo was defined as either a small acquired isolated depigmented lesion without typical segmental distribution, or two to three small acquired lesions localized in a non-segmental area with a maximum of 5 cm. The survey comprised of 21 questions concerning the patient's characteristics, the onset of focal vitiligo, progression of depigmentation and treatment history. RESULTS: We identified 128 eligible patients and the response rate was 40.6% (n = 52 completed questionnaires). Progression to non-segmental vitiligo occurred in 23%. The median follow-up duration was 7 years. In 11.5% of the patients, progression to non-segmental vitiligo occurred within 2 years after onset. Nevertheless, even after a first stable period of more than 2 years, another 11.5% of the patients advanced to non-segmental vitiligo. No associated prognostic factors at baseline of progression to non-segmental or long-lasting focal vitiligo were found. CONCLUSION: Focal vitiligo is a rare subtype of vitiligo and most patients have long-lasting focal lesions after onset of the disease. In this study, focal vitiligo progressed to typical non-segmental vitiligo, but not towards typical segmental vitiligo. Progression 2 years after onset of focal vitiligo, occurs in 50% of the patients with eventual progression to non-segmental vitiligo. There seem to be no clinical signs that predict progression in focal vitiligo.

In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy.

Basal cell carcinoma (BCC) is the most prevalent type of skin cancer. Histologic analysis of punch biopsy or direct excision specimen is used to confirm clinical diagnosis. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging modality that could facilitate early diagnosis and minimize unnecessary invasive procedures. We systematically reviewed diagnostic accuracy (sensitivity and specificity) of RCM in diagnosing primary BCCs to judge its usefulness. Eligible studies were reviewed for methodological quality using the QUADAS-2 tool. We used the bivariate random-effects model to calculate summary estimates of sensitivity and specificity. Six studies met the selection criteria and were included for analysis. The meta-analysis showed a summary estimate of sensitivity 0.97 (95% CI, 0.90-0.99) and specificity 0.93 (95% CI, 0.88-0.96). All but one of the QUADAS-2 items showed a high or unclear risk of bias with regards to patient selection. RCM may be a promising diagnostic tool, but the limited number of available studies and potential risk of bias of included studies do not allow us to draw firm conclusions. Future accuracy studies should take these limitations into account.

Consumer Quality Index Chronic Skin Disease (CQI-CSD): a new instrument to measure quality of care from the patient's perspective.

BACKGROUND: Assessing quality of care from the patient's perspective is considered to be highly relevant. As a standardized instrument in dermatology was lacking, we developed a patient experience questionnaire regarding chronic skin disease care: the Consumer Quality Index Chronic Skin Disease (CQI-CSD). OBJECTIVES: (i) To evaluate the dimensional structure of the CQI-CSD, (ii) to assess its ability to distinguish between hospitals according to patients' experiences with quality of care, (iii) to explore patients' experiences with dermatological care and priorities for quality improvement according to the patients, and (iv) to optimize the questionnaire based on psychometric results and stakeholders' input. METHODS: In a cross-sectional study 5647 adult patients who received dermatological care in the past 12 months in 20 hospitals were randomly selected and invited to fill out the questionnaire. RESULTS: Overall 1160 of 3989 eligible respondents (29% response rate, 30-87 per hospital) were included for analysis. The CQI-CSD comprised seven scales with high internal consistency (Cronbach's α = 0·74-0·92). The instrument's discriminative power was limited. Patients were positive about the care provided by nurses and doctors, but the provision of information by healthcare providers, accessibility of care and patient involvement could be improved. We optimized the CQI-CSD, resulting in a revised questionnaire containing 65 items. CONCLUSIONS: In conclusion, the CQI-CSD is a useful instrument to measure patient experiences with dermatological care.

The validity, reliability and acceptability of the SAVASI; a new self-assessment score in vitiligo.

BACKGROUND: Vitiligo is a common depigmenting skin disorder that can influence a patient's quality of life. Although patient-orientated medicine is an emerging concept, a self-assessment tool to assess the degree of depigmentation in vitiligo is not yet available. Therefore, we developed the SAVASI, a self-assessment tool that uses the same basic principles as the VASI. OBJECTIVE: To assess the validity, reliability and acceptability of the SAVASI. METHODS: To assess the validity of the SAVASI, we compared the scores assessed by the patient with the scores of the VASI assessed by the physician. To assess the intra-rater reliability, the correlation between the baseline SAVASI and the SAVASI after 2 weeks was calculated. To assess the acceptability, patients indicated the time needed to complete the SAVASI and the patient assessed the difficulty of the questionnaire on a five-point scale. The Skindex-29 was used to determine the quality of life. The overestimation of the SAVASI compared to the VASI was calculated by subtracting the VASI scores off from the SAVASI scores. RESULTS: A high correlation between the VASI and the SAVASI (ICC 0.97, 95% CI: 0.95-0.98) was found in 60 patients. The intra-rater reliability of the SAVASI (ICC 0.75, 95% CI 0.54-0.87) was adequate in 31 patients. Fifty (83%) of the patients completed the questionnaire within 10 min and only five (8%) of the patients considered the SAVASI hard. We found no correlation between overestimation of the SAVASI score and the Skindex-29 score. CONCLUSION: The SAVASI is a valid, reliable and acceptable self-assessment tool to measure the degree of depigmentation in vitiligo. With the SAVASI the degree of depigmentation can reliably be assessed by the patient themselves which can be useful in large (epidemiological) studies. Furthermore, this could contribute to the patient's disease insight and therapy loyalty.

Vitiligo Area Scoring Index and Vitiligo European Task Force assessment: reliable and responsive instruments to measure the degree of depigmentation in vitiligo.

BACKGROUND: Vitiligo is a common skin disorder causing depigmented macules that can impair a patient's quality of life. Currently, there are no standardized outcome measures to assess the degree of depigmentation. Moreover, there is limited knowledge on the measurement properties of outcome measures in vitiligo. OBJECTIVES: To assess the reliability and responsiveness of the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force assessment (VETFa), two well-described clinician-reported outcomes. METHODS: We included three vitiligo patient groups. In one group of 31 patients, the interobserver reliability was assessed by three observers. In 27 patients the intraobserver reliability was assessed by two repeated measures by one of the observers. To assess the responsiveness the repigmentation was calculated after 6 months of phototherapy in 33 patients and tested against hypotheses. RESULTS: The interobserver reliability was high for VASI [intraclass correlation coefficient (ICC) 0·93] and VETFa depigmentation (ICC 0·88). The intraobserver reliability was high for VASI (ICC 0·93) and VETFa depigmentation (ICC 0·97). The smallest detectable changes (SDCs) were 7·1% and 10·4% for interobserver reliability and 4·7% and 2·9% for intraobserver reliability in VASI and VETFa depigmentation, respectively. All four responsiveness hypotheses formulated a priori were confirmed. CONCLUSIONS: VASI and VETFa are reliable and responsive instruments to assess the degree of depigmentation in vitiligo. VASI and VETFa for depigmentation are potential instruments for vitiligo research in the future. However, for use in individual patient care, caution is needed when interpreting score changes in individual patients because of the relatively large SDC.

Drug survival is not significantly different between biologics in patients with psoriasis vulgaris: a single-centre database analysis.

BACKGROUND: Drug survival depends on several factors such as dosing, effectiveness, quality-of-life improvement and safety, and could be seen as an overall marker for treatment success. Such data for biologics in psoriasis treatment are sparse. OBJECTIVES: To determine differences in drug survival between different biologics for psoriasis. METHODS: Drug survival, dosing, Psoriasis Area and Severity Index (PASI) and Skindex-29 at weeks 12 and 52, and adverse events of patients with psoriasis treated with a biologic registered in the local database of the Academic Medical Center, Amsterdam, were analysed. Patients were divided into those naive or non-naive for treatment episodes with biologics. RESULTS: Drug survival did not differ significantly for naive treatment episodes between the biologics (etanercept 85% to 64%, adalimumab 77% to 77%, infliximab 75% to 75% for year 1-4), or for non-naive treatment episodes (etanercept 86% to 42%, adalimumab 84% to 56%, infliximab 68% to 43% for year 1-4; ustekinumab 84% to 57% for year 1-3). The naive group showed better drug survival and PASI 75 response at week 12, although the difference was not significant. A similar improvement of mean ∆PASI and mean ∆Skindex-29 was observed at weeks 12 and 52 for all biologics for both groups, although no significant difference was seen between groups. Treatment termination was due mainly to nonresponse for all biologics. CONCLUSIONS: There was no significant difference in drug survival, mean ∆PASI or Skindex-29 response at weeks 12 or 52 between the biologics or between the naive and non-naive groups. Treatment termination was due mostly to nonresponse. Sequential treatment with the available biologics can be effective.