Patients' perspective, quality of life and treatment goals in Hailey-Hailey disease: Lessons learned from the German National Registry.

BACKGROUND: Hailey-Hailey disease (HHD) remains a difficult-to-treat dermatosis and little is known about the patient's perception of the disease activity, the treatment success and its impact on quality-of-life (QoL). OBJECTIVE: To obtain better understanding of HHD patients' needs regarding their medical condition, financial burden, QoL, subjective well-being and treatment thereof as well as satisfaction to evaluate common treatments' 'real-life' relevance. METHODS: With initiation of the national registry for Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH) MDHHgermany, patients with HHD diagnosis were included starting June 2020. To assess subjective symptoms, patients filled out questionnaires such as the DLQI (dermatological life quality index), numeric rating scale (NRS) for itch, pain and burning sensation, as well as the SWLS (satisfaction with life scale) questionnaire to quantify overall satisfaction in life. Additionally, data on therapies were collected along with the patients' satisfaction of those and their medical care. Furthermore, patients assessed financial aspects and work ability. RESULTS: One hundred and two patients were recruited from dermatology clinics, office-based dermatologists and self-help platforms across Germany between June 2020 and February 2023, 90 were eligible and analysed (mean: 49.91 years, 73.33% females, 26.67% males). 39.77% stated according to the DLQI their life is severely/very severely affected. Satisfaction with life was mediocre. Burning sensation was most pronounced among subjective symptoms (NRS 5.85 ± 2.80). Systemic treatments were rated as ineffective according to 56.92%, 25.56% had never received one. Most prescribed systemic treatments were corticosteroids (73.8%), followed by low-dose naltrexone (LDN) (26.2%), retinoids (15.4%) and antibiotics (13.8%). Satisfaction with medical care was generally low. CONCLUSION: Our 'real-life' data state a major disease burden and impact on the QoL for affected individuals, as well as limited disease control due to inadequate therapies. MDHHgermany can provide insights into improvement of healthcare support with this debilitating disease and improve QoL. In the long term, it aims to provide basis for further clinical trials, epidemiological studies and immunological investigations.

Bone density in youth with prediabetes: results from the National Health and Nutrition Examination Survey, 2005-2006.

Youth with type 2 diabetes might have suboptimal peak bone mass, but it is unknown whether similar effects are evident in youth with prediabetes. Results from this study suggest that diabetes-related effects on peak bone mass likely occur before disease onset, and involve the muscle-bone unit. INTRODUCTION: Type 2 diabetes might adversely influence bone health around the age of peak bone mass, but it is unknown whether diabetes-related effects on areal bone mineral density (aBMD) are evident in youth with prediabetes. We compared age-related trends in aBMD and associations between lean body mass (LBM) and aBMD between children and adolescents with prediabetes vs. normal glucose regulation. METHODS: Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (2005-2006) in youth ages 12-20 years (49% female, 34% black) with prediabetes (n = 267) and normal glucose regulation (n = 1664). Whole body aBMD and LBM were assessed via DXA. LBM index (LBMI) and Z-scores for aBMD and LBMI were computed. RESULTS: Unadjusted between-group comparisons revealed greater mean weight and LBMI Z-scores in youth with prediabetes vs. normal glucose regulation, but similar bone Z-scores between the two groups. While accounting for differences in BMI Z-score, there was a significant interaction between prediabetes status and age with respect to whole body aBMD Z-score (P < 0.05), such that children with prediabetes tended to have increased aBMD but adolescents and young adults with prediabetes tended have lower aBMD. Furthermore, the positive association between LBMI and whole body aBMD was moderated in youth with prediabetes (P < 0.001), who had slightly lower whole body aBMD for a given LBMI (P = 0.068). Lumbar spine bone measures did not differ between the two groups. CONCLUSIONS: Type 2 diabetes-related threats to peak bone mass might occur prior to disease onset, therefore potentially impacting a considerable proportion of US youth.

[Confocal line-field OCT]. / Konfokale Line-Field-OCT.

Optical coherence tomography (OCT) and confocal laser microscopy (CLSM) are established non-invasive methods in clinical dermatological routine diagnosis. Whereas CLSM is especially useful to distinguish between nevi and melanoma, OCT is suitable for the diagnosis and differentiation of non-melanoma skin cancer. Line-field confocal optical coherence tomography (LC-OCT) is a new innovative device, which has better cellular resolution than OCT and a higher penetration depth than CLSM. Similar to CLSM, LC-OCT also allows 3D images in real time to be taken. Therefore LC-OCT is very useful for the examination of skin lesions of all kinds, since it unites the features of CLSM and OCT.

Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM: To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION: LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

[Cancer-associated genodermatoses]. / Tumorassoziierte Genodermatosen.

Hereditary tumor syndromes are characterized by a familial occurrence of tumors/cancer. A hereditary tumor syndrome should be suspected if a familial occurrence of cancer is seen and/or persons at younger age are affected. Some of the currently known tumor syndromes are associated with specific skin symptoms that can aid the physician in establishing the correct diagnosis. Examples are fibrofolliculoma in Birt-Hogg-Dubé syndrome, epidermal cysts, sebaceous cysts, neurofibroma in Gardner syndrome and sebaceous neoplasms or keratoacanthoma in Muir-Torre syndrome. If a genetic tumor syndrome is suspected, genetic testing and counselling should be performed in the index patient and is also recommended for family members. Affected patients should be offered regular clinical surveillance by the appropriate medical disciplines. Since curative therapy does not exist so far, preventive screening is of great importance.

Delayed diagnosis of Birt-Hogg-Dubé syndrome due to marked intrafamilial clinical variability: a case report.

BACKGROUND: Birt-Hogg-Dubé syndrome is a genetic syndrome caused by mutations in the FLCN gene. The main symptoms are lung bullae and pneumothorax, benign and malignant kidney tumors, and facial fibrofolliculoma. The risk of pneumothorax is considerable between ages 20-40 years, but decreases markedly after this age range and first-time pneumothorax after age 50 years is rare. Fibrofolliculomas usually occur between ages 35 and 45 years, while the risk for kidney cancer increases steadily with age, starting in young adulthood. However, we demonstrate here that within the same family patients might develop symptoms significantly before or after the usual age range, obscuring the typical clinical pattern and delaying diagnosis. CASE PRESENTATION: The 43 year old index patient had a history of lung bullae and recurrent pneumothoraces starting 14 years earlier. His father (age 83 years) and one of the paternal uncles experienced their first pneumothorax unusually late after the age of 60 years. The uncle subsequently had four more pneumothoraces, and was diagnosed with kidney in his early 70s. Considerable differences in age of onset were also observed with regard to facial fibrofolliculomas that both paternal uncles developed very early around age 20 years, but which the father only started to show in his eighth decade. Birt-Hogg-Dubé syndrome was finally diagnosed when the index patient started to develop fibrofolliculomas within the typical age range. CONCLUSIONS: The family described here illustrates that Birt-Hogg-Dubé syndrome can be difficult to recognize, if presenting with considerable intrafamilial clinical variability. With a life-time kidney cancer risk of about 14-35% the consequences of delayed diagnosis might be grave for the affected family members. The possibility of Birt-Hogg-Dubé syndrome should therefore be taken into consideration in apparently sporadic patients presenting with lung bullae and pneumothorax.

Optical coherence tomography of basal cell carcinoma: influence of location, subtype, observer variability and image quality on diagnostic performance.

BACKGROUND: We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here. OBJECTIVES: To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes. METHODS: A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion. RESULTS: Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required. CONCLUSION: OCT is useful in the diagnosis of BCC.

The impact of sentinel node dissection on disease-free and overall tumour-specific survival in melanoma patients: a single centre group-matched analysis of 1192 patients.

BACKGROUND: Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence, removal of potential lymph node micrometastasis will alter survival outcome. OBJECTIVE: The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus SLND group to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma. METHODS AND MATERIALS: A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumour thickness and localization of primary tumour. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in; and hence, subject to change over time. RESULTS: Kaplan-Meier testing revealed significant differences in survival in favour of the SLND group. Mean overall tumour-specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group respectively (P-value: 0.024). Disease-free survival (log-rank test: 0.003) and time to lymph node progression (P-value: <0.01) also differed significantly between the two groups. CONCLUSION: SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumour-specific survival of melanoma patients.

Morphologic features of basal cell carcinoma using the en-face mode in frequency domain optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has become a valuable non-invasive tool in the in vivo diagnosis of non-melanoma skin cancer, especially of basal cell carcinoma (BCC). Due to an updated software-supported algorithm, a new en-face mode - similar to the horizontal en-face mode in high-definition OCT and reflectance confocal microscopy - surface-parallel imaging is possible which, in combination with the established slice mode of frequency domain (FD-)OCT, may offer additional information in the diagnosis of BCC. OBJECTIVES: To define characteristic morphologic features of BCC using the new en-face mode in addition to the conventional cross-sectional imaging mode for three-dimensional imaging of BCC in FD-OCT. METHODS: A total of 33 BCC were examined preoperatively by imaging in en-face mode as well as cross-sectional mode in FD-OCT. Characteristic features were evaluated and correlated with histopathology findings. RESULTS: Features established in the cross-sectional imaging mode as well as additional features were present in the en-face mode of FD-OCT: lobulated structures (100%), dark peritumoral rim (75%), bright peritumoral stroma (96%), branching vessels (90%), compressed fibrous bundles between lobulated nests ('star shaped') (78%), and intranodular small bright dots (51%). These features were also evaluated according to the histopathological subtype. In the en-face mode, the lobulated structures with compressed fibrous bundles of the BCC were more distinct than in the slice mode. CONCLUSION: FD-OCT with a new depiction for horizontal and vertical imaging modes offers additional information in the diagnosis of BCC, especially in nodular BCC, and enhances the possibility of the evaluation of morphologic tumour features.

Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin.

OBJECTIVES: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. METHODS: 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. RESULTS: The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. CONCLUSION: This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Optical coherence tomography of actinic keratoses and basal cell carcinomas - differentiation by quantification of signal intensity and layer thickness.

BACKGROUND: Previous studies have shown that actinic keratoses (AKs) and basal cell carcinomas (BCCs) can be diagnosed by optical coherence tomography (OCT) based on morphological characteristics. There is a lack of systematic studies that give standardized information on signal intensity and layer thickness of AKs and BCCs. OBJECTIVE: The aim of this study was to find out if AKs and BCCs can be objectively diagnosed through standardized measurement of signal intensity and layer thickness and to use OCT as a non-invasive objective method for the diagnosis and evaluation of AKs and BCCs. Additionally, tumour and skin layer thickness were investigated in correlation with histology. METHODS: In this experimental study, 301 lesions (188 BCCs and 113 AKs) of 125 patients were clinically as well as dermoscopically diagnosed and investigated with OCT before therapy. Normal perilesional skin served as control. RESULTS: It is possible to differentiate BCCs and AKs from normal skin in OCT due to the decrease of local signal intensity in affected skin layers in relation to adjacent healthy skin. In AKs, a strong thickness increase of the stratum corneum and epidermis compared to normal skin were observed. For the distinction between AKs and BCCs, a drop of signal intensity in the dermis of AKs towards BCCs and a thicker epidermis of AKs in contrast to BCCs were registered. All results are statistically highly significant (P < 0.0001). Besides, a strong correlation of tumour and skin layer thickness of BCCs and AKs in OCT with histology was found. CONCLUSION: Through standardized measurement of signal intensity and layer thickness, BCCs and AKs can be objectively diagnosed and distinguished from each other with OCT. This will further improve the use of OCT as a non-invasive objective method for the diagnosis and treatment monitoring of these diseases.

Comparison of different optical coherence tomography devices for diagnosis of non-melanoma skin cancer.

PURPOSE: To compare the diagnostic imaging ability of three different optical coherence tomography (OCT) devices in non-melanoma skin cancer (NMSC). METHODS: Thirty actinic keratoses (AKs) and 27 basal cell carcinomas (BCCs) of 29 patients were examined with three different OCT devices, VivoSight® , Callisto® and Skintell® . RESULTS: Complete data sets were available for 16 BCCs and 10 AKs of 18 patients. All OCT devices were able to discriminate BCCs and AKs significantly from perilesional normal skin due to lower signal intensities as well as a thicker stratum corneum and epidermis in AKs. A significant decrease in the signal intensity and thickness of all skin layers was noted with Skintell® in contrast to VivoSight® and Callisto® . OCT comparisons revealed only slight differences between VivoSight® and Callisto® . Regarding BCC tumor thickness VivoSight® and Callisto® correlated well, histology did not correlate with the three OCT devices, whereas Skintell® showed no correlation with VivoSight® , Callisto® or histology. CONCLUSION: All tested OCT devices could identify BCCs and AKs objectively through standardized measurement of signal intensity and skin layer thickness. Due to their technical specifications (resolution, penetration depth), each of the OCT systems offers additional and special information on NMSC.

The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study.

BACKGROUND: The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown. OBJECTIVES: To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions. METHODS: This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis. RESULTS: Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P < 0·001). The positive predictive value for the diagnosis of BCC using OCT was 85·2% [95% confidence interval (CI) 78·6-90·4], and the negative predictive value was 92·1% (95% CI 83·6-97·0). The accuracy of diagnosis for all lesions increased from 65·8% with clinical evaluation to 76·2% following additional dermoscopy and to 87·4% with the addition of OCT. CONCLUSIONS: OCT significantly improved the diagnostic specificity for BCC compared with clinical assessment and dermoscopy alone.

Reflectance confocal microscopy for monitoring the density of Demodex mites in patients with rosacea before and after treatment.

BACKGROUND: Demodex mites seem to serve as a pathogenic trigger in many Demodex-associated diseases such as rosacea. In facial skin of patients with rosacea significantly higher numbers of Demodex mites have been shown compared with healthy controls. Reflectance confocal microscopy (RCM) allows the detection and quantification of Demodex mites in vivo noninvasively. It is hypothesized that a reduction of Demodex mites under rosacea therapy can be monitored by RCM. OBJECTIVES: To use RCM to monitor the density of Demodex mites in patients with rosacea before and after treatment. METHODS: In 25 patients with facial rosacea RCM was performed before and after therapy. Mosaics of 5 × 5 mm(2) and 8 × 8 mm(2) were scanned, and the total numbers of mites per follicle and per area were counted, along with the number of follicles per area. RESULTS: In all patients Demodex folliculorum could be detected and quantified using RCM. RCM showed significant differences pre- and post-treatment (P = 0.0053 for 5 × 5 mm(2) and P < 0.001 for 8 × 8 mm(2)). The mean numbers of mites per follicle were 0.63 (range 0.16-2.28) per 8 × 8 mm(2) area and 0.70 (range 0.11-2.20) per 5 × 5 mm(2) area before treatment, and 0.41 (range 0.074-1.75) and 0.51 (range 0.094-1.70), respectively, after treatment. The corresponding mean numbers of mites were 155 (range 45-446) and 86.2 (range 12-286), respectively, before treatment and 96.2 (range 18-363) and 58.5 (range 12-230), respectively, after treatment. CONCLUSIONS: By RCM, a reduction in the density of Demodex mites in facial skin of patients with rosacea under therapy, correlating to clinical improvement, can be quantified and monitored noninvasively. Possible reasons for this therapeutic effect are discussed.