A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway.

BACKGROUND AND OBJECTIVES: Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist setmelanotide in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with setmelanotide, changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. METHODS: In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist setmelanotide. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. RESULTS: We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of setmelanotide treatment. DISCUSSION: Setmelanotide treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

Hair shaft abnormalities in alopecia areata evaluated by optical coherence tomography.

BACKGROUND/PURPOSE: Optical coherence tomography (OCT) is able to provide highly reproducible measurements of hair shaft thickness, including hair shaft diameter, cross-sectional surface area and hair shape, similar to histology but in vivo. Variations in the caliber of hair shafts have been described in patchy hair loss like alopecia areata (AA) using electron microscopy. The aim of this study was to evaluate whether OCT is useful for the evaluation of hair shaft abnormalities in AA. METHODS: The measurements were performed on patients with AA (n=9), aged 2-66 years. Fifty hairs from the border of an alopecic area and 50 hairs from an unaffected area without hair loss were examined using the OCT technique. The hair parameters were characterized by the cross-section (CS) and the form factor. The ratio of the maximal and minimal diameters of the hair at a fixed measuring distance from the scalp surface determined the form factor (d(max)/d(min)). RESULTS: In all cases, the CS of hairs from an AA patch was significantly lower compared with hairs of an unaffected area. However, the form factor did not indicate any disturbances in hair growth. CONCLUSIONS: The results demonstrate that structural abnormalities of hair shafts are found in active lesions of AA, but not in clinically unaffected hairs. The OCT technique is a promising method to gain more insight into the pathogenesis of AA in a non-invasive way.

MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.

Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to severe obesity. Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight over an observation period of 45-61 weeks. Compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling pathway for selected MC4R variants. Our data demonstrate the potency of setmelanotide in treatment of individuals with diverse MC4R-related pathway deficiencies.

The effectiveness of standardized skin care regimens on skin dryness in nursing home residents: A randomized controlled parallel-group pragmatic trial.

BACKGROUND: Aged residents of institutional long-term care facilities are at high risk for developing skin and tissue diseases. Besides various common skin problems, dry skin (xerosis cutis) is one of the most frequent skin conditions in this setting. OBJECTIVES: To investigate the effectiveness of two structured skin care regimens in comparison to routine skin care on xerosis cutis in nursing home residents. DESIGN: A multi-center, pragmatic, randomized, controlled, investigator blinded study with three parallel groups. SETTINGS: The study was conducted in a random sample of ten out of 291 institutional long-term care facilities of the federal state of Berlin, Germany. PARTICIPANTS: Long-term care residents being 65+ years affected by dry skin were included. METHODS: The residents were allocated into one of three study groups. Two interventional groups used standardized skin care regimens, consisting of a body wash and twice daily applications of leave-on products for eight weeks. The third control group performed skin care as usual. All participating residents were examined at baseline and after 4 and 8 weeks. Xerosis cutis was measured with the Overall Dry Skin score. Instrumental skin barrier measurements were performed at baseline and after 8 weeks. Diaries were used to document washing and skin care frequencies. RESULTS: In total, 133 residents were included and allocated to one of the three groups. Mean age was 83.8 (SD 8.3) years, 65.4% were female and most residents had care levels I (42.9%) or II (42.9%) according to the German Social Code Book XI. Mean Barthel score was 46.8 (SD 24.2) and mean Braden score was 17.6 (SD 3.7). Leg skin areas were drier compared to arms and trunk areas. At the end of the study the Overall Dry Skin scores in the intervention groups were lower compared to the control group. There were statistically significant improvements of skin dryness in both intervention groups compared to the control group over time. CONCLUSIONS: The results of this pragmatic trial indicate that structured skin care regimens are effective in reducing skin dryness in aged nursing home residents within eight weeks. TRIAL REGISTRATION: The study is registered at https://clinicaltrials.gov/ct2/show/NCT02216526.

Prevalence and associated factors of skin diseases in aged nursing home residents: a multicentre prevalence study.

OBJECTIVES: The aim of this study was to measure the prevalence of skin diseases in aged nursing home residents and to explore possible associations with demographic and medical characteristics. DESIGN: Descriptive multicentre prevalence study. SETTING AND PARTICIPANTS: The study was conducted in a random sample of ten institutional long-term care facilities in the federal state of Berlin, Germany. In total, n=223 residents were included. RESULTS: In total, 60 dermatological diseases were diagnosed. The most frequently diagnosed skin disease was xerosis cutis (99.1%, 95% CI 97.7% to 100.0%) followed by tinea ungium (62.3%, 95% CI 56.0% to 69.1%) and seborrheic keratosis (56.5%, 95% CI 50.2% to 63.0%). Only few bivariate associations have been detected between skin diseases and demographic and medical characteristics. CONCLUSION: Study results indicate that almost every resident living in residential care has at least one dermatological diagnosis. Dermatological findings range from highly prevalent xerosis and cutaneous infection up to skin cancer. Not all conditions require immediate dermatological treatment and can be managed by targeted skin care interventions. Caregivers need knowledge and diagnostic skills to make appropriate clinical decisions. It is unlikely that specialised dermatological care will be delivered widely in the growing long-term care sector. TRIAL REGISTRATION NUMBER: This study is registered at https://clinicaltrials.gov/ct2/show/NCT02216526.