Emerging role of dermal compartment in skin pigmentation: comprehensive review.

The variations in human skin colour mainly occur due to differences in the distribution of melanin pigment throughout the body, synthesized by epidermal melanocytes which are further taken up by keratinocytes present in epidermis. Recently, it has been discovered that besides these cells, dermis derived fibroblast factors also play a prominent role in regulating skin pigmentation. There exists a signal crosstalk between epidermal melanocytes, keratinocytes and dermal fibroblasts and any impairment in these signalling pathways may give rise to pigmentary disorders. Vitiligo is a hypopigmentary disorder and alteration in the expression level of several fibroblast-specific factors has been reported in the lesional skin of vitiligo patients. In such patients, there is decrease in the expression levels of factors such as basic fibroblast growth factor, stem cell factor (SCF) and keratinocyte growth factor (KGF) along with a steep increase in the expression levels of Dickkopf 1. Patients affected with hyperpigmentary disorder like melasma exhibit a marked increase in SCF and KGF expression levels leading to increase in melanin production and those affected with solar lentigo experience upregulation in the expression levels of SCF, KGF and HGF (hepatocyte growth factor). Hence, we conclude that new therapeutic strategies can be adopted to cure these pigmentary disorders by targeting factors involved in crosstalk signalling between epidermal melanocytes, keratinocytes and dermal fibroblasts.

Psychological disturbances in patients with pigmentary disorders: a cross-sectional study.

BACKGROUND: Data on prevalence and factors influencing psychological burden in pigmentary disorders are scarce. OBJECTIVE: To determine the point prevalence of anxiety disorder, depression and somatoform disorder in patients with melasma, vitiligo and acquired dermal macular hyperpigmentation (ADMH). METHODS: A prospective cross-sectional study involving 100 patients each with melasma, ADMH and vitiligo with lesions on exposed body parts was conducted in the pigmentary clinic of a tertiary care referral hospital from June 2015 to December 2017. Dermatology life quality index, PRIME-MD Patient Health Questionnaire, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Patient Health Questionnaire-15 were used for assessment of quality of life, psychiatric comorbidities, depression, general anxiety disorder and somatoform disorders, respectively, and correlated with age, gender, occupation, marital status, severity and progression of the disease. RESULTS: The prevalence of anxiety disorder in patients with melasma, vitiligo and ADMH was 11.6%, 21% and 18.7%, respectively. Depression was seen in 12.8%, 27% and 24.1% patients with melasma, vitiligo and ADMH, respectively. Somatoform disorder was more common in vitiligo (17.9%) as compared to ADMH (14.3%) and melasma (8.1%). There were positive correlations between the severity of disease and the point prevalence of anxiety and depression in all disorders. CONCLUSION: A high point prevalence of anxiety, depression and somatoform disorders was observed with pigmentary diseases, especially vitiligo and ADMH. The prevalence of anxiety and depression correlated with the disease severity and activity. Future research involving comparison with the general healthy population is required for a more affirmative conclusion.

Contact sensitization to hair colours in acquired dermal macular hyperpigmentation: results from a patch and photo-patch test study of 108 patients.

BACKGROUND: Acquired dermal macular hyperpigmentation (ADMH) is an umbrella term including lichen planus pigmentosus, erythema dyschromicum perstans and pigmented contact/cosmetic dermatitis. OBJECTIVE: To establish contact sensitization to hair colours as an aetiological factor for ADMH. METHODS: Detailed clinical examination, skin biopsies, and patch and photo-patch testing with Indian standard series and patient's own cosmetic products were performed. RESULTS: Thirty-nine (36.1%) patients were found to demonstrate a positive patch/photo-patch test with 35/39 reacting to their own products (all were hair colours) and 16/39 reacting to antigens from commercial series (commonly paraphenylenediamine). Fourteen patients developed delayed hyperpigmentation on positive patch-test sites at 1 month. Higher mean age, symptomatic pigmentation (pruritus, burning and photosensitivity), hair margins involvement (outer surface, helix and lobule of ear; temples and preauricular area), ill-defined lesions, epidermal atrophy and epidermal melanization extending >3 layers were significantly common in patch-test-positive patients. Well-defined lesions, perioral involvement and associated lichen planus were clinical pointers towards patch-test negativity. CONCLUSION: Index study exemplifies that patch-test results have distinct clinical and histopathological correlates in ADMH. Hair dye contact sensitization appears to be an important aetiological factor in about one-third patients presenting with ADMH.

Reliability assessment and validation of the dermal pigmentation area and severity index: a new scoring method for acquired dermal macular hyperpigmentation.

BACKGROUND: Dermal pigmentation area and severity score (DPASI) is a recently proposed scoring system for acquired dermal macular hyperpigmentation (ADMH). OBJECTIVE: To determine the reliability and validity of DPASI. METHODS: After standardized training, three researchers independently rated 55 patients with ADMH on two consecutive days within 1 week, to determine intra-rater and inter-rater reliability. Validation was performed by comparing DPASI with the physician global assessment score. RESULTS: Test-retest reliability of individual raters tested by Pearson's r showed good correlation for all three raters (r = 0.984, P < 0.0001; r = 0.983, P < 0.000 and r = 0.970, P < 0.0001). Inter-rater agreement computed by intra-class correlation coefficient also showed good correlation (ICC = 0.997, P < 0.0001). Internal consistency as measured by Cronbach's alpha was 0.997. The score faired well in face and content validity (I-CVI of 0.87). On usability assessment, the scale had a median score of 4 on a scale from 1 to 5. The meantime taken to score the patients were 307.2 ± 83, 308.9 ± 84.4, 350.15 ± 91.8 s by three observers, respectively. CONCLUSION: The DPASI is a reliable measure of ADMH severity. The use of dermoscopy decreases inter and intra-observer variation resulting in a more objective score.

Four compartment method as an efficacious and simplified technique for autologous non-cultured epidermal cell suspension preparation in vitiligo surgery: A randomized, active-controlled study.

BACKGROUND: Autologous non-cultured epidermal cell suspension (NCES) is a successful surgical method for repigmentation of stable, refractory vitiligo. The need for laboratory equipment and expertise restricts its use to only a few research centres; hence, there is a requisite to simplify the technique of NCES preparation. OBJECTIVES: To evaluate the efficacy of NCES prepared by four compartment (4C) method compared to the laboratory-based method (lab-NCES). METHODS: Anatomically based matched lesions (41 pairs) in 30 stable vitiligo patients were randomized to receive NCES prepared by 4C method or lab-NCES. Each patient was evaluated at 4, 8, 16 weeks after surgery by a blinded observer with regard to extent of repigmentation, colour match, patient global assessment (PGA) and pattern of repigmentation. RESULTS: Repigmentation outcome in 4C method as compared to lab-NCES was as follows: excellent (≥90%) repigmentation: 34% vs. 37%, P = 1.000, good (≥75%) repigmentation: 68% vs. 71%, P = 1.000; colour match: 59% vs. 54%, P = 0.794, patient satisfaction based on PGA score - 23.02 vs. 23.39 (P = 0.210) and major pattern of repigmentation (diffuse) - 76% vs. 71% (P = 0.618). LIMITATIONS: Short follow-up period of 16 weeks. CONCLUSION: Four compartment method is a simple and effective technique for vitiligo surgery in routine clinical practice.

A retrospective study of lichen planus pigmentosus with focus on palmoplantar involvement.

Lichen planus pigmentosus (LPP) is a rare disease characterized by persistent and asymptomatic slate-grey pigmentation, which mostly affects patients with skin types IV-VI. The face and neck are the most commonly involved sites, followed by the trunk and extremities. LPP is believed to spare the palms, soles and nails. In this report, we describe palmoplantar involvement in 10 (4.65%, 10/215) patients with LPP, and compare its clinicodemographic features with those of classic LPP. LPP lesions on the palms and soles present as asymptomatic, well-circumscribed, hyperpigmented, brown-black patches without any history of prior lichen planus lesions. They are mostly observed in young patients with rapidly spreading active disease, who often require systemic treatment to control the disease activity. Strikingly, palmoplantar involvement is frequently associated with other atypical LPP variants. It is important to identify palmoplantar involvement in LPP, as it has a different clinical course and associations compared with classic LPP.

Phototherapy using narrowband ultraviolet B and psoralen plus ultraviolet A is beneficial in steroid-dependent antihistamine-refractory chronic urticaria: a randomized, prospective observer-blinded comparative study.

BACKGROUND: Literature on the efficacy of phototherapy in steroid-dependent antihistamine-refractory chronic urticaria (CRU) is limited. OBJECTIVES: To assess and compare the efficacy of psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (NB-UVB) in steroid-dependent CRU. METHODS: In this randomized, prospective observer-blinded comparative study, 50 patients with steroid-dependent CRU (6 months of spontaneous urticaria with no response after 3 consecutive months of antihistamines and steroid dependence) were administered either PUVA (group A) or NB-UVB (group B) for 90 days, with a post-treatment follow-up of 90 days. The treatment efficacy was assessed using the average urticaria activity score 7 (aUAS7) and outcome scoring scale (OSS) every 2 weeks. RESULTS: The mean values of aUAS7 progressively decreased from 4·9 ± 0·8 and 5·0 ± 0·7 at baseline to 1·9 ± 0·7 and 1·4 ± 0·7 in groups A and B, respectively, by day 90. This further decreased to 1·5 ± 0·8 and 1·4 ± 1·0 at day 180 in both groups. The values of OSS progressively increased from baseline (1·6 ± 0·5 in group A and 1·3 ± 0·5 in group B) to 3·9 ± 0·3 and 4·0 ± 0·3 in groups A and B, respectively, by day 90, and 3·9 ± 0·5 and 4·0 ± 0·6 by day 180. NB-UVB fared statistically better than PUVA at different time points. Adverse events encountered were minimal and did not warrant treatment discontinuation. CONCLUSIONS: Phototherapy, especially NB-UVB, is an effective, safe and affordable therapeutic modality for steroid-dependent CRU and should be tried prior to third-line treatment options such as omalizumab, ciclosporin and other immunosuppressants.

Glabrous lesional stem cells differentiated into functional melanocytes: new hope for repigmentation.

BACKGROUND: Vitiligo is characterized by the loss of pigment-producing cells, melanocytes and one of the important goals of treatment is replenishing the melanocytes from existing reservoirs. Reservoir for melanocyte stem cell has been reported to be present in the skin hair follicles, but glabrous skin does not have hair follicles. Therefore, repigmentation of glabrous lesional skin is very difficult and almost rare. There is no explanation for melanocyte reservoir in the glabrous lesional skin of vitiligo patients. OBJECTIVE: This study is designed to check the glabrous lesional skin for the presence of stem cells as source of melanocytes for repigmentation. METHODS: Skin grafts were collected from glabrous lesional skin of vitiligo patients. Immunohistochemistry of glabrous lesional skin was performed to check for the presence of stem cells. These glabrous lesional stem cells were isolated, cultured and characterized. After characterization, glabrous lesional stem cells were differentiated into melanocytes. RESULTS: Our results demonstrate that NGFRp75-positive stem cells are present in the glabrous lesional skin of vitiligo patients and can be differentiated into melanocytes. These dermal stem cells showed self-renewal capacity and were capable of differentiating into melanocytes which are required for the repigmentation. CONCLUSION: Presence of stem cells in the glabrous lesional skin which are capable of self-renewal and differentiating into melanocytes gives new hope for vitiligo patients having lesion on the glabrous skin. However, still repigmentation of glabrous lesional skin is very difficult and rare with current available treatments. This clearly means that treatments available till date are not effective enough to activate these dermal stem cells differentiation and their migration to the lesional epidermis. Stimulating these stem cells to differentiate into melanocytes and migrate to lesional epidermis can be ideal for repigmentation of the glabrous lesions.