CURRENT BEST EVIDENCE
Year : 2019 | Volume
: 6 | Issue : 1 | Page : 50--54
Current best evidence in pigmentary dermatology
Vishal Thakur, Amit Dalla, Keshavamurthy Vinay
Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Dr. Keshavamurthy Vinay
Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012
|How to cite this article:|
Thakur V, Dalla A, Vinay K. Current best evidence in pigmentary dermatology.Pigment Int 2019;6:50-54
|How to cite this URL:|
Thakur V, Dalla A, Vinay K. Current best evidence in pigmentary dermatology. Pigment Int [serial online] 2019 [cited 2022 Aug 17 ];6:50-54
Available from: https://www.pigmentinternational.com/text.asp?2019/6/1/50/262051
LONG-TERM OUTCOME OF SURGICAL-INDUCED REPIGMENTATION IN VITILIGO
Altalhab S, AlJasser MI, Mulekar SV, Al Issa A, Mulekar S, Diaz J, et al. Six-year follow-up of vitiligo patients successfully treated with autologous non-cultured melanocyte-keratinocyte transplantation. J Eur Acad Dermatol Venereol 2019. doi: 10.1111/jdv.15411. [Epub ahead of print]
Vitiligo is an acquired pigmentary disorder associated with loss of melanocytes leading to depigmented patches over body and significant psychosocial impacts. Various medical and surgical modalities for the treatment of vitiligo are available but response to these modalities is highly variable and sometimes not satisfactory. Noncultured epidermal cell suspension has established its efficacy in medically resistant vitiligo patients. However, studies on long-term outcome of noncultured epidermal cell suspension with regard to the maintenance of repigmentation are limited.
This retrospective study assessed the long-term maintenance of surgically induced repigmentation after melanocyte–keratinocyte transplantation (MKTP) and factors affecting the outcome. Data of the patients undergone MKTP from 2004 to 2015 were retrieved. Criteria for eligibility to MKTP procedure were vitiligo of any type with disease stability and absence of Koebner phenomenon for at least 6 months. Repigmentation of the grafted area was first evaluated at 3 months following MKTP and was graded as excellent (75%–100%), good (50%–75%), fair (25%–50%), and poor (<25%). Relapse was defined as reappearance of more than 10% depigmentation in a previously treated and repigmented site whereas recurrence was defined as appearance of new lesions on previously untreated and normal appearing skin. All patients who achieved good to excellent repigmentation at the 6-month follow-up and who had at least 6 years of follow-up were evaluated. In total, 602 patients out of 714 treated patients (84.3%) achieved good to excellent repigmentation at the 6 months evaluation. Forty-nine patients were lost to follow-up and remaining 553 patients who had long-term follow-up, that is, 6 years, were included in final analysis. One hundred three (18.6%) patients had relapse during the follow-up period and 53 of these patients had appearance of new lesions after surgery. Male gender, age at surgery ≥23 years, nonsegmental vitiligo, age at onset of vitiligo >13 years, fingertip involvement, and new lesion onset were associated with a higher probability of relapse whereas affected body surface area <1% and mechanical dermabrasion were independently associated with lower rates of relapse.
Limitations of the study were its retrospective nature and the procedures were conducted in a reference center. Thus, the high rate of success might not be generalizable.
The ability to maintain repigmentation achieved after vitiligo surgery is of paramount importance as persistence of repigmentation precludes the need for repeated surgeries, improves patients’ quality of life, and establishes the efficacy of surgical modality. Most of the published studies have reported their results, that is, extent of repigmentation on the short term, 1 to 2 years after the intervention, whereas the literature on long‐term follow‐up, that is, more than 2 years, is rather limited. Follow-up periods in vitiligo surgery have varied, with a maximum of 14 years showing different results. Studies have shown that patients with segmental vitiligo tend to retain repigmentation more than patients with nonsegmental vitiligo. Majority of studies have reported some loss of acquired repigmentation up to 20% over a period. However, recurrences at the site of surgery, as well as the development of new patches over other body sites, have also been reported, particularly in the nonsegmental type of vitiligo. Other factors that may affect the long-term outcome include duration of stability of the disease, surface area chosen for surgery, site of surgery, and postsurgery treatment. Some of the difficulties in conducting long-term studies to evaluate stability of surgical-induced repigmentation include a gradual loss to follow-up and cost of long-term observation.
CUTANEOUS PIGMENTATION AND DIGITAL ULCER IN SYSTEMIC SCLEROSIS
Leroy V, Henrot P, Barnetche T, Cario M, Darrigade AS, Manicki P, et al. Association of skin hyperpigmentation disorders with digital ulcers in systemic sclerosis: analysis of a cohort of 239 patients. J Am Acad Dermatol 2019;80:478-84.
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by skin thickening and internal organ involvement; it is associated with high morbidity and mortality. Cutaneous pigmentation in SSc have been reported in 30% to 90% of patients in different studies and three morphological patterns have been described: vitiligo-like depigmentation with perifollicular hyperpigmentation (salt-and-pepper pigmentation), diffuse hyperpigmentation with accentuation in sun-exposed areas, and combined hyperpigmentation and hypopigmentation localized in the areas of sclerosis. However, studies assessing cutaneous pigmentation associated with SSc are mostly descriptive. This retrospective study analyzed the prevalence and patterns of cutaneous pigmentation observed in SSc patients and its association with various clinical features in patients with SSc. In this study, 239 patients of SSc were included and five patterns of cutaneous pigmentation were defined: a diffuse hyperpigmentation affecting the entire skin; hyperpigmentation localized to sun-exposed areas; hypopigmentation localized on the face, neck, upper chest, and upper back; diffuse hypopigmentation affecting the limbs and trunk; and hypopigmentation with hypopigmented macules distributed mainly on acral areas. Involvement of various internal organs, that is, cardiovascular, pulmonary, gastrointestinal, and musculoskeletal, were also analyzed with respect to cutaneous pigmentation. Out of total 239 patients, 169 patients had limited cutaneous SSc (LSSc) and 70 patients were classified as diffuse cutaneous SSc (DSSc). Cutaneous pigmentation was seen in 88/239 (36.8%) patients with 58 and 35 patients having hyperpigmentation and hypopigmentation, respectively. Most common pattern of cutaneous pigmentation was diffuse hyperpigmentation (38.6%) followed by hyperpigmentation in sun-exposed areas (27.3%). Cutaneous pigmentation was seen in 55.7% patients with DSSc whereas patients with LSSc had pigmentation in 31.9%. Diffuse hyperpigmentation was significantly associated with highly modified Rodnan skin score and absence of anticentromeric antibodies, shorter duration of Raynaud phenomenon, and presence of digital ulcers. Thus, authors concluded that the cutaneous hyperpigmentation may be a useful diagnostic tool and marker of vascular involvement in patient with systemic sclerosis. However, the findings of this study need to be confirmed by larger population-based studies as the major limitation of the study was its single-center retrospective design.
Pattern of cutaneous pigmentation and its correlation with other clinical features in patients with SSc may help us in identifying the subset of patients who have increased risk of vascular complications such as digital ulcers as these are associated with significant morbidity. Endothelin-1, a vasoconstrictor, has been implicated in the vascular complications such as pulmonary artery hypertension and digital ulcers. Endothelin-1 is also postulated as a melanogenic factor leading to hyperpigmentation in patients with SSc. Thus, endothelin-1 may be a common pathogenic factor responsible for both cutaneous and vascular complications and targeting this early in the course of disease in patients with cutaneous hyperpigmentation may prevent these devastating complications. However, well-designed prospective studies are needed.
CONTACT SENSITIZATION IN ACQUIRED DERMAL MACULAR HYPERPIGMENTATION
Bishnoi A, Vinay K, Arshdeep, Parsad D, Handa S, Saikia UN, et al. Contact sensitization to hair colours in acquired dermal macular hyperpigmentation: results from a patch and photo-patch test study of 108 patients. J Eur Acad Dermatol Venereol 2019. doi: 10.1111/jdv.15576. [Epub ahead of print]
Acquired dermal macular hyperpigmentation (ADMH) encompasses dermatoses characterized by asymptomatic, nonscaly, hyperpigmented macules and patches that on histopathology demonstrate interface dermatitis along with melanin incontinence in dermis. Various entities have been described under this broad term including lichen planus pigmentosus, erythema dyschromicum perstans, ashy dermatoses, and pigmented cosmetic/contact dermatitis. Among various etiological factors implicated, contact sensitization to hair colors and other personal cosmetics are being increasingly recognized as important contributors. To corroborate the above facts, authors carried out patch tests and photo patch tests in patients with ADMH. A total of 108 patients, all having involvement of face and neck, were patch tested using Indian Standard Series and patient’s own cosmetic products. In addition, comparison of clinical and histopathological features was carried out between patch test positive and negative patients.
Majority of study patients were females in their forties (80.5%). Hair dyes/colors were most common personal cosmetics used, almost half of them could temporarily correlate the development of hyperpigmentation to dye usage. Thirty-nine out of 108 tested positive on patch testing. Self-products exhibited more positivity than commercial series as 34 patients reacted to their own products (all were hair colors) and 16 patients reacted to antigens from commercially available series, with paraphenylenediamine (PPD) being the most common antigen from Indian Standard Series demonstrating a positive reaction.
Two different clinical phenotypes were recognized by the authors − first phenotype was characterized by a relatively older age, significantly longer duration of hair color usage, symptomatic hyperpigmentation, onset on hair margins, ill-defined hyperpigmented patches showing sparing of creases, and preferential involvement of outer surface, helix, and lobule of ear, temples, preauricular area (sites affected by application of hair dyes) and upper back. This phenotype correlated significantly with positive patch tests. Conversely, the second phenotype represented relatively younger patients having perioral area as the site of onset, well-defined hyperpigmented macules and patches, and minimal or no symptoms associated with their hyperpigmentation. This phenotype correlated significantly with negative patch tests and significantly lacked the involvement of ear helices and lobules. The presence of classical cutaneous and mucosal lichen planus was also significantly more common in this phenotype. On comparing the histopathological features, enhanced epidermal melanization (with melanin pigment extending above the basal layer) was encountered in both patch-test positive and negative subsets; however, patch-test negative patients had epidermal melanization extending till one to three bottom layers of epidermis whereas melanization extended beyond bottom three epidermal layers in patch-test positive patients. A severe dermal inflammatory infiltrate was significantly more common in the patch-test positive group.
The above results suggested that PPD and other potential allergens in hair colors/personal cosmetics can be implicated in the pathogenesis of ADMH. Major limitations of the study were as follows: no testing of controls was carried; complete cosmetic, textile, and photo patch series were not applied; and effect of cessation of hair color on severity of ADMH was not assessed.
The study further strengthens the etiopathological role played by cosmetics and sun exposure in the development of ADMH. Patch testing these patients with both their personal cosmetics and standard series can help in better management of this enigmatic pigmentary disorder. Although the authors observed clinicopathological differences between patch test positive and negative patients, the overall and long-term effect of avoidance of hair colors and other personal cosmetics on disease severity needs to be studied in larger studies with longer follow-up period.
INTRADERMAL TRANEXAMIC ACID IN MELASMA
Pazyar N, Yaghoobi R, Zeynalie M, Vala S. Comparison of the efficacy of intradermal injected tranexamic acid (TA) vs. hydroquinone (HQ) cream in the treatment of melasma. Clin Cosmet Investig Dermatol 2019;12:115-22.
Melasma is a common benign-acquired dermatosis characterized by light to dark brown macules or patches, most commonly on the face, usually in a symmetrical distribution. Apart from cosmetic disfigurement, it also leads to psychosocial distress. Treatment modalities for elisma include use of sunscreens, HQ, triple combination topicals, peeling, and laser. Recently, TA has been proposed as a new treatment for elisma. The main mechanism of the hypopigmenting effects of TA is due to its antiplasmin activity (plasmin has melanogenic and angiogenic properties). Various forms of TA are used orally, topically, and as a microinjection for the treatment of melasma. There are scant controlled studies that have assessed intradermal microinjection of TA as an effective and safe method.
This study was undertaken to compare the efficacy of intradermal injected TA vs. HQ cream in the treatment of melasma. In this prospective split face controlled clinical trial, 49 patients were randomly divided into two groups of A (24 persons) and B (25 persons). Majority of patient had skin type III and epidermal type of melasma. Patients received TA intradermal injections every 2 weeks on the right side of the face with a concentration of 4 mg/mL in group A and a concentration of 10 mg/mL in group B. The left side in both the groups was treated twice daily with topical 4% HQ cream, and treatment continued for 12 weeks in both the groups. All patients were recommended topical sunscreens for 12 weeks. Melasma Area and Severity Index (MASI) scores were measured for each side of the face at baseline and at weeks 4, 8, 12, and 24. Forty-one patients (21 in group A and 20 in group B) completed the study. The MASI score in the 12th week significantly decreased compared to the baseline for group A, group B, and HQ cream. However, no statistically significant difference was observed between the MASI score of patients in groups A and B. Also, the comparison of TA at the concentration of 4 mg/mL to the 4% HQ cream showed that the MASI scores in the 8th week (P = 0.02) and the 12th week (P = 0.02) were significantly less in the HQ group. However, no significant difference was observed between the MASI score changes in Group B (10 mg/mL) and the 4% HQ group. The advantages of this study were the presence of the HQ as the control group and higher concentration of TA; however, no difference was observed between 4 and 10 mg/mL. The authors concluded that intradermal injection of TA can be an effective treatment for melasma.
Major limitations of this study were the small number of participants, lack of blinding for the investigator, the inadequate duration of treatment and follow-up, and use of the MASI score, which is a subjective assessment method.
Although several treatment options exist for this common-acquired pigmentary disorder, managing melasma still remains a great challenge. Various recent studies have focused on usefulness of TA in treating melasma; this study goes a step further by comparing it with HQ. Certain key issues regarding use of TA in melasma are variable efficacy of oral and topical TA in various studies, finding optimal concentration of topical/injectable TA, defining appropriate dosing intervals for injectable preparations, and usefulness in combination with other already available topical agents. Further clinical trials with larger sample size from different geographical areas are required to further elucidate these key issues.
VALIDATION OF PHYSICIAN GLOBAL ASSESSMENT FOR VITILIGO
van Geel N, Wolkerstorfer A, Ezzedine K, Pandya AG, Bekkenk M, Grine L, et al. Validation of a physician global assessment tool for vitiligo extent: results of an international vitiligo expert meeting. Pigment Cell Melanoma Res. 2019. doi: 10.1111/pcmr.12784. [Epub ahead of print]
Extent of the disease helps in defining the disease severity and deciding the treatment modalities. The affected body surface area (BSA) is an important tool to assess vitiligo severity. Recently, Vitiligo Extent Score (VES) has been validated to measure affected BSA. However, a Physician Global Assessment (PGA) score for vitiligo has not been validated that may be helpful in standardizing definitions of inclusion criteria for clinical trials.
In this study, authors validated a PGA score for extent of vitiligo based on a workshop comprising of 29 vitiligo experts from different countries. This PGA score can be used to stratify and interpret the numeric scores obtained by other instruments (e.g., VES). The aim of the study was to assess the validity of PGA score for disease extent and determine the median BSA values per category for limited, moderate, extensive, and very extensive vitiligo. The workshop was based on questions and a series of photographs of patients with nonsegmental vitiligo. The physicians were asked to score the grade of extent on the five‐point global assessment scale for each patient. The total affected BSA of each patient was assessed for vitiligo extent to gather information with respect to median values per category for vitiligo extent. The reliability of the PGA was evaluated by assessing the interrater agreement among all participants. The interrater agreement was interpreted as follows: below 0.4 was considered poor, 0.4–0.59 was considered fair, 0.6–0.74 was considered good, and higher than 0.74 was defined as excellent. A good interrater agreement (>0.6) was observed within each separate continent that did not differ significantly. The highest agreement was achieved for raters from North and
South America (0.817; 95% confidence interval, CI: 0.694–0.911 and 0.720; 95% CI: 0.424–0.878, respectively). The overall agreement among all raters was 0.671 (95% CI: 0.530–0.816), which is deemed acceptable. All hypotheses formulated for validity testing were confirmed, and a high correlation was found with VES, self-assessed VES (SA-VES), and BSA. Median VES values per category were as follows: limited 1.10 [inter-quartile range (IQR): 0.21–1.67], moderate 3.17 [IQR: 1.75–6.21], extensive 9.58 [IQR: 6.21–13.03], and very extensive 42.67 [IQR: 21.20–42.67]. Exact cutoff points per category could not be defined because of small sample size.
This study demonstrated the possible categorization of vitiligo with respect to extent of the disease. Such categorization may help in further management of the disease as in psoriasis or eczema. This study also provided a guide for the interpretation of the numerical output of the VES based on a physician global assessment. Such defined categories for the affected BSA in vitiligo can be valuable for inclusion criteria in clinical trials. However, in this study, moderate disease was defined as a median VES of 3.17 that may not reflect the actual severity of the disease. Although this has been mentioned by the authors as the aim of the study was to assess the extent not severity.
EFFICACY OF Q-SWITCHED Nd-YAG LASER IN FACIAL LICHEN PLANUS PIGMENTOSUS
Shah DSD, Aurangabadkar DS, Nikam DB. An open-label non-randomized prospective pilot study of the efficacy of Q-switched Nd-YAG laser in management of facial lichen planus pigmentosus. J Cosmet Laser Ther 2019;21:108-15.
Lichen planus pigmentosus (LPP) is a cosmetically disturbing rare dermatosis characterized by dark brown, black, or slate–gray mottled or reticular pigmentation affecting the photo-exposed areas, especially face and neck. Microscopic features of LPP include variably dense lichenoid inflammatory infiltrate with basal cell vacuolization, pigmentary incontinence, and melanophages in the dermis. It has been associated with hepatitis C virus, sun exposure, and contact allergents such as mustard oil and nickel. Various treatment options such as oral and topical steroids, high-dose vitamin A, isotretinoin, dapsone, topical calcineurin inhibitors, chemical peels, and topical retinoids had been used for the treatment of LPP. Although they are quite effective in stabilizing the disease and prevent further progression, the residual pigmentation that results from pigment incontinence in the dermis is often resistant to conventional treatments. Q-switched Nd-YAG laser (QSNYL) is an established modality in the treatment of various dermal pigmentary conditions such as nevus of Ota and tattoos. As longer wavelength has less affinity for epidermal melanin and can penetrate deeper, 1064-nm QSNYL has become a treatment of choice in many hyperpigmentary diseases in patients with type IV to VI skin. The authors evaluated efficacy of 1064-nm QSNYL in 13 patients with LPP who were adequately treated with medical therapies and had stable disease without any worsening or progression of the disease for at least 6 months but with persistent facial macular pigmentation. The treatment was done with 5 mm spot, with the fluence that caused minimal frosting (3–4.6 J/cm2) and 5-Hz repetition rate. A single pass with minimal overlap covering the entire affected area was given. The fluence was increased on subsequent sessions based on the therapeutic response (minimal frosting) and patient tolerability. Treatments were done once in 4 to 8 weeks for an average of five sessions or till there is a significant clearing of pigment. Patients were asked to continue the application of 0.1% tacrolimus ointment and strict sun protection using broad-spectrum sunscreen. Patients were followed every month and till 6 months after the last treatment. All patient belonged to skin type IV and V with 69.2% of patient being females. Pigmentation was bluish gray in most of the cases. Response to treatment was graded as Grade I: <25% improvement, Grade II: 26%–50% improvement, Grade III: 51%–75% improvement, Grade IV: >75% improvement, and Grade V: >90% improvement. All patients showed a satisfactory response to treatment at the end of five to six sessions. Five patients showed Grade V improvement (38.4%), five patients showed Grade IV response (38.4%), and three patients showed Grade III response (23%). The authors observed no difference in outcome depending on site of the lesion, age or sex of the patient, or color of the pigmentation. Patients were followed up for 6-month posttreatment with an advise to continue sunscreen and none relapsed during this period. With the help of above laser, the authors have attempted to target upper dermal melanophages, which contain most of the pigment in LPP and proposed QSNYL in combination with topical tacrolimus as an effective treatment modality in the treatment of stable LPP. Major limitations of this study were small sample size, lack of a control arm, and randomization.
LPP is a cosmetically disfiguring condition, predominantly affecting middle-aged females. Many treatment options are available that are effective in halting the progression of the disease; however, the treatment of persistent pigmentation still remains a challenge. This study further gives weightage to various recent reports demonstrating the usefulness of QSNYL in treatment of various dermatosis described under the umbrella term “acquired dermal macular hyperpigmentation.” Larger double-blind studies are required to further explore the effectiveness of this treatment modality.
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