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Disorders of Hyperpigmentation
Abstract
Disorders of hyperpigmentation appear more pronounced in individuals with skin of color and tend to be more challenging to treat. The exaggerated response of melanocytes in these individuals to cutaneous trauma is seen as a hallmark of skin of color (Grimes in Seminars in cutaneous medicine and surgery. WB Saunders, pp. 77–85, 2009). A study with 1076 dermatology patients in Saudi Arabia found pigment disorders to be the fourth most common skin disease (Alakloby in Saudi Medical Journal 26(10):1607–1610, 2005). A study of 2000 Black patients in Washington, DC, found pigment disorders to be the third most common skin disorder (Halder et al. in Cutis 32(4):388, 390, 1983). The majority of these patients were noted to have post-inflammatory hyperpigmentation, with melasma being the second most frequent disorder (Halder et al. in Cutis 32(4):388, 390, 1983). The most common causes of hyperpigmentation are post-inflammatory hyperpigmentation, melasma, lichen planus pigmentosus, erythema dyschromicum perstans, drug-induced hyperpigmentation, and metabolic causes of hyperpigmentation, which will all be discussed in this chapter.
... UV-B radiation causes oxidative stress and upregulation of matrix metalloproteinases (MMPs) which contribute to skin photoaging [3]. Hyperpigmentation is caused by the overproduction of melanin in skin tissue and is associated with skin disorders [4] such as melasma, café au lait macules, lichen planus pigmentosus and postinflammatory hyperpigmentation (PIH) [5], which affect the quality of life and also might be a risk factor for skin cancer melanoma. Compounds which can control hyperpigmentation disorders are attractive candidates for their use in clinical dermatology, as well as in personal-care cosmetic products for correction of uneven pigmentation. ...
Skin hyperpigmentation disorders arise due to aberrant regulation of melanin synthesis and export. Current treatments include natural compounds like kojic acid and hydroquinone, which suffer from limitations due to adverse reactions. Thermorubin (TR) is a secondary metabolite derived from the fungus Thermoactinomyces antibioticus and has previously demonstrated to possess anti-inflammatory properties by inhibition of matrix metalloproteinases (MMPs), as well as antimicrobial activity. In the current study, we explored whether TR might be a used as a candidate for the treatment of skin hyperpigmentation disorders by studying its effects on melanin synthesis and melanin export in B16F10 mouse melanoma cells and primary human melanocytes derived from darkly-pigmented (DP) skin. Non-toxic doses of TR were first identified in B16F10 mouse melanoma cells. These doses were subsequently tested for their effects on both extracellular and intracellular melanin levels under conditions of basal and hormone-stimulated melanogenesis. Our results demonstrated that TR at 25 µM inhibited total melanin levels with selective inhibition of extracellular melanin in B16F10 cells under both basal and hormone-stimulated conditions. The mechanisms of inhibition did not include tyrosinase inhibition, either in cellular lysates or cell-free system. However, TR potently inhibited activity of α-glucosidase enzyme in vitro and exhibited antioxidant activity. Furthermore, our results with primary human melanocytes from DP skin showed that TR at 10 µM significantly suppressed dendricity along with an increase in accumulation of intracellular melanin. These findings point to a mechanism of action of TR as an exclusive inhibitor of melanosome export. Taken together, our preliminary results demonstrate that TR might offer a novel ingredient as a skin depigmenting agent for inclusion in cosmetic formulations. Further studies delineating molecular mechanisms of hypopigmentation of TR and testing in human skin tissue-equivalents are warranted.
Background:
Lichen planus pigmentosus inversus (LPPI) is a rare variant of LP. Only 31 cases have been reported in the literature.
Methods:
Here we report a series of 10 patients with LPPI from North Africa.
Results:
Ten cases of LPPI, clinically suspected and histologically confirmed, were seen over 3 years (2013-2015). The mean age of patients was 62.4 years old. Eight patients were women and two were men. Main folds involved were the axillae and groin. All patients were treated by topical steroids without success.
Conclusions:
Our series of LPPI seems that this disorder is underreported mainly among 3 dark-skinned persons as we have seen these ten cases within three years.
Background:
Erythema dyschromicum perstans, a rare dermatosis of obscure etiopathogenesis and significant cosmetic morbidity, have no satisfactory treatment.
Observations:
Two patients with having characteristic asymptomatic and slowly progressive, slate-grey macular lesions with distinct red borders involving the face, neck, upper trunk and limbs were diagnosed clinicopathologically as erythema dyschromicum perstans. Both were treated successfully with topical tacrolimus 0.1% ointment.
Conclusions:
Overall, response to several therapeutic modalities including clofazimine and dapsone therapy is said to vary from complete failure to variable or inconsistent. Topical tarolimus provides an effective and safe alternative therapeutic option in erythema dyschromicum perstans.
Melasma is a chronic acquired hypermelanosis of the skin, characterized by irregular brown macules symmetrically distributed on sun-exposed areas of the body, particularly on the face. It is a common cause of demand for dermatological care that affects mainly women (especially during the menacme), and more pigmented phenotypes (Fitzpatrick skin types III-V). Due to its frequent facial involvement, the disease has an impact on the quality of life of patients. Its pathogeny is not yet completely understood, although there are some known triggering factors such as sun exposure, pregnancy, sexual hormones, inflammatory processes of the skin, use of cosmetics, steroids, and photosensitizing drugs. There is also a clear genetic predisposition, since over 40% of patients reported having relatives affected with the disease. In this manuscript, the authors discuss the main clinical and epidemiological aspects of melasma.
Twenty-five year old male patient presenting with asymptomatic brown spots, on
cervical, axillary, inguinal and popliteal regions, for the last nine months.
Pathological examination showed hydropic degeneration of the basal layer, pigmentary
incontinence and moderate inflammatory lymphocytic infiltrate in the dermis. Lichen
planus pigmentosus inversus is a rare subtype of lichen planus characterized by
hyperchromic, asymptomatic or mildly pruritic macules, measuring from millimeters to
centimeters in diameter, with defined borders, affecting intertriginous areas, most
commonly in the axillae and groin of Caucasian patients. It presents unique lichenoid
histology. We report a case with typical clinical features, histology and
evolution.
Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG) 1064 nm, Alexandrite 755 nm, and Ruby 694 nm) were used in test areas. The Alexandrite 755 nm laser proved to provide effective clearing of the minocycline hyperpigmentation requiring just 2 treatments, with minimal treatment discomfort and down time.
Erythema dyschromicum perstans (EDP) is a pigmentary disease of unknown etiology in which damage to basal cells is thought to be mediated by adhesion molecules. The aim of this study was to characterize the histopathology and immunopathology of EDP. Forty-three patients from Medellín, Colombia, with the diagnosis of EDP were evaluated. Skin biopsy specimens were obtained for histopathology and immunohistochemistry, using monoclonal antibodies directed against the following markers: CD4, CD8, CD56, CD1a, CD68, CLA, HLA–DR, ICAM-1 and LFA-1.A dermal lymphocytic infiltrate was observed in all cases, with a perivascular location in 86%. Other histologic features included melanophages in all specimens, vacuolization of the basement membrane zone (BMZ) 58% and exocytosis of lymphocytes (53.5%). The mean number of total leukocytes was 1510 cells mm−2 of tissue. There was a predominance of CD8+ T lymphocytes in the dermis and HLA–DR+, ICAM-1+ keratinocytes in the epidermis. Exocytosis of cutaneous lymphocyte antigen (CLA) + cells was observed in areas of BMZ damage, suggesting that response to antigenic stimulation may play a role in the development of EDP.
Postinflammatory hyperpigmentation is a common sequelae of inflammatory dermatoses that tends to affect darker skinned patients with greater frequency and severity. Epidemiological studies show that dyschromias, including postinflammatory hyperpigmentation, are among the most common reasons darker racial/ethnic groups seek the care of a dermatologist. The treatment of postinflammatory hyperpigmentation should be started early to help hasten its resolution and begins with management of the initial inflammatory condition. First-line therapy typically consists of topical depigmenting agents in addition to photoprotection including a sunscreen. Topical tyrosinase inhibitors, such as hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice extracts, can effectively lighten areas of hypermelanosis. Other depigmenting agents include retinoids, mequinol, ascorbic acid, niacinamide, N-acetyl glucosamine, and soy with a number of emerging therapies on the horizon. Topical therapy is typically effective for epidermal postinflammatory hyperpigmentation; however, certain procedures, such as chemical peeling and laser therapy, may help treat recalcitrant hyperpigmentation. It is also important to use caution with all of the above treatments to prevent irritation and worsening of postinflammatory hyperpigmentation.
To describe the pattern of skin disease in the Eastern Province and compare it with similar studies carried out in other regions of Saudi Arabia.
All new dermatology cases reporting at King Fahd Hospital of the University in Al-Khobar, Saudi Arabia, seen between August 2002 to July 2003 were reviewed.
One thousand and seventy-six new patients within the period of the study were seen. Dermatitis/ eczema was the most frequent dermatosis (19.6%) with atopic dermatitis forming 35.9% among eczemas, followed by acne (13.8%), viral infection (13.5%), of which 11.9% had viral warts; pigmentary disorders (9.7%) with vitiligo comprising 5% of the total. In fungal infections (9.6%), dermatophytoses formed 6.3% of the total patients, alopecias 7.2%, papulosquamous disorders 6.4%, of which 3.4% had psoriasis and 1.7% had lichen planus; urticaria 5.7%, pyoderma 4.8%, and the parasitic infections, 1%.
This comparative study showed that eczema was the most frequent diagnosis among all skin diseases and parasitic infections were the least frequent diseases. Generally, the Eastern Province study is closely comparable to other studies in the country with higher frequencies of viral and fungal infections and acne.
Ashy dermatosis, also known as erythema dyschromicum perstans, is an acquired benign disease, characterized by blue-gray pigment patches with erythematous borders. The cause is still unclear, but probably has an immunologic basis.
The aim of this study was to determine gene frequencies of the HLA-DR alleles in Mexican patients with ashy dermatosis and compare them with ethnically matched healthy control subjects to reveal the genetic susceptibility to develop ashy dermatosis.
We included 23 consecutive patients with clinical and histopathologic confirmed diagnosis of erythema dyschromicum perstans. Patients and control subjects received a questionnaire to determine their ethnic origin and a peripheral blood sample was taken for DNA extraction. Finally, Genetic HLA-DRB1 was performed by polymerase chain reaction sequence-specific oligonucleotide reverse dot blot hybridization.
Of the 23 patients included in this study, 65% were women and 35% were men. We observed that the disease was located in the trunk in 17 patients (74%) and the upper limbs in 15 patients (65%). The most frequent allele was HLA-DR4 (65%) (pC < 1 x 10(-6), odds ratio = 6.0, 95% confidence interval = 2.8-12.7) whereas in control subjects it was 23%. The most frequent molecular subtype in both patients and healthy control subjects was DRB1( *)0407, being statistically significant after comparing the two groups (pC < 1 x 10(-6), odds ratio = 7.0, 95% confidence interval = 3.1-15.8).
Since this is a disease strongly influenced by ethnicity, extrapolation to other ethnic groups is limited.
Many factors influence the ethiopathogenesis of erythema dyschromicum perstans, but it is strongly suggested to have an important genetic susceptibility conferred by genes located within the major histocompatibility complex region.
Background:
Melasma is a common pigmentary disorder among Asians and treatment is challenging. Oral tranexamic acid (TA) has emerged as a potential treatment for refractory melasma. Large-scale studies on its use, outcomes, and safety are limited.
Objective:
We sought to evaluate treatment outcomes and adverse effects of oral TA in melasma in an Asian population.
Methods:
We conducted a retrospective analysis of patients who received oral TA for melasma in a tertiary dermatologic center from January 2010 to June 2014.
Results:
In all, 561 patients (91.4% female, 8.6% male) were enrolled. Median duration of treatment was 4 months. The majority (503 [89.7%]) improved, 56 (10.0%) had no improvement, and 2 (0.4%) worsened. Patients without family history of melasma had better response rates than those with family history (90.6% vs 60.0%, P = .01). Of the 503 who improved, response was seen within 2 months of TA initiation, with a relapse rate of 27.2%. Adverse events occurred in 40 (7.1%). Most were transient, but 1 developed deep vein thrombosis requiring prompt discontinuation. She was later given the diagnosis of familial protein S deficiency.
Limitations:
This was a retrospective study.
Conclusion:
Oral TA may be an effective adjunct for refractory melasma. Careful screening for personal and familial risk factors for thromboembolism should be done before initiation.
Background:
Lichen planus pigmentosus (LPP) is a cosmetically distressing pigmentary disorder often posing a therapeutic challenge. Isotretinoin has been shown to be effective in oral and cutaneous LP, but its role in LPP is yet unknown.
Objective:
To evaluate the efficacy and safety of isotretinoin in the management of LPP.
Methods:
In this prospective study, 32 clinically and histologically proven patients with LPP were recruited. Subjects were treated with fixed low-dose (20 mg/day) oral isotretinoin once daily for 6 months along with topical sunscreens. Response was graded as mild (<25%), moderate (26-50%), and good (>50%) improvement based on decrease in intensity and progression of hyperpigmentation.
Results:
Twenty-seven patients (17 females and 10 males), aged 20-62 years, completed the study. Twenty-three (85.2%) patients had active disease and pruritus at presentation. Treatment outcome was moderate improvement in 15 patients (55.7%) followed by good in seven (21.8%) and mild in two (6.2%). Pruritus subsided at the earliest at 9-14 days, and disease stabilized by 4-6 weeks in treatment-responsive patients. Patients with a shorter duration (≤5 years) of disease and limited body area involvement had a better outcome.
Conclusions:
Low-dose isotretinoin seems to be a promising treatment modality in stabilizing and decreasing the pigmentation in LPP particularly in early and limited disease.
Background:
Melasma is a frequent and difficult to treat skin disorder. Results of laser therapy are inconsistent.
Objective:
To determine the safety and efficacy of low-fluence Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser for melasma treatment and assess recurrence rates and histopathologic findings before and after treatment.
Methods:
Twenty patients were treated with 10 weekly sessions of low-fluence 1064-nm QS Nd:YAG laser at 1-week intervals. The modified Melasma Area and Severity Index (mMASI) score was evaluated at baseline; 1 week; and 1, 3, and 6 months after treatment. Epidermal melanin quantification was performed on 10 biopsy samples and compared before and after treatment.
Results:
All patients showed improvement by mMASI scores, range (21%-75%) compared with that at baseline. No permanent side effects occurred. The recurrence rate was 81%. By histopathology, a slight, nonsignificant (p = .305) decrease in melanin deposition was seen in all layers of the epidermis 1 week after the laser treatments ended.
Conclusion:
The results confirm the safety and effectiveness of low-fluence QS Nd:YAG laser for treating melasma; however, the high recurrence suggests poor long-term results when the laser is used as a monotherapy.
Background and objectives:
Laser procedures in skin of color (SOC) patients are challenging due to the increased risk of dyspigmentation and scarring. A novel 755 nm alexandrite picosecond laser has demonstrated effectiveness for tattoo removal and treatment of acne scars. No studies to date have evaluated its applications in pigmentary disorders. The purpose of this retrospective study was to evaluate the safety profile and efficacy of the picosecond alexandrite laser compared to the current standard treatment, Q-switched ruby and neodynium (Nd):YAG nanosecond lasers, for pigmentary disorders in SOC patients.
Study design/materials and methods:
A retrospective photographic and chart evaluation of seventy 755 nm alexandrite picosecond, ninety-two Q-switched frequency doubled 532 nm and 1,064 nm Nd:YAG nanosecond, and forty-seven Q-switched 694 nm ruby nanosecond laser treatments, in forty-two subjects of Fitzpatrick skin types III-VI was conducted in a single laser specialty center. The picosecond laser was a research prototype device. Treatment efficacy was assessed by two blinded physician evaluators, using a visual analog scale for percentage of pigmentary clearance in standard photographs. Subject assessment of efficacy, satisfaction, and adverse events was performed using a questionnaire survey.
Results:
The most common pigmentary disorder treated was Nevus of Ota (38.1%), followed by solar lentigines (23.8%). Other pigmentary disorders included post-inflammatory hyperpigmentation, congenital nevus, café au lait macule, dermal melanocytosis, Nevus of Ito, and Becker's nevus. Clinical efficacy of the Q-switched nanosecond lasers and picosecond laser treatments were comparable for lesions treated on the face with a mean visual analog score of 2.57 and 2.44, respectively, corresponding to approximately 50% pigmentary clearance. Subject questionnaires were completed in 58.8% of the picosecond subjects and 52.0% of the Q-switched subjects. Eighty four percent of subjects receiving Q-switched nanosecond laser treatments and 50% of the subjects receiving alexandrite 755 nm picosecond laser treatments felt satisfied to completely satisfied. Side effects observed in subjects treated with the alexandrite 755 nm picosecond laser were similar to those commonly observed and reported with the nanosecond Q-switched technology. All side effects were temporary, resolving within one month, and no long-term complications were noted. All patients who were very satisfied with their picosecond laser treatment for Nevus of Ota noted a delayed improvement only after 3 months.
Conclusion:
The 755 nm alexandrite picosecond, 694 nm ruby, 532 nm, and 1064 nm neodynium:YAG nanosecond lasers appear to be safe and effective modalities for removal of pigmentary disorders in skin of color patients with no long-term complications if used appropriately. This study demonstrates the potential of the 755 nm alexandrite picosecond laser in further clinical applications beyond tattoo removal. While the Q-switched lasers were effective, promising results were also observed using an early version of the novel picosecond laser for the removal of pigmentary lesions in SOC patients. As we continue to improve our understanding of the 755 nm picosecond laser, this device may prove to be a safe and effective alternative to the Q-switched lasers for the treatment of facial pigmented lesions in patients with skin of color.
Melasma is a common acquired skin disorder. While different treatments are currently being used, in many cases it is refractory to treatment. According to the effects of topical steroids in decreasing skin pigmentation, we studied the efficacy of this new method for treatment of melasma. A total of 42 women with facial melasma, admitted to the department of dermatology of Hamadan, were enrolled in the study. They were divided randomly into two groups (A and B), group A (case) received subepidermal triamcinolone injections with a dose of 4mg per cc and 5mm intervals until complete blanching of melasma lesions, and group B (control) received Kligman's formula (hydroquinone5%, tretinoin 0.1%, and dexamethasone 0.1%). At the first visit, we completed the MASI score papers, and we repeated that at weeks 4 and 8 of the study. We followed them for two months, every two weeks. At each visit, side effects and clinical response to treatment were noted. A decrease in MASI was observed in both group (11.57 ± 4.33 vs 9.31 ± 3.75 at 4th week and vs 8.01 ± 3.1 at 8th week, P-value < 0.001 in group A, and 10.46 ± 5.61 vs 9.76 ± 5.21 at 4th week and vs 8.96 ± 4.96 at 8th week, P-value< 0.001 in group B). In comparison between 2 groups, response to treatment was much better in group A than group B (P-value<0.001). In comparison to topical treatments, based on these findings, triamcinolone microinjection is a new, safe and strong therapeutic method for treatment of melasma. © 2015 Tehran University of Medical Sciences. All rights reserved.
Lichen planus pigmentosus is a well-recognized variant of lichen planus; however, its etiopathogenesis is still unclear. An effective and safe treatment for lichen planus pigmentosus is needed; therefore, the authors examined a series of five patients with lichen planus pigmentosus with successful response to a combination of topical tacrolimus and oral dapsone.
Background and objectives:
Photo-aging in Chinese often presents with benign pigmentary lesions. Q-switched lasers for pigmentary lesions in Asians had reported a risk of post-inflammatory hyperpigmentation (PIH) up to 25%. Longer pulse widths in the millisecond domains were advocated with reduced risk of PIH. Recently, picosecond lasers of various wavelengths were introduced with proven efficacy in tattoo removal. The objective of this study is to assess the efficacy and safety of a novel picosecond 755-nm alexandrite laser for the treatment of benign pigmented lesions in Asians retrospectively.
Methods:
A list of all patients who received picosecond 755-nm alexandrite laser treatment at a private dermatology center in Hong Kong was included. Those who had any other laser or topical treatment during the period of picosecond laser treatment were excluded. The age, skin phototype, type of pigmentary lesion, number of treatments performed was recorded. The baseline and most recent standardized photographs were assessed by trained physicians for comparison. A score of 0-4, representing poor 0-24%, fair 25-49%, good 50-74%, excellent 75-95%, and complete 95%+ improvement was given. Adverse events associated with the laser treatment were also recorded. All patients were followed up until 6 months after the last laser session.
Results:
A total of 13 subjects were included in the present study. The number of treatment sessions received ranged from one to seven. The benign pigmentary lesions consist of Nevus of Ota, café-au-lait patches, lentigines, Becker's nevus, Hori's macules, and nevus spilus. Among patients with Nevus of Ota, one patient achieved complete clearance after four treatments and two other patients had excellent clearance after three and four sessions, respectively. Patients with café-au-lait had fair to good clearance after one to seven treatment sessions. One patient who has Hori's macules was resistant to laser treatments and a fair response was achieved after eight treatments. In the present series, two patients (4.8%) developed transient hypopigmentation, which had improved upon subsequent follow-up in both cases and none had post-inflammatory hyperpigmentation.
Conclusions:
The novel picosecond 755-nm alexandrine laser is effective for the treatment of benign pigmentary lesions in Chinese, especially for the clearance of Nevus of Ota. Picosecond laser appears to be associated with a much lower risk of PIH for treatment of pigmentary lesions in Asians.
Drug-induced pigmentation represents 10 to 20% of all cases of acquired hyperpigmentation and this hypothesis must be systematically raised in unexplained pigmented lesions especially in elderly people. The pathogenesis of drug-induced pigmentation is variable according to the causative medication and can involve an accumulation of melanin, sometimes following a nonspecific cutaneous inflammation and often worsened by sun exposure, an accumulation of the triggering drug itself, a synthesis of special pigments under the direct influence of the drug or deposits of iron following damage to the dermal vessels.
The influence of sun exposure is usually obvious in most cases, either by sun-induced melanin synthesis stimulation with formation of complexes between melanin and the causative drug or by transformation of the drug in visible particles usually taken up by dermal macrophages under the influence of sunlight.
The main drugs implicated in causing skin pigmentation are nonsteroidal anti-inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, tetracyclines, heavy metals and psychotropic drugs. Clinical features are very variable according to the triggering molecule, with a large range of patterns and shades which are sometimes more or less reminiscent of the culprit drug. Histological findings are very variable as well but the colored particles are often concentrated within dermal macrophages which are sometimes localized in a distinctive fashion with respect to dermal structures such as vessels or adnexes. Treatment is often limited to sun-avoidance or interruption of treatment with the offending drug but laser therapy recently gave rise to hope of a cure in some cases. These measures are often followed by a fading of the lesions but the pigmentation may last for a long time or may even become permanent in a small percentage of patients.
Article Information
Accepted for Publication: June 12, 2014
Corresponding Author: Heather K. Hamilton, MD, Waldorf Dermatology & Laser Associates, PC, 57 N Middletown Rd, Nanuet, NY 10954 (heatheraklein@yahoo.com).Published Online: October 8, 2014. doi:10.1001/jamadermatol.2014.1838.
Conflict of Interest Disclosures: None reported.
Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus that tends to occur in middle-aged individuals with darker pigmented skin. Clinical findings include hyperpigmented, brown to gray-brown macules and patches in sun-exposed areas, typically on the head and neck. Histopathologic features include epidermal atrophy, vacuolar degeneration of the basal layer of the epidermis, perivascular lymphohistiocystic infiltrate in the upper dermis, and dermal melanophages. We present a unique case of LPP that was characterized by an atypical initial inflammatory phase and subsequent circinate lesions with central clearing.
We report 4 patients with relatively asymptomatic, annular brownish plaques arising in the skin creases. The lesions had remained stable for months despite many topical treatments. Histological amination revealed an atrophic epidermis with a dermal lichenoid inflammatory infiltrate showing marked pigmentary incontinence. These clinical and pathological features were consistent with lichen planus pigmentosus-inversus, a rare, recently described variant of lichen planus, with only 10 cases reported to date. It has been suggested that the intensity and speed of onset of the inflammatory response could be modulated by keratinocyte surface markers, which could also determine the typical morphology of the lesions of this disease.
Hyperpigmentation of the skin is a common dermatologic condition in all skin types but most prominent in brown-skinned population. In skin of color any inflammation or injury can be accompanied by alterations in pigmentation (hyper/hypo-pigmentation). Postinflammatory hyperpigmentation (PIH) can be observed in many skin conditions including acne, eczema, and contact dermatitis. In the control of skin pigmentation, parallel to the cross-talk between keratinocytes and melanocytes, increasing evidence has underlined the crucial role exerted by the interactions between mesenchymal and epithelial cells through the release of fibroblast-derived growth factors. Among these factors, the keratinocyte growth factor (KGF), alone or in combination with interleukin-1α, induces melanin deposition in vitro and hyperpigmented lesions in vivo. Furthermore, a moderate increase of KGF and a high induction of its receptor have been shown in solar lentigo lesions, suggesting the involvement of this growth factor in the onset of the hyperpigmented spots. Several studies highlight the possible contribution of the fibroblast-derived melanogenic growth factors to the hyperpigmentated lesions, in the context of the mesenchymal - epithelial interactions modulating melanocyte functions.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Summary Background Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood.
Objectives To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin.
Methods Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana–Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff–van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined.
Results The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin.
Conclusions Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.
Lichen planus pigmentosus-inversus is a rare variant of lichen planus, with less than 20 cases reported in the medical literature. It presents as asymptomatic to mildly pruritic, hyperpigmented macules and/or patches involving intertriginous and flexural areas and skin folds in light-skinned individuals. The unique pattern of skin involvement, clinical features, and histology are distinctive. The combination of hyperpigmented lesion(s) isolated to non-sun exposed, intertriginous, and flexural areas with lichenoid histology is unique and separates it from other similar entities, such as lichen planus actinus and erythema dyschromicum perstans/ashy dermatosis. The case well highlights this unusual condition and represents the first case reported in the United States.
Melasma is a common disorder of hyperpigmentation affecting millions of people worldwide. While it is thought to be triggered or exacerbated by sun exposure and hormones, much remains to be understood about its pathogenesis. A thorough understanding of the etiology of melasma and the research tools available to study this condition are crucial to enhancing management and developing novel targeted therapies of this often frustrating condition.
Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus, for which no effective treatment is available. Objectives The aim of this study was to determine the clinical, epidemiological and histopathological characteristics of LPP patients in Kuwait.
Thirty-three LPP patients who attended the Dermatology outpatient clinics at Farwaniya Hospital, Kuwait from the year 2002 to 2008 were studied for clinical, epidemiological and histopathological findings. Thirteen of these patients were treated with topical tacrolimus 0.03%. Ointment applied topically twice daily for the duration varying from 6 to 12 weeks.
Of the 33 patients, 21 were men and 12 were women. The duration of eruption ranged from 6 weeks to 3 years. The face and neck were the commonest sites, affecting 18 (54.5%) patients. The pattern of pigmentation was diffuse in 18 (54.54%) patients, reticular in seven (21.2%), blotchy in five (15.2%), linear in two (6.1%) and perifollicular in one (3%). Twenty patients had positive serology for hepatitis C virus (HCV), with significantly higher serum liver enzymes (ALT and AST). Of the 13 patients, who were treated with tacrolimus Ointment, seven (53.8%) showed appreciable lightening of the pigmentation after an average of 12 weeks.
We conclude that HCV may be one of the factors associated with LPP, in those who have a tendency to develop LPP. However, this possible association should be interpreted carefully. In addition, tacrolimus ointment could have a beneficial role in the treatment of LPP.
Dyschromias, in particular hyperpigmentation, are major issues of concern for people of color. Pigmentary disorders such as melasma and postinflammatory hyperpigmentation (PIH) can cause psychological and emotional distress and can pose a negative impact on a person's health-related quality of life. The precise etiology of these conditions is unknown. Therapies for melasma and PIH target various points during the cycle of melanin production and degradation. Therapies for these conditions include topical agents and resurfacing procedures. Hydroquinone remains the gold standard of topical agents. Other efficacious agents include kojic acid, azelaic acid, mequinol, and retinoids. Cosmeceutical agents include licorice, arbutin, soy, N-acetyl glucosamine, and niacinamide. Resurfacing procedures that have been used to treat melasma and PIH include chemical peels, microdermabrasion, lasers, and intense pulsed light. These procedures are best used in combination with topical bleaching agents. Given the propensity of darker skin to hyperpigment, resurfacing procedures should be used with care and caution. Maximal results are best achieved with repetitive, superficial, resurfacing modalities. In addition, ultraviolet protective measures such as broad-spectrum sunscreens are fundamental to the successful management of these conditions.
Normal human epidermal melanocytes became swollen and more dendritic with an increase in the amount of tyrosinase and immunoreactive b-locus protein when they were cultured for 2 days with the following arachidonic acid metabolites: prostaglandin (PG) D2, leukotriene (LT) B4, LTC4, LTD4, LTE4, thromboxane (TX) B2 and 12-hydroxy eicosatetraenoic acid (12-HETE). The effect of LTC4 was particularly strong compared to that of PGE2, about which we have previously reported. On the other hand, PGE1, PGF2 alpha and 6-ketoPGF1 alpha did not show any significant stimulatory effect. These data suggest that arachidonate-derived chemical mediators, especially LTC4, may be responsible for the induction of post-inflammatory hyperpigmentation of the skin.
Clinical and epidemiologic evidence has shown acanthosis nigricans to be closely related to defective tissue utilization of insulin in a number of previously recognized (e.g., obesity, lipodystrophy, and leprechaunism) as well as recently characterized (e.g., type A and type B syndromes) disorders. This article reviews the relationship of acanthosis nigricans to these insulin-resistant states. It also focuses attention on the possibility that interaction between excessive amounts of circulating insulin with insulin-like growth factor receptors on keratinocytes and dermal fibroblasts leads to the development of acanthosis nigricans.
Melasma is characterized by a facial hypermelanosis of light to dark brown color, being more common in women of Hispanic origin. In this study, 27 men with melasma were evaluated clinically and histologically to compare their features with those of previous studies. Three patterns of localization were recognized, namely, centrofacial, malar, and mandibular. On the basis of Wood's light examination, an epidermal, a dermal, and a mixed type were identified. Epidermal hyperpigmentation only and epidermal and dermal hyperpigmentation were found in histologic analysis of the cases. Significant etiologic factors included exposure to sunlight in 66.6% as well as a familial predisposition in 70.4% of the cases. This study demonstrated that melasma in men shares the same clinicohistologic characteristics as in women, but hormonal factors do not seem to play major significant role.
A young white girl had a peculiar poikilodermatous pigmentary disturbance and a megaloblastic anemia. Both changes were resolved with vitamin B12 therapy. Epidermal cells in areas of pigmentation were found to have abnormally large nuclei similar to those previously described in the mucosal epithelium of patients with vitamin B12 deficiency. The epidermal nuclear size returned to normal following treatment, supporting the assumption that these enlarged nuclei were indicative of the deficiency. The data suggest that a common mechanism linked with the vitamin B12 deficiency state may be responsible for both the pigmentary disturbance and the cytologic abnormality. The absence of cytologic changes in the skin of normally pigmented areas in this patient and in a second case of vitamin B12 deficiency without a pigmentary disturbance is consistent with this theory.
A study was done to determine the frequency of common dermatoses seen in private dermatology practices composed of predominantly black patients. This was then compared to similar previous studies. New trends in common dermatoses in private black patients were found. The most common dermatosis noted was acne vulgaris, followed by eczema, pigmentary disorders, seborrheic dermatitis, and alopecias.
Irregular disfiguring skin hyperpigmentation due to inflammation may develop in black persons. We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream). Fifty-four subjects completed a 40-week randomized, double-blind, vehicle-controlled study. Twenty-four subjects applied tretinoin daily to the face, arms, or both areas, and 30 subjects applied vehicle cream. At base line and after 40 weeks of treatment, each subject's post-inflammatory hyperpigmented lesions and normal skin were assessed by clinical and colorimetric evaluations and by analysis of biopsy specimens.
The facial post-inflammatory hyperpigmented lesions of the tretinoin-treated subjects were significantly lighter after the 40 weeks of therapy than those of the vehicle-treated subjects (P < 0.001); overall improvement was first noted after four weeks of tretinoin treatment. At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05). The epidermal melanin content in the lesions decreased by 23 percent with tretinoin and by 3 percent with vehicle (P = 0.24). Normal skin was minimally lightened by tretinoin as compared with vehicle, according to both clinical evaluation (0.1 vs. -0.1 unit change on an 8-point scale; P = 0.055) and colorimetry (P < 0.001). Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed.
Topical application of tretinoin significantly lightens post-inflammatory hyperpigmentation and, to a clinically minimal but statistically significant degree, lightens normal skin in black persons.
Treatment of postinflammatory hyperpigmentation in patients of Fitzpatrick skin types IV, V, and VI is difficult. Glycolic acid peels are useful for pigment dyschromias in caucasians; however, there are no controlled studies examining their safety and efficacy in dark-complexioned individuals.
To determine if serial glycolic acid peels provide additional improvement when compared with a topical regimen of hydroquinone and tretinoin.
Nineteen patients with Fitzpatrick skin type IV, V, or VI were randomized to a control or peel group. The control group applied 2% hydroquinone/10% glycolic acid gel twice daily and 0.05% tretinoin cream at night. The peel patients used the same topical regimen and, in addition, received six serial glycolic acid peels (68% maximum concentration). Patients were evaluated with photography, colorimetry, and subjectively.
Sixteen patients completed the study. Both treatment groups demonstrated improvement, but the patients receiving the glycolic acid peels showed a trend toward more rapid and greater improvement. The peel group also experienced increased lightening of the normal skin.
This pilot study demonstrates that serial glycolic acid peels provide an additional benefit, with minimal adverse effects, for the treatment of postinflammatory hyperpigmentation in dark-complexioned individuals.
Two cases of hyperthyroidism with hyperpigmentation are presented. In both cases, hyperpigmentation was seen on the lower extremities, most strikingly on the shins, backs of the feet and the nail bed. Histology of the pigmented skin showed basal melanosis and heavy deposition of haemosiderin around dermal capillaries and sweat glands. Treatment with mercazol in both cases resulted in no significant waning of pigmentation. Distribution of hyperpigmentation, haemosiderin deposition and poor response to the treatment may be characteristic features of the pigmentation caused by hyperthyroidism, and may represent differences from the pigmentation seen in Addison's disease.
This is a retrospective study on the epidemiology of 205 patients with melasma seen in a tertiary dermatological referral centre in Singapore.
The mean age of the 205 patients with melasma was 42.3 years with a female preponderance of 21:1 female to male ratio. There were proportionally more Chinese with melasma than the other races compared to the racial distribution of patients attending our clinic. Ninety percent of our patients had skin type III or IV. The mean age of onset of melasma was 37.6 years. Most sought treatment only 5 years after the appearance of their melasma. Forty-six percent of melasma were light brown, the majority of which were distributed on the malar areas (89%). More than 2/3 had epidermal melasma. Eighty-eight percent had mild localised melasma (occurring on < 20% of the total facial area). Only 26.8% of our patients reported sun exposure, 25 (12.1%) reported pregnancy and 27 (13.1%) reported oral contraceptives as precipitating factors. A positive family history of melasma was observed in 21 (10.2%) patients. Sunscreen forms the backbone in the treatment of melasma in our patients. Most patients were prescribed a sunscreen together with hydroquinone containing bleaching cream (54%) as first line treatment. Patients with epidermal type of melasma responded slightly better to treatment than those with dermal type of melasma (28% experienced > 25% reduction in pigmentation compared to 16% respectively (n.s.)).
Overall, 53% of our patients experienced some reduction of pigmentation with 28% experiencing > 25% reduction and 7% experiencing > 75% reduction. In 40%, the pigmentation remained stable with treatment. Treatment of melasma remains an enigma. More studies need to be undertaken to improve treatment response to alleviate the psychosocial impact melasma has on the patient.
Hyperpigmentation is a common disorder of the skin, particularly in brown-skinned patients. Melasma is a common cause of facial hyperpigmentation and can be resistant to treatment. A combination of topical creams and gels, chemical peels, and sunscreens may be necessary for significant improvement. Erythema dyschromicum perstans is a dermal pigmentation seen on the trunk and proximal extremities, most commonly presenting in dark-skinned Hispanics. Drug-induced and postinflammatory hyperpigmentation may last for many months after the offending drug or dermatitis has been eliminated. These disorders, including their management, is reviewed in this article.
Drug-induced pigmentation represents 10 to 20% of all cases of acquired hyperpigmentation and this hypothesis must be systematically raised in unexplained pigmented lesions especially in elderly people. The pathogenesis of drug-induced pigmentation is variable according to the causative medication and can involve an accumulation of melanin, sometimes following a nonspecific cutaneous inflammation and often worsened by sun exposure, an accumulation of the triggering drug itself, a synthesis of special pigments under the direct influence of the drug or deposits of iron following damage to the dermal vessels. The influence of sun exposure is usually obvious in most cases, either by sun-induced melanin synthesis stimulation with formation of complexes between melanin and the causative drug or by transformation of the drug in visible particles usually taken up by dermal macrophages under the influence of sunlight. The main drugs implicated in causing skin pigmentation are nonsteroidal anti-inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, tetracyclines, heavy metals and psychotropic drugs. Clinical features are very variable according to the triggering molecule, with a large range of patterns and shades which are sometimes more or less reminiscent of the culprit drug. Histological findings are very variable as well but the colored particles are often concentrated within dermal macrophages which are sometimes localized in a distinctive fashion with respect to dermal structures such as vessels or adnexes. Treatment is often limited to sun-avoidance or interruption of treatment with the offending drug but laser therapy recently gave rise to hope of a cure in some cases. These measures are often followed by a fading of the lesions but the pigmentation may last for a long time or may even become permanent in a small percentage of patients.
We examined seven patients with lichen planus pigmentosus (LPP) clinically and microscopically. Clinically, all patients had a striking predominance of lesions in an intertriginous location, with most of them in the axillae. Microscopically, two biopsies were of significance. Except for the regressive lichen planus, which is usual in LPP, the active inflammatory phase was also present. In these biopsies the very intensive hydropic degeneration of basal keratinocytes was combined with the absence of compensatory increased proliferation of keratinocytes, i.e. without acanthosis. The short duration of this process probably led to the quick transformation into a long noninflammatory regressive phase with incontinence of the pigment. These specific morphogenetic dynamics are possibly why most of the morphs of LPP present as brown, non-pruritic, small inflammatory macules. Because of the highly characteristic inverse location of the lesions in our patients we propose the designation LPP-inversus for this variant of the disease.
Lichen planus pigmentosus is a fairly common disorder of pigmentation in Indians, but reports comprising a sizeable number of patients are lacking in the literature. We now describe the clinical and epidemiological features and histopathological findings for 124 lichen planus pigmentosus patients. A retrospective analysis of medical records of patients attending our centre during the past 12 years was undertaken. Of the 124 patients (56 male, 68 female), the majority (48.4%) had the disease for 6 months to 3 years. The face and neck were the commonest sites affected with pigmentation varying from slate grey to brownish-black. The pattern of pigmentation was mostly diffuse (77.4%), followed by reticular (9.7%), blotchy (7.3%) and perifollicular (5.6%). Lichen planus was noted in 19 patients with typical histopathological changes of the disorder. Lichen planus pigmentosus, a distinct clinical entity commonly encountered in the Indian population, should be considered in the spectrum of lichenoid disorders as a variant of lichen planus.
Erythema dyschromicum perstans (EDP) is a rare disorder of pigmentation that is most common in Hispanic patients. In adults, EDP has a slow onset and is unlikely to resolve spontaneously. The etiology and clinical course in children is poorly defined. Physical examinations, chart reviews, and telephone interviews were performed for eight pediatric patients with EDP who were followed at Children's Memorial Hospital in Chicago between 1990 and 1998. All the patients available for long-term follow-up (five of the eight) experienced complete clearance without recurrence in an average of 2.5 years. In all of our patients, the onset was noted from July to December. The administration of aminopenicillins was coincident with the development of EDP in two of the patients. Review of the English-language literature reveals that 25 prepubertal children have previously been reported. Including our patients, 69% of prepubertal children with EDP experienced resolution. We concluded that the clinical course of childhood (prepubertal) EDP differs from that of adult EDP, and it is more likely to resolve within 2-3 years.
The spectrum of cutaneous disease occurring in ethnic populations is as broad and diverse as the ethnic populations themselves. Many skin diseases are seemingly common to most of the ethnic populations, however, including blacks, Hispanics, Asians, and Native Americans. These diseases include acne vulgaris; pigmentary disorders; eczematous dermatitis; and infection caused by bacteria, fungi, and viruses. Diseases of a more cosmetic nature have emerged over recent years and include the pigmentary disorders melasma and postinflammatory pigmentation, acne keloidalis nuchae, scalp and facial folliculitis, keloidal scarring, alopecia, and photoaging. The identification of cutaneous diseases affecting the rapidly increasing ethnic populations serves to focus resources both research and clinical in these areas.
Despite new technologies, few studies have assessed the histologic alterations in patients with melasma. Using current technologies, the present study was designed to re-evaluate the light microscopic, immunohistochemical, and ultrastructural changes of the hyperpigmented and adjacent normal skin of patients with melasma. Twenty-one patients were included in this study. Two millimeter punch biopsies were taken from the hyperpigmented and adjacent normal skin of the face. The integrity of the epidermis and dermis was assessed by light microscopy, computer-assisted image analysis, immunohistochemistry, and electron microscopy. Stains included hematoxylin-eosin and Fontana-Masson for melanin detection. Immunostaining was performed using Mel-5 antibody and CD1a antibody as markers for melanin and Langerhans cells, respectively. However, mild lymphohistiocytic infiltrates were present in 75% of the hyperpigmented areas. The areas of hyperpigmentation showed increased deposition of melanin in the epidermis and dermis of all cases. There was a statistically significant increase in the content of epidermal melanin. There were no quantitative increases in melanocytes in the hyperpigmented areas of skin. However, the melanocytes in the hyperpigmented areas were larger, intensely stained cells with very prominent dendrites. Electron microscopy revealed more melanosomes in keratinocytes, melanocytes, and dendrites in the involved skin in comparison to the uninvolved skin. The results of this study suggest that melasma is a consequence of specific hyperfunctional melanocytes that cause excessive melanin deposition in the epidermis and dermis.
Previous investigations have reported the efficacy of tazarotene 0.1% cream for the treatment of dyschromia associated with photoaging and for acne vulgaris. The present investigation assessed tazarotene 0.1% cream for the treatment of postinflammatory hyperpigmentation (PIH) in a double-blind, randomized, vehicle-controlled study of 74 patients from darker racial ethnic groups who had acne. Once-daily application of tazarotene cream was shown to be effective against PIH, achieving significantly greater reductions compared with vehicle in overall disease severity and in the intensity and area of hyperpigmentation within 18 weeks (P< or =.05). Mean levels of erythema, burning, and peeling were no more than trace in both groups throughout the study, and mean levels of dryness were no more than mild in both groups. In our study, tazarotene cream was effective and well tolerated in the treatment of PIH in patients with darker skin.
Facial and neck pigmentations are significant cosmetic problems. They are common in middle-aged women, related to endogenous (hormones) and exogenous factors (cosmetics, perfumes, sun exposure), and often represent paramount causes of emotional distress. Although melasma is the most common cause of facial pigmentation, there are many other forms including drug-induced and postinflammatory hyperpigmentation. We review pathogenesis, clinical and histopathological data, effect on quality of life, and treatment options in facial hyperpigmentation disorders.