Melanosis coli: A comprehensive review / Melanosis coli: una revisión exhaustiva

Melanosis coli (MC) is a common condition characterized by a black or brown pigment deposited in the colorectal mucosa. It is a reversible condition that is influenced by many factors, such as living habits and bowel function. However, the epidemiology and etiology of MC are still unclear. Most studies show that there is a significant correlation between the use of anthraquinone laxatives and the occurrence of MC. At present, the mechanism of the apoptosis theory is widely recognized as regards the pathogenesis of MC. There is no specific clinical manifestation of MC, and its diagnosis is mainly based on a complimentary examination, such as endoscopic and histopathological tests. General treatment, such as changing living habits, is preferred, and medical or surgical treatment should not be considered in the absence of serious malignancy. The aim of this review is to systematically present and outline the concepts of the epidemiology, etiology, histopathology, pathogenesis, clinical manifestations, diagnosis and treatment of MC, in order to improve the understanding of this condition

La melanosis coli (MC) es una entidad común caracterizada por el pigmento negro o marrón depositado en la mucosa colorrectal. Es una entidad reversible que está influenciada por muchos factores, como los hábitos de vida y la función intestinal. Sin embargo, la epidemiología y la etiología de la MC todavía no están claras. La mayoría de los estudios apoyan que existe una correlación significativa entre el uso de laxantes antraquinónicos y la aparición de MC. Actualmente, el mecanismo de la teoría de la apoptosis es ampliamente reconocido con respecto a la patogénesis de la MC. No existe una manifestación clínica específica de la MC, y el diagnóstico de la MC se basa principalmente en un examen auxiliar, como las pruebas endoscópicas e histopatológicas. Se prefiere el tratamiento general, como el cambio de hábitos de vida; por el contrario, no se debe considerar el tratamiento médico o quirúrgico en ausencia de una malignidad grave. El objetivo de esta revisión es entregar y resumir sistemáticamente los conceptos de la epidemiología, la etiología, la histopatología, la patogénesis, las manifestaciones clínicas, el diagnóstico y el tratamiento de la MC para mejorar la comprensión de esta entidad

Melanism influences the use of social information in a polymorphic owl.

Social information use has well-known fitness benefits. However, causes underlying the apparent inter-individual variability in the propensity to use social information are poorly studied. Melanins are pigments responsible for most of intra-specific color variation in vertebrates and their variation is often associated with changes in behaviour. Here, we explored whether melanism is related to individual propensity to use social information in the color polymorphic scops owl Otus scops. We manipulated social information on predation risk at nests by broadcasting calls of the sympatric little owl Athene noctua and found that owlets of brownish females exposed to alarm calls had lower levels of natural antibodies than those of greyish females. In parallel, we found changes in parental behaviour contingent on coloration because when exposed to the risky treatment brownish females returned earlier to nests than greyish females and owlets raised by brownish females were fed with smaller prey than those raised by greyish ones. These results provide support for a previous ignored role of melanins on the propensity to use social information, which may help to explain the maintenance of melanin-based color polymorphisms wherever social environments are variable.

Premature cell senescence in human skin: Dual face in chronic acquired pigmentary disorders.

Although senescence was originally described as an in vitro acquired cellular characteristic, it was recently recognized that senescence is physiologically and pathologically involved in aging and age-related diseases in vivo. The definition of cellular senescence has expanded to include the growth arrest caused by various cellular stresses, including DNA damage, inadequate mitochondria function, activated oncogene or tumor suppressor genes and oxidative stress. While senescence in normal aging involves various tissues over time and contributes to a decline in tissue function even with healthy aging, disease-induced premature senescence may be restricted to one or a few organs triggering a prolonged and more intense rate of accumulation of senescent cells than in normal aging. Organ-specific high senescence rate could lead to chronic diseases, especially in post-mitotic rich tissue. Recently, two opposite acquired pathological conditions related to skin pigmentation were described to be associated with premature senescence: vitiligo and melasma. In both cases, it was demonstrated that pathological dysfunctions are not restricted to melanocytes, the cell type responsible for melanin production and transport to surrounding keratinocytes. Similar to physiological melanogenesis, dermal and epidermal cells contribute directly and indirectly to deregulate skin pigmentation as a result of complex intercellular communication. Thus, despite senescence usually being reported as a uniform phenotype sharing the expression of characteristic markers, skin senescence involving mainly the dermal compartment and its paracrine function could be associated with the disappearance of melanocytes in vitiligo lesions and with the exacerbated activity of melanocytes in the hyperpigmentation spots of melasma. This suggests that the difference may arise in melanocyte intrinsic differences and/or in highly defined microenvironment peculiarities poorly explored at the current state of the art. A similar dualistic phenotype has been attributed to intratumoral stromal cells as cancer-associated fibroblasts presenting a senescent-like phenotype which influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. Here, we present a framework dissecting senescent-related molecular alterations shared by vitiligo and melasma patients and we also discuss disease-specific differences representing new challenges for treatment.

Efficacy and tolerability on melasma of a topical cosmetic product acting on melanocytes, fibroblasts and endothelial cells: a randomized comparative trial against 4% hydroquinone.

BACKGROUND: Recent data demonstrated that an altered basal membrane, activated melanocytes and secreted factors from keratinocytes but also fibroblasts and endothelial cells are involved in the pathophysiology of melasma. OBJECTIVES: To evaluate the efficacy and tolerability on melasma of a new topical skin-lightening cosmetic product combination (CCP) targeting several factors identified to be involved in melasma pathogenesis compared to 4% hydroquinone (HQ). METHODS: Forty-three women with melasma were enrolled in a 12-week double-blind, randomized, parallel-group trial and treated with CCP or 4% HQ cream. Efficacy was evaluated with the modified Melasma Area Severity Index (mMASI) score and colorimetric change. Cutaneous tolerability and patient satisfaction were also investigated. RESULTS: The mMASI score decreased for both products from baseline and over the study period. At week 12, 90% of the subjects who received the combination products had an improvement in pigmentation vs. 79% with HQ. Similarly, both products significantly increased Individual Typological Angle parameters. For both measures, no statistically significant difference was observed between CCP and HQ in terms of change from baseline. CPP was very well tolerated. CONCLUSIONS: Cosmetic product combination is as effective as HQ in the management of facial dyspigmentation and represents a safe alternative.

Neurofibromatosis tipos 1 y 2 / Neurofibromatosis type 1 and 2

La neurofibromatosis (NF) comprende un grupo de enfermedades genéticas de herencia autosómica dominante, que se clasifican de la siguiente manera: neurofibromatosis tipo 1 (NF1), neurofibromatosis tipo 2 (NF2) y schwannomatosis (también conocida como neurofibromatosis tipo 3). Esta última es una enfermedad muy infrecuente, con una prevalencia aproximada de 1/126 000 personas, por lo que solo profundizaremos las dos primeras. La NF1, también conocida como la enfermedad de Von Recklinghausen, es la más frecuente de las tres y afecta principalmente la piel y el sistema nervioso periférico. Se caracteriza por la presencia de máculas "café con leche", pecas axilares o inguinales, nódulos de Lisch (hamartomas en el iris) y neurofibromas (tumores de la vaina de nervios periféricos). Otras manifestaciones menos frecuentes, aunque de mayor gravedad, incluyen gliomas del nervio óptico, meningiomas, neurofibromas malignos, escoliosis y displasia de la tibia. Su diagnóstico se suele realizar al nacimiento o durante los primeros años de vida, y se estima que un 50% de quienes la padecen presenta dificultades cognitivas. No hay datos concluyentes sobre la mortalidad en los pacientes con NF1, aunque se sabe que la expectativa de vida es menor que en la población general. La NF2 tiene una prevalencia considerablemente menor que la NF1 y su inicio es más tardío, afectando principalmente a adultos jóvenes. La presentación clínica típica se caracteriza por acúfenos, hipoacusia y ataxia en contexto de la presencia de schwannomas vestibulares bilaterales. Otros hallazgos menos frecuentes incluyen schwannomas de nervios periféricos, meningiomas, ependimomas o astrocitomas. La esperanza de vida es de unos 36 años, con una supervivencia media desde el momento del diagnóstico de 15 años. (AU)

Neurofibromatosis (NF) includes a group of genetic diseases with an autosomal-dominant inheritance pattern, and they are classified as follows: Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and Schwannomatosis (also known as neurofibromatosis type 3). This last one is a very rare disease, with an approximate prevalence of 1/126000, so we will only deepen in the first two. NF1, also known as von Recklinghausen disease, is the most frequent, and mainly affects the skin and peripheral nervous system. Its typical manifestations are the presence of café-au-lait macules, axillary or inguinal freckles, Lisch nodules (hamartomas in the iris) and neurofibromas (peripheral nerve sheath tumors). Less frequent manifestations, although more serious, include optic nerve gliomas, meningiomas, malignant neurofibromas, scoliosis and tibial dysplasia. The diagnosis is usually made at birth or during the first years of life, and approximately 50% of patients present cognitive difficulties. There is no conclusive data on mortality in patients with NF1, although it is known that life expectancy is lower than in general population. NF2 has a considerably lower prevalence than NF1, and its onset is later in life, mainly affecting young adults. Its typical clinical presentation is characterized by tinnitus, hearing loss and ataxia in the context in the presence of bilateral vestibular schwannomas. Less frequent findings include peripheral nerve schwannomas, meningiomas, ependymomas or astrocytomas. Life expectancy is about 36 years old, with a median survival from the moment of diagnosis of 15 years. (AU)

Melasma pathogenesis: a review of the latest research, pathological findings, and investigational therapies.

Melasma is an acquired hyperpigmentation disorder most commonly affecting females with darker skin types. It is triggered by several factors including sun exposure, genetic influences, and female sex hormones. The pathology of melasma extends beyond melanocytes and recent literature points to interactions between keratinocytes, mast cells, gene regulation abnormalities, neovascularization, and disruption of basement membrane. This complex pathogenesis makes melasma difficult to target and likely to recur post treatment. A better understanding of the latest pathological findings is key to developing novel and successful treatment options. This review aims to provide a summary of the more novel pathological findings and latest investigational therapies.

Clinical efficacy of laser combined with menstrual regulation in the treatment of female melasma: a retrospective study.

The aim of this study was to evaluate the clinical efficacy of using a Medlite C6 Q-switch Nd:YAG laser combined with menstrual regulation-based traditional Chinese medicine (TCM) in the treatment of female melasma. Forty cases of female patients with melasma, who were treated between December 2013 and December 2015 at the Jiangsu Provincial Hospital of Traditional Chinese Medicine, were reviewed retrospectively. Twenty patients received Q-switch Nd:YAG 1064 nm laser treatments combined with menstrual regulation treatments (experimental group), and 20 patients were treated only with the laser (control group). All treatments lasted for 6 months. The patients' faces were photographed before, immediately, and 6 months after treatment. The therapeutic efficacy was assessed by the reduction in the Melasma Area and Severity Index (MASI) score and the total skin damage score, and this was then compared between the two groups. Immediately and 6 months after the treatment, both the MASI and total skin damage scores in the experimental group were significantly lower compared to those in the control group (P < 0.001). The experimental group had significantly higher basic recovery and effectiveness rates than the control group (P = 0.020 and P = 0.008, respectively) and had a significantly lower invalidity rate (P < 0.001). Results from Medlite C6 Q-switch Nd:YAG laser treatment combined with menstrual regulation are superior than those obtained using only a laser for the treatment of female melasma.

Treatment of melasma using tranexamic acid: what's known and what's next.

Tranexamic acid is a procoagulant agent that is approved by the US Food and Drug Administration for treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. Through its inhibitory effects on the plasminogen activation pathway, tranexamic acid also mitigates the UV radiation-induced pigmentation response. Systemic tranexamic acid has consistently been reported as an effective treatment of melasma, though its broad use may be limited by the risk for thromboembolism. Limited studies have investigated the efficacy of topical tranexamic acid, with or without the use of adjunctive therapies to increase uptake. This review summarizes the effects of tranexamic acid on the pathophysiology of melasma and the available evidence on the off-label treatment of melasma using systemic and topical tranexamic acid.

Efficacy of functional microarray of microneedles combined with topical tranexamic acid for melasma: A randomized, self-controlled, split-face study.

To evaluate the efficacy of a functional microarray of microneedles (MNs) plus topical tranexamic acid (TA) for melasma in middle-aged women in China.Thirty female subjects with melasma were enrolled in this study. The left or right side of the face was chosen randomly to be pretreated with a functional microarray of MNs, followed by topical 0.5% TA solution once per week for 12 weeks. The other half-face was the control, treated with a sham device plus topical 0.5% TA solution. At baseline and at weeks 4, 8, and 12 of treatment, clinical (photographic) evaluations and parameters determined by Visia were recorded. At baseline and week 12, patient satisfaction scores and the biophysical parameters measured by Mexameter were also recorded. Side effects were evaluated at baseline and at the end of the 12 weeks.In total, 28 women (93.3%) completed the study. The brown spots' scores measured by Visia were significantly lower on the combined therapy side than on the control side at 12 weeks after starting treatment; there was no significant difference between sides at 4 or 8 weeks. After 12 weeks, melanin index (MI) decreased significantly in both 2 groups, and the MI was significantly less on the combined side at week 12. Transepidermal water loss, roughness, skin hydration, skin elasticity, and erythema index showed no significant differences between 2 sides at baseline, 4, 8, and 12 weeks after treatment. Physicians' evaluations of photographs showed better results at week 12 with combined therapy: >25% improvement was observed in the MNs plus TA side in 25 patients, and in the TA side in only 10 patients. Subjective satisfaction scores on both sides increased significantly. The participants were more satisfied with the results of the combined therapy side than the control side. No obvious adverse reactions were observed throughout the study.Combined therapy with a functional microarray of MNs and topical TA solution is a promising treatment for melasma.

Ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis.

This article explores three neurocutaneous syndromes (NCSs), i.e. genetic disorders producing developmental abnormalities of the skin and an increased risk of neurological complications. In this review, different aspects of ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis are examined: clinical features, genetic defect, mutation spectrum, pathogenesis, and neurobiological basis; indications for clinical practice are also provided to the readers. The aim of this review is to stress the importance of cooperation among dermatologists, neurologists and psychiatrists, in order to provide patients suffering from these diseases with timely diagnosis and targeted treatments.

Repigmentación melánica de la melanosis gingival: revisión sistemática / Melanin repigmentation of gingival melanosis: systematic review

La melanosis gingival o pigmentación melánica fisiológica es definida como una alteración caracterizada por un cambio en la coloración de la encía, en la cual la encía adquiere una tinción oscura ocasionada por una acumulación de melanina. Objetivo El propósito de esta revisión fue evaluar la literatura actual sobre el grado de repigmentación gingival luego del tratamiento de la melanosis. Material y método Búsqueda detallada en las bases de datos PubMed, Cochrane y Embase para obtener la información sobre las técnicas de tratamiento y resultados posoperatorios de cada procedimiento quirúrgico. Resultados De los 219 artículos identificados inicialmente, 22 cumplieron con los criterios de inclusión (reportes de casos, series de casos, ensayos clínicos y revisiones sistemáticas). Las técnicas con el escalpelo evidenciaron una repigmentación al cabo de 3 meses a 3 años y las técnicas con el uso de láser diodo entre 18-24 meses. Las técnicas de criocirugía, electrocirugía, laser Er:YAG y láser Nd:YAG evidenciaron escasa o nula repigmentación. Conclusión La repigmentación melánica es más común en las técnicas que utilizan el escalpelo, siendo el rango de recurrencia entre 3 meses a 3 años. La heterogeneidad de los estudios limita la realización de un metaanálisis con respecto a los resultados de tratamiento de la melanosis gingival.

Gingival melanosis or physiological gingival melanin pigmentation is a disorder that causes a change in the colour of the gums, which acquire a dark stain caused by an accumulation of melanin Objective The purpose of this review was to assess the current literature on treatment of gingival melanosis and assessing the degree of gingival repigmentation. Material and method A detailed search was conducted in the PubMed, Cochrane and Embase databases for information on treatment techniques and post-operative results of each surgical procedure. Results Of the 219 articles initially identified, 22 met the inclusion criteria (case reports, case series, clinical trials, and systematic reviews). Scalpel techniques showed a repigmentation after 3 months - 3years, and techniques using laser diode between 18-24 months. Techniques with cryosurgery, electro-surgery, Er: YAG laser and Nd: YAG laser showed little or no repigmentation. Conclusion Melanin repigmentation is more common in techniques that use the scalpel, with recurrences ranging from between 3months and 3years. The heterogeneity of the studies limited the performing of a meta-analysis on the results of treatment of gingival melanosis.

Effect of body mass and melanism on heat balance in Liolaemus lizards of the goetschi clade.

The body temperature of ectotherms depends on the environmental temperatures and behavioral adjustments, but morphology may also have an effect. For example, in colder environments, animals tend to be larger and to show higher thermal inertia, as proposed by Bergmann's rule and the heat balance hypothesis (HBH). Additionally, dark coloration increases solar radiation absorption and should accelerate heat gain (thermal melanism hypothesis, TMH). We tested Bergmann's rule, the HBH and the TMH within the ITALIC! Liolaemus goetschilizard clade, which shows variability in body size and melanic coloration. We measured heating and cooling rates of live and euthanized animals, and tested how morphology and color affect these rates. Live organisms show less variable and faster heating rates compared with cooling rates, suggesting behavioral and/or physiological adjustments. Our results support Bergmann's rule and the HBH, as larger species show slower heating and cooling rates. However, we did not find a clear pattern to support the TMH. The influence of dorsal melanism on heating by radiation was masked by the body size effect in live animals, and results from euthanized individuals also showed no clear effects of melanism on heating rates. Comparison among three groups of live individuals with different degrees of melanism did not clarify the influence of melanism on heating rates. However, when euthanized animals from the same three groups were compared, we observed that darker euthanized animals actually heat faster than lighter ones, favoring the TMH. Although unresolved aspects remain, body size and coloration influenced heat exchange, suggesting complex thermoregulatory strategies in these lizards, probably regulated through physiology and behavior, which may allow these small lizards to inhabit harsh weather environments.

Neurocutaneous melanosis.

Neurocutaneous melanosis is a rare neurocutaneous syndrome that is associated with a high rate of mortality early in life. Individuals with large cutaneous melanocytic nevi (LCMN) are at risk, especially when the nevi are posterior, midline and accompanied by satellite nevi. Disrupted production and migration of melanocytic precursors from neural crest likely are responsible. Although the cutaneous lesions are at risk for melanoma, the most likely source of morbidity and mortality comes from "benign" melanocytic proliferation in the brain or central nervous system melanoma. Seizures and hydrocephalus are the common neurologic manifestations and typically arise in the first years of life. Brain magnetic resonance imaging in infants before myelination has matured is most sensitive for detecting abnormal melanosis in the brain, which preferentially involves the leptomeninges, cerebellum and anterior temporal lobes. Treatment is symptomatic and death occurs in many within 3 years of onset of neurologic symptoms. This prognosis may limit the extent to which extensive procedures or interventions are undertaken.

Common Neurocutaneous Syndromes.

Neurocutaneous syndromes are a diverse group of neurologic disorders with concurrent skin manifestations. Most neurocutaneous syndromes have a genetic basis and are believed to arise from a defect in the differentiation of the primitive ectoderm. In this regard, the skin can be a window into the central nervous system and can aid in the diagnosis of neurologic disease in children. The cutaneous signs may be subtle, which places great importance on the physical examination skills of clinicians providing primary care to children. Early recognition can help with proper diagnosis, formulating a treatment plan, anticipating potential complications, making appropriate referrals, and offering genetic counseling to families.

The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: a randomized clinical trial.

BACKGROUND: Treatment of melasma is unsatisfactory most of the times. Hormonal role is shown to exist in pathogenesis of the melasma, and sex-hormone related drugs may have an effect on melasma. AIM: To investigate efficacy of 1% flutamide cream versus 4% hydroquinone cream on melasma. METHODS: In a parallel randomized clinical trial, 74 women with melasma were allocated to receive a sunscreen along with 4% hydroquinone cream or 1% flutamide cream. Melasma Area and Severity Index (MASI), mexameter melanin assay, and patient satisfaction were investigated. RESULTS: Mean age of the participants was 33.8 years. Mean length of time suffering from Melasma was 96.3 months. The subjects reported in average 1.1 hours per day of exposure to sunlight. Mean standardized total patient satisfaction score was 28.8 (standard deviation [SD] 17.2) in flutamide group patients versus 18 (SD 15.5) in control group (P<0.01). Regardless of treatment group, the skin darkness assessed upon MASI scales was reduced over the treatment course (P<0.001). Using mixed effects, longitudinal modeling showed better treatment efficacy based on MASI scale for flutamide group compared to the hydroquinone group (P<0.05). However, longitudinal analysis of mexameter scores did not reveal any significant difference in melanin measurements between flutamide and hydroquinone. CONCLUSION: Topical flutamide appeared as effective as topical hydroquinone in treating melasma using mexameter assessment but with a better MASI improvement trend and higher patient satisfaction in flutamide treatment versus topical hydroquinone. As the present study is possibly the first clinical experience on efficacy of topical flutamide on melasma, it would be quite unreasonable to recommend clinical use of it before future studies replicate the results on its efficacy and safety.

Splenic melanosis in agouti and black mice.

An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic melanosis is correlated with hair or skin pigmentation, it must reflect the amount and perhaps the quality of pigment produced in hair follicle melanocytes. The present paper is our first study on splenic pigmentation in mice of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters (Mesocricetus auratus). After euthanasia skin and spleen was evaluated macroscopically, photographed and collected for further analysis using Fontana-Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR) at X-band. Spleens of the agouti mice revealed splenic melanosis but were slightly weaker pigmented than their black counterparts, while the presence of pheomelanin was difficult to determine. The fur of both phenotypes was of similar melanin content, with the same tendency as in the spleens. The contribution of pheomelanin in the agouti fur was on the border of detectability by EPR. Histological and EPR analysis confirmed the presence of melanin in the melanotic spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis does reflect the hair follicle pigmentation not only in black, but also in agouti mice.

The association of the sebum excretion rate with melasma, erythematotelangiectatic rosacea, and rhytides.

BACKGROUND: Rosacea and melasma are two common skin conditions in dermatology. Both conditions have a predilection for the centrofacial region where the sebaceous gland density is the highest. However it is not known if sebaceous function has an association with these conditions. AIMS AND OBJECTIVES: We aimed to assess the relationship between facial glabellar wrinkle severity and facial sebum excretion rate for individuals with rosacea, melasma, both conditions, and in those with rhytides. Secondly, the purpose of this study was to utilize high resolution 3D facial modeling and measurement technology to obtain information regarding glabellar rhytid count and severity. MATERIALS AND METHODS: A total of 21 subjects participated in the study. Subjects were divided into four groups based on facial features: rosacea-only, melasma-only, rosacea and melasma, rhytides-only. A high resolution facial photograph was taken followed by measurement of facial sebum excretion rate (SER). RESULTS: The SER was found to decline with age and with the presence of melasma. The SER negatively correlated with increasing Wrinkle Severity Rating Scale. Through the use of 3D facial modeling and skin analysis technology, we found a positive correlation between clinically based grading scores and computer generated glabellar rhytid count and severity. CONCLUSION: Continuing research with facial modeling and measurement systems will allow for development of more objective facial assessments. Future studies need to assess the role of technology in stratifying the severity and subtypes of rosacea and melasma. Furthermore, the role of sebaceous regulation may have important implications in photoaging.