Skin Barrier Function and Its Relationship With IL-17, IL-33, and Filaggrin in Malar Melasma.

BACKGROUND: The pathogenesis of melasma remains unclear. Interleukin (IL)-17, a proinflammatory mediator, disturbs barrier function. Filaggrin (FLG) is a protein involved in epidermal barrier homeostasis and may be affected by IL-17 and IL-33. OBJECTIVE: To evaluate epidermal barrier function in malar melasma and its association with the expression of FLG, IL-17, and IL-33. METHODS: Twenty patients with malar melasma were included in this study. Colorimetric and transepidermal water loss (TEWL) was measured in lesional and adjacent unaffected skin at baseline and 30 minutes after barrier disruption using the tape-stripping test. Biopsies from melasma and perilesional skin were performed to evaluate the presence of FLG by immunohistochemistry, and profilaggrin, IL-17, and IL-33 expression were analyzed by reverse transcription-qualitative polymerase chain reaction. RESULTS: After the stripping test, the erythema and TEWL values were higher in the melasma than in the unaffected skin ( P = 0.01). Thirty minutes later, TEWL diminished, but it remained higher than in the perilesional skin. Profilaggrin increased as TEWL gradually decreased (R = -0.68, P = 0.04). FLG and IL-17 were higher in the melasma than in the perilesional skin ( P = 0.003). IL-17 and profilaggrin expression were positively associated (R = 0.60, P = 0.04). IL-33 expression was higher in the adjacent normal skin than in the melasma ( P = 0.01). CONCLUSION: This study found subclinical inflammation in the skin adjacent to the melasma, dysfunction of the epidermal barrier in lesions associated with chronic inflammation, and an abnormal differentiation process promoting an increase in FLG. These findings highlight the need to preserve the integrity of the facial stratum corneum in these patients.

Nutritional deficiency dermatitis related to branched-chain amino acid restriction in a child with maple syrup urine disease.

We present a one-year-old girl with maple syrup urine disease with dermatitis secondary to the restriction of amino acids as part of the treatment. We present the clinical evolution and histopathological correlation.

DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo.

BACKGROUND: Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. OBJECTIVE: To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. METHODS: Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. RESULTS: The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. CONCLUSIONS: We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.

A Case of Prostatic Carcinoma Manifesting as Cutaneous Facial Nodule.

Prostate cancer is the second most frequently diagnosed cancer worldwide and the fifth most common cause of cancer deaths among men. Cutaneous metastasis is an uncommon phenomenon in prostatic cancer, occurring in 0.06-0.3% of cases. Case Presentation. A 56-year-old man presented to our outpatient clinic with a one-month history of a 1.5 cm in diameter, solitary, asymptomatic, purple nodule located on his upper right cheek. After biopsy, prostatic cancer metastasis was diagnosed. Discussion. A literature review revealed 59 articles documenting 71 cases of this diagnosis. The review recorded epidemiological data, including age, duration, morphology, location, and outcome of patients. Conclusions. The skin is an uncommon site for metastasis of prostate cancer, and the review showed that its presence is associated with a poor prognosis (approximately 10 months from diagnosis).

Analysis of cutaneous pigmentation in a sample / Análisis de la pigmentación cutánea en una muestra.

Background: The blend of hemoglobin, carotenes, and melanin defines the skin color. Constitutive pigmentation is genetically determined, facultative color is induced when skin is exposed to environment. The objective was to quantify both pigmentations in a sample of Mexican population and to analyze its relationship with sex, age, and phototype. Methods: We evaluated 259 individuals during the winter. Skin colorimetry was obtained by diffuse reflectance spectrometry, using the International Commission of Illumination coordenates. L*a*b* parameters were measured and the individual typological angle (ITA) was estimated from forehead, thorax, neck, forearms, and buttocks areas. Results: Facultative pigmentation differed from constitutive in L*, a*, and ITA° values. In men, L* and ITA° parameters were lower. Constitutive pigmentation was similar between sexes. Phototypes III, IV, and V showed differences in L*, b*, and ITA°. Facultative values such as L*, a*, ATI°, and the constitutive a* reduce as age increases. Conclusions: The cutaneous tones of a sample of population were quantified recognizing their values for white, light brown, and dark brown skin. A reference frame for research related to cutaneous pigmentation in Mexico is presented.

Antecedentes: La mezcla de melanina, hemoglobina y carotenos definen el color cutáneo. La pigmentación constitutiva está determinada genéticamente, la facultativa se induce cuando la piel se expone al ambiente. El objetivo fue cuantificar ambas pigmentaciones en una muestra de población mexicana, y analizar su relación con el género, edad y fototipo. Métodos: Se evaluaron 259 personas durante un periodo invernal. La colorimetría cutánea se obtuvo mediante espectrometría de reflectancia difusa utilizando las coordenadas de la Comisión Internacional de Iluminación. Se registraron los valores L*a*b* y se estimó el ángulo tipológico individual (ATI°) en frente, tórax, cuello, antebrazos y glúteos. Resultados: La pigmentación facultativa difirió de la constitutiva en los parámetros L*, a*, y ATIº. En hombres, los valores facultativos de L* y ATI° fueron menores. La pigmentación constitutiva fue similar entre sexos. Los fototipos III, IV y V muestran diferencias en L*, b* y ATI°. Los valores facultativos L*, a*, ATI° y el constitutivo a* se reducen al incrementarse la edad. Conclusiones: Se cuantificaron los tonos cutáneos de una muestra de población reconociéndose los valores para la piel blanca, morena clara y morena oscura. Se presenta un marco de referencia para estudios relacionados con la pigmentación cutánea en México.

Repigmentation patterns induced by NB-UVB and their relationship with melanocytic migration and proliferation in vitiligo.

BACKGROUND/PURPOSE: Vitiligo is the most commonly acquired depigmentation disorder of the skin and is characterized by the destruction of melanocytes. Ultraviolet phototherapy with narrow band (UVB-NB) induces proliferation, differentiation, maturation, and migration of melanocytes. The clinical repigmentation is featured by follicular, marginal, and diffuse patterns. The aim of this study was to observe the process involved in the melanocyte migration and proliferation among these patterns and the unresponsive lesions following UVB-NB phototherapy. The focal adhesion kinase (FAK) and c-KIT were used as markers of melanocyte migration and differentiation, respectively. METHODS: A total of 17 vitiligo patients under UVB-NB therapy were selected. The patients expressed the three repigmentation patterns as well as unresponsive lesions at the conclusion of a 30-session cycle. Skin biopsies were evaluated by immunohistochemistry and qRT-PCR. RESULTS: We found an increased expression of c-KIT in the follicular pattern compared to the diffuse pattern that was expressed predominantly of FAK. Marginal pattern expressed both proteins. The unresponsive achromic lesions showed poor expressions of both markers. CONCLUSION: Proliferation was prominent in the follicular pattern, but migration was prominent in the diffuse pattern. For the marginal pattern, both dynamics were present. The absence of these markers in vitiligo lesions suggests a lack of response to UVB-NB.

[Allopurinol hypersensitivity syndrome. A report of two cases]. / Síndrome de hipersensibilidad por alopurinol. Informe de dos casos clínicos.

Patients in treatment with allopurinol are in risk of having life threatening adverse reactions particularly at the beginning of the treatment. Two percent of the patients prescribed with this drug have associated severe cutaneous adverse reactions. We present two cases of allopurinol hypersensitivity syndrome in mexican patients in which asymptomatic hyperuricemia was the indication to its use. The general physician and the specialist must be alert of this syndrome that causes elevate morbidity and mortality.

Los pacientes bajo tratamiento con alopurinol pueden presentar reacciones adversas potencialmente mortales, particularmente al inicio del tratamiento. Las reacciones cutáneas adversas por alopurinol tienen una prevalencia aproximada del 2 %. Presentamos dos casos de síndrome de hipersensibilidad por alopurinol en pacientes mexicanos en quienes la hiperuricemia asintomática fue la indicación para su uso. El médico general y el especialista deben estar alerta ante este síndrome que ocasiona alta morbilidad y mortalidad.

[Analysis of the cumulative solar ultraviolet radiation in Mexico]. / Análisis de la radiación solar ultravioleta acumulada en México.

BACKGROUND: The incidence of skin cancer has increased in Mexico in recent years. Ultraviolet radiation is the main risk factor associated. Due to the need to develop strategies to prevent skin cancer, the aim of the study was to estimate the UV intensity in several representative regions of Mexico, the average annual UV dose of these populations, and the potential benefit of applying sunscreen at different ages. METHODS: The intensity of UV radiation was quantified by remote and terrestrial radiometry. The dose of UV exposure was measured in minimal erythema doses using validated models for face and arms. The benefit of using a sunscreen was calculated with the use of a sunscreen with SPF 15 from birth to age 70. RESULTS: The UV radiation is lower in December and greater in the period from May to July. The region with a lower annual dose is Tijuana; and the higher annual dose is in the Mexico City area. The annual difference between these regions was 58 %. Through life, a low SPF sunscreen can reduce up to 66 % of the received UV dose. CONCLUSIONS: The geographical location is a risk factor for accumulation of UV radiation in Mexico. Since childhood, people receive high amounts of it; however, most of this dose can be reduced using any commercially available sunscreen, if applied strategically.

Introducción: La incidencia del cáncer de piel en México se ha incrementado en los últimos años. La radiación UV es el principal factor de riesgo asociado. Debido a la necesidad de desarrollar estrategias para evitarla, el objetivo del estudio fue estimar la intensidad UV en diversas regiones representativas del país, la dosis UV promedio anual de esas poblaciones y el beneficio potencial de la aplicación de un filtro solar a diferentes edades. Métodos: se cuantificó la intensidad de la radiación UV mediante radiometría terrestre y remota. La dosis de exposición UV se midió en dosis mínimas eritematógenas utilizando modelos validados para cara y brazos. El beneficio de realizar fotoprotección se calculó para el uso de un filtro con FPS 15 desde el nacimiento hasta los 70 años. Resultados: la radiación UV es menor en diciembre y máxima de mayo a julio. La localidad con menor dosis anual es Tijuana y la máxima el Distrito Federal. La diferencia anual entre estas regiones es de 58 %. Durante la vida, un filtro solar de baja potencia puede reducir hasta 66 % la dosis recibida. Conclusiones: la localización geográfica es un factor de riesgo para la acumulación de radiación UV en México. Desde la infancia, la población recibe dosis elevadas de radiación UV. La mayoría de esas dosis puede reducirse mediante cualquier filtro solar disponible en el comercio, si es aplicado de forma estratégica.

Relationship between transient receptor potential vanilloid-1 expression and the intensity of sensitive skin symptoms.

BACKGROUND: Sensitive skin (SS) is a hyper-reactive condition of the skin secondary to external factors, without objective signs of lesion. Its pathogenesis is still under investigation. Transient receptor potential vanilloid-1 (TRPV1) is a cation channel that responds to low pH and is related to nociception, neurogenic inflammation, and pruritus. AIMS: To determine the expression of TRPV1 in subjects with SS and correlate it with the degree of symptoms and skin pigmentation. PATIENTS/METHODS: We included 31 subjects self-diagnosed as having SS. Colorimetric values were obtained for assessment of skin phototype, and the lactic acid stinging test (LAST) was performed. Two skin biopsies from the nasolabial fold of each volunteer were obtained. Qualitative analysis of TRPV1 was carried out with immunohistochemistry. Quantitative analysis of TRPV1 was carried out with qRT-PCR. RESULTS: LAST was positive in 74% of the subjects, 56% of those having tan and brown skin. Immunohistochemistry staining for TRPV1 was greater in positive subjects (P = 0.03), but showed no correlation with the intensity of symptoms. Positive subjects also had higher TRPV1 mRNA expression compared to negative subjects (P < 0.001). This expression showed a positive correlation with the intensity of referred symptoms (R = 0.75, P < 0.001) and skin pigmentation (R = 0.63, P < 0.001). CONCLUSIONS: TRPV1 expression is upregulated in subjects with sensitive skin, and it correlates with the intensity of the symptoms. Our findings suggest a role for this receptor in the pathogenesis of sensitive skin syndrome.

CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma.

The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1ß, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.

Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia.

Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC) may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia.

Goose skin in a girl with Ehlers-Danlos syndrome.

Pellagra is a nutritional disorder secondary to niacin deficiency. The classical triad is dermatitis, diarrhea, and dementia. We report the case of a young girl with hypermobility-type Ehlers-Danlos syndrome who exhibited the classical pellagra symptoms, despite apparent adequate nutritional intake. Her condition resolved after oral niacin supplements were administered. Although this association has not previously been recognized, an inherited connective tissue disorder may be related to the appearance of pellagra.

Mycosis fungoides-like lesions in a patient with diffuse cutaneous sporotrichosis / / Lesiones que semejan una micosis fungoide en un paciente con esporotricosis cutánea difusa

Background. Sporotrichosis is a subacute or chronic mycosis acquired by traumatic inoculation or inhalation of fungal conidia. It is caused by the dimorphic fungus Sporothrix, which causes different clinical presentations, being the cutaneous and lymphocutaneous variants being the most frequent. The disseminated cutaneous form is a rare presentation occurring in a minority of cases in Mexico. Case report. We report an atypical case of disseminated sporotrichosis in an alcoholic and iatrogenically immunosuppressed patient, whose clinical lesions resembled tumoral-stage mycosis fungoides. Histological examination and culture revealed the presence of Sporothrix schenckii. Conclusions. The patient was treated with itraconazole 200 mg per day for 4 months with clinical resolution. To the best of our knowledge, this is the first report of this type of clinical manifestation (AU)

Antecedentes. La esporotricosis es una micosis subaguda o crónica adquirida por inoculación traumática o inhalación de conidias fúngicas. Está causada por el hongo dimórfico Sporothrix, y puede presentar distintas manifestaciones clínicas, si bien las variantes linfocutánea y cutánea son las más frecuentes. La forma cutánea diseminada es una presentación infrecuente que se ha observado en una minoría de casos en México. Caso clínico. Informamos de un caso atípico de esporotricosis diseminada en un paciente alcohólico y con inmunosupresión iatrogénica, cuyas lesiones se asemejaban a una micosis fungoide en fase tumoral. La observación histológica y el cultivo demostraron la presencia de Sporothrix schenckii. Conclusiones. El paciente fue tratado con 200 mg de itraconazol diarios durante 4 meses con resolución clínica. Este es el primer informe en relación con esta manifestación clínica (AU)

Hyperpigmentation and atrophy in folds as cutaneous manifestation in a case of mitochondrial myopathy.

Mitochondrial myopathies are inborn metabolism defect diseases manifested by symptoms reflecting failure of the final step in the mitochondrial respiratory chain. Clinical expression of these conditions can vary widely, but typically includes organ systems with a high energy demand, such as striated muscle, myocardium, and nervous and liver tissues. In contrast, cutaneous manifestations are rare and are non-specific, most commonly presenting as pigmentation disorders. In this case report, we present a case of Alpers syndrome accompanied by hyperpigmentation and atrophy in skin folds.

Subcutaneous Emphysema Induced by Cryotherapy: A Complication due to Previous Punctures.

Cryosurgery is a common therapeutic modality used in dermatology; therefore we must be aware of its possible adverse effects. We report a case of a patient with subcutaneous emphysema which occurred following the application of cryotherapy after multiple punctures of local anesthetic and intralesional steroids in a chest keloid scar. Despite the fact that this condition was gradually resolved after expectant observation, we warn about this complication when sprayed cryotherapy is preceded by multiple punctures on cutaneous lesions above bony surfaces. In similar settings, cryotherapy must be first administered or a cotton-tip applicator should be used.

Hailey-Hailey disease improved by fractional CO2 laser.

Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is an autosomal dominant skin condition that affects the adhesion of epidermal keratinocytes. Although the initial manifestation of flaccid vesicles on erythematous or normal skin in flexure sites frequently goes unnoticed, large, macerated, exudative plaques of superficial erosions with crusting are observed at the time of diagnosis. There is no specific treatment for HHD, and most cases are symptomatically supported. However, infrared laser ablation has been somewhat helpful. We present a case successfully treated with fractional CO2 laser showing a long-term favourable outcome and no adverse effects. Thus, this modality could be an alternative to full ablation for this condition.

Mycosis fungoides-like lesions in a patient with diffuse cutaneous sporotrichosis.

BACKGROUND: Sporotrichosis is a subacute or chronic mycosis acquired by traumatic inoculation or inhalation of fungal conidia. It is caused by the dimorphic fungus Sporothrix, which causes different clinical presentations, being the cutaneous and lymphocutaneous variants being the most frequent. The disseminated cutaneous form is a rare presentation occurring in a minority of cases in Mexico. CASE REPORT: We report an atypical case of disseminated sporotrichosis in an alcoholic and iatrogenically immunosuppressed patient, whose clinical lesions resembled tumoral-stage mycosis fungoides. Histological examination and culture revealed the presence of Sporothrix schenckii. CONCLUSIONS: The patient was treated with itraconazole 200mg per day for 4 months with clinical resolution. To the best of our knowledge, this is the first report of this type of clinical manifestation.