Benjamín Moncada

Histochemical and immunohistochemical study in melasma: evidence of damage in the basal membrane.

The pathogenesis of melasma has not been clearly elucidated. Using Fontana Masson; diastase-resistant periodic acid-Schiff stains; and immunohistochemistry to stem cell factor (SCF), its receptor c-kit, anti-mast cell tryptase, and anti-collagen type IV antibody, we evaluated melasma lesions and compared them with perilesional skin and photoprotected skin. Samples were taken from lesional and photoprotected nonlesional skin in 24 patients. In other 24 patients, we took biopsies of lesional and perilesional skin. With Fontana Masson, we observed many pigmented basal cells protruding into the dermis of the melasma skin. Periodic acid-Schiff stain and anti-collagen type IV showed damage on the basal membrane in 95.5% and 83%, respectively, in melasma lesion. The immunoreactivity of SCF and the prevalence of mast cells were increased in the dermis of melasma compared with perilesional dermis. The expression of c-kit was significantly increased at lesional epidermis; a frequent protrusion of c-kit-positive basal cells into the dermis was evident in 70% versus that in 29% of perilesional skin. The expression of c-kit was increased at lesional dermis of melasma compared with perilesional skin. We found a low correlation between c-kit expression and prevalence of mast cells; these were increased in melasma skin. The results may suggest a role of SCF, c-kit, and mast cells in the pathogenesis of melasma. We were surprised by the unexpected evidence of damage to basal membrane (BM), which could facilitate the fall or the migration of active melanocytes and melanin into the dermis allowing the constant hyperpigmentation in melasma.

Immunopathology of polymorphous light eruption: T lymphocytes in blood and skin

Polymorphous light eruption (PLE; actinic prurigo) is a relatively common dermatologic disease. People suffering from it have a pruritic skin eruption on exposed areas. PLE may be an immunologically mediated disease. Sixteen patients with PLE were studied. T lymphocytes and the helper and suppressor-cytotoxic subsets were assessed in peripheral blood by an indirect immunofluorescent method with the use of monoclonal antibodies. Total T lymphocytes were significantly increased as compared to controls. By an indirect immunoperoxidase technic with the use of monoclonal antibodies, characterization of the dermal cell infiltrate was done. Predominance of T total, T helper, and cells marked with Ia antigen were found. These findings suggest that an abnormal immune response is responsible for the tissue damage in PLE.

A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma

Background. Multiple modalities have been used in the treatment of melasma with variable success. Niacinamide has anti-inflammatory properties and is able to decrease the transfer of melanosomes. Objective. To evaluate the therapeutic effect of topical niacinamide versus hydroquinone (HQ) in melasma patients. Patients and Methods. Twenty-seven melasma patients were randomized to receive for eight weeks 4% niacinamide cream on one side of the face, and 4% HQ cream on the other. Sunscreen was applied along the observation period. They were assessed by noninvasive techniques for the evaluation of skin color, as well as subjective scales and histological sections initially and after the treatment with niacinamide. Results. All patients showed pigment improvement with both treatments. Colorimetric measures did not show statistical differences between both sides. However, good to excellent improvement was observed with niacinamide in 44% of patients, compared to 55% with HQ. Niacinamide reduced importantly the mast cell infiltrate and showed improvement of solar elastosis in melasma skin. Side effects were present in 18% with niacinamide versus 29% with HQ. Conclusion. Niacinamide induces a decrease in pigmentation, inflammatory infiltrate, and solar elastosis. Niacinamide is a safe and effective therapeutic agent for this condition.

Immune sensitization against epidermal antigens in polymorphous light eruption

To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.

Presence of activated lymphocytes in the peripheral blood of patients with halo nevi

BACKGROUND The involution of the central pigmented lesion in halo nevus (HN) seems to be mediated by an immune response against self antigens expressed by melanocytes. OBJECTIVE We assessed the presence of activated lymphocytes in the peripheral blood lymphocytes from patients with HN. METHODS Peripheral blood was obtained from patients with HN associated with benign pigmented lesions (5) or melanoma (2) as well as from patients with melanoma without HN (5) and healthy subjects (10). Activated lymphocytes were detected by flow cytometry analysis using monoclonal antibodies (mAb) against CD69, CD71, CD98, HLA-DR, and activated beta(1) integrins (HUTS-21 mAb). RESULTS The peripheral blood lymphocytes from patients with HN, associated with either benign or malignant lesions, exhibited a significantly higher expression of all activation markers studied compared with patients with melanoma without HN or compared with healthy subjects. Therefore the peripheral blood of HN patients contained a significant fraction of lymphocytes with an activated (CD69(+), HLA-DR(+), CD98(bright)), cell proliferating (CD71( bright)), and high adhesive (HUTS-21(bright)) phenotype. These activated cells disappeared from peripheral blood after the surgical resection of the skin lesion. CONCLUSION Our findings further support the involvement of immune activation in HN phenomenon.

Use of Raman spectroscopy for the early detection of filaggrin-related atopic dermatitis

Background: Filaggrin (FLG) gene mutations, which result in complete or incomplete loss of proFLG/FLG peptides, have been reported as an important predisposing factor for atopic dermatitis (AD) and secondary atopic phenotypes such as atopic asthma.

The effect of methotrexate on the expression of cell adhesion molecules and activation molecule CD69 in psoriasis.

Background  The mechanism of the action of methotrexate (MTX) in the treatment of psoriasis has not been completely elucidated.

Pentoxifylline in the Treatment of Actinic Prurigo

Background: Actinic prurigo (AP) is a chronic familial photodermatosis usually seen in Latin-American Mestizo and Indian populations. It frequently begins in childhood and is more prevalent in females. The pathogenesis of AP has not been clearly elucidated, but previous studies have suggested an immune-mediated condition. Many drugs have been employed to treat AP patients with variable success. Objective: To assess the clinical efficacy of pentoxifylline (PTX) in the treatment of AP patients by measuring its effects on lesions and pruritus. Methods: 10 patients with severe AP were included to receive PTX in a 6-month open-label uncontrolled study. Results: Clinical improvement of lesions was evident in all patients. Relief in pruritus was evident after 1 month of treatment and was maintained while receiving PTX. Five patients were followed up for 2 years, 2 obtained complete remission, and 3 had an important reduction in the use of corticosteroids. Conclusion: PTX was useful in the treatment of our actinic prurigo patients. It may induce a complete or partial remission of lesions and allow a decrease in the use of topical corticosteroids.

Lichen Amyloidosis Improved by 0.1% Topical Tacrolimus

Lichen amyloidosis (LA) is a chronic pruritic disorder characterized by cutaneous amyloid deposition without systemic involvement. Clinical features consist in intensely pruritic hyperkeratotic papules that coalesce into plaques, mostly found on the anterior legs, upper back, forearms and thighs. Treatments available are generally nonsatisfactory, and new therapeutic options are long overdue. They usually rely on topical or intralesional corticosteroids [1–3], although UV therapy [2], dimethyl sulfoxide [4], surgical procedures [5], retinoids [6], calcipotriol [1] and oral immunosuppressants [7] have also been reported to be beneficial. A previously healthy 46-year-old woman presented to our outpatient clinic with an 18-month history of intensely pruritic hyperkeratotic brown papules that coalesced into infiltrated plaques on the ventral side of her left shin and both elbows quite characteristic of LA (fig. 1). She had previously been treated with clobetasol propionate 0.05% ointment and intralesional triamcinolone acetonide along with sedative antihistaminics, producing only a limited and transient response. With the purpose to ameliorate the itch in this patient, we tried tacrolimus 0.1% ointment twice a day on the affected areas given its proven effectiveness in lichenified atopic dermatitis [8]. After a 2-week trial, we observed resolution of the pruritus, but, more strikingly, a marked improvement in thickness of the plaques was obtained after 2 months of continuous application (fig. 2). Scratching is probably the first and single most important feature in the development of lesions of LA [9]. Following this, keratin peptides of apoptotic keratinocytes are transformed by dermal macrophages and fibroblasts into amyloid fibrils [10]. Because deposition of amyloid is not the cause but may be the result of friction, treatment should be aimed at alleviating the pruritus instead of removing

Molecular structure and concentration of melanin in the stratum corneum of patients with melasma.

Melasma is an abnormal acquired hyperpigmentation of the face of unknown origin, it is considered a single disease and very little has been found regarding its pathogenesis. It is usually assumed that melasma is due to excessive melanin production, but excessive retention or abnormal metabolism of this molecule has not yet been considered. In order to search for an alternate explanation for the excessive pigmentation in melasma the molecular structure and concentration of melanin in the stratum corneum of patients with melasma was analyzed using Raman spectroscopy and optical transmission spectroscopy, respectively. From this study it became apparent that in melasma melanin is concentrated in the deeper layers of the skin but its exteriorization remains the same as for healthy skin. Raman spectroscopy measurements showed degraded molecules of melanin in some subjects, which may help explain the variable success rate of the standard therapy.