A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions. / [Articulo traducido] Serie de 69 dermatosis relacionadas con la COVID-19 con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

Relationship between ultraviolet index (UVI) and first-, second- and third-degree sunburn using the Probit methodology.

In this paper, a relation between the ultraviolet index (UVI) as a Sun exposure time and its effects in the form of burns according to the skin type has been elaborated. Moreover, we present a new expression that relates the intensity of solar radiation and the UVI, as well as expressions to obtain the percentage of population affected both by first and second degree lllsunburn for every skin-type. The results have been adjusted and validated through experimental results taken from the bibliography. Finally, this paper presents a table where the population can easily interpret the UVI values and calculate the maximum time one can be exposed to solar radiation without getting sunburn. In addition, this article aims to raise awareness of the potential harm caused by solar radiation by indicating the percentage of population affected by different types of sunburn depending on skin-type. Moreover, ultraviolet exposure to sunlight could not just result in sunburn, but also have long-term effects on eyes, or even cause immune system disorders or melanoma. Therefore, managing risk perception with this useful table could familiarize the population with actual harm prevention.

Pyrimethanil degradation by photo-Fenton process: Influence of iron and irradiance level on treatment cost.

This study evaluates the combined effect of photo-catalyst concentration and irradiance level on photo-Fenton efficiency when this treatment is applied to industrial wastewater decontamination. Three levels of irradiance (18, 32 and 46W/m2) and three iron concentrations (8, 20 and 32mg/L) were selected and their influence over the process studied using a raceway pond reactor placed inside a solar box. For 8mg/L, it was found that there was a lack of catalyst to make use of all the available photons. For 20mg/L, the treatment always improved with irradiance indicating that the process was photo-limited. For 32mg/L, the excess of iron caused an excess of radicals production which proved to be counter-productive for the overall process efficiency. The economic assessment showed that acquisition and maintenance costs represent the lowest relative values. The highest cost was found to be the cost of the reagents consumed. Both sulfuric acid and sodium hydroxide are negligible in terms of costs. Iron cost percentages were also very low and never higher than 10.5% while the highest cost was always that of hydrogen peroxide, representing at least 85% of the reagent costs. Thus, the total costs were between 0.76 and 1.39€/m3.

Induction of Autoantibodies and Autoimmune Diseases in Patients with Psoriasis Receiving Tumor Necrosis Factor Inhibitors. / Inducción de anticuerpos y enfermedades autoinmunes en pacientes con psoriasis tratados con fármacos anti-TNFα.

BACKGROUND: The induction of antinuclear antibodies (ANA) and the onset of autoimmune diseases have been reported after treatment with tumor necrosis factor (TNF) inhibitors, though controversy persists. OBJECTIVES: To determine the frequency of onset of autoimmune diseases and of the appearance of autoantibodies in psoriasis patients administered TNF inhibitors (adalimumab and etanercept) subcutaneously and to correlate this with the effectiveness of treatment, adverse effects, and the order of use of TNF inhibitors. We also tried to identify any factors that might predict the appearance of ANA and autimmune diseases. METHODS: We performed a retrospective study of a cohort of 121 patients monitored over an 11-year period. ANA were measured at baseline and at 3, 6, and 12 months; positive results were followed up by study of antibodies to double-stranded DNA. Extractable nuclear antigen (ENA) antibodies were also studied at baseline and at 3, 6, and 12 months. Patients with a baseline assay of ANA and ENA at least one more assay during the first year were included in the study, and these antibodies were measured annually thereafter. Psoriasis area severity index was calculated and adverse effects were recorded at each visit. RESULTS: A significant increase in ANA positivity was observed during treatment of moderate-to-severe psoriasis with adalimumab and etanercept, but this was not associated with the onset of autoimmune diseases. No correlation was observed with treatment efficacy, the order of use of TNF inhibitors, or the appearance of adverse effects. No predictive factors for the appearance of ANA were identified, except for the body mass index. CONCLUSIONS: We recommend ANA measurement and screening for autoimmune diseases prior to treatment with TNF inhibitors, but not routine serial measurements of ANA during follow-up except in patients with signs or symptoms suggestive of autoimmune disease.

Low cost UVA-LED as a radiation source for the photo-Fenton process: a new approach for micropollutant removal from urban wastewater.

Light Emitting Diode (LED) technology has matured sufficiently to be considered as an alternative UVA radiation source in photoreactors. Currently, low energy consuming LEDs with a wide range of wavelengths and radiant flux are readily available. In this study, UVA-LEDs were used as a radiation source for the photo-Fenton process as tertiary treatment. The water matrix used was a simulated secondary effluent doped with 200 µg L-1 of the pesticide acetamiprid (ACTM) due to its recalcitrant nature. All experiments were carried out in a LED-box reactor at pH 2.8. The main purpose of this research was to gain some insight into the relationships among energy supply, LED consumption, UVA irradiance and reaction rate. The effect of LED wavelength on energy efficiency for ACTM degradation was studied by varying the iron concentration and liquid depth. Three wavelengths (365, 385 and 400 nm) and two iron concentrations (5 and 11 mg L-1) for two different liquid depths (5 and 15 cm) were evaluated in order to obtain more energy efficient conditions. The results suggest that while the wavelength of 365 nm with 11 mg Fe2+ L-1 was the best condition for ACTM degradation, the wavelength of 385 nm had slower kinetics, but higher energy efficiency.

[Neutrophilic urticaria or urticaria with predominantly neutrophilic inflammatory infiltrate: study of its clinical and histopathologic characteristics and its possible association with rheumatic disease]. / Urticaria con infiltrado inflamatorio de predominio neutrofílico o urticaria neutrofílica. Estudio de sus características clínicas e histopatológicas y de su posible asociación con enfermedad reumatológica.

INTRODUCTION: Neutrophilic urticaria, described by Winkelmann in 1985, has yet to be completely defined and its clinical significance is poorly understood. Nevertheless, recent publications suggest that it could be a marker for rheumatic disease. The primary objective of this study was to compare the prevalence of rheumatic disease in 2 groups of patients with urticaria: those with conventional urticaria (non-neutrophilic inflammatory infiltrate) and those with neutrophilic urticaria. MATERIAL AND METHODS: We retrospectively reviewed all biopsy samples taken from urticarial lesions in our hospital between January 1, 1999 and June 28, 2009. Urticaria was classified according to predefined morphologic and histopathologic patterns. We compared the clinical and histologic characteristics of neutrophilic urticaria with those of conventional urticarias in the 84 patients included. RESULTS: Of the 84 patients, 57.1% had neutrophilic urticaria. We did not find significant differences between the percentages of patients with rheumatic disease between the neutrophilic and nonneutrophilic urticaria groups. In patients with acute urticaria, we found a significantly higher proportion of samples with histopathologic signs of neutrophilic urticaria as opposed to conventional histopathology. Patients with neutrophilic urticaria also had higher white blood cell counts. CONCLUSIONS: The percentage of samples with neutrophilic urticaria in this series (57.1%) is higher than the percentages reported in the literature, possibly because we tended to biopsy recent lesions. We highlight that the presence of neutrophils in the biopsies of urticaria is a common finding and does not appear to be associated with other diseases.

Conjunctival-corneal intraepithelial neoplasia (Bowen disease) treated with orthovoltage.

PURPOSE: To report an exceptionally large conjunctival-corneal intraepithelial neoplasia (CCIN) (Bowen disease), for which the size of the tumor made classical treatment difficult, and to highlight the role of orthovoltage as an alternative treatment mode with good results. METHODS: Observational case report of a healthy 61-year-old man with CCIN. Given its extension, alternative treatment was performed with orthovoltage, thus avoiding surgery, with adjuvant cryotherapy and mitomycin C, and potential complications. After administering topical anesthetic, a therapeutic contact lens was placed on the cornea; then, the eyelids were held open with a blepharostat. A 1-mm lead plate with a window was placed over the blepharostat. The shape of the window reproduced the shape of the tumor to protect the rest of the eye structures from radiation. Orthovoltage was administered with direct field radiation that was focused on the tumor through the window. The patient received 500 cGy in 2 sessions/week for 2 weeks (2000 cGy) and then 7 sessions 300 cGy daily (2100 cGy). RESULTS: Evolution was good without side effects. After one-year follow-up, the patient was asymptomatic, without alterations of ocular surface or deep structures. CONCLUSIONS: Safely administered orthovoltage may be a good therapeutic option for the treatment of CCIN when complete surgical resection is complicated by the extension of the tumor. Compared with topical treatment, radiation is easier to administer, shortens and simplifies the treatment, and is independent of patient compliance.

[Safety information for tacrolimus: present and future]. / Datos de seguridad del tacrolimus: presente y futuro.

In this article there were regarded the most frequent side effects that appear in the patients who have been treated with topical tacrolimus, and the association between topical tacrolimus and the development of tumors is unfolded. The irritation in the site of application of the tacrolimus can manifiest as pruritus, sensation of burning and/or eritema located to the area of the application. It is the most frequent side effect, independently of the duration of the study. The cutaneous infections, especially the viral ones, tend to be more numerous in patients with atopic dermatitis that receive topic tacrolimus. After reviewing the medical literature one concludes that nowadays there doesn t exist scientific evidence of an increase of skin cancer, lymphomas or systemic immunosuppression in those patients that use or have used topical tacrolimus. Nevertheless, it is not possible to exclude the possibility that there appear cutaneous and/or systemic long-term side effects.

[Topical pimecrolimus and tacrolimus and the risk of cancer]. / Pimecrolimus/tacrolimus tópicos y riesgo de cáncer.

In this review the controversy regarding the association between topical pimecrolimus and tacrolimus and the development of tumors is unfolded. After reviewing the literature we conclude that, currently, there is no scientific evidence of an increased incidence of skin cancer, lymphomas or systemic immunosuppression in those patients that use or have used topical calcineurin inhibitors. Published studies lack adequate number of patients and/or the follow-up time is short enough to conclude that topical use of calcineurin inhibitors might be associated with the reported cases of skin cancer and lymphoma. Nevertheless the possibility of long term cutaneous and/or systemic side effects cannot be excluded.

Solar photocatalytic degradation of some hazardous water-soluble pesticides at pilot-plant scale.

The technical feasibility and performance of photocatalytic degradation of six water-soluble pesticides (cymoxanil, methomyl, oxamyl, dimethoate, pyrimethanil and telone) have been studied at pilot-plant scale in two well-defined systems which are of special interest because natural solar UV light can be used: heterogeneous photocatalysis with titanium dioxide and homogeneous photocatalysis by photo-Fenton. TiO(2) photocatalysis tests were performed in a 35L solar pilot plant with three Compound Parabolic Collectors (CPCs) under natural illumination and a 75L solar pilot plant with four CPC units was used for homogeneous photocatalysis tests. The initial pesticide concentration studied was 50 mg L(-1) and the catalyst concentrations employed were 200 mg L(-1) of TiO(2) and 20 mg L(-1) of iron. Both toxicity (Vibrio fischeri, Biofix) and biodegradability (Zahn-Wellens test) of the initial pesticide solutions were also measured. Total disappearance of the parent compounds and nearly complete mineralization were attained with all pesticides tested. Treatment time, hydrogen peroxide consumption and release of heteroatoms are discussed.

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF.

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.

Lovastatin inhibits its own synthesis in Aspergillus terreus.

Lovastatin suppresses its own synthesis in the microfungus Aspergillus terreus. The inhibitory effect was documented by spiking identical batch cultures with pure lovastatin (0, 50, 100 and 250 mg/l) 24 h after initiation from spores.

Angiokeratoma corporis diffusum in a Spanish patient with aspartylglucosaminuria.

Angiokeratoma corporis diffusum (ACD), initially considered to be synonymous with Fabry's disease, represents a well-known cutaneous marker of some other lysosomal enzyme disorders. Aspartylglucosaminuria (AGU) is a rare hereditary disorder mostly affecting the Finnish population, with only a few sporadic patients of non-Finnish origin. To date, only three patients with AGU have been reported with cutaneous lesions of ACD. A 19-year-old Spanish woman presented with a 10-year history of progressive ACD affecting the limbs, buttocks and trunk. After the age of 6 years she had developed progressive mental deterioration, coarse facies and macroglossia with a scrotal appearance. Peripheral blood smears showed many vacuolated lymphocytes. Enzyme analysis in cultured fibroblasts revealed a decreased activity of aspartylglucosaminidase. By the age of 31 years the patient had developed a bipolar psychosis, polycystic ovarian disease and severe impairment of cognitive skills. This is the first case of AGU detected in a Spanish patient presenting with cutaneous lesions of ACD. To our knowledge, macroglossia with a scrotal appearance and polycystic ovarian disease have not been reported in previous cases of AGU.