The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals, Alderley Park, United Kingdom) is under development as an anticancer agent. We ...studied the pharmacodynamic effects of ZD1839 on EGFR in the skin, an EGFR-dependent tissue, in cancer patients participating in ZD1839 phase I clinical trials.
We studied 104 pre- and/or on-ZD1839 therapy ( approximately at day 28 of therapy) skin biopsies from 65 patients receiving escalating doses of daily oral ZD1839. We measured ZD1839 effects on EGFR activation by immunohistochemistry using an antibody specific for the activated (phosphorylated) EGFR. Effects on receptor signaling (activated mitogen-activated protein kinase MAPK), proliferation, p27(KIP1), and maturation were also assessed.
Histopathologically, the stratum corneum of the epidermis was thinner during therapy (P <.001). In hair follicles, prominent keratin plugs and microorganisms were found in dilated infundibula. ZD1839 suppressed EGFR phosphorylation in all EGFR-expressing cells (P <.001). In addition, ZD1839 inhibited MAPK activation (P <.001) and reduced keratinocyte proliferation index (P <.001). Concomitantly, ZD1839 increased the expression of p27(KIP1) (P <.001) and maturation markers (P <.001) and increased apoptosis (P <.001). These effects were observed at all dose levels, before reaching dose-limiting toxicities.
ZD1839 inhibits EGFR activation and affects downstream receptor-dependent processes in vivo. These effects were profound at doses well below the one producing unacceptable toxicity, a finding that strongly supports pharmacodynamic assessments to select optimal doses instead of a maximum-tolerated dose for definitive efficacy and safety trials.
Selective immunoglobulin E deficiency (SIgED) is still an unrecognised primary immunodeficiency despite several observations supporting its existence. This study aimed to describe the skin ...manifestations associated with SIgED. We retrospectively assessed medical records of patients with SIgED, the diagnosis being based on serum IgE levels ≤2 Uk/L associated with normal serum levels of immunoglobulins G, M, and A. A total of 25 patients (24 female) with SIgED were included in the study. Eleven patients (44%) presented chronic spontaneous urticaria (CSU), five (20%) angioedema always associated with CSU, five erythema (20%), and six eczema (24%). Other, less frequent manifestations were lichen planus, anaphylactoid purpura, thrombocytopenic purpura, bullous pemphigoid, bullous pyoderma gangrenosum, and atypical skin lymphoproliferative infiltrate associated with reactive lymphadenopathy, chronic cholestasis, arthritis, and fibrosing mediastinitis. Fifteen patients (60%) had different types of associated autoimmune diseases, Hashimoto's thyroiditis being the most frequent (
= 5, 20%), followed by arthritis (
= 4, 16%), autoimmune hepatitis, neutropenia, vitiligo, and Sjögren's syndrome (
= 2, 8% each). Five malignancies were diagnosed in four patients (16%). An ultralow IgE serum level may be the only biomarker that reveals the presence of a dysregulated immune system in patients with a broad spectrum of skin manifestations.
Byline: Carlos Cuenca-Barrales, Maria Teresa Monserrat-Garcia, Javier Jesus Dominguez-Cruz, Mariona Sunol-Capella, Teresa Zulueta-Dorado, Raquel Fernandez, Jose Manuel Mascaro, Asuncion Vicente, Jose ...Bernabeu-Wittel
Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity ...(LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk.
Prospective analysis of 55–75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses’ Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time.
Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.
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•One-year changes of leisure-time physical activity (LTPA), sedentary behaviour and diet quality according to MetS severity have been assessed in older population (n = 4359) at high cardiovascular risk.•Decreasing MetSSS was associated with anti-inflammatory dietary pattern, high leisure-time physical activity, high Mediterranean diet adherence, low sedentary time, and low depression risk.•Decreasing MetSSS was associated with high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, bluefish and low intake of refined cereals, red and processed meat, cookies/sweets and snacks/ready-to-eat-meals.•Decreasing MetSSS was associated with high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamin B1, B6, B9, C, D, potassium, magnesium and phosphorus and low glycaemic index and SFA, TFA and carbohydrates intake.•Decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test and decreased sedentary and TV-viewing time.
Cutaneous infection by Phaeoacremonium parasiticum Fernandez-Pittol, Mariana J; Alejo-Cancho, Izaskun; Rubio, Elisa ...
Revista iberoamericana de micologia,
04/2019, Letnik:
36, Številka:
2
Journal Article
Recenzirano
Odprti dostop
AbstractBackgroundPhaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing ...subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. Case reportWe describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. ConclusionsThe diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown.
Patients treated with haematopoietic stem cell transplantation are at increased risk of cutaneous malignant neoplasms. There are no reports on the characteristics of melanocytic lesions in patients ...with chronic graft versus host disease and the value of recognizing these difficult lesions in high-risk patients. The objective of this study is to describe the clinical and dermoscopic characteristics of melanocytic lesions in patients with chronic graft versus host disease in order to understand their morphology. A prospective cross-sectional study was performed; 10 melanocytic lesions on the trunk and extremities were selected from each patient. A statistically significant association was found between regression and high total dermoscopic score and 7-point checklist score. Lesions were excised or included in short-term digital follow-up. Melanocytic lesions in patients with chronic graft versus host disease developing after allogeneic-haematopoietic stem cell transplantation exhibit marked structural and colour changes similar to melanoma. This is believed to result from the inflammatory process associated with graft versus host disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Background Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are older and have associated multiple comorbidities. Topical and systemic corticosteroids ...are considered the first-line treatment for BP, and immunosuppressants are used as steroid-sparing treatments. However, both have side-effects and contraindications, which are even more common in this older population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease these side-effects while achieving equal or better effectiveness and response rates. Omalizumab is a monoclonal antibody that targets IgE and has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. Objectives To assess the efficacy and safety of omalizumab for the treatment of BP. Methods We carried out a multicentre, retrospective, observational study including patients diagnosed with BP who received omalizumab for ≥ 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment were measured, and we evaluated the possible correlation with clinical response. We excluded patients treated with omalizumab for < 3 months, as we consider this duration to be insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment, we used the percentage of body surface area improvement. Results We included 36 patients. The vast majority had associated multiple comorbidities, and all patients had used other systemic therapies apart from corticosteroids before omalizumab. In total, 83% experienced some kind of treatment response and 42% of all patients treated achieved complete response. We did not find any correlation between higher IgE levels and a better response (P = 0.2). All patients tolerated omalizumab without reported side-effects. Conclusions Omalizumab is a good therapeutic alternative for BP as it provided clinical response in most patients, and nearly one-half of the cases achieved complete response. It showed no side-effects, which is crucial in older patients with BP.
Toxic epidermal necrolysis (TEN) is a rare life-threatening mucocutaneous reaction characterized by epidermal detachment. Treatment success relies on early diagnosis, rapid withdrawal of the ...causative drug and supportive care. However, clinical evidence for therapeutic management and specific treatment is insufficient and controversial. We describe the successful management of a TEN case secondary to sulfadoxine managed in our intensive care unit. The patient presented a generalized exanthema with mucocutaneous detachment affecting 45% of the body surface area, positive Nikolsky sign, perianal enanthema and conjunctival hyperemia. Treatment with intravenous immunoglobulins and corticosteroids was prescribed, as well as calcium folinate to prevent myelotoxicity of the causative drug. In this case, hemodialysis was dismissed due to the low efficiency of this technique in removing the triggering drug. Our case report confirms the efficacy of corticosteroids, IGIV, topical treatment on mucocutaneous lesions and supportive care for the management of TEN secondary to sulfadoxine.
Summary
Background
Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis with a special predisposition to affect body folds, particularly the intergluteal cleft. This disease is ...resistant to most topical and systemic treatments, as shown in the review of the literature we provide here. Itching and discomfort are often a difficult problem to solve.
Patients and Methods
Two patients with PP that had not responded to multiple topical treatments were treated with photodynamic therapy (PDT). Changes in plaque size, thickness and symptoms were assessed after treatment.
Results
Pruritus disappearance was observed in both patients after treatment with PDT. Partial clearance of the plaques was observed in one case. In the other case, a moderate clearance of hyperkeratosis was observed, although the size of the lesions persisted unchanged.
Conclusions
PDT seems to be a good therapeutic alternative in the treatment of PP, as it can provide symptomatic relief and clinical improvement of the lesions. However, it does not appear to be a curative treatment. Moreover, long‐term response is still unknown.
Jellyfish stings often cause immediate local skin reactions, and, less frequently, the affected individuals may develop delayed allergic reactions days or months after the sting. Here, we present 4 ...such cases. In all cases, color Doppler ultrasonography was performed at the time of diagnosis, and in 3 of the cases, clinical follow‐ups with ultrasonographic evaluations were performed. Ultrasonography initially showed dermal thickening with decreased echogenicity that progressively normalized during follow‐up. Ultrasonography was useful in quantifying inflammation by measuring the thickness of the dermis and was more precise than standard clinical follow‐up of cutaneous lesions in these cases.
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