Cilj: Osvijestiti liječnike o potencijalnom riziku razvoja progresije melanocitnih kožnih lezija i eventualnog nastanka malignog melanoma u pacijenata kronično liječenih adalimumabom (Humirom), ...antagonistom tumorskog faktora nekroze-alfa (TNF-alfa). Prikaz slučaja: U dermatološku ambulantu javio se tridesetosmogodišnji muškarac jer je unatrag mjesec dana primijetio makroskopski vidljivu promjenu postojeće melanocitne lezije na području kože abdomena, u vidu njezinog povećanja i promjene boje. Pacijent je unazad tri godine počeo osjećati zakočenost toraksa i leđa, jutarnju križobolju te bolove u leđima koji bi se smanjili uzimanjem nesteroidnih antireumatika. Na temelju kliničkih, laboratorijskih i radioloških nalaza, pacijentu je dijagnosticiran aksijalni spondiloartritis zbog kojeg mu je, dva mjeseca kasnije, u kroničnu terapiju uveden adalimumab. Primjena adalimumaba dovela je do izrazitog poboljšanja bolesnikovog stanja te ga je nastavio redovito uzimati. Nakon dvije godine kontinuirane terapije adalimumabom pacijent je uočio promjenu postojećeg nevusa na trbuhu, o čemu je obavijestio dermatologa koji je izvršio eksciziju lezije u cijelosti. Patohistološkom analizom potvrđen je displastični nevus visokog stupnja. Zaključak: Povezanost adalimumaba s razvojem melanoma još nije dovoljno istražena, iako mnogi dokazi govore u prilog tome. Važno je da liječnici budu upoznati s mogućim rizikom progresije postojećih melanocitnih lezija, kao i mogućim razvojem malignog melanoma te educiraju pacijente, savjetuju im redovne kontrole i povećan oprez, a sve u cilju pravovremenog otkrivanja i prevencije potencijalno ozbiljnih nuspojava adalimumaba. Istraživanja koja se bave ovom tematikom malobrojna su i potrebne su daljnje studije koje će u obzir uzeti više rizičnih čimbenika za nastanak melanoma.
Aim: To make doctors aware of the potential risk of developing melanocytic skin lesions and the possible development of malignant melanoma in patients chronically treated with adalimumab (Humira), a tumor necrosis factor-alpha (TNF-alpha) antagonist. Case report: A 38-year-old man came to the dermatology clinic because a month ago, he noticed the macroscopically visible change of the previously existing melanocytic lesion on the skin of the abdominal wall, in the form of enlargement and color change. Three years ago, the patient began to feel tightness in the thorax and back, morning low back pain and back pain, which would be reduced by taking non-steroidal anti-rheumatic drugs. Based on clinical, laboratory and radiological findings, the patient was diagnosed with axial spondyloarthritis, for which, two months later, adalimumab was introduced into his chronic therapy. The use of adalimumab led to a marked improvement in the patient’s condition, and he continued to take it regularly. After two years of continuous therapy with adalimumab, the patient noticed a change in the pre-existing nevus on his abdomen. He informed the dermatologist, who performed a total excision of the lesion. The pathohistological analysis confirmed a dysplastic nevus with a high degree of dysplasia. Conclusion: The association of adalimumab with melanoma development has not yet been sufficiently investigated, although much evidence supports this. Physicians must be aware of the possible risk of progression of pre-existing melanocytic lesions and the possible development of malignant melanoma, educate patients, and advise regular monitoring and caution to detect and prevent potentially serious side effects of adalimumab. Research on this topic is not numerous, and further studies are needed to consider several risk factors for melanoma.
Background: Tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of various inflammatory pathologies and cancer. We aimed to investigate its expression ...in normal human skin, inflammatory skin diseases and epidermal neoplasms.
Methods: Immunohistochemistry for TWEAK was performed in samples of healthy skin, plaque psoriasis, lichen planus, prurigo nodularis, discoid lupus erythematosus, lichen sclerosus, seborrheic keratosis, common warts, actinic keratosis, Bowen's disease, keratoacanthoma and basal and squamous cell carcinoma. Double immunofluorescence was used to investigate co‐localization of TWEAK with cytokeratin‐10 and proliferating cell nuclear antigen (PCNA).
Results: TWEAK was robustly expressed in the epidermis of healthy skin and decreased in inflammatory conditions, both in the context of epidermal hyperplasia and atrophy. Decreased TWEAK immunoreactivity was regularly observed in common warts, actinic keratosis and Bowen's disease, particularly in areas of marked proliferation as evidenced by PCNA‐positive nuclei. In squamous cell carcinoma, expression of TWEAK ranged from strong to completely absent, and it mostly corresponded with the expression of cytokeratin‐10. TWEAK was absent in keratoacanthoma and basal cell carcinoma.
Conclusions: TWEAK is a constitutively expressed epidermal protein whose downregulation might be an early indicator of disturbed differentiation or pathologic proliferation of keratinocytes that accompany inflammatory and neoplastic skin diseases.
Peternel S, Manestar‐Blažić T, Brajac I, Prpić‐Massari L, Kaštelan M. Expression of TWEAK in normal human skin, dermatitis and epidermal neoplasms: association with proliferation and differentiation of keratinocytes.
TNF-related apoptosis-inducing ligand (TRAIL) is recognized as an important regulator of immune responses during infections and various autoimmune-mediated pathologies. Its role in inflammatory ...dermatoses is largely unknown. We aimed to investigate the expression of TRAIL and its receptors DR4 and DR5 in psoriasis vulgaris. Immunohistochemistry for TRAIL, DR4 and DR5 was performed on samples of lesional (
n
= 10) and non-lesional (
n
= 10) skin of patients with plaque psoriasis and skin of healthy volunteers (
n
= 10). Expression of TRAIL and its receptors was further examined by means of double immunofluorescence staining and co-localization with CD4, CD8, CD11c, CD68, CD16 and CD56 markers. Immunohistochemical staining for TRAIL was significantly enhanced in psoriatic lesional as well as non-lesional epidermis compared to the epidermis of healthy skin. Lesional epidermis also showed increased immunoreactivity for DR5. In addition, expression of TRAIL and both of its receptors was significantly increased in the dermis of lesional skin. As evidenced by double immunofluorescence, TRAIL was readily expressed by most of the examined cells of the inflammatory infiltrate in psoriatic lesions. In contrast, the expression of DR4 was found mostly among CD4+ and CD8+ cells but was only nuclear, while DR5 showed cytoplasmic staining in rare CD16+, CD56+ and CD68+ cells. According to abundant in situ presence of TRAIL and its receptors in lesional psoriatic skin, it seems that this cytokine participates in the complex interplay between keratinocytes and cells of the dermal infiltrate and thus contributes to the inflammatory cycle in psoriasis vulgaris.
Summary Autoimmune diseases arise when the immune system turns against normal components of the body. Overwhelming evidence indicate that the immune system deteriorates with age. The mechanism that ...leads to autoimmunity is complex and not fully understood, and in many cases there is no effective therapy. Another process related to aging is the accumulation of senescent cells. These cells are considered to confer deleterious effects, including the promotion of organismal aging and age-related pathologies. We hypothesize that autoimmune diseases are caused by two age related process: (1) different rate of senescent cells accumulation in the immune system and target tissue/organ, (2) heterogeneous accumulation of senescent cells in tissues/organs. Separately or combined, these two processes are at the base of autoimmune diseases. If the hypothesis is correct, the control of the formation, accumulation and elimination of senescent cells can be used to prevent and/or treat autoimmune diseases. The accumulation or removal of senescent cells would modify the microenvironment and therefore the immune reaction. Many other problems caused by immunosenescence can be also partially explained by our hypothesis. Basically, the accumulation of senescent cells is a finely regulated process. Every imbalance in the accumulation of senescent cells between the immune system and the potential target organs can initiate a chronic inflammation or autoimmunity.
Summary Generally, the cumulative UV exposure correlates with the site-specific incidence of skin cancer but more detailed analysis showed that the frequency of BCC of some facial regions cannot be ...explained with site-specific UV exposure. Apoptosis plays a central role in cancer development due to suppressed process of programmed cell death. Anatomic localization, UV and senescence can influence expression of apoptosis related molecules resulting in advantage of cancer cells development and tumor progression. Anti-tumor immune response, as an important factor in elimination of cancer cells, is also modified by UV radiation and aging, further contributing to cancer progression and its development. Hypothesis : UV radiation, senescence and proliferation intensity influence the expression of apoptosis related molecules in normal keratinocytes. Mutated cells express altered molecules with different degree of antigenicity. We propose that small differences in the expression of pro- and anti-apoptotic molecules in the keratinocytes in association with the local immune reaction (modulated also by UV radiation) determine the type of the non-melanoma skin cancer as well as their frequency (site-specific incidence). In vitro and in vivo models could explain how the modulation of UV can influence the apoptotic system and local immune reaction, while animal experiments could explain different site-specific incidence (frequency) of the same tumor. Better understanding of these mechanisms could lead to development of different therapeutic approaches for early elimination of cancer prone cells or cells in early stages of cancer development. The same model could be used to explain the site-specific localization of other types of cancer (i.e. melanoma) or benign tumors.
The aim of this study was to investigate the contribution of progesterone in the development of primary varicose veins on lower limbs during pregnancy. In 50 primiparae with varicose veins, serum ...progesterone level was quantitatively determined in the 14th week of pregnancy and results were compared with those obtained in a control group of 25 primiparae without visible varicose veins. The mean serum progesterone concentration recorded in pregnant women with dilated veins (159.9+/-15.8 nmol/L) was significantly higher as compared with the control group (159.9+/-15.8 nmol/L vs. 40.4+/-1.6 nmol/L; P<0.0001). These findings supported the role of hormonal factor in the development of varicose veins in women.
Different studies have demonstrated that offspring longevity depends on parental longevity and parental age at conception. The present paper suggests, based on the telomere theory of aging, that the ...longevity of the offspring is proportional to the telomere length and inversely proportional to the telomere state of integrity in the sperm cell and oocyte at conception. These two characteristics of telomeres depend on the age of parents. Telomeres become longer in gametes during the course of life, but at the same time they accumulate mutations (reduced state of integrity) that cause a faster loss of repetitive sequences. Because of these two mechanisms with opposing effects, there could exist an ideal age of the parents for the transmission of maximal longevity. The different longevity of men and women could partly be the result of different telomere dynamics of the sex chromosomes.
The hypothesis also explains the risk of some birth defects associated with parental age at birth (telomeres are taken as a cause of birth defects).
Cilj: Ulcus cruris krajnja je posljedica komplikacija povezanih s venskom hipertenzijom donjih ekstremiteta, a nastaje zbog nemogućnosti cijeljenja nedovoljno opskrbljenog sklerotičnog tkiva. Danas ...se napredno liječenje vrijeda potkoljenice bazira na oblogama za rane koje mogu ili ne moraju sadržavati analgetike da bi umanjile bolove. Cilj ove jednogodišnje studije bio je analizirati učinke obloge s ibuprofenom na bolove u bolesnika s vrijedom potkoljenice u svrhu poboljšanja njihove kvalitete života. Metode: U ovoj jednogodišnjoj studiji obradili smo 288 bolesnika; 28 bolesnika koristilo se oblogama s ibuprofenom bez peroralne analgetske terapije, dok je 30 bolesnika primalo peroralnu analgetsku terapiju s oblogama sa srebrom kao kontrolna skupina. Rezultati: Uočili smo statistički značajan pad intenziteta bola u prva dva dana liječenja, ali ne značajan u odnosu na cijeljenje ulkusa u kontrolnoj skupini. Zaključak: Na osnovi ovih rezultata zaključujemo da bi obloge s analgeticima mogle biti lijek izbora za kronične nožne ulkuse s intenzivnim bolovima.
