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Data on various cutaneous adverse events as a result of widespread SARS-CoV-2 vaccination is currently accumulating. However, data on cutaneous reactions following booster dose of COVID-19 vaccines are still limited.1, 2 Herein, we present a case of pityriasis rubra pilaris (PRP) following a booster dose of the BNT163b2 (Pfizer–BioNTech) mRNA COVID-19 vaccine.

Owing to the widespread use of COVID-19 vaccines, the number of cutaneous vaccine-related adverse events has recently increased. We present two cases of lichen planus in elderly women following COVID-19 mRNA vaccination. The first patient presented with new-onset LP, whereas the second patient experienced an extensive LP flare after a 10-year remission.

Recently, several biologics have been associated with thedevelopment of new-onset or exacerbation of prior sar-coidosis.1–5We report a case of new-onset sarcoidosisinduced by secukinumab in a patient with severe plaquepsoriasis.

Lichen planus is a chronic inflammatory mucocutaneous disorder commonly affecting the skin, nails, hair, and mucous membranes (1). Although its main cause is still unclear, lichen planus is defined as a T cell- mediated inflammatory disease (2). CD8+ T lymphocytes activate their cytotoxic armamentarium and induce basal keratinocyte apoptosis (2). The susceptibility of basal keratinocytes to CD8+ T lymphocytes is enhanced through MHC class I expression on keratinocytes triggered by interferon (IFN)- gamma (3). The cytotoxic process is mainly mediated by the release of lytic molecules, such as perforin, granzyme B, and granulysin (GNLY) (4–8). The upregulation of perforin and granzyme B has been previously demonstrated in the peripheral blood and lesional skin of patients with lichen planus (4–8). GNLY is a member of the saposin-like lipid-binding protein (SAPLIP) family and has a cytotoxic effect on tumour cells and a variety of microorganisms (9, 10). It is located in the cytotoxic granules of T cells, which are released upon antigen stimulation, and in the cytotoxic granules of natural killer (NK) cells. GNLY presence has only recently been observed in lichen planus lesions, but the expression level of this molecule in peripheral blood and subsequent determination of cells that express this molecule in blood and lesions remains unknown (8). In this study we examined the dynamics of GNLY expression in different cytotoxic subtypes of peripheral blood lymphocytes and in the skin lesions of patients with lichen planus.

Psoriasis is one of the most common chronic inflammatory skin disorders worldwide with a significant number of patients suffering from moderate to severe disease and requiring systemic therapy. Over the past two decades, better knowledge of disease pathophysiology has translated into treatment advances for both primary disease and its associated comorbidities. However, it is important to review the use of biologic or targeted therapy in a clinical setting in order to understand how to optimize therapeutic results and recognize any unmet needs in this patient subpopulation. We conducted a retrospective study on a cohort of patients diagnosed with psoriasis that had received at least one dose of biologic or targeted therapy for the treatment of psoriasis at the Rijeka Clinical Hospital Center. By documenting treatment trends and specific patient characteristics, we will be able to address any unmet needs in this patient population and provide individualized care strategies.

Case report of a patient developing severe bullous hemorrhagic Sweet syndrome following application of the first dose of the SARS- CoV-2 Oxford AstraZeneca vaccine.

Targeted biologics have been successfully used for the treatment of moderate to severe psoriasis1 . However, in parallel to the increasing use of biological agents, the number of paradoxical adverse events (PAEs) is increasing as well2 . Herein, we report a case of a palmoplantar pustular reaction in a patient with severe psoriasis treated with ixekizumab. A 50-year-old-woman with a 30-years-history of psoriasis was referred to our Department due to progressive exacerbation of severe chronic plaque psoriasis (PASI 16.8) in spite of methotrexate therapy. Thus, ixekizumab at scheduled dosage was started. Initially, a rapid improvement of psoriatic lesions was observed.

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2–4% of the world’s population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients’ social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.

Pojavnost atopijskog dermatitisa (AD) tijekom posljednjih desetljeća u porastu je, što je osobito izraženo u zemljama zapada. Smatra se da je uzrok smanjena izloženost mikroorganizmima tijekom najranijeg djetinjstva i posljedično smanjena stimulacija imunološkog sustava. Budući da crijevna mikroflora predstavlja prvi i najveći izvor mikrobnog opterećenja, promjene u njezinu sastavu i raznovrsnosti smatraju se čimbenikom nastanka AD-a. To je razlog zašto se probiotici, zahvaljujući svojoj sposobnosti manipulacije sastavom mikroflore i imunomodulatornim učincima, smatraju mjerom prevencije i liječenja atopijskog dermatitisa. Dosadašnje studije ukazuju na njihov preventivni potencijal, no kao terapijska intervencija nisu pokazali pozitivne učinke. Ipak, primjena probiotika u AD-a za sada je ostala predmetom istraživanja, a buduće studije trebale bi razjasniti zaslužuju li oni mjesto među ostalim preventivnim i terapijskim mjerama te razriješiti nedoumice glede njihove primjene., The prevalence of atopic dermatitis (AD) has risen over the past decades, and this is especially expressed in western countries. Reduced microbial exposure during infancy and therefore reduced stimulation of immune system is considered to be the cause for this rising prevalence. Intestinal microbiota represents the first and major source of microbial exposure and therefore the changes in its composition and diversity are considered to be responsible for development of AD. That is why probiotics are, owing to their ability to manipulate the composition of microbiota and their immunomodulatory effects, considered to be a promising prevention and therapeutic intervention of atopic dermatitis. Former studies indicate that they have a preventing potential, but their therapeutic effects have not been proven. However, probiotic use in AD is a subject of reasearches at the moment, and future studies should clearify if they deserve a place among the other preventive and therapeutical measures and resolve uncertanities regarding their administration.

Lichen planus is a chronic mucocutanous disorder histopathologically characterized with a keratinocytes apoptosis, subsequent basal cell layer liquefaction and accumulation of the inflammatory infiltrate in papillary dermis. A formation of apoptotic bodies in basal cell layer is due to a cytotoxic lymphocyte attack to the basal keratinocytes. It has been demonstrated that the cytotoxic molecules included in this attack are perforin and granzyme B. Both molecules are found upregulated in CD8+ lymphocytes that are in close contact to keratinocytes. However, their amount is lower in lichen planus than in other skin disease characterized by liquefaction and vacuolar degeneration of the basal epidermal layer. This could speculate about other cytotoxic molecule such as granulysin that could mediate keratinocyte apoptosis. Therefore, in this article we hypothesize about the crucial role of granulysin molecule in keratinocytes killing that could contribute to a lichen planus pathogenesis.

The clinical triad of pyoderma gangrenosum (PG), acne and suppurative hidradenitis (HS) has been described under the acronym PASH syndrome and is considered to represent a distinct entity in the group of autoinflammatory diseases. It is a fairly new, only recently recognized disorder with a limited number of reported cases and without defined treatment recommendations. We aimed to summarize currently available data on the use of tumor necrosis factor (TNF) antagonists in the management of PASH syndrome and report on our own experience with the use of adalimumab in a patient presenting with this specific constellation of clinical signs and symptoms. Among the 11 cases identified in the literature, infliximab and adalimumab were the most commonly used agents, both exhibiting favorable effects in the majority of, but not all, patients. This was particularly evident in terms of relatively rapid remission of PG whereas HS lesions seemed to be more resistant to treatment. In our patient, adalimumab monotherapy resulted in a remarkable and sustained remission, although significant improvement of HS lesions was observed only from week 16 of therapy onwards. In summary, TNF antagonists are a promising treatment for PASH; however, conclusions regarding the choice of a specific agent, optimal dosing or use in combination with other treatment modalities cannot yet be drawn.

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.

It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be "non-psychosomatic") were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and psoriasis.

Psoriasis is a chronic papulosquamous skin disease, histologically characterized by epidermal hyperproliferation and dermal infiltration of inflammatory cells. The majority of T lymphocytes infiltrating dermis are CD4+ T lymphocytes secreting type 1 and type 17 cytokines. These cytokines are responsible for triggering keratinocyte proliferation as well as chemokine secretion and subsequent migration of other inflammatory cells in the skin. Contrarily, lymphocytes that accumulate in epidermis are mainly CD8+ T lymphocytes. According to the recent findings, these cells can also secrete type 1 and type 17 cytokines. However, it is demonstrated so far that epidermal CD8+ T lymphocytes contain higher amounts of cytolytic molecules, such as perforin, granzyme B and granulysin whose role in psoriasis pathogenesis is still unknown. Therefore, in this article we hypothesize the active involvement of cell mediated cytotoxicity in killing the proliferating keratinocytes as a mechanism of potential self-defense and possible brake in psoriatic plaque formation, maintaining skin homeostasis.

Cilj: Istražiti učestalost haplotipskih sveza HLA-DRB1-DQA1-DQB1 te produženog haplotipa Cw*0602-B57-DRB1*07-DQA1*0201 DQB1*0201 u pacijenata s pozitivnom i negativnom obiteljskom anamnezom psorijaze. Ispitanici i metode: Istraživanje povezanosti gena sustava HLA razreda I i II sa psorijazom obuhvatilo je 118 nesrodnih pacijenata s vulgarnom psorijazom. Učestalost haplotipskih sveza ispitana je serološki i metodom hibridizacije specifičnim probama. Rezultati: Utvrđena je povišena učestalost haplotipa DRB1*07-DQA1*0201- -DQB1*0201 i DRB1*07-DQA1*0201-DQB1*0303 u psorijatičara s pozitivnom obiteljskom anamnezom te također produženog haplotipa Cw6-B57-DRB1*0701-DQA1*0201- -DQB1*0201 (P = 0,004). U psorijatičara s negativnom obiteljskom anamnezom učestalost produženog haplotipa gotovo je ista kao u kontrolnoj skupini. Zaključak: Rezultati istraživanja ukazuju na jaču i značajniju povezanost s podložnim haplotipovima HLA za pacijente s pozitivnom obiteljskom anamnezom psorijaze, stoga upućuju na značajnu ulogu gena sustava HLA u nasljeđivanju psorijaze., Aim: To analyze the distribution of HLA-DRB1-DQA1-DQB1 haplotypes as well as the extended haplotype Cw*0602-B57-DRB1*07 DQA1*0201-DQB1*0201 in patients with positive and negative family history of psoriasis. Patients and methods: The association of HLA genes classes I and II with psoriasis has been studied in 118 patients with chronic stable psoriasis. The frequency of HLA haplotypes was analyzed by means of serology and hybridization with specific oligonucleotide probes. Results: The group with positive family history showed a significant association with DRB1*07-DQA1*0201-DQB1*0201 and DRB1*07- DQA1*0201-DQB1*0303 as well as with the extended haplotype Cw6-B57-DRB1*0701- DQA1*0201-DQB1*0201 (P = 0,004). The frequency of extended haplotype in the group with negative family history was similar to the control group. Conclusion: Psoriatics with positive family history show stronger association with susceptible

The aim of the study was to analyze the Microsporum canis infections in the Rijeka area, Croatia, observed between 1990 and 2001. A total of 724 cases of dermatophytosis caused by M. canis were diagnosed in 320 individuals with the tinea capitis and 404 with tinea corporis. The M. canis infections constituted 32.8% of all dermatophytes isolated during the study period.

Zusammenfassung Die Haufigkeit von Dermatomykosen und ihr Erregerspektrum im Raum Rijeka, Nordwestkroatien, wurde im Zeitraum vor und wahrend des Krieges 1990– 1994 sowie in der Nachkriegszeit 1995– 1999 analysiert. Insgesamt 20463 Patienten mit klinisch manifesten Dermatomykosen wurden an der Klinik fur Dermatovenerologie in Rijeka untersucht. Im Zeitraum 1990-1994, waren 2462 Proben positiv, im Zeitraum 1995– 1999. waren 2250 Proben positiv. Die am haufigsten isolierten Dermatophyten waren Trichophyton mentagrophytes und Microsporum canis, gefolgt von Microsporum gypseum, Epidermophyton floccosum, Trichophyton verrucosum und Trichophyton rubrum. Die grossere Anderung im Dermatophytenspektrum wurde in der Nachkriegszeit beobachtet, verursacht durch die Bevolkerungswanderung aus den anderen Regionen nach Rijeka. Dies zeigte sich mit dem Verschwinden von T. verrucosum und T. rubrum und dem Auftauchen von Trichophyton violaceum. Diese antropophile Art wurde die dritthaufigste. Unsere Befunde wurden mit denen aus fruheren Studien in der selben Region und mit den aus anderen Landern verglichen.

The Hair Follicle (HF) is a vital component of mammalian skin and represents a unique, highly regenerative system that undergoes phases of rapid growth, regression, and resting periods. The hair cycling is of profound clinical relevance since majority of the hair growth disorders occur as a result of cycle changes. The influence of many molecules governing the formation of HF has been investigated and many of important cycle mediators have been identified. Cellular and molecular events during cycling are controlled by a network of sequential activation of autocrine, paracrine and endocrine signaling pathways. This implies variations in the expression or activity of the Wnt family molecules, Fibroblast Growth Factor (FGF), Transforming Growth Factor β (TGF-β), Hedgehog pathway, β-Catenin pathway, noggin, transcription factor Stat3, Epidermal Growth Factor (EGF), Insulin Growth Factor-1 (IGF- 1), Vascular Endothelial Growth Factor (VEGF), Thyrotropin Releasing Hormone (TRH), Polyamine, Spermidine, Neurotrophins (NT3, NT4), prolactin, retinoids, Bone Morphogenetic Protein 4 (BMP4), cathepsin L, 17-β estradiol, dihydrotestosterone and many others. Despite considerable progress in this area, the key elements of cycle control have not been identified. Therefore, for the most common hair disorders several agents are available, even none of these is curative or preventive. The one of the prime challenges of hair research is a better understanding of the molecular controls of hair cycling and developing drug which would effectively manipulate the cycle. Future therapy strategies will be based on new and better knowledge about the HF biology. Until than, alopecia areata, telogen effluvium and androgenetic alopecia, will remain unsolved medical problems.

This open study was conducted in 72 outpatients with acne vulgaris, to compare the clinical efficacy and tolerability of azithromycin and minocycline. Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles every 10 days and minocycline was administered 100 mg daily for 6 weeks. Improvement was assessed 6 weeks after initiation of treatment with a four-graded scale. A satisfactory clinical response was observed in 75.8% of the patients treated with azithromycin and in 70.5% of those treated with minocycline. There were no significant differences between these two acne treatments in terms of reduction of the number of lesions (p> 0.05). Both agents were well tolerated and mild side effects were reported in 10.3% of azithromycin and 11.7% of minocycline treated patients. We conclude that azithromycin is at least as clinically effective and well tolerated as minocycline as treatment of facial comedonic and papulopustular acne.

Hrvatsko dermatovenerološko društvo Hrvatskoga liječničkog zbora ustrojilo je radnu skupinu vodećih hrvatskih stručnjaka koji se bave psorijazom. Radna je skupina kritički proučila mjerodavnu znanstvenu literaturu te donijela smjernice za dijagnostiku i liječenje psorijaze., Croatian dermatovenerological society of the Croatian Medical Association formed the working group which consists of leading experts for psoriasis in Croatia. After a critical analysis of relevant scientific papers, the working group has developed guidelines for the diagnosis and treatment of psoriasis

The aim of this study was to determine the prevalence of true local anesthetic (LA) allergy among patients referred for suspected hypersensitivity and to describe the main characteristics of adverse drug reactions (ADR) induced by LA in our population. We retrospectively analyzed the medical files of patients referred to the Department of Dermatovenereology, University Hospital Center Rijeka, Rijeka, Croatia, for the investigation of LA hypersensitivity in the period between January 2000 and December 2012. A total of 331 patients underwent skin testing and, in cases of negative results, subcutaneous exposition to LA. In patients with suspected delayed reaction, patch test was performed. Altogether, 331 patients reported 419 independent ADR occurring during 346 procedures. Most commonly, patients reported having only one ADR, but 41 (12.4%) of them had two reactions, 14 (4.2%) had three, five (1.5%) had four and in one patient (0.3%) five ADR to LA were observed. The majority of reactions occurred during dental procedures when most commonly lidocaine and articaine were used. Local reactions were reported in 44 patients, whereas 490 general symptoms occurred during 375 independent ADR in 287 patients. The most common symptoms were cardiovascular system reactions in 89 patients (18.2%). Allergic reaction was detected in three patients (0.91%). One patient showed immediate-type reaction to bupivacaine and two patients had a delayed-type reaction to lidocaine. Adverse reactions to LA are common and are mostly due to their pharmacological properties and drug combinations or psychogenic origin. Allergic accidents to LA are rare.

Psoriasis is probably as old as mankind. Today, it is a well defined skin disease, in which genetic, environmental and immunologic factors participate in etiopathogenesis. However, despite its frequency, chronicity and visibility, it is quite hard to find a description of psoriasis in the works of the ancient physicians. Dermatology developed slowly, first with appearance of the protodermatologists at the end of the 18th century, and continued with the arrival of the first dermatologists. From those times psoriasis became a distinct entity. However, until the last century, the descriptions of disease considered «morbi in pulchredine», were rather vague, the denomination not standardized and the translation from one language to others discrepant. Different authors called the disease with various names, while diverse diseases had the same names. The confusion in terminology and description of psoriasis lasted for centuries.

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., Aim: Ulcus cruris represents one end-point of complications linked to the venous hypertension of lower extremities, as inadequately supplied sclerotic tissue breaks down and healing is largely impaired. Today the advanced leg ulcer treatment is based on wound dressing that can contain analgesics in order to diminish pain. The aim of this non randomized one year study was to analyze the effects of ibuprofen-releasing foam dressing on wound pain in leg ulcers in order to ameliorate the quality of life in patients. Methods: In this one-year study 288 patients with leg ulcers were analyzed, among which 28 patients were prescribed ibuprofen-releasing foam dressing without peroral analgesic therapy, while 30 patients continued peroral analgesic therapy with silver-releasing foam dressing as a control group. The primary endpoint was to determine wound pain relief in the first two days among patients treated with. Results: We observed a statistically significant decrease of pain intensity in the first two days of therapy, but not a significant different rate of ulcer healing compared to the control group. Conclusion: Based on these results we concluded that foams with analgesics could be a treatment of choice for chronic leg wounds with intense pain.

Cilj: Perioralni dermatitis je kronična ekcematoidna i papulopustulozna upalna dermatoza kože lica od koje najčešće obolijevaju žene mlađe i srednje dobi. Etiopatogeneza je nepoznata, a od mogućih etioloških čimbenika u obzir dolaze dugotrajna uporaba topičkih kortikosteroida, kozmetičkih preparata na bazi petrolata i parafina, infektivni uzročnici, hormoni, gastrointestinalni poremećaj, neurogena upala i emocionalni stres. Prikaz slučaja: Prikazana je 49-godišnja žena s izrazitim eritemom kože lica, edemom kapaka te brojnim grupiranim papulama i papulopustulama na koži lica, uz brojne subjektivne simptome. Bolesnica je samoinicijativno duže od godinu dana na licu primjenjivala potentni kortikosteroidni pripravak. Rasprava i zaključak: Prikaz slučaja govori u prilog hipotezi o važnoj ulozi topičkih kortikosteroida u patogenezi perioralnog dermatitisa. U radu je prikazan i pregled recentne literature o etiologiji, patogenezi i liječenju bolesti., Aim: Perioral dermatitis is a chronic papulopustular and eczematous facial dermatitis which predominantly affects young to middle aged women. The etiology of perioral dermatitis is unknown, and possible etiological factors include long time use of topical corticosteroids, cosmetics with petrolatum or paraffin base, microbiological factors, hormonal factors, gastrointestinal disturbances, neurogenic inflammation and emotional stress. Case report: A 49-year-old woman presented with expressive facial skin erythema, edema of the eyelids, a number of grouped papules and papulopustules on the face, accompanied with a number of subjective symptoms. Patient used potent corticosteroid preparations on the face for more than a year. Discussion and conclusion: The case supports the hypothesis that topical corticosteroids have an important role of in the pathogenesis of perioral dermatitis. This paper presents an overview of recent literature on the etiology, pathogenesis and treatment of the disease.

Lower limb symptoms have frequently been associated with increased severity of venous disease. In clinical practice they are reported by patients at all stages of chronic venous disease. This study assessed the contribution of Daflon 500 mg in improving venous symptoms and promoting venous ulcer healing in patients with primary chronic venous disease.

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.

Alopecia areata (AA) is a frequent disease with nonscarring hair loss on the scalp and/or body. Hair follicle in alopecia areata is not irreversibly destroyed, so potential for hair regrowth remains. Considering unknown etiopathogenesis, treatment of AA is symptomatic and directed toward halting disease activity. Lymphocytic inflammatory infiltrate around hair follicle, increased levels of autoantibodies, cytokine abnormalities and increased prevalence of autoimmune comorbidities, support the hypothesis of AA as an organ-specific autoimmune disorder. Therefore, investigations are directed toward new immunomodulatory or immunosuppressive drugs with induction effect on hair growth. New biologic drugs and their influence on hair growth as well as genetic therapy for alopecia areata are currently under investigation. Contemporary principles in therapy of alopecia areata and treatments available will be discussed in this article.

Koža je najgušće inerviran organ ljudskog tijela, u vrlo bliskom kontaktu sa živčanim sustavom. U međusobnu intenzivnu komunikaciju uključene su sve strukture živčanog, endokrinog i imunološkog sustava, kao i sve stanice kože. Interakcija je posredovana različitim tipovima kožnih živčanih vlakana koja otpuštaju neuromedijatore i aktiviraju specifične receptore na ciljnim stanicama kao što su keratinociti, mastociti, Langerhansove stanice, endotelne stanice, stanice mikrovaskulature, fibroblasti i infiltrirajuće imunološke stanice. Ove interakcije utječu na brojne fiziološke i patofiziološke funkcije, uključujući rast i razvoj stanica, diferencijaciju, imunost, vazoregulaciju i cijeljenje rana. Nova saznanja o čimbenicima uključenim u ove interakcije utvrdila su suvremeni koncept neurobiologije kože., The skin is the most densely innervated organ in the body and there is a close relationship between the skin and the nervous system. Monodirectional and/or bidirectional pathways exist in which the central and peripheral nervous system, endocrine and immune system, and almost all skin cells are involved. The interaction between peripheral nerves and immune system is mediated by different types of cutaneous nerve fibers which release neuromediators and activate specific receptors on target cells in the skin such as keratinocytes, mast cells, Langerhans cells, microvascular endothelial cells, fibroblasts, and infiltrating immune cells. These interactions influence a variety of physiologic and pathophysiologic functions including cellular development, growth, differentiation, immunity, vasoregulation, leukocyte recruitment, pruritus, and wound healing. Information is emerging about the factors involved in these immunomodulatory mechanisms. Recent findings have established a modern concept of cutaneous neurobiology.

Psorijaza je diljem svijeta jedna od najčešćih upalnih bolesti kože kroničnog tijeka. Dok se blagi oblici bolesti uspješno liječe primjenom lokalne terapije, trećina bolesnika s umjereno teškim do teškim oblikom bolesti zahtijeva primjenu sustavne terapije. Tradicionalni lijekovi za sustavnu primjenu u dosadašnjem su iskustvu, kao i u mnogim kliničkim studijama, pokazali visoku učinkovitost u liječenju psorijaze. Metotreksat, ciklosporin i acitretin cjenovno su isplativi i pružaju odličnu kontrolu bolesti. Njihova primjena ograničena je isključivo mogućnošću teških nuspojava koje se pažljivim praćenjem bolesnika mogu uspješno kontrolirati i svesti na minimum., Psoriasis is one of the most common chronic inflammatory skin disease worldwide. While mild forms of the disease can be successfully controlled by applying local therapy, one third of patients with moderately severe to severe form of psoriasis, requires the application of systemic therapy. As indicated in many clinical studies, the conventional drugs for systemic use in so far experience have shown high efficacy in treating psoriasis. Methotrexate, cyclosporin and acitretin are cost affordable and provide excellent disease control. Their application is limited only by the possibility of serious side effects, which can be successfully controlled and kept to a minumum through carefully monitoring of patient.

Procjenjuje se da virusne infekcije pridonose nastanku 15 – 20 % svih malignih tumora ljudi. Kao obligatorni intracelularni paraziti, virusi kodiraju proteine koji reprogramiraju signalne puteve odgovorne za kontrolu proliferacije, diferencijacije, smrti stanice, genomskog integriteta, kao i prepoznavanja od strane imunološkog sustava. Virusni sustavi podržavaju koncept da je za razvoj tumora potrebna akumulacija međusobno povezanih događaja. Virusi koji su do sada prihvaćeni kao etiološki čimbenici ljudskih malignoma uključuju hepatitis B virus, Epstein-Barr virus, humani papiloma virus, virus leukemije ljudskih T-stanica, hepatitis C virus, te još nekoliko ljudskih onkogenih virusa. Obično protekne niz godina od infekcije do razvoja tumora i većina inficiranih osoba ne razvije rak, iako imunološki kompromitirane osobe pokazuju veći rizik za nastanak tumora povezanih s virusima. Malo je vjerojatno da je virus sam dovoljan da transformira normalnu stanicu u tumorsku. Vjerojatnija je mogućnost da kombinirano djelovanje virusnih proteina i mutacije staničnih gena zajedno vode tumorogenezi., It is estimated that viral infections contribute to 15-20 % of all human cancers. As obligatory intracellular parasites, viruses encode proteins which reprogramme host cellular signalling pathways which in turn control proliferation, differentiation, cell death, genomic integrity, and recognition by the immune system. Viral systems support the concept that cancer development occurs by accumulation of multiple cooperating events. Viruses are now accepted as etiologic factors of human cancer, and include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus and hepatitis C virus, plus several candidate human cancer viruses. Many years may pass between initial infection and tumor appearance. Most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. It is unlikely that a tumor virus is sufficient to convert a normal cell to a tumor cell. Rather, a combination of the action of viral proteins and cellular gene mutation cooperate to drive tumorogenesis.

Psoriasis is a chronic, recurrent skin disease that lasts a whole life. A quarter of adults are suffering from severe forms of psoriasis that requires the application of the systemic treatment. Despite the development of new groups of medicines, traditional therapy is still of great importance. Methotrexate, cyclosporine and acitretin are cost-effective and provide excellent disease control. Methotrexate and acitretin are good choice in terms of maintenance therapy, whereas cyclosporin would ideally be used as intermittent therapy. Fear of serious side effects of traditional drugs can be avoided by setting individualized plan for each patient and careful monitoring.

Alopecija areata (AA) česta je bolest koja se očituje neožiljnim gubitkom dlake na vlasištu i/ili tijelu. Folikul dlake u alopeciji areati nije nepovratno uništen, stoga potencijal za ponovni rast kose ostaje. Budući da je etiopatogeneza nepoznata, liječenje AA je simptomatsko i usmjereno na zaustavljanje aktivnosti bolesti. Limfociti oko dlačnog folikula, povišena razina autoprotutijela, poremećaj citokina te udruženost s drugim autoimunosnim bolestima, podupiru hipotezu da je AA organ-specifična autoimunosna bolest. Nova su istraživanja stoga usmjerena na razvoj lijekova koji bi imunomodulatornim ili imunosupresivnim djelovanjem potaknuli rast dlake. Proučavanje utjecaja novih bioloških lijekova na rast kose, kao i razvoj genske terapije u tijeku su. U radu će biti raspravljeni suvremeni principi i dostupne metode liječenja alopecije areate., Alopecia areata (AA) is a frequent disease with nonscarring hair loss on the scalp and/or body. Hair follicle in alopecia areata is not irreversibly destroyed, so potential for hair regrowth remains. Considering unknown etiopathogenesis, treatment of AA is symptomatic and directed toward halting disease activity. Lymphocytic inflammatory infiltrate around hair follicle, increased levels of autoantibodies, cytokine abnormalities and increased prevalence of autoimmune comorbidities, support the hypothesis of AA as an organ-specific autoimmune disorder. Therefore, investigations are directed toward new immunomodulatory or immunosupresive drugs with induction effect on hair growth. New biologic drugs and their influence on hair growth as well as genetic therapy for alopecia areata are currently under investigation. Contemporary principles in therapy of alopecia areata and treatments available will be discussed in this article.

Since psoriatic epidermis is also characterized by hyperproliferation of keratinocytes, we aimed to investigate the expression of two DDR markers, p53-binding protein 1 (53BP1) foci and phosphorylated histone H2AX (gammaH2AX), in psoriatic lesions. Immunohistochemical and immunofluorescent staining was performed on paraffin-embedded tissue of lesional skin of patients with psoriasis and skin of healthy volunteers. The percentage of keratinocytes positive for Ki-67, 53BP1 and gammaH2AX and the number of foci per nucleus were determined. The number of cells positive for proliferation marker Ki-67, as well as the number of cells positive for gammaH2AX and 53BP1 foci, was significantly higher in psoriasis when compared to normal skin. In addition, the mean number of 53BP1 foci per nucleus, in cells expressing foci, was higher in psoriatic than in normal epidermis. Positive cells were predominantly localized in the basal and suprabasal epidermal layers. These results indicate that psoriasis, similarly to preneoplastic lesions, is characterized by high proliferative index and increased expression of DDR markers. It is possible that potent activation of DDR in psoriasis overcomes the effects of DNA replication stress and represents a part of the barrier to malignant transformation.

Psorijaza je kronična, recidivirajuća bolest kože koja traje čitav život. Četvrtina bolesnika boluje od teškog oblika psorijaze koji zahtijeva primjenu sustavne terapije. Unatoč razvoju novih skupina lijekova, tradicionalna terapija i dalje je veoma važna. Metotreksat, ciklosporin i acitretin cijenom su prihvatljivi i pružaju odličnu kontrolu bolesti. Metotreksat i acitretin dobar su izbor u smislu terapije održavanja, dok je ciklosporin idealan kao intermitentna terapija. Strah od teških nuspojava tradicionalnih lijekova može se izbjeći individualnim određivanjem terapije i pažljivim nadzorom bolesnika., Psoriasis is a chronic, recurrent skin disease that lasts a whole life. A quarter of adults are suffering from severe forms of psoriasis that requires the application of the systemic treatment. Despite the development of new groups of medicines, traditional therapy is still of great importance. Methotrexate, cyclosporine and acitretin are cost-effective and provide excellent disease control. Methotrexate and acitretin are good choice in terms of maintenance therapy, whereas cyclosporin would ideally be used as intermittent therapy. Fear of serious side effects of traditional drugs can be avoided by setting individualized plan for each patient and careful monitoring.

Current research in pathogenesis of psoriasis vulgaris suggests that the inflammatory mechanisms are immune based and most likely initiated and maintained by T cells. However, the question of lymphocyte being an initiator of psoriatic events remains open so far. Clinical observations such as plaque symmetry, stress-induced onset or exacerbations, pruritus, and possibility of generalization, suggest a role of the nervous system and neurogenic inflammation in pathogenesis. A key to understanding the role of melanocyte in psoriasis is their ability to act as regulatory cell in maintaining epidermal homeostasis. In suggested hypothetic event, melanocyte, acting as a local "stress sensor", provide communicatory link between CNS and skin. The disease probably begins with so far unknown signal directed through neuronal network to the melanocyte, placed in the center of epidermal unit. That signal governs keratinocyte cellular activities and lead to reactive abnormal epidermal differentiation and hyperproliferation. Increased proliferation of basal keratinocytes and high metabolic demands creates angiogenesis in papillary dermis and elongation of dermal papillae. Stimulated melanocytes and basal keratinocytes become an important source of proinflammatory cytokines that attract lymphocytes in dermis. In conclusion, according to our hypothesis, lymphocyte infiltrate in psoriasis is secondary event rather than vice versa as presented in the literature.

Apoptosis is a process of programmed cell death that maintains the homeostasis of the skin. Apoptotic cell death regulates keratinocyte proliferation and formation of stratum corneum as well. The process by which keratinocytes undergo apoptosis is a multistep program mediated by binding of specific death ligands to death receptors or by the release of effectors cell granules. Dysfunctional apoptosis has an important role in the development of several skin diseases. Psoriasis is a common chronic inflammatory skin disease characterized by hyperproliferation with incomplete differentiation of epidermal keratinocytes and decreased keratinocyte apoptosis. Psoriatic keratinocytes possess an enhanced ability to resist apoptosis what might be one of the key pathogenetic mechanisms in psoriasis. In addition, psoriasis is nowadays also recognized as the most prevalent autoimmune disease resulting from aberrant activation of both, innate and adaptive immunity. However, the role of cell cytotoxicity mediated by cytotoxic CD8+ T cells (CTLs) and NK cells in psoriasis is as yet unclear. Here, we shall review the role of different apoptotic pathways in psoriasis.

Alopecija areata neožiljni je upalni gubitak dlake na vlasištu i/ili tijelu, nepoznate etiopatogeneze. Najčešće zahvaćeno mjesto je vlasište. Histopatologija se očituje povećanim brojem katagenih i telogenih folikula te nazočnošću upalnog limfocitnog infiltrata u peribulbarnoj regiji. U liječenju alopecije areate najčešće se primjenjuju kortikosteroidi. U radu je opisana klinička i patohistološka slika uz suvremene metode liječenja alopecije areate., Alopecia areata is a nonscarring, inflammatory hair loss on the scalp, and/or body. Etiology and pathogenesis are still unknown. The most common affected site is the scalp. Histopathology is characterized by an increased number of the catagen and telogen follicles along with the presence of inflammatory lymphocytic infiltrate in the peribulbar region. Corticosteroids are the most popular drugs for the treatment of this disease. Clinical features, histological data as well as modern treatment options will be discussed in this article.

In 1790, an infectious disease appeared in the village of Škrljevo near Rijeka, and spread to the nearby villages and then to Istria, Slovenia and other parts of Croatia. In 1800, the nature of the disease was first investigated by the protomedicus Massich, who believed it was a combination of syphilis and scabies. After him, the protomedicus of the region G. B. Cambieri, who graduated in Pavia and came to Rijeka in 1797, studied the illness, gave a description of the disease and believed it was a morbus sui generis, and termed it morbus of Scherlievo. He was a gifted physician, used all his knowledge, skills and organization capabilities to arrest the disease, and published his works in Italian journals (in 1812 and 1819). Cambieri studied the disease in thousands of patients in local hospitals, and took the initiative to open a new Civic Hospital with a department of syphilidology. He divided the disease into four stages and with permission of the authorities he tried different therapies. With time, he found the disease to be a form of syphilis and treated it with mercury compounds. After his death in 1838, he left his money to the Hospital of Holy Spirit in Rijeka (Cambieri Foundation), which permitted its development

Cilj: Cilj rada je prikaz slučaja bolesnika s generaliziranim oblikom vitiliga koji je liječen lokalnim kortikosteroidima i uskospektralnom UVB fototerapijom, kao i pregled novih oblika liječenja vitiliga. Prikaz slučaja: Četrdesetdvogodišnji bolesnik zaprimljen je zbog generalizirane pojave vitiliga. Kliničkim pregledom uočene su depigmentirane mliječnobijele makule simetrično raspoređene po koži lateralnih strana trupa, gornjih i donjih ekstremiteta, kao i vratu te periorbitalno na desnoj strani lica. U terapiju je uvedena kortikosteroidna krema, mometazon furoat, a potom i uskospektralna UVB fototerapija koja se provodila tri puta tjedno uz povećanje doze za 20% prilikom svakog obasjavanja do pojave blagog eritema. Ukupna primljena doza iznosila je 69.213 J/cm2. Liječenje je dovelo do poboljšanja u smislu mjestimične repigmentacije vitiliginoznih lezija, zaustavljena je progresija postojećih, kao i nastajanje novih lezija. Rasprava i zaključak: Iako postoje brojne dostupne metode liječenja, ne postoji univerzalna terapija koja bi bila učinkovita u svih bolesnika s vitiligom. Raznolikost kliničke slike vitiliga posljedica je različitih patogenetskih mehanizama, stoga zahtijeva i različite pristupe u liječenju. Nova istraživanja na polju etiopatogeneze vitiliga omogućit će razvoj novih učinkovitijih modaliteta liječenja koji bi doveli do trajnog izlječenja bolesti., Aim: To present a patient with generalized vitiligo who was treated with topical corticosteroids and narrow band ultraviolet B phototherapy and to give an overview of treatment modalities for vitiligo. Case report: A 42 year-old men was admitted because of generalized vitiligo. Clinical examination revealed depigmented milky-white macules distributed symmetrically on lateral sides of trunk, upper and lower extremities, neck and periorbital region of the right facial side. A topical corticosteroid, mometazon furoat, was prescribed once a day and narrow band UVB phototherapy was initiated. Phototherapy was administered three times a week with the initial dose of 0.3 J/cm2 and dose increment at the rate of 20% of the previous dose until the formation of a mild erythema. Total dose received was 69.213 J/cm2. After received therapy, repigmentation was partially achieved, and the progression, as well as the appearance of the new vitiliginous lesions, were stopped. Discussion and conclusion: Various modalities of treatment are used in therapy of vitiligo, but there is still no universal therapy that could be effective in all vitiligo patients. Different clinical manifestations of vitiligo are the result of different pathogenetic mechanisms and require different treatment approaches. Therefore, future research is needed in order to clarify the etiopathogenetic mechanisms and provide new, more effective therapeutic opportunities

The aim of this prospective study was to investigate the effectiveness of sub-tenon application of triamcinolone for neovascular age-related macular degeneration. The study included 38 eyes (26 patients; 14 women and 12 men, aged 63 to 82 years) with newly diagnosed subfoveal neovascular age-related macular degeneration. Each eye received sub-tenon injection of 0.5 mL suspension of triamcinolone-acetonide (20 mg of active substance). Follow up period was 12 months. After initial application, the injections were repeated on individual case, none to five times. Elevated intraocular pressure occurred in five patients (seven eyes) and was treated with topical antiglaucomatous therapy. Transient ptosis of upper eyelid occurred in one case and completely recovered in two days. The mean visual acuity was 0.13 +/- 0.17 on the beginning of the study and 0.22 +/- 0.22 at the end of the study. Visual acuity improved in 15/38 (39%) eyes, remained unchanged in 10/38 (26%) eyes, and worsened in 13/38 (35%) eyes. Improvement by three or more lines on Snellen optotype occurred in two cases. Comparing our results to those from other authors, sub-tenon application of triamcinolone did not prove as effective as when applied intravitreally, but is substantially less expensive and easier to perform.

Bowel-associated dermatosis-arthritis syndrome (BADAS) is defined by the presence of pustular vasculitic skin lesions usually associated with blind loops of the bowel, either after Billroth II or ileojejunal bypass surgery or caused by a chronic inflammatory bowel disease such as Crohn's disease or ulcerative colitis.A 50-year-old patient is presented with an unusual case of pustulo hemorrhagic vasculitis over the lower arms and legs that appeared ten days before the first symptoms of appendicitis, partially regressed, and reappeared five days after appendectomy. Laboratory tests showed anemia, an elevated erythrocyte sedimentation rate, and C-reactive protein as well as a polyclonal increase in IgG and IgA levels, erythrocyturia and proteinuria. Histopathological examination of a skin biopsy indicated the suspected diagnosis. During hospitalization the patient developed arthropathy with swelling of the metacarpophalangeal and interphalangeal joints and ankles. The patient was treated with systemic antibiotics and corticosteroids, which caused resolution of the symptoms.This report speculates that appendicitis was the possible cause of BADAS in this case.