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Introduction The objective of this study was to demonstrate that BCD-057 is similar to innovator adalimumab (iADA) in terms of efficacy, safety, and pharmacokinetics in steady state in the target population of patients with moderate to severe plaque psoriasis (NCT02762955). Methods Patients were randomized in 1:1 ratio to receive 80 mg of BCD-057 or iADA at week 0 and 40 mg thereafter every other week from week 1. At week 24 patients from iADA group were re-randomized (1:1) to continue iADA or to be switched to BCD-057. The primary efficacy endpoint was 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75), secondary endpoints included PASI percent improvement and relative change in affected Body Surface Area (BSA) from baseline at weeks 16, 24, 33, and 55. Safety was assessed through monitoring of adverse events (AEs) and antidrug antibodies. Pharmacokinetics was evaluated at steady state. Results Overall, 346 adult patients were included in the study (174/172 patients in BCD-057/iADA arms, respectively). At week 16 PASI 75 was achieved by 60.34% and 63.37% of patients in BCD-057 and iADA arms, respectively (p = 0.5622). Bounds of the calculated 95% confidence interval (CI) for the difference between PASI 75 responses in arms [-13.26%; 7.2%] fall within the equivalence margin [-15% to 15%] demonstrating equivalent efficacy of BCD-057 and iADA. At week 55 81.61%, 85.56%, and 80.49% of patients in BCD-057, iADA and iADA/BCD-057 arms achieved PASI 75. Comparison of the secondary endpoints did not show significant differences between arms. A comparable pharmacokinetics was shown at steady state. Safety profiles and proportions of patients with antidrug antibodies were similar between arms. The switch from the iADA to BCD-057 did not affect the immunogenicity profile. Conclusion Obtained data demonstrate that BCD-057 and iADA are highly similar in clinical efficacy, pharmacokinetics, safety, and immunogenicity in patients with moderate to severe plaque psoriasis.

Hair shedding in female patients is a frequent complaint in dermatological, endocrinological, and gynecological consults. Previously, the Sinclair Hair Shedding Scale was developed to assess normal versus excessive hair shedding in female pattern hair loss (FPHL) subjects. However, the prevalence of hair shedding in females not suffering from FPHL is unknown. To gain better understanding of hair shedding in the general population, we recruited 300 subjects visiting a public hospital for conditions other than alopecia. Of the 300 subjects recruited, 263 did not suffer from FPHL. Among those subjects, approximately 40% reported experiencing excessive hair shedding (as defined by the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our subject population, approximately 60% of subjects with FPHL reported excessive hair shedding on hair washing days. To best of our knowledge, this is the first study to quantify the prevalence of hair shedding in women. While, no treatment currently exists for this condition, we hope that this study would encourage physicians and researchers to address this frequent concern.

Vitiligo is an acquired, chronic, multifactorial disorder which involves complex interactions between genetic risk fac-tors and environmental triggers. It is characterized by scattered circumscribed depigmented macules and patches any-where on the skin that result from loss of functional melanocytes. According to our statistical data, 1.6% of the general population in Croatia suffers from vitiligo, but varies based on region. It affects all age groups equally, with female patients being more affected (53.95%) than male patients, and no difference in severity of vitiligo. We present a case of a sudden onset of vitiligo vulgaris from a female patient in her twenties, treated at the Department of Dermatology and Venereol-ogy. Her 12-year-old brother simultaneously developed acrofacial vitiligo, six months after their mother died in a car accident. She has been previously diagnosed with type I diabetes and autoimmune endocrinopathies. The depigmented patches covered approximately 60% of her body, with Koebner response on trauma. Although no characteristic UV fl uo-rescence was detected on the affected area, histopathological and immunohistochemical analyses revealed a complete loss of melanocytes, while Langerhans` and dermal dendritic cells replaced the DOPA-positive melanocytes. TSH levels were elevated, and the ultrasound showed thyroid enlargement, which substantiated for a hypothyroidism therapy. Treatment by systemic corticosteroids for a 6 month period was successful in stabilizing the disease.

Malignant melanoma genesis is a very complex process that involves a sequence of pathogenetic cellular events. Mutation of various genes and numerous other cellular mechanisms play an important role in the course of malignant melanocyte alteration and their malignant transformation from naevi into melanoma. Apoptosis is an active, genetically controlled process of programmed cell death, which leads to cell destruction and cell death without involvement of surrounding cells or inflammatory response. In this process, disrupted mechanisms of cell regulation and apoptosis take place in malignant melanoma cells, thus leading to their uncontrolled proliferation and melanocyte growth. Apoptosis is a process that involves two major pathways, the intrinsic and extrinsic apoptotic pathway, which interlace at certain points and ultimately result in apoptosis. It can be said that molecular events regulating cell survival, normal growth arrest, apoptosis and cell differentiation, contribute to the overall pathogenesis of malignant cell growth. It is presumed that in the future, understanding of molecular aberrations and cellular processes, such as cell signaling, cell cycle regulation and cell apoptosis, will be essential for better patient monitoring and rational design of effective treatment.

Angiokeratomas of the vulva are relatively rare finding and a limited number of cases have been reported in the literature. Clinically, angiokeratomas of the vulva are benign vascular lesions usually occurring in middle-aged or older women. Microscopically these lesions are characterized by epidermal hyperkeratosis, papillomatosis, acanthosis, and marked dilatation of the papillary dermal vessels. In most patients, genital lesions are asymptomatic ; however, bleeding, dyspareunia and other symptoms have been described. We report a case of a 45-year-old woman with numerous blue-to-red, scaly papules that spread over the entire area of both labia majora. The patient reported occasional pruritus and burning sensations, discomfort during the intercourse, and significant psychological burden. Histopathologic analysis of the lesion confirmed the diagnosis of angiokeratoma, and all lesions were electrocauterized under local anesthesia. The results of the treatment were very satisfactory, with no side effects or complications. During one- year follow-up, no relapses were noted and the patient remained asymptomatic. Therefore, dermatovenereologists should be aware of angiokeratomas and respective therapeutic options when examining a patient with pruritic, painful, or bleeding lesions in the genital region.

Basal cell carcinoma (basalioma, BCC) is undoubtedly the most common malignant skin cancer and the most common human malignancy in general, with the continuous increase in its incidence. BCC is generally a disorder of white individuals, especially those with fair skin. UV radiation is the most important risk factor in the development of BCC. Short-wavelength UVB radiation (290-320 nm, sunburn rays) is believed to play a greater role in BCC formation than long-wavelength UVA radiation (320-400 nm, tanning rays). A latency period of 20- 50 years is typical between the time of UV damage and the clinical onset of BCC. Therefore, in most cases BCC develops on chronically sun-exposed skin in elderly people, most commonly in the area of head and neck. UVB radiation damages DNA and its repair system and alters the immune system resulting in a progressive genetic alterations and formation of neoplasm. UV-induced mutations in the TP53 tumor- suppressor gene have been found in about 50% of BCC cases. The mutations that activate the Hedgehog intercellular signaling pathway genes, including PTCH, Sonic hedgehog (Shh) and Smoothened (Smo) play a significant role in cutaneous carcinogenesis. Epidemiologic studies demonstrate the higher incidence of the BCC in more equatorial latitudes than in polar latitudes. Other risk factors for the development of BCC include sun bed use, family history of skin cancers, skin type 1 and 2, immunosuppression, previous radiotherapy, and chronic exposure to toxic substances such as inorganic arsenic. Although rarely metastatic, its malignant nature is sometimes emphasized by the local tissue destruction, disfigurement, and even death if left untreated. Due to extremely high incidence of BCC medical professionals should be aware of the importance of the public education on the etiology of this tumor and the importance of the UV protection.

Erythema multiforme (EM) is a skin disease caused by numerous potential triggering agents. It is characterized by symmetrically distributed, round, erythematous iris lesions, with remarkable tendency of recurrence. The purpose of this randomized retrospective study was to summarize our experience concerning the etiology, clinical variants and management of EM. We present 12 EM patients, along with laboratory, clinical and histopathologic analysis, and an overview of the treatment used. According to clinical presentation and histopathologic analysis, there were six cases of EM major, five cases of EM minor and one case of Stevens-Johnson syndrome. In five patients, EM was associated with the use of certain drugs (terbinafine, azithromycin, diclofenac, piroxicam). In three patients, the disease was triggered by the herpes simplex virus infection. In four cases, the etiologic factor (involved in the occurrence) of EM remained unknown. We also present an unusual case of an HIV-positive patient with multiple acral target lesions without mucosal involvement, which developed upon antiretroviral therapy discontinuation. To our knowledge, no case of such EM occurrence has yet been reported. There are various etiologic factors and numerous clinical presentations of EM, including acral target lesions and atypical widely distributed cutaneous and mucosal lesions.

Photoallergic dermatoses are skin lesions following sun exposure, characterized by activation of immunological mechanisms, involving photosensitizers and photoallergens that can cause photosensibilization in some individuals. In this group of disorders, photoallergic contact dermatitis should be accentuated. It manifests as contact allergic dermatitis on sun-exposed skin areas, following direct contact with photoallergens during UV exposure (predominantly UVA). Under influence of light, photosensitizers get activated, followed by fusion with cutaneous proteins which renders them to complete antigens, and consequential initiation of immunological mechanisms with resulting pathological skin lesions. The most common photoallergens are: sulfonamide antibiotics, phenothiazines, and halogenated salicylanilides. Photoallergic dermatoses are comprised of several disorders, although the causative photoallergen remains unknown (e.g. solar urticaria, polymorphous light eruption and hydroa vacciniforme). Solar urticaria is a rare, acute urticarial reaction on both sun- exposed and covered skin areas, which appears soon after exposure to sun or artificial lighting. Polymorphous light eruption is a relatively common polymorphous skin eruption, which usually appears in spring. Its pathogenesis is unknown, presumably photoallergic reaction. Hydroa vacciniforme is a rare photodermatosis of unknown etiology, which usually presents in summer-time. It is characterized by vesicobullous eruptions, with residual nonesthetic varioliform scarring.

Cicatricial pemphigoid is an autoimmune bullous disease characterized by mucous membrane fibrosis with resulting scarring, predominantly in the conjunctival and oral mucosa, which rarely involves skin changes. The majority of patients present with painful erosions or desquamative scarring gingivitis, resulting in eating and drinking disorders. Typical ocular lesions include chronic scarring conjunctivitis with progressive subconjunctival fibrosis, fornix foreshortening and synechia formation between the bulbar and palpebral conjunctiva, occasionally resulting in blindness. A 69-year-old woman was admitted to our Department for intense pain and severe burning sensation in the oral cavity, induced by several erosions and solitary blisters, lasting for 3 years. She was also diagnosed with the right eye symblepharon, lid entropion, trichiasis, leukoma and blindness of the right eye. The diagnosis of cicatricial pemphigoid was based on clinical picture and histopathology combined with immunofluorescence methods, with therapy initiated thereupon. Systemic corticosteroid (methylprednisolone) therapy in combination with azathioprine proved successful in the treatment of oral lesions as well as for stabilization of ocular lesions. Unfortunately, the patient was diagnosed in the advanced stage when scarring had already occurred. Prompt recognition of cicatricial pemphigoid and close patient monitoring are an imperative for the future prognosis of the disease.

Psoriasis is a chronic, hereditary disease generally characterized by eruption of erythematous, silvery-scaled plaques, predominantly on the elbows, knees, scalp and trunk, affecting between 1-2% of the population worldwide. Psoriasis is a multifactorial disease of unknown etiology. It has been shown that in some patients alcohol abuse has been associated with psoriasis. Chronic alcohol abuse results in the impairment of health-related, social and occupational functioning. Therefore the association of psoriasis and alcoholism represents one of the major psychodermatological issues where a multidisciplinary approach (including dermatologist, psychiatrist, psychologist and others) is crucial for optimal outcome.

Acroangiodermatitis (synonym pseudo-Kaposi sarcoma) is a dermatological condition characterized by purple-colored nodules, plaques or patches, mostly on the extensor surfaces of lower extremities, usually in patients with chronic venous insufficiency and arteriovenous malformations of the legs, but also in hemodialysis patients with iatrogenic arteriovenous shunts, paralyzed limbs and amputation stumps. Acroangiodermatitis in patients with chronic venous insufficiency manifests usually as bilateral skin lesions located on the dorsa of the feet, halux and second toe, or on the medial aspect of lower legs. Acroangiodermatitis may look like Kaposi sarcoma, but in contrast to Kaposi sarcoma, acroangiodermatitis is not characterized by progression of changes, and there is a lack of spindle cells and silt-like vessels on histopathologic analysis. Three cases of acroangiodermatitis encountered in our clinical practice are described. The patients presented with livid-erythematous patches on lower legs and skin changes connected with chronic venous insufficiency, treated at the Department Phlebology Unit. Results of the histopathologic analysis indicated acroangiodermatitis. Thus, in clinical practice it is important to recognize acroangiodermatitis and to exclude Kaposi sarcoma, as sometimes there is similarity with this entity. Topical therapy with neutral and local corticosteroid preparations is often useful, however, the use of compressive bandages and dermatologic follow up are recommended.

Porphyrias are an uncommon, heterogeneous group of metabolic diseases caused by inherited or acquired deficiency of specific enzymes in the heme biosynthetic pathway resulting in an excess of porphyrins (red-brown pigments) and their precursors. Accumulation of heme precursors, such as porphyrinogens that are spontaneously oxidized to porphyrins, is responsible for various clinical features. Porphyrias are classified into three groups: erythropoietic, hepatic and hepatoerythropoietic, depending on the primary organ affected. Porphyria cutanea tarda (PCT) is the most common porphyria, characterized by defective uroporphyrinogen III decarboxylase enzyme. There are three types of PCT with typical skin manifestations. Patients with PCT present with skin fragility, erosions, vesicles, bullae, and milia in sun-exposed areas of the skin, sometimes periorbital mottled hyperpigmentation and hypertrichosis, sclerodermoid changes and ulceration. We present the most common pathogenetic, clinical, diagnostic, and therapeutic features of PCT and other types of porphyria.