Andrija Stanimirović

Use of biologics for psoriasis in Central and Eastern European countries.

To evaluate the use of biological agents for the treatment of psoriasis and to explore country‐specific differences within six Central and Eastern European (CEE) countries, namely Bulgaria, Croatia, the Czech Republic, Hungary, Poland and Romania.

Expression of p53, bcl-2 and growth hormone receptor in actinic keratosis, hypertrophic type

According to novel investigations, actinic keratosis (AK) is not a premalignant lesion but is a malignant lesion in the evolution to invasive squamous cell carcinoma (SCC). Thus, we analyzed p53, bcl-2 and growth hormone receptor (GHR) expression in hypertrophic-type AK (HAK) to determine the relative importance of these protooncogenes in the biological behavior of HAK. Expression of p53, bcl-2 and GHR was determined by immunohistochemistry in 33 HAK specimens and surrounding perilesional normal skin (PNS). The relative proportions of immunoreactive cells were determined. Of the 33 HAK specimens, 30 (91%) showed immunopositive staining for p53, 33 (100%) for bcl-2, and 12 (36%) for GHR. Highly positive p53 expression in HAK lesions could indicate that p53 mutation is an early and crucial event in lesion development. The detected pattern of the p53/bcl-2 ratio in HAK suggests an important role for another gene: the proapoptotic gene bax. Our findings indicate that GHR expression could be a biological marker of progression of HAK to SCC.

Treatment of cutaneous leishmaniasis with 20% paromomycin ointment.

Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania. In Mediterranean countries, the most common causative agents are Leishmania (L.) major, L. infantum and L. tropica. In Croatia, cutaneous leishmaniasis is a rare disease, the last case being reported in 1988. Our patient was a 5‐year‐old boy with a left cheek skin lesion in the form of papule with central exulceration, hyperkeratotic crust and erythema of a 6‐month duration. The diagnosis of cutaneous leishmaniasis was based on history data (stay in the southernmost region of Croatia and multiple mosquito bites), light microscopic histology (dense infiltrates of large histiocytes with extracellular bodies), and positive Montenegro (leishmanin) test. A new therapy with aminosidine (paromomycin), an aminoglycoside antibiotic, in the form of ointment at a concentration of 20%, was for the first time used in Croatia. Four‐week therapy resulted in complete regression of the skin lesions with residual hyperpigmentation. During therapy, no local or systemic side effects were observed. Thus, topical therapy with paromomycin could be considered an efficient therapeutic alternative in the management of cutaneous leishmaniasis.

Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length‐assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26–50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB‐UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant‐to‐treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

Correlation between Bcl-2 and Bax in atrophic and hypertrophic type of actinic keratosis

Background  Recent investigations consider actinic keratosis (AK) as an earliest visible pattern of squamous cell carcinoma (SCC). We have analysed the expression of apoptosis‐related proteins TP53, Bcl‐2 and Bax in 30 atrophic and 30 hypertrophic AK cases.

Paederus dermatitis featuring chronic contact dermatitis

Paederus dermatitis is a distinct variant of acute irritant contact dermatitis caused by mucocutaneous contact with the specific toxin of an insect belonging to the genus Paederus. It is characterized by the sudden onset of erythema and vesiculobullous lesions on exposed skin, with special predilection for the periorbital region. Paederus species have been mostly identified in Africa, Asia, Australia, and Central/South America. We report a 51-year-old woman who experienced 4 recurrences of periorbital erythema and edema in the previous year. No consistent etiology could be established at the beginning. Only after taking a detailed medical history was it discovered that 1 year before our examination, the patient had traveled to Kenya, where she had experienced contact with the insect. This fact led us to the diagnosis of Paederus dermatitis. After appropriate treatment, a complete regression was observed over a 3-week period.

Styling without shedding: Novel topical formula reduces hair shedding by contracting the arrector pili muscle

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α1 adrenergic receptor agonist, can be used to contract the arrector pili muscle of the follicular unit; thus, increasing the force required to pluck hair and reducing shedding during brushing. While demonstrating efficacy, phenylephrine has several drawbacks when applied to the scalp, including the possibility cardiovascular events. We hypothesized that a high concentration of a weak α1 agonist would allow for: (a) rapid penetration through the stratum corneum eliciting a quick response; (b) a low probability of cardiac adverse events owing to the low receptor binding affinity; and (c) an efficacy of the weak α1 agonist similar to that of phenylephrine at the local site of application. Accordingly, we developed a novel topical solution, AB‐102, containing a high concentration of a weak α1 agonist. Several studies were conducted to test the safety and efficacy of AB‐102. In a dose escalating safety study, utilizing a wearable holter monitor, we observed no cardiac or hemodynamic adverse events. In addition, in a controlled efficacy study, AB‐102 reduced the number of hairs shed during brushing by up to 77% (average of 38%).

Treatment of penile actinomycosis

Actinomycosis is an uncommon disease, which can affect patients of all ages, more frequent adults, particularly men (Könönen & Wade, 2015; Wong, Turmezei, & Weston, 2011). Penile localization is extremely rare and usually connected to the penis pilonidal sinus (Chikkamuniyappa, Scott, & Furman, 2004; Min, Park, & Paik, 2012; Rao, Sharma, Thyveetil, & Karim, 2006; Rashid, Williams, Parry, & Malone 1992; Saharay, Farooqui, & Chappell, 1996; Val-Bernal, Azcarretazábal, & Garijo, 1999). A 45-year-old male with medical history of arterial hypertension, epilepsy, and surgical correction of the distal penile hypospadia in childhood was admitted to our department because of fever and chills that started 1 day before admission. On admission, the patient was febrile, hypotensive, tachycardic, and mildly dehydrated. Laboratory test results showed erythrocyte sedimentation rate 62 mm/1st hr, Creactive protein 192.2 mg/L, white blood cell count 23.2 × 10/L with 85% neutrophils in differential count. After admission, a painful red fluctuant inflamed mass of the distal part of penile shaft was observed (Figure 1a). Analysis of the pus demonstrated polymorphonuclears and detritus and Actinomyces odontolyticus was isolated. The patient was treated with clindamycin intravenous (900 mg TID) for 3 weeks followed by oral amoxicillin (500 mg QID) for the next 3 months with rapid clinical response (Figure 1b,c,e,f )). During the treatment one fistula in the penile flap was observed and dilated for successful abscess drainage (Figure 1d). For the treatment of actinomycosis, penicillin is the preferred choice, but tetracyclines, erythromycin, and clindamycin have excellent results. Because the fact that most Actinomyces spp. infections are polymicrobial (skin localization suggests Staphlococcus spp.) and excellent clinical response to the therapy we treated our patient with clindamycin. In case of actinomycosis, a prolonged course of antimicrobial therapy with high doses is necessary, usually 2–6 weeks intravenously, followed by 6–12 months orally (Könönen & Wade, 2015; Wong et al., 2011). Our patient was treated in total for less than 4 months, and was cured with no signs of relapse 6 months after the treatment ended. Superficial localization of infection and minimally invasive surgical approach for drainage of abscess contributed to

Juvenile Onset Hypopigmented Mycosis Fungoides: A Case Series Of 3 Patients

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Primary cutaneous lymphomas (PCLs) are exceedingly rare in children and adolescents, with mycosis fungoides (MF) being the most frequent PCL diagnosed in childhood. The incidence of MF is 6.4 per 1, 000, 000 per year in adults, but the occurrence in children and young adults is rare and has not been well established yet. Hypopigmented mycosis fungoides (HMF) is an atypical and rare subtype of MF characterized by solely hypopigmented patches or in combination with erythematous patches or plaques. There are no criteria that define a typical case of HMF. We present three cases of juvenileonset HMF at Department of Dermatology and Venereology, University Hospital Center Zagreb between November 2014 and January 2015. Patients were between 9 and 12 years old at the time of diagnosis. The diagnosis was reached based on clinical, histopathological and immunohistochemical correlation. All patients were investigated at the time of diagnosis with complete blood count, peripheral smear, ultrasonography of abdomen and pelvis, and chest X-ray. They were all without extracutaneous progression of disease. Narrowband UVB (311nm) phototherapy and/or potent topical steroids were used as a first- line treatment. HMF is rare in Caucasians and with only few cases described in children. Juvenile-onset MF is often misdiagnosed at early stages as benign condition. HMF may simulate atopic dermatitis, pityriasis alba, pityriasis lichenoides, tinea versicolor, vitiligo, postinflammatory hyperpigmentation or leprosy (Hansen? disease). Although HMF has good prognosis, it is a malignant skin lymphoma and should always be treated as such. Treatment modalities for juvenile MF are based on general strategies for adults according to disease stage.

Therapeutic Use of Monoclonal Antibodies in Psoriasis-Immunological Principles and Immune- Based Adverse Effects

Autoimmune bullous diseases are a group of intraand subepidermal disorders with different course and prognosis. Most of them are serious diseases which have to be treated for longer period and controlled by experienced dermatologist. Pemphigus group of diseases is characterized by acantholysis in the epithelium of mucous membranes or / and the skin. These diseases can have significant morbidity and morality as a result of complications of the disease or side-effects of the therapy. Mainstay of the therapy of pemphigus are corticosteroids. Usually together with corticosteroids, steroid-sparing agents i.e. azathioprine or mycophenate mofetil are introduced to reduce side-effects of corticosteroids and to make remision periods longer. Patients who do not respond to these therapies should be treated with intravenous immunoglobulins, cyclophosphamide or rituximab.Histamine intolerance (HIT) develops as a result of an impaired diamine oxidase (DA0) activity due to gastrointestinal disease or through DA0 inhibition, as well as through a genetic predis-position which was proven in a number of patients. The intake of histamine- rich foods as well as alcohol or drugs which cause either the release of histamine or the blocking of DA0 can lead to various disorders in many organs (gastrointestinal system, skin, lungs, cardiovascular system and the brain), depending on the expression of histamine receptors. Dermatologic sequels can be rashes, itch, urticaria, angioedema, dermatitis, eczema and even acne, rosacea, psoriasis and other. The recognizing of symptoms due to HIT is especially important in treating such patients. Because of the possibility of symptoms affecting numerous organs, a detailed history of symptoms following the intake of histamine rich foods or drugs that interfere with histamine metabolism is essential for making a diagnosis of HIT. Considering that such symptoms ran be a result of multiple factors, the existence of HIT is usually underestimated, 5 expectations are being made from the future studies.