Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

Background: There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. Methods: In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. Results: The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. Conclusions: These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.

A neglected causative agent in diabetic foot infection: a retrospective evaluation of 13 patients with fungal etiology

Background/aim: Clinicians often neglect fungal infections and do not routinely investigate deep tissue from the wound for fungal culture and sensitivity due to insufficient information in the literature. In this study, we aimed to evaluate fungal etiology of invasive fungal diabetic foot which is rarely reported in the literature. Materials and methods: The patients who were unresponsive to antibiotic therapy and those with positive fungal in bone or deep tissue culture were enrolled in the study. Detailed hospital records were retrieved for demographics and clinical features. Results: A total of 13 patients who were diagnosed with invasive fungal diabetic foot (ten females, three males, mean age 59.8 ± 9 years) were included. All of the patients had type-2 diabetes mellitus. Eleven (84.6%) patients had mixed infection. The most common cause of fungal infections of diabetic foot ulcers was the Candida species. Ten (76.9%) patients underwent amputation, two (15.4%) patients refused amputation, and one patient died before surgery. Conclusion: Invasive fungal infections may also be a causative pathogen in deep tissue infections. Therefore, fungal pathogens should be considered in patients unresponsive to long-term antibiotic therapy. Early detection of fungal infections in high-risk individuals is critical for the prevention of severe consequences such as foot amputation.

The efficacy and safety of omalizumab in refractory chronic spontaneous urticaria: real-life experience in Turkey.

INTRODUCTION: This study used real-world data to evaluate the effectiveness and reliability of omalizumab in treating recalcitrant chronic spontaneous urticaria in Turkish patients. METHODS: Study data were collected retrospectively from eight tertiary-care hospitals in Turkey. This study included 132 patients with chronic spontaneous urticaria that were resistant to H1 antihistamine treatment in a dose up to four times the licensed dose and were treated with 300 mg/month of omalizumab for 6 months. RESULTS: The mean weekly urticarial activity score (UAS7) after omalizumab treatment improved significantly compared to the pre-treatment score (p < 0.001). Treatment response was detected primarily in the 1st and 2nd months after treatment. No significant association was observed between omalizumab's treatment effectiveness and disease-related parameters or laboratory data. The mean dermatology life quality index was 23.12 ± 6.15 before treatment and decreased to 3.55 ± 3.60 6 months after treatment (p < 0.001). No side effects were reported in 89.4% (118) of the patients. CONCLUSIONS: This study showed that UAS7 decreased significantly and quality of life improved in omalizumab-treated patients. Moreover, treatment effectiveness was mainly observed in the first 2 months after treatment. However, no association was observed between omalizumab treatment effectiveness and disease-related parameters or laboratory data.

Dry eye and Meibomian gland dysfunction with meibography in patients with lamellar ichthyosis.

PURPOSE: To evaluate the dry eye findings and Meibomian gland dysfunction as demonstrated with meibography in patients with lamellar ichthyosis. METHODS: Twenty-four eyes of 12 patients with lamellar ichthyosis (Group 1) and twenty-four eyes of 12 healthy individuals (Group 2) were enrolled. Comprehensive eye examination along with corneal and conjunctival fluorescein staining with Oxford scoring, tear film break-up time, Schirmer 1 test, ocular surface disease index (OSDI) score assessment, and evaluation of upper and lower eyelid Meibomian glands using infrared filter of slit-lamp biomicroscope (SL-D701, TOPCON, Tokyo, Japan) were performed. The Meibomian glands were graded from grade 0 (no loss of Meibomian glands) to grade 3 (gland dropout >2/3 of the total Meibomian glands). RESULTS: The mean ages of Group 1 and Group 2 were 25.3±15.6years (range, 9-61 years) and 25.3±13.3years (range, 9-52 years), respectively (p=0.997). No significant difference in terms of best-corrected visual acuity, Schirmer 1 test and Oxford scores were detected in between groups. Mean tear film break-up time was lower (p=0.013), and OSDI score, lower, upper and total (upper+lower) meiboscores were significantly higher in Group 1 as compared with Group 2 (p<0.001, p=0.001, p=0.001, p=0.001, respectively). CONCLUSION: Lamellar ichthyosis is associated with evaporative type dry eye disease with decreased tear film break-up time, normal Schirmer 1 values and Meibomian gland dysfunction that can objectively be demonstrated with meibography. For this reason, in order to prevent undesired complications, these patients should be examined and treated for dry eye disease especially targeting Meibomian gland dysfunction.

Use of Tigecycline for Diabetic Foot Infections

OBJECTIVE: The aim of this study is to evaluate tigecycline for diabetic foot infections (DFIs). MATERIALS AND METHODS: In this prospective observational study, the investigators included patients who had consultation with the Diabetic Foot Council of Ege University Faculty of Medicine (Izmir, Turkey) between March 2013 and July 2015 and who used tigecycline during their treatment. Treatment success was assessed by design-specific criteria for each evaluation. RESULTS: The study included 105 cases. Of those, 37 (35.2%) were women (mean [± standard deviation] age, 61.9 ± 11.9 years). The success rate of tigecycline treatment was 93.3% in mild infections, 56.2% in moderate, 57.7% in severe, and 61.9% in all cases. The authors found a 9-fold decrease (P = .046) in the success of tigecycline treatment among those who developed moderate or severe DFIs and a 6.4-fold decrease (P < .0001) among those who had arterial stenosis. For 33 (71.7%) of 46 (43.8%) patients who experienced a side effect, tigecycline treatment was continued as it could be tolerated. CONCLUSIONS: If tigecycline is to be the treatment choice, extra attention must be paid to patients with arterial stenosis, severe DFIs, and side effects. The common disadvantage is the high side effect rate, especially nausea. However, it is generally not necessary to discontinue the medication in cases with nausea. Therefore, tigecycline may be used as a choice of therapy in mild DFIs.

Risk factors for amputation in patients with diabetic foot infection: a prospective study.

There is a variety of diagnostic and therapeutic algorithms for diabetic foot infections (DFIs). Some of them are too difficult to be applied in routine clinical approach. In the routine clinical approach, it is necessary to find new risk factors and end up with a quick and easy assessment of DFIs. In this study, we aimed to evaluate the independent risk factors for osteomyelitis, amputation and major amputation in patients with DFI using standard scoring procedures. We prospectively studied 379 patients with DFI. The variables were analysed using logistic analysis. A total of 126 cases (33·2%) underwent amputation. The odds ratios in the amputation model were 3·09 for osteomyelitis (P < 0·001), 4·90 for arterial stenosis (AS) (P < 0·001), 3·67 for the history of DFI (P = 0·001), 2·47 for ulcer duration >60 days (P = 0·001), 3·10 for ulcer depth > 15 mm (P < 0·001) and 10·28 for fungal DFI (P = 0·015). In this study, the unusual result of well-known literature was fungal DFI as an independent risk factor for amputation in patients with DFI.

Ocular response analyser measurements and central corneal thickness in ocular rosacea patients.

Rosacea is a chronic cutaneous disorder which is known to cause inflammation and increased proteolytic activity on the ocular surface that might lead to corneal biomechanical alterations. The aim of this study is to evaluate the corneal biomechanical properties of ocular rosacea patients and compare the measurements with healthy individuals as measured with Reichert ocular response analyser (ORA). Besides full eye examination [best corrected visual acuity (BCVA), intraocular pressure (IOP) measured with Goldmann applanation tonometry (IOP-G)], central corneal thickness (CCT), and ORA [corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated IOP (IOPcc), Goldmann correlated IOP (IOPg)] measurements of 30 eyes of 15 ocular rosacea patients (study group) and 30 eyes of 15 healthy individuals (control group) were performed. For comparisons paired t test was used. Mean age of study group was 45.26 ± 11.65 (range 25 and 63) and control group was 45.00 ± 8.91 (range 26 and 58) years (p = 0.865). No significant difference in BCVA, CCT, IOP-G, IOPcc was detected among groups. However, IOPg, CH, and CRF in the study group were significantly lower than in the control group (p = 0.013, p = 0.013, p = 0.009, respectively). IOPg, CH, and CRF parameters of ocular rosacea patients were significantly lower than normal individuals. These differences and their probable clinical reflections that might effect making decisions in conditions such as glaucoma should be investigated in larger number of patients.

Anatomocosmetic implication rules of the corrugator supercilii muscle for youthful eye appearance.

The dynamic balance of the eyebrows is maintained by the frontal muscle which acts as a brow elevator, and the brow depressors include corrugator supercilii muscle (CSM), procerus, depressor supercilii, and orbicularis oculi muscles. The glabellar rhytids might appear as a result of negative emotions, such as anger, anxiety, fatigue, fear, or disapproval. For youthful and calmer eyes, CSM may restore the muscle balance more safely and effectively for the treatments of forehead rejuvenation. In 50 cadaver hemibrows, CSM was dissected to investigate the location, position, muscle patterns, and its relationships to other muscles. The location of the CSM was variable; five different CSM patterns were defined. Pattern 1: rectangular-shaped classical type was observed with the frequency of 42.5 %. Also, three bellies were present in 25 %, and duplicate muscle in 12.5 %. Irregular flat (15 %) and hypoplastic types (5 %) were introduced as previously unidentified patterns. In muscle specimens, 30 % had complete symmetry, 45 % complete asymmetry, and 25 % semi-assymetry. Mean CSM thickness, length, and width were measured as 1.62 ± 0.4, 29.24 ± 6.4, and 12.62 ± 3.3 mm, respectively. The distances of the medial origo of the CSM-midline and the lateral origo of the CSM-midline were measured as 5.54 ± 4.89 and 14.62 ± 4.17 mm. The different patterns of the CSM were undefined previously. The findings manifest the necessity of botox treatment peculiar to each individual. As, insertion points have been releasing fibres to the peripheral muscles, it is an evidence of its complicated structure. The muscles in the glabella are difficult to demarcate precisely from surface anatomy due to overlapped muscles with intermingled borders, where they are attached as individual patterns. Hence, it might be disadvantageous that different patterns may lead to the risk of asymmetry of the face and brow ptosis in the postinjection period.

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations.

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.

Evaluation of dry eye and meibomian gland dysfunction with meibography in patients with rosacea.

PURPOSE: To evaluate the dry eye tests and meibography of patients with ocular rosacea. METHODS: Thirty-six eyes of 18 patients with ocular rosacea (group 1) and 38 eyes of 19 healthy individuals (group 2) were enrolled. Besides full-eye examination, corneal and conjunctival fluorescein staining and Oxford scoring, tear film break-up time, Schirmer 1 test, ocular surface disease index score assessment, and evaluation of upper and lower eyelid meibomian glands using infrared captures of an optical coherence tomography (OCT) (Spectralis HRA+OCT; Heidelberg Engineering) device were performed (grade 0: no loss of meibomian glands, grade 1: gland dropout area <1/3 of the total meibomian glands, grade 2: gland dropout area 1/3 to 2/3 of the total meibomian glands, grade 3: gland dropout >2/3 of the total meibomian glands). RESULTS: The mean ages of group 1 and group 2 were 50.2 ± 9.5 (range, 32-65), and 46.3 ± 14.1 years (range, 25-70), respectively (P = 0.225). No significant difference in best-corrected visual acuity and meiboscores of upper eyelids were detected in between groups. Schirmer 1 and tear film break-up time in group 1 were significantly lower than in group 2 (P = 0.005, P < 0.001, respectively). Ocular surface disease index and Oxford scale scores and meiboscores of lower and total (upper + lower) eyelids were significantly higher in group 1 than in group 2 (P = 0.04, P = 0.018, P < 0.001, P = 0.03, respectively). CONCLUSIONS: Ocular rosacea causes dry eye and significant meibomian gland loss that can objectively be demonstrated with meibography. The infrared camera of OCT-that is widely found in many ophthalmology departments-might be used to evaluate meibomian gland dysfunction in these individuals.

Cutaneous side effects of chemotherapy in pediatric oncology patients.

Pediatric oncology patients can present with various skin lesions related to both primary disease and immunosuppressive treatments. This study aimed to evaluate the cutaneous side effects of chemotherapy in pediatric oncology patients. Sixty-five pediatric oncology patients who were scheduled to undergo chemotherapy from May 2011 to May 2013 were included in the study. Three patients were excluded from the results, as 2 patients died during treatment and 1 patient withdrew from the study; therefore, a total of 62 patients were evaluated for mucocutaneous findings. Patients were grouped according to their oncological diagnoses and a statistical analysis was performed. There was no statistical significance in the incidence of cutaneous side effects of chemotherapy among the different diagnostic groups. Awareness among dermatologists of the possible cutaneous side effects of chemotherapy in pediatric patients and their causes can promote early diagnosis and treatment in this patient population.

Genotype and Anterior Segment Phenotype in a Cohort of Turkish Patients with Lamellar Ichthyosis.

PURPOSE: To evaluate the ocular surface and topography findings of lamellar ichthyosis, and to investigate the correlation of these findings with mutations in TGM1, CYP4F22 and NIPAL4 genes. METHODS: Twelve patients with lamellar ichthyosis were evaluated. Routine ophthalmic examination including Schirmer 1, tear break-up time and ocular surface staining score, topography, and genetic evaluation for coding exons of TGM1, NIPAL4 and CYP4F22 genes were performed. RESULTS: The mean age of the patients was 19.75 ± 9.15 (range, 4-31) years. Mean Schirmer 1 scores of the right and the left eyes were similar (18.75 ± 3.10 mm). Mean tear break-up time of the right and the left eyes were 6.58 ± 2.74, 6.58 ± 3.02 seconds, respectively. Mean ocular surface staining grade was 0.36 ± 0.20 in the right, and 0.39 ± 0.17 in the left eyes. Keratoconus was detected in two patients. Two patients with bilateral cataract formation were found. Genetic sequencing revealed that one case had homozygous R326X mutation in the CYP4F22 gene, two cases had homozygous A176D mutation in the NIPAL4 gene, and three had homozygous M1T mutation in the same gene. Mutations were detected in patients with keratoconus and in a patient with bilateral cataract formation. CONCLUSIONS: In lamellar ichthyosis, eyelid malformations together with decreased tear break-up time might cause sight-threatening complications. Genetic counseling for mutations might enable the physician to predict the possibility of upcoming ocular problems in lamellar ichthyosis patients.

Viral infections of the face.

Viral infections affecting the face may cause significant morbidity, cosmetic disfigurement, and psychological distress. The success of therapy needs whole and correct evaluation of the clinical signs and symptoms. Some viruses such as Papillomaviridae, Herpesviridae, and Polyomaviridae primarily infect the facial skin, whereas others affect the face infrequently, as in parapox virus infections. Sometimes, involvement of the face can be a part of more generalized eruption and systemic symptoms in viral infections caused by Todaviridae, Flaviviridae, Arenaviridiae, and Flaviviridae. Clinical diagnosis can be challenging in various viral diseases when they occur in nonendemic geographic areas. The objective of this review was to concentrate on epidemiologic and clinical characteristics of the viral illnesses with facial skin involvement.

Follicular mucinosis and follicular mycosis fungoides: clinicopathological evaluation of seven cases.

OBJECTIVE: Follicular mucinosis is a disease characterized by follicular degeneration and mucin accumulation. It can be seen in mycosis fungoides, although idiopathic or forms associated with other diseases are also known. Follicular mycosis fungoides is a type of mycosis fungoides with different clinicopathological and prognostic features. MATERIAL AND METHOD: Seven cases with follicular centered lesions and multiple biopsies (2-6) were included. Cases were evaluated according to their clinical, histological and immunophenotypical features and follow-up data. RESULTS: All cases were male, and the mean age was 40.3 (range 18-61). Clinical complaints were follicular prominence, erythema and alopecia at head and neck, trunk, and lower limbs. Follicular mucinosis (6/7), and dermal lymphoid infiltration showing minimal-intensive folliculotropism accompanied by eosinophils was seen. Lymphoid infiltration was composed of small-medium sized cells, with scattered hyperchromatic nuclei in six cases. In one case there was only minimal cytological atypia. Intense folliculotropism of atypical lymphocytes and dense dermal infiltration without follicular mucinosis was seen in one case. Local and/or systemic treatments were applied and partial remission was achieved histologically. In three cases new and increasing lesions were seen. Density of infiltration and atypia were increased. CONCLUSION: The findings supported the opinion that follicular mucinosis is an important finding seen in mycosis fungoides. There can be important differences concerning the amount of infiltration and degree of atypia. In cases where the density of infiltration associated with follicular mucinosis is not diagnostic for MF, there can be progression over time. Long-term follow up is necessary in such cases where the differential diagnosis is difficult.

Adverse cutaneous drug reactions among hospitalized patients: five year surveillance.

CONTEXT: Cutaneous Adverse Drug Reactions (CADRs) are observed in 2-3% of hospitalized patients. The clinical presentation of the CADRs varies among different populations. OBJECTIVE: To study the CADRs in hospitalized patients and their outcome. MATERIALS AND METHODS: Patients hospitalized at our department between 2005 May and 2010 May were retrospectively reviewed for the diagnosis of CADRs. RESULTS: A total of 94 patients (3.3%) were diagnosed with CADR among 2801 hospitalized patients. Of them, 56 patients were female (59.6%) and 38 patients were male (40.4%). The culprit drugs were antibiotics (24.5%), non-steroid anti-inflammatory drugs (NSAID) (22.4%), anticonvulsants (13.8%), antihypertensive agents (8.5%), paracetamol with or without pseudoephedrine or phenylephrine (6.4%), intravenous contrasts (3.2%), terbinafine (2.1%), biologic agents (2.1%) and various other medications (17.0%). The most common clinical type of CADRs was morbilliform exanthemas in 59.6% of the patients, followed by erythroderma (6.4%), drug reactions with eosinophilia and systemic symptoms (6.4%), lichenoid drug reaction (5.3%), urticaria and angioedema (4.3%), acute generalized exanthematous pustulosis (4.3%), drug-induced vasculitis (3.2%), drug induced psoriasis (2.1%), Stevens-Johnson syndrome/toxic epidermal necrolysis overlap (2.1%), psoriasiform drug reaction (2.1%). Fixed drug reaction, erythema multiforme, bullous drug reaction, drug induced panniculitis were observed in one each. No deaths occurred on the follow-up. Fever was observed in 35.1% of the patients. Eosinophilia was present in 51.1% of them. Latency period ranged between 0-15 days in 59 patients (62.8%), 15-30 days in 19 patients (20.2%), 30-90 days in 13 patients (13.8%), 90-120 days in three of them (3.2%). The latency for anticonvulsant drugs was statistically longer than the other group of drugs (p: 0.027). DISCUSSION AND CONCLUSIONS: CADRs were more common in women and most of them were caused by antimicrobial agents followed by NSAIDs and anticonvulsants. Latency period of anticonvulsants were longer than the other groups.

Development of squamous cell carcinoma on an inflammatory linear verrucous epidermal nevus in the genital area.

Inflammatory linear verrucous epidermal nevus is a rare cutaneous disorder characterized by pruritic, erythematous, and verrucous papules and plaques along the lines of Blaschko. Histopathologically, there is a benign verrucous proliferation of keratinocytes together with alternating parakeratosis and orthokeratosis as well as inflammatory changes. We report a patient who developed squamous cell carcinoma (SCC) on an inflammatory linear verrucous epidermal nevus and we discuss the importance of regular follow-up of patients with epidermal nevi.

Generalized pustular eruptions due to terbinafine.

Terbinafine, a widely used antifungal agent, may rarely cause cutaneous side effects with an incidence of 2.7%. Generalized pustular eruptions are quite uncommon but severe adverse cutaneous reactions of terbinafine have been reported. The main pustular eruptions due to terbinafine include acute generalized exanthematous pustulosis and drug induced pustular psoriasis. In this report, two cases of acute generalized exanthematous pustulosis and one case of generalized pustular psoriasis triggered with terbinafine are presented.