Factors Related to Omalizumab Drug Survival and Treatment Responses in Chronic Urticaria.

INTRODUCTION: This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice. METHODS: This study included 386 patients with chronic urticaria. Demographic characteristics, clinical features, laboratory parameters, and omalizumab treatment data were analyzed retrospectively. The 7-day urticaria activity score (UAS7) and urticaria control test (UCT) were used to assess disease severity and treatment responses. RESULTS: Well-controlled disease (UAS7 ≤6) was achieved in 59.3% of patients at a median of 2 months. Complete response was significantly higher in patients treated with omalizumab for ≥12 months (p < 0.001). Family history of asthma (p = 0.01) was less frequent, and disease duration (p = 0.041) was shorter in patients with well-controlled disease. Total treatment duration was longer in patients with relapse (p < 0.001) and serum Helicobacter pylori IgA positivity (p = 0.029). DISCUSSION/CONCLUSION: Treatment response is better in patients treated with omalizumab for ≥12 months. However, prolonged treatment does not prevent relapse. Our findings suggest that continuous or intermittent therapy is an appropriate alternative treatment option in patients with severe chronic urticaria; however, continuous therapy can be preferred to maintain the patient's quality of life.

Predictors of drug survival of biologic therapies in psoriasis patients.

INTRODUCTION: We aimed to investigate the clinical, immunological, and genetic factors affecting the response to anti-TNFα (tumor necrosis factor-α) and interleukin-12/23 therapies and drug survivals. METHODS: A total of 180 patients were divided into two groups: 89 patients who used at least two biologic agents, with the initial biologic agent used less than 12 months (group A), and 91 biologic-naive patients who have been receiving a single biologic agent for more than 12 months (group B). ELISA (enzyme-linked immunosorbent assay) was used to analyze anti-drug antibodies (ADAs) in blood samples. Clinical data of the patients were retrospectively analyzed. HLA-SSO (sequence-specific oligonucleotide) Typing Kits were used for HLA-C typing. IBM SPSS v.21 was used for statistical analysis.Results: Infliximab had the longest drug survival as the first biologic agent in group A (p = .015). Etanercept had the lowest ADA count compared to the other anti-TNF agents (p = .001). HLA-Cw6 negativity, late-onset psoriasis, smoking and alcohol use were determined to be risk factors for treatment failure in group A. HLA-Cw6 was found to be associated with type I psoriasis (p = .000). CONCLUSIONS: Although our study is retrospective of a relatively low number of patients, this is a preliminary study focusing on two different patient populations based on therapy response.

Psoriasis and 5HT-R2C Gene Polymorphism: Association between Clinical, Demographic and Therapeutic Parameters in the Turkish Population.

We aimed to investigate the relationship between single nucleotide polymorphism (SNP) in the promoter region of the 5-HT-R2C gene and stress-related disease psoriasis in the Turkish population. The putative association between the 5-HTR2C variant (rs6318 Cys23Ser allele) and patients with psoriasis was investigated. 100 patients with psoriasis and 100 age-sex matched, unrelated healthy subjects representing the control group were included in the study. The PCR-RFLP method was used for genotyping the 5-HTR2C variation. There was no statistically difference in terms of genotype distributions and allele frequencies between the control subjects and patients with psoriasis (P=0.360 and P=0.439, respectively). The comparison between the presence and absence of the 5-HTR2C gene rs6318 G allele within the determined clinical subsets resulted in a significant difference with regard to treatment methodology only when conventional therapy and one or more medical therapy was compared (P=0.021). This study is the first clinical study to investigate the association between 5-HTR2C polymorphism and psoriasis. The role of the 5-HTR2C gene should be examined with more parameters in a larger case series.

Clinical and Demographical Characteristics of Familial Behçet's Disease (Southeast Marmara Region).

BACKGROUND: Familial aggregation in Behçet's disease (BD) has been reported in Turkish and Japanese populations. While the frequency of familial cases has been reported to be 2-5% worldwide, this rate reaches up to 15% in the Middle East. OBJECTIVE: This study aimed to determine the incidence of familial BD cases followed in the BD polyclinic and to compare their clinical and demographic characteristics to those observed in sporadic cases. METHODS: Data related to BD patients who were followed between 1995 and 2014 were collected from computerized archive records and were assessed for detailed family histories. Only first-degree relatives (brother, sister, mother, father, children) were considered to be cases of familial BD. Clinical and demographic -features were retrieved. Our BD polyclinic is located in the Southeast Marmara Region in Turkey. RESULTS: BD was detected in 36 first-degree relatives of 33 patients out of 840 patients with BD. A total of 45 patients were diagnosed as familial BD;23 were female, and 22 were male. In our patients, the incidence of familial BD was determined to be 3.9%. The rates for HLA-B5 positivity, ocular involvement, genital ulcers, and erythema nodosum were determined to be 86.6% (26/30), 26.6%, 82.2%, and 60%, respectively. None of the patients had neurological involvement, but 2 had vascular involvement. CONCLUSION: This study may contribute to the epidemiological data of BD from Turkey.

A Report of 13 Cases of Merkel Cell Carcinoma: Single-Center Experience and Review of the Literature.

BACKGROUND: There is limited data knowledge of Merkel cell carcinoma (MCC) in Turkey aside from a few case reports. OBJECTIVE: The aim of this study was to describe the clinical characteristics, demographic features, therapeutic parameters, and outcome of primary cutaneous MCC cases from Turkey. METHODS: Digital medical records of the 13 MCC patients who were followed-up at a tertiary referral center were retrospectively analyzed. Clinic, demographic, tumor characteristics, and survival of the patients were retrieved. RESULTS: Most of our patients were elderly. Female predominance was noticed. The most common primary site of the tumors was the lower extremities. The overall survival was 42 months, 68% at first year, 68% at third years, and 29% at fifth years. CONCLUSION: This is the first largest report from Turkish population with female predominance, and lower extremity tendency.

Cyclosporine-A for severe childhood atopic dermatitis: clinical experience on efficacy and safety profile

Background/aim: Management of atopic dermatitis (AD) in children is still challenging. The aim of this study was to evaluate the efficacy and safety profile of cyclosporine-A (CsA) treatment in children with severe and recalcitrant AD. Materials and methods: Medical records of 43 children followed between January 2010 and December 2015 and treated with systemic CsA were evaluated retrospectively. Treatment efficacy was assessed according to the physician's global assessment (PGA) score. According to the treatment response, patients were grouped as nonresponder, moderate responder, or good responder. Effects of the variables on treatment response were evaluated by analysis of variance (ANOVA). The safety profile of CsA was assessed by clinical and laboratory findings at each visit. Results: The median initial dose of CsA was 3 mg/kg daily, ranging between 2.5 and 5 mg/kg daily. The mean duration of CsA therapy was 4.9 ± 4.24 months. Seventeen patients (39.5%) achieved good response in a treatment period of 3 to 14 months. After discontinuation of CsA, of the 17 patients, relapse was observed in 4 (23.5%). Moderate response was observed in 12 (27.9%) patients; however, 14 (32.6) patients did not respond to the treatment. Five patients reported mild side effects. Conclusion: Low-dose CsA seems to be an effective and safe treatment option for severe and recalcitrant AD in children.

Retrospective Analysis of 91 Kaposi's Sarcoma Cases: A Single-Center Experience and Review of the Literature.

BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving primarily the skin. OBJECTIVE: The aim of this study was to describe the clinical, demographic, histopathological characteristics, treatment modalities, and outcome of 91 KS patients, and compare them with other contemporary research. METHODS: Medical records of 91 KS patients followed between January 2005 and September 2017 were evaluated retrospectively. RESULTS: Most of our patients were male (male-to-female ratio was 4.05). The median age at diagnosis was 69 years (range, 6-93 years). The duration of the lesions varied between 3 and 25 years. The lower extremities were the most commonly involved area (51.6%). Of the 91 patients, classic type KS was seen in 75 patients. Radiotherapy was used successfully in approximately half of our patients. Recurrence was observed in approximately one third of the patients. All KS patients in this study except 1 were classic KS. CONCLUSION: The clinical and demographic characteristics of our patients were compatible with the previous literature suggesting that KS is a tumor that tends to be limited to the skin. Close follow-up of patients is important to monitor for recurrence. This is the largest report from Turkey to date.

The efficacy of narrowband UVB treatment in pediatric vitiligo: a retrospective analysis of 26 cases.

BACKGROUND/AIM: Narrowband UVB (Nb UVB) treatment is commonly used for the management of psoriasis and atopic dermatitis, and is less often used for vitiligo in children. The aim of this study was to evaluate the efficacy and short-term safety of Nb UVB phototherapy in children diagnosed with vitiligo retrospectively. MATERIALS AND METHODS: A total of 26 patients younger than 18 years with the diagnosis of vitiligo and managed with Nb UVB phototherapy as documented in archive records were evaluated. Clinical response was assessed according to repigmentation of the lesions: good response when there was more than 75% repigmentation, moderate response when there was 25%-74% repigmentation, poor response when repigmentation was less than 24%, and unresponsive when there was no pigmentation and new lesions occurred. RESULTS: A total of 26 patients received Nb UVB treatment; 14 were girls and 12 were boys. The age at onset of the disease varied between 2 and 18 years, with a mean age of onset of 10.07 ± 4.53 years. Repigmentation rate of >75% was detected in 45.4% of cases. CONCLUSION: Nb UVB phototherapy seems to be a well-tolerated effective and safe treatment option in children, especially those unresponsive to topical treatment and those with widespread lesions. However, long-term risks such as photocarcinogenesis and photoaging should kept in mind.

Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides.

We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3(+), CD4(+), CD8(+), TCRαß(+), TCRγδ(+), CD7(+), CD4(+)CD7(+), CD4(+)CD7(-), and CD71(+)), B cells (HLA-DR(+), CD19(+), and HLA-DR(+)CD19(+)), NKT cells (CD3(+)CD16(+)CD56(+)), and NK cells (CD3(-)CD16(+)CD56(+)). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression.

Efficacy of low-dose ultraviolet a-1 phototherapy for parapsoriasis/early-stage mycosis fungoides.

Mycosis fungoides (MF) and parapsoriasis (PP) are major dermatologic conditions for which phototherapy continues to be a successful and valuable treatment option. UVA-1 phototherapy is effective in the management of cutaneous T-cell mediated diseases. The aim of the study was to evaluate the efficacy and safety of low-dose UVA-1 phototherapy for the management of PP/early-stage MF. A total of 30 patients, diagnosed with MF (n:19) or PP (n:11) were enrolled to the study. All patients were managed with low-dose UVA-1 (20 or 30 J cm(-2)). Response was assessed clinically and immunohistochemically. UVA-1 treatment led to clinical and histological complete remission (CR) in 11 of 19 MF patients (57.9%), partial remission (PR) in three of 19 (15.8%), after a mean cumulative dose of 1665 (range, 860-3120) J cm(-2) and mean number of 73 exposure (range, 43-107) sessions. Five patients with PP (45.5%) showed CR, and PR was observed in six patients with PP (54.5%) after a mean cumulative dose of 1723 (range, 1060-3030) J cm(-2) and mean number of 74 exposure (range, 53-101) sessions. We conclude that low-dose UVA-1 therapy seems to be an effective, safe, and well-tolerated treatment option for patients with PP/early-stage MF.

Effects of Malassezia yeasts on serum Th1 and Th2 cytokines in patients with guttate psoriasis.

BACKGROUND: Systemic and focal infections caused by microorganisms have been known to induce or exacerbate psoriasis. Although the role of yeast species of the genus Malassezia in the pathogenesis of psoriasis is not fully understood, it is thought that these lipophilic yeasts may represent a triggering factor in the exacerbation of psoriatic lesions. OBJECTIVES: This study investigated the effects of Malassezia yeasts on serum Th1 and Th2 cytokines in patients with guttate psoriasis (GP) in order to define their role in the pathogenesis of psoriasis. METHODS: Fifty patients with GP and 29 clinically healthy individuals were included in the study. All samples consisted of scales and scrapings taken from the scalps, trunks, and upper limbs of both psoriasis patients and healthy subjects. Psoriasis patients and healthy subjects were grouped according to their positivity or negativity for Malassezia yeasts as ascertained by direct microscopy and/or culture. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of Th1 and Th2 cytokines in these groups. RESULTS: No significant differences in positivity for Malassezia yeasts were found between psoriatic skin and healthy skin in samples taken from different body sites. Serum interleukin-13 (IL-13) levels were significantly lower in the psoriasis group compared with the control group (P = 0.04). Levels of other cytokines did not differ significantly between the psoriasis and control groups. Mean levels of Th2 cytokines (IL-4, IL-10, IL-13), but not of Th1 cytokines (IL-2 and IFN-γ), were significantly lower in psoriasis patients positive for Malassezia yeasts compared with those negative for Malassezia yeasts and control subjects (P = 0.04, P < 0.001 and P = 0.01, respectively). CONCLUSIONS: The isolation of Malassezia yeasts from GP lesions does not necessarily mean that these species are pathogenic, but their downregulating effects on anti-inflammatory Th2 cytokines may contribute to the occurrence of GP.

Narrowband ultraviolet B (311 nm, TL01) phototherapy in chronic ordinary urticaria.

BACKGROUND: Chronic ordinary urticaria (COU) can severely reduce quality of life and be difficult to control. Ultraviolet (UV) A and UVB phototherapy has been reported to decrease the release of histamine from either mast cells and/or basophils. Previous small studies have suggested that UVB phototherapy is a good alternative treatment for COU. OBJECTIVES: The purpose of this study was to assess the efficacy of narrow-band UVB (NB-UVB) phototherapy for COU. MATERIALS AND METHODS: Twenty-two patients (three male, 19 female) received NB-UVB phototherapy. These patients had not responded to at least two H1 antihistamines, and most had been treated with a variety of antihistamine combinations. Clinical responses were assessed according to an outcome scoring scale. During both visits, patients were administered the following: the visual analogue scale (VAS) on present pruritus and/or whealing; chronic urticaria impact on patients' quality of life according to the interference with daily activities, quality of sleep, and flare-up rates. RESULTS: The median number of treatments was 31.4 (9-44), and the mean top dose was 9.46 J/cm(2) (1.1-16.4 J/cm(2)). NB-UVB treatment led to clearance in 10 patients (45%), marked improvement in five (22%), and moderate improvement in seven (31%) patients according to an outcome scoring scale. Mild side effects were observed in two patients. Six patients who cleared or observed marked improvement remained clear at follow-up for a period of six months to one year, and other patients had a few recurrent lesions that did not need retreatment. For VAS scores and total chronic urticaria impact on patients' quality of life scores, the differences between baseline and after treatment scores were significantly lower (P < 0.001, P < 0.001, respectively). CONCLUSION: Narrow-band UVB (NB-UVB) therapy is an effective, well-tolerated treatment option in second-line therapy for COU. This therapy can lead to subjective relief of pruritus and whealing and objective reduction of whealing. Further larger studies with longer follow-up periods are necessary to determine the proper clinical response and long-term complications of this therapy in COU.

Neurological and neurophysiological effects of oral isotretinoin: a prospective investigation using auditory and visual evoked potentials.

Over the last decade, accumulating evidence has indicated that retinoids may be capable of affecting the development, differentiation and function of nervous tissue. The purpose of the present study was to investigate whether oral isotretinoin can affect brainstem and cortical sensorial activities. We performed neurological and neurophysiological studies (brainstem auditory and visual evoked potentials) in 32 patients with various skin diseases receiving isotretinoin. A significant increase of the third (L(III)) and fifth peak latency (L(V)) in left and right ear (p = 0.03, p = 0.02 for L(III), p = 0.03, p = 0.04 for L(V) respectively), and a significant increase in the latency of wave one and interpeak latency (IPL) I-V in the left ear were found after isotretinoin administration, as compared to the pretreatment (p = 0.0036 and p = 0.02, respectively). No significant differences of other latencies, IPLs and the value of visual evoked potential P-100 implicit time were observed. However, a marked increase in latency P-100 wave was found in 6 patients after therapy. It seems reasonable to suggest that neurophysiological and neurological evaluation of audiological and ocular nerve (or retinal) function may be added to the list of investigations that are performed in patients treated with oral isotretinoin.

Narrowband UVB (311 nm, TL01) phototherapy for pityriasis lichenoides.

BACKGROUND/PURPOSE: Narrowband (NB) UVB (NB-UVB) phototherapy has recently demonstrated high levels of efficacy and tolerability in a variety of skin diseases. The purpose of the present study was to assess the efficacy of NB-UVB phototherapy in the management of pityriasis lichenoides (PL). METHODS: The therapeutic response in 31 PL patients (23 pityriasis lichenoides et varioliformis acuta; PLEVA, eight pityriasis lichenoides chronica; PLC) treated with NB-UVB phototherapy between 2000 and 2007 was assessed. RESULTS: NB-UVB treatment led to a complete response (CR) in 15 out of 23 PLEVA patients (65.2%) with a mean cumulative dose of 23 J/cm(2) after a mean number of 43.4 exposures and a partial response (PR) in eight patients (34.8%) with a cumulative dose of 15.6 J/cm(2) after a mean number of 32.3 exposures. NB-UVB treatment led to CR in seven out of eight PLC patients (87.5%) with a mean cumulative dose of 18.4 J/cm(2) after a mean number of 45.8 exposures and PR in one patient (12.5%) with a cumulative dose of 9.1 J/cm(2) after a mean number of 19 exposures. Relapses occurred in four PL patients within a mean time period of 6 months. CONCLUSION: NB-UVB therapy is an effective, safe and practical alternative treatment modality for the management of PLEVA and PLC.

Acitretin-induced subungual hemorrhage.

A 20-year-old woman with a 2-year history of histologically confirmed palmoplantar keratoderma due to psoriasis, resistant to several topical agents, was admitted to the Department of Dermatology, Uludag University, Bursa, Turkey. Therapy with oral acitretin (0.5 mg/kg/day, 35 mg/day) was initiated. A month after starting acitretin treatment, she noted slight reddening of the second left fingernail. Clinical examination revealed red-brown discoloration of the second fingernail associated with subungual hemorrhage involving the proximal nail bed (lunula region) (Fig. 1). The nail change was asymptomatic. The patient complained only of discoloration underneath the nail plate. No abnormalities were detected on the skin, mucous membranes, or toenails/other fingernails. The patient denied exposure to microtrauma or any other drugs. The erythrocyte sedimentation rate, full blood cell count, electrolytes, renal and hepatic tests, and serum lipids were normal. Coagulation tests, including blood clotting time, international normalized ratio, activated partial thromboplastin time, thrombin time, platelet number, and function tests, were within normal levels. Treatment with acitretin was discontinued, and the nail change resolved completely after 3 weeks. A similar episode of subungual hemorrhage recurred, however, within 48 h after re-challenge with a lower dose of acitretin (25 mg/day). The drug was definitively stopped and the eruption faded again within a week. An objective causality assessment suggests that subungual hemorrhage was probably related to acitretin in this patient.

Urticaria and angio-oedema due to ziprasidone.

Antipsychotic medications are commonLy associated with adverse cutaneous reactions (ACRs) in approximately 5% of patients. Angio-oedema accompanying urticaria is one of the most serious ACRs. The 36-year-old female patient who was diagnosed with ;Paranoid schizophrenia' 6 years ago, was commenced on ziprasidone 120 mg/day. On day 30 of the treatment, the patient presented urticarial papules and plaques all over the body and angio-oedema in the face. The patient was diagnosed as ;Urticaria + Angio-oedema'. The development of ACRs after the initation of ziprasidone monotherapy, disappearance of lesions after the discontinuation of this antipsychotic, and positive intradermal skin test all suggests a possible causal relationship between ACRs and ziprasidone. To our knowledge, this is the first reported case of urticaria and angio-oedema due to ziprasidone monotherapy. Ziprasidone is a valid and effective choice amongst antipsychotic medications, but this case calls for caution regarding ACRs at the time of prescribing.