Increased rates of contact allergy to selected preservatives in patients with allergic contact dermatitis in Turkey.

BACKGROUND: Preservatives are a frequent cause of allergic contact dermatitis (ACD) and have caused numerous epidemics. OBJECTIVES: The objective of this study is to determine the prevalence of preservative sensitivity, assess the change in the frequency of sensitivity, identify new preservatives with increased sensitivity rates, and evaluate the situation in Turkey by comparing our findings with current literature. METHODS: A total of 201 patients diagnosed with ACD between 2018 and 2020, were patch tested with the European baseline series and additional seven preservative haptens. The change in the prevalence of sensitivity to each preservative hapten was investigated by comparing the data from the study conducted in our department between 2000 and 2004. RESULTS: Results showed that 17.4% (n = 35) of the patients were positive to preservatives. Comparison with previous data from 2000 to 2004 revealed an increase in the frequency of sensitization. The most prevalent allergen was methyldibromo glutaronitrile (9.5%), followed by methylchloroisothiazolinone/methylisothiazolinone (6.5%), and methylisothiazolinone (5%). CONCLUSION: The increase in preservative sensitivity in Turkey is the most remarkable finding. Although MDBGN was prohibited in cosmetic products, MCI/MI and MI are still widely used. Our findings suggest that awareness of preservative sensitivity should be increased and additional precautions should be taken, also in Turkey, regarding the use of preservatives.

EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

A Comparison of Adult and Juvenile Behcet Patients and a Look at Clinical Trends: Retrospective Data from a Turkish Follow-Up Cohort Study.

BACKGROUND: Previous reports indicate that juvenile Behçet's disease (BD) may have a different course than adult BD. However, as a direct comparison with adult Behçet patients has only been made in a limited number of studies, the issue is still controversial. OBJECTIVES: The primary aim of our study was to compare clinical manifestations in a large cohort of juvenile and adult Behçet patients registered in a single centre. The secondary aim of our study was to compare the data of newly diagnosed patients registered between 1998 and 2020 with the data of those registered between 1976 and 1997. METHODS: Data were collected retrospectively from medical records of patients registered between 1998 and 2020. Juvenile BD was defined as fulfilment of International Criteria for Behçet's Disease at or before 16 years of age. RESULTS: A similar course of disease was noted in juvenile and adult Behçet patients with no significant difference in the frequency of mucocutaneous findings, major organ involvement, and positivity of the pathergy test. A comparison of the periods, 1976-1997 and 1998-2020, revealed no significant difference in the prevalence of mucocutaneous lesions and major organ involvement. CONCLUSIONS: Our results indicate that juvenile and adult Behçet patients have a similar course with a similar frequency of clinical manifestations. Contrary to reports suggesting an overall tendency to milder disease over time, no decrease in the risk of major organ involvements was observed. A significant trend towards a decline in pathergy test positivity was noted.

Patch test results of the European baseline series among 1309 patients in Turkey between 2013 and 2019.

BACKGROUND: Prevalences of sensitivity to contact allergens change over time as a result of variations in allergen exposure. OBJECTIVES: The aim of the study was to describe trends in sensitisation to allergens of the European baseline series in Turkey between 2013 and 2019. METHODS: The patch test results of 1309 patients with suspected allergic contact dermatitis (ACD) were analysed retrospectively, and the prevalence of contact allergies to European baseline series allergens was compared with previous data (for 1998-2005). RESULTS: A total of 534 (40.8%) patients exhibited one or more positive patch test reaction. The five most frequent allergens were nickel sulfate (19.6%), potassium dichromate (6.5%), cobalt chloride (6%), Myroxylon pereirae resin (5%), and p-phenylenediamine (PPD; 3.7%). Statistically significant increases in the prevalence of sensitisation to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; P < .001), Myroxylon pereirae resin (P < .001), PPD (P = .008), and fragrance mix I (P = .036) were observed in the 2013 to 2019 period compared with the 1998 to 2005 period. Conversely, positive reactions to neomycin sulfate (P = .029), clioquinol (P = .031), and primin (P = .001) decreased significantly. CONCLUSION: This study provides a comprehensive profile of ACD in Turkey. The remarkable increase in the MI and MCI/MI contact allergy observed underlines the urgent need for regulatory measures to reduce exposure to MI and MCI/MI in Turkey.

Hidradenitis suppurativa: Clinical characteristics and determinants of treatment efficacy.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that causes a significant decline in quality of life. There are numerous treatment options; however, real-life data on the efficacy of these treatments is limited. This study was performed in two centers to describe clinical characteristics and assess treatment outcome in a cohort of 139 patients with HS. Data on demographic and clinical characteristics, Hurley stage and comorbidities were collected from patient charts and evaluated retrospectively. Treatment response was measured with HS clinical response index (HISCR). Mean body mass index was 27.8±4.88. Inflammatory comorbidities were present in 23%. Among first-line drugs systemic doxycycline resulted in 60% HISCR followed by rifampicin-clindamycin combination (46.4%). Isotretinoin had the lowest HISCR (30.7%) in this group. For second-line therapies, all acitretin treated patients achieved response and patients treated with tumor necrosis factor alpha (TNF-α) inhibitors had the highest HISCR. Currently recommended first-line therapies have moderate efficacy in HS. Acitretin appears to be a reasonable alternative for the highly effective TNF-α inhibitors in patients with severe and resistant HS. Overall, these results support that excessive inflammatory response play an important role in pathogenesis of HS.

The Contact Sensitivity of Turkish Children and Adolescents to European Baseline Series Allergens between 2013 and 2023.

INTRODUCTION: Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically relevant allergens. OBJECTIVE: The aim of this study was to identify the most frequently observed allergens among Turkish children and adolescents patch-tested in 2013-2023. METHODS: The patch test results of 160 patients (age ≤18) were analyzed retrospectively. The frequency of contact allergens and distribution of positive results in terms of sex, age group (children and adolescents), and the presence of atopic dermatitis (AD) were identified. RESULTS: Forty-nine patients (30.6%) (34 girls and 15 boys) exhibited positive patch test reactions to a minimum of one allergen, and contact sensitivity was statistically significantly higher in girls (P=0.034). The five most frequent allergens were nickel sulfate (10.6%), MCI/MI (8.1%), cobalt chloride (5.6%), p-phenylenediamine (PPD) (5%), and MI (3.5%). No significant association was observed between patch test positivity and age groups (P>.05). Nickel sulfate sensitivity was significantly higher in girls than in boys (P=.043). A positive reaction was detected in 31.3% of patients with AD and in 33.7% of those without (P>.05), and a statistically significant relationship was observed between contact sensitivity to fragrance allergens and AD (P=.046). CONCLUSION: Metals and preservatives represent the most frequent allergens in Turkish children and adolescents. Metal sensitivity is expected to decrease as legislation is enforced. Regulatory measures are now required to reduce MI and MCI/MI contact allergy in Turkey.

Diagnosis of immediate hypersensitivity to ß-lactam antibiotics can be made safely with current approaches.

BACKGROUND: Diagnosing immediate hypersensitivity to ß-lactam antibiotics is still a significant problem. Recently, a new penicillin testing reagent was introduced to the market. In this study, the recommendations of the European Network of Drug Allergy (ENDA) for the diagnosis of immediate reactions to ß-lactams were followed, and the negative predictive value of this approach with currently available reagents was assessed. METHODS: Eighty patients (age range: 6-74 years) with a history of immediate reactions to ß-lactams were included. All cases underwent skin testing with benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM), followed by the culprit drug if necessary. If this step was negative, a drug provocation test was offered. If this step also yielded a negative result, then the patients were recommended to use ß-lactam antibiotics in future whenever their use was indicated. RESULTS: Overall, 29 patients (36.2%) were diagnosed as ß-lactam allergic. The majority of the cases (72.4%) were diagnosed by positive skin tests to either PPL or MDM, whereas 10.3% were diagnosed by skin testing with culprit drugs and 17.2% with drug provocation tests. Regarding the use of the tested drug in the long term, almost half of the contacted patients had had an indication to use the tested drug and the majority had taken the whole course without problems. CONCLUSIONS: Although currently available new penicillin tests provide sufficient allergy data, all the steps recommended by ENDA should be followed in the diagnosis of immediate reactions to ß-lactams. If these steps are negative, the patients usually tolerate ß-lactams and only a few develop mild, non-life-threatening reactions in the long term.

Prognostic factors for relapse and poor outcome in neuro-Behçet's syndrome: results from a clinical long-term follow-up of a single centre.

OBJECTIVE: To describe the clinical characteristics of neuro-Behçet's syndrome (NBS) and to define the factors associated with relapses and poor outcome. METHODS: Among 2118 patients with Behçet's syndrome who fulfilled the international study group criteria, 208 (9.8%) patients had NBS. Retrospective data of 125 NBS patients (55.5% male; mean age 37.2 ± 11.8 years) were analysed. We divided patients into two subgroups, either parenchymal (p-NBS) or non-parenchymal (np-NBS), according to international consensus recommendations for NBS. We assessed the predictor factors associated with relapse and poor outcome-which was defined as a modified Rankin score (mRS) ≥ 3 at last follow-up and/or death-using Cox and logistic regression analyses, respectively. RESULTS: In total, 79 (63.2%) patients presented with p-NBS and 46 (36.8%) presented with np-NBS. Ocular involvement was more common in p-NBS than np-NBS (55.7% vs. 37.0%, p = 0.04), whereas vascular involvement excluding cerebral vein thrombosis was more frequent in patients with np-NBS (19.0% vs. 52.2%, p < 0.001). Forty-two patients (33.6%) experienced at least one relapse. Factors associated with relapse were BS diagnosis at a younger age and cranial nerve dysfunction (HR 0.96 95% CI 0.93-0.99 and 2.36 95% CI 1.23-4.52, respectively). After a median of 68 (Q1-Q3: 25-125) months, 23 patients (18.4%) had a poor outcome. Indicators of a poor outcome were higher initial mRS and the progressive p-NBS type (OR 8.28 95% CI 1.04-66.20 and 33.57 95% CI 5.99-188.21, respectively). CONCLUSION: Our findings indicate that clinical characteristics and prognosis differ between NBS subgroups, of which patients with p-NBS have worse outcomes.

Systematized Epidermal Nevus Syndrome Involving the Upper and Lower Eyelids Bilaterally

A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.

Diagnostic Sensitivity of Different Applications of Pathergy Test for Behçet's Disease.

OBJECTIVES: This study aims to compare the sensitivity of the intradermal application of the pathergy test with the "three-step pathergy test". PATIENTS AND METHODS: The study included 60 patients with Behçet's disease (BD) (23 males, 37 females; mean age 33.9±9.7 years; range, 11 to 57 years) and 100 patients with recurrent aphthous stomatitis as the control group (39 males, 61 females; mean age 32.4±12.1 years; range, 11 to 66 years). Simultaneous intradermal pathergy test and three-step pathergy test were applied to each patient. RESULTS: Twenty-six patients (43.3%) with BD had positive three-step pathergy test and 18 (30%) of them had positive intradermal pathergy test. A statistically significant relationship was found between the three-step pathergy test positivity and male sex while no relationship was detected between the disease activity and the positivity of the pathergy test. In the three-step pathergy test, pathergy positivity with intramuscular method was statistically significantly higher than with intravenous method. CONCLUSION: The three-step pathergy test in patients with BD was found to have higher sensitivity compared with the intradermal pathergy test. The intramuscularly applied pathergy test was the main cause of increase in sensitivity. Further studies are needed to develop new applications of pathergy test that would increase the sensitivity and which are also easy to apply.

Promising effect of intravenous immunoglobulin therapy for epidermolysis bullosa pruriginosa.

BACKGROUND: Epidermolysis bullosa pruriginosa (EBP) is rare a clinical variant of dystrophic epidermolysis bullosa characterized by trauma-induced bullae formation, milia and nail dystrophy accompanied by severe pruritus. Treatment pruritus of EBP focuses on immunosuppressive treatment with limited efficacy. Treatment strategies are not well-established. AIM: To provide the genetic characterization of a multi-generational EBP family and discuss the efficacy of intravenous immunoglobulin treatment in EBP. MATERIALS & METHODS: The clinical characteristics of patients diagnosed with EBP in three consecutive generations were determined. The mutation is analyzed in the index patient's genomic DNA by Sanger sequencing, and this mutation was confirmed in other affected members of the family. Index case with severe phenotype was treated with intravenous immunoglobulin (IVIG). RESULTS: A heterozygous single nucleotide transition, c.6127G>A, in exon 73 of COL7A1 was identified in all affected members. Physical examination of patients revealed lichenoid papules on extensor surfaces of extremities, excoriations, milia formation and nail dystrophy. Majority of patients had elevated serum IgE levels (%86 (6/7)) without a medical history for atopy. Female patients had generalized involvement and severe phenotype. The skin lesions of the index case were refractory to high dose systemic steroids and cyclosporine treatment. Lesions improved significantly with intravenous immunoglobulin therapy. CONCLUSION: In severe cases, unresponsive to other therapies, IVIG may be a preferable therapeutic approach to modulate the inflammatory response in patients with EBP.

Moderation analysis exploring associations between age and mucocutaneous activity in Behçet's syndrome: A multicenter study from Turkey.

The aim of the present study was to examine the effects of age on mucocutaneous activity by using moderation analysis in Behçet's syndrome (BS). In this cross-sectional study, 887 BS patients (female : male, 481:406; mean age, 38.4 ± 10.9 years) followed in 13 tertiary centers in Turkey were included. Mucocutaneous activity was evaluated by using the Mucocutaneous Index (MI) according to sex and disease course. Moderation analysis was performed to test the effect of age on mucocutaneous activity. A moderator variable is a third variable and affects the relationship between independent and outcome variables. Age was chosen as a potential moderator variable (interaction effect), MI score as the outcome variable and sex as an independent variable in the analysis. The moderation analysis tested the effects of age in three steps: whole BS patient group, patients without systemic involvement and those with systemic involvement. The moderation model was only significant in BS patients with systemic involvement (P = 0.0351), and a significant relationship was observed between female sex and MI score (P = 0.0156). In addition, the interaction plot showed that female patients had increased MI scores compared with male patients, especially in the 28-year-old age group (P = 0.0067). Moreover, major organ involvement was newly diagnosed in the majority of these young female BS patients. Our results suggest that the relationship between sex and mucocutaneous activity was moderated by age in the systemic involvement group. Also, increased mucocutaneous activity may be associated with new major organ involvement in young female BS patients with systemic involvement.

Effect of Patch Testing on the Course of Allergic Contact Dermatitis and Prognostic Factors That Influence Outcomes.

BACKGROUND: Allergic contact dermatitis (ACD) has been shown to adversely affect the quality of life of patients. OBJECTIVE: The aim of the study was to study the effect of patch test on the severity of dermatitis, the quality of life of patients, and the prognostic factors influencing the outcome. METHODS: The study included 111 patients patch tested with the preliminary diagnosis of ACD. Patients with clinically relevant positive patch test reactions were included in the ACD group. All patients were assessed with the Investigator Global Assessment and the Dermatology Quality of Life Index before and 6 months after patch testing. RESULTS: At the sixth-month control, more significant regressions in the mean Investigator Global Assessment and Dermatology Quality of Life Index scores were noted in the ACD group. The allergens were correctly remembered by 75% of the patients. The improvement was more significant in patients with ACD who correctly remembered the allergens and made appropriate lifestyle changes. Multiple allergen positivity was identified as a poor prognostic factor. CONCLUSIONS: The effect of patch test on the prognosis of contact dermatitis depends not only on providing necessary information to patients but also on the number of positive reactions, patient's ability to recall the allergens, how much the avoidance was achieved, and patient-related factors such as sex.

Congenital pilar leiomyoma.

Piloleiomyomas are benign smooth muscle tumors arising from the arrectores pilorum muscles in the skin. They usually occur as multiple firm dermal nodules located on the extremities and trunk. Solitary lesions are rare. Leiomyomas usually develop during adolescence or early adult life. Congenital pilar leiomiyoma is an extremely rare entity. We present a case of congenital solitary pilar leiomyoma located on the face.

Long-term results of rituximab-intravenous immunoglobulin combination therapy in patients with epidermolysis bullosa acquisita resistant to conventional therapy.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare subepidermal bullous disease. Long-term remission in this disease is difficult using current treatments, unlike that in patients with other autoimmune bullous diseases. OBJECTIVE: We retrospectively evaluated the effectiveness and side effects of rituximab-intravenous immunoglobulin (IVIg) combination treatment in five patients with EBA resistant to conventional treatment. PATIENTS AND METHODS: Rituximab (375 mg/m2) was administered for four consecutive weeks to four patients, and their treatment continued with IVIg at a dose of 2 g/kg/month. One patient received two cycles of rituximab for three consecutive weeks, IVIg in the fourth week, followed by monthly IVIg administrations as in the other patients. RESULTS: The total number of IVIg therapy cycles ranged from 10 to 26 (mean 19.4). Mean skin involvement, mucosal involvement, and disease severity scores decreased after a mean follow-up of 22.6 months (range, 10-28 months). In an analysis performed during months 24-28, the number of CD19-positive B cells was found to be below the normal reference range in four patients. LIMITATIONS: This was a retrospective study with a limited number of patients. CONCLUSION: Rituximab-IVIg combination treatment seems to be effective and safe for treating patients with EBA resistant to conventional treatments.

Development of poorly differentiated invasive squamous cell carcinoma in giant Bowen's disease: a case report with dermatoscopy.

Bowen's disease (BD) is an in situ form of squamous cell carcinoma (SCC), often occurring in the chronically UV-damaged skin of elderly people. The risk of progression of BD to invasive SCC varies between 3% and 5%, and one-third of invasive tumors may metastasize. Herein we discuss the dermatoscopic findings of a case of giant Bowen's disease, which progressed to poorly differentiated invasive SCC.

Factor V Leiden mutation and PAI-1 gene 4G/5G genotype in thrombotic patients with Behcet's disease.

Behcet's disease is a chronic systemic vasculitis with particular systemic features including thrombotic events. The present study was designed to analyse the role of the factor V Leiden and the prothrombin G20210A mutations and plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk of patients with Behcet's disease. A total of 50 unrelated patients with Behcet's disease (34 male, 16 female) were the subjects of the study. Twenty-seven of 50 patients with a history of thrombosis comprised group 1, and 23 patients with no thrombosis comprised group 2. In group 1, nine of the 27 patients (33%) were found to have the factor V Leiden mutation (7.1% in healthy population), and the 4G/4G genotype was found in 23% of the patients (26% in control). No patient had the prothrombin G20210A mutation (2.2% in healthy control). In group 2, two patients (9%) had the factor V Leiden and one patient (4%) had the prothrombin G20210A mutations. The 4G/4G polymorphism was found in 30.5% of the patients. The differences in the frequencies of factor V Leiden mutation between group 1 and group 2 (odds ratio, 5.3; 95% confidence interval, 1.0-27.5) and between group 1 and the healthy population were statistically significant ( 0.05). No statistically significant association was found for the prothrombin G20210A mutation and the 4G/5G genotype between the two groups or between each group and the healthy population, indicating that the prothrombin G20210A mutation and the 4G/4G polymorphism do not play a role in the development of thrombosis in Behcet's disease. These data suggested that the factor V Leiden mutation might be a risk factor for the development of thrombosis in Behcet's disease patients.