S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Retrospective analysis of methylprednisolone treatment alone and in combination with methotrexate in patients with extensive alopecia areata.

Alopecia areata (AA) is a chronic autoimmune disorder that primarily affects the hair follicle. Systemic corticosteroids and methotrexate (MTX) are among the therapeutic options in severe cases. This study aimed to show whether the combination therapy of methylprednisolone (MP) and MTX was superior to MP alone in the management of extensive AA. A total of 26 patients with extensive AA, 14 treated with MP alone and 12 treated with the combination of MP and MTX, were retrospectively evaluated in terms of gender, age, severity of disease, clinical characteristics, disease duration, dose and duration of medications, therapy response, and side effects. Of the 26 patients with extensive AA, 14 were male and 12 were female, and the average age was 17.02 ± 10.70 years. All patients had more than 50% hair loss, 23 had extensive multifocal AA, and three had alopecia totalis. A total of 14 patients were treated with MP alone (starting dose: 0.3-0.5 mg/kg, maximum 32 mg/day), and 12 were treated with MP + MTX (starting dose: 5-15 mg/week, maximum 20 mg/week). A total of 12 of the 14 patients (85.7%) who were treated with MP alone showed a complete response, with the response rate of the patients who showed more than 50% response being 92.85%. Seven of the 12 patients (58.3%) who were treated with MP + MTX achieved complete healing, and all patients on this regimen had more than 50% treatment response. Our results showed that the combination therapy of MP and MTX was not superior to MP alone in the management of extensive alopecia areata.

A multicentre prospective analysis of the incidence of pemphigoid diseases in Turkey.

BACKGROUND: The differentiation between the pemphigoid diseases is essential for treatment and prognosis. In Turkey, data on the incidence of these diseases are insufficient. Our aim in this study is to determine the incidence, demographics and clinical characteristics associated with diseases of the pemphigoid group. METHODS: We prospectively analysed 295 patients with pemphigoid who visited dermatology clinics of tertiary referral hospitals in 12 different regions of Turkey within a year. The diagnosis was based on clinical, histopathological, direct immunofluorescence (DIF) and serological (multivariant enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence and mosaic-based BIOCHIP) examinations. Clinical and demographic findings, aetiological factors and concomitant diseases observed in the patients were recorded. RESULTS: A total of 295 (female/male ratio: 1.7/1) patients with pemphigoid were diagnosed in 1-year period. The overall incidence rate of pemphigoid diseases was found to be 3.55 cases per million-years. The ratio of pemphigoid group diseases to pemphigus group diseases was 1.6. The most common pemphigoid type was bullous pemphigoid (BP, 93.2%). The others were epidermolysis bullosa acquisita (3.1%), pemphigoid gestationis (2.4%), linear IgA disease (1%) and mucous membrane pemphigoid (0.3%). The most common (26.8%) possible trigger of the bullous pemphigoid was gliptin derivative drugs. The most common concomitant diseases with pemphigoid were cardiovascular (27.8%) and neurological diseases (23.7%). CONCLUSIONS: This study showed that the increased frequency of bullous pemphigoid reversed the pemphigoid/pemphigus ratio in Turkey. Further studies are warranted regarding the reasons for this increase.

Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Drug survival of biologic treatments in Turkish patients with psoriasis.

Psoriasis is a chronic, immune-mediated disease deriving from a polygenic predisposition. Treatment paradigm of the moderate to severe psoriasis has changed in the last two decades as biologics have been developed. Real-world data concerning biologics in the treatment vary from country to country. We aimed to investigate the efficacy and drug survival of biologic agents in patients treated in our clinic in Turkey. Data for 211 biologic protocols were examined for 125 patients treated with a biologic at least once for a minimum duration of 16 weeks at our department. The drug survival rate for 3 years was highest among ustekinumab (UST) users. The primary failure rate in the present study was higher among tumor necrosis factor-alpha inhibitors compared to UST (P < .0001). The higher primary failure rate was found in etanercept users and the highest secondary failure rate was observed in infliximab, while the lowest primary and secondary failure rates were determined in UST users. UST use and articular involvement emerged as significant positive predictors of drug survival in naïve patients. Our study is the first study presenting real-life data and biologic survival in the treatment of psoriasis in Turkey, and UST exhibited significantly higher drug survival scores, particularly in naive patients.

Sun-protective behaviours of Turkish young adults.

BACKGROUND: The prevalence of skin cancers, including melanoma, has increased significantly in the past five decades. The main environmental factor implicated in their development is excessive sun exposure. Data on sun-protective behaviours in the Turkish population are very limited. OBJECTIVES: We aim to assess sun protection behaviours and the prevalence of exposure through broad participation among a young adult population in a national university in Turkey. METHODS: A multiple-choice questionnaire including 27 questions to evaluate sun protection behaviours was sent to e-mail addresses of all undergraduates. From 40 000 undergraduates, 17 769 of them were included in the study, with a response rate of 44.4%. RESULTS: Sunscreen usage was the most preferred sun protection method, used by 64% of the study population, followed by the use of sunglasses (60%), tending to remain in the shade (49%), the use of a hat (34%) and wearing long-sleeved clothing (23%). Forty-four percentage of the students used at least two methods, whereas 7% did not use any sun protection method. The prevalence rates of the use of sunscreen, sunglasses, wearing long-sleeved clothing and preferring to remain in the shade in the summer were all significantly higher among women. In addition, the prevalence rates of the use of sunscreen and preferring to remain in the shade were higher among students in the faculty of medicine. CONCLUSION: We found that when compared to the countries with the highest incidences of skin cancer, such as Australia and the United States, young adults in Turkey are protecting themselves more from the sun. This rate was even higher among women and faculty of medicine undergrads.

The prevalence of sacroiliitis in patients with acne vulgaris using isotretinoin.

BACKGROUND/OBJECTIVE: Acne vulgaris is a chronic inflammatory disease affecting the pilosebaceous unit in the skin. Isotretinoin is a synthetic vitamin A derivative regarded as the most effective agent in the treatment of acne. There have recently been increasing reports of adverse effects of isotretinoin on the skeletal system. Our aim in this study was to evaluate the rheumatic side-effects triggered by this drug, and particularly the prevalence of sacroiliitis. MATERIALS AND METHODS: A total of 73 patients receiving isotretinoin due to moderate or severe acne vulgaris were included. All patients were questioned about inflammatory low back pain and musculoskeletal pains during the treatment process. Inflammatory low back pain was evaluated using Assessment of Spondyloarthritis International Society (ASAS) criteria. Patients meeting ASAS criteria were evaluated with radiography and when necessary with sacroiliac magnetic resonance. RESULTS: The dose range for isotretinoin was between 0.4 and 0.8 mg/kg/day (mean 0.53 mg/kg/day). Treatment lasted for 6-8 months (mean 6.8 months). Lethargy was determined in 37 (50.7%) patients, myalgia in 31 (42.5%) and low back pain in 36 (49.3%). Mechanical low back pain symptoms were present in 20 of the patients describing low back pain and inflammatory low back pain in 16. Acute sacroiliitis was determined in six patients (8.2%) following a sacroiliac magnetic resonance imaging (MRI). Five (83.3%) of the patients with sacroiliitis were female and one (16.7%) was male. No statistically significant difference was determined between male and female patients in terms of prevalence of sacroiliitis (p = 0.392). CONCLUSION: The incidence of sacroiliitis in patients using isotretinoin is quite high. Patients using isotretinoin must be questioned about sacroiliitis findings and must be subjected to advanced assessment when necessary. Further studies regarding the development of sacroiliitis under isotretinoin therapy are now needed.

Assessment of demodex presence in acne-like rash associated with cetuximab.

CONTEXT: Cetuximab is an epidermal growth factor receptor inhibitor. It is frequently used in the treatment of solid tumors. However, it has a high potential to cause acne-like rash. Demodex mites, which are known to increase in number in immunosuppressive circumstances, are closely related to the acneiform lesions. OBJECTIVE: The aim of this study is to evaluate the presence of demodex mites in acne-like rash that appears under the treatment of Cetuximab. METHODS: We reviewed the medical records of patients who applied to our clinic with cetuximab induced papulopustular rashes between November 2014 and March 2016. Demodex sampling was performed by standardized skin surface biopsy (SSSB) in a total of 11 patients (eight males and three females). Infestation was defined as at least 5 living parasites/cm2 of skin. RESULTS: Upon the SSSB examination in 10 out of the 11 patients, no demodex mites were detected. Demodex mites were found in only one of the patients. This patient, in whom two dead Demodex folliculorums were found through facial sampling, was also regarded as negative since his demodex density was under the threshold limit value. CONCLUSION: In this study, it has been concluded that acne-like rash that develops under the treatment of cetuximab is not related to the presence of demodex mites. Papulopustular eruptions that develop under cetuximab treatment should not be directly correlated with the presence of demodex; first SSSB and demodex presence should be evaluated.

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆.

BACKGROUND: Pyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. OBJECTIVE: We aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. METHODS: We performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. RESULTS: We included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ±â€¯17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. STUDY LIMITATIONS: Retrospective nature of the present study. CONCLUSIONS: Analyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

Evaluation of the Quality of Life and the Demographic and Clinical Characteristics of Patients With Pemphigus With Oral Mucosal Involvement: A Multicenter Observational Study.

INTRODUCTION: Pemphigus vulgaris (PV) is an autoimmune disease primarily affecting the oral mucosa. OBJECTIVES: This study aimed to determine the demographic, clinical and treatment characteristics of PV patients with oral mucosal involvement and to assess the impact on their quality of life. METHODS: We conducted a prospective observational study among 106 patients diagnosed with PV and presenting oral mucosal involvement. Demographic data, clinical and treatment characteristics, and quality of life questionnaires were recorded. RESULTS: The study included 106 patients, 55 (51.89%) were male and there was a predominance of the mucocutaneous subtype in 83 individuals (78.38%). Oral mucosa was the initial site of manifestation in 44 patients (41.51%). Bilateral buccal mucosa was the most frequently affected site. The predominant symptom reported was a burning sensation, noted in 91 patients (85.85%). Oral mucosal examination revealed erosions in 85.85% of the patients. Systemic steroids were the most commonly administered treatment, and rituximab was used in 18 patients (16.98%). A positive and significant correlation was found between pemphigus severity and Oral Health Impact Profile-14, Dermatology Life Quality Index and Dermatological Quality of Life Scale scores (P < 0.05). The presence of superficial ulcers, flaccid bullae, lesion diameter ≥1 cm, and >10 lesions were factors that markedly diminished quality of life. Complete response to treatment was noted in all patients administered rituximab. CONCLUSIONS: The most common area of involvement was bilateral buccal mucosa, and the severity of PV closely correlated with a decline in quality of life measures. These results highlight the need for careful clinical oversight of PV, taking into account its effects on patients quality of life.

Spitz nevus arising upon a congenital glomuvenous malformation.

There are several reports of the collision of vascular and pigmentary anomalies (e.g., phakomatosis pigmentovascularis) and the association between congenital melanocytic nevi and infantile hemangiomas. We report a case of Spitz nevus arising in skin overlying a congenital plaque-like glomuvenous malformation (GVM). This is the first report of a Spitz nevus arising in direct contiguity to a GVM.

Isotretinoin-induced inflammatory back pain and sacroiliitis in patients with moderate-to-severe acne vulgaris.

INTRODUCTION: Isotretinoin has been reported to induce inflammatory back pain (IBP) and sacroiliitis in the patients with acne vulgaris. The aim of this study is to investigate the incidence of IBP and sacroiliitis in patients receiving isotretinoin treatment compared with oral antibiotics for acne vulgaris. MATERIALS AND METHODS: A total of 201 patients with moderate-to-severe acne vulgaris who received isotretinoin (n = 100) or oral antibiotics (n = 101) were included in the study. All patients were monthly questioned for IBP symptoms during their treatment. Patients described IBP were also evaluated for sacroiliitis by c-reactive protein, sedimentation rate, HLAB27, and sacroiliac magnetic resonance imaging (MRI). Isotretinoin was discontinued in all patients diagnosed as sacroiliitis, and these patients were reevaluated after 3 months. RESULTS: IBP was observed in 21 (10.4%), and sacroiliitis was detected in 11 (11%) patients on isotretinoin treatment; in oral antibiotic group, we did not observe IBP or sacroiliitis. The incidence of IBP and sacroiliitis differed significantly between the isotretinoin and oral antibiotic groups (p < 0.0001, p = 0.02). Complete regression was observed in the great majority of patients following cessation of isotretinoin. CONCLUSIONS: Our study is the largest prospective controlled study that investigated the incidence of sacroiliitis in patients receiving isotretinoin and compared with patients using oral antibiotics.

Frequency of skin cancer and evaluation of risk factors: A hospital-based study from Turkey.

OBJECTIVES: Skin cancers are the most common type of cancer with a significantly increasing incidence. The purpose of the study was to uncover the one-year frequency of melanoma and non-melanoma skin cancers (NMSC) and to determine the risk factors in the development of skin cancer. METHODS: The study included 7396 people from all age groups admitted to the dermatology clinic between October 2020 and 2021. The sociodemographic characteristics, sun protection habits, chronic diseases, and drug and vitamin use were evaluated. Lesions with clinical suspicion of skin cancer were excised. RESULTS: The frequency of skin cancer was found to be 2.7%, basal cell cancer (BCC) 1.2%, squamous cell cancer (SCC) 1.1%, malignant melanoma (MM) was 0.4%. Daily black tea consumption was found to be a risk factor for three type of skin cancer, BCC (p = 0.021), SCC (p = 0.006), and MM (p = 0.002), respectively. Obesity was observed as a risk factor for BCC (p = 0.005) and MM (p = 0.008). We found that having a history of alcohol use were an independent risk factor for all skin cancer types and BMI <30 for SCC. Vitamin D and supplemental drugs intake were observed as protective factors for BCC (p = 0.035, p = 0.007, respectively). Daily coffee consumption was determined as a protective factor for SCC (p < 0.001) and MM (p = 0.049). CONCLUSION: This study estimates the frequency of NMSC and melanoma. Also provides evidence to determine the risk factors and probably protective factors for the development of skin cancers.

Incidence and Prognosis of COVID-19 in Patients with Psoriasis: A Multicenter Prospective Study from the Eastern Black Sea Region of Turkey.

COVID-19 infection can have a poor prognosis, especially in patients with chronic diseases and those receiving immunosuppressive or immunomodulating therapies. This study aimed to investigate the severity of COVID-19 infection in patients with psoriasis and compare the infection severity for systemic treatments and comorbidities. We conducted a study in the dermatology clinics of five different centers in the Eastern Black Sea region of Turkey. Four hundred and eighty-eight patients were included, and 22.5% were confirmed as having COVID-19 infection. In our study, the frequency of hospitalization rates due to COVID-19 infection were similar (15.4%, 25.9% respectively) in patients receiving biological treatment and receiving non-biological systemic treatment (P=0.344). Hospitalization rates were higher in patients with hypertension, androgenetic alopecia, and acitretin use (P=0.043, P=0.028, P=0.040). In conclusion, current biologic treatments and non-biologic systemic treatments in patients with psoriasis did not appear to increase the risk of the severe form of COVID-19, except for acitretin.

Environmental risk factors in pediatric psoriasis: a multicenter case-control study.

To analyze the effect of possible risk factors, including breastfeeding, on the development of childhood-onset psoriasis, a multicenter case-control study with prospective collection of data was performed. Using a standard questionnaire, personal and specific variables including family history of psoriasis, maternal and environmental tobacco smoke exposure, body mass index (BMI), exclusive and partial breastfeeding for at least 3 and 12 months, cow's milk intake before 1 year, birth delivery method, and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18. Overall, patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls. The odds ratios (OR) for smoking and stressful life events were 2.90 (95% confidence interval [CI]=2.27-3.78) and 2.94 (95% CI=2.28-3.79), respectively. In addition, children with psoriasis were more likely to have a higher BMI (>26) than controls (OR=2.52; 95% CI=1.42-4.49). High BMI, environmental tobacco smoke exposure at home, and stressful life events may influence the development of pediatric psoriasis.

Evaluation of factors that may affect disease development and severity in childhood atopic dermatitis.

BACKGROUND: Atopic dermatitis is a chronic, relapsing, inflammatory disease. Data concerning the role of perinatal conditions in the development of the disease are few and inconsistent. The purpose of this study was to investigate the effects of skin care on the severity of the disease, also to evaluate the relations of perinatal conditions with disease development and severity. METHODS: Seventy-five patients with atopic dermatitis aged 2-10 years, their parents and 65 healthy age-compatible volunteers and their parents were included in the study. The Scoring Atopic Dermatitis (SCORAD) score was used to assess the severity of the disease. RESULTS: Emollient use (regular/irregular) was higher in patients with severe disease compared to those with mild and moderate disease, but no significant difference was determined in regular use rates (P=0.029, and P=0.504, respectively). Topical corticosteroid use and sleep disturbance rates in the previous three months in the subjects regularly using emollients were low (P=0.032, and P=0.005, respectively). The incidence of severe disease was higher in the patients born in the winter (P=0.033). Severe disease rates were significantly high in the subjects in the patient group with advanced maternal age, a history of cesarean delivery and incubator use (P=0.017, P=0.046, and P=0.025, respectively). CONCLUSIONS: Low topical corticosteroid requirement and sleep disturbance rates in the subjects regularly using moisturizers emphasize the importance of emollient use in treatment. The association of cesarean delivery, history of incubator, and birth in winter with severe disease suggests that disease severity is related to less exposure to environmental allergens in the hygiene hypothesis.

Prevalence and Dermoscopic Patterns of Acral Melanocytic Nevi in Turkey.

Although nevi are frequently encountered in the acral region, very limited studies have reported their prevalence in specific populations. We aimed to determine the prevalence of acral nevi, their dermoscopic patterns, and evaluate patient awareness in a Turkish population. We prospectively examined 2644 patients admitted to the outpatient dermatology clinics between October 2016 and October 2017. The characteristics of the detected acral nevi and dermatoscopic images were recorded. A questionnaire of demographic characteristics was completed from all patients. Two hundred six of the 2644 patients had at least one acral nevus. Two hundred sixty nevi were examined. The general prevalence of acral nevi was 7.8%. Women were more likely to have acral nevi than men (8.7% vs. 6.3%; P=0.028). Moreover, darker-skinned patients were also had significantly more acral nevi (8.6% in skin type III-IV vs. 6.0% in skin type I-II; P<0.001). The prevalence of acral nevi was 9.4% before the age of 20, 9.5% in patients aged 20-40 years, and 4.6% after the age of 40. In addition, 51.5% of all nevi exhibited a parallel furrow, 13.5% were lattice-like, and 7.7% had a homogeneous pattern. The overall nevus awareness rate was 73.8% and was significantly higher in women at 78.3%. Our study is the first large-scale study of that showed the prevalence of acral nevi in Turkey. According to our study, the prevalence of acral nevi was higher in patients with female sex and darker skin type. We also found that the prevalence of acral nevi decreased over 40 years of age. The general awareness of nevi was higher in women.