Annular skin tumors and lymphoproliferative diseases.

Determining the shape of a skin lesion may provide a diagnostic clue in dermatology practice, more commonly for inflammatory diseases but also for skin tumors. The annular formation may develop by diverse mechanisms in skin tumors. Annular lesions may occur from the onset of the tumor as sparing the central area or depression and/or ulceration in the center of the tumor or outward expansion of the primary lesion. Clustering of multiple papulonodular lesions sparing the central area or relatively independent processes acting on the central and peripheral components of the tumor may also result in an annular appearance. We have explored a wide variety of benign and malignant skin tumors and lymphoproliferative diseases forming an annular shape.

Clinical course of psoriasis patients that discontinued biologics during the COVID-19 pandemic.

BACKGROUND: Since psoriasis is a chronic disease, it is not recommended to discontinue the treatment agents used. However, in real life, the treatment of psoriasis patients may be interrupted for various reasons. During the pandemic period, the treatment of many patients was also interrupted. OBJECTIVES: To evaluate relapse and clinical worsening in psoriasis patients whose biological therapy was interrupted during the pandemic and reveal associated factors. METHODS: The study included patients aged ≥18 years, who were followed up with moderate and severe chronic psoriasis controlled by the last biological agent [Psoriasis Area Severity Index (PASI) 75 response achieved] but had to discontinue their treatment during the pandemic. The patients' demographic and clinical characteristics, clinical course after the discontinuation of these agents, presence of clinical worsening, and relapse were evaluated. Risk factors were analyzed with the logistic regression analysis. RESULTS: The study included 169 patients, with a mean age of 47.3 ± 14.5 (18-87) years. The mean biologics-free time was 18.2 ± 12.3 (2-56) weeks. Clinical worsening was detected in 41.4% and relapse in 48.5% of the patients. The significant risk factors for clinical worsening and relapse in both univariate and multivariate analyses were alcohol use during the biologics-free period, total time off biologics, and the presence of an additional triggering factor. The use of secukinumab and ustekinumab was found to be a protective factor against clinical worsening in multivariate analyses. CONCLUSION: As the biologics-free period is prolonged, the likelihood of clinical worsening and relapse increases, therefore, we do not recommend discontinuing biological agents.

Cutaneous reactions after COVID-19 vaccination in Turkey: A multicenter study.

OBJECTIVES: In this study covering all of Turkey, we aimed to define cutaneous and systemic adverse reactions in our patient population after COVID-19 vaccination with the Sinovac/CoronaVac (inactivated SARS-CoV-2) and Pfizer/BioNTech (BNT162b2) vaccines. METHODS: This prospective, cross-sectional study included individuals presenting to the dermatology or emergency outpatient clinics of a total of 19 centers after having been vaccinated with the COVID-19 vaccines. Systemic, local injection site, and non-local cutaneous reactions after vaccination were identified, and their rates were determined. RESULTS: Of the 2290 individuals vaccinated between April 15 and July 15, 2021, 2097 (91.6%) received the CoronaVac vaccine and 183 (8%) BioNTech. Systemic reactions were observed at a rate of 31.0% after the first CoronaVac dose, 31.1% after the second CoronaVac dose, 46.4% after the first BioNTech dose, and 46.2% after the second BioNTech dose. Local injection site reactions were detected at a rate of 35.6% after the first CoronaVac dose, 35.7% after the second CoronaVac dose, 86.9% after the first BioNTech dose, and 94.1% after the second BioNTech dose. A total of 133 non-local cutaneous reactions were identified after the CoronaVac vaccine (2.9% after the first dose and 3.5% after the second dose), with the most common being urticaria/angioedema, pityriasis rosea, herpes zoster, and maculopapular rash. After BioNTech, 39 non-local cutaneous reactions were observed to have developed (24.8% after the first dose and 5% after the second dose), and the most common were herpes zoster, delayed large local reaction, pityriasis rosea, and urticaria/angioedema in order of frequency. Existing autoimmune diseases were triggered in 2.1% of the patients vaccinated with CoronaVac and 8.2% of those vaccinated with BioNTech. CONCLUSIONS: There are no comprehensive data on cutaneous adverse reactions specific to the CoronaVac vaccine. We determined the frequency of adverse reactions from the dermatologist's point of view after CoronaVac and BioNTech vaccination and identified a wide spectrum of non-local cutaneous reactions. Our data show that CoronaVac is associated with less harmful reactions while BioNTech may result in more serious reactions, such as herpes zoster, anaphylaxis, and triggering of autoimmunity. However, most of these reactions were self-limiting or required little therapeutic intervention.

Long-term efficacy and safety of ustekinumab for moderate-to-severe psoriasis: A 9-year real-life experience from a tertiary referral center in Turkey.

There is a paucity of data on long-term (≥5-year) outcomes of ustekinumab therapy for psoriasis in real-life clinical practice. This observational, retrospective study aimed to evaluate the long-term efficacy and safety profile of ustekinumab in 52 adult patients with moderate-to-severe chronic plaque psoriasis who were treated with ustekinumab for at least 28 weeks and a maximum of 105 months in our tertiary referral center in Turkey, between 2010 and 2019. Response to therapy was assessed using Psoriasis Area and Severity Index (PASI). Logistic regression analysis was performed to determine significant associations (p-value <0.05) with response to treatment. The PASI50, PASI75, PASI90, and PASI100 response rates were 97.8%, 88.9%, 53.3%, and 35.5%, respectively, at year 1 and 100%, 80.0%, 60.0%, and 40.0%, respectively, at year 5. Non-obesity was independently associated with PASI90 response at year 2 (p = 0.043), while biologic-naivety was independently associated with PASI90 responses at year 2 (p = 0.047) and year 3 (p = 0.021). An absolute PASI score of ≤3 was achieved by 82.2% and 80.0% of the patients at year 1 and year 5, respectively. Nine patients received adjuvant therapy and nine underwent ustekinumab dose escalation. These strategies were effective for recapturing clinical response in most patients. Ustekinumab was generally well-tolerated with no dose-related and cumulative toxicity, or drug interaction over a mean of 33.5 ± 21.1 months. The main reasons for discontinuation were secondary failure and loss to follow-up. Our 9-year real-life clinical experience demonstrates that ustekinumab is an efficacious and safe treatment option for long-term therapy of moderate-to-severe plaque psoriasis.

Comparison of three different dose regimens of methylprednisolone as initial therapy for pemphigus vulgaris of moderate severity: A single-center retrospective study from Turkey.

BACKGROUND: Currently, no consensus exists on the dosing regimen of corticosteroids in relation to disease severity in pemphigus vulgaris. OBJECTIVE: To evaluate the efficacy of three initial dose regimens of methylprednisolone in the treatment of moderate pemphigus. METHODS: We retrospectively analysed the data of 46 patients with moderate pemphigus vulgaris, who initially received either low (0.60-0.80 mg/kg/day), moderate (0.81-1.20 mg/kg/day) or high (1.21-2.0 mg/kg/day) doses of methylprednisolone. RESULTS: The median time to disease control and hospital stay was shortest in the high-dose group (8.5 days and 27.5 days, respectively). The low-dose group had the highest rate of adjuvant therapy (88.8%, P = 0.035). Cumulative methylprednisolone doses and corticosteroid-related adverse events were similar in the moderate- and high-dose groups. The initial methylprednisolone dose showed a significant inverse correlation with time to disease control (r = -0.319, P = 0.031) and a weak inverse correlation with length of hospital stay (r = -0.282, P = 0.058). LIMITATIONS: Retrospective design and small patient size are major limitations. CONCLUSION: In the treatment of moderate pemphigus vulgaris, high initial doses of corticosteroid seem to provide early disease control and shortened hospital stay without notable increases in cumulative corticosteroid doses. This treatment strategy may lower the risk for nosocomial infections and reduce the economic burden of pemphigus.

Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi-drug refractory patients: A case series of high efficacy and safety profile.

Secukinumab, the first monoclonal antibody that inhibits interleukin-17A, has been shown to have rapid and long-lasting efficacy in the treatment of moderate-to-severe psoriasis. However, there are still difficult-to-treat cases in which even dose-escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low-dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real-life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low-dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.

Surveillance of psoriatic patients on biologic treatment during the COVID-19 pandemic: A single-center experience.

There are few studies on how patients with psoriasis who are on biologic therapy are affected by the COVID-19 pandemic. We analyzed the impact of the COVID-19 pandemic on patients with psoriasis receiving biologic therapy, patients' current status at a single center in Turkey. A total of 133 patients (mean age; 44.6 ± 13.5 years) were on maintenance biological treatment for moderate-to-severe psoriasis during the pandemic. A standardized questionnaire was administered by phone interviews to determine patients' perceptions, attitudes, and adherence to therapy and identify the frequency of COVID-19 infection, psoriasis status, and new comorbidities during the pandemic. All patients had been receiving a biological agent including ustekinumab, etanercept, adalimumab, secukinumab, infliximab, ixekizumab, or certolizumab pegol. Ninety-one patients (68.4%) had at least one comorbid condition, including psoriatic arthritis (35.3%), hypertension (19.5%), diabetes mellitus (16.5%), obesity, coronary artery disease, and dyslipidemia. During the first 3 months of the pandemic, 52 patients (39%) suspended their biological therapies for short (n = 33) or long (n = 19) periods without medical advice for reasons of fear, worry, and anxiety. All but one patient restarted their medications as a result of therapeutic counseling. Five patients reported suspicious symptoms, but only one had PCR-confirmed COVID-19. Our findings suggest that biologic treatment for moderate-to-severe psoriasis would not pose an additional risk for COVID-19 infection and its life-threatening complications, even in the presence of a high frequency of cardiometabolic comorbidities, provided that all patients are informed and necessary pandemic-directed precautions are well adopted by the patients.

The impact of COVID-19 pandemic on the management of patients with chronic urticaria: An observational two-center study from Turkey.

The Coronavirus Disease 2019 (COVID-19) outbreak significantly affected the clinical practice in hospitals and the management of many diseases. The aim of this study was to evaluate the effect of pandemic-related factors on the severity and course of chronic urticaria (CU). A total of 194 CU patients who were on regular follow-up, were enrolled in the study. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). Patients were divided into two subgroups according to their disease aggravation as "aggravated" and "non-aggravated". Two groups were compared in terms of demographic, clinical, COVID-19-associated parameters, and parameters related with the effect of COVID-19 pandemic on CU management. The omalizumab use was statistically higher (P = .017), and the systemic corticosteroid use was statistically lower (P = .025) in the "aggravated" group. Adherence to quarantine was significantly lower in the "aggravated" group (P = .027). 173 patients (89.2%) were unable to contact a dermatologist during the pandemic. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic. CU aggravated in one patient with COVID-19 and remained stable in the other. This study showed that CU patients, especially those on omalizumab therapy, had difficulties in attending medical care and even in the maintenance of their existing therapies during the pandemic. Creating novel follow-up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this life-disturbing condition.

Use of biologic therapies for psoriasis during pregnancy and long-term outcomes of exposed children: A 14-year real-life experience at a tertiary center in Turkey and review of the literature.

Data regarding the use of biologic therapies for psoriasis during pregnancy are scarce with even more limited knowledge about the long-term safety of in utero exposure. We retrospectively evaluated nine pregnancies in six women with psoriasis who were exposed to biologic therapies between 2006 and 2019 in our psoriasis clinic, a tertiary referral center in Turkey. Pregnancy outcomes included the delivery of seven healthy babies without any complications, one elective abortion, and one ectopic pregnancy. All exposed children, aged between 14 months and 13 years (median age: 4.0 years), showed normal growth and neuropsychological development without immunodeficiencies, allergies, malignancies or other diseases. Based on up-to-date collective data in the literature and our real-life clinical experience presented here, exposure to biologic therapies during pregnancy for psoriasis does not seem to be associated with adverse pregnancy or neonatal outcomes. Our results are also reassuring with respect to long-term outcomes of exposed children, but need to be confirmed through further large prospective studies. Nevertheless, use of biologic therapies during late pregnancy, particularly during the third trimester, should be reserved for high-need patients with psoriasis and definitely requires a delicate risk/benefit balance on a case-by-case basis.

Infliximab for the treatment of recalcitrant generalized pustular psoriasis of pregnancy: Report of a challenging case.

Pustular psoriasis of pregnancy (PPP), also known as impetigo herpetiformis, is a rare gestational dermatosis that may induce life-threatening complications for both the mother and fetus. Treatment of recalcitrant generalized PPP may be challenging as available therapeutic options are limited. We herein present a 24-year-old pregnant woman with generalized PPP accompanied by high fever, fatigue, leukocytosis, and elevated levels of serum acute phase reactants. The patient was resistant to a combination treatment of high-dose cyclosporine (7.5 mg/kg/d, peroral), systemic methylprednisolone (1 mg/kg/d, intramuscular), and empirical antibiotherapy. However, she dramatically improved with infliximab (5 mg/kg, intravenous infusion), which was introduced at week 28 of pregnancy. Even within 24 hours after the first infusion of infliximab, pustular lesions began to regress with a rapid decline in fever. Following the third infusion, clearance of pustular lesions with a slight erythema was observed. Serum levels of leukocytes and acute phase reactants returned to normal. There were no adverse events related to infliximab therapy. At 40 weeks, the patient gave birth to a healthy baby. Our experience reported herein suggests that infliximab may serve as a rapidly acting, highly effective, and well-tolerated "rescue" therapy in recalcitrant generalized PPP, which poses a big therapeutic challenge for clinicians.

Psoriasiform skin eruption in a patient receiving certolizumab-pegol for ankylosing spondylitis: Report of a case and review of the literature.

Certolizumab-pegol is the first and only pegylated TNF-α antagonist approved in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. We herein present a case of certolizumab-pegol induced generalized psoriasiform eruption in a patient with ankylosing spondylitis. The diagnosis was based on typical clinical and histopathological findings and further confirmed with Naranjo Adverse Drug Reaction Probability Scale which revealed a total score of nine supporting a definite causal relationship between the drug and skin eruption. As an important finding, a significant improvement of the generalized plaque lesions was achieved upon a therapy including high-potency topical corticosteroid and oral antihistamine without discontinuation of certolizumab-pegol. Moreover, we also present a literature review of the previously published cases with certolizumab-pegol induced psoriasiform eruption. Since all of these cases had Crohn's disease or rheumatoid arthritis as the underlying disease, this is the first case report of certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing spondylitis, to the best of our knowledge.

Novel Clinical Observations on Benign Cephalic Histiocytosis in a Large Series.

BACKGROUND/OBJECTIVES: Benign cephalic histiocytosis (BCH) is a rare form of non-Langerhans cell histiocytosis in infants and young children characterized by self-healing macules and papules occurring primarily in the head and neck region. So far there have been nearly 60 reported cases in the English-language literature. METHODS: In this retrospective study, we evaluated clinical features and follow-up data of 11 patients diagnosed with BCH between 2004 and 2016 in the Department of Dermatovenereology, Istanbul Medical Faculty. RESULTS: There were 5 girls and 6 boys (median age 24 months, range 9-72 months). The median age at the onset of lesions was 8 months (range 3-36 months). The lesions first appeared on the face in 10 patients and on the trunk in 1. Proximal parts of the extremities and trunk were also involved in nine patients (81.8%). Patients were categorized into two groups based on their clinical features; five had 20 to 30 predominantly red-brown dome-shaped papules and six had 50 to hundreds of yellow-brown or predominantly pinkish brown flat papules. Four patients were lost to follow-up. In seven patients with a mean follow-up of 5 years, four had nearly complete resolution and three showed remarkable regression without treatment. CONCLUSION: With 11 additional cases from a single center, BCH seems to be an underrecognized disease. Its clinical presentation is not uniform. Considering that most of the patients in this series and those previously reported had extracephalic involvement, the term "cephalic" needs to be reevaluated.

The clinical spectrum of xanthomatous lesions of the eyelids.

Yellowish papules, nodules, or plaques, namely "xanthomatous" lesions, may be seen on the eyelids in the course of various disorders. The prototype is "xanthelasma palpebrarum" (XP) that is localized only to the eyelids and may be associated with hyperlipidemia. On the other hand, different types of normolipemic disorders may also cause xanthomatous eyelid lesions. Among these, Langerhans cell histiocytosis, diffuse normolipemic xanthoma, and non-Langerhans cell histiocytoses (papular xanthoma, juvenile xanthogranuloma, xanthoma disseminatum, adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, Erdheim-Chester disease, Rosai-Dorfman disease, and reticulohistiocytosis) can be listed. The eyelid findings of this heterogeneous group of disorders are challenging to differentiate from each other due to common clinical aspects that may even sometimes mimic XP. Nodularity, induration, ulceration, diffuse eyelid involvement, and extension from eyelids to the neighboring skin may represent the clinical features of xanthomatous lesions other than XP. It is necessary to obtain a thorough history and exclude XP and then perform detailed dermatological and systemic examination, biopsy for histopathologic confirmation, and appropriate specific imaging screens. As some of the conditions may be associated with other systemic disorders, especially malignancies, the differentiation of xanthomatous eyelid lesions has a critical importance, and clinical signs can be guiding.

Vernachlässigte klinische Merkmale der follikulotropen Mycosis fungoides: eine große klinische Fallserie.

HINTERGRUND UND ZIEL: Als seltene Form der Mycosis fungoides (MF), ist die follikulotrope MF (FMF) durch ein breites Spektrum klinischer Symptome gekennzeichnet. Dazu gehören, neben den vorherrschenden follikulären Läsionen, auch viele atypische Manifestationen. Das Ziel der vorliegenden Studie war eine klinische Bewertung von FMF-Patienten, unter besonderer Berücksichtigung von vernachlässigten dermatologischen Merkmalen. PATIENTEN UND METHODIK: Insgesamt wurden 27 FMF-Patienten aus dem 572 Patienten umfassenden MF-Register unserer Abteilung retrospektiv bezüglich ihrer Demographie sowie der klinischen Merkmale, Behandlungsformen, Nachsorge und Therapieergebnisse bewertet. ERGEBNISSE: Neben den bekannten klinischen Symptomen der FMF fanden wir Lichen-spinulosus-artige Läsionen mit begleitender Hypopigmentierung (n = 3) und Alopezie (n = 2), infiltrierte/erhabene, erythematöse Plaques im Gesicht, die zunächst als Lupus tumidus angesehen wurden (n = 2), pseudotumorale Läsionen, die klinisch eine MF im Tumorstadium vortäuschten (n = 1), dauerhafte Exkoriationen (n = 1), erythematöse, Rosazea-artige Papeln im Gesicht (n = 1) sowie kuppelförmige, asymptomatische, mit Muzin gefüllte (in der Histologie) Papeln/Knoten (n = 2), die andere krankheitsbedingte Läsionen überlagerten. Es kamen mehrere Therapieansätze mit unterschiedlichem Ergebnis zur Anwendung. Acht (29,6 %) Patienten hatten FMF im Spätstadium. SCHLUSSFOLGERUNGEN: Das Bewusstsein für vernachlässigte klinische Symptome kann wesentlich dazu beitragen, verspätete Diagnosen dieser aggressiven MF-Variante zu verringern.

Underrecognized clinical features of folliculotropic mycosis fungoides: a large clinical series.

BACKGROUND AND OBJECTIVE: A rare variant of mycosis fungoides (MF), folliculotropic MF (FMF) is characterized by a broad clinical spectrum that primarily includes follicle-based lesions but also many atypical clinical manifestations. The objective of the present study was to conduct a clinical analysis of patients with FMF, with a particular focus on highlighting underrecognized dermatological features. PATIENTS AND METHODS: Overall, 27 FMF patients enrolled in our department';s MF registry, which includes 572 patients, were retrospectively reevaluated with regard to demographics, clinical features, treatment modalities, follow-up, and outcomes. RESULTS: Besides the well-known clinical features of FMF, we found lichen spinulosus-like lesions in association with hypopigmentation (n = 3) and alopecia (n = 2), infiltrated/elevated erythematous facial plaques initially considered to be lupus tumidus (n = 2), pseudotumoral lesions clinically mimicking tumor-stage MF (n = 1), persistent excoriations (n = 1) and erythematous facial papules mimicking rosacea (n = 1), as well as white dome-shaped asymptomatic papules/nodules filled with mucin (on histology) (n = 2) that overlay other disease-related lesions. Various therapeutic methods were used with variable results. Eight (29.6 %) patients had late-stage disease. CONCLUSIONS: Awareness of underrecognized clinical manifestations may be key to reducing delayed diagnosis of this aggressive MF variant.

Foot contact dermatitis: nitrofurazone as the main cause in a retrospective, cross-sectional study over a 16-year period from Turkey.

BACKGROUND: The major causative agents in allergic contact dermatitis of the foot may differ from country to country. Sufficient data on foot eczema in patients from Turkey are lacking. OBJECTIVE: To identify the clinically relevant contact allergens in foot eczema and determine the role of patch test series and patients' own materials in the detection of the responsible allergens. METHODS: Among 1753 patients patch tested between 1996 and 2012 in our clinic, 53 with suspected allergic foot eczema were enrolled in this retrospective, cross-sectional study. Forty nine patients were patch tested with the extended European baseline series, 49 with supplemental series including rubber, leather, topical drugs, textile, cosmetic series containing preservatives and emulgators and varnish/plastic/glue series, and 37 with their own substances. RESULTS: Thirty of the 53 patch tested patients showing sensitization to at least one clinically relevant allergen were diagnosed with allergic foot eczema. The main eliciting agent was nitrofurazone (n = 8), followed by leather shoe allergens, ie, potassium dichromate (n = 6), p-tert-butylphenol formaldehyde resin and formaldehyde, in the second range. Rubber shoe allergens were less frequently observed (n = 3). In more than 1/3 of the patients, the causative agent could only be identified by testing the patient's own substances and/or supplemental series. CONCLUSION: Nitrofurazone was the leading causative agent followed by leather shoe allergens. Pediatric patients were frequently sensitized with shoe allergens. Patch testing with patient's own substances had a critical value in the detection of the causative agent in a significant number of patients.

Pigment Loss in Patients with Large Congenital Melanocytic Nevi: Various Clinical Presentations Documented in a Large Series.

BACKGROUND/OBJECTIVES: The association between vitiligo and congenital melanocytic nevi remains incompletely understood. The objective of this study was to investigate the frequency of depigmentation, including vitiligo, in patients with a large congenital melanocytic nevus (LCMN), which is a rare melanocytic tumor variant. METHODS: We retrospectively reviewed the files of 92 patients with an LCMN, including photographic documentation regarding the presence of pigment loss on the nevus mass, around the nevus, around the satellites, and elsewhere on the body. RESULTS: Depigmentation was observed in 8 (8.7%) of 92 patients with an LCMN. Depigmented areas within the main nevus mass were observed in six patients, and adjacent or remote vitiligo was observed in four patients. One patient also demonstrated halo depigmentation around some satellite nevi. CONCLUSION: The coexistence of an LCMN with vitiligo does not appear to be rare and may occur with a spectrum of clinical presentations.