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Background: Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis., Objectives: To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis., Methods: In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [-15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28., Results: Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of -0.6% (95% confidence interval; -3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST., Limitations: Data were only through week 28., Conclusion: SB17 was clinically biosimilar to UST up to week 28., Competing Interests: Conflicts of interest Dr Feldman has received research, speaking, and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung Bioepis, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate, and the National Psoriasis Foundation. Dr Feldman is founder and part owner of Causa Research and holds stock in Sensal Health. Dr Narbutt is an investigator and/or lecturer for Novartis, Eli Lilly, Almirall, AbbVie, Celltrion, Pfizer, Leo Pharma, Janssen, and UCB and participated in SB17-3001 study as an investigator and received investigational grant from Samsung Bioepis. Dr Girolomoni has received personal fees from AbbVie, Abiogen, Almirall, Amgen, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Samsung Bioepis, and Sanofi. Drs Brzezicki, Reznichenko, Zegadlo-Myłik, Pulka, Dmowska-Stecewicz, Klujszo, Rekalov, and Rajzer participated in SB17-3001 study as an investigator and received investigator grants from Samsung Bioepis. Authors J. Lee, M. Lee, and Dr Rho are employees of Samsung Bioepis Co, Ltd and owns stocks of Samsung Biologics., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None declared for the authors with the exception of Ketty Peris who has served on advisory board, received honoraria for lectures and/or research grants for AbbVie, Almirall, Lilly, Galderma, Leo Pharma, Pierre Fabre, Novartis, Sanofi, Sun Pharma, Janssen; Andrea Chiricozzi who served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Lilly, Janssen, Novartis, Pfizer, and Sanofi Genzyme; Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and research grants from AMGEN, Almirall, Abbvie, BMS, Galderma, Kyowa Kyrin, Leo Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi-Regeneron, Sunpharma; Maria Esposito who served as advisory board member, speaker and consultant and has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Eli Lilly, Janssen, Novartis, and Sanofi Genzyme, UCB; Cataldo Patruno who served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Amgen, Eli Lilly, Leo Pharma Novartis, Pfizer, Pierre Fabre, Sanofi.

Competing Interests: Conflicts of interest DS is a speaker for Leo Pharma, Novartis, and Sanofi Genzyme. PG is a consultant or speaker for AbbVie, Almirall, Celgene, Ducray, Janssen, Leo Pharma, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Sandoz, and UCB. GG has received personal fees from AbbVie, Abiogen, Almirall, Amgen, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Eli Lilly, Fresenius Kabi, Galderma, Leo Pharma, Pfizer, Regeneron, Sanofi Genzyme, and Samsung. GD and MM have no conflicts of interest to disclose.

Background: The association between chronic plaque psoriasis and lymphohematologic malignancies (LHMs) remains controversial., Objective: To investigate the risk of LHMs in patients with psoriasis according to the best evidence., Methods: A systematic review and meta-analysis of observational cohort studies was undertaken to assess the association of psoriasis with different LHMs. A literature search for relevant studies was performed on February 28, 2021. The random-effects model in conducting meta-analyses was applied. To evaluate the risk of bias, the Newcastle-Ottawa Scale was employed., Results: A total of 25 observational studies were selected, comprising collectively 2,501,652 subjects. A significantly increased risk for LHM (hazard ratio [HR], 1.55; 1.24-2.94) and lymphoma (HR, 1.27; 1.08-1.50) in patients with moderate-to-severe plaque psoriasis compared to the general population was found. In detail, increased risks for Hodgkin lymphoma (HR, 1.71; 1.27-2.30), non-Hodgkin lymphoma (HR, 1.27; 1.08-1.50), multiple myeloma (HR, 1.32; 1.03-1.69), and leukemia (HR, 1.28; 1.00-1.65) were found. The risk of cutaneous T-cell lymphoma was markedly augmented in patients with psoriasis (HR, 6.22; 3.39-11.42)., Limitations: Possible ascertainment bias related to the diagnosis of LHMs., Conclusion: The increased risk of LHMs, particularly cutaneous T-cell lymphoma, in patients with psoriasis could be related to exposure to systemic immunosuppressive therapies, comorbidities, and sustained immune activation, particularly in the skin., Competing Interests: Conflict of interest Dr Bellinato has no conflict of interest to declare. Dr Gisondi has been a consultant and/or speaker for AbbVie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. Dr Girolomoni served as consultant and/or speaker for AbbVie, Abiogen, Almirall, Amgen, Biogen, Boeringher-Ingelheim, Bristol-Meyers Squibb, Celltrion, Eli Lilly, Genzyme, Leo Pharma, Menlo therapeutics, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, and UCB., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Based on increased cardiometabolic comorbidities, inflammation, and an overlap in genetics with Alzheimer disease, psoriasis patients might be at risk for cognitive dysfunction and dementia., Objective: To compare cognition, magnetic resonance imaging (MRI)-markers, and dementia risk in psoriasis and nonpsoriasis participants in the population-based Rotterdam Study., Methods: We identified 318 psoriasis and 9678 nonpsoriasis participants (mean age 66.1 years, 58% women). The association of psoriasis with cognitive function, mild cognitive impairment, and MRI-markers of brain damage was examined by linear and logistic regression. Dementia risk was calculated using Cox regression. Models were adjusted for age, sex, education, and cardiovascular risk factors., Results: Cognitive test scores and volumetric, microstructural, focal measures on brain MRI did not differ between psoriasis (28% systemic and ultraviolet treatment) and nonpsoriasis participants, and psoriasis was not associated with mild cognitive impairment (adjusted odd ratio 0.87, 95% confidence interval 0.53-1.43). During 115.000 person-years of follow-up, 810 incident dementia cases (15 among psoriasis patients) occurred. After adjusting for confounders, psoriasis was associated with a lower risk of developing dementia (adjusted hazard ratio 0.50, 95% confidence interval 0.28-0.91)., Limitations: Limited dementia cases among psoriasis patients., Conclusion: In this population-based study, psoriasis was not associated with preclinical markers or higher dementia risk., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Chronic nodular prurigo (CNPG) is a multifactorial skin disease characterized by itchy papules and nodules, usually resistant to standard treatment and associated with markedly impaired quality of life., Objective: To describe dupilumab effectiveness and tolerability in treating adult patients with CNPG refractory to both topical and systemic therapies., Methods: Retrospective, multicenter study including adult patients affected by CNPG, who were treated with dupilumab for at least 16 weeks., Results: Twenty-seven CNPG patients showed clinical improvement in terms of skin lesions, itch, sleeplessness, and quality of life. A consistent proportion of patients (24/27; 88.9%) had at least 16-week continuous treatment and achieved Investigator Global Assessment score 1 (11/24; 45.8%). An increased number of patients achieved at least a 2-grade reduction in Investigator Global Assessment score (19/24; 79.2%). Numeric rating scale values for itch and sleeplessness decreased from 8.9 to 2.7 and from 8.2 to 1.7, respectively (P < .001) after 16-week therapy. Ten patients achieved 36 weeks of continuous treatment while maintaining clinical efficacy., Limitations: Major limitations included lack of validated assessment tools at the initial data collection, a limited cohort of treated patients, and a short-term observation period., Conclusion: Dupilumab was proven effective in reducing itch and improving CNPG skin lesions., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Clinical and pathologic criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial., Objective: The aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathologic investigation., Methods: Eleven European university dermatology units collected all diagnosed cases from January 2000 to December 2016. Board-certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student t test, exact test of goodness-of-fit, Fisher's exact test, and the Cochran-Mantel-Haenszel test for repeated measures., Results: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and reported more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed a significant association of mucin deposition (P = .000083), direct immunofluorescence positivity for granular immunoglobulin M, and C3 deposits on the basement membrane zone (P = .0041) for I-SCLE and of leukocytoclastic vasculitis (P = .0018) for DI-SCLE., Limitations: This is a retrospective study., Conclusion: An integrated clinical and immunopathologic evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, and leukocytoclastic vasculitis is found in DI-SCLE., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Secukinumab has demonstrated high, sustained efficacy in psoriasis to 52 weeks on a fixed-interval regimen., Objective: We sought to compare a retreatment-as-needed versus a fixed-interval regimen., Methods: In this double-blind study, adults with moderate to severe plaque psoriasis were randomized 1:1 to subcutaneous secukinumab at 300 mg (n = 484) or 150 mg (n = 482) weekly from baseline until week 4, and at week 8. At week 12, patients achieving 75% or more improvement from baseline Psoriasis Area and Severity Index score (PASI 75) were rerandomized to 2 dose levels of secukinumab retreatment as needed (n = 217, 300 mg; n = 206, 150 mg) or fixed interval (n = 217; n = 203). Primary end point was noninferiority of retreatment as needed versus fixed interval for maintaining PASI 75 to week 52., Results: Secukinumab induced high responses by week 12 (84.4%-91.1% PASI 75 responders). From week 12 to week 52, more patients on fixed interval (78.2%, 300 mg; 62.1%, 150 mg) maintained PASI 75 versus retreatment as needed (67.7%; 52.4%); statistical noninferiority of retreatment as needed was not established. Overall safety, including very low incidences of treatment-emergent anti-drug antibodies (<0.5%), was similar between regimens., Limitations: The primary end point was developed without any known precedent., Conclusion: Secukinumab fixed interval showed clear benefit versus the study-specified retreatment-as-needed regimen for maintaining efficacy. Both regimens exhibited safety consistent with previous trials. The potential of retreatment as needed with secukinumab warrants further investigation., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Histiocytoid Sweet syndrome (HSS) is a rare variant of Sweet syndrome (SS). The nature of histiocytoid cells is still uncertain., Objective: We sought to offer a comprehensive overview on clinical features of HSS and further information on immunohistochemical phenotype of the infiltrate., Methods: The clinical, histologic, and immunohistochemical features of 12 of our patients with HSS and all cases retrieved through a PubMed search were analyzed., Results: Lesions consisted of erythematous-violaceous papules and plaques, randomly distributed mostly on the trunk and the limbs. Three patients had myelodysplastic syndrome and 1 had a monoclonal gammopathy. The infiltrate was mainly composed of CD68(+)CD163(+)myeloperoxidase(+)myeloid cell nuclear differentiation antigen(+)CD117(-)CD15(-)CD34(-), a phenotype suggestive of M2-like macrophages. A few mature neutrophils and lymphocytes were also present. Review of all HSS cases showed no sex predominance and no extracutaneous infiltrates; inconstant presence of fever and blood neutrophilia; association with hematologic or solid neoplasms (26%), autoimmune conditions (12%), and infectious diseases (10%); and good response to steroid treatment, with rare relapses or recurrences., Limitations: The study includes a limited case series. The pathogenesis of the disease remains to be clarified., Conclusions: HSS lesions are infiltrated mostly by M2-like macrophages. The clinical features present more similarities than differences with SS., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Available psoriasis surveys offer valuable information about psoriasis and psoriatic arthritis (PsA), but are limited by methodology or enrollment requirements., Objective: To further the understanding of the unmet needs of psoriasis and PsA patients., Methods: This was a large, multinational, population-based survey of psoriasis and/or PsA patients in North America and Europe. Patients were selected by list-assisted random digit dialing and did not have to currently be under the care of a health care provider, a patient organization member, or receiving treatment; 139,948 households were screened and 3426 patients completed the survey., Results: The prevalence of psoriasis/PsA ranged from 1.4% to 3.3%; 79% had psoriasis alone and 21% had PsA. When rating disease severity at its worst, 27% (psoriasis) and 53% (PsA ± psoriasis) of patients rated it as severe. Psoriasis patients indicated that their most bothersome signs or symptoms were itching (43%), scales (23%), and flaking (20%). Of psoriasis patients, 45% had not seen a physician in a year; >80% of psoriasis patients with ≥ 4 palms body surface area and 59% of PsA patients were receiving no treatment or topical treatment only. Of patients who had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy, most often for safety/tolerability reasons and a lack/loss of efficacy., Limitations: The survey lacked a control group, did not account for ethnic and health care system differences across countries, and was limited by factors associated with any patient survey, including accurate recall and interpretation of questions., Conclusions: Several identified unmet needs warrant additional attention and action, including improved severity assessment, PsA screening, patient awareness, and treatment options., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Few studies have examined the association between elevated serum uric acid (SUA) levels and psoriasis, and their results have been inconclusive because most of these studies did not take into account the confounding effects of coexisting features of the metabolic syndrome., Objective: We compared the prevalence of hyperuricemia and SUA levels between psoriatic patients and control individuals., Methods: Levels of SUA were measured in 119 consecutive psoriatic patients and 119 control individuals matched for age, sex, and body mass index., Results: Compared with control subjects, psoriatic patients had higher SUA levels (5.61 ± 1.6 vs 4.87 ± 1.4 mg/dL; P < .001) and a remarkably greater prevalence of asymptomatic hyperuricemia (19% vs 7%; P < .001). Multivariate logistic regression analysis revealed that psoriasis was the strongest predictor of hyperuricemia (odds ratio 3.20; 95% confidence interval 1.32-7.58; P < .01) after adjusting for age, sex, and metabolic syndrome features., Limitations: The cross-sectional design of this study does not allow us to draw any conclusion about a causal relation between psoriasis and hyperuricemia., Conclusions: Hyperuricemia is a common finding in psoriatic patients. Its treatment might be clinically useful for the global treatment of patients., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Unlabelled: There are a number of systemic disorders that can manifest with urticarial skin lesions, including urticarial vasculitis, connective tissue diseases, hematologic diseases, and autoinflammatory syndromes. All of these conditions may enter into the differential diagnosis of ordinary urticaria. In contrast to urticaria, urticarial syndromes may manifest with skin lesions other than wheals, such as papules, necrosis, vesicles, and hemorrhages. Lesions may have a bilateral and symmetrical distribution; individual lesions have a long duration, and their resolution frequently leaves marks, such as hyperpigmentation or bruising. Moreover, systemic symptoms, such as fever, asthenia, and arthralgia, may be present. The most important differential diagnosis in this group is urticarial vasculitis, which is a small-vessel vasculitis with predominant cutaneous involvement. Systemic involvement in urticarial vasculitis affects multiple organs (mainly joints, the lungs, and the kidneys) and is more frequent and more severe in patients with hypocomplementemia. Clinicopathologic correlation is essential to establishing a correct diagnosis., Learning Objectives: After completing the learning activity, participants should be able to distinguish urticarial lesions suggesting diagnoses other than common urticaria; assess patients with urticarial lesions, and suspect systemic diseases presenting with urticarial skin lesions., (Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Unlabelled: Acute urticaria is self-limiting, and a cause can be identified in many patients. Chronic urticaria is a long lasting disease, and patients are commonly examined for an autoimmune origin and for associated diseases. Although the diagnosis of urticaria is straightforward in most patients, it may pose some difficulties at times and it may require a careful differential diagnosis with a number of conditions. Urticarial syndromes comprise both cutaneous and systemic disorders. Part I of this two-part series focuses on the clinical and histologic features that characterize common urticaria and on the cutaneous diseases that may manifest with urticarial lesions and must be considered in the differential diagnosis., Learning Objectives: After completing the learning activity, participants should be able to distinguish between the typical wheals of urticaria and urticarial lesions suggesting other diagnoses and to assess patients with urticarial lesions in order to exclude or confirm other cutaneous diseases., (Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Drug-induced scleroderma has been rarely reported, mostly with the features of diffuse scleroderma or acrosclerosis, and exceptionally with the characteristics of morphea. We report the case of an adult white woman, enrolled in a double-blind, placebo-controlled, multicentric trial evaluating the efficacy and safety of the cathepsin K inhibitor balicatib for osteoporosis. Typical morphea lesions developed on the patient's trunk 9 months after the beginning of therapy. Lesions completely resolved after drug withdrawal and a single brief course of systemic steroids. No recurrence occurred in a 2-year follow-up. Fifteen cases of drug-induced morphea could be retrieved from the literature. Drug withdrawal determined complete remission in only a few patients. Different drug classes have been implicated. Some of these, including balicatib, alter directly connective tissue metabolism.

Background: Rosacea is a common chronic dermatosis that involves the cutaneous microvasculature of the face. There are no objective measures for assessing the severity of erythematotelangiectatic rosacea., Objective: Our purpose was to characterize and provide objective measures of vessel changes in erythematotelangiectatic rosacea by videocapillaroscopy., Methods: We compared 30 patients with erythematotelangiectatic rosacea with 30 age- and sex-matched patients with facial seborrheic dermatitis and 30 healthy control subjects. Videocapillaroscopy was performed both on the cheeks and on the nailfold region. The analyzed parameters of the face were morphological (background color, vessel irregularities) and quantitative (polygonal net perimeter, telangiectasia, and vessel diameters)., Results: Characteristic alterations of skin vessels were observed in facial rosacea, with a pattern distinct from that of facial seborrheic dermatitis. In particular, rosacea showed neoangiogenesis and significantly larger polygons (13.21 +/- 3 vs 7.8 +/- 3 mm; mean +/- standard deviation, P < .001), more prominent telangiectases (267.8 +/- 108 vs 118.2 +/- 35 microm; P < .001) and larger mean vessel diameter (46.71 +/- 9 vs 24 +/- 10 microm; P < .001) compared with seborrheic dermatitis. Seborrheic dermatitis displayed more polygon irregularities and vessel tortuosity. In contrast, no differences were found in the nailfold region., Limitations: Vessel irregularities and overall erythema may be difficult to quantify., Conclusions: Videocapillaroscopy may represent a valid adjunctive method in the early diagnosis and measurement of erythematotelangiectatic rosacea.

Background: Keratinocytes participate in initiation and amplification of T-cell-mediated skin diseases. During these disorders, histamine can be released from both residents skin cells and immigrating leukocytes, and can affect the functions of dendritic cells, monocytes, and lymphocytes. Little information is available on the effects of histamine on keratinocytes., Objective: To examine the presence of functional H1 receptors on human keratinocytes and the capacity of histamine to modulate the expression of inflammatory molecules in these cells., Methods: Primary cultures of resting and cytokine-activated keratinocytes from healthy subjects were analyzed for histamine H1 receptor expression and the production of inflammatory mediators after exposure to histamine receptor agonists and antagonists., Results: Cultured keratinocytes constitutively expressed the H1 receptor mRNA and protein, which was not influenced by IFN-gamma, TNF-alpha, or IL-4. H1 but not H2 agonists induced calcium fluxes in keratinocytes. Treatment of keratinocytes with histamine (10 -7 to 10 -4 mol/L) or beta-histine increased the IFN-gamma-induced expression of membrane intercellular adhesion molecule 1 and MHC class I but not MHC class II molecules. Moreover, H1 stimulation promoted basal CC chemokine ligand (CCL)-5/RANTES and GM-CSF secretion and augmented IFN-gamma-induced release of the chemokines CCL2/monocyte chemoattractant protein 1, CCL5/RANTES, CCL20/macrophage inflammatory protein 3alpha, and CXC chemokine ligand 10/IFN-induced protein of 10 kd, as well as GM-CSF. Administration of the H1 antihistamine levocetirizine, but not of the H2 antihistamine cimetidine, abolished histamine-dependent expression of all of the investigated proinflammatory molecules in a dose-dependent manner (0.01-10 mumol/L). Levocetirizine at higher doses also reduced intercellular adhesion molecule 1, CCL5/RANTES, and GM-CSF release induced solely by IFN-gamma., Conclusion: Histamine exerts proinflammatory effects on keratinocytes via the H1 receptor, and these effects are efficiently inhibited by levocetirizine.

Scleromyxedema is a generalized, papular, and sclerodermoid form of lichen myxedematosus associated with monoclonal gammopathy and systemic changes. Despite anecdotal reports of success with various agents, no satisfactory treatments are currently available. We report 3 adult patients with recalcitrant scleromyxedema associated with paraproteinemia who were treated with thalidomide. All 3 patients had marked improvement of the skin lesions and joint mobility after the first 2 months of therapy, with further amelioration after 4 months, and reduction in paraprotein levels.

Background: Lichenoid dermatoses are composed of a wide spectrum of disorders with a common histopathologic interface pattern but diverse causes and pathophysiology., Objective: We describe a series of young patients with a peculiar annular lichenoid dermatitis, the clinical appearance of which initially suggested diagnoses of morphea, mycosis fungoides, or annular erythema., Results: The study involved 23 patients (median age 10 years; age range 5-22 years). Lesions consisted of persistent asymptomatic erythematous macules and round annular patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histology revealed a peculiar lichenoid dermatitis with massive necrosis/apoptosis of the keratinocytes limited to the tips of rete ridges, in the absence of dermal sclerosis and epidermotropism of atypical lymphocytes. The infiltrate was composed mainly of memory CD4(+) CD30(-) T cells with few B cells and macrophages. Analysis of T-cell receptor-gamma-chain gene rearrangement in skin biopsy specimens revealed polyclonality in all the 15 cases studied. Topical and systemic corticosteroids or phototherapy were effective in most patients with relapse after treatment withdrawal., Conclusions: We suggest that this is a distinctive inflammatory condition, and we propose to term it "annular lichenoid dermatitis of youth."

Background: There is currently no definitive cure for urticaria pigmentosa (UP). Psoralen plus ultraviolet A therapy is efficacious in alleviating symptoms and reducing cutaneous lesions., Objective: The purpose of this study was to assess the effect of ultraviolet A1 (UVA1) in adult patients with UP and to compare the effectiveness of high-dose (130 J/cm(2)/day for 10 days) and medium-dose (60 J/cm(2)/day for 15 days) UVA1 radiation., Methods: Ten and 12 adult patients with UP were treated with high-dose or medium-dose UVA1, respectively. The number of skin lesions and dermal mast cells, the presence of Darier's sign, the intensity of pruritus, and quality of life measures were evaluated before, at the end of treatment, and 2 and 6 months later., Results: Baseline characteristics were similar among the 2 groups of patients. In the majority of patients, the number of lesions was not significantly reduced. However, the number of mast cells in lesional skin decreased markedly in most patients by the end of treatment, and it remained low for the whole study period. Pruritus and quality of life improved considerably by the end of treatment, and the improvement was maintained during the 6-month follow up. No significant differences were observed between patients receiving high- or medium-dose UVA1., Conclusions: UVA1 phototherapy ameliorates both objective and subjective symptoms of adult patients with UP and induces long-term remission in most cases. Medium-dose UVA1 appears at least as effective as high-dose UVA1.

Background: Mid-dermal elastolysis is a rare entity defined by the selective loss of elastic tissue in the mid dermis. Many cases appear induced or aggravated by ultraviolet (UV) light exposure. Pathogenesis is still uncertain., Objective: Our purpose was to report on the clinical and histologic features of 11 patients with mid-dermal elastolysis. Moreover, we analyzed by immunohistochemistry leukocyte subsets and expression of metalloproteinase (MMP) with the potential to degrade elastic tissue in 7 cases., Results: All patients were women with a mean age of 31.4 years. Disease duration ranged from 4 months to 17 years. Affected areas included the trunk, neck, and upper aspect of limbs. Two patients also had Hashimoto's thyroiditis and uterine carcinoma, respectively, whereas 1 patient had undergone silicone mammoplasty. In all patients, disease onset was associated with intense UV light exposure. Moderate leukocyte infiltration in the dermis was observed mostly in recent lesions and was composed of CD3(+) T cells and some CD68(+) macrophages with a normal number of factor XIIIa(+) dermal dendritic cells. Elastin, but not fibrillin-1 immunoreactivity disappeared from the mid dermis. MMP-9 was detected in epidermal keratinocytes and in the cytoplasm of large, angulated, multinucleated cells located in lesional dermis. These cells were negative for leukocyte, dendritic cell, macrophage, and T-cell markers and were absent in old lesions. Staining for MMP-7 and MMP-12 did not differ from control skin., Conclusion: Onset of mid-dermal elastolysis appears strongly associated with UV exposure, which may induce fibroblast-like cells to express MMP-9 that in turn could be involved in the degradation of elastic fibers.

Follicular lesions can either associate with typical patch-/plaque-type mycosis fungoides or, more rarely, be the only clinical manifestation of the disease. We describe 2 adult patients who presented with alopecia and disseminated follicular erythematous papules, and comedones and cysts, respectively. In both patients, histology showed a folliculotropic infiltrate of atypical lymphocytes that spared the epidermis, in the absence of follicular mucinosis. Molecular genetic analysis confirmed the oligo/monoclonal nature of the T-cell infiltrate. Reported cases of purely follicular mycosis fungoides without mucinosis are reviewed.

Background: Histamine is a well-known mediator eliciting different responses in immune and nonimmune cells, but its role in modulating dendritic cell (DC) functions has been marginally investigated., Objective: The purpose of this investigation was to analyze whether human monocyte-derived DCs express functional histamine receptors according to their maturation stage., Methods: DCs were derived from monocytes and used as immature or LPS-differentiated cells. DCs were tested for histamine receptor expression, chemotaxis, cytokine release, and the capacity to induce T-cell differentiation in response to specific histamine receptor agonists., Results: Immature and mature DCs expressed the mRNA for H1, H2, and H3 histamine receptors. Histamine induced intracellular Ca2+ transients, actin polymerization, and chemotaxis in immature DCs. Maturation of DCs resulted in the loss of these responses. In maturing DCs, however, histamine dose-dependently enhanced intracellular cAMP levels and stimulated IL-10 secretion while inhibiting production of IL-12. As a consequence, histamine might contribute to the impairment of generation of allogeneic type 1 responses via maturing DCs. Specific histamine receptor agonists or antagonists revealed that Ca2+ transients, actin polymerization, and chemotaxis of immature DCs were due to stimulation of H1 and H3 subtypes. Modulation of IL-12 and IL-10 secretion by histamine involved the H2 and H3 receptors exclusively., Conclusions: Our study suggests that histamine has important biological effects on DC activities, opening the possibility that histamine released during inflammatory or immune responses could regulate DC functions and ultimately favor type 2 lymphocyte-dominated immunity.

Background: Dermatophagoides pteronyssinus is a trigger of atopic dermatitis. Many D pteronyssinus allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines and chemokines by bronchial epithelial cells., Objective: We sought to investigate whether D pteronyssinus allergens can exert a similar activity on skin keratinocytes., Methods: Primary cultures of keratinocytes from healthy subjects or patients with atopic dermatitis and normal human bronchial epithelial cells were compared for cytokine production in response to D pteronyssinus extract., Results: Keratinocytes, but not bronchial epithelial cells, displayed a modest dose-dependent release of IL-1alpha and IL-1 receptor antagonist but no induction of their mRNA after exposure to D pteronyssinus. However, D pteronyssinus also degraded these cytokines. On the other hand, D pteronyssinus extract induced bronchial epithelial cells, but not keratinocytes, to increased expression of IL-8/CXCL8 and GM-CSF mRNA and protein. These effects were efficiently abrogated by a mixture of cysteine and serine protease inhibitors. Both IL-8 and GM-CSF were fully resistant to D pteronyssinus proteolytic attack. No induction of monocyte chemoattractant protein 1/CCL2, RANTES/CCL5, or IFN-gamma-induced protein of 10 kd/CXCL10 was detected in either cell type. Only bronchial epithelial cells expressed protease-activated receptor (PAR) 4 mRNA, whereas PAR-1, PAR-2, and PAR-3 mRNA was found in both cell types. D pteronyssinus did not affect PAR mRNA signals., Conclusions: Although D pteronyssinus can cause proteolysis-dependent release of cytokines from keratinocytes, it appears incapable of activating de novo expression of cytokines and chemokines, arguing against a direct proinflammatory activity of house dust mite on the skin.

Background: Atopic dermatitis (AD) and psoriasis are genetically determined inflammatory skin disorders. Keratinocytes actively participate in cutaneous inflammatory responses by elaborating various chemokines., Objective: We investigated the capacity of IL-4, IFN-gamma, and TNF-alpha to modulate the expression of CCL and CXCL chemokines in cultured keratinocytes from patients and healthy individuals, as well as chemokine expression in situ., Methods: Keratinocyte cultures were established from normal-looking skin of adult patients with AD or psoriasis vulgaris and from healthy subjects. Monocyte chemoattractant protein 1 (MCP-1)/CCL2, RANTES/CCL5, IL-8/CXCL8, and IFN-gamma-induced protein of 10 kd (IP-10)/CXCL10 production was evaluated at the mRNA and protein levels by using RNase protection assay and ELISA, respectively. The expression of the same chemokines was studied in chronic lesional skin by means of immunohistochemistry or in situ hybridization., Results: Only IL-8 mRNA was detected in unstimulated ke-ratinocyte cultures. MCP-1 and IP-10 were potently induced by IFN-gamma, whereas IL-8 and RANTES were preferentially upregulated by TNF-alpha and, to a lesser extent, by IFN-gamma. IL-4 weakly induced IP-10, RANTES, and IL-8 but not MCP-1. Keratinocytes of patients with AD invariably responded with significantly earlier and higher RANTES expression. By contrast, keratinocytes of patients with psoriasis displayed much higher levels of both constitutive and induced IL-8 and a stronger induction of MCP-1 and IP-10. RANTES and MCP-1 mRNA(+) keratinocytes were detected in the basal layer of lesions of patients with AD and psoriasis. IP-10 and IL-8 were consistently upregulated in the epidermis of patients with psoriasis but not in lesions of patients with AD., Conclusions: Keratinocytes of patients with AD and psoriasis show an intrinsically abnormal and different chemokine production profile and may thus favor the recruitment of distinct leukocyte subsets into the skin.

Recent studies suggest that skin keratinocytes from patients with atopic dermatitis (AD) and nonatopic subjects differ in their intrinsic ability to respond to proinflammatory stimuli. In this study keratinocyte cultures established from the normal-looking skin of six adult patients with AD and six healthy, nonatopic control subjects were compared in their response to interferon (IFN)-gamma, a potent proinflammatory lymphokine whose expression is increased in chronic AD lesions. Basal expression of IFN-gamma receptor as well as IFN-gamma-induced membrane expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 were evaluated by flow cytometry. Keratinocyte release of IL-1alpha, IL-1 receptor antagonist (IL-1ra), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha were measured by ELISA on culture supernatants after treatment with IFN-gamma or medium alone. Expression of membrane IFN-gamma receptor was similar in keratinocytes cultured from nonatopic subjects and subjects with AD. IFN-gamma (10 to 500 U/ml) induced comparable levels of membrane HLA-DR and ICAM-1 in both groups of keratinocytes. In contrast, spontaneous release of IL-1alpha, IL-1ra, GM-CSF, and TNF-alpha was increased in the supernatants of unstimulated keratinocytes from patients with AD compared with keratinocytes from control subjects, with IL-1ra and GM-CSF reaching statistically significant difference. Moreover, IFN-gamma-induced release of all the cytokines tested was much higher for keratinocytes from patients with AD, but the IL-1ra/IL-1alpha ratio for the two groups of keratinocytes was not substantially different, either basally or after IFN-gamma stimulation. The results indicate that keratinocytes from patients with AD are hyperresponsive to IFN-gamma in terms of cytokine release.