Publications by authors named "Denis Jullien"

56 Publications

Use of Complementary and Alternative Medicines by Patients with Psoriasis: Results from a Study with 2562 Patients.

Am J Clin Dermatol 2021 Feb 21. Epub 2021 Feb 21.

Department of Dermatology, Timone Hospital, University Hospital of Marseille, Marseille, France.

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http://dx.doi.org/10.1007/s40257-021-00587-7DOI Listing
February 2021

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq.

Dermatology 2021 Feb 3:1-9. Epub 2021 Feb 3.

Department of Dermatology, Hôpital Henri Mondor, Créteil, France,

Background: Obesity is associated with an increased risk of psoriasis.

Objective: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis.

Methods: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival.

Results: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19).

Conclusion: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.
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http://dx.doi.org/10.1159/000513398DOI Listing
February 2021

Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

J Allergy Clin Immunol 2021 01 16;147(1):60-71. Epub 2020 Oct 16.

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, United Kingdom. Electronic address:

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.
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http://dx.doi.org/10.1016/j.jaci.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566694PMC
January 2021

Dermpath & clinic: Pigmented epithelioid melanocytoma.

Eur J Dermatol 2020 Aug;30(4):451

Dermatology Department, Edouard Herriot Hospital, Lyon, France.

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http://dx.doi.org/10.1684/ejd.2020.3825DOI Listing
August 2020

Distal phalangeal bone erosions observed by HR-pQCT in patients with psoriatic onycholysis.

Rheumatology (Oxford) 2020 Sep 4. Epub 2020 Sep 4.

Université Claude Bernard Lyon I, Lyon.

Objectives: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms.

Methods: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method.

Results: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001).

Conclusion: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis.

Trial Registration: ClinicalTrails.gov, https://clinicaltrials.gov, NCT02813720.
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http://dx.doi.org/10.1093/rheumatology/keaa415DOI Listing
September 2020

Dermpath & Clinic: Lichen planus pemphigoides.

Eur J Dermatol 2020 Apr;30(2):211-213

Department of Dermatology, Edouard Herriot Hospital, Lyon, France.

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http://dx.doi.org/10.1684/ejd.2020.3792DOI Listing
April 2020

Chilblain-like acral lesions during the COVID-19 pandemic ("COVID toes"): Histologic, immunofluorescence, and immunohistochemical study of 17 cases.

J Am Acad Dermatol 2020 09 2;83(3):870-875. Epub 2020 Jun 2.

Department of Dermatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.

Background: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known.

Objective: To investigate the pathologic features of chilblain-like lesions.

Methods: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results).

Results: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels).

Conclusions: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.
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http://dx.doi.org/10.1016/j.jaad.2020.05.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265862PMC
September 2020

Long-Term Infliximab Treatment in Psoriasis Patients: A National Multicentre Retrospective Study.

Dermatol Res Pract 2020 9;2020:2042636. Epub 2020 Mar 9.

French Society of Dermatology, Paris, France.

Background: Although infliximab (IFX) has been available since 2005, there are very little data on the long-term drug survival of infliximab in real-life.

Objective: Our aim was to identify and describe psoriasis patients treated with IFX for longer than 6 years.

Methods: Psoriasis patients treated with IFX for longer than 6 years were retrospectively included. Demographic and clinical data were collected in May 2018.

Results: Between January 2005 and December 2012, 43 patients were maintained on IFX for 6 years or longer. IFX was introduced as a 4.5 line of systemic therapy. The mean duration of IFX treatment was 8.5 years (6-12). In May 2018, 30 patients (70%) were still maintained on IFX at 4-6 mg/kg every 8-10 weeks with an efficiency of about 100%. IFX was stopped in 13 patients (30%) mainly for loss of efficacy in 6 patients (46%). Three patients developed solid cancer including bladder cancer, lung cancer, and prostate cancer. . Retrospective study.

Conclusion: We report the efficacy and safety of IFX maintained for up to 12 years in psoriasis patients. The long-term use of IFX was associated with a high BMI confirming the critical role of weight-based dosing for this drug.
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http://dx.doi.org/10.1155/2020/2042636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085387PMC
March 2020

Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review.

Br J Haematol 2020 06 19;189(5):869-878. Epub 2020 Mar 19.

Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Centre National de Référence des Histiocytoses, Hôpital Saint-Louis, Paris, France.

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).
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http://dx.doi.org/10.1111/bjh.16449DOI Listing
June 2020

Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy: A Post Hoc Analysis of a Randomized Clinical Trial.

JAMA Dermatol 2020 05;156(5):545-552

Centre de référence des maladies bulleuses auto-immunes, Department of Dermatology, Rouen University Hospital, Normandie University, INSERM U1234, Rouen, France.

Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus.

Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab.

Design, Setting, And Participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019.

Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen.

Main Outcomes And Measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated.

Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab.

Conclusions And Relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy.

Trial Registration: NCT00784589.
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http://dx.doi.org/10.1001/jamadermatol.2020.0290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081151PMC
May 2020

Multiple acantholytic dyskeratotic acanthomas in a liver-transplant recipient.

Dermatol Online J 2019 Apr 15;25(4). Epub 2019 Apr 15.

Department of Dermatology, Edouard Herriot Hospital Group, Lyon Department of Pathology, Centre Hospitalier Lyon Sud, Pierre Bénite.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma characterized pathologically by the presence of acantholysis and dyskeratosis. Few cases have been reported until now, one of them in a heart-transplant patient. We present here a new case of this rare lesion that developed in a liver-transplant patient and review the salient features of this uncommon condition.
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April 2019

The IgG2 Isotype of Anti-Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis.

Arthritis Rheumatol 2019 08 8;71(8):1360-1370. Epub 2019 Jul 8.

Normandy University, University of Rouen, INSERM U1234, Rouen University Hospital, Rouen, France.

Objective: Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM.

Methods: This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model.

Results: Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti-TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality.

Conclusion: Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.
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http://dx.doi.org/10.1002/art.40895DOI Listing
August 2019

Successful treatment of TNFα inhibitor-resistant pityriasis rubra pilaris with ixekizumab and acitretin.

Eur J Dermatol 2019 04;29(2):218-220

Department of Dermatology, Edouard-Herriot Hospital, Lyon I University, Lyon, France.

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http://dx.doi.org/10.1684/ejd.2019.3502DOI Listing
April 2019

Large International Validation of ABSIS and PDAI Pemphigus Severity Scores.

J Invest Dermatol 2019 01 6;139(1):31-37. Epub 2018 Oct 6.

Department of Dermatology, Rouen University Hospital, and INSERM U 1234, Centre de référence des maladies bulleuses autoimmunes, Normandie University, Rouen, France.

The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.
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http://dx.doi.org/10.1016/j.jid.2018.04.042DOI Listing
January 2019

Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies.

J Am Acad Dermatol 2019 Jan 19;80(1):251-265.e19. Epub 2018 Jun 19.

Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Background: Wide-ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported.

Objectives: To assess the prevalence and incidence of PsA in patients with psoriasis.

Methods: Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta-analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis.

Results: A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI]) of PsA among patients with psoriasis was 19.7% (95% CI, 18.5%-20.9%). In children and adolescents (<18 years of age), the pooled prevalence was 3.3% (95% CI, 2.1%-4.9%). The PsA prevalence was 22.7% (95% CI, 20.6%-25.0%) in European patients with psoriasis, 21.5% (95% CI, 15.4%-28.2%) in South American patients with psoriasis, 19.5% (95% CI, 17.1%-22.1%) in North American patients with psoriasis, 15.5% (95% CI, 0.009%-51.5%) in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7%-16.3%) in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1%-27.6%) in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person-years.

Limitations: Between-study heterogeneity may have affected the estimates.

Conclusions: We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.
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http://dx.doi.org/10.1016/j.jaad.2018.06.027DOI Listing
January 2019

Basal-Cell Carcinoma With Matrical Differentiation: Report of a New Case in a Renal-Transplant Recipient and Literature Review.

Am J Dermatopathol 2018 Aug;40(8):e115-e118

Departments of Dermatology, and.

Basal-cell carcinoma with matrical differentiation (BCC-MD) is one of the rarest pathologic variants of basal-cell carcinoma, of which 41 cases have been so far reported in detail. One of them developed in a heart-transplant recipient. We report a new case of BCC-MD occurring in a renal-transplant recipient and review the relevant literature. A 75-year-old white man who had received a renal allograft 7 years ago developed a tumor on the left temple clinically suggestive of basal-cell carcinoma. Microscopically, the tumor associated features typical of basal-cell carcinoma (basaloid lobules with peripheral palisading and clefting) and pilomatricoma (presence of shadow/ghost cells). The 2 tumor components expressed variably beta-catenin, HEA/Ber-EP4, CD10, PHLDA-1, MIB-1/Ki67, calretinin, and bcl-2. BCC-MD has no distinctive clinical features. It affects predominantly male patients with a mean age of 69 years. More than half of cases appear on the head/neck area. Some cases harbor CTNNB1 mutations. Differential diagnosis includes tumors with matrical differentiation, namely pilomatrix carcinoma. The outcome is usually favorable after surgical excision, although regional lymph node metastases developed in 2 patients.
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http://dx.doi.org/10.1097/DAD.0000000000001146DOI Listing
August 2018

sQUIZ your knowledgeǃ: A recent red lesion on the forearm.

Eur J Dermatol 2018 Apr;28(2):280-282

Department of Dermatology, Edouard Herriot Hospital, Lyon, France.

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http://dx.doi.org/10.1684/ejd.2018.3305DOI Listing
April 2018

Clinical and Therapeutic Aspects of Linear Psoriasis: A Study of 30 Cases.

Am J Clin Dermatol 2018 Aug;19(4):609-615

Service de Dermatologie, Hôpital Victor Dupouy, 69 rue du Lieutenant-Colonel Prud'hon, 95100, Argenteuil, France.

Background: Psoriasis affects 2-4% of the population, with the most common clinical type being plaque psoriasis. The linear form of psoriasis is very rare. The literature on linear psoriasis (LP) consists of only case reports, and data are few.

Objective: This study aimed to better understand LP in a large-scale study.

Patients And Methods: We retrospectively retrieved the medical records from 14 French medical centers of patients newly diagnosed clinically with LP, with or without the support of histology, between 1 February and 31 July 2015. For each case, we assessed the clinical features, treatments and treatment efficacy.

Results: In total, 30 cases of LP (mean age 26.8 years, 13 males) were reported. Mean age at onset of LP was 20.0 years, with 18 developing LP in childhood. Ten patients had a family history of psoriasis, and two had psoriatic arthritis. A total of 19 cases were linear at onset, with concomitant classical psoriasis; these were termed "superimposed" LP. The remaining 11 cases were not associated with classical psoriasis and were termed "isolated" LP. In four of the superimposed cases, LP developed when the patient was receiving systemic treatment: methotrexate (n = 2), etanercept (n = 1) or infliximab (n = 1). Topical steroids were effective in 76% of cases in which they were used, and systemic treatment was effective in < 66%. Treatments were less effective in LP than in classical psoriasis.

Discussion: We identified a wide range of LP, with two profiles: isolated LP and superimposed LP. Topical treatment usually evoked clinical response, with relative resistance to systemic therapy. Methotrexate and anti-tumor necrosis factor (TNF)-α therapies can possibly unmask LP.
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http://dx.doi.org/10.1007/s40257-018-0354-9DOI Listing
August 2018

sQUIZ your knowledge! Persistent facial plaques.

Eur J Dermatol 2017 Dec;27(6):681-683

Department of Dermatology, Edouard Herriot Hospital, Lyon, France, Department of Pathology, Lyon-Sud Hospital, Pierre Bénite, France.

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http://dx.doi.org/10.1684/ejd.2017.3182DOI Listing
December 2017

Thoracic manifestations of segmental neurofibromatosis.

BMJ Case Rep 2017 Sep 25;2017. Epub 2017 Sep 25.

Department of Pneumology, Hospices Civils de Lyon, National Reference Center for Rare Pulmonary Diseases, Lyon, France.

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http://dx.doi.org/10.1136/bcr-2017-221253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747818PMC
September 2017

Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study.

Transpl Int 2017 Nov 3;30(11):1172-1180. Epub 2017 Aug 3.

Department of Dermatology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post-transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post-transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age- and sex-standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9-fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow-up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post-transplant melanoma has considerably increased over the last decade.
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http://dx.doi.org/10.1111/tri.13011DOI Listing
November 2017

Management of psoriatic arthritis among cutaneous psoriasis patients: from pathogenesis to therapy.

G Ital Dermatol Venereol 2017 Oct 23;152(5):458-473. Epub 2017 May 23.

Department of Dermatology, Edouard Herriot Hospital, Claude Bernard Lyon I University, Lyon, France -

Psoriatic arthritis (PsA) is an inflammatory rheumatism belonging to spondyloarthritis family and which occurs in about 30% of patients with psoriasis. The pathogenesis entails a genetic predisposition, environmental and immunologic factors. Most of the time, cutaneous lesions precede apparition of articular manifestations and dermatologists who treat psoriatic patients have to regularly screen for early PsA, especially in patients with risk factors (notably nail psoriasis). Early detection greatly increases the chances for successful treatment and can prevent slow joint destruction. EULAR and GRAPPA have recently published PsA treatment recommendations. Pharmacological therapies for PsA begin with non-steroidal anti-inflammatory drugs, then conventional synthetic as methotrexate, and lastly biological disease-modifying anti-rheumatic drugs. There are significant metabolic comorbidities and increased cardiovascular morbidity in patients with PsA. This aspect must be taken into account in PsA management by pharmaceutical and non-pharmaceutical approach (including educational programs). Close collaboration between dermatologists, rheumatologists and primary care clinicians is recommended to provide optimum care and to prevent the occurrence of structural damages or quality of life alteration.
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http://dx.doi.org/10.23736/S0392-0488.17.05680-2DOI Listing
October 2017

Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study.

Ann Rheum Dis 2017 Sep 8;76(9):1591-1597. Epub 2017 May 8.

Eli Lilly and Company, Indianapolis, Indiana, USA.

Objectives: To examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark.

Methods: Using nationwide registry data, we estimated the number of patients with incident PsA within each 1-year period between 1997 and 2011 and calculated the rate of PsA cases within gender and age subgroups. Incidence rates were presented per 100 000 person-years.

Results: There was a female predominance ranging from 50.3% (1998) to 59.2% (2010), and the mean age at time of diagnosis was 47-50 years. We identified a total of 12 719 patients with PsA (prevalence=0.22%), including 9034 patients where the PsA diagnosis was made by a rheumatologist (prevalence=0.16%). Incidence rates of PsA (per 100 000 person-years) increased from 7.3 in 1997 to a peak incidence of 27.3 in 2010. Incidence rates were highest for women and patients aged 50-59 years, respectively. The use of systemic non-biologic agents, that is, methotrexate, leflunomide, ciclosporin or sulfasalazine increased over the 15-year study course and were used in 66.3% of all patients. Biologic agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab or ustekinumab) were used in 17.7% of patients with PsA.

Conclusions: We found a clear trend of rising PsA incidence on a national level. While the cause remains unclear, our findings might be explained by increased attention by patients and physicians.
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http://dx.doi.org/10.1136/annrheumdis-2016-210963DOI Listing
September 2017

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

Lancet 2017 May 22;389(10083):2031-2040. Epub 2017 Mar 22.

Department of Dermatology, Rouen University Hospital and INSERM U1234, Centre de référence des maladies bulleuses autoimmunes, Normandie University, Rouen, France.

Background: High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.

Methods: We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1:1) to receive either oral prednisone alone, 1·0 or 1·5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0·5 or 1·0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589.

Findings: Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38·4-71·7; p<0·0001. This difference corresponded to a relative risk of success of 2·61 (95% CI 1·71-3·99, p<0·0001), corresponding to 1·82 patients (95% CI 1·39-2·60) who would need to be treated with rituximab plus prednisone (rather than prednisone alone) for one additional success. No patient died during the study. More severe adverse events of grade 3-4 were reported in the prednisone-alone group (53 events in 29 patients; mean 1·20 [SD 1·25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean 0·59 [1·15]; p=0·0021). The most common of these events in both groups were diabetes and endocrine disorder (11 [21%] with prednisone alone vs six [22%] with rituximab plus prednisone), myopathy (ten [19%] vs three [11%]), and bone disorders (five [9%] vs five [19%]).

Interpretation: Data from our trial suggest that first-line use of rituximab plus short-term prednisone for patients with pemphigus is more effective than using prednisone alone, with fewer adverse events.

Funding: French Ministry of Health, French Society of Dermatology, Roche.
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http://dx.doi.org/10.1016/S0140-6736(17)30070-3DOI Listing
May 2017

Risk of Aggressive Skin Cancers After Kidney Retransplantation in Patients With Previous Posttransplant Cutaneous Squamous Cell Carcinomas: A Retrospective Study of 53 Cases.

Transplantation 2017 Apr;101(4):e133-e141

1 Department of Dermatology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. 2 Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. 3 Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Unité de Recherche Clinique, Lyon, France. 4 Université de Lyon, Laboratoire Santé Individu Société, Lyon, France. 5 Department of Dermatology, Nantes University Medical Center, Nantes, France. 6 Department of Dermatology, Saint Louis Hospital, APHP, University Paris VII, Paris, France. 7 Department of Dermatology, Tenon Hospital, APHP, University Paris VI, Paris, France. 8 Department of Transplantation and Nephrology, Edouard Herriot Hospital, Université de Lyon, Lyon, France. 9 Department of Nephrology-Transplantation, Necker Hospital, APHP, Paris, France. 10 Department of Dermatology, Charles-Nicolle University Medical Center, Rouen, France. 11 Department of Renal Medicine and Transplantation, Nantes University Medical Center, Nantes, France.

Background: The course of skin cancer after retransplantation in organ-transplant recipients who have already developed posttransplant skin cancer has not been assessed.

Methods: This retrospective multicentric study included 53 patients with a history of cutaneous squamous cell carcinoma (SCC) after a first kidney transplantation who received a second kidney transplantation. The primary endpoint was the occurrence of aggressive cutaneous SCC after the second transplantation. Secondary endpoints included the course of skin cancers over 3 periods (first transplantation, return to dialysis, second transplantation), the time to occurrence, and risk factors for aggressive SCC after retransplantation.

Results: The first SCC developed in 47 patients with a functional graft and in 6 after return to dialysis. After the first transplantation, 17 (33.3%) patients developed SCC in dialysis and 39 (73.6%) after the second transplantation, respectively. Twenty aggressive SCC developed over the study period. They occurred in 14 (26.4%) patients after retransplantation vs 5 (9.4%) after the first transplantation with a median delay of 50 months and were responsible for 5 deaths. Fair skin type, multiple tumors before retransplantation, treatment with azathioprine, T cell-depleting antibodies, and delayed revision of immunosuppression were associated with an increased risk of aggressive cutaneous SCC after retransplantation.

Conclusions: Candidates to retransplantation with a history of posttransplant SCC have a high risk of aggressive SCC. Our data suggest that the risk could be reduced by a tailored immunosuppression. A wait period may be required depending on the clinicopathological characteristics of the previous SCC and discussed on an individual patient basis.
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http://dx.doi.org/10.1097/TP.0000000000001644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228575PMC
April 2017

Chromatibody, a novel non-invasive molecular tool to explore and manipulate chromatin in living cells.

J Cell Sci 2016 07 20;129(13):2673-83. Epub 2016 May 20.

Toxalim, Université de Toulouse, INRA, Université de Toulouse 3 Paul Sabatier, 31027 Toulouse, France

Chromatin function is involved in many cellular processes, its visualization or modification being essential in many developmental or cellular studies. Here, we present the characterization of chromatibody, a chromatin-binding single-domain, and explore its use in living cells. This non-intercalating tool specifically binds the heterodimer of H2A-H2B histones and displays a versatile reactivity, specifically labeling chromatin from yeast to mammals. We show that this genetically encoded probe, when fused to fluorescent proteins, allows non-invasive real-time chromatin imaging. Chromatibody is a dynamic chromatin probe that can be modulated. Finally, chromatibody is an efficient tool to target an enzymatic activity to the nucleosome, such as the DNA damage-dependent H2A ubiquitylation, which can modify this epigenetic mark at the scale of the genome and result in DNA damage signaling and repair defects. Taken together, these results identify chromatibody as a universal non-invasive tool for either in vivo chromatin imaging or to manipulate the chromatin landscape.
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http://dx.doi.org/10.1242/jcs.183103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958301PMC
July 2016

Hidradenitis suppurativa (HS): An unrecognized paradoxical effect of biologic agents (BA) used in chronic inflammatory diseases.

J Am Acad Dermatol 2016 Jun 8;74(6):1153-9. Epub 2016 Mar 8.

Dermatology Department, Hôpital Edouard Herriot, Université Claude Bernard Lyon I, Lyon, France.

Background: Paradoxical hidradenitis suppurativa (HS) induced by biologic agents (BA) is scarcely reported.

Objective: We sought to describe the clinical characteristics and outcome of patients developing paradoxical HS under BA.

Methods: This was a multicenter nationwide retrospective study asking physicians to report all cases of HS, confirmed by a dermatologist, occurring during treatment of an inflammatory disease by a BA.

Results: We included 25 patients (15 inflammatory rheumatism, 9 Crohn's disease, 1 psoriasis) treated by 5 BA (adalimumab = 12, infliximab = 6, etanercept = 4, rituximab = 2, tocilizumab = 1). Median duration of BA exposure before HS onset was 12 (range 1-120) months. Patients were mostly Hurley stage I (n = 13) or II (n = 11). Simultaneously to HS or within 1 year, 11 patients developed additional inflammatory diseases, including paradoxical reactions (psoriasis = 9, Crohn's disease = 3, alopecia areata = 1, erythema elevatum diutinum = 1). Complete improvement of HS was more frequently obtained after BA discontinuation or switch (n = 6/10, 60%) rather than maintenance (n = 1/14, 7%). Reintroducing the same BA resulted in HS relapse in 3 of 3 patients.

Limitations: Retrospective nature and lack of complete follow-up for some patients are limitations.

Conclusion: HS is a rare paradoxical adverse effect of BA, but fortuitous association cannot be excluded in some cases. We observed a trend toward better outcome when the BA was discontinued or switched.
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http://dx.doi.org/10.1016/j.jaad.2016.01.018DOI Listing
June 2016

Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis.

J Am Acad Dermatol 2015 Aug 6;73(2):242-8. Epub 2015 Jun 6.

Department of Dermatology at Hôpital Edouard Herriot, Université Claude Bernard Lyon 1, Lyon, France.

Background: Skin psoriasis precedes the onset of psoriatic arthritis (PsA) in 84% of patients with psoriasis. Dermatologists have an important role to screen psoriasis patients for PsA. The efficiency of PsA screening remains unknown.

Objective: We sought to determine the point prevalence of undiagnosed PsA in patients with psoriasis using a systematic search of the literature and meta-analysis.

Methods: PubMed, Cochrane, and Embase database searches yielded 394 studies for review. No study aimed to determine the prevalence of undiagnosed PsA in patients with psoriasis. We assumed that the prevalence of newly diagnosed PsA in patients with psoriasis at the time they seek medical care could be a sound estimate of this value. Seven epidemiological studies and 5 studies on PsA screening questionnaires allowed us to clearly identify patients with newly diagnosed PsA and were selected for review.

Results: The prevalence of undiagnosed PsA was 15.5% when all studies were considered and 10.1% when only epidemiological studies were considered.

Limitations: Data were obtained from studies not designed to address the question at hand. Heterogeneity was high (I(2) = 96.86%), and therefore a random effects model was used.

Conclusion: The high prevalence of undiagnosed PsA in patients with psoriasis adds to the recommendation that dermatologists need to screen all patients with psoriasis for PsA.
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http://dx.doi.org/10.1016/j.jaad.2015.05.001DOI Listing
August 2015

Acrodermatitis continua of Hallopeau treated successfully with ustekinumab and acitretin after failure of tumour necrosis factor blockade and anakinra.

Dermatology 2015 27;230(2):97-100. Epub 2014 Nov 27.

Dermatology Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.

Acrodermatitis continua of Hallopeau (ACH) is a rare form of chronic acral pustular eruption. Considered to be a variant of pustular psoriasis, it is a refractory condition that may not respond to conventional treatments. We report herein the case of a 53-year-old patient whose ACH was refractory to all conventional systemic treatment modalities and to anti-tumour necrosis factor. Because he had increased plasma levels of interleukin (IL)-1β, he received anakinra for 7 weeks, without further improvement however. Achievement of complete response was obtained with ustekinumab 90 mg s.c. every 12 weeks combined with acitretin; the plasma level of IL-1β concomitantly returned to normal. This case report is associated with a review on recent data on ACH treatment with biological agents, including anakinra and ustekinumab.
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http://dx.doi.org/10.1159/000367690DOI Listing
December 2015

Hidradenitis suppurativa after renal transplantation: complete remission after switching from oral cyclosporine to oral tacrolimus.

J Am Acad Dermatol 2014 Nov 15;71(5):e210-1. Epub 2014 Oct 15.

Department of Dermatology, Edouard Herriot Hospital Group, Hospices Civils de Lyon, Lyon, France.

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http://dx.doi.org/10.1016/j.jaad.2014.06.031DOI Listing
November 2014