Publications by authors named "Cristina Bulai-Livideanu"

31 Publications

VEXAS syndrome in a patient with previous spondyloarthritis with favorable response to intravenous immunoglobulin anti-IL17 therapy.

Rheumatology (Oxford) 2021 Mar 10. Epub 2021 Mar 10.

Rheumatology Department, Pierre-Paul Riquet University Hospital, Toulouse III-Paul Sabatier University, Toulouse, France.

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http://dx.doi.org/10.1093/rheumatology/keab211DOI Listing
March 2021

Tapinarof-induced folliculitis: The paradigm of activation of the aryl hydrocarbon signaling pathway.

J Am Acad Dermatol 2021 Mar 4. Epub 2021 Mar 4.

Dermatology Department, Paul Sabatier University, University Hospital of Toulouse, Toulouse, France.

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http://dx.doi.org/10.1016/j.jaad.2021.01.104DOI Listing
March 2021

Neuropsychiatric, cognitive and sexual impairment in mastocytosis patients.

Orphanet J Rare Dis 2021 Mar 5;16(1):118. Epub 2021 Mar 5.

Mastocytosis National Expert Centre (CEREMAST), Department of Dermatology, Toulouse University Hospital, 24 Chemin de Pouvourville, 31059, Toulouse, France.

Background: Mastocytosis is a rare disease characterised by the accumulation and/or proliferation of abnormal mast cells (MCs) in one or several organs. It may present with a number of different symptoms that involve various organ systems. The current study aims to assess the prevalence of MC mediator-related symptoms in a cohort of mastocytosis patients with a specific focus on neurological, psychiatric, cognitive and sexual symptoms. We also assessed the impact of the disease on patients' professional lives. Patients were administered a validated multidimensional questionnaire to collect information on patients' perception of the severity of their symptoms. From the questionnaires we extracted the neurological, cognitive, psychiatric and sexual symptoms and the impact of the disease on patients' professional lives as well as their grading. The affective status was assessed using the 17-item version of the Hamilton Depression Rating Scale.

Results: We included 139 patients. Mastocytosis was classified as systemic in 113 patients and cutaneous in 26 patients. The prevalence of MC mediator-related systemic symptoms was as follows: cutaneous (71%), gastro-intestinal (48%), cardio-vascular (36%), musculoskeletal (26.6%), fatigue (24%), urinary (14.4%) and respiratory (10%). Headaches and vertigo were noted in respectively 55% and 32% of patients. Irritability, episodes of memory loss and difficulty concentrating were reported in 54%, 52% and 40% of cases, respectively. Sexual impairment was noted in 24% of patients. No associations were found between neuropsychiatric/cognitive impairment and age, gender, diagnostic delay, disease form, the presence of cutaneous lesions, the level of serum and bone marrow tryptase and the presence of KIT mutation in bone marrow and/or skin. Depression was noted in 49% of patients. One in four patients reported a negative impact of the disease on their professional lives.

Conclusion: This current study provides some insights regarding symptoms related to mastocytosis and their impact on patients' professional lives.
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http://dx.doi.org/10.1186/s13023-021-01747-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934538PMC
March 2021

532 nm Q-switched laser for the treatment of hyperpigmentation induced by topical tacrolimus.

J Cosmet Laser Ther 2020 Feb 21;22(2):90-92. Epub 2020 Mar 21.

Department of Dermatology, Paul Sabatier University, Toulouse University Hospital, Toulouse, France.

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http://dx.doi.org/10.1080/14764172.2020.1740273DOI Listing
February 2020

Omalizumab in the treatment of adult patients with mastocytosis: A systematic review.

Clin Exp Allergy 2020 06 25;50(6):654-661. Epub 2020 Mar 25.

Department of Dermatology, Mastocytosis National Reference Center (CEREMAST), Toulouse University Hospital, Toulouse, France.

BACKGROUND: Mastocytosis is associated with mast cell (MC) mediator-related symptoms for which limited therapies are available. OBJECTIVE: Our aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator-related symptoms in adult patients with mastocytosis. RESULTS: We identified one multi-centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post-honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients. CONCLUSIONS AND CLINICAL RELEVANCE: Omalizumab appears to prevent some life-threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.
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http://dx.doi.org/10.1111/cea.13592DOI Listing
June 2020

Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Blood 2020 04;135(14):1101-1110

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Antoine, Service de Médecine Interne, Paris, France.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.
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http://dx.doi.org/10.1182/blood.2019002300DOI Listing
April 2020

Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS.

J Allergy Clin Immunol Pract 2019 Sep - Oct;7(7):2387-2395.e3. Epub 2019 Apr 5.

Imagine Institute, INSERM U1163 and CNRS ERL 8654, Paris Descartes University, Sorbonne Paris Cité, Paris, France; Department of Hematology, Necker Children's Hospital, APHP, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Necker Children's Hospital, APHP, Paris, France.

Background: Patients with mast cell diseases may suffer from various distressing symptoms, which can be insufficiently controlled with available therapies, severely affecting their quality of life. There is a need for new and safe treatment options for these patients.

Objectives: We aimed to evaluate safety and efficacy of omalizumab administration in patients with a symptomatic mast cell disorder.

Methods: We included 55 patients with a mast cell disorder associated with debilitating symptoms who received omalizumab treatment between January 2015 and December 2017, after a multidisciplinary team meeting at the French National Reference Center for Mastocytosis.

Results: A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (54.5%), and a partial response for 12 patients (21.8%), resulting in an overall best response rate of 78.2% (43 of 55 patients). The response was persistent at least 3 months in 33 of 43 responding patients (76.7%). At the last follow-up, the final overall response rate was 58.2% (32 of 55 patients). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms. Safety profile was acceptable, except for one severe adverse event (edema of the larynx and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (29%), mainly of low to mild intensity, yet causing interruption of treatment in 5 patients (9%).

Conclusion: Omalizumab seems to be a useful therapeutic option to control mast cell-mediator symptoms and displays a favorable safety profile.
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http://dx.doi.org/10.1016/j.jaip.2019.03.039DOI Listing
October 2020

Combining Omalizumab with Another Biotherapy.

Acta Derm Venereol 2019 Apr;99(4):448-449

Department of Dermatology, Military Teaching Hospital Bégin, 69 avenue de Paris, FR-94160 Saint Mandé, France. E-mail:

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http://dx.doi.org/10.2340/00015555-3140DOI 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

Hydroxychloroquine as a novel therapeutic approach in mast cell activation diseases.

Clin Immunol 2018 09 10;194:75-79. Epub 2018 Jul 10.

Inserm, U1037, Centre de Recherche en Cancérologie de Toulouse (CRCT), Toulouse F-31037, France; Paul Sabatier University, Mastocytosis National Reference Center (CEREMAST), Department of Dermatology, Toulouse University and CHU, Toulouse, France. Electronic address:

There is no therapeutic agent approved in cutaneous mastocytosis and mast cell activation syndrome. We report the efficacy of hydroxychloroquine in four patients with cutaneous mastocytosis (n = 2) and mast cell activation syndrome (n = 2). We show that this molecule reduces the long-term survival of primary human mast cells, interferes with lysosome function and leads to the accumulation of non-functional tryptase in the mast cell granules. Furthermore, hydroxychloroquine decreases the production of pro-inflammatory mediators.
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http://dx.doi.org/10.1016/j.clim.2018.07.004DOI Listing
September 2018

Prevalence of CD30 immunostaining in neoplastic mast cells: A retrospective immunohistochemical study.

Medicine (Baltimore) 2018 May;97(21):e10642

UMR U.1037, Centre de recherche sur cancer de Toulouse, Université Paul-Sabatier Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopole Department of Dermatology, Paul Sabatier University, Mastocytosis National Reference Center (CEREMAST), Toulouse University and CHU, Toulouse, France Laboratory of Molecular and Investigative Pathology-LAPE, Faculty of Medical Sciences, State University of Campinas Medical School, Campinas, Brazil Laboratoire d'excellence Labex TOUCAN, Toulouse, France.

Mastocytosis is a rare disease characterized by clonal neoplastic proliferation of mast cells (MCs). It ranges from skin lesions as cutaneous mastocytosis (CM) which may spontaneously regress to highly aggressive neoplasms with multiorgan involvement corresponding to some aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL), and/or mast cell sarcoma (MCS).There is increasing evidence of CD30 expression in neoplastic MCs of the bone marrow. This expression has been described almost exclusively in aggressive forms of systemic mastocytosis (SM).The aim of the present study is to evaluate CD30 expression both in cutaneous and systemic forms of mastocytosis. Forty-two mastocytosis cases were reviewed, including cutaneous (n = 29) and systemic (n = 13) forms to assess the prevalence of CD30 expression. Thirty-nine out of 42 (92.8%) cases were CD30 positive. In cases of CM, 28/29 (96.5%) cases were CD30 positive, 11/13 cases of SM (84.6%) were positive for CD30. MCs in normal skin biopsies and in urticaria lesions were CD30-negative. This study found that CD30 is also frequently expressed in CM as well as in systemic forms. This finding is a major departure from the prevailing concept that CD30 expression is often related to aggressive systemic forms of mastocytosis.
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http://dx.doi.org/10.1097/MD.0000000000010642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392733PMC
May 2018

Extracorporeal Photopheresis: An Efficacious and Well-Tolerated Treatment for Cutaneous and Oral Mucosal Chronic Graft-versus-Host Disease.

Dermatology 2018 22;234(1-2):23-30. Epub 2018 May 22.

Dermatology Department, University Hospital and Paul Sabatier University of Toulouse, Toulouse, France.

Background: Extracorporeal photopheresis (ECP) is a second-line therapy for steroid-refractory chronic graft-versus-host disease (cGVHD).

Objective: We describe the long-term efficacy and tolerability of ECP according to the cutaneous phenotype of cGVHD and report on the reduced need for immunosuppressant drugs in this setting.

Patients And Methods: Fourteen patients (8 females) with cutaneous and/or mucosal cGVHD, treated with ECP between October 2010 and May 2016 within a single center, were included. Final analyses included patients who had received ECP for at least 12 months. We prospectively evaluated the efficacy of ECP using lesion-specific clinical scores and by recording changed doses of systemic immunosuppressants.

Results: Of the 14 patients, sclerotic skin lesions were present in 10 (71%). The mRODNAN score decreased in all patients from month 9 onwards, with 40 and 77% reductions at 12 and 36 months, respectively. Six patients (43%) presented with cutaneous lichenoid lesions: this score was reduced in all patients by month 3, reaching a 93% reduction by month 12. Five patients (36%) experienced oral mucosal lichenoid lesions: these scores were decreased by 55% at month 12 and by 100% by month 33. The use of systemic immunosuppressants was reduced in all patients; 4 patients could stop all immunosuppressant drugs after 2 years. ECP was stopped in 3 patients after a complete response. No major ECP-associated adverse effects were observed.

Discussion And Conclusion: ECP was an effective long-term therapy for oral and cutaneous cGVHD: consequently, dose levels of therapeutic immunosuppression could be reduced.
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http://dx.doi.org/10.1159/000488238DOI Listing
January 2019

Palmar erythema: inaugural manifestation of HIV infection.

Eur J Dermatol 2017 12;27(6):668-669

Service de Dermatologie, CHU Toulouse Larrey, Université Paul Sabatier, Toulouse, France.

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http://dx.doi.org/10.1684/ejd.2017.3146DOI Listing
December 2017

Prevalence and risk factors for fragility fracture in systemic mastocytosis.

Bone 2017 Dec 14;105:219-225. Epub 2017 Sep 14.

Department of Dermatology, Mastocytosis Expert Center of Midi-Pyrénées, Paul Sabatier University, Toulouse University Hospital, Toulouse, France. Electronic address:

Objectives: Systemic mastocytosis (SM) is characterized by the accumulation of mast cells in tissues other than the skin. Bone involvement although frequent has not been thoroughly evaluated. Primary objective was to determine risk factors associated with fragility fractures (FF) in SM. Secondary objectives were to evaluate the ability of bone marrow tryptase (BMT) level to identify patients with FF, and to describe bone involvement in SM.

Methods: We analyzed retrospectively all consecutive patients seen in our expert center, with a diagnosis of SM according to the 2001 WHO criteria, and with complete bone assessment. We collected data about lifetime fractures, types of cutaneous manifestations, degranulation symptoms, blood and BMT levels, bone mineral density assessed by densitometry and KIT mutation. We performed a univariate analysis investigating the factors associated with FF and then a logistic multivariable regression analysis. We assessed the ability of bone marrow tryptase to identify patients with FF.

Results: Eighty-nine patients with SM were included. Thirty-six patients (40.4%) suffered from osteoporosis and twenty-five (28.1%) experienced lifetime FF. Univariate analysis identified age at diagnosis and disease onset, presence of telangiectasia macularis eruptiva perstans, digestive symptoms, mast cells activation symptoms, elevated BMT, low femoral and lumbar BMD, as associated with FF. Multivariate analysis identified elevated BMT, low femoral T score and older age at diagnosis as independently associated with FF.

Conclusions: Low femoral T-score, BMT level, and older age at diagnosis are markers associated with FF in SM. BMT may represent an important biomarker to predict FF in SM patients.
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http://dx.doi.org/10.1016/j.bone.2017.09.005DOI Listing
December 2017

Efficacy of hospital inpatient topical treatment for severe adult atopic dermatitis: a retrospective study of 56 patients.

Eur J Dermatol 2017 08;27(4):418-419

Department of Dermatology, Larrey Hospital and Toulouse University, Toulouse, France, UDEAR-INSERM 1056, Toulouse, France.

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http://dx.doi.org/10.1684/ejd.2017.3033DOI Listing
August 2017

Azathioprine Hypersensitivity Syndrome: Two Cases of Febrile Neutrophilic Dermatosis Induced by Azathioprine.

Case Rep Dermatol 2017 Jan-Apr;9(1):6-11. Epub 2017 Jan 19.

Paul Sabatier University, University Hospitals of Toulouse, Toulouse, France; Department of Dermatology, University Hospitals of Toulouse, Toulouse, France.

Background: Azathioprine is an immunosuppressive agent used in the treatment of immune-mediated diseases. Azathioprine hypersensitivity syndrome is a rare adverse reaction occurring a few days to weeks after the administration of azathioprine.

Case 1: A 36-year-old male with ulcerative colitis presented with erythematous plaques, pustules and erosions on the lower back, buttocks and thighs associated with high fever (39°C) 2 weeks after the initiation of azathioprine 100 mg/day. Additional findings included leukocytosis (18.6 g/L) with neutrophilia (11.1 g/L) and elevated C-reactive protein (128 mg/L). Histopathology showed a dense infiltrate of neutrophils in the hair follicles. We increased the dose of prednisone to 1 mg/kg/day (60 mg/day) and azathioprine was discontinued. He had marked improvement within 3 weeks and did not have any relapse with a 1-year follow-up.

Case 2: A 57-year-old male with ulcerative colitis presented with erythematous plaques and pustules on the lower limbs associated with high fever (40°C) 1 week after the initiation of azathioprine 75 mg/day. Leukocytosis with neutrophilia (13.6 g/L) and elevated C-reactive protein (344 mg/L) were among the laboratory findings. Histopathology showed a dense infiltrate of neutrophils in the hair follicles. The dose of prednisone was increased to 20 mg/day and azathioprine was discontinued, which led to complete remission within 7 days. He did not have any relapse with a 6-month follow-up.

Conclusion: The development of acute neutrophilic dermatitis 2 weeks after the initiation of azathioprine and the complete resolution after its withdrawal were in favor of azathioprine hypersensitivity syndrome. It should not be confused with Sweet syndrome associated with inflammatory bowel disease, as maintenance of azathioprine treatment may lead to life-threatening reactions.
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http://dx.doi.org/10.1159/000454876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301102PMC
January 2017

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study.

Lancet 2017 02 7;389(10069):612-620. Epub 2017 Jan 7.

Department of Hematology, Université Paris Descartes, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; Institut Imagine INSERM U1163 and CNRS ERL8654, Université Paris Descartes, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France; AB Science, Paris, France. Electronic address:

Background: Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18-75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8-24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073.

Findings: Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible responses [weighted generalised estimating equation]) compared with 7·4% for placebo (48·9 of 656·5; difference 11·3%; odds ratio 3·6; 95% CI 1·2-10·8; p=0·0076). Frequent severe adverse events (>4% difference from placebo) were diarrhoea (eight [11%] of 70 in the masitinib group vs one [2%] of 63 in the placebo group), rash (four [6%] vs none), and asthenia (four [6%] vs one [2%]). The most frequent serious adverse events were diarrhoea (three patients [4%] vs one [2%]) and urticaria (two [3%] vs none), and no life-threatening toxicities occurred. One patient in the placebo group died (unrelated to study treatment).

Interpretation: These study findings indicate that masitinib is an effective and well tolerated agent for the treatment of severely symptomatic indolent or smouldering systemic mastocytosis.

Funding: AB Science (Paris, France).
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http://dx.doi.org/10.1016/S0140-6736(16)31403-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985971PMC
February 2017

Enzalutamide induced acute generalized exanthematous pustulosis.

J Dermatol Case Rep 2016 Nov 13;10(2):35-38. Epub 2016 Nov 13.

Paul Sabatier University, Department of Dermatology, Larrey Hospital and Institut Universitaire du Cancer, Toulouse, France.

Introduction: (Xtandi®) is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013.

Objective: We report the first case of acute generalized exanthematous pustulosis (AGEP) induced by .

Observation: A 62-year-old male patient with no significant medical history, was diagnosed in April 2014 with metastatic prostatic adenocarcinoma. In April 2015 the patient received a second line oral therapy with , 160 mg/day, coupled with a subcutaneous implant of 10.8 mg of , an agonist analog of natural luteinising hormone releasing hormone (LH-RH). Ten days after starting treatment and four days after introduction of first subcutaneous implant, the patient experienced an acute skin reaction. It is about of the plaques covered with widespread millimetric non-follicular pustules. Complete resolution of skin lesions occurred within four weeks. According to the AGEP validation score of the European Study of Severe Cutaneous Adverse Reactions, the total score in the current case was 7, interpreted as probable AGEP. According to criteria that assess adverse drug reactions, it was concluded that was responsible for this case of AGEP (suggestive imputation).

Conclusions: Dermatologist can be confronted with adverse skin drug reactions attributable to new therapeutic molecules. The slow resolution of symptoms seems be due to the long half-life of .
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http://dx.doi.org/10.3315/jdcr.2016.1226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124370PMC
November 2016

Photo-induced graft-versus-host disease.

Photodermatol Photoimmunol Photomed 2016 Sep 19;32(5-6):291-295. Epub 2016 Oct 19.

Department of Dermatology, Toulouse University Hospital, Paul Sabatier University, Toulouse, France.

Overlap chronic graft-versus-host disease (GVHD) associates both features of acute and chronic GVHD. Trigger factors for chronic GVHD are unclear. We describe two patients who received allogenic haematopoietic stem-cell transplantation, and who later developed overlap chronic GVHD after sun exposure. Available data from in vivo investigations suggest ultraviolet B radiation (UVB) has a beneficial effect on acute and chronic GVHD. The role of sun irradiation as a trigger for isomorphic cutaneous GVHD has been rarely reported in the literature. Herein, we demonstrate for the first time, using repetitive broadband phototesting, that UVB triggers chronic GVHD.
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http://dx.doi.org/10.1111/phpp.12273DOI Listing
September 2016

Surgical Treatment of Facial Basal Cell Carcinoma: Patient-Based Assessment of Clinical Outcome in a Prospective Cohort Study.

Dermatology 2016 28;232(5):550-557. Epub 2016 Sep 28.

Department of Dermatology, Paul Sabatier University and Toulouse University Cancer Institute, Toulouse, France.

Background: There are limited data on the esthetic, functional, and morphological outcomes of surgical treatment of facial basal cell carcinoma (BCC).

Objective: The aim of our study was to assess the determinants of the evaluation of both the patients and the investigator of the esthetic, functional, and morphological impact of the surgical treatment of facial BCC.

Methods: A prospective observational study evaluated 111 patients treated surgically for facial BCCs (n = 135 BCCs), using the Patient and Observer Scar Assessment Scale (POSAS), a validated and reliable scale designed for the evaluation of all types of scars by professionals and patients.

Results: Scar assessment rated by the patients was very good. Skin aging was associated with a better surgical outcome as evaluated by POSAS (OR = 0.30, 95% CI: 0.09-0.98; p = 0.04). Conversely, histologically infiltrative or sclerosing BCC (OR = 2.33, 95% CI: 0.95-5.71; p = 0.06) was independently associated with poorer POSAS. In terms of the investigator's evaluation, aging signs (protective factor: OR = 0.17, 95% CI: 0.04-0.73; p = 0.01), location on the H-zone of the face (risk factor: OR = 2.95, 95% CI: 1.07-8.15; p = 0.03), and histologically infiltrative or sclerosing BCC (risk factor: OR = 2.89, 95% CI: 1.01-8.29; p = 0.04) were independently associated with POSAS.

Conclusion: Esthetic, functional, and morphological outcomes of facial BCC surgery provide high patient satisfaction overall. Taking wider margins requires specific measures to improve the surgical outcome.
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http://dx.doi.org/10.1159/000447354DOI Listing
July 2017

Improvement of Microstomia in Scleroderma after Carbon Dioxide Laser Treatment.

Case Rep Dermatol 2016 May-Aug;8(2):142-50. Epub 2016 May 24.

Department of Dermatology, Paul Sabatier University, Toulouse, France.

Limited mouth opening (LMO) is a frequent complication of systemic sclerosis (SS). Its management is complex and there are limited treatment options. We report four patients with SS and severe LMO [interincisal distance (IID) <30 mm] treated with pulsed carbon dioxide (CO2) laser. Pulsed CO2 laser treatment of the white lips was performed after all patients had signed a written informed consent in the absence of alternative treatment. Treatment was carried out under locoregional anaesthesia using a Sharplan 30C CO2 laser in the Silk Touch® resurfacing mode. One to three laser sessions were performed at intervals of 8-12 months between sessions. Assessments were performed at 3 and 12 months with measurement of the IID using a ruler, calculation of the Mouth Handicap in Systemic Sclerosis (MHISS) scale and global evaluation by the patients. Adverse events were also reported. In all four patients, an improvement in IID occurred 3 months after the first session with a mean gain of +5 mm (range: 2-7). At 12 months, a mean gain of +8.5 mm (range: 7-10) in IID was observed. The MHISS score decreased by a mean of •14 (range: 11-17). All patients showed improvement of lip flexibility or mouth opening, allowing better phonation and mastication and easier dental care. Adverse effects were transient erythema and/or dyschromia. CO2 laser appears to be effective and well tolerated in the improvement of LMO in SS.
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http://dx.doi.org/10.1159/000445821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924459PMC
July 2016

Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

Medicine (Baltimore) 2016 Jun;95(24):e3901

Service de médecine interne, Hôpital Tenon, Université Pierre et Marie Curie, Paris, France Service de Médecine Interne, CHU de Caen, Université Basse Normandie, Caen, France Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire, Université de Caen-Basse Normandie, Caen, France Faculté de Médecine et AP-HP Necker-Enfants Malades, Centre de Référence des Mastocytoses, Paris Cedex 15, France Inserm, U1068, CRCM [Signaling, Hematopoiesis and Mechanism of Oncogenesis], Institut Paoli-Calmettes,Marseille, Aix-Marseille Univ, CNRS, UMR7258, Marseille, France Mastocytosis Competence Center of Midi-Pyrénées, Department of Dermatology, Toulouse University Hospital, Toulouse, France Service de Médecine Interne, Université Claude Bernard Lyon1, Groupe Hospitalier Lyon-Sud. Chemin du Grand Revoyet, Pierre Bénite, France Service de Dermatologie, Hôpital Tenon, Université Pierre et Marie Curie-Paris 6, Paris, France Service d'Hématologie Adultes, Université Paris Descartes, Paris Sorbonne Cité, Faculté de Médecine et AP-HP Necker-Enfants Malades, Institut Imagine, Université Paris Descartes, Paris Cedex 15, France Service de Médecine interne, Hôpital St Antoine, Université Pierre et Marie Curie-Paris 6, Paris, France Service de Médecine interne, Université de Rennes 1, Hôpital Sud CHU Rennes, Rennes, France Service de Médecine interne, Hôpital Pitié Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France Service de Médecine interne, CHU, Nantes, France Service de Médecine interne, Hôpital Européen Georges Pompidou, Université Paris 5, Paris, France Université de Lille, UFR Médecine, Lille, France; CHRU Lille, Pôle Spécialités Médicales et Gérontologie, Département de Médecine Interne et Immunologie Clinique, Lille Cedex, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), Lille Cedex, France; LIRIC UMR 995, EA2686, France Médecine interne et Maladies vasculaires. Centre de compétences Maladies rares CHU, Angers, France Laboratoire d'Hématologie, Groupe Hospitalier Pitié-Salpêtrière 83, Bd de l'Hôpital, Paris, France LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France Université Paris Descartes, Service de Maladies Infectieuses et Tropicales, Université Paris Descartes, Sorbonne, Paris 6, AP-HP, Hôpital Necker-Enfants malades, Centre d'Infectiologie Necker-Pasteur, IHU Imagine, Paris.

Mastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.
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http://dx.doi.org/10.1097/MD.0000000000003901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998476PMC
June 2016

Angiolymphoid hyperplasia with eosinophilia treated with low-dose methotrexate.

JAAD Case Rep 2015 Nov 27;1(6):342-4. Epub 2015 Sep 27.

Paul Sabatier University, Toulouse, France; Department of Dermatology, University Hospitals of Toulouse, Toulouse, France.

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http://dx.doi.org/10.1016/j.jdcr.2015.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809377PMC
November 2015

Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

J Am Acad Dermatol 2016 Jul 19;75(1):64-8. Epub 2016 Mar 19.

Department of Dermatology of Nice, University Hospital of Nice, Nice, France.

Background: There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS).

Objective: We sought to characterize patients with hypertrophic PWS presenting during childhood.

Methods: Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded.

Results: A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS.

Limitations: As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation.

Conclusion: PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications.
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http://dx.doi.org/10.1016/j.jaad.2016.02.1167DOI Listing
July 2016

Telangiectasia macularis eruptiva perstans (TMEP): A form of cutaneous mastocytosis with potential systemic involvement.

J Am Acad Dermatol 2016 May 19;74(5):885-91.e1. Epub 2016 Feb 19.

Paul Sabatier University, Toulouse, France; Department of Dermatology, Mastocytosis Competence Center of Midi-Pyrénées, Toulouse University Hospital, Toulouse, France; Mastocytosis Competence Center of Midi-Pyrénées, Toulouse, France; Toulouse University Hospital, Toulouse, France. Electronic address:

Background: Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized.

Objective: We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult patients with cutaneous mastocytosis, and to assess the presence of systemic involvement.

Methods: We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrénées from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated.

Results: Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation-related symptom.

Limitations: Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP.

Conclusion: TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases.
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http://dx.doi.org/10.1016/j.jaad.2015.10.050DOI Listing
May 2016

Association of mastocytosis with inflammatory joint diseases: a series of 31 patients.

Semin Arthritis Rheum 2014 Dec 17;44(3):362-5. Epub 2014 Jun 17.

Department of Hematology, Hôpital Necker EnfantsMalades (AP-HP), Paris, France; Institut Imagine, Université Sorbonne Paris cité, Hôpital Necker-Enfants Malades (AP-HP), Paris, France.

Objectives: We studied the clinical phenotypes and tolerance to treatments in a series of patients affected by both inflammatory joint diseases and mastocytosis.

Methods: This retrospective multicenter study was conducted on behalf of 3 networks focused on mastocytosis, pediatric, and adults' inflammatory joint diseases. Patients who displayed both mastocytosis and inflammatory joint diseases were included.

Results: A total of 31 patients were included. They had spondyloarthritis (SpA) (16 patients), rheumatoid arthritis (6 patients), juvenile idiopathic arthritis (2 patients), and undifferentiated arthritis (7 patients). The median ages at diagnosis of arthritis and mastocytosis were 44 and 40.5 years, respectively. Disease-modifying anti-rheumatic drugs (DMARDs) were required in 22 patients, comprising mostly methotrexate (13 patients), salazopyrin (8 patients), anti-tumor-necrosis-factor agents (7 patients), and corticosteroids (9 patients). They were well tolerated. Adverse events occurred in 2/24 patients receiving non-steroidal anti-inflammatory drugs. The prevalence of SpA among the 600 patients included in the mastocytosis cohort was 2.33%, which is significantly higher than the prevalence of SpA in the French population (p < 0.001).

Conclusions: This study suggests that mastocytosis is associated with a higher prevalence of SpA than expected, and that DMARDs, notably anti-TNFα agents, are well tolerated in patients with mastocytosis. Mast cells might be involved in the development of SpA.
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http://dx.doi.org/10.1016/j.semarthrit.2014.05.016DOI Listing
December 2014

Purpuric lesions induced by UVA1 spectrum (340-400 nm) phototesting in an adult with persistent and severe hydroa vacciniforme.

Photodermatol Photoimmunol Photomed 2010 Apr;26(2):104-6

Department of Dermatology, Paul Sabatier University, Larrey University Hospital, Toulouse, France.

A 28-year-old man had presented a severe photosensitivity since his infancy. In March 2008, the clinical examination showed large crusts on the dorsum of his hands, on the edge of his ears with destruction of the underlying cartilage, and on his nose and cheeks. He also presented erythematosus fibrous scars on the temples. The diagnosis of hydroa vaccinforme was made. Phototesting including repeated UVA1 phototest was strongly positive with purpuric lesions from day 7 to day 10 and hypertrophic scars at day 67. A sequential histological study of the UVA1 triggered lesions was performed and showed bullous cleavage, dense inflammatory infiltrate in the whole dermis with numerous neutrophilic cells, nuclear dusts, superficial focal thrombosis of small blood vessels at day 10. We report an unusual case of hydroa vaccinforme with purpuric lesions leading to fibrous scars and with important infiltration of neutrophils in the dermis of the photoinduced lesions.
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http://dx.doi.org/10.1111/j.1600-0781.2010.00493.xDOI Listing
April 2010