Importance:Diffuse cutaneous mastocytosis (DCM) is a rare and severe subtype of pediatric mastocytosis, characterized by extensive skin involvement. Comprehensive studies on the clinical and molecular features of DCM remain limited. Objective:To describe the clinical, molecular, and treatment-related characteristics and outcomes of a cohort of pediatric patients with a clinical presentation of DCM. Design, Setting, and Participants:This retrospective study analyzed pediatric patients with a clinical presentation of DCM from January 1996 to October 2023 at Necker Children's Hospital in Paris, France. Main Outcome and Measures:Data on clinical presentation, laboratory results, and KIT sequencing from skin biopsies and bone marrow, if available, were collected and analyzed. These data were compared with previously published findings from a pediatric cohort with maculopapular cutaneous mastocytosis (MPCM). Results:The study included 33 pediatric patients, 18 (54.5%) of whom were male, with a clinical presentation of DCM, including 4 with aggressive systemic mastocytosis (ASM) and 29 with DCM. The mean (SD) age at the onset of the first clinically significant signs was 2.2 (2.2) months. A disease-revealing massive bullous eruption was noted in 9 patients (27.2%). Compared to MPCM, patients with a clinical presentation of DCM had a higher mean baseline serum tryptase level (47.5 μg/L [SD, 38.7; range, 5.0-178.0 μg/L] vs 7.4 μg/L [SD, 6.4; range, 1-45.2]; P < .001), a higher prevalence of anaphylaxis (4 [12.1%] vs 5 [2.4%]; P = .02), and a more frequent association with ASM (4 [12.1%] vs 2 [0.9%]; P = .004). KIT codon 816 variants were identified in 4 patients (19.0%), other KIT variants in 14 patients (66.7%), and wild-type KIT in 3 patients (14.3%). All 4 patients with KIT codon 816 variants had ASM. Seven patients (21.2%) received early systemic treatment (imatinib, midostaurin, or sirolimus depending on the type of KIT variants), starting at a mean (SD) age of 80.8 (135.6) months and continuing for a mean (SD) of 4.0 (2.6) years, with generally good tolerance and efficacy. Of the 15 patients without systemic treatment for more than 6 years, 13 (86.6%) exhibited spontaneous regression. Conclusion and Relevance:In this cohort study, DCM presentation differs significantly from MPCM, with a higher risk of anaphylaxis and aggressive systemic forms, the latter being consistently associated with the KIT D816V variant. Tyrosine kinase inhibitors and sirolimus were generally effective and well tolerated in this pediatric population, with the choice of treatment depending on the type of KIT variants.

Mastocytosis is a clonal disorder driven by KIT mutations, but resistance to tyrosine kinase inhibitors (TKIs) remains a major challenge. Following the discovery of an AXL L197M mutation in a patient with congenital aggressive mastocytosis, we demonstrated unexpected wild-type AXL expression in neoplastic mast cells (MCs) across mastocytosis subtypes, challenging current views concerning mastocytosis pathophysiology. AXL was undetectable in steady-state MCs but several factors, including IFN-α and IFN-β, induced its expression, consistent with the inflammatory nature of mastocytosis and the high interferon levels in patient plasma. Ectopic expression of WT or L197M AXL in the ROSA KIT D816V cell line enhanced proliferation and survival by upregulating pSTAT5, pSTAT3, pFAK, p-p38α, survivin and BCL2. Both AXL forms conferred resistance to the KIT inhibitor PKC412/midostaurin by sustaining BCL2, MCL1, and BCL-XL expression while reducing caspase-3 activation. L197M AXL induced slightly stronger resistance to apoptosis than WT, but this difference was not significant. Combined KIT and AXL targeting (PKC412+R428) restored TKI sensitivity by downregulating BCL-XL, Livin and cIAP1, and activating caspase-3, highlighting the therapeutic potential of dual KIT/AXL pathway inhibition. Importantly, neoplastic MCs from a mast cell leukemia patient harboring the KIT F522C mutation and unresponsive to PKC412 strongly expressed AXL and displayed marked in vitro sensitivity to R428 alone, highlighting AXL as a potential therapeutic target in aggressive mastocytosis not driven by KIT D816V. These findings identify AXL as a previously unrecognized driver of malignant MC survival and TKI resistance, and support AXL inhibition as a promising therapeutic strategy in aggressive mastocytosis. Key Points ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. * AML : acute myeloid leukemia AdvSM : advanced systemic mastocytosis ASM : aggressive systemic mastocytosis BM : bone marrow BMMC : bone marrow mast cell CML : chronic myeloid leukemia CM : cutaneous mastocytosis EMT : epithelial-to-mesenchymal transition FDA : Food and Drug Administration IFNα : interferon alpha IFNβ : interferon beta IFNγ : interferon gamma IHC : immunohistochemistry ISM : indolent systemic mastocytosis TKI : tyrosine kinase inhibitor IPA : Ingenuity pathway analysis MC, MCs : mast cell, mast cells MCL : mast cell leukemia SCF : stem cell factor WBM : whole bone marrow WT : wild type Association Laurette Fugain, https://ror.org/00x20kz95 The French Society of Dermatology (SFD) IDEX-Université Paris Cite- ED561 Institut des Maladies Génétiques Imagine and CARNOT Imagine [1]: pending:yes

Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long-lasting responses are limited. The mutation-Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin-treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM-AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C-index = 0.689), followed by GPSM (C-index = 0.677) and IPSM (C-index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high-risk SM-AHN, 33 months for intermediate/high-risk ASM, 58 months for low-risk SM-AHN and was not reached for low-risk ASM ( p  < 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management.

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation.

BACKGROUND AND AIMS:Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS:Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS:A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS:MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.

Background: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary a-tryptasemia (HaT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. Objective: We evaluated the prevalence of HaT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HaT. Methods: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HaT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. Results: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HaT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HaT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HaT2 patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HaT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). Conclusion: Here we confirm the increase incidence of anaphylaxis in HaT+ mastocytosis patients. The increased prevalence of HaT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement. (J Allergy Clin Immunol 2024;153:349-53.)

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3–22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Introduction: Mastocytosis is a spectrum of diseases characterized by the accumulation of atypical mast cells (MC) in tissues. The most frequent form in adult patients is systemic mastocytosis (SM) including indolent SM, bone marrow mastocytosis, smoldering SM and advanced SM (adv-SM). Adv-SM encompasses aggressive SM (ASM), MC leukemia (MCL), SM associated with hematological neoplasms (SM-AHN) and is associated with a poor outcome. Prior the use of tyrosine kinase inhibitors (TKIs), therapeutic options were limited in adv-SM patients. The first TKI developed for adv-SM with KIT D816V mutation was midostaurin, which greatly improved outcomes for patients. However, most patients are primary refractory or relapse early (<12 months) after midostaurin onset. To identify high risk adv-SM patients, a prognostic score the so-called Mutation-Adjusted Risk Score (MARS) have been developed. However, given the heterogeneity of outcomes according to subtype of adv-SM, the identification of high-risk patients within each subtype is critical to optimize therapy. To address this question, we investigated predictive value on outcome of MARS score risk in midostaurin treated Adv-SM patients in a larger group of patients, according to each subtype of adv-SM. Methods: We conducted a nationwide retrospective study of all patients with Adv-SM patients included in the French national mastocytosis reference center registry (CEREMAST). Main inclusion criteria were: (i) adults patients treated with midostaurin in France since 2009 (ii) diagnosis of adv-SM according to WHO 2016 classification (iii) presence of C findings. Patients that have received combination therapy (i.e. azacytidine) or with chronic type of MCL without C finding or lymphoid neoplasm AHN or AML prior midostaurin onset were excluded. Response to midostaurin was assessed according to Valent criteria and MARS score was used to stratify patients into 3 risk groups (high risk, intermediate and low). Results: Overall, 170 patients treated with midostaurin were identified, including 46 ASM patients, 11 MCL patients and 113 SM-AHN patients. Among SM-AHN patients, chronic myelomonocytic leukemia was the most frequent neoplasm (52%). Response to midostaurin was significantly different regarding subtype of adv-SM (73% in ASM vs 27% in MCL vs 50% in SM-AHN, p=0.006). With a median follow-up of 19 months since midostaurin start, median overall survival (OS) was 69, 9.9 and 32 months (p=0.0013) and time to treatment failure (TTF) was 30, and 3.6 and 9 months in ASM, MCL and SM-AHN (p<0.0001), respectively. MARS risk group distribution was heterogeneous between ASM, MCL and SM-AHN (p=0.026). In MARS low risk group, median OS was not reached (NR) and 58 months in ASM and SM-AHN respectively (p=0.034, Figure 1). Median OS for both low risk ASM and low risk SM-AHN were significantly different compared with intermediate/high-risk (int/high-risk) groups (NR vs 33 months for ASM, p=0.003 and 58 months vs 24 months, p=0.017). Int/high-risk SM-AHN was the only group with a median OS not significantly different compared with MCL (24 months vs 9 months p=0.266) Median TTF was 60 months for low risk ASM, 26 months for low risk SM-AHN and only 6.7 months for high/int-risk ASM, 8.4 months for high/int-risk SM-AHN and 3.6 months for MCL. For the 19 patients who underwent hematopoietic stem cell transplantation (HSCT), median OS was 88 months but did not reach statistical significance compared to non-transplanted patients (47 months, p=0.15). In multivariate analysis, MARS and WHO mastocytosis subtype were the only variables independently associated with OS ( figure 2). MARS and midostaurin response were not predictive for both AHN progression and AML transformation in SM-AHN, which occurred in 31% and, 22% of patients respectively. In contrast, presence of portal hypertension/ascites (68% vs 29%, p<0.001) and abnormal karyotype (40 vs 11%, p=0.007) were predictive of AML transformation. Conclusions: We report herein the largest cohort of adv-SM patients treated with midostaurin. We identified portal hypertension/ascites and karyotype abnormalities as risk factors predictive of AML evolution. Subtype of adv-SM are heterogeneous and, together with MARS, are predictive for both OS and TTF. According to these variables, 5 sub-groups of adv-SM have been identified with different outcomes prompting for specific management.

The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery.

Nanoscale enzyme reactors (NERs) of glucose oxidase in conductive mesoporous carbons were prepared in a two-step process of enzyme adsorption and follow-up enzyme crosslinking. MSU-F-C, a mesoprous carbon, has a bottleneck pore structure with mesocellular pores of 26 nm connected with window mesopores of 17 nm. This structure enables the ship-in-a-bottle mechanism of NERs, which effectively prevents the crosslinked enzymes in mesocellular pores from leaching through the smaller window mesopores. This NER approach not only stabilized the enzyme but also expedited electron transfer between the enzyme and the conductive MSU-F-C by maintaining a short distance between them. In a comparative study with GOx that was simply adsorbed without crosslinking, the NER approach was proven to be effective in improving the sensitivity of glucose biosensors and the power density of biofuel cells. The power density of biofuel cells could be further improved by manipulating several factors, such as by adding a mediator, changing the order of adsorption and crosslinking, and inserting a gold mesh as an electron collector.

Mast cells are key actors of innate immunity and Th2 adaptive immune response which counterbalance Th1 response, critical for anti-viral immunity. Clonal Mast Cells Activation Disorders (cMCADs) such as mastocytosis and clonal mast cells activation syndrome are characterized by an abnormal mast cells accumulation and/or activation. No data have been published on the anti-viral immune response of patients with cMCADs. The aims of the study were to collected, in a comprehensive way, outcomes of cMCADs patients who experienced a biologically-proven COVID-19 and to characterize both anti-endemic coronaviruses and specific anti-SARS-CoV-2 immune responses in these patients. Clinical follow-up and outcome data were collected prospectively for one year within the French rare disease network CEREMAST encompassing patients from all over the country. Anti-SARS-CoV-2 and anti-endemic coronaviruses specific T-cells were assessed with an enzyme-linked immunospot assay (EliSpot) and anti-SARS-CoV-2 humoral response with dosage of circulating levels of specific IgG, IgA and neutralizing antibodies. Overall, 32 cMCADs patients were identified. None of them required non-invasive or mechanical ventilation; two patients were hospitalized to receive oxygen and steroid therapy. In 21 patients, a characterization of the SARS-CoV-2-specific immune response has been performed. A majority of patients showed a high proportion of circulating SARS-CoV-2-specific interferon (IFN)-γ producing T-cells and high levels of anti-Spike IgG antibodies with neutralizing activity. In addition, no defects in anti-endemic coronaviruses responses were found in patients with cMCADs compared to non-cMCADs controls. Patients with cMCADs frequently showed a spontaneous IFN-γ T-cell production in absence of any stimulation that correlated with circulating basal tryptase levels, a marker of mast cells burden. These findings underscore that patients with cMCADs might be not at risk of severe COVID-19 and the spontaneous IFN-γ production might explain this observation. Author Summary Mast cells are immune cells involved in many biological processes including the anti-microbial response. However, previous studies suggest that mast cells may have a detrimental role in the response against viruses such as SARS-CoV-2, responsible for COVID-19. When a mutation occurs in mast cells, it can lead to a group of diseases called clonal mast cells activation disorders (cMCADs), characterized by deregulated activation of these cells. Hence, patients with cMCADs might be more susceptible to severe COVID-19 than general population. We therefore conducted a 1-year study in France to collect data from all cMCADs patients included in the CEREMAST rare disease French network and who experienced COVID-19. Interestingly, we did not find any severe COVID-19 (i.e. requiring non-invasive or mechanical ventilation) in spite of well-known risk factors for severe COVID-19 in a part of cMCADs patients. We then have studied the immune response against SARS-CoV-2 and other endemic coronaviruses in these patients. We did not observe any abnormalities in the immune response either at the level of T and B lymphocytes. These findings underscore that these patients might not be at risk of severe COVID-19 as one might have feared.

Le syndrome d’activation mastocytaire (SAMA) est un groupe de situations cliniques durant lesquelles les mastocytes libèrent de manière excessive et inappropriée des médiateurs. Le diagnostic repose sur : (i) la présence de symptômes liés à la libération excessive des médiateurs mastocytaires impliquant au moins 2 organes ou systèmes : la peau, les systèmes respiratoire, digestif, vasculaire et/ou neurologique ; (ii) une élévation de la tryptasémie lors d’une poussée ; (iii) une réponse à un traitement évitant les conséquences de la libération des médiateurs mastocytaires. Le SAMA est idiopathique lorsqu’aucune pathologie primitive expliquant une dégranulation mastocytaire excessive n’est identifiée (par exemple une mastocytose ou une allergie). La forme pédiatrique est en cours de caractérisation. Étude observationnelle de cohorte bicentrique prospective. Étaient inclus les enfants [< 18 ans], avec un SAMA idiopathique. Après une première visite, les patients recevaient le traitement recommandé (association anti-histaminiques de type I et de type II et anti-leucotriène). Un score clinique reprenant les symptômes d’activation mastocytaire sur 50 points, était mesuré avant et 3 mois après le début du traitement. Les patients présentant une baisse d’au moins 30 % du score clinique étaient inclus. Ont été recueillis : données démographiques, symptômes d’activation mastocytaire, données biologiques (tryptase, IgE totales), et médullaires (phénotypage mastocytaire, recherche de mutation dans le gène KIT) Ont été inclus 41 patients [24 garçons ; âge moyen 3,3 ans [0–16 ans]. Le SAMA était familial dans 27,9 % des cas. Un antécédent personnel ou familial d’hypermobilité articulaire était décrit (30 %). Les deux organes les plus fréquemment atteints étaient la peau (100 %) [urticaire (62,8 %), angiœdème (48,8 %), prurit (44,2 %), flushs (58,1 %)] et le système digestif (93 %) [douleurs abdominales (83,7 %), nausées/vomissements (39,5 %), diarrhées (65,1 %), RGO (25,6 %)]. Des troubles du sommeil (48,8 %), des douleurs ostéo-articulaires (27,9 %), une asthénie (30,2 %) étaient décrits. Un facteur déclenchant alimentaire était le plus fréquent (55 % ; > 10 aliments incriminés chez 38 % des patients). La tryptase moyenne basale était de 5,4 ng/mL [0,5–10,1]. Le myélogramme (n = 18, 44 %) n’a pas montré de prolifération clonale mastocytaire médullaire. Le score clinique diminuait en moyenne de 58,8 % [41,6–76] après le début du traitement. Nous décrivons la première cohorte pédiatrique de SAMA idiopathique. L’association fréquente à une hypermobilité articulaire et l’agrégation familiale justifient la recherche d’un possible mécanisme génétique. L’absence de maladie primitive associée rend compte du taux de base normal de la tryptase qui n’augmentera que lors d’une dégranulation mastocytaire. Ne pas méconnaître le SAMA isolé, source d’errance médicale, permet de débuter un traitement combiné efficace.

Background: Few studies have evaluated the efficacy of carbon dioxide (CO2) laser ablation for treating neurofibromatosis type 1 (NF1). Objective: To evaluate laser treatment safety and patient satisfaction at the French National Referral Centre for Neurofibromatosis. Methods: Retrospective survey with a specific questionnaire. The principal outcome measures included pain evaluation and assessments of treatment safety. Results: We included 106 patients, 70% of whom had more than 50 neurofibromas. Laser treatment was performed mostly for aesthetic reasons, or due to pain, recurrent local trauma or familial influence, under a local anaesthetic, during outpatient visits. The mean pain score was 4.0 ± 2.7 during the administration of local anaesthesia, 2.4 ± 2.1 during laser treatment and <2 48 h after treatment in 56% of cases. The mean satisfaction score for the treatment was 4.6 ± 3.4 and was not associated with disease phenotype. Conclusions: CO2 laser treatment for NF could be considered more frequently and might help to decrease the social impact of the disease.

Background The concept of individual burden, associated with disease, has been introduced recently to determine the “disability” caused by the pathology in the broadest sense of the word (psychological, social, economic, physical). Inherited ichthyosis belong to a large heterogeneous group of Mendelian Disorders of Cornification. Skin symptoms have a major impact on patients’ Quality of Life but little is known about the burden of the disease on the families of patients. Objectives To develop and validate a specific burden questionnaire for the families of patients affected by ichthyosis. Methods Two steps were required. First, the creation of the questionnaire which followed a strict methodological process involving a multidisciplinary team and families. Secondarily, the validation of the questionnaire, including the assessment of its reliability, external validity, reproducibility and sensitivity, was carried out on a population of patients affected by autosomal recessive congenital ichthyosis. A population of parents of patients affected by ichthyosis was enrolled to answer the new questionnaire in association with the Short Form Q12 questionnaire (SF-12) and a clinical severity score was filled for each patient. Results Ninety four families were interviewed to construct the verbatim in order to create the questionnaire and a cognitive debriefing was realized. The concept of burden could be structured around five components: “economic”, “daily life”, “familial and personal relationship”, “work”, and “psychological impact”. As a result, “Family Burden Ichthyosis” (FBI) reproducible questionnaire of 25 items was created. Forty two questionnaires were analyzable for psychometric validation. Reliability (Cronbach’s alpha coefficient = 0.89), reflected the good homogeneity of the questionnaire. The correlation between mental dimensions of the SF-12 and the FBI questionnaire was statistically significant which confirmed the external validity. The mean FBI score was 71.7 ± 18.8 and a significant difference in the FBI score was shown between two groups of severity underlining a good sensitivity of the questionnaire. Conclusions The internal and external validity of the “FBI” questionnaire was confirmed and it is correlated to the severity of ichtyosis. Ichthyoses, and other chronic pathologies, are difficult to assess by clinical or Quality of Life aspects alone as their impact can be multidimensional. “FBI” takes them all into consideration in order to explain every angle of the handicap generated.