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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 α-tryptasemia (HαT, 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 HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. METHODS: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT 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 HαT 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). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). CONCLUSION: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.
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Anafilaxia , Mastocitose Sistêmica , Mastocitose , Humanos , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Estudos Retrospectivos , Prevalência , Mastocitose/epidemiologia , Mastocitose/genética , Mastocitose/patologia , Anafilaxia/patologia , Mastócitos/patologia , Triptases/genéticaRESUMO
BACKGROUND: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. METHODS: We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. RESULTS: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. CONCLUSION: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.
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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.
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Hepatomegalia , Fígado , Mastocitose Sistêmica , Humanos , Mastocitose Sistêmica/patologia , Mastocitose Sistêmica/complicações , Estudos Retrospectivos , Feminino , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Biópsia , Hepatomegalia/patologia , Hepatomegalia/etiologia , Idoso , Hipertensão Portal/patologia , Hipertensão Portal/etiologia , França , Cirrose Hepática/patologia , Mastócitos/patologia , Fosfatase Alcalina/sangue , PrognósticoRESUMO
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.
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Inibidores de MTOR , Mastocitose Sistêmica , Sirolimo , Humanos , Mastocitose Sistêmica/tratamento farmacológico , Projetos Piloto , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , França , Idoso , Sirolimo/uso terapêutico , Sirolimo/efeitos adversos , Inibidores de MTOR/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Everolimo/uso terapêutico , Everolimo/efeitos adversos , Resultado do Tratamento , Serina-Treonina Quinases TOR/antagonistas & inibidores , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Allergic contact dermatitis to gloves is mostly induced by rubber accelerators. The European baseline series (EBS) appears insufficient to detect glove allergy. Since 2017, it is recommended to use the European rubber series (ERS) and to test the patients' own gloves. OBJECTIVES: To investigate the clinical profile of glove-wearing patients with hand eczema (HE) and to evaluate their sensitisation profile to glove allergens and the value of testing the patients' own gloves. METHODS: We conducted a French multicentre study of patients evaluated for HE between 2018 and 2020 and tested with the EBS, the ERS and their own gloves in patch tests and semi-open (SO) tests. RESULTS: A total of 279 patients were included; 32.6% of patients had positive tests to their own gloves or to glove allergens. Almost 45% of the sensitisations to glove allergens were detected only by the ERS. Among the patients tested both in patch tests and SO tests with their own gloves with positive results, 28% had positive SO tests only. Polyvinylchloride (PVC) gloves were positive in four patients. CONCLUSION: Our series confirms the need to test the ERS. All the patients' gloves must also be tested including PVC gloves. SO tests with gloves are useful as a complement to patch tests.
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Dermatite Alérgica de Contato , Eczema , Dermatoses da Mão , Humanos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Borracha/efeitos adversos , Eczema/etiologia , Alérgenos/efeitos adversos , Testes do Emplastro , Cloreto de Polivinila/efeitos adversos , Dermatoses da Mão/induzido quimicamente , Luvas Protetoras/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVES: The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week. MATERIALS AND METHODS: The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT. RESULTS: A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty-nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days. CONCLUSION: According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product.
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Dermatite Alérgica de Contato , Dermatologia , Alérgenos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Relação Dose-Resposta a Droga , Humanos , Testes do Emplastro/métodos , Estudos ProspectivosRESUMO
BACKGROUND: An aqueous antiseptic containing "chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol" (CBB) is widely used in France. The only previous documented study dealing with allergic contact dermatitis (ACD) to this antiseptic is one small case series in children. The French Vigilance Network for Dermatology and Allergy (REVIDAL-GERDA) has collected many cases in the last few years. OBJECTIVES: To evaluate the clinical and sensitization profiles of patients diagnosed with ACD to CBB. METHODS: We performed a retrospective study of patients with contact dermatitis to CBB and positive tests to CBB and/or at least one of its components. All patients had to be tested with all components of CBB. RESULTS: A total of 102 patients (71 adults and 31 children) were included. The lesions were extensive in 63% of patients and 55% had delayed time to diagnosis. CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components. CONCLUSION: CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children.
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Anti-Infecciosos Locais , Dermatite Alérgica de Contato , Adulto , Alérgenos , Anti-Infecciosos Locais/efeitos adversos , Compostos de Benzalcônio , Álcoois Benzílicos , Criança , Clorexidina/efeitos adversos , Clorexidina/análogos & derivados , Cloretos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Humanos , Testes do Emplastro/efeitos adversos , Estudos RetrospectivosAssuntos
Toxinas Botulínicas Tipo A , Dermatite Alérgica de Contato , Humanos , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/diagnóstico , Feminino , Toxinas Botulínicas Tipo A/efeitos adversos , Albumina Sérica Humana/efeitos adversos , Testes do Emplastro , Fármacos Neuromusculares/efeitos adversos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Airborne allergic contact dermatitis caused by paints containing isothiazolinones has been recognized as a health hazard. OBJECTIVES: To collect epidemiological, clinical and patch test data on airborne allergic contact dermatitis caused by isothiazolinone-containing paints in France and Belgium. METHODS: A descriptive, retrospective study was initiated by the Dermatology and Allergy Group of the French Society of Dermatology, including methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)- and/or MI-sensitized patients who developed airborne allergic contact dermatitis following exposure to isothiazolinone-containing paint. RESULTS: Forty-four cases were identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5% of also had mucosal symptoms. In several cases, the dermatitis required systemic corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A median delay of 5.5 weeks was necessary to enable patients to enter a freshly painted room without a flare-up of their dermatitis. Approximately one-fifth of the patients knew that they were allergic to MI and/or MCI/MI before the exposure to paints occurred. CONCLUSION: Our series confirms that airborne allergic contact dermatitis caused by paints containing isothiazolinones is not rare, and may be severe and long-lasting. Better regulation of isothiazolinone concentrations in paints, and their adequate labelling, is urgently needed.
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Dermatite Alérgica de Contato/etiologia , Tiazóis/efeitos adversos , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Dermatite Ocupacional/etiologia , Desinfetantes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pintura , Testes do Emplastro/efeitos adversos , Estudos Retrospectivos , Água , Adulto JovemAssuntos
Corantes/efeitos adversos , Corantes de Rosanilina/efeitos adversos , Urticária/induzido quimicamente , Acetaminofen/efeitos adversos , Administração Oral , Analgésicos não Narcóticos/efeitos adversos , Antibacterianos/efeitos adversos , Neoplasias da Mama/cirurgia , Corantes/administração & dosagem , Excipientes , Feminino , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Testes Intradérmicos , Metaciclina/efeitos adversos , Pessoa de Meia-Idade , Corantes de Rosanilina/administração & dosagem , Biópsia de Linfonodo Sentinela , Testes CutâneosRESUMO
Introduction: Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies. Objective: To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy. Methods: This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated. Results: Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87). Conclusions: Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.
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BACKGROUND: Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population. OBJECTIVE: To evaluate the sensitivity of a standardized allergy workup for diagnosing the cause of FDE, with a focus on in situ repeated open application tests (ROATs). METHODS: In a retrospective multicenter study, we analyzed the practice of conducting a complete allergy workup for the etiological diagnosis of FDE. It consisted of 3 steps: in situ patch tests (PTs) for all cases except pure mucosal involvement, followed by in situ ROAT if in situ PT results were negative, and finally a drug challenge (DC). The in situ ROAT involved daily application of the suspected drug on a previously affected FDE site for 7 days. RESULTS: Of 98 suspected FDE cases, 61 patients (median age 61 y; male-to-female ratio 1.8) with a complete allergy workup were included. In 4 cases, even the DC yielded negative results. Among the remaining 57 patients with a positive workup, implicated drugs included paracetamol (12 cases), ß-lactams (11 cases), imidazoles (9 cases, including 5 with metronidazole), nonsteroidal anti-inflammatory drugs (8 cases), iodinated contrast media (4 cases), cotrimoxazole (3 cases), and various other drugs in 10 patients. The diagnosis was confirmed by in situ PT in 17 of 54 cases (31.5%), in situ ROAT in 14 of 40 cases (35%) (with 4 cases showing remote reactivation of FDE sites), and DC in 26 cases. CONCLUSIONS: The sequential allergy workup involving successively in situ PT, in situ ROAT, and DC is a reliable and safe method for diagnosing the cause of FDE. In situ tests exhibited a sensitivity of over 50%.
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Toxidermias , Hipersensibilidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Testes do Emplastro , Toxidermias/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Hipersensibilidade/complicaçõesAssuntos
Compostos de Anilina/efeitos adversos , Automóveis , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Poliuretanos/efeitos adversos , Adulto , Compostos de Anilina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poliuretanos/química , Estudos RetrospectivosRESUMO
A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.