Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study.

BACKGROUND: Mastocytosis is characterized by the accumulation/proliferation of abnormal mast cells. The frequency of isolated cutaneous involvement in adults with mastocytosis has not been fully determined. The main objective of our study was to assess the frequency of isolated cutaneous mastocytosis (CM) in adults with mastocytosis skin lesions. The second objective was to compare the clinical, histological, biological and imaging features in patients with isolated CM and patients with systemic mastocytosis (SM). METHODS: We included all patients with histology-proven mastocytosis skin lesions between January 2009 and December 2017. The mastocytosis diagnosis was made according to the international diagnostic criteria. All data were collected from a dedicated specific case report. RESULTS: Among 160 patients with mastocytosis skin lesions, 25 patients had isolated CM (15.6%), 105 had SM and 30 (18.7%) patients had undetermined mastocytosis. Skin KIT mutation (OR: 51.9, 95% CI: 3.9-678, P = 0.001) and high bone marrow tryptase (OR: 97.4, 95% CI: 10.3-915, P = 0.001) were strong predictors of SM. The prevalence of osteoporosis was higher in the SM population than in the isolated CM population. Moreover, a decrease in bone mineral density over a short period of follow-up (1-2 years) was associated with SM. There were no differences between the two groups regarding the frequency of mast cell activation symptoms, the presentation of skin lesions, the number of mast cells in the dermis and the level of serum tryptase. We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients. CONCLUSION: Only a small minority of adults with mastocytosis skin lesions has isolated cutaneous involvement. In 18.7% of mastocytosis cases, even complete workup does not allow for a precise classification of patients.

Higher prevalence of vertebral fractures in systemic mastocytosis, but not in cutaneous mastocytosis and idiopathic mast cell activation syndrome.

Little is known about osteoporosis in mast cell disorders (MCDs) not related to systemic mastocytosis. We described osteoporosis and fractures in MCDs and showed that systemic mastocytosis was the only studied MCDs associated with osteoporotic vertebral fractures. INTRODUCTION: To describe osteoporosis (OP) and fragility fractures in mast cell disorders (MCDs). METHODS: We retrospectively analyzed data concerning all successive patients with systemic mastocytosis (SM), cutaneous mastocytosis (CM), and mast cell activation syndromes (MCAS) diagnosed in our mastocytosis expert center between 2004 and 2015. We collected data concerning demographic profiles, clinical signs of MCD, osteoporosis, fractures, densitometry, and biological assessment of MCD. We compared CM and MCAS patients with SM patients with regard to the characteristics of OP and fragility fractures. RESULTS: We assessed 89 SM patients, 20 CM patients, and 20 MCAS patients. Osteoporosis was less frequent in CM (15.0%) and MCAS (10.0%) than in SM (44.9%). Similarly, fractures were less frequent in non-SM MCDs, respectively 5.0%, 5.0%, and 28.1%. SM patients displayed high prevalence of vertebral fractures (22.5%), mostly multiple. Conversely, in non-SM patients, vertebral fractures appeared to be uncommon (5%) and more frequently associated with risk factors for osteoporosis. CONCLUSIONS: SM is associated with multiple vertebral osteoporotic fractures, whereas CM and MCAS do not appear to be associated with this phenotype.

Bone marrow tryptase as a possible diagnostic criterion for adult systemic mastocytosis.

BACKGROUND: Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ. OBJECTIVE: The main objective was to evaluate the accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis in patients with a clinical suspicion of mastocytosis. METHODS: We included all adult patients evaluated in our centre between December 2009 and 2013 for suspected mastocytosis as part of a standardized procedure and who had a bone marrow and serum tryptase assay on the same day. The diagnosis of systemic mastocytosis was established on the basis of the World Health Organization criteria as the gold standard. The accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis was assessed by a receiver operating characteristics curve analysis. The different sensitivity and specificity values, corresponding to the set of possible bone marrow tryptase level cut-off values, were estimated with 95% confidence intervals. RESULTS: Seventy-three patients were included. The diagnosis of systemic mastocytosis was established in 43 patients (58.9%). The median bone marrow tryptase level was 423 µg/L [95% CI: 217-868] in the systemic mastocytosis group and 7.5 µg/L [95% CI: 4.6-17.1] in the non-systemic mastocytosis group (P < 0.001). A cut-off value of 50 µg/L for bone marrow tryptase identified systemic mastocytosis with a sensitivity of 93.0% [95% CI: 80.9-98.5%] and a specificity of 90.0% [95% CI: 73.5-97.9%]. CONCLUSION AND CLINICAL RELEVANCE: The bone marrow tryptase level appears to be a valuable diagnostic criterion for confirming systemic mastocytosis. If this diagnosis can reliably be excluded by evaluation of the bone marrow tryptase level, there would be no need to perform a bone marrow biopsy.

[Allergen-specific immunotherapy in the treatment of pollen allergy]. / Immunothérapie allergénique dans le traitement de l'allergie aux pollens.

Since its description by Noon in 1911, desensitization or allergen-specific immunotherapy (SIT) has been largely given by sub cutaneous injection in the treatment of allergic diseases. It remains the only treatment for allergic diseases aimed at the etiology. The development of sublingual route as an alternative to sub cutaneous injection, and of new forms of medication, has led to large-scale clinical trials, many of them performed with allergen tablets, particularly in the field of pollen allergy. These studies have confirmed that SIT is efficient in reducing allergic respiratory symptoms. Data on long term benefits and sustained efficacy after stopping treatment have also been published. These show an impact on the natural history of allergic disease and, in particular, a reduction in the risk of asthma in desensitized rhinitic subjects and in the acquisition of new sensitivities. The basic mechanisms of immunotherapy are becoming better understood and allow us to envisage improvements in this technique in the future. The sublingual route improves the risk/benefit ratio of desensitization and reduces the risk of serious side effects. These data suggest that the indications for SIT may be extended in a large number of patients with allergic respiratory diseases.

[Severe drug hypersensitivity reaction (DRESS syndrome) to doxycycline]. / DRESS syndrome sous doxycycline.

BACKGROUND: While many cases of DRESS reaction to minocycline have been described, few of these involve doxycycline. CASE STUDY: A 59-year-old woman of African origin was repatriated after a journey to Ghana for hyperthermia with infiltrated maculopapular exanthema, facial oedema (no mucosal involvement) and polyadenopathy. Laboratory tests revealed hypereosinophilia, hepatic cytolysis and mononucleosis syndrome. Cutaneous histology was non-specific. The patient had been taking doxycycline as antimalarial prophylaxis for three weeks before the onset of symptoms. DRESS to doxycycline was diagnosed. Patch-tests with doxycycline three months later proved negative. The patient's HLA phenotype was A3/A30 and B39/B42. DISCUSSION: An intrinsic causal relationship with doxycycline was likely in this case (I3). Although patch-test sensitivity and specificity with doxycycline remains unknown in DRESS exploration, a negative result does not necessarily rule out the diagnosis. A number of cases of DRESS to doxycycline have been described recently, possibly as a result of more frequent prescription (malarial prophylaxis, acne). Subjects of African ethnicity or having specific HLA phenotypes are at higher risk of developing drug hypersensitivity. CONCLUSION: This patient is the third case of DRESS to doxycycline described in the literature. The originality of this case lies in the allergological investigation using patch-tests and HLA determination.

Prevalence and risk factors for allergic contact dermatitis to topical treatment in atopic dermatitis: a study in 641 children.

BACKGROUND: There is little information regarding the risk of sensitization associated with topical atopic dermatitis (AD) treatment. OBJECTIVES: To assess the frequency of sensitization to topical treatment of AD in children and to determine risk factors associated with skin sensitization. METHODS: Six hundred and forty-one children with AD were systematically patch tested with seven agents of common topical treatment: chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child. The following variables were recorded: age, sex, age at onset of AD, associated asthma, severity of AD, and history of previous exposure to topical agents used in the treatment of AD. Skin prick tests to inhalant and food allergens were used to explore the IgE-mediated sensitization. RESULTS: Forty-one positive patch tests were found in 40 patients (6.2%). Allergens were emollients (47.5%), chlorhexidine (42.5%), hexamidine (7.5%), tixocortol pivalate and bufexamac (2.5% each). Risk factors associated with sensitization to AD treatment were AD severity [OR: 3.3; 95% confidence interval (CI):1.5-7.1 for moderate to severe AD], AD onset before the age of 6 months (OR: 2.7; 95% CI: 1.2-6.1), and IgE-mediated sensitization (OR: 2.5; 95% CI: 1.1-5.9). CONCLUSIONS: Topical treatment of AD is associated with cutaneous sensitization. Antiseptics and emollients represent the most frequent sensitizers and may be included in the standard series in AD children when contact dermatitis is suspected. Risk factors associated with sensitization to AD topical treatments are AD severity, early AD onset and IgE-mediated sensitization.