P.A. Apoil

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

Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ.

Prevalence and risk factors for fragility fracture in systemic mastocytosis

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.

Are changes necessary in the medical management of a patient with snakebite regarding the incidence of hypersensitivity reaction to antivenom polyvalent immune fab

We read with interest the case reported by Rizer et al. [1], in which the authors suspected Crotalidae polyvalent immune Fab (CroFab) hypersensitivity related to a-gal allergy. This hypothesis was put forward because the patient presented with allergic symptoms, while FabAV was administered. The blood level of specific a-1,3 galactose IgE was therefore tested and was measured at 45,000U/L (normal <3500U/L). We disagree with the authors, as it is not possible to affirm that the clinical reaction observed after CroFab administration was related to a-gal hypersensitivity. First, CroFab sensitization was not confirmed by a cutaneous test (skin prick tests and intradermal reactions). Second, although the a-gal epitope has been identified on many medications including antivenoms, it has never been demonstrated that this epitope is structurally expressed on CroFab [2]. It would have been of interest to perform inhibition of thyroglobulin ImmunoCAP by antivenom using sera from patients harboring specific IgE (sIgE) against a-gal to affirm the presence of the a-gal epitope [2]. Third, although the blood level of sIgE was high when measured after the antivenom had been administered, these results should be interpreted with particular caution as prevalence of a-gal sIgE positivity shows considerable variation and has been reported to range from 5.5% to 24.5% in Europe [3]. The new question raised by this case report [1] is: are changes necessary in the medical management of a patient with snakebite? In the United States, the incidence of hypersensitivity reaction to Crotalidae polyvalent immune Fab ranges from 23% to 56% depending on study methodology, but the most recent results evaluate this incidence at 8% [4]. In France, ViperFAVVR (which contains purified F(ab0)2 fragments of equine antibodies) is the most common antivenom for the treatment of Vipera aspis and Vipera berus envenomation. Unlike CroFab, national guidelines in France recommend the use of only one dose of ViperFAVR . In Europe, the incidence of hypersensitivity reactions has not been precisely reported, but some authors described immediate hypersensitivity reactions in 21/37 cases of which seven were anaphylactic [5]. Such adverse reactions may explain why the administration protocol of ViperFAVR recommends the placement of two perfusion lines before administration. The first intravenous line is used to give the antivenom and the second to manage the potential hypersensitivity reaction. Should patients admitted to the emergency department for snakebite be systematically asked about a past history of hypersensitivity to meat or to antivenoms with the presence of a-gal sensitization? Is measurement of a-gal sIgE enough to affirm the diagnosis of hypersensitivity? If a-gal sIgE is found to be high in the patient’s serum, should the antivenom be administered, since symptoms of hypersensitivity, should they appear, are usually mild and easily treated symptomatically? After discharge, physicians should refer the patient to an allergy specialist for skin testing and immunological tests such as immunoCAP inhibition confirming a-gal epitope implication in the allergic reaction. Nonetheless, the first step would be to prove the presence of the a–gal epitope using monoclonal anti-a-gal antibody on every antivenom available.