Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality.

BACKGROUND: The Red Española de Mastocitosis (Spanish Network on Mastocytosis) score (REMAs) and the National Institutes of Health idiopathic clonal anaphylaxis score (NICAS) were developed for more efficient screening of mast cell (MC) clonality in MC activation syndromes. In a limited idiopathic anaphylaxis case series, the NICAS showed higher accuracy compared with the REMAs. OBJECTIVE: To compare the performance of the REMAs against the NICAS in the diagnosis of MC clonality. METHODS: We compared the diagnostic value of the REMAs against the NICAS in 182 patients (63% men, median age 56 years) who presented with anaphylaxis triggered by Hymenoptera venom allergy (45%), drugs (15%), food (11%), idiopathic anaphylaxis (20%), and mixed causes (10%). KIT mutation was assessed in parallel in whole blood and bone marrow (BM) and, when negative, in highly purified BM MC. TPSAB1 was genotyped in a subset of 71 patients. RESULTS: We found higher accuracy and rates of correctly classified patients for the REMAs (82% and 84%) compared with the NICAS (75% and 75%; P = .02 and P = .03, respectively), particularly among men (P = .05), patients with systemic mastocytosis (P = .05), those presenting anaphylaxis owing to any cause featuring urticaria (P = .04), cardiovascular symptoms (P = .02), and/or presyncope (P = .02) and those with a blood-negative/BM-positive KIT mutational profile (P = .002), but not hereditary α-tryptasemia-associated genotypes. Combined assessment of the REMAs and KITD816V in blood yielded an overall improved classification efficiency of 86% versus 84% for REMAs. CONCLUSIONS: The combined use of the REMAs and blood detection of KITD816V is recommended, but more sensitive blood-based molecular assays to detect KITD816V are needed.

Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021.

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.

Mastocytosis in the skin accompanied by pseudo-Kaposi's sarcoma.

Mastocytosis is a heterogeneous group of diseases characterized by abnormal proliferation of neoplastic mast cells in the skin and/or other extracutaneous tissues. Most patients with skin involvement can be subclassified into one of the three subtypes of cutaneous mastocytosis currently recognized by the World Health Organization (i.e., mastocytoma, maculopapular cutaneous mastocytosis and diffuse cutaneous mastocytosis); however, some patients may occasionally present with atypical skin lesions that cannot be ascribed to any of these disease subtypes. Here, we report three patients diagnosed with mastocytosis and an unusual cutaneous involvement mimicking Kaposi's sarcoma. Skin biopsies showed neoplastic mast cell infiltrates together with features commonly seen in acroangiodermatitis, and immunohistochemistry for human herpesvirus 8 was negative. One patient fulfilled the criteria for aggressive systemic mastocytosis, showed no response to cytoreductive therapy, and died because of disease progression. The remaining two patients had indolent and smoldering systemic mastocytosis, respectively, but they showed several features associated with an unfavorable prognosis such as extensive involvement of the hematopoiesis by the KIT D816V mutation, increased serum ß2-microglobulin, and decreased serum lactate dehydrogenase. The presence of pseudo-Kaposi's sarcoma skin lesions is an uncommon finding in mastocytosis which may alert physicians to the possible existence of underlying features indicative of a poor prognosis.

Use of Rapid Drug Desensitization in Delayed Hypersensitivity Reactions to Chemotherapy and Monoclonal Antibodies.

Background: Rapid drug desensitization (RDD) allows first-line therapies in patients with immediate drug hypersensitivity reactions (DHR) to chemotherapeutic drugs (ChD) and monoclonal antibodies (mAb). Desensitization in delayed drug reactions has traditionally used slow protocols extending up to several weeks; RDD protocols have been scarcely reported. Patients and Method: We retrospectively analyzed the patients referred to the Allergy Department, who had experienced a delayed DHR (> 6 h) related to a ChD or mAb and underwent an RDD protocol. The rate of successful administration of the offending drug and the presence of adverse reactions were evaluated. Results: A total of 93 RDDs were performed in 11 patients (including 6 men and 5 women, with a median age of 61 years). The primary DHR were maculopapular exanthema (MPE) (8), generalized delayed urticaria (1), MPE with pustulosis and facial edema (1), and facial edema with desquamative eczema (1). The meantime for the onset of symptoms was 3 days (range 1-16 days). RDD was performed using a protocol involving 8-13 steps, with temozolomide (25), bendamustine (4), rituximab (9), infliximab (24), gemcitabine (23), and docetaxel (8), within 4.6-6.5 h. Sixteen breakthrough reactions were reported during the RDD (17.2 %) in 5 patients; all were mild reactions including 11 delayed and 5 immediate reactions. All patients completed their treatment. Conclusions: RDD is a potentially safe and effective procedure in patients suffering from delayed reactions to ChD and mAb. It allows them to receive full treatment in a short period, thereby reducing time and hospital visits.

Immediate reactions to iodinated contrast media.

BACKGROUND: Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients. OBJECTIVE: To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period. METHODS: Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM. RESULTS: A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%). CONCLUSION: This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results.