Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients

Brockow, Knut; Jofer, C.; Behrendt, Heidrun; Ring, Johannes

doi:10.1111/j.1398-9995.2007.01569.x

Cited by 468 publications

(436 citation statements)

References 50 publications

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“…In advanced SM, patients usually suffer from mediator-related symptoms as well as organ damage produced by local MC infiltrates (1)(2)(3)(12)(13)(14). During the past few years, several promising new drugs, potentially useful as cytoreductive agents in ASM and MCL, have been developed and tested in preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical problems in SM result from MC infiltration with consecutive end-organ damage and from various MC-derived mediators (1)(2)(3)(11)(12)(13)(14). Whereas clinically relevant organ damage is seen in aggressive SM (ASM) and MC leukemia (MCL) (1)(2)(3)(4)(5)11), mediator-related symptoms can develop in any category of SM (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

“…Whereas clinically relevant organ damage is seen in aggressive SM (ASM) and MC leukemia (MCL) (1)(2)(3)(4)(5)11), mediator-related symptoms can develop in any category of SM (12)(13)(14). In patients in whom mediator-related symptoms are severe or even life-threatening, an IgE-mediated allergy may be detected (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of SM is based on the subtype of disease and the presence of symptoms (11)(12)(13)(14)(15)(16)(17). Patients with mediator-related symptoms are usually treated with MC-stabilizing drugs, histamine receptor antagonists, or immunotherapy (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…Patients with mediator-related symptoms are usually treated with MC-stabilizing drugs, histamine receptor antagonists, or immunotherapy (12)(13)(14)(15)(16)(17). For severe cases, glucocorticosteroids or IgE-blockage has been proposed (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

et al. 2015

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Proteomic-based drug testing is an emerging approach to establish the clinical value and antineoplastic potential of multi-kinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the target interaction-profiles and the mast cell (MC)-targeting effects of two pharmacologically relevant midostaurin metabolites, CGP52421 and CGP62221. All three compounds, midostaurin and the two metabolites, suppressed IgE-dependent histamine secretion in basophils and MC with reasonable IC 50 values. Midostaurin and CGP62221 also produced growth-inhibition and dephosphorylation of KIT in the MC leukemia cell line HMC-1.2, whereas the second metabolite, CGP52421, that accumulates in vivo, showed no substantial effects.Chemical proteomic profiling and drug-competition experiments revealed that midostaurin interacts with KIT and several additional kinase-targets. The key downstream-regulator FES was recognized by midostaurin and CGP62221, but not by CGP52421 in MC lysates, whereas the IgEreceptor-downstream target SYK was recognized by both metabolites. Together, our data show that the clinically relevant midostaurin metabolite CGP52421 inhibits IgE-dependent histamine release, but is a weak inhibitor of MC proliferation which may have clinical implications and may explain why mediator-related symptoms improve in SM patients even when disease progression occurs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

et al. 2015

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Mastocytosis

Grattan,

Radia

2016

Rook's Textbook of Dermatology, Ninth Edition

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Mastocytosis is a rare multisystem disorder of increased mast cell numbers in the skin and other tissues. Molecular genetic analysis of bone marrow reveals a mutation of KIT in nearly all adult patients with systemic disease. Although mastocytosis is primarily a haematological disorder, it often presents with skin lesions to dermatologists or paediatricians. Patients may also present with symptoms or complications of the disease to allergists, metabolic bone disease specialists or accident and emergency departments. A diagnosis of mastocytosis can be confirmed by lesional skin biopsy. Systemic mastocytosis is usually diagnosed by bone marrow biopsy. Local or systemic symptoms from mast cell mediator release are common. Complications of adult disease include anaphylaxis, osteoporosis and the lifetime development of associated haematological non‐mast cell diseases. At least 50% of children will grow out of mastocytosis by puberty, particularly those with early‐onset disease. Treatment is aimed primarily at symptom control with antimediator drugs, including H1 antihistamines, but patients with advanced systemic disease may require cytoreductive drugs.

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Vesiculopustular, Bullous and Erosive Diseases of the Neonate

Mahon

Martinéz

2019

Harper's Textbook of Pediatric Dermatology

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Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients

Abstract: Adult patients and children with extensive skin disease with mastocytosis have an increased risk to develop severe anaphylaxis; thus, an emergency set of medication including epinephrine is recommended.

Cited by 468 publications

References 50 publications

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

Mastocytosis

Vesiculopustular, Bullous and Erosive Diseases of the Neonate

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