Orphanet Journal of Rare Diseases | French Guidelines for the Management of Nonadvanced Mastocytosis in Adults

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This literature provides comprehensive management recommendations for nonadvanced mastocytosis in adults, covering standardized guidance from diagnostic criteria to treatment strategies, offering clinicians systematic frameworks to improve patient quality of life.

 

Literature Overview
This article titled 'French guidelines for the management of nonadvanced mastocytosis in adults', published in Orphanet Journal of Rare Diseases, reviews the latest French guidelines on adult nonadvanced mastocytosis management. The article systematically describes clinical phenotypes, diagnostic criteria, treatment options, and recommended monitoring strategies for mastocytosis, providing clinicians with a structured management framework.

Background Knowledge
Mastocytosis is a rare disease characterized by abnormal proliferation and accumulation of mast cells in various tissues. In adults, it primarily presents as cutaneous mastocytosis (CM) or systemic mastocytosis (SM), with approximately 85% of patients showing cutaneous involvement. Aberrant mast cell activation can cause diverse symptoms including allergic reactions, osteoporosis, or gastrointestinal disorders. Although genetically determined, the clinical manifestations and disease progression exhibit high heterogeneity, making diagnosis and treatment particularly challenging. Current therapies mainly focus on symptom control through antihistamines, proton pump inhibitors, while targeted therapies like tyrosine kinase inhibitors (TKI) demonstrate efficacy in specific subtypes. The publication highlights urgent needs for standardized treatment of nonadvanced mastocytosis, emphasizing the central role of gene mutations (e.g., KIT D816V) in diagnosis and the importance of multidisciplinary collaboration in treatment decisions.

 

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Research Methods and Experiments
Developed based on recommendations from the French Health Authority (HAS) in June 2022, this guideline integrates expert consensus, systematic literature reviews, and clinical experience. The research team analyzed multiple clinical phenotypes of mastocytosis, including cutaneous (CM), systemic (SM), and bone marrow mastocytosis (BMM), proposing standardized diagnostic workflows. Additionally, the study evaluated various treatment approaches such as second-generation anti-H1/H2 histamine antagonists, leukotriene inhibitors, mast cell membrane stabilizers, and targeted TKIs like avapritinib for specific cases. Novel scoring systems including REMA and modified REMA were also introduced to help clinicians assess potential risks of systemic diseases.

Key Conclusions and Perspectives

• Adult mastocytosis primarily presents as systemic mastocytosis (SM), though cutaneous manifestations often coexist with systemic involvement.
• KIT D816V mutation serves as the primary molecular marker for mastocytosis, playing a crucial diagnostic role.
• Cutaneous lesions can be diagnosed through histology, immunohistochemistry, and molecular biology methods, with Darier's sign positivity indicating mast cell activation.
• Diagnostic scoring systems (e.g., REMA, NICAS) help identify patients at high risk for systemic mastocytosis.
• TKI avapritinib has been approved in Europe for treating indolent systemic mastocytosis (ISM), showing effective symptom control and mast cell burden reduction in clinical trials.
• Second-generation anti-H1/H2 histamine antagonists, leukotriene inhibitors, and mast cell membrane stabilizers (e.g., cromolyn sodium) are primary treatment modalities for symptom management.
• Osteoporosis and pathological fractures are common complications requiring basic calcium and vitamin D supplementation.
• Monoclonal therapies (e.g., omalizumab) can be used for mast cell activation syndrome (MCAS).
• Treatment selection should consider symptom severity, quality of life impact, and potential side effects, particularly long-term skeletal risks.
• Multidisciplinary management (dermatology, hematology, allergy, rheumatology, psychological support) is recommended for all mastocytosis patients.

Research Significance and Prospects
This study establishes systematic and standardized management protocols for adult nonadvanced mastocytosis, enhancing diagnostic accuracy and treatment consistency. With emerging targeted therapies like novel KIT mutation-specific TKIs (BLU-263, bezutclastinib) and immunomodulators, the guidelines will continue evolving. Additionally, innovative scoring systems (e.g., MC-QoL, ISM-ASF) will enable more precise assessment of disease burden and treatment response.

 

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Conclusion
The 'French guidelines for the management of nonadvanced mastocytosis in adults' provides clinicians with a practical framework for systematic management. The guidelines emphasize the central role of KIT D816V mutation in diagnosis and recommend skin biopsy and bone marrow examination for all suspected cases. For treatment, second-generation antihistamines, mast cell membrane stabilizers, and targeted TKIs (e.g., avapritinib) are advised under specific conditions. Patient-reported quality of life (QoL) and disease burden should be quantitatively assessed using standardized questionnaires (e.g., DLQI, Burden-Masto). The study stresses the necessity of multidisciplinary teams including dermatology, hematology, allergy, nutrition, and psychology. While current treatments remain symptomatic, ongoing clinical trials with novel targeted therapies promise more precise personalized approaches. These guidelines offer clear diagnostic and therapeutic pathways, reducing misdiagnosis and improving patient outcomes.

 

Cristina Bulai Livideanu, Stéphane Barete, Ghandi Damaj, Julien Rossignol, and Olivier Hermine. French guidelines for the management of nonadvanced mastocytosis in adults. Orphanet Journal of Rare Diseases.