Current Challenges in Diagnosis and Management of Mast Cell Disorders

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 6255

Special Issue Editor

1. Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
2. Department of Medicine Solna, Unit of Immunology and Allergy, Karolinska Institutet, SE-14186 Stockholm, Sweden
Interests: anaphylaxis; mastocytosis. MCAS; KIT D816V mutation; tryptase; total IgE; HAT

Special Issue Information

Dear Colleagues,

Mast cell disorders (MCDs) constitute a heterogeneous group of conditions that may be caused by an increased number of mast cells (MCs) and/or pathologically activated MCs. These disorders can vary in severity and comprise clonal (e.g., mastocytosis) and nonclonal (idiopathic) variants. Clonal MC disorders, characterized well by intrinsic MC defects, include KIT mutation D816V, and/or expression of aberrant MC receptors. The latter may cause a “hyperactive” state of MCs, leading to excessive release of mediators from MCs. It is essential to obtain accurate diagnosis due to the substantial overlapping in clinical presentation of these conditions.

Mastocytosis is a rare variant of clonal MC disorder and affects both children and adults. The World Health Organization (WHO) introduced a classification of mastocytosis which divides the condition into 2 main groups: cutaneous mastocytosis (CM), and systemic mastocytosis (SM) involving at least 1 extracutaneous organ. SM has been further classified into several subgroups including indolent systemic mastocytosis (ISM); systemic smoldering mastocytosis (SSM); systemic mastocytosis with an associated hematologic neoplasm (SM-AHN); aggressive systemic mastocytosis (ASM); mast cell leukemia (MCL); and mast cell sarcoma (MCS).

Mast cell activation syndrome (MCAS) is another special variant of MCDs, characterized by severe, recurrent, and episodic symptoms caused by systemic MC mediator release. Patients with MCAS often present with symptoms of anaphylaxis. The diagnosis of MCAS is based on three diagnostic criteria: (1) the typical clinical symptoms consistent with severe, acute MC activation; (2) an event-related increase in serum tryptase above the individual's baseline tryptase (sBT), according to the formula: sBT + 20% of sBT (= 120% of sBT = sBT × 1.2) plus 2 ng/mL; and (3) the response to drugs directed against MC activation or the production or effects of MC mediators.   

In this Special Issue, we invite original research articles and reviews focused on the latest developments in mastocytosis and other related MCDs. We are particularly interested in the novel biomarkers that could be used to predict patients with different variant of mast cell disorders.

Dr. Theo Gulen
Guest Editor

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Keywords

  • mastocytosis
  • mast cell
  • mast cell activation syndromes
  • anaphylaxis
  • novel biomarkers
  • serum tryptase
  • KIT D816V mutation

Published Papers (5 papers)

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Research

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12 pages, 1268 KiB  
Article
Diagnostic Evaluation of Hypersensitivity Reactions to Antibiotics in a Large Cohort of Mastocytosis Patients
by Jesper Jarkvist and Theo Gülen
Diagnostics 2023, 13(13), 2241; https://doi.org/10.3390/diagnostics13132241 - 30 Jun 2023
Cited by 2 | Viewed by 967
Abstract
Background: Anaphylactic reactions are a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. Although data on the frequency of drug hypersensitivity reactions is limited in mastocytosis, it is hypothesized that these patients may be predisposed to hypersensitivity reactions to certain [...] Read more.
Background: Anaphylactic reactions are a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. Although data on the frequency of drug hypersensitivity reactions is limited in mastocytosis, it is hypothesized that these patients may be predisposed to hypersensitivity reactions to certain drugs, including antibiotics. Nevertheless, this issue has not been systematically investigated. Thus, we investigate the prevalence and clinical features of hypersensitivity reactions to antibiotics (HRA) in mastocytosis. Methods: A 15-year retrospective study was conducted among 239 (≥18 years old) consecutive mastocytosis patients who were investigated in our center. All patients underwent a thorough allergy work-up, where self-reported reactions were individually evaluated by an allergist. Results: Overall, 34 patients (14.2%) were deemed to have HRA. Most patients reacted with cutaneous symptoms (74%), and anaphylaxis was rare, confirmed only in two of 34 patients (0.8%). Beta-lactams were the most common elicitors (63%). There were no differences in age, gender, atopic status and tryptase levels between mastocytosis patients with and without antibiotic hypersensitivity. Conclusions: The present study indicates a similar prevalence of HRA in mastocytosis compared to those of the general population. Moreover, antibiotics appear to be rare elicitors of anaphylaxis in these patients. Hence, our results suggest that mastocytosis patients without a history of HRA may be treated with these drugs without special precautions. Full article
(This article belongs to the Special Issue Current Challenges in Diagnosis and Management of Mast Cell Disorders)
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Review

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13 pages, 2783 KiB  
Review
Challenges in the Diagnosis of Cutaneous Mastocytosis
by Knut Brockow, Rebekka Karolin Bent, Simon Schneider, Sophie Spies, Katja Kranen, Benedikt Hindelang, Zsuzsanna Kurgyis, Sigurd Broesby-Olsen, Tilo Biedermann and Clive E. Grattan
Diagnostics 2024, 14(2), 161; https://doi.org/10.3390/diagnostics14020161 - 11 Jan 2024
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Abstract
Background: Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult. Methods: This study compiles personal experiences together [...] Read more.
Background: Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult. Methods: This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM). Results: The nomenclature of the term “CM” is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier’s sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement. Conclusions: Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course. Full article
(This article belongs to the Special Issue Current Challenges in Diagnosis and Management of Mast Cell Disorders)
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13 pages, 286 KiB  
Review
Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis
by Matthew P. Giannetti, Jennifer Nicoloro-SantaBarbara, Grace Godwin, Julia Middlesworth, Andrew Espeland, Julia L. Douvas and Mariana C. Castells
Diagnostics 2024, 14(2), 123; https://doi.org/10.3390/diagnostics14020123 - 05 Jan 2024
Viewed by 1051
Abstract
Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, [...] Read more.
Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy. Full article
(This article belongs to the Special Issue Current Challenges in Diagnosis and Management of Mast Cell Disorders)
13 pages, 1766 KiB  
Review
Recent Advances in the Therapeutic Management of Advanced Systemic Mastocytosis
by Scott Veitch and Deepti H. Radia
Diagnostics 2024, 14(1), 80; https://doi.org/10.3390/diagnostics14010080 - 29 Dec 2023
Viewed by 1016
Abstract
Advanced systemic mastocytosis (AdvSM) is a rare haematological neoplasm characterised by the accumulation of neoplastic mast cells (MCs) in various organs, resulting in organ dysfunction and reduced life expectancy. The subtypes include aggressive SM (ASM), SM with an associated haematological neoplasm (SM-AHN) and [...] Read more.
Advanced systemic mastocytosis (AdvSM) is a rare haematological neoplasm characterised by the accumulation of neoplastic mast cells (MCs) in various organs, resulting in organ dysfunction and reduced life expectancy. The subtypes include aggressive SM (ASM), SM with an associated haematological neoplasm (SM-AHN) and mast cell leukaemia (MCL). The gain of function KIT D816V mutation is present in most cases. The availability of tyrosine kinase inhibitors (TKIs) has revolutionised the treatment landscape for patients with this life-limiting disease. Patients are now able to achieve molecular remission, improved quality of life and improved overall survival. This review focuses on the targeted therapies currently available in clinical practice and within the clinical trial setting for AdvSM. This review also highlights possible future therapeutic targets and discusses therapeutic strategies for this multimutated and clinically heterogeneous disease. Full article
(This article belongs to the Special Issue Current Challenges in Diagnosis and Management of Mast Cell Disorders)
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21 pages, 8382 KiB  
Review
Current Challenges in the Diagnosis of Pediatric Cutaneous Mastocytosis
by Hanna Ługowska-Umer, Justyna Czarny, Agnieszka Rydz, Roman J. Nowicki and Magdalena Lange
Diagnostics 2023, 13(23), 3583; https://doi.org/10.3390/diagnostics13233583 - 01 Dec 2023
Viewed by 981
Abstract
Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and the absence of extracutaneous involvement. Based on the morphology of skin lesions, CM can be divided into three major [...] Read more.
Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and the absence of extracutaneous involvement. Based on the morphology of skin lesions, CM can be divided into three major forms: maculopapular CM (MPCM), diffuse CM (DCM) and mastocytoma of the skin. A positive Darier’s sign is pathognomonic for all forms of CM. MPCM is the most common form, presenting with red-brown macules or slightly raised papules. Mastocytoma is characterized by solitary or a maximum of three nodular or plaque lesions. DCM is a rare, severe form which presents as erythroderma, pachydermia and blistering in the infantile period of the disease. CM is associated with MC mediator-related symptoms, most commonly including pruritus, flushing, blistering, diarrhea and cramping. Anaphylactic shock occurs rarely, mainly in patients with extensive skin lesions and a significantly elevated serum tryptase level. Childhood-onset MPCM and mastocytoma are usually benign diseases, associated with a tendency for spontaneous regression, while DCM is associated with severe mediator-related symptoms, an increased risk of anaphylaxis and, in some cases, underlying systemic mastocytosis (SM). In contrast to adults, SM is a rare finding in children, most commonly presenting as indolent SM. However, advanced SM sporadically occurs. Full article
(This article belongs to the Special Issue Current Challenges in Diagnosis and Management of Mast Cell Disorders)
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