Key Clinical Message
A change in clinical behavior of a disease should prompt search for differential diagnoses. Here, the appearance of ulcerated skin nodules in a preexisting cutaneous mastocytosis ...revealed a concurrent lymphomatoid papulosis – a CD30+ lymphoproliferative skin disease with histological features of a malignant lymphoma, but with a benign self‐healing course.
A change in clinical behavior of a disease should prompt search for differential diagnoses. Here, the appearance of ulcerated skin nodules in a preexisting cutaneous mastocytosis revealed a concurrent lymphomatoid papulosis – a CD30+ lymphoproliferative skin disease with histological features of a malignant lymphoma, but with a benign self‐healing course.
Next‐generation sequencing (NGS) is becoming increasingly used for diagnostic mutation analysis in myeloid neoplasms and may also represent a feasible technique in mastocytosis. However, detection of ...the KIT D816V mutation requires a highly sensitive method in most patients due to the typically low mutation levels. In this study, we established an NGS‐based KIT mutation analysis and analyzed the sensitivity of D816V detection using the Ion Torrent platform. Eighty‐two individual NGS analyses were included in the study. All samples were also analyzed using highly sensitive KIT D816V mutation‐specific qPCR. Measurements of the background level in D816V‐negative samples supported a cutoff for positivity of 0.2% in three different NGS panels. Clinical samples from patients with SM that tested positive using qPCR with a D816V allele burden >0.2% also tested positive using NGS. Samples that tested positive using qPCR with an allele burden <0.2% tested negative using NGS. We thereby demonstrate that caution should be taken when using the potentially very sensitive NGS technique for KIT D816V mutation analysis in mastocytosis, as many patients with SM have D816V mutation levels below the detection limit of NGS. A dedicated and highly sensitive KIT D816V mutation analysis therefore remains important in mastocytosis diagnostics.
Following the bite in August, 2001, the reaction developed rapidly, and he immediately lost consciousness and went into cardiac arrest before the ambulance arrived. Because of delayed resuscitation, ...he had hypoxic brain damage to the basal ganglia, resulting in spastic tetraplegia. Despite having only slightly raised serum tryptase of 11·5 ?g/L (normal range <11·4 ?g/L), bone marrow examination showed spindle shaped mast cells expressing CD25, and the typical Kit-mutation (D816V) was detected by PCR of peripheral blood leucocytes.1 From the patient's description of the appearance of the mosquitoes that bit him, and knowledge of the geographic region where the incidents occurred, Culex pipiens was identified by an expert from the Bernhard Nocht Institute, Hamburg, Germany, as the most likely of the 100 known mosquito species in central Europe to be responsible for inducing such reactions.
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.
This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM).
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
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.
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.
Treatment strategies in mastocytosis Siebenhaar, Frank; Akin, Cem; Bindslev-Jensen, Carsten ...
Immunology and allergy clinics of North America,
05/2014, Letnik:
34, Številka:
2
Journal Article
Recenzirano
Treatment recommendations for mastocytosis are based mostly on expert opinion rather than evidence obtained from controlled clinical trials. In this article, treatment options for mastocytosis are ...presented, with a focus on the control of mediator-related symptoms in patients with indolent disease.
Systemic mastocytosis (SM) is characterized by the growth of neoplastic mast cells (MCs). Most adults with indolent SM carry the KIT D816V mutation. We recently introduced the D816V+ allele fraction ...as a disease marker in SM using a sensitive and quantitative KIT D816V mutation analysis that consistently allows mutation detection in peripheral blood (PB) and bone marrow (BM). The D816V+ allele fraction represents a quantitative measure which allows KIT D816V‐positivity to be analyzed as a continuous variable instead of a categorical variable (negative/positive) as previously described. Serum tryptase represents an established disease marker in SM, and it remains to be tested whether tryptase and the D816V+ allele fraction are associated or represent independent disease markers. In this study, correlation analysis between serum tryptase, the D816V+ allele fraction in PB and BM, and the MC fraction was performed in 57 indolent systemic mastocytosis (ISM) patients. We detected significant correlations between the D816V+ allele fraction, the mature neoplastic MC fraction, and serum tryptase which represent three different biological measures of disease burden. Mutation analysis was performed in two or more PB samples in 39 patients, and the results demonstrated high stability with no overall tendency to increasing D816V+ allele fractions over time. Considerable variation was nevertheless observed in the correlation analyses. Serum tryptase reflects the mature MC load, whereas the D816V+ allele fraction includes cells other than mature MCs to a variable extent. We conclude that tryptase and the D816V+ allele fraction represent different, although correlated, measures of disease status in SM.
Pediatric Expression of Mast Cell Activation Disorders Broesby-Olsen, Sigurd; Carter, Melody; Kjaer, Henrik Fomsgaard ...
Immunology and allergy clinics of North America,
08/2018, Letnik:
38, Številka:
3
Journal Article
Recenzirano
Mast cell activation disorders is a term proposed to cover diseases and conditions related to activation of mast cells and effects of mast cell mediators. In its broadest sense, the term encompasses ...a wide range of diseases from allergic asthma to rhinoconjunctivitis, urticaria, food allergy, anaphylaxis, mastocytosis, and other conditions where MC activation is contributing to the pathogenesis. This article focuses on clinical presentations, challenges, and controversies in pediatric mastocytosis and gives an overview of current knowledge and areas in need of further research.
We report an atopic dermatitis patient with recurrent hand dermatitis who developed a severe allergic contact dermatitis from the use of Elidel® cream. Diagnostic patch tests showed an isolated ...contact allergy to the emulsifier oleyl alcohol present in the product. Pimecrolimus appeared to have had an aggravating effect on the dermatitis in spite of its immunosuppressive effects. The initial clinical appearance of the patient’s widespread dermatitis was atypical with resemblance to subacute cutaneous lupus erythematosus. Even though emulsifiers are widely used in topical products, contact allergic reactions to these are relatively uncommon.
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