Indolent Systemic Mastocytosis with Elevated Serum Tryptase, Absence of Skin Lesions, and Recurrent Severe Anaphylactoid Episodes

2005 ◽  
Vol 136 (3) ◽  
pp. 273-280 ◽  
Author(s):  
Stefan Florian ◽  
Maria-Theresa Krauth ◽  
Ingrid Simonitsch-Klupp ◽  
Wolfgang R. Sperr ◽  
Robert Fritsche-Polanz ◽  
...  
Keyword(s):  
Systemic Mastocytosis ◽  
Elevated Serum ◽  
Skin Lesions ◽  
Serum Tryptase ◽  
Indolent Systemic Mastocytosis

Imatinib Mesylate in the Treatment of Systemic Mastocytosis, a Phase I/II Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1516-1516 ◽  
Author(s):  
H.J. Droogendijk ◽  
J.C. Kluin-Nelemans ◽  
P.L.A van Daele
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Mast Cell ◽  
Mast Cells ◽  
Imatinib Mesylate ◽  
Systemic Mastocytosis ◽  
Skin Lesions ◽  
Tissue Response ◽  
Serum Tryptase ◽  
Kit Receptor

Abstract Introduction: mastocytosis comprimes a group of diseases characterized by abnormal proliferation and accumulation of mast cells in one or more organs. A cutaneous and systemic form of mastocytosis is distinguished. Systemic mastocytosis defines the disease process in which mast cell proliferation exceeds the skin. The clinical manifestations of systemic mastocytosis depend on the tissues involved and the tissue response to the accumulation of mast cells. Although in general the disease progresses slowly, it may develop into a malignant disease. Currently there is no cure for systemic mastocytosis. Mast cells develop from pluripotent bone marrow progenitor cells that express CD34 antigen and are dispersed as precursors which undergo proliferation and maturation in different tissues. Normal mast cell development involves the action of stam cell growth factor and c-kit receptors, which are expressed by mast cells at their different developmental stages. Deregulation and/or abnormalities of the c-kit receptor are assumed to play a causal role in disordered mast-cell proliferation. In most patients a mutation in the gene for c-kit exists. One of the mutations is the D816V mutation. Aim of the study:imatinib mesylate, formerly called ST1571, is a potent inhibitor of c-kit receptor tyrosine kinase activity. In this study, we evaluate whether imatinib mesylate is safe and effective in the treatment of patients with systemic mastocytosis. Primary end-points of study are reduction in urinary N-methylhistamine excretion, serum tryptase activity, skin lesions, number of mast cells in sections of bone marrow, hepato-and/or splenomegaly and symptoms.Adverse effects on therapy are also considered. Results: up to now, 10 patients with systemic mastocytosis are treated with 400 mg of imatinib mesylate orally once daily. During the first 2 weeks of the study the patients also received 30 mg of prednisolone daily. In general imatinib mesylate is well tolerated. The first results show a 38–80% reduction in urinary N-methylhistamine excretion and 30–66% reduction in serum tryptase activity. Skin lesions diminish in two of the six patients with cutaneous mastocytosis,. Number of mast cells in sections of bone marrow are reduced in 63% (5/8) of the patients. Hepato-and/or splenomegaly is slightly decreased in two of the three patients with organomegaly. Finally 60 % of all patients experiences relief of symptoms. In eight patients the D816V mutation was found. In contrast with former studies imatinib mesylate is also effective in these patients. Further results are to be awaited. Conclusion: imatinib mesylate is safe and seems effective in the treatment of patients with systemic mastocytosis (including patients with the D816V mutation).

Diagnostic and Prognostic Significance of Tryptase in Clinical Hematology: A Single Center Experience from 1070 Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2316-2316
Author(s):  
Wolfgang R. Sperr ◽  
Aischa El-Samahi ◽  
Michael Girschikofsky ◽  
Stefan Winkler ◽  
Hans Semper ◽  
...  
Keyword(s):  
Renal Failure ◽  
Healthy Subjects ◽  
Systemic Mastocytosis ◽  
Prognostic Significance ◽  
Elevated Serum ◽  
Hematologic Malignancies ◽  
Serum Tryptase ◽  
Myeloid Neoplasms ◽  
Helminth Infections ◽  
Increased Risk

Abstract Recent data suggest that tryptase is expressed in neoplastic cells in various myeloid neoplasms. In this study, serum tryptase levels were determined by a fluoroenzyme-immunoassay in 165 healthy subjects, in 925 patients (pts) with hematologic malignancies (myeloproliferative disorders, MPD, n=150; myelodysplastic syndromes, MDS, n=233; acute myeloid leukemia, AML, n=317; acute lymphatic leukemia, ALL, n=26, Non Hodgkin′s lymphomas, NHL, n=30; systemic mastocytosis, SM, n=89), and in a large cohort of control cases (pregnant women, n=11; hepathopathy, n=7; renal failure, n=18; helminth infections, n=29; reactive leukocytosis/thrombocytosis or idiopathic cytopenia, n=115). In healthy subjects, the 95%-percentile ranged between 2.4 and 9.5 ng/ml (median 5.7 ng/ml). Healthy controls aged ≤ 16 years had a slightly lower median serum tryptase level compared to older control subjects (p=0.03). Among pts with non hematologic disorders, slightly elevated serum tryptase levels (up to 24 ng/ml) were detectable in 6/18 pts with severe renal failure and in 3/29 pts with helminth infections. When analyzing hematologic malignancies, tryptase levels >15 ng/ml could be detected in pts with myeloid neoplasms exclusively, whereas in most pts with lymphoproliferative disorders, tryptase levels were normal. Among myeloid neoplasms, elevated tryptase levels were recorded in 83% of the pts with SM, 36% of pts with AML, 34% of the pts with CML, and 29% of the pts with MDS. The highest tryptase levels, sometimes exceeding 1000 ng/ml, were found in pts with SM or AML-M4eo. In pts with CML, elevated tryptase levels were found to be associated with an unfavorable prognosis concerning survival (survival in CML pts with tryptase <15 ng/ml: 100% vs 71% in those with >15 ng/ml, after 60 months, p<0.007). In most pts with AML, SM, or CML, the initially enhanced serum tryptase levels decreased in response to successful cytoreductive or targeted therapy. In pts with AML, a persistently elevated serum tryptase in complete hematologic remission (CR) was found to be associated with an increased risk of relapse compared to those with normal tryptase in CR. In summary, tryptase is a new and simple diagnostic marker of myeloid neoplasms. In SM, AML, and CML, tryptase is also a useful marker to monitor (minimal residual) disease during treatment with cytoreductive or targeted drugs. Moreover, in AML and CML, measurement of tryptase is of prognostic significance. All in all, tryptase is recommended as a new important serum-marker in clinical hematology.

scholarly journals Unusual Urticaria Pigmentosa in an Asian Man With Indolent Systemic Mastocytosis: A Case Report

2020 ◽  
Author(s):  
Chamard Wongsa ◽  
Mongkhon Sompornrattanaphan ◽  
Torpong Thongngarm ◽  
Weerapat Owattanapanich ◽  
Panitta Sitthinamsuwan ◽  
...  
Keyword(s):  
Skin Color ◽  
Systemic Mastocytosis ◽  
Early Recognition ◽  
Asian Population ◽  
Skin Lesions ◽  
Urticaria Pigmentosa ◽  
Careful Examination ◽  
Delay In Diagnosis ◽  
Ige Mediated ◽  
Indolent Systemic Mastocytosis

Abstract Background: The diagnosis of mastocytosis remains challenging. Given that the disease has a low prevalence and its clinical presentations range from asymptomatic to severe life-threatening conditions, physicians’ lack of awareness of mastocytosis is the main barrier to its diagnosis. Skin involvement is common. In adults, skin lesions are highly suggestive of systemic mastocytosis; however, clinical demonstration of lesions is difficult if they are minimal in number. In Asian, who had dark brown skin color, urticaria pigmentosa was not easy to identify. Here we present the case of indolent systemic mastocytosis with an unusual urticaria pigmentosa. Case presentation: A 48-year-old man had had recurrent severe honeybee anaphylaxis since he was 23. He had small, subtle, brownish skin lesions on his chest and abdomen, which he and previous physicians had not recognized. The skin lesions were compatible with urticaria pigmentosa, also known as maculopapular cutaneous mastocytosis. His clinical findings and an elevated baseline tryptase level triggered a thorough systemic mastocytosis investigation. The skin and bone marrow were infiltrated by abnormal, spindle-shaped mast cells, and KIT and TET2 mutations were in the patient’s serum. The honeybee anaphylaxis mechanism in this patient was IgE mediated, supported by a positive result of specific IgE to honeybee. The final diagnosis was indolent systemic mastocytosis with IgE-mediated honeybee anaphylaxis. As venom immunotherapy is unavailable in Thailand, we prescribed treatment with a regular, oral, nonsedating H1-antihistamine and an epinephrine self-injector. At the 2-year follow-up, the patient had not progressed to advanced systemic mastocytosis nor experienced any anaphylactic episodes.Conclusion: Urticaria pigmentosa is a small, round, brown, or red maculopapular lesion. In the Asian population with dark brown skin color, physician should be exclusively careful examination, particularly in a hidden area and in anaphylaxis cases. Early recognition of urticaria pigmentosa in the adult patient might reduce the delay in diagnosis of indolent systemic mastocytosis.

Tryptase and histamine metabolites as diagnostic indicators of indolent systemic mastocytosis without skin lesions

Allergy ◽  
2012 ◽  
Vol 67 (5) ◽  
pp. 683-690 ◽  
Author(s):  
J. J. Doormaal ◽  
E. Veer ◽  
P. C. Voorst Vader ◽  
P. M. Kluin ◽  
A. B. Mulder ◽  
...  
Keyword(s):  
Systemic Mastocytosis ◽  
Skin Lesions ◽  
Indolent Systemic Mastocytosis

Clinical, Biological, and Molecular Characteristics of Well-Differentiated Systemic Mastocytosis: a study in 18 Patients by Spanish Network on Mastocytosis (REMA)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5246-5246
Author(s):  
Iván Alvarez-Twose ◽  
Laura Sánchez-Muñoz ◽  
María Jara-Acevedo ◽  
Cristina Teodosio ◽  
Andrés García-Montero ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Systemic Mastocytosis ◽  
Skin Lesions ◽  
Categorical Variables ◽  
Molecular Characteristics ◽  
Skin Involvement ◽  
Serum Tryptase ◽  
Kit Mutation ◽  
Well Differentiated

Abstract BACKGROUND: Well-differentiated systemic mastocytosis (WDSM) has recently been described as a novel form of mast cell disease. WDSM is characterized by a marked increase of bone marrow (BM) mast cells, usually with compact aggregates, with normal phenotype and morphology as well as the absence of the typical D816V somatic KIT mutation. OBJECTIVE: To describe and compare clinical, morphological, biological and molecular characteristics in a group of 18 patients who fullfilled criteria for WDSM with a group of 32 patients with indolent systemic mastocytosis (ISM). PATIENTS AND METHODS: All the patients were diagnosed on the basis of BM aspirate and biopsy findings after they were thought to have a systemic mastocytosis. A rigorous skin examination together with a clinical work-up and a complete laboratory analysis including peripheral blood count, routine biochemistry and serum tryptase levels were performed. The Mann-Whitney U and the chi-square tests were used to assess the statistical differences of continuous and categorical variables, respectively. RESULTS: WDSM patients were 4 males and 14 females with a median (range) age of 24 years (2–72) at diagnosis. Median (range) age at the time of the first observation of skin lesions was 2 years (0–41). In 16 of the 18 patients (89%), skin lesions appeared under the age of 14, five of them being younger than 1 year old. All the WDSM patients had skin involvement but the typical maculo-papular lesions were found only in 18% of patients while in the remaining 82% of cases, cutaneous lesions were plaques or nodules. Interestingly, 78% of WDSM patients had cutaneous neck involvement in contrast with only 13% in the ISM group (p&lt;0.001). There were no significant differences in mast cell mediators-related symptoms such as pruritus, flushing, abdominal pain or diahrrea between the two groups while anaphylactic reactions were significantly more frequent in the WDSM group than in the ISM group (59% vs 19%, p=0.004). Overall, bone loss was found in 38% and 37% of WDSM and ISM patients, respectively. Among all the biochemical parameters analyzed, only median serum cholesterol (mg/dL), ferritin (ng/mL) and tryptase levels (ng/mL) were significantly lower in patients with WDSM when compared to ISM patients (150 vs 168.5, p=0.043; 31.3 vs 56.6, p=0.004; 11 vs 31.6, p&lt;0.001; respectively). There were no significant differences in the median percentage of mast cells in the BM study as assesed by flow cytometry between both groups (0.055% in WDSM group and 0.08% in ISM group). In contrast, the presence of both fibrosis and lymphoid aggregates in the BM biopsy were more frequent in patients with ISM than in patients with WDSM (52% vs 0%, p&lt;0.001; 55% vs 14%, p=0.01; respectively). Somatic KIT mutation at codon 816 was found in 31 of the 32 ISM patients (97%) while only in one (6%) WDSM patient (p&lt;0.001). Additionally, 2 WDSM patients were found to carry variant mutations at codons other than at codon 816 (N819Y and I817V, respectively). From the remaining 15 WDSM patients, clonality of mast cell population was demonstrated by human androgen receptor (HUMARA) assay in the 5 female patients in whom the assay was made. CONCLUSIONS: WDSM is a variant of systemic mastocytosis with several characteristics that are distinguishable from ISM, such as: early onset of skin lesions, atypical skin involvement (plaques or nodules and cutaneous neck involvement), frequent anaphylactic episodes, lower serum tryptase levels than ISM despite no differences in BM mast cell infiltration, and infrequent detection of typical activating D816V KIT mutation.

scholarly journals Anaphylactoid Reaction to Intravenous Contrast in Patient with Systemic Mastocytosis

2009 ◽  
Vol 37 (4) ◽  
pp. 646-649 ◽  
Author(s):  
T. N. Weingarten ◽  
G. W. Volcheck ◽  
J. Sprung
Keyword(s):  
General Anaesthesia ◽  
Anaphylactoid Reaction ◽  
Systemic Mastocytosis ◽  
Elevated Serum ◽  
Treatment Strategies ◽  
Repeated Measurements ◽  
Serum Tryptase ◽  
Intravenous Contrast ◽  
Iodinated Contrast ◽  
Anaphylactoid Reactions

Systemic mastocytosis is a rare disorder characterised by tissue infiltration of morphologically abnormal mast cells and has been associated with severe anaphylactoid reactions during general anaesthesia. We report the case of a 43-year-old woman who developed a severe anaphylactoid reaction to iodinated contrast media. Persistently elevated serum tryptase levels led to further evaluation and the eventual diagnosis of systemic mastocytosis. This case highlights the importance of repeated measurements of serum tryptase levels following severe anaphylactoid reactions. The anaesthetist should also be aware of the propensity of these patients to develop severe anaphylactoid reactions during general anaesthesia and use treatment strategies to minimise this risk.

Idiopathic anaphylaxis

2019 ◽  
Vol 40 (6) ◽  
pp. 457-461
Author(s):  
Canting Guo ◽  
Paul A. Greenberger
Keyword(s):  
Systemic Mastocytosis ◽  
Clinical Manifestations ◽  
Panic Attacks ◽  
Serum Tryptase ◽  
C1 Esterase Inhibitor ◽  
Disease Modifying Therapy ◽  
Indolent Systemic Mastocytosis ◽  
Idiopathic Anaphylaxis ◽  
Esterase Inhibitor

Idiopathic anaphylaxis (IA) is defined as anaphylaxis without any identifiable precipitating agent or event. The clinical manifestations of IA are the same as allergen-associated (immunologic) anaphylaxis and include urticaria, angioedema, hypotension, tachycardia, wheezing, stridor, pruritus, nausea, vomiting, flushing, diarrhea, dysphagia, light-headedness, and loss of consciousness. Patients usually tend to have the same manifestations on repeated episodes. IA is a prednisone-responsive disease that is ultimately a diagnosis of exclusion. Approximately 40% of patients are atopic. Serum tryptase (or urine histamine or its metabolite) will be elevated acutely, but, if elevated in the absence of anaphylaxis, should suggest alternative diagnoses, including indolent systemic mastocytosis. A focused history, examination, and follow-up will dictate whether a patient's symptoms may be attributable to disorders that mimic anaphylaxis, such as indolent systemic mastocytosis, carcinoid syndrome, pheochromocytoma, hereditary angioedema or acquired C1 esterase inhibitor deficiency, or panic attacks. The presence of urticaria may help limit the differential diagnosis because urticaria does not usually accompany any of the above-mentioned disorders, except for indolent systemic mastocytosis. IA is classified according to the symptoms as well as the frequency of attacks. Patients who experience six or more episodes in a year, or two or more episodes in 2 months are classified as having IA-frequent (IA-F). Patients who experience fewer episodes are classified as having IA-infrequent (IA-I). This distinction is important because patients with IA-F will initially require prednisone as disease-modifying therapy, whereas most patients who with IA-I will not require prednisone. Patients with IA must carry and know when and how to self-administer epinephrine.

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