Patients with elevated basal tryptase (sBT) >15 μg/l and anaphylaxis may have an underlying mastocytosis. A monoclonal mast cell activation syndrome with aberrant mast cells (MC) at extracutaneous sites has been described in patients with severe hypotension or anaphylaxis.

Methods

As MC in patients with elevated sBT might be altered in the skin as well, we studied MC in normal neck skin in anaphylaxis and urticaria patients with elevated sBT.

Results

A mean of 93.1 (SD 19.1) MC/mm² was counted in normal neck skin in 14 patients with anaphylaxis, 84.0 (SD 13.6) in seven patients with urticaria, 142.0 (SD 24.0) in two patients with eczema, 124.4 (SD 43.2) in five patients with systemic mastocytosis (SM) in comparison with autopsy skin (39.1 MC/mm², SD 12.4). In five of 14 (35.7%) of the anaphylaxis and three of five (60%) SM patients more than 25% of MC were spindle shaped and expressed CD25 antigen.

Conclusions

We could show for the first time that the normal skin can harbour clonal MC in anaphylaxis patients. Analogous to the criteria for mastocytosis, we suggest a skin score criteria including an elevated number of MC, spindle shape, CD25 expression, c-Kit mutation and sBT values >20 μg/l. In patients with anaphylaxis and elevated sBT, skin should be biopsied and, as with the approach for mastocytosis diagnosis in the bone marrow, MC should be analysed for their number, clonality and c-Kit mutation. This approach should be confirmed in further studies. Patients with aberrant skin MC should be handled as mastocytosis patients.

References

1Valent P, Horny HP, Li CY, Longley BJ, Metcalfe DD, Parwaresch RM et al. Mastocytosis (mast cell disease). In: ED Jaffe, NL Harris, H Stein, JW Vardiman. editors. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001: 291–302.
Google Scholar
2Weber A, Knop J, Maurer M. Pattern analysis of human cutaneous mast cell populations by total body surface mapping. Br J Dermatol 2003; 148: 224–228.
10.1046/j.1365-2133.2003.05090.x
CAS PubMed Web of Science® Google Scholar
3Wilkinson B, Jones A, Kossard S. Mast cell quantitation by image analysis in adult mastocytosis and inflammatory skin disorders. J Cutan Pathol 1992; 19: 366–370.
10.1111/j.1600-0560.1992.tb00607.x
CAS PubMed Web of Science® Google Scholar
4Kim MS, Kim YK, Lee DH, Seo JE, Cho KH, Eun HC et al. Acute exposure of human skin to ultraviolet or infrared radiation or heat stimuli increases mast cell numbers and tryptase expression in human skin in vivo. Br J Dermatol 2009; 160: 393–402.
10.1111/j.1365-2133.2008.08838.x
CAS PubMed Web of Science® Google Scholar
5Rosen LB, Frank B. Mast cells in sun-exposed and non-sun-exposed skin. An autopsy study. Am J Dermatopathol 1987; 9: 208–211.
10.1097/00000372-198706000-00005
CAS PubMed Web of Science® Google Scholar
6Grimbaldestone A, Simpson A, Finlay-Jones JJ, Hardt PH. The effect of ultraviolet radiation exposure on the prevalence of mast cells in human skin. Br J Dermatol 2003; 148: 300–306.
10.1046/j.1365-2133.2003.05113.x
PubMed Web of Science® Google Scholar
7Janssens AS, Heide R, den Hollander JC, Mulder PG, Tank B, Oranje AP. Mast cell distribution in normal adult skin. J Clin Pathol 2005; 58: 285–289.
10.1136/jcp.2004.017210
CAS PubMed Web of Science® Google Scholar
8Garriga MM, Friedmann MM, Metcalfe DD. A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders. J Allergy Clin Immunol 1988; 82: 425–432.
10.1016/0091-6749(88)90015-2
CAS PubMed Web of Science® Google Scholar
9Smith CH, Kepley C, Schwartz LB, Lee TH. Mast cell number and phenotype in chronic idiopathic urticaria. J Allergy Clin Immunol 1995; 96: 360–364.
10.1016/S0091-6749(95)70055-2
CAS PubMed Web of Science® Google Scholar
10Natbony SF, Phillips ME, Elias JM, Godfrey HP, Kaplan AP. Histologic studies of chronic idiopathic urticaria. J Allergy Clin Immunol 1983; 71: 177–183.
10.1016/0091-6749(83)90096-9
CAS PubMed Web of Science® Google Scholar
11Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 2010; 126: 1099–1104.
10.1016/j.jaci.2010.08.035
CAS PubMed Web of Science® Google Scholar
12Metcalfe DD. Mast cells and mastocytosis. Blood 2008; 112: 946–956.
10.1182/blood-2007-11-078097
CAS PubMed Web of Science® Google Scholar
13Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment, recommendations and response criteria. Eur J Clin Invest 2007; 37: 435–453.
10.1111/j.1365-2362.2007.01807.x
CAS PubMed Web of Science® Google Scholar
14Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with „idiopathic” anaphylaxis. Blood 2007; 110: 2331–2333.
10.1182/blood-2006-06-028100
CAS PubMed Web of Science® Google Scholar
15Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 2012; 157: 215–225.
10.1159/000328760
PubMed Web of Science® Google Scholar
16Valent P. Mast cell activation syndromes: definition and classification. Allergy 2013; 68: 417–424.
10.1111/all.12126
CAS PubMed Web of Science® Google Scholar
17Aberer E, Savic S, Bretterklieber A, Reiter H, Berghold A, Aberer W. Disease spectrum in patients with elevated serum tryptase levels. Australas J Dermatol 2015; 56: 7–13.
10.1111/ajd.12146
PubMed Web of Science® Google Scholar
18Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1977; 1: 466–469.
10.1016/S0140-6736(77)91953-5
CAS PubMed Web of Science® Google Scholar
19Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau A et al. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009; 64: 1417–1426.
10.1111/j.1398-9995.2009.02179.x
CAS PubMed Web of Science® Google Scholar
20Yanagi H, Sankawa H, Saito H, Iikura Y. Effect of lidocaine on histamine release and Ca2+ mobilization from mast cells and basophils. Acta Anaesthesiol Scand 1996; 40: 1138–1144.
10.1111/j.1399-6576.1996.tb05577.x
CAS PubMed Web of Science® Google Scholar
21Alvarez-Twose I, González-de-Olano D, Sánchez-Muñoz L, Matito A, Jara-Acevedo M, Teodosio C et al. Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms. Int Arch Allergy Immunol 2012; 157: 275–280.
10.1159/000329856
CAS PubMed Web of Science® Google Scholar
22Álvarez-Twose I, Zanotti R, González-de-Olano D, Bonadonna P, Vega A, Matito A et al. Spanish Network on Mastocytosis (REMA). Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM. J Allergy Clin Immunol 2014; 133: 520–528.
10.1016/j.jaci.2013.06.020
PubMed Web of Science® Google Scholar
23Alvarez-Twose I, Morgado JM, Sánchez-Muñoz L, García-Montero A, Mollejo M, Orfao A et al. Current state of biology and diagnosis of clonal mast cell diseases in adults. Int J Lab Hematol 2012; 34: 445–460.
10.1111/j.1751-553X.2012.01427.x
PubMed Web of Science® Google Scholar
24Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 2009; 123: 680–686.
10.1016/j.jaci.2008.11.018
CAS PubMed Web of Science® Google Scholar
25Sonneck K, Florian S, Müllauer L, Wimazal F, Födinger M, Sperr WR et al. Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: monoclonal mast cell activation syndrome. Int Arch Allergy Immunol 2007; 142: 158–164.
10.1159/000096442
PubMed Web of Science® Google Scholar
26Gülen T, Hägglund H, Sander B, Dahlén B, Nilsson G. The presence of mast cell clonality in patients with unexplained anaphylaxis. Clin Exp Allergy 2014; 44: 1179–1187.
10.1111/cea.12369
CAS PubMed Web of Science® Google Scholar
27Wiednig M, Beham-Schmid C, Kranzelbinder B, Aberer E. Clonal mast cell proliferation in pruriginous skin in hypereosinophilic syndrome. Dermatology 2013; 227: 67–71.
10.1159/000351807
PubMed Web of Science® Google Scholar
28Valent P, Aberer E, Beham-Schmid C, Fellinger C, Fuchs W, Gleixner KV et al. Guidelines and diagnostic algorithm for patients with suspected systemic mastocytosis: a proposal of the Austrian competence network (AUCNM). Am J Blood Res 2013; 3: 174–180.
CAS PubMed Google Scholar
29Daley T, Metcalfe DD, Akin C. Association of the Q576R polymorphism in the interleukin-4 receptor α chain with indolent mastocytosis limited to the skin. Blood 2001; 98: 880–882.
10.1182/blood.V98.3.880
CAS PubMed Web of Science® Google Scholar
30Krishna MT, Ewan PW, Diwakar L, Durham SR, Frew AJ, Leech SC et al. Diagnosis and management of hymenoptera venom allergy: British Society for Allergy and Clinical Immunology (BSACI) guidelines. Clin Exp Allergy 2011; 41: 1201–1220.
10.1111/j.1365-2222.2011.03788.x
CAS PubMed Web of Science® Google Scholar
31Ruëff F, Vos B, Oude Elberink J, Bender A, Chatelain R, Dugas-Breit S et al. Predictors of clinical effectiveness of Hymenoptera venom immunotherapy. Clin Exp Allergy 2014; 44: 736–746.
10.1111/cea.12275
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume70, Issue7

July 2015

Pages 864-872

Anaphylaxis with clonal mast cells in normal looking skin – a new entity?

Abstract

Background

Methods

Results

Conclusions

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Anaphylaxis with clonal mast cells in normal looking skin – a new entity?

Abstract

Background

Methods

Results

Conclusions

References

Citing Literature

References

Related

Information