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Empty mast cell syndrome: fallacy or fact?
  1. Omar E Mohamed1,
  2. Richard L Baretto1,
  3. Ian Walker2,
  4. Cathryn Melchior1,
  5. Jane Heslegrave1,
  6. Ruth Mckenzie2,
  7. Chidanand Hullur2,
  8. Anjali Ekbote1,
  9. Mamidipudi Thirumala Krishna1,3
  1. 1 Allergy and Immunology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  2. 2 Anaesthesia, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  3. 3 Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
  1. Correspondence to Dr Omar E Mohamed, University Hospitals Birmingham NHS Foundation Trust, Birmingham B9 5SS, UK; yaomar2000{at}


Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as ‘empty mast cell (MC) syndrome’, is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4–6 weeks postanaphylaxis to avoid false-negative results.

This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.

  • anaphylactic reactions
  • diagnosis
  • molecular pathology

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  • Handling editor Stephen R A Jolles.

  • Correction notice This paper has been corrected since it appeared Online First. Author name 'Mamidupudi' has been corrected to 'Mamidipudi'.

  • Contributors OEM and MTK conceived this review. The review was undertaken by RLB, IW, CM, JH, RM, CH and AE. OEM led the drafting of the manuscript. All authors critically commented on the drafts and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RLB reports grants, personal fees and honoraria for lectures from Thermofisher, Novartis and ALK Abello outside the submitted work. MTK received honoraria for lectures from Thermo Fisher and ALK Abello, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.