Lipedema is an estrogen-dependent disorder and estrogen directly activates mast cells (white blood cells associated with allergies and inflammation) and enhances histamine release. Histamine in turn can play a role in lymphatic dysfunction and vascular permeability changes.
While direct evidence linking histamine specifically to lipedema pathophysiology remains limited in available research data, the estrogen-mast cell-histamine-lymphatic axis provides a plausible mechanistic framework for understanding an aspect of this complex disorder.
How Histamine Affects the Lymphatic System
Histamine increases lymphatic endothelial permeability (leakier lymphatics) and changes lymphatic contractility (less pumping) which can lead to more edema.[1]
Does this mean lipedema patients have MCAS (Mast Cell Activation Syndrome)?
This connection with histamine and mast cell activation does not mean that all patients with lipedema have MCAS. MCAS is a separate disorder with its own constellation of symptoms, its own specific diagnostic criteria, and a different inflammatory profile than lipedema.[2] If someone has MCAS and lipedema, it’s possible that the combined conditions may result in even higher histamine levels, but there are no studies to date that shows that MCAS is present in higher levels in patients with lipedema.[3]
Could antihistamines be beneficial in lipedema?
There are several plausible mechanisms for antihistamines to be beneficial in lipedema including effects on vascular permeability, anti-edema, and anti-inflammatory effects, however no direct studies have been conducted to date on this topic.
Limitations on this approach and theory are that we do have evidence of lipedema having a different M2 macrophage predominant profile that differs from a classic allergic inflammatory profile and would not explain some of the other characteristics of lipedema.[4]
Sources
1. Mast Cell Degranulation Alters Lymphatic Contractile Activity Through Action of Histamine. Microcirculation. 2006. Plaku KJ, von der Weid PY.
2.AAAAI Mast Cell Disorders Committee Work Group Report: Mast Cell Activation Syndrome (MCAS) Diagnosis and Management. The Journal of Allergy and Clinical Immunology. 2019. Weiler CR, Austen KF, Akin C, et al.
3. Often Seen, Rarely Recognized: Mast Cell Activation Disease–a Guide to Diagnosis and Therapeutic Options. Annals of Medicine. 2016. Afrin LB, Butterfield JH, Raithel M, Molderings GJ.
4. A Distinct M2 Macrophage Infiltrate and Transcriptomic Profile Decisively Influence Adipocyte Differentiation in Lipedema.Frontiers in Immunology. 2023. Wolf S, Rannikko JH, Virtakoivu R, et al.
