It starts with the name: Eosinophilic fasciitis & its basic definition problems.
(Image from Camard et. al, 2022)
A Quick Dive Into Deep Tissue: Defining the Name “Eosinophilic Fasciitis” Helped Me Understand Some Fundamental Problems
The name Eosinophilic fasciitis can be broken down into its components to mean: inflammation of the fascia pertaining to eosinophils. I’ll take it one step further and define “eosinophils” and “fascia.”
Eosinophils
Eosinophils are one of the least numerous types of white blood cells (basophils are the least numerous), making up just 1-3% of the white blood cells in the body. Eosinophils are easily identified in microscopic examination by their double lobed structure and the fact that they contain large numbers of granules that are readily stained with a dye called eosin. Hence the name of the cell, which is latin for “loving eosin.” Circulating eosinophil numbers increase in the body with allergic reactions and in response to some parasites. Their numbers in the body can be decreased with steroids. (Curtis, 2006)
Fascia
Fascia was always a vague concept to me—sort of a connective tissue catch all whose location in the body I could never quite pin down. Turns out, the basis for my confusion is systemic:
Researchers do not agree on one comprehensive "fascia" definition. Despite the scientific uncertainty, there is an agreement with medical text that the fascia covers every structure of the body, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue has a ubiquitous distribution in the body system; it is able to wrap, interpenetrate, support, and form the bloodstream, bone tissue, meningeal tissue, organs, and skeletal muscles. The fascia creates different interdependent layers with several depths, from the skin to the periosteum {tissue surrounding bone}, forming a three-dimensional mechano-metabolic structure.
(Bordoni et. al, 2022)
There are four organizations that have published four different definitions of “fascia” that you can read more about here. In the context of Eosinophilic fasciitis, it might be most useful to consider the oldest definition of “fascia,” which excludes the epidermis, or the topmost portion of the skin. So, inflammation that extends deeper into the tissues underlying the epidermis could be characterized as “fasciitis.”
Clear As Mud, So What’s the Diagnostic Criteria?
In 2018 the following Diagnostic Criteria for Eosinophilic fasciitis was proposed, but has yet to be scientifically validated. It’s important to note that the American College of Rheumatology abandoned the development of Diagnostic Criteria in 2015. I wrote a post about it here. Since Eosinophilic fasciitis is primarily managed by dermatologists, I thought there was a chance of the existence of a consensus criteria in dermatology. If it exists, I haven’t found it yet. To meet the following provisional criteria for Eosinophilic fasciitis, the major criterion must be met, and at least one of the minor criteria must be met:
EF = Eosinophilic fasciitis; sclerotic = hardened; histology = tissue study; fibrosis = excessive and abnormal growth of collagen (example: elastin) and fibrous sugar proteins (example: fibronectin), and many more structures that make up the “extracellular matrix.”
The diagnostic criteria above makes the most sense in the context of the images that appear at the top of this post. The top two images of the skin’s surface show thickening and hardening of the top layers of the skin. The depressed lines, where blood vessels are visible, have more plasticity (flexibility) than the surrounding thick and hardened skin. It is this plasticity that causes the flexible tissue surrounding the blood vessels to recede into the surrounding, hardened skin. The bottom left image shows thickening of deep tissue seen on Magnetic Resonance Imaging (MRI). The bottom left image is a tissue sample of Eosinophilic fasciitis showing lymphocytes and one eosinophil in the sample.
Is it Auto-inflammatory, Autoimmune or Something Else?
There are some indications that Eosinophilic fasciitis is auto-inflammatory. Auto-inflammatory = governed by the innate (immediate) immune response. Allergies are an example of an auto-inflammatory process.
Auto-Inflammatory Evidence
Eosinophils are involved in allergic response. Histamine, a byproduct in the breakdown of Mast cells, is often elevated in the tissues and blood of patients with Eosinophilic fasciitis. Possible inflammatory triggers include
strenuous exercise
physical trauma
exposure to certain medications (such as statins, ramipril, heparin, pembrolizumab, immune checkpoint inhibitors, and anti-tumor necrosis factor agents)
initiation of hemodialysis
infection with Borrelia burgdorferi
use of adulterated rapeseed oil (epidemic outbreak in Spain in 1980s)
radiotherapy
graft-versus-host disease
Other signs of an auto-inflammatory process include:
lack of specific, associated auto-antibodies
presence of elevated, general inflammatory markers in the blood: elevated Erythrocycte sedimentation rate (ESR) and C-reactive protein (CRP)
associated fever, in many cases
(Mazilu et. al, 2023)
Autoimmune Evidence
It’s likely that Eosinophilic fasciitis exists somewhere on the auto-inflammatory autoimmune spectrum. Autoimmune = governed by the adaptive (learned) immune response, primarily B- and T-lymphocytes (two sub-types of one type of white blood cell):
documented concurrent autoimmune diseases, including Systemic lupus erythematosus, Sjögren’s syndrome, Primary biliary cirrhosis and Thyroid disease
documented concurrent hematologic disorders, “such as immune-mediated anemia or thrombocytopenia, pancytopenia, aplastic anemia, pure red cell aplasia, Hodgkin lymphoma, myelomonocytic leukemia, chronic lymphocytic leukemia, other leukemias and lymphomas, multiple myeloma, and other myeloproliferative disorders); cancers [melanoma, lung]”
associated arthritis and/or joint pain
associated muscle pain and/or inflammation
in rare cases, neurological problems and/or inflammation of the fluid-filled sacs that surround organs has been noted
(Mazilu et. al, 2023)
Something Else?
The overall consensus in what I’ve read to date pretty firmly places Eosinophilic fasciitis on the auto-inflammatory/autoimmune spectrum. Idiopathic (unknown cause) was the only other disease category proposed, which is decidedly unsatisfactory.
Next week, I’ll write about the complicated connections Eosinophilic fasciitis has to several other named autoimmune diseases. For those who are new to AutoimmuneDx, I am currently writing posts based on reader-requests for more information and analysis on particular autoimmune diagnoses. If you would like me to take a closer look at a particular diagnosis, please leave a comment below. If you don’t feel comfortable commenting publicly, email me at autoimmunedx@gmail.com.
References
Bordoni B, Mahabadi N, Varacallo M. Anatomy, Fascia. 2022 Jul 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29630284.
Camard M, Maisonobe T, Flamarion E. The groove sign in eosinophilic fasciitis. Clin Rheumatol. 2022 Dec;41(12):3919-3920. doi: 10.1007/s10067-022-06311-y. Epub 2022 Jul 30. PMID: 35907103.
Curtis L. Mosby’s Dictionary of Medicine, Nursing & Health Professions (7th edition). Reference Reviews. 2006;20(7):40-40. doi:10.1108/09504120610691718
Mazilu D, Boltașiu Tătaru LA, Mardale DA, Bijă MS, Ismail S, Zanfir V, Negoi F, Balanescu AR. Eosinophilic Fasciitis: Current and Remaining Challenges. Int J Mol Sci. 2023 Jan 19;24(3):1982. doi: 10.3390/ijms24031982. PMID: 36768300; PMCID: PMC9916848.