Grasping for Research-Backed Differences: Sclerodermas differ, but don't give up their secrets easily.
I just typed the word “grasping” into Substack’s AI image generator, and the above image was created. I don’t know why creepy seems to be built into AI-generated images. You can see it in the partial ring finger, the fused fingers, the jagged fingernails, the disjointed layers of arms, and the odd, interposed bark arms. This image is such an apt pairing for a post about differentiating Sclerodermas. It’s so close to conveying a cohesive story, but so far from making real, coherent sense. As a metaphor, I just had to use it.
The Struggle Is Real
I looked for case study images that might tell a coherent story about the way Eosinophilic fasciitis looks—and I came up short. I looked for tissue pathology standards that differentiate Eosinophilic fasciitis from other Sclerodermas—and I came up short. I thought the problem was with my understanding. Then, I thought the problem was with “their” understanding. Then, I just couldn’t stop empathizing with these authors trying doggedly to find scientific touchstones for differentiating Sclerodermal disease characteristics. After all, if the answer is “I know it when I see it,” each clinician’s knowing and seeing differs. The scientific method doesn’t work with inconsistencies. Inconsistencies block the slow building of scientific knowledge, which is the only path to truth.
Images
In an effort to really understand the difference between Eosinophilic fasciitis and Localized scleroderma (Morphea), I went searching for case studies in each diagnosis that included pictures. If you recall my post from two weeks ago, it included a title image of what’s known as the “groove sign” in Eosinophilic fasciitis. Based on that image, it seemed to me that even if the underlying disease mechanisms (genetic susceptibility, immune system abnormalities, environmental exposures) of Eosiniphilic fasciitis are unknown, the clinical characteristics, at least, look straightforward. Except, what I found in the case study images for Eosinophilic fasciitis, was far from visually uniform. There are, in fact, a wide range of visual presentations, such as this one here, six examples of various types of morphea and one example of Eosinophilic fasciitis here, and an image here of Eosinophilic fasciitis that presented without the characteristic skin thickening/hardening (is it even a Scleroderma without this?), orange peel texture, or groove sign.
Tissue Pathology
Can you use skin biopsies to differentiate Systemic sclerosis from Localized scleroderma? This review of the evidence says Nope—and for that reason there’s no utility in conducting skin biopsies in an effort to differentiate the two. That’s not to say skin biopsies should not be done for a general characterizing of the disease, just that skin biopsies are ineffective for telling the difference between Systemic sclerosis and Localized sclerderma.
Of the two kinds of Scleroderma, Systemic sclerosis is considered more serious than Localized scleroderma (I include Morphea and Eosinophilic fasciitis in this sub-type) because Systemic sclerosis affects vital organs. Because of this, Systemic sclerosis has been researched more than Localized scleroderma, and many of the scientific findings about Systemic sclerosis have been applied to Localized scleroderma. I wrote about the phenomenon of prioritizing systemic disease in research here.
What about the differences between Eosinophilic fasciitis and some types of Localized sclerodermas? The difference is basic, confined to the depth of the inflammation and tissue changes found on skin biopsy.
More superficial inflammation = other sub-types of Localized scleroderma.
Deeper inflammation = Eosinophilic fasciitis.
I was looking for something more concrete—different types of white blood cells found in the tissue, different characteristics to the particular kind of thickening and hardening of the tissue. No such luck.
Drawing Lines in the Sand
The differences between Systemic sclerosis and Localized scleroderma
early signs of Systemic sclerosis that are rarely present in Localized scleroderma
Presence of Raynaud’s syndrome/phenomenon (narrowing (possibly spasming) of small blood vessels (could be limited to arteries only) in limbs (especially fingers) that cause reduced blood flow to the affected area)
Gastrointestinal symptoms, unspecified
signs of Systemic sclerosis that are rarely present in Localized scleroderma
sclerodactyly (inward curvature of the fingers due to skin hardening)
digital ulcers (ulcers on the tips of the fingers)
pitting scars
puffy fingers
calcinosis cutis (calcium salt deposits in skin)
telangiectasia (visible small blood vessels near the skin’s surface, known colloquially as “spider veins”)
The differences between Morphea (Localized scleroderma) and Eosinophilic fasciitis
the way it looks (groove sign, orange peel skin in some Eosinophilic fasciitis)
how deep the inflammation goes (very deep in Eosinophilic fasciitis)
the presence of eosinophils in the fascia of the arms or legs
symmetrical lesions in Eosinophilic fasciitis (both limbs, for example)
a history of a significant inflammatory phase may indicate Eosinophilic fasciitis over Morphea (Localized scleroderma)
But when it comes to the Localized scleroderma sub-type, Deep morphea, the differences dissolve:
histological differentiation with deep morphea, especially in the presence of widespread sclerosis, may be challenging.
The differences between Systemic sclerosis and Eosinophilic fasciitis
Unlike Systemic sclerosis, Eosinophilic fasciitis doesn’t usually appear on the face, the ends of the arms and legs (due to the relative lack of fascia in these areas of the body?). And just like with the differences between Systemic sclerosis and Localized scleroderma, Eosinophilic fasciitis does not usually include Raynaud’s phenomenon, autoantibodies, internal organ involvement and abnormal nailfold capillaroscopy (a test to look for abnormal changes to the tiny blood vessels found at the base of your nails).
(Mertens et. al, 2017)
Why it Matters
I’m looking for something that more fundamentally differentiates the Sclerodermas in order to definitively separate them into different disease processes—sex predominance, genetic variations, environmental exposures, specific differences in immune disfunction. Without these differences identified, how do you know that it’s not different stages of the same disease? Or that one type of the same disease process, for some unknown reason, is not as extensive (deep) as another? Whole Exome Sequencing is only a relatively recent development in research, but it has the potential to create yet-unknown connections between seemingly disparate autoimmune diseases, and differentiate between autoimmune diseases with similar presentations, but caused by different fundamental processes. This cost-effective technology can revolutionize autoimmune disease research, if we allocate the resources to it.
Next week, I’ll be writing about genetic variation, and the evidence for post-treatment resolution of symptoms, in Eosinophilic fasciitis. 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. If you would like me to clarify a post, a concept, a word, or anything in-between, please don’t hesitate to leave a comment or send an email.
Reference
Mertens JS, Seyger MMB, Thurlings RM, Radstake TRDJ, de Jong EMGJ. Morphea and Eosinophilic Fasciitis: An Update. Am J Clin Dermatol. 2017 Aug;18(4):491-512. doi: 10.1007/s40257-017-0269-x. PMID: 28303481; PMCID: PMC5506513.