Gabriela Cobos, MD, is a Dermatology Specialist in Boston, Massachusetts affiliated with Brigham and Women’s hospital. With more than 7 years of diverse experiences, Dr. Gabriela frequently cooperates with doctors and specialists of Brigham And Womens Physicians Organization Inc. medical group. She’s joined us to discuss Systemic Sclerosis after her session at IAS 2021.
Regarding the study you pulled from Annals of the Rheumatic Diseases on puffy fingers and their link to Systemic Sclerosis1, can you explain the importance of clarifying the relevancy between puffy fingers and antinuclear antibody negative (ANA-) Raynaud's phenomenon in relation to Systemic Sclerosis?
To give a little bit of background from that paper, what the group was trying to look at is how to classify patients with systemic sclerosis and find them earlier.
Since we know that organ damage can be happening even within three years of the onset of disease and organ damage is correlated with the morbidity alongside the mortality of the disease, the European cohort group of about 470 patients with Raynaud's phenomenon established different criteria of what should we look for as red flags or key findings that we can see in patients with Raynaud's that should make us think that this is this might be a patient that can be going on to develop systemic sclerosis.
Those three key findings were having a history of or current physical exam of puffy fingers, Raynaud's phenomenon, and then ANA positivity. When they looked at that cohort, they found that having that puffy fingers, in addition to Raynaud's and ANA positivity, the positive predictive value of having systemic sclerosis was about 88 percent.
Compared to if you look at Raynaud's phenomenon and ANA positivity, it's somewhere like 30s. For that group, it's well established. What they also found was that, for their ANA-negative patients with Raynaud's phenomenon, several of these patients that had ANA negativity but also a history or current exam of puffy hands already had sclerodactyly.
In other words, several of them already met the criteria, the new ACR criteria for systemic sclerosis. A significant amount compared to patients that did not have a history of puffy fingers, they had the nailfold capillaroscopy that could be consistent with systemic sclerosis.
All in all, puffy hands is something that should trigger us as dermatologist when you're looking at these patients with Raynaud's disease as a marker that you want to follow these patients a little bit more closely.
You don't want to just give them a diagnosis of Raynaud's and let them go on in their life. It's something you would want to do longitudinal monitoring and a thorough review of systems every time we see them in clinic for assessing for any kind of internal organ involvement.
You mentioned that the ACR- EULAR Classification of Systemic Sclerosis has been enhanced in 2013 a long shot away from its original form in 1980. Do foresee any updates or added criteria (for example, the utilization of cluster analysis) that could advance these classifications even further in the future?
At this point, we're too early on to be able to add clustering analysis to classification criteria, because the purpose of the classification criteria is more for research purposes. It's to make sure that we have patients that have the condition that we're enrolling in these kinds of trials. Clinically, sometimes they never fit that perfect criteria, so it's different.
At this time, we've added the new advances that systemic sclerosis has had since the 1980s, which it's adding the antibodies that we look at carefully, and then capillaroscopy. Those two additions are innovative from what we've had in systemic sclerosis. We're too early on to add any kind of clustering analysis data to that so far.
You mentioned it’s possible that by combining skin involvement and antibody profiles we would be able to predict clinical outcomes for these patients, what additional research is needed to make this viable?
Large-scale research is needed. One of the reasons why I want to present that clustering analysis in the IAS talk is because we have this sub-classification of either you're limited or diffused, and we look at it. It's a very binary thing.
Looking at that cluster analysis, you see that this is such a heterogeneous condition, where we look only at limited and diffused. Yes, it does serve a purpose, as diffused will be seen with more mortality, but it's not the skin alone. From that cluster analysis, you'll see that there's certain patients that have limited disease but have significant organ involvement, and that's what drives the mortality.
You would classify these groups based on organ involvement. That's where the mortality curves start to be more parallel than they are now. Things that are needed is, why do certain patients that have, let's say, ACA positivity, or anti-centromere positivity, present with more diffused skin involvement? Why do they have more internal organ involvement? That goes down to we don't still understand the pathogenesis behind systemic sclerosis. What is the trigger? We know genetics are not alone.
If you look at the monozygotic twins data, it's not high concordance between twins developing systemic sclerosis. We know that there's epigenetics that go on prior, likely, years before the disease presentation, and I think that is one of the areas that we need more research in.
Linking back to psoriasis because it's one of those diseases where we've looked at the pathway really well, we still don't know what that trigger is, but we understand the inner lupus that are involved. We understand which cells are important.
For systemic sclerosis, we're still behind in that. For the future, what research is going to guide us to is looking at the epigenetics behind the disease, and understanding the pathophysiology more thoroughly than we do now.
You noted it takes a village to treat and care for these patients. Can you elaborate on the respective responsibilities physicians in rheumatology, gastroenterology, and dermatology should be implementing when coming to contact with SSc?
One, dermatologists need to be at the forefront of this. We need to make sure that we're able to identify subtleties of presentations. When you look at the ACR classification criteria, a large majority of the criteria needed for the classification are skin involvement. Dermatologists need to be at the forefront of this.
Additionally, we should be more involved with the clinical research that goes into this disease, which our rheumatology colleagues are beyond us in this, especially the EULAR group in Europe are great at working together.
For American dermatologists, we need to make sure that we have this village of dermatology specialists that's seeing these patients who not only want to clinically manage, but then also advance the field and research.
At Brigham, I am lucky because we have so many specialists. I always think of it as the Disney World where you send people, because everyone has their own little niche. We have GI folks that are interested in systemic sclerosis, so we know who to send to for motility, for any kind of dysphasia, and management of that.
Rheumatology should be considered, as well, for joints or any other involvement related. For us here, dermatology does take a forefront in managing these patients, which is great because one of the most debilitating things for patients with systemic sclerosis can be their severe Raynaud's.
We are very comfortable here treating them with a variety of both oral medications, botulinum toxin injections, and managing that. Additionally, skin involvement, if it's severe enough, can have contractures limiting quality of life, which is another takeaway.
For the rest of the village, and it's something I now think about much more for my patients, it's how much this affects them mentally.
Some of these patients have had no other medical illness, and now they're given this diagnosis. If you google systemic sclerosis, it’s a scary disease. That's where the education from us comes from. It's heterogeneous. We don't know who's going to go on to develop what.
Having that uncertainty for patients, that's where our psych colleagues have been extremely helpful. Making sure that addressing mental health with these patients as part of my visit with them every clinic. Asking how are you doing mood-wise? How are you handling all this kind of stuff? If they want to be referred to someone making it seem like this is completely normal, which it is, but mental health is a very important part to deal with.
The other group here, particularly, they have more restriction in their mobility, sending them to physical therapy and occupational therapy off the bat to make sure that they're working on enhancing everything they can while we start medications to help with this as well.
Are there any tips or pearls of wisdom you'd like to offer your colleagues regarding SSc?
Just like I said before, dermatology needs to be a big part of this disease because it is so skin-driven and it’s important being comfortable with managing these patients. If you're not comfortable completely, then knowing the resources that we have.
As a field, we can make a lot of meaningful interventions for these patients. Always making sure that you reach out to colleagues, or if anyone in private practice. When reaching out make sure that there's a dermatologist on board with the patient's management to make sure that they're going to get the most optimal care.
Reference:
1. van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737-2747. doi:10.1002/art.38098
