Nailfold Capillary Changes and Pulmonary hypertension

Presentation about nailfold capillarscopy

1. Raynaud’s Phenomenon, Nailfold Capillaroscopy, and PAH in Rheumatic Diseases Pulm /Rheum Conference Date: 9/3/2025

2. Outlines Raynaud’s phenomenon What is NFC? How to evaluate NFC? NFC and PAH NFC in other diseases Dr. Marquez’s talk (Early detection of pulmonary hypertension in connective tissue disease, risk factors, screening modalities and their interpretation)

3. Case 34-year-old woman referred for evaluation of Raynaud’s phenomenon x 18 months, worsening in winter and cold weather Over the last 6–8 months she notes puffy fingers, no skin thickening. Noted some new telangiectasias on her face and hands Report new exercise intolerance over the past 2-3 months. Recent TTE with reportedly normal RV size/function, no estimate of elevated RVSP ROS: +GERD (on PPI), no chronic cough, or DOE. No digital ulcers. No arthritis. No weakness. Meds: Omeprazole 40 mg daily SHx : non-smoker, no alcohol, works as middle school teacher, no silica/chemical exposures PMH: Unremarkable. FHx : Mother with Hashimoto thyroiditis

4. Raynaud’s Phenomenon – Pathogenesis Ture HY, Lee NY, Kim NR, Nam EJ. Raynaud’s Phenomenon: A Current Update on Pathogenesis, Diagnostic Workup, and Treatment. Vasc Specialist Int . 2024;40. doi:10.5758/vsi.240047

5. Imaging Modality

6. What is capilloroscopy ? Non-invasive visualization of nailfold capillaries Optimal magnification: ≥200x . Classification of Primary vs. Secondary RP Useful for diagnosis and monitoring treatment response. Smith, V., Ickinger , C., Hysa, E., Snow, M., Frech, T., Sulli, A., & Cutolo, M. (2023). Nailfold capillaroscopy. Best Practice & Research Clinical Rheumatology , 101849.

7. NAILFOLD capillaroscopy 7 Most expensive Ophthalmoscope Magnification: ~15x Magnification: 10-200x Traditional microscopes or Power Eyepiece Mag: 10-40x Stereo microscopes and Video capillaroscopes (NVC) Magnification: 50-500x Low ($200–1000) High ($10,000 and up) Low to medium ($1000 and up)

8. EULAR Study Group Definition (2020) Consensus for standard interpretation of capillaroscopy findings Normal ≥ 7/mm

9. EULAR Study Group Definition Consensus for standard interpretation of capillaroscopy findings Normal ≥ 7/mm Normal ≤ 20µm Arvanitaki, Alexandra et al. Mediterranean journal of rheumatology  vol. 31,3 369-373. 10 Jun. 2020, doi:10.31138/mjr.31.3.369

10. EULAR Study Group Definition Consensus for standard interpretation of capillaroscopy findings Normal ≥ 7/mm Normal ≤ 20µm convex

11. EULAR Study Group Definition Consensus for standard interpretation of capillaroscopy findings Normal ≥ 7/mm Normal ≤ 20µm convex McBride JD, Sontheimer RD. Cuticular hemosiderin deposits aid in diagnosis of dermatomyositis/systemic sclerosis. Dermatol Online J. 2016;22(2). doi:10.5070/D3222030078

12. EULAR Study Group Definition Consensus for standard interpretation of capillaroscopy findings FAST TRACK ALGORITHM Easy Rule of Thumb to Discern an Image as Belonging to the Scleroderma Pattern (Category 2) or Not (Category 1)

13. Role of capillaroscopy in classification of RP What % of patients with RP will develop an underlying rheumatologic disease? Which diseases are most commonly associated?

14. Outcomes and Predictors of Secondary RP Koenig M , Joyal F, Fritzler MJ, et al. Arthritis & Rheumatism . 2008;58(12):3902-3912. doi:10.1002/art.24038 Baseline Follow up Median follow up was ~ 4.5 yrs 784 patients with RP, no sign of CTD Secondary RP 12.6% SSc 1% other + SSc abs + SSc pattern - 65.9% SSc at 5 years - 79.5% SSc in 10 years PPV = 79% - SSc abs - SSc pattern 1.8 % /20 years NPV = 93%

15. Direct links between RP and PAH risk in SSc Plastiras 2007 (retrospective, SSc cohort, n=114 ) PAH prevalence: 33/114 (29%) by echo criterion. PAH = RV systolic pressure ≥40 mmHg Independent predictors of PAH included RP preceding skin changes by ≥3 years ( OR 5.75 , 95% CI 1.9–17.4) Plastiras SC, Karadimitrakis SP, Kampolis C, Moutsopoulos HM, Tzelepis GE. Determinants of Pulmonary Arterial Hypertension in Scleroderma. Seminars in Arthritis and Rheumatism . 2007;36(6):392-396. doi:10.1016/j.semarthrit.2006.10.004

16. Nailfold capillaroscopy findings and PAH in SSc Study Design / Population Key Findings Conclusion / Implication Source Hofstee 2009 Ann Rheum Dis 21HC, 20 pts w/ IPAH, 40 SSc (19 SSc-nonPAH and 21 SSc -PAH) Reduction of nailfold capillary density, but not capillary loop dimensions is associated with PAH [ 4.33/mm vs 6.56/mm respectively , p = 0.001 in SSc -PAH vs. SSc-nonPAH ) Lower NFC density is associated with the severity of PAH in both SSc and IPAH PubMed Riccieri 2013 Rheumatology (Oxford) 12 SSc -PAH vs 12 SSc-noPAH PAH vs non-PAH: avascular areas >1 83% vs 17% , active/late pattern 92% vs 42% , all correlated with higher mPAP . PAH is associated with NVC findings (avascular areas, active/late pattern) that correlates with higher mPAP . PubMed Minopoulou 2021 J Clin Med Meta-analysis: 7 studies; 101 SSc -PAH vs 277 SSc-noPAH Lower capillary density and wider loops in SSc -PAH; ~7.3× higher odds of active/late pattern Quantifies the association; late/active pattern and density loss are robust markers for PAH in SSc . MDPI De Angelis 2024 J Rheumatol cross-sectional, case–control, multicentre study, 55 SSc -PAH vs 55 SSc-noPAH SSc -PAH patients showed higher frequencies of late pattern (P < 0.01), lower capillary density (P < 0.01), higher avascular areas (P < 0.01) and a higher mean NVC score (P < 0.01) In SSc -PAH, distinctive NVC abnormalities ( capillary loss and the late pattern ) are more frequent than in non-PAH and mirror the severity of PAH PubMed ↓capillary density, ↑ avascular areas, and a late pattern signal higher PAH risk and severity (↑ mPAP )

17. RP and NFC with PAH in SLE 41 SLE-PAH vs. 106 SLE- nonPAH Retrospective case-control study, PAH confirmed with RHC 21 SLE-PAH vs. 44 SLE- nonPAH Retrospective case-control study, PAH confirmed with RHC Scleroderma pattern was more common in SLE-PAH vs SLE- noPAH : 56.3% vs 15.9% (p=0.002). Multivariate: Scleroderma pattern independently predicted PAH ( OR 6.393 ; 95% CI 1.53–26.72; p=0.011). Lian, Fan et al. Rheumatology international  vol. 32,6 (2012): 1727-31. doi:10.1007/s00296-011-1880-4 Donnarumma, Juliana Fernandes Sarmento et al. Advances in rheumatology (London, England)  vol. 59,1 1. 6 Jan. 2019, doi:10.1186/s42358-018-0045-5 Nailfold capillaroscopy as a risk factor for pulmonary arterial hypertension in SLE patients Clinical features and independent predictors of pulmonary arterial hypertension in SLE

18. Multicenter, prospective and observational study SLE (n = 40), SSc (n = 70) and IIM (n = 50) vs. 51 MCTD patients (11 MCTD-PAH vs. 40 MCTD-nonPAH) positive for anti-U1 RNP antibodies PAH confirmed with RHC Findings: In MCTD, nailfold microvascular abnormalities are less prevalent than in SSc but, when present, are associated with PAH . ~50% of MCTD patients show improvement in nailfold abnormalities after immunosuppressive therapy. Todoroki, Yasuyuki et al. Rheumatology (Oxford, England)  vol. 61,12 (2022): 4875-4884. doi:10.1093/rheumatology/keac165

19. Take home points NVC distinguishes primary vs secondary RP Use EULAR Study Group Definition to describe NFC Can differentiate between scleroderma from non-scleroderma patterns. Abnormal NFC (low density/avascular, late pattern) is linked to PAH , especially in SSc .

20. References 1. Ebadi Jalal M, Emam OS, Castillo-Olea C, García- Zapirain B, Elmaghraby A. Abnormality detection in nailfold capillary images using deep learning with EfficientNet and cascade transfer learning. Sci Rep . 2025;15(1). doi:10.1038/s41598-025-85277-8 2. Ozturk L, Laclau C, Boulon C, et al. Analysis of nailfold capillaroscopy images with artificial intelligence: Data from literature and performance of machine learning and deep learning from images acquired in the SCLEROCAP study. Microvascular Research . 2025;157:104753. doi:10.1016/j.mvr.2024.104753 3. Emam OS, Ebadi Jalal M, Garcia- Zapirain B, Elmaghraby AS. Artificial Intelligence Algorithms in Nailfold Capillaroscopy Image Analysis: A Systematic Review | medRxiv . doi:10.1101/2024.07.28.24311154 4. Smith V, Herrick AL, Ingegnoli F, et al. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud’s phenomenon and systemic sclerosis. Autoimmunity Reviews . 2020;19(3):102458. doi:10.1016/j.autrev.2020.102458 5. Koenig M, Joyal F, Fritzler MJ, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: A twenty‐year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis &amp; Rheumatism . 2008;58(12):3902-3912. doi:10.1002/art.24038 6. Smith V, Vanhaecke A, Herrick AL, et al. Fast track algorithm: How to differentiate a “scleroderma pattern” from a “non-scleroderma pattern” - ScienceDirect. Accessed September 2, 2025. 7. Filippini C, Cardone D, Perpetuini D, et al. Convolutional Neural Networks for Differential Diagnosis of Raynaud’s Phenomenon Based on Hands Thermal Patterns. Applied Sciences . 2021;11(8):3614. doi:10.3390/app11083614 7. Ture HY, Lee NY, Kim NR, Nam EJ. Raynaud’s Phenomenon: A Current Update on Pathogenesis, Diagnostic Workup, and Treatment. Vasc Specialist Int . 2024;40. doi:10.5758/vsi.240047 8. Plastiras SC, Karadimitrakis SP, Kampolis C, Moutsopoulos HM, Tzelepis GE. Determinants of Pulmonary Arterial Hypertension in Scleroderma. Seminars in Arthritis and Rheumatism . 2007;36(6):392-396. doi:10.1016/j.semarthrit.2006.10.004

21. Cohort: SSc -PAH (n=20) vs IPAH (n=5); all had same-day CMR, echo, and nailfold capillaromicroscopy with post-occlusive reactive hyperaemia (PORH) testing. SSc -PAH showed more cardiac involvement on CMR : higher T2 (edema/inflammation) and a trend to higher ECV (fibrosis) than IPAH. Peripheral microvasculopathy was worse in SSc -PAH : lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH; most had a late SSc NVC pattern, while IPAH tended to be normal/non-specific. Link between periphery and heart: NFC density inversely correlated with ECV (r=−0.443) and T2 (r=−0.464), and with diastolic dysfunction markers on echo ; PORH (but not NCD) correlated with stress-perfusion (relative myocardial upslope). Bottom line: In SSc -PAH, worse nailfold microvascular function aligns with greater myocardial inflammation/fibrosis on CMR, supporting a shared SSc -driven vasculopathy affecting both periphery and heart. Vos, Jacqueline L et al. European heart journal. Cardiovascular Imaging  vol. 25,5 (2024): 708-717. doi:10.1093/ ehjci /jeae001