Nailfold capillaroscopy for the early diagnosis of the scleroderma spectrum of diseases in patients without Raynaud’s phenomenon

Abstract

Background:

The utility of nailfold capillaroscopy in the evaluation of patients without Raynaud’s phenomenon is unclear.

Objective:

This study aims to compare the utility of nailfold capillaroscopy for the early diagnosis of the scleroderma-spectrum of diseases in patients who present with Raynaud’s phenomenon, undifferentiated non-Raynaud’s phenomenon features and positive systemic sclerosis-associated antibodies without scleroderma-spectrum of disease features.

Methods:

Eligible patients were divided into three referral criteria groups: (I) Raynaud’s phenomenon; (II) Undifferentiated non-Raynaud’s phenomenon features and (III) Positive systemic sclerosis-associated autoantibodies without features to suggest scleroderma-spectrum of diseases. This includes systemic sclerosis, mixed connective tissue disease and dermatomyositis. The association between baseline scleroderma pattern on nailfold capillaroscopy (systemic sclerosis–nailfold capillaroscopy) and final diagnosis at follow-up was determined using logistic regression analysis. Test characteristics of nailfold capillaroscopy were compared and stratified by referral groups.

Results:

Of 95 patients followed-up for a mean of 1.6 years, 28 (29.5%) patients developed scleroderma-spectrum of diseases, 36 (37.9%) patients had suspected/other connective tissue disease and 27 (28.4%) patients had no connective tissue disease. Baseline systemic sclerosis-nailfold capillaroscopy was significantly associated with the development of scleroderma-spectrum of diseases in patients from Group I (odds ratio, 7.1, p = 0.01) and Group II (odds ratio 7.3, p = 0.005). In Group II patients, nailfold capillaroscopy had a sensitivity, specificity, positive and negative predictive values of 71.4%, 76.5%, 55.6% and 86.7%, respectively. Specificity (81.8%) and PPV (69.2%) were the highest in Group I patients. Nailfold capillaroscopy had the highest negative predictive value in Group III (100%), followed by Group II (86.7%) and Group I (78.3%) patients.

Conclusion:

In addition to evaluating patients with Raynaud’s phenomenon, nailfold capillaroscopy was useful in the evaluation and exclusion of scleroderma-spectrum of diseases in patients with undifferentiated non-Raynaud phenomenon features and those with systemic sclerosis-associated antibodies without features to suggest scleroderma-spectrum of diseases.

Keywords

Systemic sclerosis nailfold capillaroscopy early diagnosis

Get full access to this article

View all access options for this article.

References

Wigley

. Raynaud’s phenomenon. N Engl J Med 2002; 347: 1001–1008.

Meier

Frommer

Dinser

, et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 2012; 71(8): 1355–1360.

Foocharoen

Peansukwech

Mahakkanukrauh

, et al. Clinical characteristics and outcomes of 566 Thais with systemic sclerosis: a cohort study. Int J Rheum Dis 2020; 23(7): 945–957.

Low

Teng

Law

, et al. Disease characteristics of the Singapore Systemic Sclerosis Cohort. Proc Singapore Healthcare 2013; 22: 8–14.

Pagalavan

Ong

. Demography, clinical and laboratory features of systemic sclerosis in a Malaysian rheumatology centre. Med J Malaysia 2007; 62(2): 117–121.

Van Den Hoogen

Khanna

Fransen

, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 2013; 72: 1747–1755.

Hirschl

Lenz

, et al. Transition from primary Raynaud’s phenomenon to secondary Raynaud’s phenomenon identified by diagnosis of an associated disease: results of ten years of prospective surveillance. Arthritis Rheum 2006; 54: 1974–1981.

Cutolo

Pizzorni

Sulli

. Identification of transition from primary Raynaud’s phenomenon to secondary Raynaud’s phenomenon by nailfold videocapillaroscopy: comment on the article by Hirschl et al. Arthritis Rheum 2007; 56(6): 2102–2103.

Koenig

Joyal

Fritzler

, 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 Rheum 2008; 58(12): 3902–3912.

10.

Pavlov-Dolijanovic

Damjanov

Stojanovic

, et al. Scleroderma pattern of nailfold capillary changes as predictive value for the development of a connective tissue disease: a follow-up study of 3,029 patients with primary Raynaud’s phenomenon. Rheumatol Int 2012; 32(10): 3039–3045.

11.

Spencer-Green

Alter

Welch

. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med 1997; 103(3): 242–248.

12.

Ingegnoli

Herrick

Schioppo

, et al. Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus. Rheumatology 2021; 60: 1410–1418.

13.

Cutolo

Pizzorni

Tuccio

, et al. Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis. Rheumatology (Oxford) 2004; 43(6): 719–726.

14.

Cutolo

Sulli

Secchi

, et al. Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement? Rheumatology (Oxford) 2006; 45(Suppl. 4): iv43–iv46.

15.

Matucci-Cerinic

Allanore

Czirjak

, et al. The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy. Ann Rheum Dis 2009; 68: 1377–1380.

16.

Walker

Pope

Baron

, et al. The development of systemic sclerosis classification criteria. Clin Rheumatol 2007; 26: 1401–1409.

17.

Dalakas

Hohlfeld

. Polymyositis and dermatomyositis. Lancet 2003; 362: 971–982.

18.

Alarcon-Segovia

Villareal

. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa

Sharp

(eds) Mixed connective tissue diseases and anti-nuclear antibodies. Amsterdam: Elsevier, 1987, pp. 33–40.

19.

Reveille

. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther 2003; 5: 80–93.

20.

Lonzetti

Joyal

Raynauld

, et al. Updating the American College of Rheumatology preliminary classification criteria for systemic sclerosis: addition of severe nailfold capillaroscopy abnormalities markedly increases the sensitivity for limited scleroderma. Arthritis Rheum 2001; 44(3): 735–736.

21.

Blockmans

Beyens

Verhaeghe

. Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases. Clin Rheumatol 1996; 15(2): 148–153.

22.

Valentini

Vettori

Cuomo

, et al. Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement. Arthritis Res Ther 2012; 14: R188.