J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 11, Number 7, July 2019, pages 524-531

Clinical Manifestation and Incidence of Cardiopulmonary Complications in Early Systemic Sclerosis Patients with Different Antibody Profiles

Figure 1. The cumulative incidence of (a) LVEF < 50%, (b) RV dysfunction, (c) suspected PH, and (d) ILD in early SSc patients by different antibody profiles. The P value was from the log-rank test. LVEF: left ventricular ejection fraction; RV: right ventricular; PH: pulmonary arterial hypertension; ILD: interstitial lung disease.

**Table 1.** Demographics
	ATA positive (n = 89)	ATA negative (n = 18)	ACA positive (n = 7)	P value
Data are expressed as mean ± SD or number (%); dcSSc: diffuse cutaneous systemic sclerosis; in total group, immunosuppressive medication included: 30 cyclophosphamide (26.3%), 14 methotrexate (12.3%), five azathioprine (4.4%), and three mycophenolate mofetil (2.6%). ^aP < 0.05, ATA positive versus ATA negative; ^bP < 0.05, ATA negative versus ACA positive; ^cP < 0.05, ATA positive versus ACA positive.
DcSSc subtype	79 (88.8)^{a, c}	9 (50.0)	2 (28.6)	< 0.001
Female	50 (56.2)	14 (77.8)	5 (71.4)	0.206
Age at diagnosis (years)	52.0 ± 8.3	49.7 ± 10.1	48.6 ± 6.2	0.377
Disease duration (months)	11.7 ± 8.9^c	8.1 ± 4.6^b	21.4 ± 8.9	0.003
Follow-up duration (years)	3.9 ± 1.6	3.5 ± 1.4	3.4 ± 1.5	0.466
Presenting manifestation
Raynaud’s phenomenon	12 (13.5)	6 (33.3)	1 (14.3)	0.120
Swollen or indurated skin	18 (20.2)	3 (16.7)	0	0.666
Arthritis	6 (6.7)	1 (5.6)	0	1.000
Combined manifestation	49 (55.1)	7 (38.9)	6 (85.7)	0.120
Current medication
Immunosuppressant	42 (47.2)	6 (33.3)	4 (57.1)	0.442
Corticosteroid	39 (43.8)	7 (38.9)	2 (28.6)	0.830

Table 1. Demographics

ATA positive (n = 89)

ATA negative (n = 18)

ACA positive (n = 7)

P value

Data are expressed as mean ± SD or number (%); dcSSc: diffuse cutaneous systemic sclerosis; in total group, immunosuppressive medication included: 30 cyclophosphamide (26.3%), 14 methotrexate (12.3%), five azathioprine (4.4%), and three mycophenolate mofetil (2.6%). ^aP < 0.05, ATA positive versus ATA negative; ^bP < 0.05, ATA negative versus ACA positive; ^cP < 0.05, ATA positive versus ACA positive.

DcSSc subtype

79 (88.8)^{a, c}

9 (50.0)

2 (28.6)

< 0.001

Female

50 (56.2)

14 (77.8)

5 (71.4)

0.206

Age at diagnosis (years)

52.0 ± 8.3

49.7 ± 10.1

48.6 ± 6.2

0.377

Disease duration (months)

11.7 ± 8.9^c

8.1 ± 4.6^b

21.4 ± 8.9

0.003

Follow-up duration (years)

3.9 ± 1.6

3.5 ± 1.4

3.4 ± 1.5

0.466

Presenting manifestation

Raynaud’s phenomenon

12 (13.5)

6 (33.3)

1 (14.3)

0.120

Swollen or indurated skin

18 (20.2)

3 (16.7)

0.666

Arthritis

6 (6.7)

1 (5.6)

1.000

Combined manifestation

49 (55.1)

7 (38.9)

6 (85.7)

0.120

Current medication

Immunosuppressant

42 (47.2)

6 (33.3)

4 (57.1)

0.442

Corticosteroid

39 (43.8)

7 (38.9)

2 (28.6)

0.830

**Table 2.** Comparison of Initial Clinical Manifestations by Immunological Profile at Cohort Entry
Clinical manifestation at entry	ATA positive (n = 89)	ATA negative (n = 18)	ACA positive (n = 7)	P value
The data are presented as n (%); LVEF: left ventricular ejection fraction; RVD: right ventricular dysfunction; ILD: interstitial lung disease; sPAP: estimated systolic pulmonary arterial pressure. ^aP < 0.05, ATA positive versus ATA negative; ^bP < 0.05, ATA negative versus ACA positive; ^cP < 0.05, ATA positive versus ACA positive.
Peripheral vascular manifestations
Raynaud’s phenomenon	78 (87.6)	18 (100)	5 (71.4)	0.091
Digital pitting scar	50 (56.2)	5 (27.8)	4 (57.1)	0.082
Digital ulcer	8 (9.0)	0	1 (14.3)	0.313
Telangiectasia	29 (32.6)^a	1 (5.6)	3 (42.9)	0.028
Skin manifestations
mRSS	21.1 ± 10.2^{a, c}	12.6 ± 6.7^b	7.1 ± 8.2	< 0.001
Hypo-hyperpigmentation	72 (80.9)^c	11 (61.1)	1 (14.3)	< 0.001
Musculoskeletal manifestations
Arthritis	23 (25.8)	5 (27.8)	2 (28.6)	1.000
Joint contracture	42 (47.2)	8 (44.4)	2 (28.6)	0.692
Tendon friction rub	12 (13.5)	0	0	0.244
Suspected myositis	15 (16.9)	4 (22.2)	0	0.522
Digestive tract involvement
Gastroesophageal reflux	37 (41.6)	7 (38.9)	4 (57.1)	0.690
Dysphagia	20 (22.5)	8 (44.4)	1 (14.3)	0.130
Heart involvement
Conduction alteration	13 (14.6)	1 (5.6)	0	0.475
Pericardial effusion	4 (4.5)	1(5.6)	0	1.000
LVEF < 50%	2 (2.2)	0	0	1.000
RVD	3 (3.4)	1 (5.6)	0	0.634
Lung involvement
ILD	72 (80.9)^c	14 (77.8)^b	0	< 0.001
sPAP ≥ 50 mm Hg	4 (4.5)	2 (11.1)	0	0.502
Scleroderma renal crisis	0	0	0
Sicca symptoms
Dry eyes	10 (11.2)	3 (16.7)	1 (14.3)	0.568
Dry mouth	25 (28.1)	8 (44.4)	2 (28.6)	0.409

Table 2. Comparison of Initial Clinical Manifestations by Immunological Profile at Cohort Entry

Clinical manifestation at entry

ATA positive (n = 89)

ATA negative (n = 18)

ACA positive (n = 7)

P value

The data are presented as n (%); LVEF: left ventricular ejection fraction; RVD: right ventricular dysfunction; ILD: interstitial lung disease; sPAP: estimated systolic pulmonary arterial pressure. ^aP < 0.05, ATA positive versus ATA negative; ^bP < 0.05, ATA negative versus ACA positive; ^cP < 0.05, ATA positive versus ACA positive.

Peripheral vascular manifestations

Raynaud’s phenomenon

78 (87.6)

18 (100)

5 (71.4)

0.091

Digital pitting scar

50 (56.2)

5 (27.8)

4 (57.1)

0.082

Digital ulcer

8 (9.0)

1 (14.3)

0.313

Telangiectasia

29 (32.6)^a

1 (5.6)

3 (42.9)

0.028

Skin manifestations

mRSS

21.1 ± 10.2^{a, c}

12.6 ± 6.7^b

7.1 ± 8.2

< 0.001

Hypo-hyperpigmentation

72 (80.9)^c

11 (61.1)

1 (14.3)

< 0.001

Musculoskeletal manifestations

Arthritis

23 (25.8)

5 (27.8)

2 (28.6)

1.000

Joint contracture

42 (47.2)

8 (44.4)

2 (28.6)

0.692

Tendon friction rub

12 (13.5)

0.244

Suspected myositis

15 (16.9)

4 (22.2)

0.522

Digestive tract involvement

Gastroesophageal reflux

37 (41.6)

7 (38.9)

4 (57.1)

0.690

Dysphagia

20 (22.5)

8 (44.4)

1 (14.3)

0.130

Heart involvement

Conduction alteration

13 (14.6)

1 (5.6)

0.475

Pericardial effusion

4 (4.5)

1(5.6)

1.000

LVEF < 50%

2 (2.2)

1.000

RVD

3 (3.4)

1 (5.6)

0.634

Lung involvement

ILD

72 (80.9)^c

14 (77.8)^b

< 0.001

sPAP ≥ 50 mm Hg

4 (4.5)

2 (11.1)

0.502

Scleroderma renal crisis

Sicca symptoms

Dry eyes

10 (11.2)

3 (16.7)

1 (14.3)

0.568

Dry mouth

25 (28.1)

8 (44.4)

2 (28.6)

0.409

**Table 3.** Comparison of Cumulative Clinical Manifestations by Immunological Profile at the Last Visit
Cumulative clinical manifestation	ATA positive (n = 89)	ATA negative (n = 18)	ACA positive (n = 7)	P value
The data are presented as n (%); LVEF: left ventricular ejection fraction; RVD: right ventricular dysfunction; ILD: interstitial lung disease; sPAP: estimated systolic pulmonary arterial pressure. ^aP < 0.05, ATA positive versus ATA negative; ^bP < 0.05, ATA negative versus ACA positive; ^cP < 0.05, ATA positive versus ACA positive.
Peripheral vascular manifestations
Raynaud’s phenomenon	88 (98.9)	18 (100.0)	6 (85.7)	0.143
Digital pitting scar	76 (85.4)^a	11 (61.1)	4 (57.1)	0.016
Digital ulcer	37 (41.6)^a	2 (11.1)	1 (14.3)	0.020
Telangiectasia	75 (84.3)^a	10 (55.6)	5 (71.4)	0.016
Skin manifestations
Hypo-hyperpigmentation	85 (95.5)	15 (83.3)	5 (71.4)	0.023
Musculoskeletal manifestations
Arthritis	38 (42.7)	8 (44.4)	3 (42.9)	1.000
Joint contracture	55 (61.8)^{a, c}	5 (27.8)	1 (14.3)	0.002
Tendon friction rub	30 (33.7)^a	1 (5.6)	1 (14.3)	0.025
Suspected myositis	15 (16.9)	5 (27.8)	0	0.292
Digestive tract involvement
Gastroesophageal reflux	79 (88.8)	15 (83.3)	7 (100.0)	0.541
Dysphagia	44 (49.4)	11 (61.1)	3 (42.9)	0.686
Heart involvement
Conduction alteration	22 (24.7)	1 (5.6)	0	0.094
Pericardial effusion	4 (4.5)	0	0	1.00
LVEF < 50%	15 (16.9)	1 (5.6)	0	0.348
RVD	19 (21.3)	1 (5.6)	0	0.158
Lung involvement
ILD	78 (87.6)^c	16 (88.9)^b	2 (28.6)	0.002
sPAP ≥ 50 mm Hg	8 (9.0)	3 (16.7)	0	0.465
Scleroderma renal crisis	0	0	0
Sicca symptoms
Dry eyes	46 (51.7)	11 (61.1)	5 (71.4)	0.569
Dry mouth	43 (48.3)	9 (50.0)	4 (57.1)	0.942

Table 3. Comparison of Cumulative Clinical Manifestations by Immunological Profile at the Last Visit

Cumulative clinical manifestation

ATA positive (n = 89)

ATA negative (n = 18)

ACA positive (n = 7)

P value

Peripheral vascular manifestations

Raynaud’s phenomenon

88 (98.9)

18 (100.0)

6 (85.7)

0.143

Digital pitting scar

76 (85.4)^a

11 (61.1)

4 (57.1)

0.016

Digital ulcer

37 (41.6)^a

2 (11.1)

1 (14.3)

0.020

Telangiectasia

75 (84.3)^a

10 (55.6)

5 (71.4)

0.016

Skin manifestations

Hypo-hyperpigmentation

85 (95.5)

15 (83.3)

5 (71.4)

0.023

Musculoskeletal manifestations

Arthritis

38 (42.7)

8 (44.4)

3 (42.9)

1.000

Joint contracture

55 (61.8)^{a, c}

5 (27.8)

1 (14.3)

0.002

Tendon friction rub

30 (33.7)^a

1 (5.6)

1 (14.3)

0.025

Suspected myositis

15 (16.9)

5 (27.8)

0.292

Digestive tract involvement

Gastroesophageal reflux

79 (88.8)

15 (83.3)

7 (100.0)

0.541

Dysphagia

44 (49.4)

11 (61.1)

3 (42.9)

0.686

Heart involvement

Conduction alteration

22 (24.7)

1 (5.6)

0.094

Pericardial effusion

4 (4.5)

1.00

LVEF < 50%

15 (16.9)

1 (5.6)

0.348

RVD

19 (21.3)

1 (5.6)

0.158

Lung involvement

ILD

78 (87.6)^c

16 (88.9)^b

2 (28.6)

0.002

sPAP ≥ 50 mm Hg

8 (9.0)

3 (16.7)

0.465

Scleroderma renal crisis

Sicca symptoms

Dry eyes

46 (51.7)

11 (61.1)

5 (71.4)

0.569

Dry mouth

43 (48.3)

9 (50.0)

4 (57.1)

0.942