**7.1 Nailfold capillaroscopy and correlation with organ involvement**

There have been several studies which tried to look for correlation of capillaroscopic parameters with organ involvement in systemic sclerosis. Though the results from these studies have been variable, marked skin involvement and the presence

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**Figure 6.**

**Figure 5.**

majority of these studies.

of pulmonary arterial hypertension were found to correlate with capillary loss in

*Late SSc pattern showing severe architectural distortion and capillary dropouts.*

Sato et al. [13] and Bhakuni et al. [14] found that capillary loss was associated with higher skin scores as assessed by modified Rodnan skin scores. Also the significant loss of capillaries in diffuse cutaneous disease as compared to limited disease was observed by Bhakuni et al. [14] and Ostojic et al. [15] in their study. These studies showed, with the increasing skin thickness, the capillary density

*Nailfold Capillaroscopy in Rheumatic Diseases DOI: http://dx.doi.org/10.5772/intechopen.92786*

*Active SSc pattern showing hemorrhages and giant capillaries.*

**Figure 4.** *Early SSc pattern showing few giant capillaries.*

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

the exclusion of scleroderma [11].

late [12].

**7. Capillaroscopy in systemic sclerosis**

evident loss of capillaries (**Figure 4**).

and ramified capillaries (**Figure 6**).

Raynaud's—normal, borderline, and abnormal patterns. Authors proposed the borderline NFC abnormalities (composed of shorter and more tortuous capillaries) are due to the long-standing vasospastic reaction of the Raynaud's itself. Of interest though is the finding of abnormal capillaroscopic pattern in 8/44 patients with idiopathic Raynaud's phenomenon. These are the group of patients who might be at a higher risk for developing connective tissue disease on follow-up. On the other hand, the absence of NFC abnormalities in a patient of Raynaud's is also helpful in

Three capillaroscopic patterns have been described in SSc: early, active, and

SSc-early pattern: it is characterized by the presence of few giant capillaries, few capillary hemorrhages, relatively well-preserved capillary distribution, and no

SSc-active pattern: in active pattern frequent giant capillaries are seen with frequent capillary hemorrhages, moderate loss of capillaries, mild disorganization

SSc-late pattern: in late pattern irregular enlargement of the capillaries with few or absent giant capillaries and hemorrhages are seen. There is severe loss of capillaries with extensive avascular areas, disorganization of the normal capillary array,

There have been several studies which tried to look for correlation of capillaroscopic parameters with organ involvement in systemic sclerosis. Though the results from these studies have been variable, marked skin involvement and the presence

of the capillary architecture, and mild ramified capillaries (**Figure 5**).

**7.1 Nailfold capillaroscopy and correlation with organ involvement**

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**Figure 4.**

*Early SSc pattern showing few giant capillaries.*

**Figure 5.** *Active SSc pattern showing hemorrhages and giant capillaries.*

**Figure 6.** *Late SSc pattern showing severe architectural distortion and capillary dropouts.*

of pulmonary arterial hypertension were found to correlate with capillary loss in majority of these studies.

Sato et al. [13] and Bhakuni et al. [14] found that capillary loss was associated with higher skin scores as assessed by modified Rodnan skin scores. Also the significant loss of capillaries in diffuse cutaneous disease as compared to limited disease was observed by Bhakuni et al. [14] and Ostojic et al. [15] in their study. These studies showed, with the increasing skin thickness, the capillary density

decreases and thus patients with diffuse cutaneous disease which has higher skin scores have more marked capillary loss.

The association between the presence of pulmonary hypertension (PAH) and various capillary parameters was also studied using either echocardiography or right heart catheterization to define PAH. The first study of NFC to use right heart catheterization (RHC) evaluated 44 SSc patients and found that SSc patients with more capillary abnormalities (defined by increased apical limb width, capillary width, area, and capillary length) correlated with higher pulmonary vascular resistance, but capillary density was not evaluated in this study [16]. Hofstee et al. [17] in a recent study using RHC (mean pulmonary artery pressure (PAP) of >25 mmHg at rest or >30 mmHg during exercise as cutoff for PAH) found capillary loss to be significantly associated with PAH. Riccieri et al. [18] used echocardiography for screening (PASP>35) and RHC for confirmation of PAH. A total of 24 patients of SSc were studied of which 12 had PAH. Significantly more capillary alterations and more avascular areas were found in patients with PAH. Among the studies using echocardiographic screening for PAH, Sato et al. [13] defined PAH as PASP >35 mmHg and could not find any significant association between the presence of PAH and various capillary parameters. Castellvi et al. however found the neoangiogenesis to be significantly associated with PAH (PASP > 40 on echocardiography) [19]. One more study, did not find significant difference among NFC patterns in patients with elevated PASP [20].

The correlation between the presence of interstitial lung disease and capillaroscopy parameters is not as consistent as that for PAH. Castellvi et al. [19] found that patients with loss of capillaries on NFC had worse DLCO and FVC; however none of the three SSc patterns (early, active, and late) showed any association with FVC/DLCO ratio. Another study using FVC < 75% of predicted value and/or HRCT and/or chest radiographic changes to define ILD could not find any difference in capillary parameters in patients with and without ILD [20]. However 1 study which screened 91 patients with SSc did found that patients with ground glass opacities on HRCT had significantly higher mean avascular scores [21]. Another recent study found that degree of neoangiogenesis was higher in SSc patients with honeycombing and DLCO < 50% and a number of avascular areas inversely correlated to DLCO/AV (alveolar volume) [22].

Among serologies some studies could find an association between Scl-70 and capillary density while no association was found with anti-centromere. Anti-Scl-70 positivity is seen in around 40% of dCSSc patients and carries an increased risk of mortality owing to its association with lung fibrosis and rapidly developing skin thickness [23]*.* The association of Scl-70 with active and late pattern was reported for the first time by Cutolo et al. [24]. Anti-Scl-70 antibodies were found to be significantly more prevalent in those with the "late" scleroderma pattern of capillaroscopy than "active" and "early" pattern in the EUSTAR cohort [25]. Another study found that vascular deletion score was significantly higher in patients with anti-Scl-70 positivity; however no correlation with capillary density was found [21]. A recent study could not find significant difference in NFC parameters between Scl-70 positive and negative patients, though avascular areas were numerically higher [22].

Association of anti-centromere antibodies with any of the parameter on capillaroscopy have been inconsistent. Herrick et al. found that reduced capillary density was associated with positive anti-centromere antibody [26]. Another study found that anti-centromere was significantly more prevalent in early and active pattern on capillaroscopy than late scleroderma pattern [27]. Most of the other recent studies failed to find significant relationship between ACA positivity and

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SSc on follow-up.

*Nailfold Capillaroscopy in Rheumatic Diseases DOI: http://dx.doi.org/10.5772/intechopen.92786*

**8.1 Systemic lupus erythematosus (SLE)**

**8.2 Dermatomyositis (DM) and polymyositis**

**8.3 Mixed connective tissue disease (MCTD)**

discussed below.

with the disease activity.

NFC parameters [13, 22]. The presence of ACA has been associated with a lower frequency and severity of radiographic interstitial pulmonary fibrosis [28].

The role of NFC in other rheumatic diseases is much well established compared

to SSc. Some of the salient features of NFC in various rheumatic diseases are

Nearly half of the patients with SLE have a normal capillaroscopic pattern. Others have a tortuous, meandering capillaries, bizarre loops, and a prominent subcapillary venous plexus [29]. In a systematic review by Cutolo et al. [30], 40 studies describing the capillaroscopic patterns in SLE were studied. They found the meandering capillaries and hemorrhages are to occur more frequently in patients with SLE and significantly less hairpin shaped loops compared to healthy individuals. Of note, they found the dilated capillaries to be associated with Raynaud's and gangrene in lupus patients. In seven of these studies, NFC scores also correlated

The scleroderma pattern is observed in 20–60% of patients with more frequent and pronounced findings in dermatomyositis [31]. Juvenile dermatomyositis (JDM) can reveal phasic changes on NFC. Early stages of microhemorrhages and giant capillaries are followed later by capillary loss and neoangiogenesis [32]. In dermatomyositis, these phasic changes are less obvious. Interestingly, shorter duration of disease is associated with more sever changes—giant capillaries and reduced capillary density. Longer duration of disease is typified by the presence of extensively ramified capillaries [33]. There also appears to be a strong correlation between the NFC involvement and cutaneous activity [34]. In JDM patients, lack of resolution of NFC changes is associated with the more severe and chronic forms of the disease [32]. An association has also been described between capillary abnormalities and ILD, Raynaud's, and malignancy [35]. However, currently the data correlating with

disease activity is sparse to formulate any definitive recommendations.

tion of CD and/or improvement in dilated loops and hemorrhages [36].

**8.4 Undifferentiated connective tissue disease (UCTD)**

Scleroderma pattern is observed in 65% patients of MCTD. The presence of avascular areas has a strong correlation with the presence of interstitial lung disease [36]. In a proportion of the patients, the NFC changes can revert with normaliza-

NFC can help in the establishing the presence of a connective tissue disease in a patient with equivocal findings. Scleroderma pattern is observed in 9/65 (13.8%) of patients with UCTD in one study [37]. Approximately a quarter of the patients with UCTD may transform into SSc on follow-up [38]. Hence capillaroscopic examination could be of value in identifying the patients of UCTD who could progress to

**8. Nailfold capillaroscopy in other rheumatic diseases**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

scores have more marked capillary loss.

decreases and thus patients with diffuse cutaneous disease which has higher skin

The association between the presence of pulmonary hypertension (PAH) and various capillary parameters was also studied using either echocardiography or right heart catheterization to define PAH. The first study of NFC to use right heart catheterization (RHC) evaluated 44 SSc patients and found that SSc patients with more capillary abnormalities (defined by increased apical limb width, capillary width, area, and capillary length) correlated with higher pulmonary vascular resistance, but capillary density was not evaluated in this study [16]. Hofstee et al. [17] in a recent study using RHC (mean pulmonary artery pressure (PAP) of >25 mmHg at rest or >30 mmHg during exercise as cutoff for PAH) found capillary loss to be significantly associated with PAH. Riccieri et al. [18] used echocardiography for screening (PASP>35) and RHC for confirmation of PAH. A total of 24 patients of SSc were studied of which 12 had PAH. Significantly more capillary alterations and more avascular areas were found in patients with PAH. Among the studies using echocardiographic screening for PAH, Sato et al. [13] defined PAH as PASP >35 mmHg and could not find any significant association between the presence of PAH and various capillary parameters. Castellvi et al. however found the neoangiogenesis to be significantly associated with PAH (PASP > 40 on echocardiography) [19]. One more study, did not find significant difference among NFC patterns in patients with elevated

The correlation between the presence of interstitial lung disease and capillaroscopy parameters is not as consistent as that for PAH. Castellvi et al. [19] found that patients with loss of capillaries on NFC had worse DLCO and FVC; however none of the three SSc patterns (early, active, and late) showed any association with FVC/DLCO ratio. Another study using FVC < 75% of predicted value and/or HRCT and/or chest radiographic changes to define ILD could not find any difference in capillary parameters in patients with and without ILD [20]. However 1 study which screened 91 patients with SSc did found that patients with ground glass opacities on HRCT had significantly higher mean avascular scores [21]. Another recent study found that degree of neoangiogenesis was higher in SSc patients with honeycombing and DLCO < 50% and a number of avascular areas inversely correlated to

Among serologies some studies could find an association between Scl-70 and capillary density while no association was found with anti-centromere. Anti-Scl-70 positivity is seen in around 40% of dCSSc patients and carries an increased risk of mortality owing to its association with lung fibrosis and rapidly developing skin thickness [23]*.* The association of Scl-70 with active and late pattern was reported for the first time by Cutolo et al. [24]. Anti-Scl-70 antibodies were found to be significantly more prevalent in those with the "late" scleroderma pattern of capillaroscopy than "active" and "early" pattern in the EUSTAR cohort [25]. Another study found that vascular deletion score was significantly higher in patients with anti-Scl-70 positivity; however no correlation with capillary density was found [21]. A recent study could not find significant difference in NFC parameters between Scl-70 positive and negative patients, though avascular areas were numerically

Association of anti-centromere antibodies with any of the parameter on capil-

laroscopy have been inconsistent. Herrick et al. found that reduced capillary density was associated with positive anti-centromere antibody [26]. Another study found that anti-centromere was significantly more prevalent in early and active pattern on capillaroscopy than late scleroderma pattern [27]. Most of the other recent studies failed to find significant relationship between ACA positivity and

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higher [22].

PASP [20].

DLCO/AV (alveolar volume) [22].

NFC parameters [13, 22]. The presence of ACA has been associated with a lower frequency and severity of radiographic interstitial pulmonary fibrosis [28].
