**4. Nailfold capillaroscopy in autoimmune connective tissue diseases**

AICTD complex pathogenesis usually includes microvascular changes, with occurrence of progressive structural and functional damage of the capillaries. Therefore, NFC became an important diagnostic and prognostic tool to use while managing these disorders.

### **4.1 Systemic sclerosis (SSc)**

Systemic sclerosis has probably been the most studied disease with NFC. It is a severe AICTD in which the main pathological events are endothelial dysfunction,

fibrosis, and inflammation, which usually results in skin and vascular changes [24]. These include an important damage of microvascular network, with enlarged and giant capillaries, capillary loss with disarrangement of capillaries' architecture, and neoangiogenesis. As mentioned above, the scleroderma patterns are divided into three different patterns: "early," revealing only few enlarged capillaries, few hemorrhages, and preserved capillary density; "active," showing frequent giant capillaries and hemorrhages, mild capillary loss, and disorganization of the microvascular network; and "late," where irregular and giant capillaries can be found, as with few hemorrhages, neoangiogenesis, and avascular areas [25] (**Figure 5**).

A large multinational study based on EULAR Scleroderma Trials and Research (EUSTAR) registry disclosed a scleroderma pattern in more than 86% of SSc patients [24]. Subjects without this pattern did not have organ involvement and RP and some had negative autoantibodies. These results suggest that although these patients were classified as having an SSc, they did not have an overt disease and, then, nonspecific NFC changes may precede an evolving scleroderma pattern. In patients with overt disease, capillaroscopic findings mirror somehow internal organ involvement evolution. Following disease progression, dynamic transition of microvascular abnormalities through different NFC patterns can be found in up to 50% of SSc patients [18, 26]. On the other hand, capillaroscopy patterns can improve after up to 4 years of combined treatment, revealing a progressive significant recovery in structure and function of microcirculation, associated to ameliorated outcomes, independently of disease severity [27–29].

Capillaroscopy abnormalities became one of the diagnostic criteria for SSc in the 2013 classification [6]. NFC should not only be used for a diagnostic purpose but also for monitoring the disease process and determining its prognosis, because, as explained above, its dynamic changes occur, and its severity directly relates to the extent of organ involvement [8].

#### **4.2 Systemic lupus erythematosus (SLE)**

A systematic review was recently performed by a EULAR study group, in order to establish capillaroscopic parameters in SLE patients and its correlations with clinical and laboratory characteristics [30]. According to this study, SLE patients present more tortuous and abnormal capillaries than healthy controls, as well as more hemorrhages (**Figure 11**). An NFC score was created by these authors to set the microangiopathy severity, SLE patients being those who had the higher scores. "Nonspecific patterns" and "scleroderma-like patterns" were also described. A correlation between NFC abnormalities and clinical and laboratory parameters was established, since a relationship between NFC score and SLE activity was disclosed. Further, it is an important note to highlight that, once SLE is a heterogeneous disease, with altered vascular involvement, probably capillaroscopic changes will only be seen in the active phase of the disease [31]. Also, as the microvasculopathy profile in SLE is quite different from the SSc's, which is typically obliterative, changes as neoangiogenesis are less common in SLE patients [32, 33].

#### **4.3 Inflammatory idiopathic myositis**

In inflammatory idiopathic myopathies (IIM), it is frequent to find tortuosities, capillary loss, enlarged and giant capillaries, microhemorrhages, and neoangiogenesis, as well as a disorganization of the vascular network and avascular areas [1, 34]. In dermatomyositis (DM), patients present more severe NFC findings, compared with those with polymyositis (PM). Ramified and bushy capillaries represent a hallmark of microvascular damage in DM (**Figure 10**). In these patients,

**179**

*Cabral.*

**Figure 12.**

**Figure 11.**

*The Impact of Nailfold Capillaroscopy in the Approach of Microcirculation*

capillaroscopic abnormalities seem to be related with disease duration: in the first 6 months of disease duration, capillary density is usually reduced and giant capillaries are frequent; after that period, scleroderma pattern becomes more common. In PM patients, NFC findings do not significantly differ from healthy controls. It has also been demonstrated that there is a potential relationship between capillary changes and organ involvement, especially in patients with lung disease [35]. A recent multicenter study in antisynthetase syndrome revealed that NFC changes are usually independent from the presence of RP [27]. In these patients, the scleroderma pattern is associated to positivity for anti-Jo1 antibodies and a longer disease duration. An interesting finding was that significant correlation was established between ILD and ramified capillaries, but not with SSc-like pattern. Together, these studies suggest that NFC can become an important indicator of interstitial lung disease in patients with IIM, disclosing early this potential life-

In MCTD, different abnormalities can be found: minor changes, hemorrhages, dilated and giant capillaries, reduced density, and neoangiogenesis [19] (**Figure 12**). The patients can present with a scleroderma-like pattern, but less severe when compared to systemic sclerosis. The dilated loops are usually more dystrophic, and the dilated loops are long. The neoangiogenesis features are normally present in patients who progress to SSc. The avascular areas are more frequent in patients with

*Systemic lupus erythematosus. Images from three different patients, revealing crossing capillaries (x), dilated loops (square), meandering capillaries (black circle), tortuosities (arrow), ingurgitated venous plexus (plus sign), and loop aneurysm (\*). Images were taken using Videocap biomicroscope, version 3.0, magnification* 

*Images from 3 different patients with mixed connective tissue disease. Capillaroscopic findings include crossing (x), meandering (black circle), tortuosity (arrow), dilated loops (black square), giant capillaries (black dot), neoangiogenesis (black star), and clear avascular areas on the right image. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry* 

*DOI: http://dx.doi.org/10.5772/intechopen.90525*

threatening manifestation.

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

pulmonary involvement or under immunosuppressants [36]**.**

*×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### *The Impact of Nailfold Capillaroscopy in the Approach of Microcirculation DOI: http://dx.doi.org/10.5772/intechopen.90525*

capillaroscopic abnormalities seem to be related with disease duration: in the first 6 months of disease duration, capillary density is usually reduced and giant capillaries are frequent; after that period, scleroderma pattern becomes more common. In PM patients, NFC findings do not significantly differ from healthy controls. It has also been demonstrated that there is a potential relationship between capillary changes and organ involvement, especially in patients with lung disease [35].

A recent multicenter study in antisynthetase syndrome revealed that NFC changes are usually independent from the presence of RP [27]. In these patients, the scleroderma pattern is associated to positivity for anti-Jo1 antibodies and a longer disease duration. An interesting finding was that significant correlation was established between ILD and ramified capillaries, but not with SSc-like pattern.

Together, these studies suggest that NFC can become an important indicator of interstitial lung disease in patients with IIM, disclosing early this potential lifethreatening manifestation.
