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

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

#### **Figure 11.**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

hemorrhages, neoangiogenesis, and avascular areas [25] (**Figure 5**).

independently of disease severity [27–29].

**4.2 Systemic lupus erythematosus (SLE)**

**4.3 Inflammatory idiopathic myositis**

extent of organ involvement [8].

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

A large multinational study based on EULAR Scleroderma Trials and Research

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

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,

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,

changes as neoangiogenesis are less common in SLE patients [32, 33].

(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,

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

#### **Figure 12.**

*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 Cabral.*

### **4.5 Sjögren syndrome**

In patients with Sjögren syndrome (SSj), NFC can be normal in up to 59% of cases, if RP is absent [19]. The more frequent findings in this disease are tortuosities, crossings, and ingurgitated venous plexus (**Figure 9**). In patients carrying positive anticentromere antibody, dilated loops and giant capillaries can also be found. No correlations were stated between NFC changes and laboratory parameters.

#### **4.6 Rheumatoid arthritis**

The different abnormalities found in rheumatoid arthritis patients confirm the coexistence of microangiopathy in this disease [37]. In patients without rheumatoid vasculitis, it is frequent to find thin, long, and tortuous capillaries, with ingurgitated anarchic venous plexus and microhemorrhages [19]. These changes have no correlation with disease activity. Dilated or giant capillaries are rare and justify a closer follow-up.

#### **4.7 Psoriasis**

NFC in psoriasis usually reveals a reduced capillary density, with avascular areas, and morphologically abnormal capillaries [38]. No correlation was found between capillary density and disease duration or the extent of skin involvement, but avascular areas are more frequent in patients whose nails are also affected. If the exam is performed over the psoriasis plaques, dilated and long loops can be seen, with interstitial edema and fast blood flow [19].
