**2. Capillaroscopy procedures**

NFC is commonly performed in nailfold cuticles, as the capillary loops become more parallel to the skin surface in this area and can be observed in their full length in the last row [2]. Usually, eight fingers are examined: the 2nd, 3rd, 4th, and 5th [1, 19]. The thumbs are excluded because, in these fingers, capillaries are poorly observed and microtrauma is more frequent due to thumb's opponency. At least four images should be taken from each finger, in order to maximize nailfold area visualization (**Figure 1**). Less than eight nailfold reduces the sensitivity to detect capillary changes [20]. So, in a regular exam, at least 32 pictures are taken from each hand when using a videocapillaroscope.

The patient should stay at least 20 minutes in a climatized room (20–22°C), to reduce RP attacks, and a clinical examination should be performed in his or her hands, in order to avoid traumatic injuries and to detect sclerodactyly, edema, pitting scars, active arthritis, skin lesions, onychophagia, or other possible changes [19, 21]. As several physiological and external factors can affect NFC image quality, patients are asked to avoid cutting cuticle or even the nails in the previous week, prevent nail varnish removal, and avoid smoking or drinking caffeine-containing beverages in the preceding hours [7]. To improve the amount of light reaching the nails and then ameliorate image quality, an immersing oil is used between the skin and the lens.

Different devices can be used for microcirculation visualization:


**173**

include the following:

(**Figure 4A**).

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

option and requires specialized training [7].

**3. Nailfold capillaroscopy assessment and classification**

abnormal shapes, or visibility of the subpapillary venous plexus.

the number of loops in the distal row in a 1 mm2

• Videocapillaroscope (**Figure 1**): it has an excellent image quality and reproducibility and variable magnification from 200–600×. It has a portable system enabling its use in patients with severe joint contractures, and it carries specific software for capturing and analyzing the images, yet it is the most expensive

*Nailfold capillaroscopy should be performed in 2nd, 3rd, 4th, and 5th fingers, dividing each nailfold cuticle into 4 areas and taking images from each of them. (A) Clinical examination of the fingers should be performed before the exam begins. (B) Performing videocapillaroscopy using Videocap biomicroscope, version 3.0. (C, D).*

NFC procedure includes the assessment of morphologic and some functional parameters: skin transparency, capillary density and orientation, venous plexus visualization, presence of neoangiogenesis or microhemorrhages, capillary loop diameter, length and morphology, and characteristics of blood flow [1, 21]. The number of capillaries has been validated as the most important criterion for the patient follow-up [22].

NFC studies lead to the detection of microvascular abnormalities. Some of them, rarer, have a clear pathological significance and can disclose early an AICTDthey are called the "major abnormalities" [1]. Among those are giant capillaries, capillary architecture disorganization, microhemorrhages, neoangiogenesis, and capillary loss. Other abnormalities, more frequent, have an uncertain pathological meaning and represent an overlap between the scope of normality and microangiopathy-they are called the "minor abnormalities." Those are principally tortuosity,

Capillaroscopic parameters are usually evaluated through qualitative, semiquantitative, and quantitative analysis. The qualitative assessment implies pattern recognition and describes the global microvascular array and architecture, shape and distribution of the capillaries, and abnormalities of single loops. It readily allows a distinction between a normal capillaroscopy exam and an abnormal one [20]. The semiquantitative analysis is focused on major NFC changes. The quantitative evaluation estimates capillary density, avascular areas, diameter of enlarged capillaries, and the frequency of each abnormality. The quantification of capillaries includes

Normal capillaries are hairpin shaped and present a homogeneous distribution, in a "comb-like" structure [1] (**Figure 3**). Capillary density varies from 9 to 14 capillaries per millimeter in adults and at least 6 in children [1, 7, 23]. Abnormal shapes

• **Tortuous capillaries**: arterial and venous limbs are curled but do not cross [23]

section of the nailfold (**Figure 2**).

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

**Figure 1.**

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

#### **Figure 1.**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

(EULAR) study groups [15–17].

**2. Capillaroscopy procedures**

when using a videocapillaroscope.

(CSURI), to predict the appearance of new scleroderma ulcers and/or persistence of nonhealing lesions, within 3 months from NFC exam [14]. It has a good sensitivity, specificity, and positive predictive value, even in different devices. Its reliability has been successively demonstrated by European League Against Rheumatism

Indications for NFC do not resume to RP or other vascular acrosyndromes approach. It should be performed to any patient with microcirculation involvement from a systemic disease that includes AICTD, like systemic sclerosis, idiopathic inflammatory myositis, mixed connective tissue disease, and systemic lupus erythematosus, among others, but also other systemic diseases associated to microangiopathy, like vasculitides, diabetes, and arterial hypertension. As it also plays an important role in diagnosis, prognosis, and treatment monitoring of some diseases, capillaroscopy can be considered to act as a promising microcirculation biomarker [18].

NFC is commonly performed in nailfold cuticles, as the capillary loops become more parallel to the skin surface in this area and can be observed in their full length in the last row [2]. Usually, eight fingers are examined: the 2nd, 3rd, 4th, and 5th [1, 19]. The thumbs are excluded because, in these fingers, capillaries are poorly observed and microtrauma is more frequent due to thumb's opponency. At least four images should be taken from each finger, in order to maximize nailfold area visualization (**Figure 1**). Less than eight nailfold reduces the sensitivity to detect capillary changes [20]. So, in a regular exam, at least 32 pictures are taken from each hand

The patient should stay at least 20 minutes in a climatized room (20–22°C), to reduce RP attacks, and a clinical examination should be performed in his or her hands, in order to avoid traumatic injuries and to detect sclerodactyly, edema, pitting scars, active arthritis, skin lesions, onychophagia, or other possible changes [19, 21]. As several physiological and external factors can affect NFC image quality, patients are asked to avoid cutting cuticle or even the nails in the previous week, prevent nail varnish removal, and avoid smoking or drinking caffeine-containing beverages in the preceding hours [7]. To improve the amount of light reaching the nails and then ameliorate image quality, an immersing oil is used between the skin

• Ophthalmoscopes and traditional microscopes: they consist in low cost options and are widely available, which can be used with minimal training; the disadvantages include not only low magnifications (10–20×), but also it is hard

• Dermatoscopes: they have an intermediate cost; they are portable devices and easily available and have acceptable resolution and sensitivity for NFC abnormalities; however, they also have magnification restraint (20–40×) and can

• Stereomicroscopes: they also have an intermediate cost, they are easy to use, their magnification lens vary from 10–200×, but they are time-consuming and difficult to use in patients with joint contractures and they need an additional camera and fiber optic light source to capture the images, and a specialized

Different devices can be used for microcirculation visualization:

only detect gross NFC changes, and images are not reproducible.

handling and it has a poor reproducibility.

training is even required.

**172**

and the lens.

*Nailfold capillaroscopy should be performed in 2nd, 3rd, 4th, and 5th fingers, dividing each nailfold cuticle into 4 areas and taking images from each of them. (A) Clinical examination of the fingers should be performed before the exam begins. (B) Performing videocapillaroscopy using Videocap biomicroscope, version 3.0. (C, D).*

• Videocapillaroscope (**Figure 1**): it has an excellent image quality and reproducibility and variable magnification from 200–600×. It has a portable system enabling its use in patients with severe joint contractures, and it carries specific software for capturing and analyzing the images, yet it is the most expensive option and requires specialized training [7].

NFC procedure includes the assessment of morphologic and some functional parameters: skin transparency, capillary density and orientation, venous plexus visualization, presence of neoangiogenesis or microhemorrhages, capillary loop diameter, length and morphology, and characteristics of blood flow [1, 21]. The number of capillaries has been validated as the most important criterion for the patient follow-up [22].

### **3. Nailfold capillaroscopy assessment and classification**

NFC studies lead to the detection of microvascular abnormalities. Some of them, rarer, have a clear pathological significance and can disclose early an AICTDthey are called the "major abnormalities" [1]. Among those are giant capillaries, capillary architecture disorganization, microhemorrhages, neoangiogenesis, and capillary loss. Other abnormalities, more frequent, have an uncertain pathological meaning and represent an overlap between the scope of normality and microangiopathy-they are called the "minor abnormalities." Those are principally tortuosity, abnormal shapes, or visibility of the subpapillary venous plexus.

Capillaroscopic parameters are usually evaluated through qualitative, semiquantitative, and quantitative analysis. The qualitative assessment implies pattern recognition and describes the global microvascular array and architecture, shape and distribution of the capillaries, and abnormalities of single loops. It readily allows a distinction between a normal capillaroscopy exam and an abnormal one [20]. The semiquantitative analysis is focused on major NFC changes. The quantitative evaluation estimates capillary density, avascular areas, diameter of enlarged capillaries, and the frequency of each abnormality. The quantification of capillaries includes the number of loops in the distal row in a 1 mm2 section of the nailfold (**Figure 2**).

Normal capillaries are hairpin shaped and present a homogeneous distribution, in a "comb-like" structure [1] (**Figure 3**). Capillary density varies from 9 to 14 capillaries per millimeter in adults and at least 6 in children [1, 7, 23]. Abnormal shapes include the following:

• **Tortuous capillaries**: arterial and venous limbs are curled but do not cross [23] (**Figure 4A**).

#### **Figure 2.**

*Capillary density. Panel A: 1 capillary/mm2 ; panel B: 6 capillaries/mm<sup>2</sup> . (arrows) images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 3.**

*Examples of images of nailfold capillaroscopy captured in healthy subjects and considered as normal. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 4.**

*Examples of capillaroscopy abnormalities: Tortuosity (arrow), crossing (X), meandering (black circle), bushy capillaries (six-pointed star), subpapillary plexus visibility (plus sign), and dilated loop (black square). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*


**175**

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

venous limbs or different capillaries [7] (**Figure 5**).

• **Ramified capillaries:** there are abnormal connections between arterial and

• **Neoangiogenesis:** neoformations can be heterogeneous and may comprise shape heterogeneity, four or more capillaries within a single dermal papilla, elongated loops, branching, and interconnected capillaries [1] (**Figure 5**).

• **Bizarre loops**: capillaries with an atypical morphology, distinct from other

• **Dilated or enlarged loops**: there is not a universally accepted definition for loop enlargement, but it is usually considered if the limbs are enlarged about four times the normal width or if the width diameter is >20 μm. Nevertheless, a recent study from Cutolo et al suggests that dilations below 30 μm may be

• **Megacapillary or giant capillary**: capillaries with homogeneously enlarged

• **Hemorrhages**: microbleeding appears as dark masses adjacent to distal row, due to hemosiderin deposits. They result from disruption of the capillary wall,

• **Avascular areas**: lack of two or more successive capillaries. Loss of capillaries is associated with tissue hypoxia and subsequent digital ulcers and ischemia

arrangement of vessels with a greater caliber than the capillaries. Enlargement and congestion of venules and capillaries related to persistent opening of arteriovenous anastomoses, thus enabling a greater visibility [1] (**Figure 4**).

• **Subpapillary venous plexus visibility**: observation of large and linked

• **Capillary blood flow**: with powerful magnifications, when the blood flow is slow, it is possible to see the packs of red blood cells moving as a capillary

• **Capillary array and architecture disarrangement**: when shapes, length, and diameter vary in continuous loops, it leads to a complete distortion of a normal

Major NFC patterns divide into scleroderma and nonscleroderma pattern. Scleroderma pattern was first described by Maricq et al, through a combination of widening of the capillary loop, loss of capillaries, and disorganization of the nailfold capillary bed [1]. This pattern is frequently seen in scleroderma spectrum disorders, like systemic sclerosis, dermatomyositis, and mixed connective tissue disease and in RP without a clear diagnosis. Later, Cutolo et al further classified the scleroderma pattern into "early," "active," and "late" stages. "Early" scleroderma pattern presents with few giant capillaries and hemorrhages, relatively well-preserved capillary

• Elongated capillaries: capillary loops longer than 300 μm [7] (**Figure 7**).

loops with a branch diameter above 50 μm [1, 23] (**Figure 6**).

Other capillaroscopic parameters include the following:

either spontaneous or traumatic [1, 7] (**Figure 8**).

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

described categories [23].

[7, 23] (**Figure 2**).

sludge [1] (**Figure 9**).

capillary pattern [1] (**Figure 10**).

considered nonspecific [23] (**Figure 6**).

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

• Crossing capillaries: arterial and venous limbs cross at one point [23]

*Examples of capillaroscopy abnormalities: Tortuosity (arrow), crossing (X), meandering (black circle), bushy capillaries (six-pointed star), subpapillary plexus visibility (plus sign), and dilated loop (black square). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold* 

*Examples of images of nailfold capillaroscopy captured in healthy subjects and considered as normal. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy* 

*; panel B: 6 capillaries/mm<sup>2</sup>*

*Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of* 

*. (arrows) images were taken using* 

• **Meandering loops**: the limbs cross upon themselves or with each other several

• Bushy capillaries: the limb branches present themselves in small and multiple

**174**

**Figure 4.**

**Figure 3.**

*Clinic of Hospital Curry Cabral.*

**Figure 2.**

*Hospital Curry Cabral.*

*Capillary density. Panel A: 1 capillary/mm2*

(**Figure 4B**).

times [23] (**Figure 4A**).

*Capillaroscopy Clinic of Hospital Curry Cabral.*

buds [7] (**Figure 4C**).


Other capillaroscopic parameters include the following:


Major NFC patterns divide into scleroderma and nonscleroderma pattern. Scleroderma pattern was first described by Maricq et al, through a combination of widening of the capillary loop, loss of capillaries, and disorganization of the nailfold capillary bed [1]. This pattern is frequently seen in scleroderma spectrum disorders, like systemic sclerosis, dermatomyositis, and mixed connective tissue disease and in RP without a clear diagnosis. Later, Cutolo et al further classified the scleroderma pattern into "early," "active," and "late" stages. "Early" scleroderma pattern presents with few giant capillaries and hemorrhages, relatively well-preserved capillary

#### **Figure 5.**

*Images from three different phases of scleroderma pattern, belonging to three different patients: Early, active, and late (from left to right). Capillary density decreases from early to late pattern. Capillaroscopic findings include giant capillaries (black spot), hemorrhages (\*\*), and neoangiogenesis (star). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 6.**

*Capillary limb dilatation: Dilated (diameter* ≥ *30 μm) and giant (diameter* ≥ *50 μm) capillaries. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 7.**

*Elongated capillaries (capillary loops* ≥*300 μm). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

distribution, and no loss of capillaries. "Active" scleroderma pattern reveals frequent giant capillaries and hemorrhages, moderate loss of capillaries, mild disorganization of capillary bed, and absent or mild ramified capillaries (i.e., neoangiogenesis). "Late" scleroderma pattern shows an irregular enlargement of the capillaries, few or absent giant capillaries and hemorrhages, severe loss of capillaries with avascular areas (the *plages désertes*), and ramified or bushy capillaries (**Figure 5**).

In healthy subjects, anatomic variations occur, and capillary abnormalities can be found. The estimated prevalence of these changes are meandering loops in 25%,

**177**

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

*Examples of nailfold hemorrhages in patients with different diseases. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry* 

*Images from a single patient with Sjögren syndrome, presenting dilated loops (black square), meandering (black circle), crossing (X), reduced capillary flow with sludge (dashed arrow), and ingurgitated venous plexus (plus sign). (A: 5th finger of the right hand; B: 2nd finger of the left hand; C: 4th finger of the right hand.) images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold* 

dilated capillaries in 12%, bushy loops in 7%, bizarre loops in 2%, and giant capil-

*Dermatomyositis-images from 3 different patients, revealing reduced capillary density, with a complete distortion of the vascular array, neoangiogenesis (star), giant capillaries (black dot), and hemorrhages (\*\*). Venous plexus is also ingurgitated (plus sign). Images were taken using Videocap biomicroscope, version 3.0,* 

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

**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

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,

laries in 0.3% of the healthy population [23]**.**

*Capillaroscopy Clinic of Hospital Curry Cabral.*

managing these disorders.

**4.1 Systemic sclerosis (SSc)**

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

**Figure 8.**

*Cabral.*

**Figure 9.**

**Figure 10.**

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

#### **Figure 8.**

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

distribution, and no loss of capillaries. "Active" scleroderma pattern reveals frequent giant capillaries and hemorrhages, moderate loss of capillaries, mild disorganization of capillary bed, and absent or mild ramified capillaries (i.e., neoangiogenesis). "Late" scleroderma pattern shows an irregular enlargement of the capillaries, few or absent giant capillaries and hemorrhages, severe loss of capillaries with avascular

*Elongated capillaries (capillary loops* ≥*300 μm). Images were taken using Videocap biomicroscope, version 3.0,* 

*Images from three different phases of scleroderma pattern, belonging to three different patients: Early, active, and late (from left to right). Capillary density decreases from early to late pattern. Capillaroscopic findings include giant capillaries (black spot), hemorrhages (\*\*), and neoangiogenesis (star). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of* 

*Capillary limb dilatation: Dilated (diameter* ≥ *30 μm) and giant (diameter* ≥ *50 μm) capillaries. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy* 

In healthy subjects, anatomic variations occur, and capillary abnormalities can be found. The estimated prevalence of these changes are meandering loops in 25%,

areas (the *plages désertes*), and ramified or bushy capillaries (**Figure 5**).

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

**176**

**Figure 7.**

**Figure 5.**

**Figure 6.**

*Clinic of Hospital Curry Cabral.*

*Hospital Curry Cabral.*

*Examples of nailfold hemorrhages in patients with different diseases. Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 9.**

*Images from a single patient with Sjögren syndrome, presenting dilated loops (black square), meandering (black circle), crossing (X), reduced capillary flow with sludge (dashed arrow), and ingurgitated venous plexus (plus sign). (A: 5th finger of the right hand; B: 2nd finger of the left hand; C: 4th finger of the right hand.) images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

#### **Figure 10.**

*Dermatomyositis-images from 3 different patients, revealing reduced capillary density, with a complete distortion of the vascular array, neoangiogenesis (star), giant capillaries (black dot), and hemorrhages (\*\*). Venous plexus is also ingurgitated (plus sign). Images were taken using Videocap biomicroscope, version 3.0, magnification ×200. Courtesy of Nailfold Capillaroscopy Clinic of Hospital Curry Cabral.*

dilated capillaries in 12%, bushy loops in 7%, bizarre loops in 2%, and giant capillaries in 0.3% of the healthy population [23]**.**
