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Review Article
ARTICLE IN PRESS
doi:
10.25259/IJDVL_514_20

Nail-fold capillaroscopy for the dermatologists

Department of Dermatology and STD, University College of Medical College and GTB Hospital, New Delhi, India
Department of Dermatology, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi, India
Corresponding author: Dr. Deepak Jakhar, Department of Dermatology, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi, India. dr.deepakjakhar@yahoo.in
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Grover C, Jakhar D, Mishra A, Singal A. Nail-fold capillaroscopy for the dermatologists. Indian J Dermatol Venereol Leprol, doi: 10.25259/IJDVL_514_20

Abstract

Nail fold is one of the most accessible sites for studying changes in the microcirculation in various microangiopathies. The characterization of changes in microvasculature can provide useful clues towards the diagnosis and prognosis of a disease. The diagnostic utility of nail fold capillaroscopy has improved and expanded over the past couple of decades. Beyond connective tissue diseases, it is now explored for its role in various systemic and dermatological diseases. Incorporation of nail-fold capillaroscopy in the diagnostic criteria of systemic sclerosis has generated interest among dermatologists. The current review is aimed at providing knowledge about nail-fold capillaroscopy to dermatologists. For the purpose of review, a PubMed search was done using the keywords “nail fold capillaries” and “nail fold capillaroscopy”. All the articles were retrieved and classified into reviews and clinical studies of various types. The final data were then analyzed and presented in a narrative fashion.

Keywords

Capillaroscope
capillaroscopy
dermatology
nail fold capillaroscopy
nail fold videocapillaroscopy

Introduction

Nail-fold capillaroscopy is a non-invasive imaging technique for in vivo assessment of microcirculation.1,2 The easy availability of dermatoscopes (used as capillaroscopes) has ensured that more and more dermatologists use nail-fold capillaroscopy now, especially in conditions where it has established value such as Raynaud’s phenomenon and connective tissue diseases.1,3-10 The micro-vasculature is also affected in dermatoses like psoriasis,11 metabolic diseases like diabetes mellitus,12,13 autoimmune diseases and various other conditions.14 Here too, nail-fold capillaroscopy helps to detect and monitor early microvascular changes which may precede development of clinically significant complications such as retinopathy, neuropathy and nephropathy.13 This review aims to compile and present current knowledge of nail-fold capillaroscopy to serve as a ready reckoner for dermatologists.

Methodology

A PubMed search pertaining to published English articles using keywords “nail-fold capillaries,” and “nail-fold capillaroscopy” was done. The search yielded 163 and 96 indexed articles, respectively, which were retrieved and classified into review articles (37) and clinical studies of various types (222). These were read and information pertaining to nail-fold capillaroscopy was collected. The cross references provided were also retrieved and studied. The final data were analyzed and presented in a narrative fashion.

Nail Fold Capillaroscopy

Nail-fold capillaroscopy is specialized dermatoscopy of proximal nail fold where incident light delivered at an acute angle enables “in vivo” visualization of vascular structures in the superficial papillary dermis, thus highlighting capillary architecture. Application of linkage fluid increases transparency of proximal nail fold and reduces surface reflection.15

Initial written description of nail fold capillary evaluation is available from 1663 when Johan Christophorous Kolhaus used a primitive microscope to observe small blood vessels surrounding the nails. Subsequently, Giovanni Rasori described a close relationship between conjunctival inflammation and the presence of “inextricable knots of capillary loops” using a magnifying glass.1 Skin capillaries were also described by Purkinje (1823) while observing the nail fold with a magnifying lens.2 However, nail-fold capillaroscopy was accorded the status of an important investigation by Raynaud (1862) through his thesis evaluating local ischemic damage of hands, feet, nose and tongue.16 Lombard (1911) found that capillaries became visible on placing a drop of immersion oil. Much later, Maricq and Le Roy described specific capillaroscopic features in Systemic Sclerosis.17 Cutolo et al. classified nail-fold video capillaroscopic patterns in patients with systemic sclerosis as “early,” “active” and “late” patterns in 2000.8

Cutaneous micro-circulation

The cutaneous microcirculation is composed of superficial and deep horizontally-oriented plexuses. Superficial plexus, located 1–1.5 mm under the skin surface, gives rise to 1-3 capillary loops per dermal papilla, visible as dots or commas on the surface, as they are located at 90-degree angle to skin surface. They have an arterial and a venous limb connected by an apical loop.6,15 However, capillary loops in the nail-fold region are uniquely located, as they lie increasingly parallel to the skin surface, enabling visualization of their size, shape and morphology across their full length [Figure 1].17

Figure 1:: Diagrammatic representation of the sagittal anatomy of the proximal nail fold. The skin fold over itself forming the dorsal as well as the ventral surface of the proximal nail fold. Thus, the papillary capillaries lie increasingly horizontal near the folding edge

While capillaries can also be visualized and studied in vivo at sites such as conjunctiva and retina, the proximal nail fold offers the advantage of easy accessibility for repeated examination [Figures 2a and 2b].18 The proximal nail fold, being an acral area, is also affected early as well as maximally, by disorders affecting microvasculature.

Figure 2a:: Normal proximal nail-fold capillaries seen as regular hairpin bends (Dinolite AM7515MZT, polarized ×65)
Figure 2b:: Normal proximal nail-fold capillaries seen at higher magnification (Dinolite AM7515MZT polarized, ×180). Also note the tortuosity seen in many vessels

Equipment used

Equipment reported to visualize proximal nail fold capillaries include hand-held magnifying glass, ophthalmoscope, light stereomicroscope,19 wide-field microscope, dermatoscope,10,18,20 and videodermatoscope.21 Digital videocapillaroscopy, the gold standard technique to examine nail fold capillaries, consists of a microscope with digital video-camera providing a magnification from ×50 to ×1000. However, it is expensive and not widely available. Ophthalmoscopes and hand-held dermatoscopes offer less magnification (×10 mostly), but enable examination of a wider area of the nail fold. USB dermatoscopes are not that costly and offer magnification from ×20 to ×200.17 There are studies affirming their reliability in studying the nail-fold capillaroscopy changes.10,18-20

Technique

Nail-fold capillaroscopy should be done after minimum 15–20 min stay in a room with normal ambient temperature (20–22°C). The patient is made to sit comfortably with hands kept at the level of heart.6,8-10,22 Most precise morphologic evaluation is obtained from 4th and 5th fingers, because of highest transparency of skin and least proneness to dayto-day trauma.23 Nevertheless, it is advisable to perform nail-fold capillaroscopy in all fingers since early and initial microvascular changes may manifest in few fingers only. Use of linkage fluid (immersion oil, ultrasound gel, etc.) increases the transparency and resolution of images. Additional considerations are outlined in Table 1.

Table 1:: Important consideration before doing nail-fold capillaroscopy
  • Caffeine and smoking to be avoided 4–6 h before examination

  • Nail paint to be gently removed before nail fold capillaroscopy

  • Clean the hands and feet gently with soap and water

  • Physically injured fingers to be avoided

  • Nail-fold capillaroscopy to be performed under a cold light source to prevent vasodilation

  • Adding excessive immersion fluid obstructs the field of vision

  • At least 4 images to be taken from one finger

  • Toe capillaroscopy is an unreliable tool

  • 10–20 s video may be taken from the midline of the nail fold to capture blood flow

  • To minimize reflections, contact angle and direction of the instrument may have to be changed

The images taken are stored in JPEG/PNG/BMP formats and assessed in detail. An estimate of mean capillary density is made from the distal-most row of capillaries. Abnormal capillaroscopic changes (identified in at least two digits) are recorded as a part of overall nail-fold capillaroscopy findings.23 Overall evaluation of capillaries depends on the equipment used (quality and visibility of images); observer experience; and transparency of skin, which may be compromised in pigmented, thickened or fibrosed skin.21

Capillaroscopic parameters

Nail-fold capillaroscopy evaluation depends on quantitative and qualitative parameters.17 Quantitative parameters include mean capillary density and capillary limb width; while qualitative parameters include morphological or architectural alterations, neoangiogenesis, or presence/absence of a subpapillary plexus [Figure 3].

Figure 3a:: Schematic representation of nail fold capillaroscopy procedure
Figure 3b:: Schematic representation of microvascular architectural abnormalities

Quantitative parameters

Mean capillary density

It is the average number of distal most capillary loops visualized per millimeter of proximal nail fold margin. A wide range of values for healthy subjects (7–14 capillaries/ mm) have been reported.24-29 Variations based on ethnic, demographic, or methodological factors are known [Table 2 and Figure 4].30-32 In an Indian study, mean capillary density was reported as 8.7/mm24 while more recently it was reported to be 7.6 capillaries/mm.17

Table 2:: Important observations related to capillary density
  • Capillary density is directly related to age. Younger children have fewer capilaries30

  • Gender does not have a significant impact on mean capillary density30

  • Mean capillary density can be difficult to calculate in darker skin individuals [Figure 4]

  • Fingers have higher density than toes31

  • Fourth and fifth fingers are preferred for counting capillaries32

Figure 4:: Nail-fold capillaroscopy in pigmented skin (Dinolite AM7515MZT, polarized ×180). The contrast with vessels may not be easy to visualize

Various methods have been used to calculate mean capillary density. Sebastian et al. considered distal most capillaries for this calculation, even if they were not at the same level. Major disadvantage of this approach is that a ramified capillary is counted multiple times giving a false high value.33 Hofstee et al. suggested the “90-degree method,” wherein a capillary is considered distal loop if the angle between the apex of that capillary and the apex of its two adjacent capillaries is greater than 90 degree.34 A simplified protocol using calibration feature of USB dermatoscopes was devised by our team [Figure 5].13,17

Figure 5:: Nail-fold capillaroscopy image captured using the calibration software of the USB dermatoscope (Dinolite AM7515MZT, polarized ×180). The number of distal most capillaries can be counted over a millimeter. Area of capillary dropout can be seen where the distal most capillary loop is missing

We mark the center of proximal nail fold with an ultra-thin marker pen and then take two images (at high magnification) on either side. Both images are analyzed with the calibration software of the USB dermatoscope, counting the distal most capillary loops visible over 2 mm length on either side of the marked point, giving the number of capillaries over 4 mm in an individual digit. The sum of number of capillaries of four fingers (right and left fourth and fifth finger) is added and the sum divided by 16 to give mean capillary density/mm.

Various authors have proposed capillary density scoring systems on the basis of calculated mean capillary density, [Table 3].3,35,36 Hoerth et al. suggested a scoring system based on the age of the individual.30

Table 3:: Capillary density scoring systems used in various studies
Reference Points Capillary density per mm
Lefford and Edwards35
Ingegnoli
et al.36
0
1
2
3
>9 capillaries per mm
>7–9 capillaries per mm
>4–7 capillaries per mm
<4 capillaries per mm
Cutolo and Smith3 0
1
2
3
More than 9 capillaries
<33% reduction of capillaries (7–9 capillaries)
33–66% reduction of capillaries (4–6 capillaries)
>66% reduction of capillaries (1–3 capillaries)

Other quantitative parameters

Other reported quantitative parameters including mean capillary width, capillary length, arterial limb diameter, venous limb diameter, apex width, internal diameter and intercapillary distance [Table 4] require more sophisticated calibration tools.

Table 4:: Definition of various quantitative parameters assessed in nail-fold capillaroscopy
Parameter Definition
Mean capillary density Number of capillaries per mm length of the proximal nail fold
Capillary width Width of the capillary loop at its widest section
Capillary length Distance between the apex of capillary loop and the point where the capillary loop is no longer visible
Arterial and venous
limb diameter
Width of the arterial and venous limb at their widest sections
Internal diameter Distance between arterial and venous limbs measured at the level of capillary loop
Apex width Maximum open space measured at the apex of a capillary
Intercapillary distance Longest distance that exists between two adjacent capillary loops

Qualitative parameters

Homogenous and orderly capillaries arranged parallel, at regular inter-capillary distance are seen in normal individuals. Capillary disorganization refers to distortion of this regular pattern. Three morphological patterns described in healthy subjects are considered variations of normal [Table 5].36 Tortuous loops are the most common aberrant findings in healthy subjects.24,30 Various scoring systems for these alterations have been described [Table 6].8,37

Table 5:: Three major morphological patterns described in healthy individuals36
Pattern Definition
“Normal” Pattern 2–5 U-shaped capillary loops/mm and equal or less than 2 tortuous loops/mm
“Perfect Normal” Pattern Equal to or greater than 5 U-shaped loops/mm
“Unusual Normal” Pattern At least 1 meandering or bushy loop, or at least 1 microhemorrhage or with >4 crossed loops/mm
Table 6:: Various capillary distributions and scoring systems
Study Points Capillary distribution/mm
Cheng et al.37 Stage A
0 Regular (100%)
1 Slight irregularity
Stage B
2 Disarranged (<50%)
3 Disarranged (>50%)
Stage C
4 Local avascularity
5 Enlarged loop bordering avascularity
6 Complete avascularity
Cutolo et al.8 0 Normal Distribution
1 Mild disorganization (<33% alteration/mm)
2 Moderate disorganization (33–66% alteration/mm)
3 Severe disorganization (>66% alterations/mm)

Capillary dilatation

Dilated capillaries are seen as a local response to tissue hypoxia9,23,38 and are one of the earliest microvascular alteration [Figure 6]. A dilated capillary is more than two times wider than surrounding normal capillaries. Giant capillaries (width>10 times the width of normal capillaries) are seen in later stages. The presence of even a single giant capillary suggests a microangiopathy.23 Enlarged capillaries have been reported in 100% of systemic sclerosis patients, 56% of patients with mixed connective tissue disease and 86% of dermatomyositis patients.23,39

Figure 6:: Nail-fold capillaroscopy image showing dilated capillaries (black arrow), giant capillary (red arrow) and microhemorrhages (blue arrow) (Dinolite AM7515MZT, polarized ×180)

Micro-hemorrhages

Hemorrhages appear as extra-capillary brown aggregates of clotted blood in variable forms and sizes, enabling differentiation from extravasates and thrombosis. They indicate disease activity [Figure 6].6 These could be focal (singularly placed micro-petechiae) or diffuse (multiple micro-petechiae in groups)

Capillary dropouts

Absence of a capillary loop from its dermal papilla is defined as a capillary dropout [Figure 5]. It is the earliest marker of development of avascular areas.

Avascular areas

It is an absence of two or more adjacent capillaries from the distal row [Figure 6].40,41 It becomes larger and confluent in more advanced disease.6 Avascular areas are often surrounded by capillaries with a disturbed distribution and orientation. Surrounding capillaries tend to get oriented toward the area of capillary loss probably as a compensatory mechanism.6 Various scoring systems for avascular areas are summarized in Table 7. 8,28,42-44

Table 7:: Various scoring systems for avascularity
Points Avascularity/mm (Cutolo
et al.,8Terreri et al.,42Kabasakal et al.,29
Ingegnoli et al.43)
Avascularity/mm (Hofstee et al.44)
0 No avascular areas -
1 Mild (1–2 avascular areas) Mild (<2 consecutive capillary loss)
2 Moderate (>2 avascular area) Moderate (2–4 consecutive capillary loss)
3 Severe (Large and confluent avascular areas) Severe (>4 consecutive capillary loss; or >2 areas of >2 capillary loss)

Tortuous capillaries

A capillary limb curled but not crossing over itself is known as a tortuous capillary [Figure 7]. Less than 5% of capillaries showing this morphology is considered normal, while >10% is defined as an “increased tortuosity.”45,46

Figure 7:: Nail fold capillaroscopy from a patient of dermatomyositis showing tortuous capillaries (star marked) in the centre of the image [Dinolite AM7515MZT, polarized, 180X]

Criss-cross forms

Also known as figure of eight forms, these capillaries have crossed arterial and venous limbs.45 This is a normal variant and can be observed depending on the angle of observation.

Neoangiogenesis

It is new vessel formation seen as meandering, ramified or bushy capillaries.6,9,45,47 Bushy capillaries are loops with limbs originating from small and multiple buds [Figures 7 and 8]; while, meandering capillaries have limbs crossed upon themselves or on other capillaries, several times over [Figure 9]. Bizzare capillaries have striking atypical morphology, not conforming to previously defined categories.

Figure 8:: Nail fold capillaroscopy in a patient of systemic sclerosis showing a budding capillary (blue arrow) indicating neoangiogenesis and few dilated vessels (red arrows) [Dinolite AM7515MZT, polarized, 180X]
Figure 9:: Multiple meandering capillaries (black arrows) (Dinolite AM7515MZT, polarized ×180). Subpapillary plexus can also be seen (green arrows)

Dilated/prominent subpapillary plexus

This parameter is reflective of skin transparency, influenced by local conditions such as hyperkeratosis, pigmentation, injuries, or edema. It is the superficial cutaneous plexus located in the papillary dermis (subpapillary plexus) which gives rise to capillary loops [Figure 9]. It is visible in up to 26% of healthy individuals.29 Blood flow in subpapillary plexus is sluggish as compared to capillary loops and an abnormally slow blood flow make it even more evident.6

Dystrophic capillary loops

Capillary loops which are not well developed, not of normal size and caliber or malformed are known as dystrophic. They have been described in very few studies.48,49

Indications for Nail-Fold Capillaroscopy

Based on the literature search, nail-fold capillaroscopy has been found to show conclusive or suggestive alterations in the following indications. Reflecting on the best available evidence for each indication, a level of evidence has been assigned based on the Grade Classification System. It is assigned as: A (experimental or observational study with better evidence); B (experimental or observational study with less evidence); C (case reports/uncontrolled studies); or D (opinion piece, consensus recommendation, or study on animal models).

Rheumatological Indications

Rheumatological diseases are the primary indications for nail fold capillaroscopy. Over the years, study of nail fold capillaroscopy has been refined in these very disorders, to the extent that nail-fold capillaroscopy constitutes a part of the diagnostic criteria for Raynaud’s phenomenon and systemic sclerosis.

Raynaud’s phenomenon (Grade of recommendation - A)

Raynaud’s phenomenon can occur both as a primary or a secondary phenomenon and nail-fold capillaroscopy helps distinguish these. Absence of abnormal capillaroscopic pattern is one of the diagnostic criteria for primary Raynaud’s phenomenon [Table 8].50 In fact, in patients with Primary Raynaud’s phenomenon, if nail-fold capillaroscopy pattern is abnormal, they need to be closely followed up for the risk of developing a well-defined connective tissue diseases in future.6,51-53 Secondary Raynaud’s phenomenon accompanies various rheumatologic conditions such as systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome and dermatomyositis showing patterns accordingly.

Table 8:: Le Roy and Medsger criteria for diagnosis of Primary Raynaud’s Phenomenon51
  1. Symmetrical involvement

  2. Absence of tissue necrosis

  3. Absence of digital ulceration and gangrene

  4. Absence of a secondary cause (based on medical history and physical examination)

  5. Normal Erythrocyte sedimentation rate

  6. Negative test for antinuclear antibodies

  7. Normal capillaroscopic pattern

As Raynaud’s phenomenon may be an isolated complaint or may be the first symptom of connective tissue diseases; patients need to be regularly examined.23,54-57 In studies with over ten-year follow-up, frequency of development of autoimmune connective tissue diseases increased from 5 to 19% in those with nail-fold capillaroscopy abnormalities.46,56 In healthy individuals, the capillaroscopic patterns of a digit remains surprisingly constant over an extended period of time and abnormal findings have a positive predictive value of 47% for subsequent development of connective tissue diseases. Abnormal nail-fold capillaroscopy coupled with a positive anti-nuclear antibody or rheumatoid factor, increases the predictive value up to 55%.57 Thus, in the presence of Raynaud’s phenomenon, a follow-up nail-fold capillaroscopy analysis is recommended to be performed every six months.6,9,38,58-60

Systemic sclerosis (Grade of recommendation - A)

The “scleroderma pattern“ in systemic sclerosis was first described by Maricq et al.6,8,9,23,38,47,52,61 It is found in 83–93% cases with overt scleroderma.38,52 Maricq et al. (1983) described two types of capillaroscopic changes in systemic sclerosis: “Active” pattern reflected by extensive and confluent avascular areas and neovascularization [Figure 10]; in contrast to “slow” capillaroscopic pattern represented by giant loops with minimal capillary loss.6,52,62 Cutolo (2000) described three different capillaroscopic patterns on nail-fold videocapillaroscopy which are widely accepted and used [Table 9].8

Figure 10a:: Nail fold capillaroscopy from a patient with systemic sclerosis showing ‘early pattern’, characterized by numerous dilated and tortuous vessels (blue arrow). [Dinolite AM7515MZT, polarized, 180X]
Figure 10b:: Nail fold capillaroscopy from a pateint with systemic sclerosis showing an ‘active pattern' characterized by gross dilation, giant capillaries (blue arrow), avascular areas (black star), and microhemorrhages in various stages can be seen [Dinolite AM7515MZT, polarized, 180X]
Figure 10c:: Nail fold capillaroscopy from a patient with systemic sclerosis showing a 'late pattern' characterized by giant capillaries (blue arrow) and avascular areas (black star). [Dinolite AM7515MZT, polarized, 180X]
Table 9:: Three different patterns of capillaroscopy changes observed in SSc8
NVC Pattern Features
“Early” NVC Pattern •Appearance of few dilated and/or giant capillaries and a few hemorrhages
•In this phase, the distribution is relatively preserved without loss of capillaries. These findings are of crucial importance for the early diagnosis of SSc
“Active” NVC Pattern •Large numbers of giant capillaries and hemorrhages
•In addition, a moderate loss of capillaries, slight derangement and diffuse pericapillary edema can be found
“Late” NVC Pattern •Severe loss of capillaries with extensive avascular areas
•Also includes bushy and ramified capillaries, or more than one capillary loop in a dermal papilla. These are the morphological substrates of defective neoangiogenesis
NVC: Nail-fold videocapillaroscopy, SSc: Systemic sclerosis

Later, Maricq et al. defined “scleroderma-like” pattern in scleroderma spectrum disorders such as mixed connective tissue diseases, undifferentiated connective tissue disease, overlap syndromes and dermatomyositis with some of these showing similar parameters.6,9,23,38,47,51,63-67 In 2013, the ACR-EULAR Classification criteria68 were proposed which incorporated nail-fold capillaroscopy as an essential part of scoring and evaluating a patient with systemic sclerosis.

Various studies have explored correlation between nail-fold capillaroscopy changes, type of systemic sclerosis, severity of clinical activity and visceral involvement,6,8,21,52,69-74 but the results are not uniform.75-77 Severe capillary loss is reported more commonly in diffuse systemic sclerosis, while dilated capillaries without capillary loss were found more frequently in limited systemic sclerosis.73 Anti-topoisomerase antibody (anti-Scl-70) correlate with “active” and “late” capillaroscopic changes and probably also accelerate their appearance. Positive anti-centromere antibody was observed more commonly with “early” phase capillaroscopic pattern and probably delayed the onset of “late” capillaroscopic changes.21 Bredemeier et al. ascertained a relationship between loss of capillaries, skin involvement and activity of pulmonary disease as evaluated by high-resolution computed tomography in 91 systemic sclerosis patients.78 Alterations of nail-fold capillaroscopy pattern during follow-up of patients with connective tissue diseases could also indicate visceral vascular involvement.71,79 Structural abnormalities such as devascularization and distortion of architecture, which characterize late microvascular damage, are strong predictors of occurrence of digital ulcers.80 Available evidence indicates a positive correlation between nail-fold capillaroscopy abnormalities and involvement of target organs.80

Dermatomyositis and polymyositis (Grade of recommendation - B)

Other than systemic sclerosis, the most consistent nail-fold capillaroscopy abnormalities are reported in dermatomyositis.65,81 The pattern observed largely resembles systemic sclerosis, including the presence of two or more of the following characteristics in two or more nail folds, namely, capillary dilation, twisted enlarged capillaries, loss of capillaries, bushy capillaries, disorganization of capillary architecture and microhemorrhages [Figure 11].10 Capillary dilation and loss of capillaries though reported in both dermatomyositis and polymyositis are more commonly and severely reported in dermatomyositis.82 However, nail-fold capillaroscopy changes do not relate to the disease activity and severity.82

Figure 11:: Nail fold capillaroscopy of a dermatomyositis patient showing dilated capillaries, and tortuous vessels (red star). Few capillary dropouts can be appreciated (blue arrows) [Dinolite AM7515MZT, polarized, 180X]

Systemic lupus erythematosus (Grade of recommendation - B)

Nail-fold capillaroscopy abnormalities are less commonly and less consistently found in systemic lupus erythematosus. The most frequently reported abnormalities include extremely long capillary loops (>750 mm), meandering capillaries and a prominent sub-papillary venous plexus [Figure 12].82 When systemic lupus erythematosus is associated with Raynaud’s phenomenon and/or Anti-U1RNP antibodies, avascular areas and enlarged capillary loops may be seen.10 Nail-fold capillaroscopy changes have been found to correlate with disease activity and systemic manifestations in systemic lupus erythematosus.10

Figure 12:: Nail fold capillaroscopy of a patient with systemic lupus erythematosus. Elongated capillaries (red star) with few dilated vessels and increased tortuosity (blue arrow) can be seen [Dinolite AM7515MZT, polarized 180X]

Anti-phospholipid syndrome (Grade of recommendation - B)

In patients with anticardiolipin antibodies (IgG or IgM), symmetrical microhemorrhages have been demonstrated on nail-fold capillaroscopy.83 In a study from Brazil, significant alterations of nail-fold capillary morphology was demonstrated.84

Rheumatoid arthritis (Grade of recommendation - C)

Primary nail-fold capillaroscopy abnormalities reported in rheumatoid arthritis include elongated and tiny capillaries, tortuosity and prominent sub-papillary venous plexus, especially in those with positive anti-nuclear antibody [Figure 13].85 Most common findings include increased capillary tortuosity, increased length and prominent subpapillary plexus.45 Prominent subpapillary plexus was the most common finding in 62 rheumatoid arthritis patients, being seen in 69% cases.86

Figure 13:: Nail-fold capillaroscopy in a patient with rheumatoid arthritis (Dinolite AM7515MZT, polarized x 180). Note the irregularly dilated, elongated and increasingly tortous capillaries with a prominent subpapillary venous plexus.

Primary Sjogren’s syndrome (Grade of recommendation - B)

Nail-fold capillaroscopy abnormalities reported range from crossed capillaries, confluent hemorrhages or systemic sclerosis -type findings. Sjogren’s syndrome patients with Raynaud’s phenomenon have more frequent nail-fold capillaroscopy changes than patients without Raynaud’s phenomenon.87

Others

Nail-fold capillaroscopy abnormalities have also been reported in mixed connective tissue diseases, undifferentiated connective tissue diseases, cryoglobulinemia and cryofibrinogenemia,88 and fibromyalgia.39

Non-rheumatological Indications

This set of indications is becoming broader; however, only limited work has been done for most of these and precise nail-fold capillaroscopy parameters and changes are yet to be fully studied and defined.

Systemic diseases with microvascular changes

Diabetes mellitus (Grade of recommendation - A)

Capillary alterations have been described in diabetics, more often with poor metabolic control. Both morphological and functional nail-fold capillaroscopy changes have been reported.13,89-91 Studies have even reported a correlation between severity of microvascular changes and metabolic control.90-92

Diabetics have more tortuous and enlarged capillaries as compared to healthy controls. Nodular apical elongations are related to longer duration of disease. Frequency of enlarged capillaries and apical elongation is also higher in Type 2 diabetes with chronic complications. These findings were not influenced by the level of glycemic control13. Uniquely altered “angulated capillaries” have also been reported in Type 2 diabetics [Figure 14].13 No difference in capillary density has been found;93 in fact, regressional changes rather than proliferative changes are found. The degree of tortuosity is higher in patients with retinopathy.94 KaminskaWinciorek et al. showed an increased frequency of twisted capillaries in patients with both Type 1 and Type 2 disease.92 A higher frequency of enlarged capillaries and nodular apical elongation were reported in Type 2 diabetes patients with chronic clinical complications.95 Kaminska-Winciorek et al. and Barchetta et al. also concluded that the microvascular alterations in diabetics were not dependent on age or sex.9,95 In decompensated Type 2 diabetes, a narrowing of arterial capillary segment and increase in rate of remodeling is found. This creates newer possibilities regarding the magnitude of microcirculatory changes in Type 2 diabetes, simultaneously evaluating the efficiency of treatment by monitoring the status of the microvasculature.96

Figure 14:: Nail-fold capillaroscopy in a patient with Type 2 Diabetes mellitus (Dinolite AM7515MZT, polarized ×180). Dilated capillaries (apical dilation) (black arrow), increased tortuosity (blue arrow) with “angulated capillaries” (green arrow) can be seen. There are capillary dropouts

Arterial hypertension (Grade of recommendation - B)

Only a limited evaluation of nail-fold microvasculature has been done in hypertensives, in contrast to studies about the retinal microvasculature.23 Nail-fold capillaroscopy abnormalities in arterial hypertension include quantitative (decreased mean capillary density and loss of capillaries) and qualitative abnormalities (tortuosity, branching, enlarged capillary loops and microhemorrhages).97 Features seen include capillary rarefaction, avascular areas, microhemorrhages, edema and dystrophic capillary loops.47 Antonios et al. described decreased capillary density, increased looping and increased transcapillary filtration as hypertension related changes.98 Using dynamic measurements, increased capillary pressure has also been recorded in untreated hypertensives.99

A decreased capillary density is seen in initial stages in experimental animal models of hypertension.100 This has been documented in multiple microvascular beds, including muscle, skin, mesentery, bulbar conjunctiva, cremaster muscle and brain.101 Capillary rarefaction in skin was first published in early 1990s.102 Subsequently video microscopy revealed significantly fewer capillaries,98 confirmed later by Serné et al.103 and Debbabi et al.104 isolated systolic hypertension predominantly affects macrovasculature while isolated diastolic hypertension affects microvasculature. Bonacci et al. showed significant correlation of retinal microvascular changes with mean capillary density in nailfolds.48 Studies documenting increase in nail-fold capillary density with treatment;104 as well as those contradicting this observation,105 have been published.

Behcet’s disease (Grade of recommendation - B)

Nail-fold capillaroscopy findings include enlarged capillaries, microhemorrhages and capillary loss.106,107

Dermatological diseases

Psoriasis (Grade of recommendation - B)

Changes in the microvasculature are known to play an important part in pathogenesis of psoriasis and psoriatic arthritis; hence, we expect changes in nail-fold capillaroscopy as well. However, nail-fold capillaroscopy findings in psoriasis are conflicting, possibly representing the polymorphous nature of the disease. Mean capillary density is reduced as compared to healthy individuals, while morphological changes in the form of coiled and folded capillaries have been reported. Bhushan et al. reported a significant decrease in capillary loop diameter in psoriasis patients with nail disease.108 However, there was no difference in capillary dimensions as compared to normal controls. They also found no specific pattern of morphological changes in psoriasis. Ribeiro et al. reported decreased capillary density, increased avascular areas and morphologically abnormal capillaries as compared to controls. However, there was no association with disease duration or extent of skin involvement.109

Psoriatic arthritis (Grade of recommendation - B)

Nail-fold capillaroscopy is particularly helpful in differentiating psoriatic arthritis from rheumatoid arthritis. Psoriatic arthritis shows decreased capillary density, dilated, tortuous and disorganized capillaries along with hemorrhages [Figure 15]; while nail-fold capillaroscopy features of rheumatoid arthritis are discussed above and are inconsistent. A recent study evaluated nail-fold capillaroscopy in differentiating psoriatic arthritis sine psoriasis from rheumatoid arthritis.110 It was found that psoriatic arthritis patients show a diffuse reddish background with/without dotted vessels; whereas, rheumatoid arthritis patients showed parallel dotted vessels, short linear vessels (“fish school”) or irregular purple and ramified vessels. Both these types of features were however absent in normal controls.110

Figure 15:: Nail-fold capillaroscopy in a patient with psoriatic arthritis (Dinolite AM7515MZT, polarized ×180). Multiple dilated and tortuous vessels can be seen. There is marked disorganization of the capillary architecture

Alopecia areata (Grade of recommendation - C)

Gerkowicz et al. studied nail-fold capillaroscopy findings in alopecia areata and found abnormal images in 42% of patients with features being tortuous and branching capillaries, decreased density, enlargement of the efferent limb, or top part of the loop.111

Miscellaneous conditions

Nail-fold capillaroscopy abnormalities have also been reported in various diseases [Table 10]112-117 including acromegaly,118 hyperthyroidism,119 cardiac X syndrome,120 mitral valve prolapse syndrome,121 Crohn’s disease,122 peritoneal dialysis patients,123 Familial Mediterranean fever,124 Turner’s syndrome,125 and rosacea.126

Table 10:: Miscellaneous disease states and nail fold capillaroscopy changes
Disease state Nail fold capillaroscopy findings
Kindler syndrome112 Reduced capillary density, neoangiogenesis, dilated and giant capillaries
Primary biliary cirrhosis113 Reduced capillary density, capillary loss, dilated capillary, giant capillary, neoangiogenesis and hemorrhages
Kawasaki disease114 Reduced capillary density, increase in limb diameter and increase in the inter-capillary distance
Henoch-Schonlein purpura115,116 Reduced capillary density, tortuosity, avascular areas, hemorrhages, increased length of capillaries and edema
Anti-synthetase syndrome117 Reduced capillary density, hemorrhage, ramified capillaries, Systemic sclerosis-like pattern

Current limitations of nailfold capillaroscopy

Despite several advancements in the field of nailfold capillaroscopy, challenges remain with respect to its uniform applicability across ethnicities, type of devices used and standardization of nailfold capillaroscopy parameters. A limited visibility of nailfold capillaroscopy features is a unique constraint seen at times in patients with skin of colo. Despite the use of best devices, capillary visibility may be hindered by pigmented skin and in some cases even the trained eyes can not identify the nailfold capillaroscopy changes. Additionally, literature pertaining to the utility of nailfold capillaroscopy in assessing disease activity and correlating with other disease related parameters, is limited for disorders other than connective tissue diseases. More research is also needed regarding nailfold capillaroscopy changes in general dermatological conditions, especially where the micro-circulation may be affected.

Conclusion

Medicine today lays emphasis on diagnosing and managing diseases early and in a quick and non-invasive manner; nail-fold capillaroscopy thus assumes a useful role. With increasing availability and usage of high-quality dermatoscopes, it seems possible that nail-fold capillaroscopy can find a place in early detection as well as long-term management of patients in the near future. Nail-fold capillaroscopy has an important role to play in aiding prognostication and prevention of grave complications.

Declaration of patient consent

Patient’s consent not required as there are no patients in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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