Capillaroscopy

Authors

  • Peter Jung,

    Corresponding author
    1. Karl Landsteiner Institute for Dermatological Research, St. Pölten, Austria
    • Department of Dermatology, State Hospital St. Pölten, Austria
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  • Franz Trautinger

    1. Department of Dermatology, State Hospital St. Pölten, Austria
    2. Karl Landsteiner Institute for Dermatological Research, St. Pölten, Austria
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Correspondence to Dr. Peter Jung, State Hospital St. Pˆlten, Department of Dermatology, Propst-Fhrer-Strafle 4, 3100 St. Pölten, Austria

E-mail: peter.jung@stpoelten.lknoe.at

Summary

Microscopy of the nailfold capillaries has found increasing use in dermatology, rheumatology and angiology particularly as an important tool to distinguish between primary and secondary Raynaud disease. The best evidence is available in systemic sclerosis where specific capillaroscopic patterns have a high positive predictive value for the development of the disease. Conversely, a regular capillary pattern rules out systemic sclerosis with high degree of probability. PRINCE (prognostic index for nailfold capillaroscopic examination) was developed to identify patients at high risk of developing systemic sclerosis. CSURI (capillaroscopic skin ulcer risk index) should predict the risk of developing digital ulcers in patients with systemic sclerosis with high specificity and sensitivity.

As a consequence of recent results a pathologic capillary pattern was integrated by the EULAR Scleroderma Trials and Research Group (EUSTAR) in the diagnostic algorithm of the VEDOSS-Project (very early diagnosis of systemic sclerosis). Capillary patterns may correlate with visceral involvement and capillaroscopy thus has the potential as a screening tool to enable early diagnosis of organ involvement in systemic sclerosis.

Introduction

Capillaroscopy is an established examination method for diagnosis and monitoring of collagen-vascular diseases and finds broad use in rheumatology, dermatology and angiology. The results of numerous publications of recent years show that capillaroscopy has gained increasing importance in the early diagnosis and is not only of diagnostic but also of prognostic value. The integration of new knowledge in the clinical -routine, when patients with Raynaud syndrome consult the dermatologist, is the aim of this short review article.

Performance

Using light microscopy capillaroscopy evaluates the architecture of the skin capillaries. For this the nailfolds of the fingers, where the capillaries run parallel to the skin surface and can be evaluated in their entire architecture, are particularly suitable. In principle, drastic alterations such as megacapillaries can already be seen with a magnifying glass or a dermatoscope. For the differentiated evaluation and for monitoring a binocular light or video capillaroscope with integrated ocular micrometer with the possibility of multi-stage magnification from 40x to 260x is appropriate. For rapid differentiation between a healthy and a pathologic pattern as well as for recognition of highly pathologic alterations the 10-fold magnification of a simple dermatoscope can also be employed [1, 2]. Capillaroscopy is performed at room temperature after 15–20 min of acclimatization in a sitting position on both hands from the 2nd to the 5th finger. Immersion oil serves for better visibility of the capillaries. The best examination conditions are usually found on the 4th finger. Prerequisite for recognizing pathologic processes is the definition of a physiologic capillary pattern.

The physiologic pattern of finger capillaries consists of hairpin-like, parallel capillary loops with a mean length of 200–300 μm and a density of 7–17 capillaries/mm. The lumen of the capillaries is 8–10 μm in the arterial and 10–14 μm in the venous section [3].

Pathologic alterations of capillary morphology stand in contrast to the physiologic capillary pattern. Due to increasing interest in capillaroscopy there are appreciable efforts to -develop a uniform nomenclature. For this purpose the German working group has developed an atlas “Capillaroscopy” and defined pathologic patterns [3]. The most important capillary alterations are described in a Table (Table 1).

Table 1. Frequent pathologic patterns in capillaroscopy
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Raynaud syndrome

Capillaroscopy is of outstanding importance in the differentiation between primary Raynaud syndrome (PR) and secondary Raynaud syndrome (SR) as well as in monitoring of patients with PR, as up to 20% of patients with PR develop an SR within a time span of 10 years [4]. A meta-analysis of 639 patients [5] and a recent study [6] show that about 10% of patients with PR develop a collagen-vascular disease within 10 years. An abnormal capillary pattern had a positive predictive value of 47% in the analysis [5]. In contrast, antinuclear antibodies (ANA) had a positive predictive value of only 30% [5].

Systemic sclerosis

The role of capillaroscopy in systemic sclerosis (SSc) is particularly well-studied. Cutolo et al. have examined capillaroscopic alterations in dependence on disease duration and thus defined an “active”, an “early” and a “late” pattern (Table 2) [7] as well as documented the progression of these alterations in a longitudinal study [8]. The documented stages, according to Cutolo, reflect the development of the disease processes. Similar stages (I–IV) were defined by the German working group “Capillaroscopy” [9] with stage I and II corresponding to Cutolo's “early stage”.

Table 2. Capillaroscopic pattern according to Cutolo et al. [7] and the German study group ìCapillaroscopyì [9]
Active patternMany megacapillaries, many capillary hemorrhages, scattered capillary loss, slightly altered capillary distribution, no or only few ramifications of capillariesStage I (ectasia)Focal capillary ectasias and bleedings Density is still normal, edema possible
  Stage II (individual megacapillaries)Increasing accompanying edema, rarification of capillary density, increase of ectatic capillaries up to megacapillaries
Early patternIndividual megacapillaries, individual capillary hemorrhages, relatively normal capillary distribution, no visible loss of capillariesStage III (predominantly megacapillaries)Increases megacapillaries, deformation and edema, decreased density
Late patternIrregular ectasia of capillaries, some or lacking megacapillaries as well as hemorrhages, severe capillary loss with extensive avascular areas, disorganization of the normal capillary distribution, ramification of capillaries/ capillary bundlesStage IV (scar)Very few, predominantly deformed capillaries, severe edema, large avascular areas

In recent years also the prognostic value of capillaroscopy in SSc has received increasing attention. It was thus shown that in Raynaud syndrome a pathologic capillary pattern is an ANA-independent risk factor for the development of a definitive SSc according to the criteria of the American College of Rheumatology (ACR) [10]. Further, a new index PRINCE (prognostic index for nailfold capillaroscopic examination) was presented [11] in order to calculate the SSc risk in Raynaud patients on the basis of capillaroscopic patterns. A further index CSURI (capillaroscopic skin ulcer risk index) was developed to evaluate the risk of developing digital ulcers in patients with SSc with high sensitivity and specificity [12]. The predictive value of CSURI was confirmed in a larger prospective multicenter follow-up study with a larger patient collective [13]. A simplified algorithm for risk estimation was developed by Ingegnoli et al. [14] (Figure 1).

Figure 1.

Risk evaluation in patients with Raynaud syndrome (Ingegnoli et al. [13]).

In summary, in almost all studies megacapillaries, hemorrhages and avascular areas have crystallized as the most important alterations.

Despite all euphoria of numerous authors over the prognostic and diagnostic relevance of capillaroscopy, the specificity of capillaroscopic SSc patterns can also be viewed critically. It was shown that alterations can be found in up to 6% of the capillaries of healthy controls. Thus, in 120 examined healthy persons 94% of the capillaries did demonstrate the classical hairpin-like form; only 15% of those examined displayed no capillary alterations. Therefore, in this paper unspecific alterations and even reduced capillary density and microbleeding – changes that are classified -under the SSc pattern in other studies – were assigned less pathognomic relevance. Megacapillaries and diffuse capillary loss were not found, however, in the healthy and can be viewed as diagnostically valuable [15]. In contrast, in all studies the importance of a physiologic capillary architecture to exclude SSc is emphasized. Normal capillaroscopy thus largely excludes SSc at the time point of the examination and also has a high negative predictive value for the development of SSc.

The study results of the recent years led the consensus conference of the European League Against Rheumatism (EULAR) Scleroderma Trial and Research group (EUSTAR) to integrate a pathologic capillary pattern next to “puffy fingers”, sclerodactyly, Raynaud syndrome and serologic criteria (ANA, anticentromere antibodies, anti-topoisomerase I antibodies) as an important criterion in the early diagnosis algorithm (Figure 2) of VEDOSS (very early diagnosis of systemic sclerosis) [16].

Figure 2.

Algorithm of VEDOSS (very early diagnosis of systemic sclerosis).

According to EUSTAR the aim of early diagnosis is by way of organ screening to recognize systemic involvement promptly, in order to perhaps have a favorable therapeutic effect on the further disease process.

Interestingly, there are indications that the capillaroscopic pattern correlates with visceral involvement [17]. For example, significantly more heart and lung involvement is seen in the late stage pattern in comparison to early and active stage patterns [18]. Further, it was shown that the decreasing capillary density is associated with the development and the severity of pulmonary arterial hypertension [19].

Other collagen-vascular diseases

In comparison to SSc, capillaroscopy is less well-studied in other collagen-vascular diseases and appears to possess less diagnostic importance.

In dermatomyositis (DM) a well-defined pattern is known. Ectasias, megacapillaries and hemorrhages dominate the picture [20]. In patients with systemic lupus erythematosus (SLE) with and without the antiphospholipid antibody syndrome one characteristically sees a “colorful picture” of various alterations such as capillary fluctuations, sludge, -ramifications and elongations, tortuous -capillaries, dilated capillaries and bleeding [9, 21]. The -simultaneous occurrence of the mentioned alterations is -typical. Thus, 29% of an examined SLE collective displayed three alterations, 71% at least four alterations simultaneously [9]. Nevertheless, in LE with Raynaud syndrome more SSc patterns are found [22]. In other collagen–vascular diseases such as Sjögren syndrome, -antiphospholipid syndrome and mixed connective tissue disease (MCTD) findings are -similar [23].

In summary, other collagen-vascular diseases, with the -exception of DM, lack disease-specific alterations.

Conclusions

Capillaroscopy is an easily tolerable, non-invasive, important angiologic examination method. In the meantime capillaroscopy has achieved a firm status in the early diagnosis of SSc. Capillaroscopy is of outstanding importance in the differential diagnosis in Raynaud syndrome with a high negative -predictive value in normal findings and high specificity of the SSc pattern for the presence of development of SSc.

This possibility of early diagnosis of SSc provides a chance for the development of new “preventive” treatment concepts of SSc with early start of therapy and the goals of prevention of progression and organ damage.

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