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Статьи. Медицина

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NAIL BED CAPILLAROSCOPY IN PEDIATRIC RHEUMATOLOGY

Ie. Marushko
P.L.Shupik National Medical Academy of Postgraduate Education, Kiev, Ukraine



Nail bed capillaroscopy — informative method for examination children with systemic inflammatory diseases of connective tissue and juvenile rheumatoid arthritis. According to our data, children with systemic lupus erythematosus and juvenile rheumatoid arthritis has lesions of microcirculatory bed, more expressive in children with lupus.
Key words: Nail bed capillaroscopy, children, systemic lupus erythematosus, juvenile rheumatoid arthritis.



Introduction

Lesion of the cardiovascular system is an integral part for most rheumatic diseases, in both adults and children. A special place in this system has microcirculatory bed (MCB), which, as the final part of the whole series of vascular branching, is responsible for the direct exchange of substances between the blood and the environment of the intercellular space, and through it — with cells.

Relatively simple and non-invasive morphology imaging technique of smallest components of MCB — capillaries, is the nail bed capillaroscopy (NBC). The most widespread use of this method is found in the diagnosis and differential diagnosis of rheumatic diseases. This technique provides valuable information on the involvement of the smallest blood vessels in the systemic disease process, providing additional data to assess the severity and prognosis of disease.

Capillaroscopy roots go back in the XVII century. When in 1663, Johan Christophorous Kolhaus first used primitive microscope to study small blood vessels located in the nail bed. The turning point in the use of capillaroscopy in rheumatology was description of Hutchinson in 1901, clear differences in capillary-scopic picture (CS_picture) nail bed of patients with primary and secondary Raynaud's phenomenon (RP).

Bollinger in 1979, was first who used video capillaroscopy (FSI) on the basis of this methodology Italian doctor Cutolo (2000) described the FSI picture of three stages of progression scleroderma microangiopathy that used so far [20].

Technique of nail bed capillaroscopy. At present, the most important are capillaroscopy with digital stereo microscope and digital FSI. The first technique is more affordable, but it requires additional fiberoptic light source and uses a low degree of zooming. Second, using fiberoptic optical sensor — financially more difficult to obtain, but at this stage is considered the «gold standard» for NBC, especially in scientific research [17]. In addition to NBC a laser Doppler flowmetry (LDF), which allows to determine the rate of blood flow in the capillary.

Interpretation of the image is carried out according to the estimate of the following characteristics: density of the capillary loops, the presence of avascular zones, size of loops, loop shape, the orientation of the capillaries, microbleeds and / or micro-thrombosis, extension of papillar venous plexus [4].

The density of capillaries and the presence of avascular zones. Normal for children is the presence of regularly located 6–8 capillaries on one mm long on distal capillary number [12]. Distal capillary row is last number of capillary loops in the direction to the nail.

Reducing the number of capillaries in children less than 6/mm and / or the presence of avascular zone (no capillary for at least 500 micrometers along the distal capillary number) — the characteristics of the SS, which reflect tissue ischemia [4]. To determine the avascular zone is also possible to use more simple test: loss of two or more consecutive capillary loops compared to the maximum frequency of the location of the capillaries in the distal row [4,18].

The size of the capillary loop. The average length of capillary loop — 475 micrometers, with a length exceeding 500 micrometers in children, the loop is considered as extended [4,8]. Diameter of the efferent (venous) slightly larger diameter afferent (arterial) part of the loop, but their ratio should not exceed 2:1. Extension loop occurs when its thickness at widest point (the distance from the outer edge of the venous to the arterial outer edge) a 90–150 micrometers. With a diameter of any part of the loop, exceeding 25 micrometers capillary is considered extended, and with a diameter of more than 50 micrometers indicate giant capillary [4].

Lengthening, widening and tortuosity of capillary loops, as all or some (heterogeneity capillaries form) — the earliest capillary-scopic signs of secondary Raynaud's phenomenon [12].

Loop shape can be normal, or winding, bush. Normally, the nail fold capillaries look like inverted capital letter «U», one part of which — afferent and the other — efferent. Course of loops may be winding up to the fact that both sides can intersect, creating a picture of the «treble clef.» Tortuosity of capillaries diagnosed if marked tortuosity of 2 or more capillaries, at least on two of eight investigated fingers [7]. Tortuosity of capillaries can be expressed as a numerical value in the tortuosity index, which is calculated by dividing the number of convoluted loops on the total number of capillaries in the field of view, expressed in percentage [18]. In earlier work has been established an upper limit of the index — 20%, but recent studies in children showed significant variability tortuosity index, which put at doubt on its diagnostic value [19]. Capillary loop may take form of a bush bush. This term refers to the capillaries, in which loops knee protrudes, has a tortuous course so that the contour of loops resembles contour of bush, tree, or the Greek letter «Ù». Bush capillaries often present in angiogenesis. Angiogenesis — this neo-formation of capillaries, which is determined by the presence of significantly curved, elongated, bush capillaries often in excess of 4 or more on one dermal papilla with loss of normal adjacent capillary loops. Such a situation is typical for secondary Raynaud's syndrome, especially in systemic sclerosis and dermatomyositis [24].

Under orientation of capillaries understands the relative positions of the capillary loops. The normal course of capillary loops parallel to each other, in case of pathology parallel orientation can disappear, then loops making an angle with each other, which is called disorientation of capillaries [12].

Microbleeds (dark round spots) or micro-thrombosis (dark spots imitating the form of capillary loops) are also characteristic of secondary Raynaud's phenomenon.

Studies describing a normal CS-picture in children are scarce. The most solid of them held MT Terreri et al. (1999). In this paper NBC performed almost 329 healthy children, whose average age was 8.2 years. The authors noted that the overall CS-picture in children corresponds to that in adults, except for the density of capillaries. The last ranged from 5 to 9 stitches per 1 mm length of the distal capillary number, being less than the same index in healthy adults (9–13/1 mm), and having a direct proportional connection with the age of the child. In addition, the researchers noted that in children more often than in adults, meet anomalies in the capillary loops (36%): a form that is different from the usual U_shaped (27%), tortuosity (10%), bush (6%). However, the areas of capillary loops loss were found only in 2% of healthy children, and a thickening of capillaries was not observed at all [15]. The data presented have been confirmed by other studies of CS-picture in healthy children [18].

Nail bed capillaroscopy in case of rheumatic diseases in children and differential diagnosis of Raynaud's phenomenon. Systemic inflammatory disease of connective tissue (SIDCT) are often accompanied by disorders in the MCB. One of manifestation of vascular pathology in SIDCT is RP. This disease is manifested by periodic episodes of color changing on fingers of brushes and / or feet (usually a two-phase — with pallor or cyanosis to hyperemia, rarely — three phase: pallor, cyanosis, redness), accompanied by a feeling of cold extremities and paresthesias. Provoked similar bouts of cold and stress.

Phenomenon can be secondary as a manifestation of vascular disease in SIDCT (especially common in SSD and dermatomyositis), with a progressive course with the ulceration and scarring of the skin lesions of limbs, in severe cases — up to necrosis of soft tissue. The primary RP not associated with SIDCT, and has a benign course, rarely leads to damage of soft tissues of the extremities and a violation of the nervous and humoral regulation of vascular tone of the skin fingers of hands and / or feet [1].

In adult patients with the SIDCT many scientific works described in detail changes during NBC. This method of investigating is widely used for the differential diagnosis of primary and secondary RP, and it is believed that pathological CS-picture in a patient with RP is a predictor of subsequent SIDCT even in the absence at the time of capillaroscopy other manifestations [18]. In primary RP changes in NBC missing or minor [1]. NBC value in children continues to be studied, but already accumulated some data about its use in children cardiorheumatology.

When comparing the CS-picture of control group, the group with primary RP and children SIDCT (systemic lupus erythematosus, juvenile dermatomyositis, mixed connective tissue disease, vasculitis) P. Dolezalova et al (2003) noted lack of differences in the indices of first two groups, while among the third group there was a significant decrease in the density of of capillaries compared with the control group (mean 4.8 versus 6.7 capillaries / mm, respectively), and a significant thickening of the capillary loops. Avascular zone and disorientation of capillaries were present only in children with SIDCT [19].

Nigrovic P.A. et al (2003) showed that the differential diagnosis of isolated RP in children on the basis of a deviation in the results, at least one of the two tests (NBC and the level of antinuclear antibodies) allows with the sensitivity of 93% and specificity of 61% to determine the secondary nature of the phenomenon [21].

Usually when interpreting NBC children use 4 pattern (Table 1).



At various rheumatologic diseases NBC has a different Informativity and diagnostic value. Juvenile system scleroderma (JSSD). System scleroderma — SIDCT, which is based on obliterans microangiopathy, leading to a gradual sclerosis of tissues, most frequently skin involvement and soft tissues of the musculoskeletal system, gastrointestinal tract, lungs and kidneys [1]. The most important and studied symptoms pathology of the capillaries, which are identified by capillaroscopy, described namely in case of SSD [12]. Data about capillary-microscopic appearance of a violation in MCB in case of SSD is so vast and specific that it allowed the American College of Rheumatology (ACR) to include results of NBC as an additional item in the classification criteria of SSD in adults [27], as well as a small criterion for JSSD diagnosis [26]. CS- pattern in case of JSSD presented in Table 1.

It is known that in the limited form of SSD isolated RP may for years precede other symptoms [2].

Therefore, early differential diagnosis of primary and secondary phenomenon is extremely important for selecting management method for the patient. In the patient with isolated RP and elevated antinuclear antibody (ANA) should be excluded debut of SSD. This involves NBC and detect the presence of antibodies to topoisomerase (anti Scl-70) or anti-centromere antibodies (ACA). A recent study by R. Pavlov-Dolijanovic et al (2011) 430 patients with isolated RP showed that the presence of scleroderma pattern in NBC predicted further development in catamnesis other symptoms of SSD with a sensitivity of 95% and a specificity of 67%. The combination of these NBC changes with Anti Scl-70 or ACA further increased the probability of disease development [2].

Thus, if the patient has an isolated RP and high titer of ANA advisable to perform NBC and test for anti Scl-70 and ACA. When changes in at least one of the tests for today exhibited diagnosed early SSD and appointed more profound examination to detect typical subclinical lesions of organs and systems: pulmonary function tests, CT scans of the chest for revealing early signs of pneumosclerosis, esophageal manometry to determine the early signs of a violation of its functions. In the absence of changes observation tactics must be selected, if necessary medical treatment of RP, when there are changes — appointment treatment of SSD [2].

Juvenile dermatomyositis (JDM) and polymyositis (JPM). JDM — SIDCT that occurs before the age of 16 years, mainly affecting the muscles, skin and internal organs. The basis of the disease is an autoimmune aggression against these organs and tissues with the development of small-vessel vasculitis [1]. JPM differs from JDM absence of cutaneous manifestations. JDM is second SIDCT disease with a specific pattern of CS-picture. In adults, the CS-pattern of dermatomyositis (DM) are well understood and similar to those in SSD.

In case of DM is determined at least 2 of the following features in at least two nail fold: expansion of the capillary loops (56% with DM, 21% in PM), reducing the density of capillaries and presence of avascular areas (in DM is more common than in PM), disorientation position of capillaries, look like bush, tortuous capillaries and presence of micro_hemorrhages. These changes correlate with the activity of myositis and residual muscle weakness [12].

S.A. Akhmedzhanova (1978) conducted NBC in 23 children with dermatomyositis. Only in 2 children picture was not changed. The rest has turbidity background, which indicates the edema due to increased capillary permeability, capillary density was reduced and was 2–6/mm distal row, withe clearly anastomoses between capillaries, their tortuosity and thickening. Interesting that capillary-microscopic changes occur in the dynamics even at low activity process. The author concluded that deep progressive disease process in MCB of children with JDM, is independent from disease activity.

Dolezalova P. et al (2003) gave a detailed description of the CS-picture of MCB in children with JDM. So JDM patients had significantly reduced the density of the capillary loops in comparison with the control group (mean 4.5 versus 6.7 capillaries / mm). Capillary loops were significantly wider, tortuosity index was significantly increased, frequently met avascular zone, disorientation of capillaries and micro-hemorrhages [19].

The authors also noted a significant bush capillaries on the background of their expansion, which, in their view, is a sign of angiogenesis, which are typical for the CSpicture JDM.

CS-picture at JSSD and JDM have a lot in common, which has led some researchers to combine them into a single pattern of scleroderma-dermatomyositis [10].

The third disease characterized by such CS-pattern scleroderma-dermatomyositis is mixed connective tissue disease. This nosology, which is a combination of characteristics of different SIDCT, mostly arthritis, FP, Sjogren's syndrome, polymyositis, sclerodactyly, and accompanied by increased titers of ANA [2].

Systemic lupus erythematosus. SLE — is SIDCT, which is characterized by the uncontrolled synthesis of a wide range of antibodies predominantly to nuclear antigens of own cells and the subsequent development of immunocomplex vasculitis with damage to many organs and systems [1]. Clinical presentation and diagnosis of SLE classification criteria presented in the AKP (1997) [9]. One of the main symptoms of the disease is a small vessels vasculitis, including the capillaries. Therefore, changes in the MCB observed in case of SLE almost always.

Among adults with SLE fairly frequent finding in NBC are capillary elongation and their tortuosity. Presence of avascular zones, reducing the density of capillaries and extension of capillary loops are unique to patients with secondary RP against SLE and correlate with disease activity [12,22]. In the study of CS-pictures MCB of children with SLE P. Dolezalova et al. (2003) and F. Ingegnoli et al. (2005) found no significant differences with the control group in the density of capillaries. Changes at NBC were represented mainly by change in the form and length of the capillary loops, detection rate of which was significantly superior to detection rate in the control group. JSSD pattern was not detected in children with SLE [4,19]. Authors didn't observed specific pattern or CS-picture in children or adults with SLE. However, the identified changes correlated with disease activity, which gives reason to use KSNL for children with SLE to monitor the disease. Juvenile rheumatoid arthritis (JRA). JRA — an autoimmune disease of the musculoskeletal system with debut before the age of 16, mainly affecting the joints and can involve in pathological process internal organs and systems [1]. Systemic form of the disease characterized by a generalized inflammatory process and may manifest vasculitis, including capillaritis. This explains the fact that in case of NBC performing 100% of adults with rheumatoid arthritis has tortuosity of capillaries and 75% — their elongation [12]. The remaining violations in the MCB are rare. M.N. Syroechkovsky in 1948 and examines the state of the MCB in patients with rheumatoid arthritis with NBC. It was found that incase of acute and subacute clinical course were some changes in MCB: scarcity capillary network in some areas, narrowing of the capillaries, aneurysmal bulging of the wall, slowing and discontinuity of capillary blood flow. Sometimes the swelling due to a significant increase in permeability of the ICR, which is visualized as a background turbidity. In severe quickly progressing arthritis capillary network is sparse, with loss of capillary loops. These changes are not changed by the treatment, wich indicating their organic nature. N.F. Batyunina (1964) and J.D. Sakharov (1965) studied the capillary-scopic picture of MCB in children with JRA. Authors found significant morphological and functional disorders: capillary background turbidity, spasticatonic state of the capillaries, reducing the density of the capillary network.

Relatively recent research A. Gorska et al. (2008) with 43 patients with juvenile idiopathic arthritis (JIA) revealed the following features of the CS-pattern in this disease. The density of capillaries was not significantly different in children with JIA and the control group (mean 14.1 / mm 2 and 16.3 / mm 2, respectively).

In children with JIA were noted elongation of capillary loops. The thickness of the arterial and venous parts of the loop were significantly extended in children of the main group and averaged 35 micrometers to 24 micrometers and 45 micrometers to 27 micrometers, respectively. Extended papillar venous plexus were found in 46% of patients with JIA and 20% of healthy children, and loss some capillary loops — at 59% and 10% respectively. Authors didn't observe significant differences in the CS-picture with the active and inactive JIA [7]. Thus, in contrast to adults with rheumatoid arthritis in children with JIA marks a more expressed lesion of MCB.

However, there are not enough published data concerning the question of MCB lesion in children with JRA and SLE. Considering the urgency of studying issue of MCB lesion in children with JRA and SIDCT and the scarcity of published data on this issue, aim of our work was to study the status of microcirculatory bed in children with JRA and SLE with capillaroscopy nail bed.


Materials and methods

We observed 33 children in cardiorheumatological department of CKH №1, Kiev from November 2011 to February 2012. 21 children (10 boys and 11 girls, mean age — 12.3 years) had a diagnosis of JRA, established according to criteria of Yakovleva-Dolgopolova (1979). 8 of them were joint-visceral form of JRA (medium term of illness — 2.9 years), and 13 — mostly articular (medium term of illness — 3.5 years). 11 (52.4±10.9%) children had oligoarthritis, 10 (47.6±10.9%) — arthritis. All children with JRA have taken as a basic therapy methotrexate at a dose of 15 mg/m2 / week (12 — orally, 9 — sc). Two children with systemic forms of have the combination of polyarthritis (on average — 6 active joints during the period of illness) with periodic fever. These children besides basic therapy with methotrexate received systemic glucocorticoid therapy at a dose of 0.5 mg/kg.

12 children (11 girls) had a diagnosis of SLE, which was established according to criteria of the AKP (1997). Average period of illness was 3.6 years. In all children with SLE activity of process at the time of the study had a first degree. All children at the time of study received standard treatment (chloroquine, azathioprine) and glucocorticoids in a dose of 0.2–0.5 mg / kg / day as prednisolone. In the clinical picture of children with SLE prevailed weakness (83.3±10.8%), arthralgia (50.0±14.4%), cephalgia (41.7±14.2%), in laboratory examination — anemia 1 degree (66.7±13.6%), a moderate increase in ESR up to 20 mm/h (33.3±13.6%), increasing the level of circulating immune complexes: large (16.7±10.8%) and small (16.7±10.8%). In all children with SLE at the time of the survey determined elevated levels of antibodies to 2 — spiral DNA, elevated ANA — at 50.0±14.4%.

To all children were performed digital capillaroscopy of nail bed of the fourth finger of both hands. Were assessed parameters such as the density of the capillary loops of the distal row of capillaries, their average length, form of the loop and index of tortuosity, orientation of capillary loops and presence of micro-hemorrhages. The results of the study are given in Table 2.




Results and discussion

Results of the study generally showed that the state MCB of children with SLE more disrupted as compared to patients with JRA. Thus, the decrease in the density of capillaries, increasing the length of more than 10% of capillaries, increased tortuosity index more than for 50% were significantly more frequent for children with SLE compared with patients with JRA (÷2 = 6.3, p<0.05;÷2 = 7.07, p<0.01; ÷2 = 10.5, p<0.01, respectively). The frequency of non-parallel orientation of capillaries and detection rate of micro-hemorrhages in patients of the two groups did not differ significantly (÷2 = 3.1, p>0.05; ÷2 = 1.15, p>0.05).

Shown differences are probably related to the fact that small-vessel vasculitis (palmar and plantar capillaritis, livedo reticularis) are not common of all patients with JRA, and are more common in patients with systemic form, and in case of serious predominantly articular form, whereas in case of SLE diffuse immunocomplex vasculitis of small vessels is the basis of pathogenesis and occurs in varying degrees of severity in all patients [1].


Conclusions


Thus, the nail bed capillaroscopy is a relatively simple and non-invasive capillary microcirculation morphology imaging technique. In the investigation of capillary-scopic picture of children with JRA and SLE revealed significant alterations in the microcirculatory bed patients with JRA and SLE, with significantly more frequent pathological changes of MCB in patients with SLE.


References
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МедЭксперт. Медицинские статьи. Медицина, лечение, здоровье
    
Опубликовано: 2013/5/15 23:14:13 2895

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