Nailfold video capillaroscopy in Turner syndrome : a descriptive study

Results: Fifty patients aged between 6-37 years with Turner syndrome were studied. Eighteen (36%) patients had normal capillaroscopy with hairpin pattern in loop distribution and no avascular fields. The papilla was ratified in 13 (26%) and enlarged in four (8%). Edema occurred in 22 (44%) cases. There were three (6%) macrocapillaries and three (6%) were branched. Tortuosity was present in five (10%) patients. Hemorrhagic extravasation occurred in one (2%) case. Flow was fast in seven (14%), granulous in five (10%) and slow in six (12%).


Introduction
Turner syndrome (TS) is a relatively common chromosome disorder, caused by complete or partial X monosomy.TS affects approximately 1:2,000 female births and as many as 10% of spontaneous miscarriages have a 45,X karyotype. 1,2[19][20][21][22][23] The aim of this study is to describe the morphology of nailfold capillaries in patients with TS using videocapillaroscopy.

Methods
A descriptive cross-sectional study was carried out.Diagnosis of ST was confirmed by karyotype.Diabetic patients were excluded.This study was approved by the ethics committee of Universidade Federal do Rio de Janeiro.Subjects were studied in a temperature-controlled room in the morning following a night's fasting, 20 days after no nailfold manipulations.The subjects were comfortably seated in a chair with the observed hand at heart level with the forearm and hand bent at the elbow.All patients had their arm blood pressure measured in this position using the auscultatory method.Capillaries were visualized by microscope connected to a television monitor and computer.A few drops of immersion oil were spread on the observation area.Capillary morphology was studied in a magnification of 0.8 to 10.0 x by the same observer.The capillaries were classified in the following patterns: loop distribution, papilla, avascular fields, venous plexus, edema, form, capillary limbs, flow and hemorrhagic extravasation.The following capillary characteristics were considered normal: hairpin loop distribution, normal papilla, absent avascular fields, absent edema, normal form of capillary limbs, continuous flow and no hemorrhagic extravasation.Patients were classified in three groups according to pubertal status: prepubertal, spontaneous puberty and postpubertal, and also according to karyotype by 45,X and mosaicism.
Distribution of the presence of abnormalities by karyotype and pubertal status is presented in Table 1.Eighteen (36%) patients had normal capillaroscopy in all patterns (group 1) and 32 (64%) had abnormal capillaroscopy (group 2).Distribution of groups considering age and medication is presented in Table 2. Abnormality patterns are described in Tables 3 and 4. Number of abnormality patterns varied among patients.Eleven (22%) patients had only one abnormality, nine (18%) had two, seven (14%) had three, four (8%) had four and one (2%) had five abnormalities.All abnormalities are described in Table 5.

Discussion
Study of capillaries may express the status of vessel permeability and videocapillaroscopy is an easy and noninvasive method to study them.Since nailfold capillaries are parallel to the skin surface, they can be seen in full length by microscopy.This method only requires a period of about 20 days free of nailfold injuries.Cardiovascular complications are the main cause of increased mortality in TS.Ischemic heart disease risk factors reported in TS include hypertension, diabetes mellitus, dyslipidemia, obesity and estrogen deficiency. 4,12,13Capillaroscopy allows visibility of the capillaries but a single capillary form is not pathognomonic of a given disease.E + P = estrogen + progesterone therapy; GH = growth hormone therapy; N = no medication.* One in GH therapy and had hemorrhagic extravasation.† One in E + P therapy and had mixed loops.‡ One in E + P therapy had avascular field.Hairpin pattern is considered normal [18][19][20][21] and most cases in our study presented this form of loops.Some authors 18,19 referred that presence of the venous plexus may be normal or not, considering patient's age.This occurs during childhood and it is reported that the plexus disappears in adults.Venous plexus was absent in almost 90% of the patients, but was present in three (6%) adult patients.We are currently unable to define the significance of this presence.Tortuosity was present in 10% of cases.Leader 18 considered that tortuosity may occur in adults, but any tortuosity must be considered abnormal in children.In our study, five patients had tortuosity.Two of them were children, prepubertal and using growth hormone and three were adolescents, without use of any medication and with development of spontaneous puberty.Diagnosis of tortuosity was performed using an article by Walls & Buchanan, 20 who consider tortuosity as being pathologic only if it is present in > 20% of capillaries studied.Tortuosity may represent diabetes 24,25 or lupus erythematosus. 26Diabetes was an exclusion criterion of our research, and none of our patients presented symptoms or signs suggestive of lupus disease.Edema was the most common abnormality observed followed by ratified papilla, and the association of edema and ratified papilla occurred in about 16% of the patients.8][29] We found edema in all ages and none of our patients indicated previous trauma.Trauma in children is more common than in other ages and may not be reported correctly as such by the child, whereas adolescents and adults may inform if there was any trauma event.Hands and fingers were examined before the nailfold capillaroscopy and none presented signs of injury.

Table 5 -Number of abnormalities at capillaroscopy
Edema was observed mostly in older patients using estrogen and progesterone and in children using growth hormone, about 46 and 33%, respectively.Growth hormone therapy is associated with some collateral effects, including edema and is also correlated to insulin resistance, which can deteriorate endothelial function. 30The same effect is reported with use of estrogens 31 and the high prevalence found in this study may be explained by this collateral effect.On the other hand, estrogen receptors are present in vascular smooth muscle and endothelial cells and the use of estrogen therapy has a favorable effect on cardiovascular hemodynamics in TS. 32,33 Chan et al. studied the effects of hormone replacement therapy on endothelial function in women with TS using plethysmography.These authors analyzed the endothelium-dependent vasodilator factors, such as bradykinin and endothelium-independent vasodilator factors, such as nitric oxide, and referred that hormone replacement therapy improved endothelial function in patients with TS. 32 In the literature, it is reported that progesterone may antagonize the beneficial effect of estrogen on the vasculature. 32In our study, patients using only estrogen therapy or estrogen plus progesterone had a high prevalence (18%) of edema and ratified papilla.
We found some cases with slow or granulous flow, which were abnormal and suggested some disturbance of the capillary circulation. 19,21Seven of our patients presented fast flow.There is no consensus about fast flow -some studies report this pattern to be normal, 18 while others consider fast flow pathologic and associated with anemia. 19None of our patients had anemia.Presence of branched or macrocapillaries may indicate chronic diseases, such as dermatomyositis and sclerodemia. 21,27,28When these patterns are present, other pathologies should be investigated.The papilla was enlarged in four cases in this study and all of them also presented edema.Three group 2 patients had macrocapillaries, one of whom also had tortuosity.Moura et al. 25 found that diabetic patients had more enlarged capillaries and tortuosity than the control group.This abnormality was also described in rheumatologic disease 21,28 and other studies have described hemorrhagic extravasation. 21In our study, only one patient presented hemorrhagic extravasation and needed to be evaluated for rheumatologic disease.We compared our data with reports for healthy subjects or in some diseases, such as diabetes or lupus erythematosus, [24][25][26]29 because for TS we did not find previous reports about vascular endothelium using videocapillaroscopy. We onclude that there is a high prevalence of alterations in nailfold capillaroscopy in TS and that edema and ratified papilla are the main alterations.

Table 1 -
Distribution of groups by karyotype and pubertal status

Table 2 -
Distribution of groups by age and medication E = estrogen therapy; E + P = estrogen + progesterone therapy; GH = growth hormone therapy; GH + E = growth hormone therapy + estrogen therapy; N = no medication.

Table 3 -
Distribution of capillary patterns in group 2

Table 4 -
Distribution of abnormalities by age