Nailfold Capillaroscopy in Psoriatic Patients with Metabolic Syndrome: A Comparative Observational Study

INTRODUCTION

Psoriasis is an inflammatory disorder affecting 0.84% of the global population.^[1] Psoriasis is a systemic disease associated with metabolic, psychological, arthritic and cardiovascular comorbidities.^[2,3] Psoriasis is a prototypical T helper type 1 (Th1) inflammatory disorder characterised by increased levels of Th-1 cytokines, intracellular adhesion molecule, E-selectin, angiogenic factors and vascular endothelial growth factor. These inflammatory mediators affect angiogenesis, lipid metabolism, insulin signalling, adipogenesis and epidermal proliferation, leads to microvascular changes in psoriasis, which can precede the skin manifestations and may resolve with treatment.^[4,5] These mediators are also crucial for the development of metabolic syndrome (MeS), which explains the presence of microvascular changes in MeS.^[4] MeS consists of hypertension (HTN), abdominal obesity, dyslipidaemia and glucose intolerance, which further elevate the likelihood of developing cardiovascular disease (CVD).^[2] Microvascular changes in MeS can be assessed non-invasively using nailfold capillaroscopy (NFC).^[5] Videocapillaroscope serves as a gold standard instrument for NFC; however, it’s cost often limits its availability in most clinical settings. On the other hand, universal serial bus (USB) videodermatoscope is a widely available and less expensive instrument.^[6,7] Nailfold capillary changes in psoriasis include decreased capillary density, presence of avascular areas and increased number of morphologically abnormal capillaries.^[8] NFC has become increasingly important for diagnosing rheumatic and connective tissue disease and can also be utilised to detect neovascular alterations associated with diabetes and HTN.^[5] To the best of our knowledge, there is a paucity of literature assessing nailfold capillary changes among psoriatic patients with MeS.

MATERIALS AND METHODS

This comparative, observational study was conducted at the Department of Dermatology, University of Delhi, India, for a period of 1 year (March 2021–March 2022). Clinically diagnosed cases of psoriasis were enrolled by convenience sampling. Healthy volunteers from the Hospital staff (doctors, nurses and workers) were matched for age and sex before recruited as controls. A total of 150 participants with 75 psoriasis patients and 75 healthy controls were recruited. Pregnant and lactating females and patients of Raynaud’s phenomenon, paronychia, periungual traumatic lesions, smoker and connective tissue disorders were excluded from the study.

The psoriasis area and severity index (PASI) score was used to calculate disease severity and patients were categorised mild (PASI ≤3), moderate (PASI between 3 and 10) or severe (PASI ≥10).^[9] National Cholesterol Education Program and Adult Treatment Panel III criteria was used to make the diagnosis of MeS.^[10]

NFC was done at an ambient room temperature where the subject sits for 15–20 min and the hand resting on a dull, non-refractile surface at hearts level. The fourth and fifth digits of hand’s were used for the morphological observation due to maximum transparency of the skin in these fingers. Each finger was gently wiped with an alcohol swab and after 2–3 min, 1–2 drop of immersion oil was put on the proximal nailfold for better visualisation of the capillaries. NFC was carried out under the polarising mode of USB videodermatoscope (dinolite AM7515ZT). Cuticle near the proximal nailfold was marked using an ultra-thin marker and the images were clicked on both side of the marked point. The images were studied with the USB videodermatoscope calibration software and 2 mm distance on each side of marked point was used for counting the distal most capillary loop. A total of 4 mm length was used for the counting of capillaries. A total of 16 mm length was used in all four fingers for counting capillaries. Dividing the total number of capillaries by 16 yielded the mean nailfold capillary density. Images of capillaries were captured through USB videodermatoscope in jpg format, saved on a hard drive and analysed by two unbiased evaluators. Both quantitative (mean capillary density) and qualitative parameters (bushy, dilated, giant, bizarre, tortuous, meandering capillary, microhaemorrhage, avascular area and subpapillary venous plexus) were evaluated.^[11-13]

Written informed consent was obtained from all the participants. The research protocol was approved by the Institutional Ethics Committee.

RESULTS

Both the groups were age- and sex-matched. The duration of psoriasis ranged from as short as one month to as long as 40 years. The PASI score ranged from 0.3 to 52.7. Maximum number of cases 60 (80%) had psoriasis of <10 years. Five cases had at least one family member suffering from psoriasis. Among 75 cases, 13 (17.35%) cases had a history of comorbidities, six had diabetes mellitus (DM), five had HTN and two had both DM and HTN. All psoriatic patients with DM had MeS and three patients with HTN had MeS.

According to the National Cholesterol Education Program and Adult Treatment Panel III criteria, 25 (33.3%) psoriatic cases had MeS and 10 (13.3%) healthy controls had MeS. Cases had significantly more participants with MeS than controls (P = 0.004). Majority of the cases with MeS, 14 (18.67%) had moderate psoriasis followed by 8 (10.67%) of mild psoriasis and 3 (4%) of severe psoriasis.

Comparison of NFC changes among cases and healthy control with MeS

Twenty-five psoriatic cases and 10 healthy controls had MeS. NFC density in cases was significantly lower than in controls (6.33 ± 0.63 vs. 7.16 ± 0.73 P = 0.005). Dilated capillaries and dropouts were significantly higher in psoriatic patients than that in controls. P = 0.02. Twelve (48.0%) participants in the psoriatic group had bushy capillaries. None of the controls had bushy capillaries and the association was statistically significant (P = 0.0072) [Figures 1-3]. Rest morphological parameters (Meandering, bizarre, giant, budding, criss-cross capillary and avascular area) were higher in psoriatic patients than in healthy controls. Tortuous capillaries and microhaemorrhages were higher in healthy control than in psoriatic patients but the association was not statistically significant [Table 1].

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Figure 1:

Nailfold capillaroscopy of psoriatic patient with metabolic syndrome showing budding capillary (green arrow), dilated capillary (purple arrow), capillary drop-out (red star) and meandering capillary (yellow arrow).

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Figure 2:

Nailfold capillaroscopy of psoriatic patient with metabolic syndrome showing subpapillary venous plexus (green arrow), criss-cross capillary (purple arrows), avascular area (red star) ramified capillary (yellow arrow) and dilated capillary (blue arrow).

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Figure 3:

Nailfold capillaroscopy of healthy control with metabolic syndrome showing dilated capillary (purple arrow), tortuous capillary (green arrow) and capillary dropout (red star).

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Table 1: Comparison of NFC changes among cases and healthy control with metabolic syndrome.

Parameters	Group		P-value
	Case (n=25)	Control (n=10)
Density (mean±SD)	6.33±0.63	7.16±0.73	0.005
Tortuous, n (%)	8 (32.0)	5 (50.0)	0.444
Meandering, n (%)	13 (52.0)	3 (30.0)	0.285
Dilated, n (%)	13 (52.0)	1 (10.0)	0.028
Giant, n (%)	7 (28.0)	0 (0.0)	0.084
Bushy, n (%)	12 (48.0)	0 (0.0)	0.007
Bizarre, n (%)	5 (20.0)	0 (0.0)	0.292
Microhaemorrhage, n (%)	0 (0.0)	1 (10.0)	0.286
Dropout, n (%)	16 (64.0)	2 (20.0)	0.027
Avascular area, n (%)	8 (32.0)	0 (0.0)	0.073
Subpapillary plexus, n (%)	10 (40.0)	0 (0.0)	0.034
Criss-cross, n (%)	13 (52.0)	5 (50.0)	1.000
Budding, n (%)	6 (24.0)	0 (0.0)	0.152

SD: Standard deviation, NFC: Nailfold capillaroscopy

Comparison of NFC changes among cases and healthy control without MeS

Fifty cases and 65 healthy controls had no MeS. NFC density in cases was significantly lower than in controls (6.44 ± 0.5 vs. 7.27 ± 0.35 P < 0.001). Meandering, dilated, giant, bushy, bizarre capillaries, microhaemorrhages, dropouts and avascular areas were significantly higher in psoriatic patients without MeS than that in controls without MeS (P < 0.001). Psoriatic patients without MeS had significantly higher criss-cross, budding capillaries than healthy controls without MeS. Subpapillary venous plexus visibility was significantly higher in psoriatic patients 14 (28.0%) than in healthy control8 (12.3%) (P = 0.034) [Table 2 and Figure 4].

Table 2: Comparison of NFC changes among cases and healthy control without metabolic syndrome.

Parameters	Group		P-value
	Case (n=50)	Control (n=65)
Density, mean±SD	6.44±0.55	7.27±0.35	<0.001
Tortuous, n (%)	22 (44.0)	20 (30.8)	0.144
Meandering, n (%)	25 (50.0)	1 (1.5)	<0.001
Dilated, n (%)	26 (52.0)	7 (10.8)	<0.001
Giant, n (%)	14 (28.0)	0 (0.0)	<0.001
Bushy, n (%)	13 (26.0)	1 (1.5)	<0.001
Bizarre, n (%)	18 (36.0)	3 (4.6)	<0.001
Microhaemorrhage, n (%)	14 (28.0)	0 (0.0)	<0.001
Dropout, n (%)	32 (64.0)	9 (13.8)	<0.001
Avascular area, n (%)	22 (44.0)	0 (0.0)	<0.001
Subpapillary plexus, n (%)	14 (28.0)	8 (12.3)	0.034
Criss-cross, n (%)	28 (56.0)	17 (26.2)	0.001
Budding, n (%)	6 (12.0)	0 (0.0)	0.006

SD: Standard deviation, NFC: Nailfold capillaroscopy

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Figure 4:

Nailfold capillaroscopy of healthy control showing regular and parallel arrangement of nailfold capillary.

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DISCUSSION

Psoriasis is a systemic inflammatory condition, which confers an increased risk of cardiovascular disorders. In our present study, a significant higher prevalence of MeS were found in psoriatic patients as compared to healthy controls. Same observations were also reported by Nisa and Qazi in 2010, they found that 28% of psoriatic patients and 6% of healthy controls had MeS.^[14] Our study revealed that the disease severity was correlated with higher nailfold capillary changes but not correlated with a higher rate of MeS. Neimann et al., in 2006, recruited 1,27,706 psoriatic patients and found that the severity of the disease corelated with the higher rate of obesity and DM; however, HTN and hyperlipidaemia are not independently associated with severe disease.^[15] A study by Kothiwala et al. found that the prevalence of MeS increased with increasing disease severity.^[16] A study by Gisondi et al., in 2007, found no relationship between MeS prevalence and psoriasis severity.^[17] Similarly, Fernández-Armenteros et al., in 2019, found no relation between psoriasis severity and MeS.^[18] In our study, among each parameters of MeS systolic BP, obesity (Waist Circumference), triglycerides and FBS were significantly higher in psoriatic patients than in healthy controls, similar observations were reported by Kothiwala et al. in 2016.^[16]

Psoriatic patients without MeS had significantly lower nailfold capillary density than that in controls without MeS. Psoriatic patients without MeS demonstrated significantly higher qualitative parameters (bushy, dilated, giant, bizarre and meandering capillary, microhaemorrhage, avascular area and subpapillary venous plexus visibility) compared to healthy controls without MeS.

Nailfold capillary density in patients of psoriasis with MeS was significantly less as compared to controls with MeS. Among qualitative parameters, dilated capillary, bushy capillary, capillary dropout and subpapillary venous plexus visibility were significantly higher in psoriasis with MeS than controls with MeS. These capillary morphologies suggest that neovascularisation is driven by tissue hypoxia and local generation of vascular growth factors which are due to vascular inflammation and atherosclerosis caused by psoriasis and MeS.^[13,19] Numerous research has shown that psoriatic are strongly associated with cerebrocardiovascular diseases, depression, anxiety, osteoporosis, non-alcoholic fatty liver disease and end-stage renal disease; similarly, MeS is an independent contributor for CVDs.^[19-23] The pathogenesis of psoriasis and MeS has overlapping genetic predisposition and inflammatory pathways and having both conditions, psoriasis and MeS, leads to an increased risk of CVD.^[19,24] This ancillary inflammation in the capillary wall by MeS correlates with our NFC finding that bushy capillary, capillary dropout and visibility of subpapillary venous plexus were significantly higher in psoriatic patients with MeS than that in controls with MeS. NFC may enable us to quickly identify psoriatic patients who are at an increased risk of developing CVD.

A systematic review by Wu et al. showed that systemic treatment of psoriasis was associated with reduced vascular inflammation and cardiovascular events.^[24] Adequate control of MeS through medication or lifestyle changes has a beneficial effect on psoriasis.^[23] NFC has the potential to aid in early initiation of systemic treatment for psoriatic patients at risk of complications. NFC may further help us in the follow-up of these patients and their response to treatment.

CONCLUSION

The prevalence of MeS was higher in psoriatic patients. The severity of psoriasis is not related to the development of MeS. MeS is associated with reduced nailfold capillary density and increases abnormal capillary morphologies in both psoriatic patients and healthy control groups. NFC may contribute to the early recognition of patients which require cardiovascular preventive measures, early initiation of systemic therapy, follow-up and response to treatment. Further, longitudinal study is required to establish temporal relationships between psoriasis, MeS and nailfold capillary changes.