Role of Vascular Ultrasound in Cases of Lower Limb Hyperpigmentation.

BACKGROUND: Hyperpigmentation remains an important finding in cases of venous insufficiency and peripheral arterial disease (PAD) among the vascular causes. AIMS: This study aimed at finding the presence of arterial and/or venous insufficiency in patients of lower leg hyperpigmentation by using vascular ultrasound (US).
MATERIALS AND METHODS: Fifty patients of lower leg pigmentation were included in the study. The detailed history, general physical examination, and laboratory investigations were done. Color Doppler ultrasonography was performed to check for venous insufficiency/PADs. Qualitative variables were correlated using chi-square test/Fisher's exact test. P < 0.05 was considered statistically significant.
RESULTS: The mean age of the patients was 44.32 ± 14.16 years. Four patterns of skin changes were seen - reticulate macular, diffuse macular, lipodermatosclerosis and ulcer. Thirty-five (70%) patients had no visible varicose vein while 15 (30%) had visible varicose vein. In patients with visible varicose vein, color Doppler showed signs of venous insufficiency in all patients, but in cases of no visible varicose vein, color Doppler showed signs of venous insufficiency in 19 (54.28%) patients and showed no signs of venous insufficiency in others (P = 0.78). Only 1 (2%) patient showed atherosclerotic changes in both anterior tibial arteries.
CONCLUSION: All patients with lower leg pigmentation with or without visible varicose vein should undergo vascular US to rule out any venous insufficiency. Copyright:

Introduction

Hyperpigmentation refers to the increased pigment, resulting in the darkening of an area of skin or nail. It may be diffuse or focal. Some of the common causes of the lower leg pigmentation are pigmented purpuric dermatoses, endocrine disorders, drugs, pregnancy, trauma, burn, endogenous and exogenous eczema, peripheral arterial disease (PAD), and venous insufficiency.

The normal venous system consists of a high pressure deep venous system and a superficial system linked by communicating veins. Single-way valves prevent retrograde blood flow. These valves open to allow the blood to flow from superficial veins to deep veins.

Chronic venous insufficiency (CVI) arises from the failure of the calf muscle pump or abnormalities in the venous system, such as valve dysfunction, venous outflow obstruction, or a combination of these factors. The resulting clinical features are numerous. Pitting edema occurs because of venous hypertension and fluid leakage through the walls of distended vessels. Large, dilated veins can also appear on the cutaneous surface. Further changes include reddish brown hyperpigmentation and purpura, caused due to extravasation of red blood cells into the dermis, collection of hemosiderin within the macrophages and melanin deposition.[12] Venous ulcers can develop on and around the medial malleolus. The prevalence of skin changes including hyperpigmentation and eczema due to CVI varies between 3% and 11% of the population.[3] It is one of the leading causes of lower leg pigmentation. According to another estimate, 15%–20% of the population in India is suffering from venous diseases these days.[4]

Ultrasound (US) is the most useful and widely used modality for evaluating venous diseases of the lower extremities,[5] but its use in lower limb hyperpigmentation has not been explored sufficiently. An understanding of the lower extremity venous system is important for diagnosing and determining the pathophysiology of venous disease. Hence, this demands a combined effort of a radiologist and a dermatologist to come to a conclusion and follow-up of the case.

We undertook this study to find the presence of venous insufficiency and/or PAD in patients of lower leg hyperpigmentation by using vascular US.

Materials and Methods

A descriptive study was done in the Department of Dermatology, PGIMER and Dr. RML Hospital from November 2014 to March 2016 whereby 50 cases of pigmentation restricted to lower leg, ankle and proximal part of foot, unilateral or bilateral, with or without any other associated skin lesions, such as papules, nodules, purpura, petechiae, telangiectasia, and ulcers were included in the study. Pregnant females and patients with pigmentation suspected to be secondary to drug reactions or with associated pigmentation involving any other part of the skin were excluded from the study. The detailed history, general physical examination and laboratory investigations comprising of blood counts, blood glucose level, liver function tests, kidney function tests, and lipid profile were done. Each patient was evaluated for the presence of visible varicose vein, and peripheral pulses of lower limb arteries were checked.

Vascular US (color Doppler) was done for all the patients, and the diagnosis of venous insufficiency and/or PAD was made based on the result.

Color Doppler USG was performed using the Philips HD11 US device in Dr. RML Hospital using linear probes of frequency 5–10MHz. The probe was held at an angle of 60o with the plane to examine the veins and arteries. Doppler US demonstrated the reversal of flow from the deep to the superficial venous system in CVI.[5]

Major superficial and deep veins of the lower limb including great and short saphenous veins (SSV) and femoropopliteal veins were examined. Veins were examined with the patient in upright position. The patient was asked to remove clothing from the leg being examined. Then, he was asked to turn the leg under examination outward to allow scanning of the inner thigh and calf. The common femoral vein was evaluated for obstruction and reflux. Then, the great saphenous vein (GSV) was followed from its junction down beyond the level of any visible varicose veins. Venous insufficiency was assessed using the augmentation technique and the Valsalva maneuver. In the augmentation technique, the leg was manually squeezed to increase the venous return to the heart. With release of pressure, blood drops back to the feet. Transient reflux (<0.5 s) was considered normal, while reflux (>1.0 s) was indicative of CVI. Valsalva maneuver was also used to assess venous insufficiency. During color Doppler examination if the retrograde flow was more than 1 second, it was accepted as venous insufficiency.

The diagnosis of PAD was made using color Doppler US. The patient was examined in supine position using a 5–10 MHz linear transducer. The patient was asked to remove clothing from the leg being examined. A paste was applied to the skin over the arteries. The superficial femoral, tibial and the dorsalis pedis arteries were examined. PAD was defined as the presence of stenosis of 50% or higher in any lower extremity artery between common iliac and FPL regions. Minor stenosis was defined as <50% narrowing of vessels, moderate stenosis as 50%–75% narrowing and severe stenosis as >75% narrowing of vessels.

Statistical analysis

Categorical variables were presented in count and percentage and continuous variables were presented as mean ± standard deviation and median. Findings of Doppler USG were correlated with clinical varicosity using McNemar test of paired proportions. Qualitative variables were correlated using chi-square test/Fisher's exact test. The diagnostic test was used to find sensitivity, specificity, negative predictive value, and positive predictive value of clinically having varicosity for detecting venous insufficiency. The data were entered into MS Excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0 (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY). P < 0.05 was considered to indicate statistical significance.

Results

The mean age of the patients in our study was 44.32 ± 14.16 years. Forty-two patients were male and eight patients were female. The age and sex distribution has been shown in Table 1.

Table 1

Age and sex distribution of the patients

Age group in years	Males, n (%)	Females, n (%)	Total, n (%)
15-30	6 (12)	0	6 (12)
31-45	19 (38)	5 (10)	24 (48)
46-60	10 (20)	1 (2)	11 (22)
61-75	7 (14)	2 (4)	9 (18)

Four patterns of skin changes were observed among the patients - reticulate macular, diffuse macular, lipodermatosclerosis, and ulcer. Of the 50 patients, 32 (64%) of the patients had reticulate macular type of hyperpigmentation of lower limbs [Figures 1 and 2], 12 (24%) had diffuse macular type [Figure 3], 6% had lipodermatosclerotic changes [Figure 4] while 6% had ulcer on lower limbs [Figure 5]. Thirty-five (70%) had no visible varicose vein while 15 (30%) had visible varicose vein. The type of pigmentation in relation to clinical presence of varicose vein has been shown in Table 2. A significant difference was found between them (P < 0.05).

Figure 1

Patient showing reticulate macular type of pigmentation with no visible varicose vein and Doppler ultrasonography showing no venous insufficiency

Figure 2

Patient showing reticulate macular type of pigmentation with no visible varicose vein with Doppler ultrasonography showing venous insufficiency

Figure 3

Patient with diffuse lower leg pigmentation who also had visible varicose veins and Doppler ultrasonography showing venous insufficiency

Figure 4

Patient showing lipodermatosclerosis, who also had visible varicose veins and Doppler ultrasonography showed venous insufficiency

Figure 5

Patient with diffuse macular type of pigmentation along with ulcers on both legs in a patient with visible varicose veins and Doppler ultrasonography showing venous insufficiency

Table 2

Type of pigmentation in relation to clinical presence of varicose veins

Clinical Examination	Reticulate macular (%)	Diffuse macular (%)	Lipodermatosclerosis (%)	Ulcer (%)
Visible varicose veins	5 (10)	6 (12)	2 (4)	2 (4)
No visible varicose vein	27 (54)	6 (12)	1 (2)	1 (2)
Total	32 (64)	12 (24)	3 (6)	3 (6)

P=0.026

Out of all the patients with no visible varicose veins, color Doppler showed signs of venous insufficiency in 19 (54.29%) patients and showed no signs of venous insufficiency in 16 (45.71%) patients. The difference was comparable (P = 0.78).

The vascular US findings in all the patients with lower limb hyperpigmentation have been shown in Table 3.

Table 3

Vascular ultrasound findings in patients with lower limb hyperpigmentation

Vascular ultrasound examination findings	Patients having visible varicose veins*			Patients having no visible varicose vein†
	Males (%)	Females (%)	Total (%)	Males (%)	Females (%)	Total (%)
Doppler USG showing venous insufficiency	13 (26)	2 (4)	15 (30)	16 (32)	3 (6)	19 (38)
Doppler USG showing no venous insufficiency	0	0	0	13 (26)	3 (6)	16 (32)

*P<0.0001. †P>0.05. USG: Ultrasonography

Out of 50 patients, 2 (4%) patients had incompetent right saphenofemoral junction (SFJ) and 1 (2%) had incompetent left SFJ. Five (10%) patients had incompetent right saphenopopliteal junction (SPJ) and 3 (6%) had incompetent left SPJ.

Twenty-five (50%) patients showed right GSV insufficiency, 25 (50%) showed insufficiency in the left GSV, 16 (32%) showed insufficiency in right SSV, and 19 (38%) showed insufficiency in left SSV.

On Doppler USG, incompetent perforators were seen along the veins showing insufficiency, with a minimum of one incompetent perforator and a maximum of 4 incompetent perforators seen in the veins. It has been shown in Table 4.

Table 4

Number of incompetent perforators seen in great saphenous vein and short saphenous vein

Number of incompetent perforators	Right		Left
	GSV (%)	SSV (%)	GSV (%)	SSV (%)
1	14 (28)	12 (24)	9 (18)	12 (24)
2	10 (20)	3 (6)	11 (22)	6 (12)
3	1 (2)	0	4 (8)	0
4	0	1 (2)	0	1 (2)

GSV: Great saphenous vein, SSV: Short saphenous vein

Of the 50 patients, 1 (2%) patient showed atherosclerotic changes in anterior tibial arteries of both lower limbs. The patient did not have associated varicose vein. Moreover, he was a smoker and a known case of diabetes mellitus.

Among the other investigations, renal function tests, liver function tests, and lipid profile of all the patients were in normal range. Six (12%) patients were known diabetic and one of them had atherosclerotic changes in the anterior tibial arteries of both lower limbs. Four (8%) patients had hypertension. No bruits were heard on auscultation in any of the patients. Trendelenburg test was positive in six patients, who also had visible varicose vein and color Doppler USG was also suggestive of insufficiency.

Discussion

Of the 50 patients with lower leg hyperpigmentation taken for the study, 34 (68%) showed signs of venous insufficiency on color Doppler study as opposed to 16 (32%) patients without venous insufficiency (P < 0.0001). Thirty-five patients were without visible varicose vein and among them 19 (54.28%) showed signs of venous insufficiency while 16 (45.71%) showed no signs of venous insufficiency on color Doppler study (P = 0.7835), signifying that the chances of finding venous insufficiency were almost equal in all patients with lower leg pigmentation with no clinically visible varicose veins.

The scarcity of cases with visible varicose vein in our study was probably because we included only those patients who had lower limb hyperpigmentation. In the Edinburgh Vein study by Evans et al.,[6] 1566 random subjects from the general population were taken for examination (867 women and 699 men), out of these 39.7% of the men and 32.2% of the women had visible varicose vein on clinical examination but no further US examination was done in them. In another study done by Carpentier et al.[7] 2000 subjects were randomly selected from 4 cities in France and examined for the prevalence of varicose vein and the associated skin changes. In the study, 50.5% of women and 30.1% of men showed varicose veins, out of which only 2.8% of women and 5.4% of men also had skin changes.

In our study, four main types of pigmentary changes were observed in the patients, i.e., reticulate macular hyperpigmentation, diffuse macular hyperpigmentation, lipodermatosclerosis, and diffuse pigmentation along with ulcer. Reticulate macular type was the most common among them. Of the 32 patients with reticulate type of pigmentation, 5 (15.62%) had visible varicose vein who also had venous insufficiency on color Doppler, 12 (37.5%) had no visible varicose vein but their color Doppler study was suggestive of venous insufficiency, while 15 (46.87%) had no visible varicose vein and their color Doppler was also normal.

The different types of pigmentation named in our study are based on the morphology clinically but the exact pigment deposited might be the same in all cases as the mechanism is more or less venous insufficiency. The skin hyperpigmentation may be used as a warning sign for the varicosity. We found that irrespective of the visible varicose vein, all patients of lower limb hyperpigmentation should be thoroughly examined by color Doppler to rule out venous insufficiency.

Limitations of the study

The pigmentation was not graded for its severity and neither was it compared with the laboratory investigations performed above nor with Trendelenburg test result. The specific pigment involved (melanin or hemosiderin) was not evaluated in the study.

Conclusion

In patients with lower leg pigmentation and without clinical evidence of varicose vein, the vascular US may detect more than 50% of cases of venous insufficiency. Thus, we suggest that all patients with lower leg pigmentation with or without visible varicose vein should undergo vascular US to rule out any venous insufficiency, more particularly in those without visible varicose vein. In addition, vascular US may also detect atherosclerotic changes in the lower limb arteries of the patients with lower leg pigmentation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.