Symptoms and signs of chronic venous disorders: can we put an end to the controversy?






Marian SIMKA, MD, PhD
College of Applied Sciences
Department of Nursing
Ruda Śląska, POLAND

Symptoms and signs of chronic venous disorders: can we put an end to the controversy?


by M. Simka, Poland



Association of so-called venous symptoms (aching, itching, tingling, burning sensation, swelling, easily fatigued legs, leg heaviness, and leg restlessness) with chronic venous disease (CVD) still remains a controversial issue. Although these symptoms and decreased quality of life are common in patients with venous incompetence, and are even more frequent in those with a history of venous thrombosis or recurrent and bilateral varicose veins, research has actually revealed that these complaints are poorly correlated with objective signs of venous insufficiency. A venous source for these complaints is quite obvious in patients with advanced CVD, but a substantial part of venous symptoms, especially in patients with telangiectasias and uncomplicated varicose veins, is actually not of venous origin. In addition, such symptoms can be reported by many patients presenting with nonvenous diseases, while uncomplicated varicose veins can cause few symptoms or be asymptomatic. In many venous patients these symptoms are not permanent, but can only be seen at the end of the day. Therefore, it is important to consider and investigate an alternative cause of such “venous” complaints, especially because other pathologies can accompany CVD and produce similar symptoms. The most common pathologies that may be responsible and should be taken into account include: spinal disc herniation, hip and knee arthrosis, peripheral arterial disease, joint and ligament overload due to obesity, peripheral neuropathy, and adverse drug reactions.

Medicographia. 2015;37:20-25 (see French abstract on page 25)



There is a great deal of controversy surrounding association of so-called venous symptoms with chronic venous disease (CVD). An uncertain association of the presence of uncomplicated varicosities with these symptoms has even lead some health care providers to restrict access to treatment for asymptomatic varicose vein patients or those experiencing few symptoms.1 Clinical symptoms that are thought to be caused by chronic venous insufficiency include: aching leg pain, itching, tingling, burning sensation, swelling, easily fatigued legs, leg heaviness, and restlessness. All of these symptoms typically worsen as the day progresses.2 The presence of such complaints usually correlates with a decreased quality of life (QoL). An association of these symptoms with CVD is not as obvious as is usually believed. While some researchers found significant correlations between venous symptoms and the signs of CVD (venous reflux revealed by means of Doppler sonography, visible varicose veins, or skin changes typical for venous incompetence [hyperpigmentation, lipodermatosclerosis, and ulcers]), others argued that these symptoms were actually poorly correlated with clinical signs of venous insufficiency. In this review, I will summarize the research related to this problem in an attempt to explain conflicting results and interpretations of the studies.


Figure 1
Figure 1. The most common nonvenous causes of the so-called
“venous” symptoms.

(A) spinal disc herniation; (B) hip and knee arthrosis; (C) peripheral arterial disease; (D) peripheral neuropathy; (E) adverse drug reactions (calcium channel blocker
or other medications).


Correlating symptoms and signs

Severe chronic venous disease
The majority of patients with severe forms of CVD—those with leg edema (C3 according to the clinical, etiological, anatomical, pathophysiological [CEAP] classification), skin changes (C4), and venous ulcers (C5 and C6)—present with some of the above symptoms. The proportion of patients with venous symptoms significantly increases with the “C” class of the CEAP classification.3 Usually, in patients with advanced CVD an association of these symptoms with venous incompetence is not questioned, even if other pathologies can accompany chronic venous insufficiency and may produce similar symptoms. Also, it has been demonstrated that these patients present with decreased QoL, with progressive impairment of QoL from C3 to C5/C6.2,4,5





Less severe chronic venous disease
Venous background of clinical symptoms in patients with less severe forms of CVD, C1 and C2, remains controversial. Many of these patients are asymptomatic despite the presence of an obvious venous pathology.3,6-10 In many C1/C2 patients these complaints may actually be rooted in another coexisting pathology, such as osteoarticular, neurologic, or arterial pathology (Figure 1). For example, in the VEnous INsufficiency Epidemiologic and economic Study (VEINES; 1531 patients with CVD and 1313 controls assessed) the authors did not find significant differences it terms of venous symptoms between the controls and patients with varicose veins (C2). Thus, the authors speculated that clinical symptoms in varicose vein patients probably resulted from concomitant aspects of CVD and not from varicosities, per se.9

Poor correlation between symptoms and signs
In the Edinburgh Vein Study (a cross-sectional population study, 1566 individuals assessed) the authors did not demonstrate an association between lower-limb symptoms (leg heaviness, aching, and itching) and the presence of visible varicose veins.11 Nor did they reveal a significant correlation between venous reflux and lower-limb symptoms.12 Consequently they concluded that most of these symptoms probably had a nonvenous cause.11 A similar conclusion came from another study, where itching and burning sensations in the legs were not correlated with the severity of venous insufficiency.13 Also, an observational study by Howlager et al, looking at patients attending a vascular clinic (132 individuals assessed), did not reveal an association between severity of the symptoms and anatomic distribution of venous reflux.14

Potential correlation between symptoms and signs
On the contrary, in the San Diego population study (a crosssectional study on 2209 individuals) the researchers revealed an association between clinical symptoms and the presence of venous disease. Leg edema was the most specific symptom related to venous incompetence. Other symptoms, comprising leg heaviness, aching, and itching, although more common in the patients with venous disease, were also found quite often (5% to 15%) in individuals without CVD.15

Similar results were demonstrated by a recent Dutch study. The authors revealed small and—except for swelling of the leg and itching—nonsignificant differences in prevalence of venous symptoms between the patients with CVD and those suffering from other pathologies (arthrosis, peripheral arterial disease, or spinal disc herniation). However, the patients with venous incompetence were more likely to experience symptoms at the end of the day, which was atypical in patients with other pathologies.2

In another study, the researchers found more frequent venous symptoms among patients with telangiectasias, and even more such symptoms in patients with varicose veins. However, a substantial proportion of the individuals without venous disease also reported “venous” complaints (heaviness, swelling, aching, restless legs, cramps, itching, and tingling) and differences between the subjects with no visible venous pathology and those with either telangiectasias or varicose veins were modest.16

Much the same conclusions came from another survey. The authors of this cross-sectional study revealed venous symptoms in 60% of patients with varicose veins and demonstrated that this association was statistically significant. However, 33% of subjects without varicose veins also suffered from venous symptoms. Risk factors that were significantly associated with these symptoms included prolonged sitting or standing, and history of thromboembolism. These symptoms were more common in older women and in tall (height >175 cm) and overweight (body mass index [BMI] >25 kg/m2) men. Consequently, the authors concluded that varicose veins were not the only cause of venous symptoms. Other factors, primarily prolonged sitting and standing, could be a source of such symptoms, and improper clothes and shoes may also play a role. Of note, the researchers did not demonstrate a statistically significant correlation between these symptoms and a history of osteoarthritis. Still, venous symptoms were more common in such patients (20% vs 15% in patients with a negative history of osteoarthritis). Notably, in this study the patients were not clinically examined to reveal an osteoarticular pathology.8

In another cross-sectional study on clinical features of CVD in Italian patients (16 251 individuals assessed) the researchers found a statistically significant positive correlation between the symptoms (such as tired and heavy legs, leg pain, or leg edema) and severity of venous disease (defined by the “C” grade of CEAP). These venous symptoms were more prevalent in women and in patients with an increased BMI. However, almost all participants of this survey reported some complaints and only about 10% of the individuals surveyed were free of venous symptoms. An actual venous background of these complaints in the population studied remains questionable. Moreover, it was likely that relevant selection bias occurred in this study, since the individuals attending this survey were attracted by means of advertising in mass media. Therefore, the population was probably skewed towards people with some—not necessarily vascular—leg complaints.10 To add to the confusion, in one study patients with benign venous disease (C2/C3) reported more symptoms than those with complicated varicose veins (C4/C5).14

Venous background of leg symptoms in patients with telangiectasias and small epifascial veins (C1 in the CEAP classification) is even less certain. In a cross-sectional study aimed at the evaluation of the clinical impact of small cutaneous veins, researchers found that venous symptoms, comprising leg edema, muscle cramps, and restless legs, were more common in patients with small varicosities in comparison with healthy controls (C0), except for itching, which was less prevalent in the individuals with dilated veins. However, when adjusted for age and sex, these differences—except for leg swelling—were no longer statistically significant. Thus, the authors concluded that although venous symptoms were quite common, also in the C1 class patients, patients’ age (older subjects) and sex (women) seemed to be a better explanation for these complaints than the presence of small cutaneous varicosities. Leg swelling can be related to such dilated veins, yet their clinical relevance in the development of this symptom seemed to be low (odds ratio, 1.3).17

Chronic venous disease and quality of life

Clinical stage
There are also conflicting results for studies on QoL in early stages of CVD. In the San Diego population study the presence of venous disease, even of uncomplicated varicose veins, was associated with significant limitations of all functional scales (physical functioning, role functioning, pain, and general health perception) of the Short Form 36 (SF-36) QoL questionnaire.5 In another study, female sex was associated with a worse QoL in the patients referred to the varicose vein clinic, but this effect was no longer seen when only C2 patients were analyzed.7

Similarly, the VEINES study did not reveal significant differences in QoL between C2 patients and controls,9 and there was no association between the “C” class and QoL impairment in a study assessing the patients qualified for surgical treatment of varicose veins.7 Also, an observational study on patients assessed in vascular laboratories did not demonstrate a decreased QoL in the individuals with C1 and C2 classes. Some QoL scores were even higher in varicose vein patients than in healthy people.4,18 Likewise, in a study evaluating patients qualified for invasive varicose vein treatment, the authors found an impaired QoL that was independent of the clinical stage of venous disease.19 However, a similar cross-sectional study (570 venous patients from Serbia) revealed a progressive worsening of QoL from C1 to C6 class. Even those patients presenting with C1 and C2 classes reported an impairment of QoL and did not consider their venous incompetence as a benign cosmetic problem, but rather as a real disease.20 Worsening of QoL in C3 to C6 patients compared with the Csub>1/C2 classes was also found in another study.21

Venous reflux and inflammatory markers
Similarly, a correlation between the degree of venous reflux with QoL reduction is uncertain. Although one would expect profound venous reflux or an increased diameter of incompe tent saphenous trunk to be associated with more severe clinical symptoms and decreased QoL, research does not always confirm such a relationship. In one study, incompetence of the great or small saphenous veins had a greater impact on QoL than nonsaphenous varicosities.7 Another study revealed either a weak or no correlation between the diameter of incompetent great saphenous vein and impaired QoL in patients with varicose veins.22 Similarly, there was no association between venous symptoms and systemic inflammatory markers, such as von Willebrand factor, intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion protein 1 [VCAM-1], E-selectin, P-selectin, L-selectin, vascular endothelial growth factor [VEGF], interleukin 1α (IL-1α), IL-1β, IL-6, and tumour necrosis factor α (TNF-α).14

Interventions
Some studies examined the impact of interventions aimed at the reduction of venous incompetence (compression therapy or ablation of varicose veins) on venous symptoms and QoL. It might be assumed that if the symptoms were indeed produced by venous disease, then such treatments should result in fewer complaints and a better QoL. However, only some of the patients studied were free of symptoms after otherwise successful treatment of varicose veins.23-25 On the other hand, a recurrence of venous incompetence was not always accompanied by a return of the symptoms.26,27

Compression stockings and radiofrequency ablation
As expected, wearing compression stockings resulted in improved QoL, not only in advanced (C3 to C5) venous patients, but also in those with early (C2) disease.18 A similar improvement of QoL was demonstrated by another study in patients with incompetent great saphenous veins (clinically C2 to C4). The authors of this study revealed that improvement of QoL was mainly due to the relief of venous symptoms. In this study, an invasive treatment (radiofrequency ablation of the great saphenous vein together with phlebectomies of superficial varicosities) resulted in an even greater improvement of QoL. An important finding of this study was that relief of symptoms by compression therapy was a good predictor of successful surgical treatment. Patients who improved their symptoms with compression therapy were more likely to experience further clinical improvement after ablation of varicose veins. However, a substantial proportion of patients who did not improve their QoL after compression therapy benefited from surgical treatment of varicose veins. Thus, not all clinical symptoms of CVD could be relieved by compression alone.28

Surgical excision
In another interventional study, QoL significantly improved (71% of the patients got better) after surgical excision of varicose veins. Patients with uncomplicated (C2 to C3) and complicated (C4 to C6) venous disease experienced a similar improvement in their QoL. In this study the patients with a poorer QoL before surgery were more likely to benefit from the treatment.29 Similarly, in an observational study on patients receiving ultrasound-guided foam sclerotherapy of symptomatic incompetent great or small saphenous veins (patients with asymptomatic varicosities were not included) there was a significant improvement of QoL after the treatment. This improvement was seen in both C2 to C3 and C4 to C5 patients. Improvement of QoL was similar in patients with great and small saphenous vein varicosities. Also, considering mental domains of the QoL questionnaire, there was no difference in terms of QoL according to whether uncomplicated (C2 to C3) or complicated (C4 to C5) varicose veins were treated. On the contrary, physical aspects of QoL were significantly worse in patients with C4 to C5 venous disease. Interestingly, regarding physical domains of QoL, the patients with uncomplicated varicosities benefited more from the treatment in comparison with those with complicated varicose veins.6

Other influencing factors
It seems that CVD is not a uniform clinical entity in terms of clinical symptoms and impaired QoL. Thrombotic events, bilateral varicosities, and the recurrence of varicose veins significantly affect natural history of the disease. In the VEINES study, a multivariable regression analysis revealed that previous venous thromboembolism was a predictor of poorer QoL, independent of variables such as age, sex, country of residence, education, BMI, duration of CVD, and the presence of comorbidities.30 In this study, an analysis adjusted for the CEAP clinical class confirmed a previous thromboembolism as an independent predictor of decreased QoL.30,31 Bilateral varicose veins were demonstrated to be associated with worse QoL than unilateral venous incompetence,7 while some studies demonstrated that QoL was significantly reduced in patients with recurrent varicosities in comparison with those with primary varicose veins.6,32 In one study, QoL impairment was no worse in recurrent varicosities than primary varicosities.7

Conclusion

A reasonable explanation of the enigma of venous symptoms— considering inconsistent results of the above-presented studies— is not easy. Certainly, in many of these studies a selection bias took place, either skewing the cohorts studied towards the patients presenting with real symptomatic CVD (clinical symptoms indeed caused by venous disease), or towards the patients suffering from alternative sources of complaints, primarily osteoarticular pathologies. The first scenario was more likely if the patients qualifying for surgical treatment of varicose veins were evaluated, since they were initially screened by an experienced clinician and those with nonvenous complaints were not very likely to enter such a study. A second scenario could take place in the surveys that used advertising in mass media to select participants, thus mostly attracting people with pain or other leg symptoms primarily associated with neurological and orthopedic problems, and not with venous incompetence. Some researchers speculated that differences between the studies in terms of association of venous symptoms with CVD could result from different expressions of such complaints in particular languages, making a comparison of the studies conducted in different countries difficult.8

Nonetheless, venous symptoms seem to be nonspecific for CVD and can also be reported by patients presenting with other diseases. Many uncomplicated varicose veins can indeed be asymptomatic or cause very few symptoms.3,6-10 In some varicose vein patients, the symptoms and impaired QoL may result from concomitant components of venous disease, such as inflammatory skin changes, and are notdirectly caused by dilated veins. In many of these patients, clinical symptoms are not permanent, but can be seen at the end of the day (when clinical trials are not routinely performed) or only during hot periods of the year (again, not a typical season to perform studies). Moreover, the research is telling us that a large proportion of venous symptoms have their sources in coexisting nonvenous pathologies.2,11,15 This is of particular importance in patients in classes C1 and C2, since those with more severe forms of venous incompetence usually experience symptoms caused by venous disease. The majority of symptoms in the patients with telangiectasias and uncomplicated varicose veins do not seem to be of venous origin. Rather, especially if such symptoms are severe, an alternative cause should be considered.

Unfortunately, available QoL questionnaires do not include questions that facilitate recognition of the real cause of symptoms. Also, a thorough medical history and clinical examination, together with vascular sonographic assessment, were not used by most of the studies that evaluated an association of venous symptoms with the presence of venous disease. Instead, rather nonspecific QoL questionnaires and simple clinical tests were utilized.

Better constructed studies (such as a recent Dutch study)2 may put an end to the controversy over this problem. For the time being, from a practical point of view, it is important to distinguish patients with actual symptomatic varicosities from those patients with other sources of pain and other “venous” complaints. If such patients are initially not properly diagnosed, it is inevitable that some of them will be dissatisfied by the treatment for varicose veins, since the real cause of their complaints (eg, hip arthrosis) will not be addressed by a vascular procedure. At the moment, we lack solid information on prevalences of pathologies being the cause of such “venous” symptoms in the population of patients with CVD. Still, the most common pathologies that may be responsible and should be considered in clinical practice comprise spinal disc herniation, hip and knee arthrosis, peripheral arterial disease, joint and ligament overload due to obesity, and peripheral neuropathy.

There are also many patients who suffer from leg pain and edema after the use of different medications, especially calcium channel blockers.33 In the case of such a drug-related adverse event occurring in varicose vein patients, an invasive or pharmacological treatment for venous incompetence will not relieve symptoms. Instead, the medication should be discontinued. Similarly, in patients complaining of symptoms caused by osteoarticular, neurological, or arterial pathology, the disease that is a source of the complaints should primarily be addressed.


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Keywords: chronic venous disease; chronic venous disorder; quality of life; venous symptom