Description and definition of venous symptoms in chronic venous disorders: a review






Michel R. PERRIN, MD
Unité de pathologie vasculaire
Jean Kunlin, Lyon
FRANCE

Description and definition of venous symptoms in chronic venous disorders: a review


by M. R. Perrin, France



The precise description of venous disorders is lacking in most books or treatises devoted to venous disorders, and confusingly, there are times when both signs and symptoms are included within the same heading of “symptoms.” The absence of an accurate description may be related to the fact that most venous symptoms are nonspecific, and more or less identical to symptoms arising from nonvenous causes. Symptoms listed in various venous classifications are often not the same, and the different terms are sometimes difficult to describe accurately. Some frequently noted symptoms may also be difficult to differentiate, as they are very similar to each other, for example, pain and aching. This review aims to, firstly, describe symptoms as precisely as possible and, secondly, define the circumstances favoring their occurrence. The relationship between symptoms and signs, reflux, quality of life, venous clinical score, and inflammatory markers is reviewed. Some attempts to better ascribe leg symptoms to venous etiology are analyzed, and their value is questioned. In conclusion, an international consensus concerning the definition of venous symptoms and causes is recommended, with the knowledge that this should, in turn, improve the management of patients.

Medicographia. 2015;37:10-15 (see French abstract on page 15)



Confusingly in English literature, signs and symptoms sometimes appear under the same heading of “symptoms.” In this article, the term “symptom” only incorporates unpleasant phenomenon felt by the patient that arise from and accompany a particular disease or disorder. Consequently, the presence and severity of symptoms is subjective.

Venous symptoms remain a challenge to deal with for multiple reasons. Firstly, very few books or treatises dedicated to chronic venous disorders give a precise description and definition of so-called “venous symptoms.” This may be due to difficulty in defining these symptoms, as they are not pathognomonic. This point increases the difficulty of attributing a venous etiology or cause to these symptoms, knowing that all classes of venous disorders (from C0s to C6 of the clinical, etiological, anatomical, pathophysiological [CEAP] classification) can be associated with venous symptoms. Secondly, there is a nonconstant correlation between symptoms and signs, and routine instrumental investigations.

List of venous symptoms

CEAP classification
The CEAP classification includes aching, pain, tightness, skin irritation, heaviness, muscle cramps, and other complaints attributable to venous dysfunction in its list of venous symptoms.1

VCSS classification
The Venous Clinical Severity Score (VCSS) reports pain or other discomfort (ie, aching, heaviness, fatigue, soreness, and burning) presumed of venous origin.2 Interestingly, the symptom list is not limited as it is in the CEAP classification, as venous dysfunction may be identified (which is not always possible in daily practice). In the VCSS, the symptoms described are reported as possibly venous, which is not discriminative as it depends how venous function is investigated.

Bonn Vein Study
The Bonn Vein Study (BVS) recognizes symptoms such as swelling; feeling of swelling, tightness, and heaviness; pain during prolonged walking, sitting, or standing; cramps; itching; and restless legs.3,4

VEINES-QoL/Sym questionnaire
The subscale of the VEnous INsufficiency Epidemiological and economic Study (VEINES) called VEINES-Quality of life/ Symptoms (VEINES-QoL/Sym) listed nine venous symptoms: heavy legs, aching legs, swelling, night cramps, heat or burning sensation, restless legs, throbbing, itching, and tingling sensation. Although built to evaluate the quality of life in primary chronic venous disorders,5 the tool has been mainly used to assess the quality of life of patients with post-thrombotic syndrome.6 From this bibliographic research, it appears that the term “venous symptoms” needs to be better determined and clarified.

Description of venous symptoms

As previously mentioned venous symptoms are nonspecific, but there are some features that may help to attribute them to a venous origin.

Pain or aching
Venous pain may take on the following patterns:
– Pain along the varicose vein course (phlebalgia) and, more frequently, diffuse pain in the lower leg, mainly in the calves.
– Venous claudication due to an obstructive lesion of the deep vein usually located in the iliocaval axis.7 Intermittent claudication is defined as the outcome of a painful or bursting sensation that occurs only when the patient is walking or running and is located either in the lower limb or in the buttock. This pain disappears progressively when the patient stops, or by leg elevation that allows differentiating from arterial claudication and nonvenous neurologic compression. According to Blättler and Blättler, pure venous claudication related to axial vein obstruction can be distinguished from venous neurogenic claudication caused by dilated veins in the spinal canal that arise from the collateral circulation, by magnetic resonance imaging or contrast enhanced computed tomography. Both are cured by venous stenting.8
– Presence of painful lipodermatosclerosis or an open ulcer.





Throbbing
This infrequent symptom is depicted by patients as a pulsing pain along the pathway of varices, mainly the incompetent saphenous trunks or their major tributaries.
Tightness
Tightness is a term rarely used by patients, but may correspond to the feeling that their leg is caught in a stranglehold.
Heaviness
This symptom is described as heavy legs occurring in a longterm standing or seated position.
Fatigue
This symptom is a little bit different from heaviness and is described by patients as a feeling of tiredness, occurring after any kind of activity using the lower limb, but also after prolonged motionless standing.
Impression of swelling
This symptom is different from the sign edema, which can be measured. Some patients describe the impression of swelling with no evident edema on clinical examination.
Cramps
Cramp is an involuntary, painful, contraction of muscles. Venous cramps are usually located in the calf (gastrocnemius and soleus muscles) and occur at night.
Itching
Itching may be present in a number of different circumstances, such as in association with: (i) dermatitis (including stasis dermatitis and contact eczema); and (ii) noncomplicated varices. Duque et al showed that in the latter group, 97% complained of itching in the evening and night, 50% had some difficulty falling asleep almost every night, and 40% were awakened by itching. Itching is a frequent and intense symptom.9
Restless legs
This symptom, usually quoted as restless legs syndrome, is describedby patients as adisagreeable and indefinable feeling, frequently reported as “having the fidgets” in the lower limb, and accompanied by an irresistible need to move the legs.
Tingling
This symptom is described as a sensation of prickling or stinging in the leg.

Methods allowing identification of venous etiology

In some cases, symptoms or physical signs are highly suspect for venous etiology, but most often, circumstance of apparition and instrumental investigations are crucial for attributing a venous cause to symptoms.

Clinical circumstances of appearance
There is a consensus for agreeing that venous symptoms:
– Are influenced by the standing position, which is often considered as a trigger, or immobility in orthostatic position.
– Worsen progressively during the course of the day and are worst in the evening.
– Are exacerbated by warmth or when the ambient temperature and atmospheric humidity are high (eg, during the summer season, hot baths, floor-based heating systems, or hot waxing to remove body hair), but less intense in winter and/ or with cold temperatures.
– Are exacerbated during the luteal phase of the menstrual cycle, in other words, more intense during the period immediately prior to menstruation, and may decrease once menstruation begins.
– May occur with hormonal therapy (eg, oral contraceptive, or hormone replacement therapy), but disappear with discontinuation of such treatment.10-12

Consequently, when symptoms occur or are enhanced by the circumstances described above, a venous origin is highly probable. Nevertheless, instrumental investigations are undertaken to identify venous pathophysiological anomalies, in order to objectively diagnose venous etiology.
Instrumental investigations
Instrumental investigations are often carried out in all patients presenting with any kind of venous disorder from C0s to C6.
Duplex scanning
Duplex scanning (DS) is the first-line investigation for suspected venous disorders. This noninvasive investigation explores saphenous trunks and their first order tributaries, lower-limb deep axial veins, as well as deep femoral, gastrocnemius veins, and lower-limb perforators. Conversely, tributaries beyond the first-generation tributaries and the iliac vein in obese patients are either impossible or difficult to investigate in routine DS examination.
Venography
Venography includes ascending or descending phlebography, with or without lower-limb tourniquet use. This investigation explores the same veins, but less precisely in terms of pathophysiological disorders such as reflux.
Computed tomography and magnetic resonance imaging
These two investigations are rarely used in primary chronic venous disorders, except in pelvic congestion syndrome combined with varices or when non-postthrombotic suprainguinal vein obstruction is suspected.
Iliac vein intravascular ultrasound examination
This investigation is only undertaken in primary venous disorders, in patients presenting with severe symptomatology without severe varices and in the absence of postthrombotic syndrome.13

Microcirculation investigations
Microcirculation is not investigated routinely in the presence of primary venous disease, except in the few cases of severe chronic venous insufficiency.
Conclusion
Venous investigations, particularly DS, are very useful in patients for attributing symptoms to venous etiology in the CEAP C2 class, although there is a weak correlation between varices and symptom severity. Conversely in C0s patients, who represent 19.6% of the Vein Consult Program,12 venous valve competence of the second to the sixth generation are not investigated. We know that microscopic venous valves in the small superficial venous veins of human lower limbs can be incompetent, independent of reflux into the great saphenous vein and major tributaries (Figure 1).14,15 A plausible hypothesis is that symptoms present in C0s patient might be caused by reflux in the second to sixth generation of microvalves. Such “microrefluxes” are not currently assessable by physical examination or by DS investigation.

Relationship between symptoms and/or signs, and other markers

Venous symptoms and reflux
Pain is particularly poorly associated with the presence or absence of trunk varices and reflux, according to the Edinburgh Vein cross-sectional survey. Firstly, in men, only itching was significantly related to the presence and severity of trunk varices. In women, the correlation between symptoms and trunk varices is better: heaviness or tension (P<0.001), aching (P<0.001), and itching (P<0.005).16 Of note, this correlation was established only for saphenous varices, Pr2 to Pr4 according to the CEAP classification.16 The highest prevalence of symptoms was found when varices and telangiectasias were both present.17 Secondly, reflux in the saphenous trunks was not correlated with venous symptoms in men. In women, only heaviness (P<0.025) and itching (P=0.002; left leg) are correlated with saphenous reflux.18

Chiesa et al showed that approximately 80% of subjects with no visible signs of venous disease, including absence of varices, complain of symptoms. In contrast to the Edinburgh Vein cross-sectional survey, reflux related to valve incompetence correlated positively with worsening symptoms.19

Venous symptoms and venous disease severity
There is a significant correlation between venous symptoms, particularly pain and worsening of clinical chronic venous disorder signs (CEAP classes), in many articles.20-23 Conversely, Howlader and Smith found no correlation between symptoms and clinical classes (CEAP classification C2 to C5).24

Venous symptoms and health-related quality of life
Impact of venous symptoms on health-related quality of life has been clearly established in noncomplicated varices (CEAP classification C2). To assess quality of life, Duque et al curiously used a specific dermatologic questionnaire (Skindex-16),9 while Darvall et al used the generic Short Form12 (SF-12).25

Venous symptoms and inflammation
According to Howlader and Smith, there is no correlation between levels of inflammatory mediators and venous symptoms.24 However, Danziger, in his article on venous pain pathophysiology, underlines that capillary and venule stasis activatesendothelial cells, resulting in the synthesis and local release of inflammatory mediators such as bradykinin, platelet-activating factor, prostaglandins, and leukotriene B4, etc. In turn, these inflammatory mediators activate C nociceptors in the capillary and vein walls, resulting in diffuse pain often described as discomfort, tightness, or heaviness.26,27


Figure 1
Figure 1. Patterns of retrograde resin casting in limbs assigned
CEAP C0 or C1.

All limbs had competent great saphenous veins (GSVs) as determined by ultrasound.
The proximal end of the cast is to the right-hand side. A) Multiple territories
of small vein network filling and dilated tortuous (arrow) veins. Of note, the
GSV was intact with numerous competent valves and tributaries (arrowheads).
B) Extensive filling of the superficial venous network. Note the straight course of
the GSV (between the two arrows), presence of competent GSV valves (arrowhead),
and high degree of variability in small vessel filling in these limbs with no
major, ultrasound-detected, superficial reflux.
Abbreviation: CEAP, clinical, etiological, anatomical, pathophysiological
From reference 15: Vincent JR, Jones GT, Hill GB, van Rij AM. J Vasc Surg.
2011;54:62S-69S. © 2011, Society for Vascular Surgery.


Attempts to better ascribe leg symptoms to venous etiology

As venous symptoms are often nonpathognomonic and nonspecific, the task of attributing these symptoms to venous etiology is not easy. Carpentier et al suggested the creation of a diagnostic score in order to facilitate this process, by classifying the patients in two groups.28 The first group includes patients presenting with leg symptoms and no clinical evidence of arterial, rheumatic, or neurological disorders, but with venous dysfunction documented both clinically and by DS examination. This group was named CVD+. The second group included patients with leg symptoms and documented arterial, rheumatic, or neurological disorders, but no signs of clinical disorders or venous reflux at DS examination. This group was identified as CVD–.

In a validation series of 92 patients (67 CVD+ and 25 CVD–), Carpentier et al found that the combination of four symptoms, worsened by circumstances of apparition, was reliable in terms of high specificity (0.95) and fair sensitivity (0.75) for identifying chronic venous disorders. Unfortunately, no other paper using this score has been reported and consequently the score proposed by Carpentier and al has not yet been validated. In theory, the Carpentier’s evaluation has two biases: firstly C0s patients are difficult to classify, as they have no venous dysfunction identifiable by clinical examination or routine DS. Secondly, the same difficulty exist in patients with nonthrombotic iliac vein obstructive lesions, which are not identified by DS examination according to Neglen.29

Another approach to identifing venous responsibility has recently been used. In 2013, the BVS was reanalyzed to try to distinguish between a psychic component and somatic component by using a short questionnaire; the psychic vs somatic venous disease questionnaire (PsySoVDQ).30 The conclusion of this study is that the PsySoVDQ identified somatic and psychic components of the widespread and frequently reported leg symptoms in the general population. Nevertheless, in the majority of subjects, symptoms remained unexplained. The authors suggest a neuropsychological and neurobiological hypothesis.

Conclusion

Precise definition and description of venous symptoms are suggested in this review, in order to identify a venous origin of the so-called venous symptoms. This is crucial in providing better care for symptomatic patients. However, there are several issues that still need to be clarified. Firstly, it is still unclear whether venous symptoms are caused by a primary etiology in alterations of the major veins—related to reflux in superficial or/deep veins or compression above the inguinal ligament axial veins—or in anomalies within the veinules or capillaries. Secondly, it is still unclear whether the presence or severity of symptoms independently of signs allows us to forecast worsening venous disease. If we rely on VCSS, the maximum score attributed to symptoms is only 3/30; in other words venous symptoms count for very little in venous disorder scoring.2 Venous symptoms in epidemiological studies are very common; in the BVS more than half of the 1800 participants reported such symptoms.3,4 We know that operative treatment, particularly in noncomplicated, but symptomatic, varices does not relieve venous symptomatology in many cases. It would be a step forward to identify the patients that could potentially experience improved symptoms following operative treatment. Patients that are unlikely to improve should be recommended an alternative treatment.


References
1. Eklöf B, Rutherford RB, Bergan JJ, et al; American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg. 2004;40:1248-1252.
2. Vasquez MA, Rabe E, Mc Lafferty RB, et al. Revision of the venous clinical severity score: Venous outcomes consensus statement: Special communication of the American Venous Forum Ad Hoc Outcomes Working Group. JJ Vasc Surg. 2010;52:1387-1396.
3. Rabe E, Pannier-Fischer F, Bromen K, et al. Bonner Venenstudie der deutschen Gesellschaft für phlebologie. Epidemiologische Untersuchung zur Frage der Häufigkeit und Ausprägung von chronischen venenkrankheiten in der städtischen und ländlichen Wohnbevölkerung. JPhlebologie. 2003;32:1-14.
4. Rabe E, Pannier F. What we have learned from the Bonn Vein Study. JPhlebolymphology. 2006;13:186-191.
5. Lamping DL, Schroter S, Kurz X, Kahn SR, Abenhaim L. Evaluation of outcomes in chronic venous disorders of the leg: Development of a scientifically rigorous, patient-reported measure of symptoms and quality of life. J Vasc Surg. 2003; 37:410-419.
6. Kahn SR, Lamping DL, Ducruet T, et al; VETO Study investigators. VEINESQOL/ Sym questionnaire was a reliable and valid disease-specific quality of life measure for deep venous thrombosis. J Clin Epidemiol. 2006;59:1049-1056.
7. Delis KT, Bjarnason H, Wennberg PW, Rooke TW, Gloviczki P. Successful iliac vein and inferior vena cava stenting ameliorates venous claudication and improves venous outflow, calf muscle pump function, and clinical status in postthrombotic syndrome. Ann Surg. 2007;245:130-139.
8. Blättler W, Blättler IK. Relief of obstructive pelvic venous symptoms with endoluminal stenting. J Vasc Surg. 1999;29:484-488.
9. Duque M, Yosipovitch G, Chan YH, Smith R, Levy P. Itch, pain, and burning sensation are common symptoms in mild to moderate chronic venous insufficiency with an impact on quality of life. J Am Acad Dermatol. 2005;53:504-508.
10. Ramelet AA, Perrin M, Kern P, Bounameaux H. Symptoms in chronic venous disease. In: Phlebology. 5th ed. Paris, France: Elsevier Masson; 2008:97-103.
11. Carpentier PH, Maricq HR, Biro C, Ponçot-Makinen OC, Franco A. Prevalence, risk factors and clinical patterns of venous insufficiency of lower limbs: a population- based study in France. J Vasc Surg. 2004;40:650-659.
12. Rabe E, Guex JJ, Puskas A, et al. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012;31:105-115
13. Raju S, Neglen P. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in pathogenicity. J Vasc Surg. 2006;44: 136-143.
14. Phillips MN, Jones GT, van Rij AM, Zhang M. Micro-venous valves in the superficial veins of the human lower limb. Clin Anat. 2004;17:55-60.
15. Vincent JR, Jones GT, Hill GB, van Rij AM. Failure of microvenous valves in small superficial veins is a key to the skin changes of venous insufficiency. J Vasc Surg. 2011;54:62S-69S.
16. Bradbury A, Evans C, Allan P, Lee A, Ruckley CV, Fowkes FG. What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ. 1999;318:353-356.
17. Ruckley CV, Evans CJ, Allan PL, Lee AJ, Fowkes FG. Telangiectasia in the Edinburgh Vein Study: Epidemiology and association with trunk varices and symptoms. Eur J Vasc Endovasc Surg. 2008;36:719-724.
18. Bradbury A, Evans CJ, Allan PA, Lee AJ, Ruckley CV, Fowkes FG. The relationship between lower limbs symptoms and superficial and deep venous reflux on duplex sonography: The Edinburgh Vein Study. J Vasc Surg. 2000;32: 921-931.
19. Chiesa R, Marone EM, Limoni C, Volonte M, Petrini O. Chronic venous disorders: correlation between visible signs, symptoms, and presence of functional disease. J Vasc Surg. 2007;46:322-330.
20. Carpentier PH, Cornu-Thenard A, Uhl JF, Partsch H, Antignani PL. Appraisal of the information content of the C classes of CEAP clinical classification of chronic venous disorders: A multicenter evaluation of 872 patients. J Vasc Surg. 2003;37:827-833.
21. Carpentier PH, Maricq HR, Biro C, Ponçot-Makinen OC, Franco A. Prevalence risk factors and clinical patterns of population-based study in France. J Vasc Surg. 2004;40:650-659.
22. Kahn SR, M’Lan CE, Lamping DL, Kurz X,Berard A,Abenhaim LA; VEINES Study Group. Relationship between clinical classification of chronic venous disease and patient-reported quality of life: results from an international cohort study. J Vasc Surg. 2004;39:823-828.
23. Langer RD, Ho E, Denenberg JO, Fronek A, Allison M, Criqui MH. Relationships between symptoms and venous disease. Arch Int Med. 2005;165:1420-1424.
24. Howlader MH, Smith PD. Symptoms of chronic venous disease and association with systemic inflammatory markers. J Vasc Surg. 2003;38:950-954.
25. Darvall KAL, Bate GR, Adam DJ, Bradbury AW. Generic health-related quality of life is significantly worse in varicose vein patients with lower limb symptoms independent of CEAP clinical grade. Eur J Vasc Endovasc Surg. 2012;44:341- 344.
26. Danziger N. [Pathophysiology of pain in venous disease]. J Mal Vasc. 2007:32; 1-7.
27. Danziger N. How to describe venous pain? In: JFrom Venous Pain to Surgery. 1st ed. Paris, France: Servier Publisher; 2013:35-44.
28. Carpentier PH, Poulain C, Fabry R, et al. Ascribing leg symptoms to chronic venous disorders: the construction of a diagnostic score. J Vasc Surg. 2007;46: 991-996.
29. Neglen P. Chronic deep venous obstruction: definition, prevalence, diagnosis, management. Phlebology. 2008;23:149-157.
30. Amsler F, Rabe E, Blätter W. Leg symptoms of somatic, psychic, and unexplained origin in the population-based Bonn Vein Study. Eur J Vasc Endovasc Surg. 2013;46:255-262.


Keywords: CEAP classification; chronic venous disease; chronic venous disorder; varices; Venous Clinical Severity Score; venous symptom