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V. Pandey and M. Imran
4.11 Reflex Sympathetic Dystrophy
When leg edema is associated with discomfort, reex sympathetic dystrophy should
be examined (RSD).RSD is a progressive neurological condition that affects the
limbs and induces serious disabilities. It is typically preceded by trauma, upper or
lower limb surgery, malignancy, and pregnancy. Typically, the symptoms are disproportionately severe to the swelling. The neurological symptoms associated are autonomic, vasomotor and sensory changes, elevated limb temperatures, hyperhidrosis,
atrophy of the skin/muscle/bone, repetitive movements, tremors, and spasmodic
muscles [12].
4.12 Lymphedema
It is a common cause of lower limb oedema. It typically develops due to reduced
local lymphatic drainage with uid overload and elevated interstitial lymphatic
length; lymphedema is typically conned to the upper or lower extremities [13]. It
is classied as primary lymphedema, caused by congenital abnormalities of lymphatic structures, and secondary lymphedema, due to many causes, such as malignancies, traumas, and infections.
4.13 Inflammatory Edema
Inammatory reaction causes vast changes in the capillary endothelium. There is a
massive increase in the permeability of plasma proteins. The increased interstitial
protein draws and retains uid with it, resulting in edema. The inammatory process may be generalized or may be generalized or localized. The local inammatory
response may be due to infections, chemical substances, traumatic or mechanical
agents, or immunological factors.
4.14 Summary andConclusion
The etiology of lower limb edema is vast and ranges from simple local to complex
systemic causes. A proper clinical history and thorough physical examination help
a in excluding the different causes, but a systematic approach is mandatory in order
to pinpoint the diagnosis from such a long list. The rst and foremost approach is to
identify whether the edema is unilateral or bilateral; then one should divide the
causes on the basis of duration as acute and chronic. In a patient of pedal edema
with acute onset (<72h) of symptoms having either unilateral or bilateral involvement, a deep vein thrombosis should be ruled out using a Doppler examination in
order to avoid life-threatening complications. If a systemic disorder has been ruled
4 Aetiopathogenesis inLower Limb Oedema
53
out or considered unlikely, the most common causes of bilateral leg edema are idiopathic edema (in young women) and chronic venous insufciency (in older patients).
The patients should be investigated for cardiac, renal, or hepatic causes in patients
with chronic bilateral edema and systemic symptoms. This approach helps to utilize
the patient’s history and clinical examination, perform the required imaging to avoid
over-testing, and follow a cost-effective approach.
Funding Nil.
References
1. Paramesparan K, Iqbal A, Shah A, Botchu R.Imaging of the unilateral swollen painful lower
leg: deep vein thrombosis mimics. Indian J Musculoskelet Radiol. 2019;1(1):27–40.
2. Lent-Schochet D, Jialal I.Physiology, Edema. [Updated 2020 Jul 10]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.
nih.gov/books/NBK537065/
3. Gasparis AP, Kim PS, Dean SM, Khilnani NM, Labropoulos N.Diagnostic approach to lower
limb edema. Phlebology. 2020 Oct;35(9):650–5. https://doi.org/10.1177/0268355520938283.
Epub 2020 Jul 6. PMID: 32631171; PMCID: PMC7536506.
4. Evans NS, Ratchford EV. The swollen leg. Vasc Med 2016;21(6):562–564. https://doi.org/1
0.1177/1358863X16672576. Epub 2016 Oct 12. PMID: 27738281.
5. Eldufani J, Elahmer N, Blaise G. A medical mystery of complex regional pain syndrome.
Heliyon. 2020;6(2):e03329. https://doi.org/10.1016/j.heliyon.2020.e03329. PMID: 32149194;
PMCID: PMC7033333.
6. Khadka S, Joshi R, Shrestha DB, Shah D, Bhandari N, Maharjan M, Sthapit S.Amlodipine-
induced pedal Edema and its relation to other variables in patients at a tertiary level Hospital
of Kathmandu, Nepal. J Pharm Technol. 2019;35(2):51–5.
7. Hartupee J, Mann DL.Neurohormonal activation in heart failure with reduced ejection frac-
tion. Nat Rev Cardiol. 2017 Jan;14(1):30–8. https://doi.org/10.1038/nrcardio.2016.163. Epub
2016 Oct 6. PMID: 27708278; PMCID: PMC5286912.
8. Fountain JH, Lappin SL.Physiology, Renin Angiotensin System. [Updated 2020 Jul 27]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK470410/
9. Tan KK, Koh WP, Chao AK. Risk factors and presentation of deep venous thrombosis
among Asian patients: a hospital-based case-control study in Singapore. Ann Vasc Surg.
2007;21(4):490–5. https://doi.org/10.1016/j.avsg.2006.06.008. Epub 2007 Feb 26. PMID:
17628265.
10. Pulivarthi S, Gurram MK. Effectiveness of d-dimer as a screening test for venous throm-
boembolism: an update. N Am J Med Sci. 2014;6(10):491–9. https://doi.org/10.4103/1947-
2714.143278. PMID: 25489560; PMCID: PMC4215485.
11. Zegarra TI, Tadi P. CEAP Classication of Venous Disorders. [Updated 2020 May 31]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK557410/
12. Patel RH, Sheth R, Hus N. Complex regional pain syndrome caused by an axillary lipoma.
Cureus. 2020;12(12):e12280. https://doi.org/10.7759/cureus.12280. PMID: 33510987;
PMCID: PMC7828746.
13. Garza R 3rd, Skoracki R, Hock K, Povoski SP.A comprehensive overview on the surgical man-
agement of secondary lymphedema of the upper and lower extremities related to prior oncologic therapies. BMC Cancer. 2017;17(1):468. https://doi.org/10.1186/s12885- 017- 3444- 9.
PMID: 28679373; PMCID: PMC5497342.
Clinical Examination inLower Limb
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Edema
E.Menegatti, M.Tessari, andS.Gianesini
5.1 Introduction
Edema is dened as an abnormal increase in the amount of liquid contained in the
cells and/or in the intercellular spaces and tissues interstices.
The uid between the interstitial and intravascular spaces is regulated by the
capillary hydrostatic pressure gradient and the oncotic pressure gradient across the
capillary. Differently from what believed years ago, the ltration process is far more
complex than a simple balance between hydrostatic and oncotic pressure. Indeed,
the ltration process is also mediated by a molecular sieve of various porosities
determined by a matrix of glycoproteins and glycosaminoglycans present on the
luminal surface of the endothelial cells [1].
The extraluminal uid accumulation occurs when local and/or systemic conditions disrupt this equilibrium, leading to increased capillary hydrostatic pressure,
increased plasma volume, decreased plasma oncotic pressure (hypoalbuminemia),
increased capillary permeability, or lymphatic obstruction.
It can be a local condition that is, limited to a specic district of the body or a
generalized condition, which is also accompanied by uid pouring into the serous
cavities (anasarca) [2, 3].
5
E. Menegatti · M. Tessari
Vascular Diseases Center, Department of Translational Medicine, University of Ferrara,
Ferrara, Italy
S. Gianesini (
Vascular Diseases Center, Department of Translational Medicine, University of Ferrara,
Ferrara, Italy
Departement of Surgery, Uniformed Services University of the Health Sciences,
Bethesda, MD, USA
© The Author(s), under exclusive license to Springer Nature Singapore Pte
Ltd. 2022
S. K. Tiwary (ed.), Approach to Lower Limb Oedema,
https://doi.org/10.1007/978-981-16-6206-5_5
*)
55
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E. Menegatti et al.
The major causes of edema include:
• Increase in intravascular pressure due to venous obstruction and/or reux
• Increase in capillary vessel wall permeability
• Decrease in the intravascular osmotic pressure
• Excessive bodily uids
• Lymphatic obstruction
• Local injury
• Infection
• Medication effect
The management of a patient with edema should start always with an accurate
evaluation of the medical history and with a physical examination in order to clarify
the etiology and the best instrumental diagnostic path aimed to design the proper
therapeutic strategy [2].
5.2 Clinical History
An accurate history collection must include the description of:
– Sign and symptoms detailed report, including their timing
– Pain triggering factors
– Previous surgical, radiotherapy, or accidental trauma
– Pelvic venous disorders
– Abdominal conditions potentially altering the lymphatic drainage
– Comorbidities
– Medications, in particular the ones affecting the uid homeostasis
The key element of the history should include the timing of the edema (acute if
<72h or chronic >72h), specifying if it is unilateral or bilateral and whether it is
posture dependent.
The most likely cause of bilateral chronic leg edema in women under 50 years
old is idiopathic [4]. On the other end, the most common cause of lower limb edema
in patients over 50 is chronic venous disease (CVD), which affects up to 30% of the
population.
The most common cause of unilateral acute leg swelling is deep venous thrombosis (DVT), while less common causes can be popliteal cyst rupture, acute compartment syndrome, and gastrocnemius medial head traumatic rupture.
Chronic bilateral edema is due to the onset or exacerbation of chronic systemic
conditions, such as heart failure, pulmonary hypertension, renal disease, hepatic
disease, primary lymphedema, and medication.
Less common causes which can involve one or both limbs are secondary lymphedema (tumor, radiation, bacterial infection, or lariasis), pelvic masses causing
external compression, May-Thurner syndrome, and congenital vascular malformation [2, 5].
5 Clinical Examination inLower Limb Edema
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The importance of the observation of edema variation following postural changes
is another crucial point in clinical examination. The postural dependent edema
caused by venous insufciency is more likely to improve with elevation and worsen
with prolonged orthostatic posture. This type of edema can improve overnight. To
the contrary, the edema associated with decreased plasma oncotic pressure, such as
malabsorption and liver and renal failure, does not signicantly change with leg
elevation [6].
Pain can play a crucial role in determining the cause of leg edema. This is particularly evident in a symptomatic venous thrombosis, for example.
Deep vein thrombosis and reex sympathetic dystrophy are usually strongly
painful and associated with redness and heat of the affected area. Chronic venous
insufciency and lymphedema are characterized by a low-grade aching often associated with heaviness, while edema of cardiac origin is usually painless.
Medication has to be considered when drawing the clinical history of the patient:
antihypertensive drugs like calcium channel blockers, hormones such as steroids,
and anti-inammatory drugs can present edema as a side effect.
Finally, history of systemic disease involving the heart, kidney, liver, thyroid,
tumor, pelvic obstruction, and radiation, has to be reported since they can be directly
responsible for the onset of lower limb edema [2].
5.3 Physical Examination
In order to collect clinical information and formulate the differential diagnosis, an
accurate physical examination is of primary importance.
Edema should be characterized for distribution, pitting sign, tenderness, skin
changes, its association with varicose veins, and/or obesity.
5.3.1 Distribution
– Unilateral leg edema is generally due to a local cause such as deep vein throm-
bosis, venous insufciency, or lymphedema.
– Bilateral edema can be due to a local cause or systemic disease, such as heart
failure or kidney disease.
– Generalized edema is due to systemic disease.
– The dorsum of the foot is usually spared in lipedema, but prominently involved
in lymphedema.
5.3.2 Tenderness
Tenderness to palpation over the edematous area is usually associated with deep
vein thrombosis and lipedema, whereas lymphedema is usually non-tender.
Variations can be observed in uid vs sclerotic lymphedema.
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E. Menegatti et al.
5.3.3 Pitting
The edematous tissue appears swollen, pale, and, if incised, releasing abundant
amounts of liquid. The presence of edema in the subcutaneous tissue is easily highlighted whenever a pressure is applied, resulting in a depressed area caused by the
displacement of interstitial uid. This is considered the main semeiotic sign of pitting edema [2, 7] (Fig.5.1).
The assessment technique of the pitting edema consists in pressing rmly with
the thumb for at least 2s on each extremity [8]:
• Over the dorsum of the foot
• Bony portion of the tibia
• Lower calf above the medial malleolus
The grading of edema is determined by the pit depth (measured visually) and
recovery time from grade 0 to 4. The scale is used to rate the severity and the scores
are as follows:
• Grade 0: No clinical edema.
• Grade 1: Slight pitting (2mm depth) with no visible distortion that rebounds
immediately.
• Grade 2: Somewhat deeper pit (4mm) with no readily detectable distortion that
rebounds in fewer than 15s.
a
Fig. 5.1 Ptting edema represents a depressed area (b) that remains in the edematous tissue after
pressure is applied (a)
b
5 Clinical Examination inLower Limb Edema
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59
• Grade 3: Noticeably deep pit (6mm) with the dependent extremity full and swol-
len that takes up to 30s to rebound.
• Grade 4: Very deep pit (8mm) with the dependent extremity grossly distorted
that takes more than 30s to rebound.
Pitting edema occurs in deep vein thrombosis and venous insufciency, but also
in the early stages of lymphedema because of an inux of protein rich uid into the
interstitium, before brosis of the subcutaneous tissue. To the contrary, myxedema
and the advanced brotic form of lymphedema typically do not pit.
5.3.4 Skin changes
Changes in skin temperature, color, and texture allow us to understand the cause of
edema (Fig.5.2): [9–11]
– Warty texture (hyperkeratosis) with papillomatosis and brawny induration are
characteristic of chronic lymphedema.
– Acute DVT and cellulitis may produce increased warmth over the affected area.
– Brown hemosiderin deposits on the lower legs and ankles are consistent with
venous insufciency hypertension.
– Varicose veins, venous stasis, and dermatitis are often associated with edema and
venous insufciency.
– Lipodermatosclerosis of the pretibial and malleolar region is the result of venous
insufciency progression even leading to venous ulcer.
Examination of the feet is important in lower extremity edema. In patients with
lymphedema, there is the impossibility to pinch a fold of skin on the dorsum of the
foot at the base of the second toe (so-called Kaposi–Stemmer sign) [12, 13]
(Fig.5.3).
In patients with lipedema, which is an abnormal fat distribution and constitution
resulting in disproportionate, painful limbs, the feet are generally spared, although
the ankles often have prominent malleolar fat pads (cuff sign) [14, 15].
Fig. 5.2 Lipodermatosclerosis, dermatitis, and
venous stasis from chronic
venous insufciency
associated with edema
60
Fig. 5.3 Positive
Kaposi–Stemmer sign
E. Menegatti et al.
5.4 Diagnostic Studies
5.4.1 Laboratory Tests
Laboratory tests could be helpful to investigate systemic diseases, in particular if the
etiology is still unclear. A list of laboratory tests will help to exclude systemic diseases: complete blood count, electrolytes, creatinine, urinalysis blood sugar,
thyroid- stimulating hormone, and albumin [1].
5.4.2 Noninvasive Quantitative Methods toAssess Lower
Limb Edema
A repeatable measurement that can size precisely the limb affected by edema or
lymphedema is necessary, either to dene the disease stage or to monitor its progression; furthermore, it is also useful to record the results induced by different
medical therapies both conservative and surgical.
There are different noninvasive techniques described in the literature to assess
peripheral edema. The limb volume can be measured by direct or indirect measurements [8].
5.4.3 Water Displacement (Volume Measurements) [16]
This method allows us to directly measure the limb volume using water immersion
in a graduated displacement. The limb is immersed up to a specic level in a container previously lled with water. The volume that overows in the adjacent container following the introduction of the leg represents an indicative parameter of
limb volume.
The measurement of the leg should follow the correct standard reported in the
literature: [15]
– Water level above the pretibial region
– Water temperature ranging from 28°C to 32°C;
5 Clinical Examination inLower Limb Edema
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61
– Subjects measured in sitting and resting position
– Volume assessment performed right before and right after the 5 exercise sessions
– Time of measurements between 9 and 12 a.m.
Despite it being a gold standard for measuring leg edema, this technique presents
some defects: it requires considerable cooperation from the patient and a good joints
mobility to place the limb inside the container; therefore, it cannot be used in case
of important functional limitations. In case of skin lesions, it requires careful
hygiene and accurate disinfection in the patient. It provides data regarding the
immersed limb volume, but it does not give us indication regarding the edema distribution such as interstitial and intracellular components.
To the contrary, the method is suitable and useful for assessing the foot volume
that could be difcult and unprecise using centimetric measurement.
5.4.4 Perometer [17]
This device evaluates the limb volume using infrared light sources stimulating specic sensors tracing the circular sections of the limb. This technique is precise and
allows full leg evaluation. Its accuracy and repeatability are close to water plethysmography which remains up to now the gold standard.
5.4.5 Circumferential Method (with aTape Measure) [18]
The limb volume can be calculated indirectly starting from a precise measurement
of the limb circumferences at different levels using a exible meter.
This measurement, compared to direct ones, presents the advantage of being
rapid, inexpensive, and easily available in the clinical setting. It also provides the
spatial distribution of edema, comparing the different limb segments giving the idea
of the lower limb shape.
This technique shows an excellent inter-rater and test–retest reliability, but the
obtained values are not comparable with the absolute volume measured with direct
methods.
By assimilating the various limb segments to geometric solids, the volume is
calculated applying mathematical formulas used for volume calculation. For this
reason, the more the limb shape differs from theoretical solid on which the formula
is based, the greater the error becomes.
The circumferences assessment can be taken at intervals of centimeters, or at
predened points by measuring the distance between these. The choice of smaller
measurements ranges is based on the accuracy which also depends on the distance
of the assessment points.
For consistent measurements, each upper or lower extremity is marked with a
semi-permanent marker starting from bony prominences as reference. A critical
point is the evaluation of the hand and the foot volume which has irregular shape,
therefore hardly assimilating to geometric solids.
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E. Menegatti et al.
5.4.6 Bioimpedance (BIA)
BIA is a noninvasive technique able to measure the impedance of the human body,
and it is founded on the ability of biological tissue to impede electric current, the
so-called resistance. BIA is able to identify, even in a segmental way, the rate of
extracellular water (ECW) out of total body water [19].
BIA use for lymphedema investigation was reported since the early 1990s, considering ECW evaluation as a fundamental parameter in the assessment of venouslymphatic drainage alteration. Recently, it has been described for assessing the
edema/lymphedema measurement during follow-up after rehabilitative interventions [20, 21].
In conclusion, after the preliminary evaluation, which can also be performed in a
general medicine ofce, the patient should be addressed to a specialistic evaluation
for detailed assessment and diagnostic integration by means for example of ultrasonography and eventually lymphoscintigraphy, which is the gold standard in lymphedema assessment. A detailed description on this diagnostic technique is reported in
the related chapter of this textbook.
Maximum care must be dedicated to edema patients, particularly considering
that a common condition like lymphedema is still considered a “hidden epidemic”
because of its large epidemiology and is paradoxically often underdiagnosed and
poorly managed condition.
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