I.

Approach to Diagnosis

We are presented with a case of an 82 year old male, who had gradual left leg swelling, with the following
salient features: Intermittent Claudication, signs of inflammation: redness, tenderness, warmth, gradually
enlarging nodules, largest measuring 2x2cm, ulcer at the left calf, decreased popliteal and dorsalispedis
pulses at left leg, temporary relief from Furosemide, with Good urine output, (-) fever, cough, dyspnea,
orthopnea, dysuria.

According to Evidence Based Clinical Medicine, Approach to Leg Edema of Unclear Etiology by Ely et al (1)
In the assessment of edema, the history should include the timing of the edema, assessment for systemic
diseases and whether the edema is unilateral or bilateral

According to Harrisons Principles of Internal Medicine 19thed (2), a generalized leg swelling will be
associated with the following conditions:

1. Congestive Heart Failure

2. Hypoalbuminemia secondary to nephrotic syndrome or severe hepatic disease,
3. Myxedema caused by hypothyroidism

These will manifest with bilateral leg swelling; Unilateral causes of leg swelling also include
ruptured leg muscles, hematomas secondary to trauma and popliteal cysts.

Base on the chronicity of signs and symptoms, assessment for systemic diseases and localization of edema,
we rule out the causes of generalized swelling (Congestive Heart Failure, hypoalbuminemia secondary to
nephrotic syndrome or severe hepatic disease, myxedema caused by hypothyroidism) Thus, we are left
with Infectious causes, Inflammatory and Neoplastic causes. Infectious causes may be: (Bacterial-Cellulitis
or Parasitic-Filariasis), Inflammatory causes Deep Vein Thrombosis, Peripheral Arterial Occlusive Disease,
Chronic Venous Insufficiency, Ruptured leg muscle. On the other hand, Neoplastic causes can be primary
or metastatic.

What could be the underlying cause of the patients condition? Are we dealing with a concomitant disease
with an unknown etiology or a sequelae of another unknown pathology?

II. Differential Diagnosis

Hence we came up with the following differential diagnoses:
1. Infectious: Filariasis, Cellulitis
2. Inflammatory: PAOD, DVT, CVI, Ruptured leg muscle
3. Neoplastic: Primary or Metastatic: Lymphoma, Prostate cancer

A. DVT
DVT affects 0.1% of person per year. It is predominantly a disease of the elderly and has
a slight male preponderance. (1) The overall age- and sex-adjusted annual incidence of venous
thromboembolism (VTE) is 117/100,000 with higher age-adjusted rates among males than
 females. (2) DVT is predominantly a disease of the elderly with an incidence that rises markedly
with age. (2) Proximal vein thrombosis is of great importance and is associated with serious
chronic diseases such as active cancer, congestive cardiac failure, respiratory insufficiency or age
above 75 years. (3) Symptomatic patients with proximal DVT may present with lower extremity
pain, calf tenderness, and lower extremity swelling. In the algorithm for the diagnosis of DVT, the
first step is the pretest probability assessment using an established model such as the Wells score.
If score is <1 (DVT unlikely), D-Dimer assay is done. If the DVT is likely (probability score>2), venous
ultrasonography is indicated.

D-Dimer test is the best recognized biomarker for the initial assessment of suspected VTE,
this test is highly sensitive (up to 95%) but have poor specificity to prove VTE. False D-Dimer
results have been noted in inflammation, pregnancy, malignancy and elderly. (1) Venous
ulrasonography is the investigation of choice in patients stratified as DVT likely. (4) The major
ultrasonographic criterion for detecting venous thrombosis is failure to compress the vein lumen
under gentle probe pressure. (4) With clinical probability and presented evidences, DVT is
considered.

1. Keseime, E., Keseime C. et. Al. Deep Vein Thrombosis: A Clinical Review. Journal of Blood
Medicine 201 1:2 59-69
2. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and
pulmonary embolism: a 25-year populationbased study. Arch Intern Med. 1998;158(6):585593.
3. Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):122
130.
4. Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg.
1972;104(2):134144.

B. Chronic Venous Insufficiency

Chronic Venous Insufficiency describes a condition that affects the venous system of the
lower extremities, with the sine qua non being persistent ambulatory venous hypertension
causing various pathologies, including pain, edema, skin changes, and ulcerations. CVI often
indicates the more advanced forms of venous disorders, including manifestations such as
hyperpigmentation, healed or active ulcers. (1) Leg varicosities are often present in patients with
chronic venous insufficiency, but venous insufficiency can occur without varicose veins. (2) There
 are also environmental or behavioral factors associated with CVI, such as prolonged standing and
perhaps a sitting posture at work. (3,4) The major clinical features of CVI are dilated veins, edema,
leg pain, and cutaneous changes in the leg. Obstruction of the deep venous system may lead to
venous claudication (or intense leg discomfort with ambulation). There is an increased risk of
cellulitis, leg ulceration, and delayed wound healing. Protracted CVI may also contribute to the
development of lymphedema, representing a combined process. (1) To further define CVI, a
venous clinical severity score was developed (5,6)

Venous duplex imaging is currently the most common technique used to confirm the
diagnosis of CVI and assess its etiology and anatomy and is highly recommended in the CPG
(grade1A) (7,8,9) The presence of venous obstruction because of chronic DVT or venous stenosis
may be directly visualized or inferred from alteration in spontaneous flow characteristics. With
the similarities of its occurrence as to the patients age and course of signs and symptoms, this is
considered as causes in the patients condition.

1. Eberhardt, R &Rafetto, J. Chronic Venous Insufficiency: Contemporary Review in Cardiovascular

Medicine DOI: 10.1161/CIRCULATIONAHA.113.006898
2. Merli GJ, Spandorfer J. The outpatient with unilateral eg swelling. Med Clin North Am
1995;79:43547.
3. Jawien A. The influence of environmental factors in chronic venous insufficiency. Angiology.
2003;54:S19S31
4. Lacroix P, Aboyans V, Preux PM, Houls MB, Laskar M. Epidemiology of venous insufficiency
in an occupational population. IntAngiol.
2003;22:172176.
5. Rutherford RB, Padberg FT Jr, Comerota AJ, Kistner RL, Meissner MH, Moneta GL. Venous
severity scoring: an adjunct to venous outcome assessment. J Vasc Surg. 2000;31:13071312.
6. Kakkos SK, Rivera MA, Matsagas MI, Lazarides MK, Robless P, Belcaro G, Geroulakos G.
Validation of the new venous severity scoring system in varicose vein surgery. J Vasc Surg.
2003;38:224228.
7. Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, Gloviczki ML, Lohr JM,
McLafferty RB, Meissner MH, Murad MH,
 Padberg FT, Pappas PJ, Passman MA, Raffetto JD, Vasquez MA, Wakefield TW; Society for
Vascular Surgery; American Venous Forum. The care of patients with varicose veins and
associated chronic venous diseases: clinical practice guidelines of the Society for Vascular
Surgery and the American Venous Forum. J Vasc Surg. 2011;53(5 suppl):2S48S.
8. Folse R, Alexander RH. Directional flow detection for localizing venous valvular incompetency.
Surgery. 1970;67:114121.
9. Mattos MA, Sumner DS. Direct noninvsive tests (duplex scan) for the evaluation of chronic
venous obstruction and valvular incompetence. In: Gloviczki P, Yao JS, eds. Handbook of
Venous Disorders, 2nd Edition. New York, NY: Arnold Publisher; 2001:120131.

C. PAOD:

A study made by Ness et. al prevalence of PAD increases with age and prevalence of symptomatic
PAD occurs in 32% of 1160 men, mean age of 80 years. [1] It was noted that the most common
clinical manifestation of PAD is intermittent claudication [2]which is defined as muscle discomfort in
the lower limb precipitated by exercise and relieved by rest within 10 minutes. The Edinburgh
(pronounce as EDIN-BRA) Artery Study reported an estimated prevalence of 4.5% among men. [3]
Decrease in dorsalis pedis and popliteal pulses which are the affected vessels in 40% and 80% of
cases, respectively. [4] With the following risk factors, CAD and gout. Approximately one third to
one half of patients with symptomatic PAD have evidence of CAD based on clinical presentation and
electrocardiogram [5] (PRESENT PE findings and 2D echo findings). Confirmatory test for
PAD________________.

D. LYMPHOMA
A review of the literature, however, reveals that unilateral lower extremity oedema may be the initial and sometimes the only manifestation
in patients with secondary lymphoedema from occult malignancy. Hawkins et al3 found that of 10 cases of secondary lymphoedema from
lymphoma, unilateral leg oedema was the only presenting symptom in seven cases, with a duration as long as 6 months before diagnosis.
5
In three of the cases reported, the patients were misdiagnosed as venous insufficiency but failed to respond to conventional modalities
such as leg elevation, diuretics, anti-inflammatory agents and compression stockings. [1] CT scan findings of paraaortic lymphadenopathy
and a large enhancing, lobulated para-aortic mass is most likely Lymphoma.

E.