C. Suharti Prof. dr. SpPD-KHOM, PhD. FINASIM.

Update 2017
Normal Venous Flow in the Leg

• Normal Flow
• Superficial veins deep veins
• Feet Heart

•Superficial vein disease always

starts with abnormal valves and
interruption to normal flow

Venous Reflux
 Superficial Thrombophlebitis (ST):

ST= Superficial Venous Thrombophlebitis

 ST definition: is an inflammation of a vein (phlebitis)
associated with thrombus formation (thrombosis)

Anatomy and Physiology

 The superficial veins system runs in the fatty layers between
the skin and fibrous layers surrounding the muscle (fascia).
The vein are not supported by a resistant structure and so
can dilate and elongate and become varicose
 Clinical Features

 Redness and tenderness along the course of the vein

 Edema (swelling)
 Bleeding also can occur at the site of a varicose vein
 Some times fever and chills
 ST can also occur in the external jugular vein
(infusion site), upper extremities (infusion sites or
sites of trauma)
Superficial Thrombophlebitis
Thrombus = blood clots
Phlebitis = vein inflammation
Thrombophlebitis:
 Deep
 Superficial vein
Deep Vein Thrombosis
Physical Findings
Calf pain
Swelling with pitting edema
Swelling below knee (distal DVT), up to
groin/inguinal (proximal DVT)
Increased skin temperature
Cyanosis (severe obstruction)
Superficial venous dilatation
 Etiology

Most often associated with one of Virchow triad:

 Stasis or turbulent flow: limb immobilization and venous
obstruction
 Hypercoagulability: cancer, medications
 Intimal damage: trauma, infection, inflammation
Others: spontaneously, complication of medical/surgical
intervention
Traumatic Thrombophlebitis
 Virchov’s Triad in the pathogenesis of ST

Injury to the
vascular wall

1846, Virchow
(German pathologist)

Hyper- Stasis (Slow

coagulability blood flow)
 Stasis

 Stagnant blood in venous valve pocket

 In the horizontal position of the lower limbs the contrast
medium stays in the venous valve pocket for over 25 min.

Reflux in varicose superficial veins  endothelial hypoxia in

venous sinuses:
 Up regulates the expression of P-selectin
 Binding of leukocytes and vesicles (leukocyte particles)
containing tissue factor  nidus for initiation of thrombotic
response

Blood Rev 2009;23:225-9

Venous Reflux
 Stasis-prolonged immobilization

Travelling more than 8 hours

Stasis
 Hypercoagulability

 Hormonal (pregnancy, oral contraceptive: ↑factor VII,

↑factor VIII, ↑ factor X, ↑ factor prothrombin, ↑ fibrinogen,
↓antithrombin.
 Obesity: ↑ varicose veins
 Cigarette smoking, in combination with oral contraceptive
 Age
 ST as prodromal several systemic diseases:

 Trousseau’s Syndrome: migratory thrombophlebitis

 Mondor disease: thrombophlebitis of the superficial veins of

the breast/anterior chest wall or of the dorsal vein of the
penis.

 Thrombophlebitis associated with vasculitis: Buerger’s

disease, Polyarteritis nodosa/Bechet Syndrome
 Complications of Superficial Thrombophlebitis

 DVT (Deep Vein Thrombosis)

 PE (Pulmonary Embolism)

 Calisto study, incidence of DVT/PE: 0.2% on anticoagulant

(fondaparinux), 1.3% on placebo
• When affecting the greater
saphenous vein, thrombophlebitis
will sometimes progress into the
deep venous system (DVT).

• Damage to deep venous valves

leads to chronic deep venous
insufficiency (postphlebitic
syndrome), as well as to recurrent
pulmonary embolism, increased
risk of death
 Diagnosis and Differential Diagnoses

 Superficial thrombophlebitis is a clinical diagnosis in which the

clinician identifies tender and inflamed superficial veins

Differential Diagnosis:
 Cellulitis
 Deep venous thrombosis
 Lymphangitis
 Tendonitis
 Chronic venous insufficiency
 Treatment

Depends on: etiology, extension, symptom severity and

association with DVT, PE
 Nonsteroidal Anti-Inflammatory Drugs (NSAID): ibuprofen,
indomethacin
 Anticoagulants: heparin, low molecular heparin
 Antibiotics
 Patient education: thrombophlebitis tend to recur: elastic
stocking, slight elevation foot in the bed, avoidance long-
period standing, avoidance prolonged inactivity.
 Prognosis: good
 Rarely associated with Pulmonary Embolism
Chronic Venous Insufficiency
(CVI)
 Varicose veins (Vvs)
• Vvs result from venous hypertension owing to
incompetence of major communications between
the superficial and deep veins of the lower extremity.
• Failure of valves located at the saphenous-femoral
and saphenous-popliteal junctions↑ hydrostatic
pressure within the superficial veins.
• Elevated venous pressures  progressive venous
dilation and thickening of large venous branches 
as varicose veins (any vein abnormally dilated greater
than 3 mm)
 Abnormal flow = Venous
Reflux
Damaged Valves:
1. Blood flows to the skin

2. Blood is pushed distally and

proximally

3. Closed loop recirculation

4. Blood is retained in the leg

 Increased volume of blood
 Increased venous pressure
 Veins dilate
 Chronic Venous Insufficiency (CVI)

 CVI is a condition that occurs when the venous wall and/or valves
in the leg veins are not working effectively, making it difficult for
blood to return to the heart from the legs
 Postphlebitic (Post thrombotic ) syndrome is symptomatic
Chronic venous insufficiency after deep vein thrombosis
 Anatomy
Venous network lower
External iliac extremities affected CVI:

Proximal
 Superficial vein: great
Deep femoral saphenous vein, small
Great saphenous saphenous vein
Popliteal  Deep vein: anterior tibial,
posterior tibial, peroneal,
Anterior tibial
Distal
popliteal, deep femoral,
Posterior tibial superficial femoral, iliac
veins
 Perforating or
Dorsal venous arch
communicating veins
 Venous Ulceration
United States:

 600,000+ new venous ulcers annually

 Affects 1-4% of the population
 Recurrence rate averages 75%
 >50% out of work or disabled
 >25% depression or anxiety

American Society of Plastic Surgeons. Evidence-based clinical practice

guideline: chronic wounds of the lower extremity. 2007
 Causes Chronic Venous Insufficiency

 Valves damaged: aging,

extended sitting or
standing, reduced mobility
 Pelvic tumors
 Vascular malformations
 DVT (deep vein
thrombosis):
o CVI as a result of DVT : post-
thrombotic syndrome
o About 30% of people with
DVT will develop this problem
within 10 years after diagnosis
 Risk Factors for Chronic Venous Insufficiency

• Genetic (Heredity)
• Female gender
• Pregnancy
• Hormone therapy: progesterone, estrogen
• Age (advanced)
• History of prolonged standing or sitting
• Obesity
• Leg trauma or surgery
 CEAP Classification for Chronic Venous Disease
Clinical classification: (C) Etiology classification (E)
C0: no visible or palpable signs of venous Ec: congenital (Klippel-Treanuney
disease syndrome
C1: teleangiectases <1mm, reticular veins Ep: primary
≤3mm or malleolar flare
C2: varicose veins Es: secondary (eg postthrombotic
syndrome, trauma)
C3: edema without skin changes En: no venous caause identified
C4: skin changes ascribe to venous disease
C4A: Pigmentation, venous eczema or both
C4B: Lipodermatosclerosi, atrophy blanche
or both
C5: skin changes with healed ulceration
C6: skin changes with active ulceration
CEAP Classification for Chronic Venous Disease
Anatomic classification (A) Pathophysiologic classification
(P)
As: superficial Pr: reflux
Ad: deep Po: obstruction, thrombosis
Ap: perforator Pro: reflux and obstruction
An: no venous location Pn: no venous pathophysiology
identified identified
Teleangiectasias and Reticular veins

 Telangiectasias (spider veins):

when CVI occurs locally in
small cutaneous veins: fine
cutaneous red, purple or blue
veins less than 1mm in
diameter
.
 Reticular veins: larger 1-3 mm
subdermal blue or blue-green
veins
 Signs: itching, burning or
achiness
 Venous hypertension are transmitted
to the microcirculation  venous
microangiopathy.

 Normal reabsorption of perivascular

fluids by osmotic and pressure
gradients is impaired accumulation
of perivascular and lymphatic fluid 
o edema
o fibrosis
o impaired oxygenation of surrounding
tissue

 The disruption of normal vascular

and lymphatic flow may result in the
symptoms of chronic venous
insufficiency and lymphedema
 Signs and Symptoms
• Telangiectasias • Aching
• Reticular veins • Heaviness
• Varicosity • Early fatigue
• Thrombophlebitis • Edema
• Hyperpigmentation • Itching
• Bleeding from ulcers • Restless legs
• Ulceration • Cramps
 Diagnosis

 Diagnosis based on history and physical examination

 Duplex ultrasonography to exclude DVT
 The venous clinical severity score
Attribute Absent Mild=1 Moderate 2 Severe 3
Pain None Occasional Daily Daily
Varicose veins None Few Calf or thigh Calf and thigh
Venous edema None Limited foot and Extends above ankle Extends to knee
ankle but below knee and above
Skin None Limited to Diffuse over lower third Wider > lower
pigmentation or focal perimalleolar of calf third of calf
Inflammation None Mild cellulitis, ulcer Diffuse over lower third Wider > lower
margin limited to of calf third of calf
perimalleolar
Induration None Limited to Diffuse over lower third Wider > lower
perimalleolar of calf third of calf
Ulcer number 0 1 2 ≥3
Ulcer duration NA <3mo >3mo but <1yr Not heale >1 yr
Ulcer size NA Diameter <2cm 2-6 cm >6cm
Compressive Not intermittent Most days Fully compliance
therapy used
NA, not available. Circulation 2014: 130:333-346
Differential Diagnosis of Lower Extremity Edema

 Venous obstruction  Medications (Calcium

 Chronic right-sided heart channel blockers)
failure  Lymphatic obstruction
 Venous insufficiency  Preeclampsia–eclampsia
 Cirrhosis  Myxedema
 Cellulitis  Malignancy
 Low albumin  Pelvic tumor
 Pregnancy
 Deep venous thrombosis
 Treatment (1)
Conservative Treatment
• Avoid long periods of standing or sitting
• Exercise regularly
• Lose weight if overweight.
• Elevate legs while sitting and lying down (above the level of
heart); ≥30 minutes, 3x/day.
• Wear compression: stockings (>20 mm Hg), pneumatic device
• Antibiotics (to treat skin infections).
• Topical treament: zinc oxide-impragnated bandages, covered
by compression bandage, changed weekly
• Practice good skin hygiene.
 Treatment (2)
Surgical (not effective)
 Endovenous Thermal Ablation
 Sclerotherapy
 Compression stockings:
 20 to 30 mm Hg: indicated for smaller
varicose veins and mild CVI
 30 to 40 mm Hg: indicated for larger
varicose veins and moderate disease
 40 to > 60 mm Hg: indicated for severe
disease
 Stocking should be put on when patients
awaken, before leg edema worsens with
activity, with maximal pressure at the
ankles, gradually less pressure Compression Elastic Stocking
proximally

Mayo Clin Proc. March 2014.89(3):394-408. http://dx.doi.org/10.1016/j.mayocp.2013.11.015

Graduated compression stocking Intermittent Pneumatic
(GCS) Compression (IPC)
Upper thigh 8mmHg
Lower thigh 10mmHg
Popliteal 8mmHg
Calf 14mmHg
Ankle 18mmHg
LYMPHANGITIS
• Lymphangitis: an inflammation of the lymphatic
channels that occurs as a result of infection at a site
distal to the channel.
• The lymphatic system: a network of vessels, glands,
and organs located throughout the body.
Functions:
 as part of the immune system
 transports fluids, fats, proteins, and other substances in
the body
 Lymph nodes (glands), filter the lymph fluid. Bacteria
and viruses are processed in the lymph nodes to
generate an immune response to fight infection.
• When pathogenic organisms enter the lymphatic
channels (directly through an abrasion or wound or
complication of infection) local inflammation 
infection, manifesting as red streaks on the skin.

• The inflammation or infection then extends

proximally toward regional lymph nodes. Bacteria
can grow rapidly in the lymphatic system.
 Etiology
• In individuals with normal host defenses: group A
beta-hemolytic streptococci (GABHS) are the most
common
• These organisms elaborate fibrinolysins and
hyaluronidase, which aid their invasion of lymphatic
channels  rapidly progress  serious
complications.
• Other organisms :
 Staphylococcus aureus
 Pseudomonas species.
 Etiology (2)

• In immuno-compromised host: Gram-negative rods,

gram-negative bacilli, and fungi
• Wuchereria bancrofti - This filarial nematode is a
major cause of acute lymphangitis worldwide.
• Individuals with diabetes, immunodeficiency,
varicella, chronic steroid use, or other systemic
illnesses have increased risk of developing serious or
rapidly spreading lymphangitis.
 Prognosis

• Uncomplicated patients: prognosis is good.

• Antimicrobial regimens are effective in more
than 90% of cases.
• Without appropriate antimicrobial therapy,
however, cellulitis may develop or extend
along the channels; necrosis and ulceration
may occur.
 Morbidity and mortality

• Lymphangitis may spread within hours. The

morbidity and mortality associated with the
disease is related to the underlying infection.
• Lymphangitis caused by GABHS can lead to
bacteremia, sepsis, and death.
 Differential Diagnosis Lymphangitis

• Cellulitis
• Septic thrombophlebitis
• Superficial thrombophlebitis
• Necrotizing fasciitis
• Myositis
 Medication
• Analgesics: control pain
• Anti-inflammatory: reduce inflammation and
swelling.
• Antibiotics: for GABHS and Saureus infections:

 Dicloxacillin  Ceftriaxone
 Cephalexin  Clindamycin
 Cefazolin  Nafcillin
 Cefuroxime  Trimethoprim and
sulfamethoxazole (TMP/SMZ)
LYMPHADENOMA
 LYMPHADENOMA
(Malignant Lymphoma)
Medical Dictionary

 Lymphadenoama: any neoplastic disorder of lymphoid tissue

(malignant lymphoma).

Lymphadenopathy: lymph nodes which are abnormal in size,

number or consistency.
Common causes of lymphadenopathy:
Infection: lymphadenitis
Autoimmune disease
Malignancy
 Causes
Lymph node enlargement is a common sign of infectious,
autoimmune, or malignant disease:
Reactive acute infection Viral, bacterial
Reactive chronic infection Tuberculous lymphadenitis
Infectious mononucleosis Acute infection by Epstein-Barr virus
(enlargement of cervical lymph
nodes
Toxoplasmosis (parasitic disease) Generalized lymphadenopathy
Tumor Primary: Hodgkin and non-Hodgkin
Lymphoma
Secondary: metastases
Autoimmune disease SLE, Rheumatoid arthritis
Immunocompromised AIDS
 Step-by-step diagnostic approach
• Determine: localized or generalized, size, mobility
and consistency of the lymph nodes.
• If localized, the regions drained by the nodes should
be examined for evidence of infection, skin lesions or
neoplasms.
• When the history and physical signs are diagnostic
for a specific disorder, such as a localized skin
infection or pharyngitis, no further testing is
indicated and treatment should be initiated.
 History
• Age of the patient
• Symptoms of infection: pharyngitis, skin ulceration
• Symptoms of metastatic malignancy: localized
symptoms: difficulty in swallowing, hoarseness and
pain (head and neck cancer), cough and hemoptysis
(lung cancer).
• Constitutional or B symptoms: fever, night sweats
and/or unexplained weight loss greater than 10% of
bodyweight over 6 months are concerning for
lymphoma.
 Physical examination
• Size: lymph nodes <1 cm are rarely of clinical
significance, >2 cm, persistent >4 weeks should be
thoroughly evaluated.
• Consistency: rock-hard nodes (commonly
malignancies), tender nodes (suggest inflammatory
disorder).
• Mobility: fixed or matted nodes (suggest metastatic
carcinoma), freely movable (may infections, collagen
vascular disease and lymphoma).
 Physical examination (2)

• Distribution: generalised lymphadenopathy

(systemic disease)

• Localised (enlarged lymph nodes in one region;

regional: 2 or more contiguous regions; generalised:
≥ 2 non-contiguous regions).
 Investigations
• Clinical assessment
• Ultrasound
• FNA lymph nodes if ultrasound features suggest
pathology
• Excision biopsy
 FNA in diagnosis of lymphadenopathy

• Confirmation that the lesion is lymph node

• Distinction between neoplastic-non neoplastic
• Distinction between specific infection-non
specific lymphadenopathy
• Distinction between lymphoid and metastatic
malignancy
• Lymphoma: must excision biopsy (nodal
architecture needs to be intact).
 Diagnostic yield
• Ideally, axillary and inguinal nodes are avoided
as they often demonstrate reactive
hyperplasia
• Preferred supraclavicular, cervical,
epitrochlear
• Complications are rare but include vascular
and nerve injury
When to refer?
 Combination of the following symptoms may
require referral
• Fatigue • Bleeding
• Drenching night sweats • Recurrent infection
• Fever • Bone pain
• Weight loss • Alcohol-induced pain
• Generalized itching • Abdominal pain
• Breathlessness • Lymphadenopathy
• Bruising • Splenomegaly

The urgency of referral depends on the severity symptoms and

signs, and findings of investigations.
 Urgent referral
If ≥1 the following LN features:
• Non tender, firm or hard
• Greater than 2cm in size
• Progressively enlarging
• Other features of general ill-health fever or
weight loss
• Axillary nodes involved
• Supraclavicular nodes involved
• Persisting for 6 weeks or more
 LYMPHADENOMA
(Malignant Lymphoma)

 Lymphoma is a group of diseases cause by malignant

lymphocytes that accumulate in lymph nodes

 The major subdivision of lymphoma is:

o Hodgkin Lymphoma
o Non-Hodgkin Lymphoma
 Based on the histological presence of Reed-Sternberg cell in
Hodgkin Lymphoma
 HODGKIN LYMPHOMA
(Clinical Features)

 Most patient present with enlargement of superficial LN:

painless, non-tender, asymmetrical, firm, discrete, rubbery
 Site: cervical nodes, axillary, inguinal
 In some cases, the size of the nodes decreases and increases
spontaneously
 Splenomegaly, hepatomegaly
 Mediastinal involvement
 Cutaneous Hodgkin disease
 Constitutional symptoms: fever, pruritus, alcohol-induced pain
In the area of disease present, weight loss, profuse sweating
(especially at night), weakness, fatigue, anorexia, cachexia.
 Diagnosis and Histological Classification

 The diagnosis is made by histological examination of an

excised lymph node.
 The distinctive multinucleate polyploid Reed Sternberg cell:
diagnosis of 4 classic types
 Histological Classification Classic Hodgkin Lymphoma:
o Nodular sclerosis
o Mixed cellularity
o Lymphocyte depleted
o Lymphocyte rich
o Nodular-lymphocyte-predominant (Reed-Sternberg cell s
absent)
 CLINICAL STAGING
Stage
I The disease is confined to one lymph node area
II The disease is in two or more lymph node areas on one side
of the diaphragm
III The disease is in lymph node areas on both sides of the
diaphragm. Spleen disease include stage III
IV The disease has spread from the lymphatic system to one or
more other organs, such as the bone marrow or liver
Treatment for Hodgkin's disease depends both on the stage of the disease and whether or
not symptoms are present. Stages are labeled with an A if no symptoms are present. If
symptoms are present, the stage is labeled with a B.
These symptoms include:
o loss of more than 10% of body weight over the previous six months
o fevers above 100 degrees F
o drenching night sweats
 Treatment

 Radiotherapy: stage I and II

 Combined modality: radiotherapy and chemotherapy
 Chemotherapy: cyclical chemotherapy is used for stage III
and IV, and also stage I and II patients who have bulky disease
(diameter tumor> 10 cm).
 The combination of Adriamycin, Bleomycin, Vinblastine and
Dacarbazine (ABVD) is now most widely used.
 RESISTANT, PROGRESSIVE, AND RECURRENT
HODGKIN'S DISEASE

 Resistant Hodgkin's disease: some cancer cells remain

following treatment
 Progressive Hodgkin's disease: the cancer continues to spread
during treatment
 Recurrent Hodgkin's disease: the disease returns after
treatment
 An autologous bone marrow (ABMT) and/or
 Peripheral blood stem cell transplantation (PBSCT), is
recommended for treating resistant or recurrent Hodgkin's
disease
 Non-Hodgkin’s Lymphoma
 A large group of lymphoid tumours, most commonly of B-cell
origin. Clinical presentation and natural history are more
variable than in Hodgkin lymphoma
 Classification and histopathology:
o REAL (1994): Revised American European Lympoma
classification
o WHO classification
 Low- and High-grade NHL
o Low-grade: relatively indolent, respond well to chemotherapy,
but very difficult to cure
o High-grade: aggressive and need urgent treatment but are
often curable.
o Intermediate-grade
 Clinical Features of NHL

 Superficial lymphadenopathy
 Constitutional symptoms: fever, night sweats and weight loss
 Oropharyngeal involvement (Waldeyer’s ring)  sore throat
 Cytopenia: Anemia, neutropenia with infection or
thrombocytopenia.
 Abdominal disease: Liver or spleen are often enlarged,
involvement retroperitoneal or mesenteric node. The
gastrointestinal tract is the most commonly involved
extranodal site after bone marrow.
 Others: skin, brain, testis, thyroid (Skin: T-cell lymphomas:
mycosis fungoides and Sezary syndrome)
 Specific Subtype of NHL
Low-grade NHL
 Follicular lymphoma
 Lymphocytic lymphoma: closely related to CLL (chronic
Lymphocytic Leukemia)
 Lymphoplasmacytoid lymphomas: associated production of
monoclonal immunoglobulin IgM (Waldenstrὅm’s
macroglobulinaemia
 Mantle cell lymphoma
 Marginal zone lymphoma
 High-grade NHL

 Diffuse large B-cell lymphoma (DLBCL)

 Burkitt’s lymphoma
 Lymphoblastic lymphoma
 T-Cell Lymphoma

 Peripheral T-cell NHL

 Angioimmunoblastic lymphadenopathy
 Mycosis fungoides
 Sezary syndrome
 Adult T-cell leukemia/lymphoma
 Angiocentric lymphoma
 Anaplastic large cell lymphoma
 Management
Low grade:

 Asymptomatic : No treatment ;
 Radiotherapy for localised disease (Stage 1);
 Chemotherapy: Chlorambucil, Fludarabine
 Monoclonal antibody: Rituximab
 SCT/BMT
 Management

Aggressive ( high/intermediate grade)

Chemotherapy:
Mainstay CHOP, every 3 weeks, at least 6 cycles

 Cyclophosphamide,
 Doxorubicin Hydrochloride
 Vincristine,
 Prednisolone
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