Lymphoedema refers to swelling in the tissues due to obstruction of lymph drainage
Lymphedema is also defined as the interstitial collection of protein-rich fluid due to disruption of lymphatic flow.
When lymph vessel is obstructed, lymph accumulates in the distal parts leading to low grade inflammation and lymph vessels
Lymphatic dysfunction means that lymphatic system is not working well
- Physiologic basis of lymphedema — Lymphedema occurs when the lymphatic load exceeds the transport capacity of the lymphatic system, which causes filtered fluid to accumulate in the interstitium. As opposed to generalized edematous states, the rate of capillary filtration is normal in patients with lymphedema
Causes of lymphoedema
Causes of Lymphoedema can be:
- Primary: is due to a congenital and or inherited condition associated with pathologic development of the lymphatic vessels.
- Secondary: This occurs as the result of other conditions or treatments
- Congenital lymphatic obstruction (Milroy’s disease): failure for the lymph vessel especial in lower limb to develop. This is also called hereditary or primary lymphoedema
- Surgical removal of lymph vessel and lymph nodes due to cancer to prevent secondary tumors and further disease spread i.e. removal of axillary nodes during mastectomy may lead to lymphoedema of the affected arm
- Tumours can compress lymph vessel blocking lymph flow and tissue drainage
- Filariasis: It is a disease caused by tissue dwelling nematode, transmitted by mosquito bite
- Malignant metastasis of lymph node and lymph vessel
Signs and symptoms of lymphoedema
Typical signs and symptoms of lymphedema include:
- The onset of lymphedema is usually insidious. Affected patients may initially experience aching pain at the affected area and a sense of heaviness or fullness of the limb. Over time, the skin becomes dry and firm with less pitting and is fibrous to palpation.
- Two-thirds of cases of lymphedema are unilateral, although the laterality depends on the precipitating event. For example, an axillary node dissection will increase the risk of lymphedema in the ipsilateral arm while a pelvic node dissection increases the risk of bilateral lower extremity edema.
- At onset, swelling in the affected limb is typically characterized as “soft” and “pitting”. Pitting is variable in patients with lymphedema and reflects movement of the excess interstitial water in response to pressure. It is generally absent with progressive lymphedema, reflecting the evolution of fibrosis and adipose tissue deposition.
For patients who had previously undergone a lymph node dissection and radiation, lymphedema is typically characterized by slowly progressive ipsilateral swelling of an arm following axillary node dissection or a leg following inguinal node dissection. The swelling may first be apparent only in the proximal portion of the limb, or it can affect only a portion of the distal limb including the digits.
Among patients with breast cancer, there may also be swelling over the ipsilateral breast and/or upper chest wall. Other manifestations include a feeling of heaviness, tightness, aching or discomfort in the limb, and restricted range of motion.
- Skin changes — With worsening lymphedema, dermal thickening becomes clinically apparent, which is manifested by cutaneous fibrosis. The overlying skin of the affected limb also becomes hyperkeratotic, which can lead to verrucous and vesicular skin lesions.
- Discomfort — A feeling of heaviness, tightness, aching or discomfort in the affected limb commonly accompanies swelling.
- Restricted range of motion — With later stages of lymphedema, patients may develop restricted range of motion in the affected limb as a result of the increased weight, which may limit their ability to perform activities of daily living (ADLs).
Summary of Clinical Features
- Swelling in arms and legs
- Tissues of the neck and head may be affected also.
- Reduced mobility due to swelling
- Heaviness of the affected area
- Skin changes i.e discoloration
- Blister formation
- Leaking of fluid from the skin
- Poor vision, ear pain and nasal congestion in case of head and neck lymphoedema
- Difficult in swallowing
- Difficulty in breathing and talking
- Lymphangitis and cellulitis occur as complications which presents as streaky red patch on area affected, fever, chills and itching
Diagnosis and Investigation of lymphoedema
- History: Components of history that should be addressed include:
- Age of onset
- Area(s) of involvement
- Associated symptoms (e.g., pain)
- Medications — While none is directly associated with an increased risk of lymphedema, some are associated with edematous states (e.g., NSAIDs agents) or are contraindicated in the treatment of lymphedema (e.g., diuretics)
- Progression of symptoms
- Past medical history, including of medical conditions associated with lymphedema, any prior travel, infections, surgery or prior RT
- Family history
2. Physical Examination.
- The physical exam should evaluate the vascular system, skin, and soft tissue, and palpation of the lymph nodes.
If primary lymphedema is suspected, evaluation should include documentation of any physical signs or congenital anomalies associated with an inherited condition. Examples include:
- Short stature (Turner Syndrome)
- Port wine stains or hemangiomas (Klippel-Trenaunay-Weber Syndrome)
- Shield chest (Turner Syndrome, Noonan Syndrome)
- A positive Stemmer sign is indicative of lymphedema. It is characterized by the examiner’s inability to lift the skin of the affected limb compared to the contralateral limb. It is also described as difficulty lifting the skin of the dorsum of the fingers or toes of the affected limb. A positive Stemmer sign can be found in any stage of lymphedema. While it is possible to have a false negative Stemmer sign, a false positive sign is rare.
- Opto electronic volume try — Volume can be assessed utilizing an infrared, optoelectronic measurements. This technique utilizes infrared beams to scan the limb and calculate a volume.
- Circumferential measurements — Circumferential measurements on the affected and contralateral arm are a simple and inexpensive method to estimate edema. Measurements can be taken at any point in the arm or leg, or circumferentially around the head, neck, or trunk, as long as the clinician is utilizing anatomic landmarks to reproduce the measurements. Measurements in the arm are made at four points in both the affected and contralateral arm:
- Metacarpal-phalangeal joints
- Ten centimeters distal to the lateral epicondyles
- Fifteen centimeters proximal to the lateral epicondyles
- Water displacement detects changes in volume of less than 1 percent. For patients with limb lymphedema, volume difference of 200 mL or more between the affected and opposite limbs is typically considered as a cutoff point to define lymphedema.
- Bioimpedance spectroscopy — Bioimpedance spectroscopy (BIS) is a reliable and accurate tool to determine volume. Using electrical current, resistance measurements are used to compare the composition of fluid compartments.
- Computed tomography (CT) scan can demonstrate accumulation of fluid within soft tissue with good sensitivity
- MRI has also been used in the evaluation of lymphedema.
- Lymphoscintigraphy — Lymphoscintigraphy is a technique used to image the flow of fluid from the skin to the lymph nodes, particularly in the extremities.
- X-ray of lymphatic system by introducing a dye between toes or in the groin
- Genetic testing — For patients diagnosed with primary lymphedema or suspected of lymphedema tarda, referral to a medical geneticist or genetic counselling service is suggested for evaluation of the family history and recommendations for further work-up.
- Blood smear to isolate filarial worms
Stages of Lymphedema.
Staging — Lymphedema is staged using the criteria of the International Society of Lymphology. It involves two criteria to diagnose and classify lymphedema: the “softness” or “firmness” of the limb (reflecting fibrotic soft tissue changes) and the outcome after elevation:
- Stage 0 — Stage 0 lymphedema is a subclinical or latent condition where swelling is not evident despite impaired lymphatic transport. Most patients are asymptomatic, but some report a feeling of heaviness in the limb. Stage 0 may exist for months or years before the onset of overt lymphedema occurs (stage I to III).
- Stage I – There is accumulation of fluid that subsides with 24-hour limb elevation. The appearance is that of soft edema that may pit, with no evidence of dermal fibrosis. This is sometimes called reversible edema.
- Stage II – Stage II lymphedema does not resolve with 24-hour limb elevation alone. This reflects the evolution of dermal fibrosis. As the fibrosis progresses, the limb may no longer pit on examination. This is sometimes called spontaneously irreversible lymphedema.
- Stage III – Stage III lymphedema is characterized by lymphostatic elephantiasis. On exam, pitting is absent, and the skin reveals trophic skin changes such as fat deposits, acanthosis, and warty overgrowths.
Classification of lymphedema
Several classification systems are used, including the American Physical Therapy Association (APTA) & National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Of these, we prefer the APTA classification system. Both schemas are described below.
APTA uses girth as an anthropometric measurement to classify lymphedema. The maximum girth difference between the affected and unaffected limb is used to determine the class of lymphedema. See ‘Circumferential measurements‘ below):
- Mild lymphedema — maximum girth difference <3 cm
- Moderate lymphedema — 3 to 5 cm difference
- Severe lymphedema — difference >5 cm
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) — categorizes lymphedema based upon exam findings & the presence of functional impairment:
- Grade 1 — Trace thickening or faint discoloration
- Grade 2 — Marked discoloration; leathery skin texture; papillary formation; limiting instrumental activities of daily living (ADL)
- Grade 3 — Severe symptoms limiting self care ADL
Management of lymphoedema
- Compression of the affected limb to promote lymph drainage
- Wrapping the affected limb in elastic bandage to maintain continuous pressure on swollen limb to reduce the size and improve mobility
- Use of compression garments (special designed socks), stockings, or sleeves that have a comfortable fit over the swollen limb (manual lymphatic drainage/lymphatic drainage massage)
- Exercise can help fluid move from the vessels and reduce on swelling such as knee bending, wrist rotation, swimming, walking, etc for 20 to 30 minutes daily
- Routine skin care
- Liposuction in advanced stages of lymphedema when other options fail
- Anti biotic are prescribed prevent spread of infections
- Treat secondary fever with analgesics
- Ensure good diet to improve immunity
- Lymphatic venous anastomosis
- Apply pressure on the affected areas
- Complete decongestive therapy
- Surgery due to obstruction
Lymphangitis refers to inflammation of lymph vessels due bacterial infection.
Microbes in the lymph, draining the area infected, spread along the walls of lymph vessel. This may be stopped in the first lymph node or continue involving whole lymph drainage network to even blood.
Potential pathogens include
Lymphangitis commonly develops after cutaneous inoculation of microorganisms into the lymphatic vessels through a skin wound or as a complication of a distal infection.
Pathophysiology of Lymphangitis
- The major function of the lymphatic system is to resorb fluid and protein from tissues and extravascular spaces. The absence of a basement membrane beneath lymphatic endothelial cells affords the lymphatic channels a unique permeability, allowing resorption of proteins that are too large to be resorbed by venules.
- Lymphatic channels are situated in the deep dermis and subdermal tissues parallel to the veins and have a series of valves to ensure one way flow. Lymph drains via afferent lymphatics to regional lymph nodes and then by efferent lymphatics to the cisterna chyli and the thoracic duct into the subclavian vein and venous circulation.
- Lymphangitis develops after cutaneous inoculation of microorganisms that invade the lymphatic vessels and spread toward the regional lymph nodes. Organisms may invade lymphatic vessels directly through a skin wound or an abrasion or as a complication of a distal infection.
Pathophysiology of Edema
Circulation of lymph is a complex process. All body tissues are bathed in interstitial fluid and when in excess, it accumulates leading to oedema.
Therefore edema occur due to;
- Excessive production of interstitial fluid as in increased capillary permeability due to inflammation, colloid osmotic pressure in hypoproteinemia, high venous pressure in thrombosis
- Inadequate removal/ transport of interstitial fluid by lymphatic system lead to accumulation of interstitial fluids a condition called lymphoedema
Normally 2-4 liters of interstitial fluids is filtered per day and is returned to vascular circulation. Fluid flux across capillary depend on hydrostatic and oncotic pressure (positive in arterial end and negative in the venular end)
- Extremity oedema is due to right sided heart failure, constrictive pericarditis, renal diseases, liver cirrhosis and hypoproteinemia
- Acute or chronic obstruction in the venous system
- Abnormalities in lymphatic system
- Allergic disorders
Clinical Manifestation of Lymphangitis
Characterized by erythematous streaks with pain and rapid spread, or by nodular swellings along the course of the lymphatic vessels.
- Acute lymphangitis – occur in skin abrasion with infection at a distal site, such as interdigital dermatophyte infection or cellulitis of the lower leg. This may be accompanied by lymphangitis with red, tender streaks extending proximally with involvement of regional lymph nodes (lymphadenitis). Fever may also be present as a systemic symptoms.
- In individuals with normal immunity the cause is Streptococcus pyogenes; can also occur in Staphylococcus aureus infection. In immunocompromised patients, gram-negative organisms are important causes of lymphangitis following lower limb cellulitis.
- Pasteurella multocida from dog and other animal bites can result in localized infection with concomitant lymphangitis. It occurs in up to 30 percent of Erysipelothrix infections, a zoonosis occurring in persons in contact with fish and some animals. Cutaneous anthrax can present with extensive edema, regional lymphadenopathy, and lymphangitis.
- Lymphangitis associated Rickettsiosis has been described with the causative organism R. sibirica mongolotimonae and in African tick bite fever due to R. africae. The presence of an inoculation eschar suggests tick-transmitted infection.
- Nodular lymphangitis (also known as sporotrichoid lymphangitis, sporotrichoid spread, or lymphocutaneous syndrome) presents as painful or painless nodular subcutaneous swellings along the course of the lymphatic channels.
- Sporotrichosis has been described in the setting of gardening trauma or injury due to a thorn or wood splinter. It can have an incubation period of up to three months and presents in a cutaneous or a lymphocutaneous form accompanied by lymphangitis; painless ulcers may also be observed. Lesions on the upper limbs are the most common presentation
- lesions may ulcerate with accompanying regional lymphadenopathy. The incubation period between exposure and the onset of nodular lymphangitis can be prolonged and the presentation may be indolent with few or no systemic symptoms.
- Causes of nodular lymphangitis include: Sporothrix schenckii, Nocardia (most often N. brasiliensis), M. marinum, leishmaniasis, tularemia, and systemic mycoses:
- M. marinum has been described to cause “fish tank granuloma,” an entity that can occur following a hand injury while cleaning a fish tank. It has an incubation period of up to eight weeks. Infection due to rapidly growing mycobacteria can also occur in the setting of thorn or splinter injury. Other mycobacterial causes of lymphangitis include M. kansasii, M. chelonae, and M. fortuitum.
- Nocardia infections may present with cutaneous, subcutaneous, or lymphocutaneous manifestations following traumatic injury. Although this may mimic the appearance and clinical course of acute staphylococcal or streptococcal infection, the clinical course is usually much more indolent.
- Cutaneous leishmaniasis can present with subcutaneous nodules with lymphangitis or lymphadenitis up to 24 weeks following exposure. This presentation is more frequent with New World leishmaniasis caused by L. braziliensis or L. mexicana than with Old World Leishmaniasis due to L. major or L. tropica.
- Nodular lymphangitis is a rare manifestation of Francisella tularensis and Burkholderia pseudomallei infection. The initial skin lesion of F tularensis infection may be a papule or an ulcer or contain an eschar. The systemic mycoses, including coccidioidomycosis, blastomycosis, and histoplasmosis, can present with nodular lymphangitis.
Filarial lymphangitis — The presence of the parasite within the lymphatic channels causes inflammation and subsequent dilatation, thickening, tortuosity of the lymphatic channels with valvular incompetence. Often occurs in a retrograde progression with distal or peripheral spread away from the regional lymph nodes where the adult parasite resides. It can also occur as a result of inflammation due to dying parasites.
Wuchereria bancrofti, B. malayi, and B. timori are the causes of lymphangitis due to lymphatic filariasis.
Diagnosis of Lymphangitis.
- Clinical features, & laboratory analysis of clinical specimens.
- Swab, aspirate, and biopsy of the primary site, nodule, or distal ulcer for histology and microscopy (including gram, fungal and acid fast staining), as well as culture (including bacterial, fungal, and mycobacterial cultures).
- Serology (e.g., F. tularensis, Histoplasma)
- Blood film (e.g., filaria)
- Imaging —Lymphangiography (using dye injection into the lymphatics) and lymphoscintigraphy (using intradermal technetium injection at distal site of affected limb) have been used to evaluate for lymphedema and lymphatic obstruction . This may be useful if surgical management of lymphedema is a consideration.
Treatment of Lymphangitis
- Some cases of nodular lymphangitis require surgical debridement. In the setting of lymphedema with significant lymphatic obstruction, surgical intervention may also be appropriate. Pending diagnostic evaluation, empiric antibiotic therapy with activity against skin flora may be initiated.
DISEASES OF LYMPH NODES
Lymphadenitis refers to inflammation of lymph nodes due bacterial infection spreading from infected lymph vessels.
The lymph nodes become enlarged, tender, congested with blood and chemotaxins.
If the phagocytes and antibody production is overwhelmed abscess may form with in the node Neighboring tissues may become involved and infected materials may be transported to other nodes and blood
Lymphadenititis may be acute or chronic. In children cervical lymph nodes are more affected
Causes of acute lymphadenititis
- Measles Typhoid
- Cat-scratch fever Wound
- Skin infections
Causes of chronic lymphadenititis
- Unresolved acute infections
Signs and symptoms of lymphadenitis
- Tenderness of the affected nodes
- Redness of the skin around the affected nodes
- Fever in severe cases
This refers to enlargement of lymph nodes.
Causes of Lymphadenopathy
It may be local or generalized
Causes of generalized lymphadenopathy include;
- Infection like TB, HIV, syphilis
- Acute and chronic lymphoid leukemia
- Lymphoma like Hodgkin’s and Non-Hodgkin’s lymphoma
Causes of localized lymphadenopathy include
- Localized infection ie scalp infection leads to cervical lymph nodes enlargement,
- infection of the upper extremity lead to axillary lymph nodes enlargement, infection of the lower limbs lead to inguinal lymph nodes enlargement and infection of the throat or tonsils lead to mandibular lymph node enlargement
- Carcinoma that spread to lymphatics lead to regional lymphadenopathy i.e. stomach cancer lead to supraclavicular lymphadenopathy, breast cancer lead to axillary lymphadenopathy.
DISEASES OF THE SPLEEN
Splenomegaly refers to enlargement of the spleen more than its normal size (12x 7 cm).
The enlarged spleen may be non palpable but it is detectable on scan. It becomes palpable only when enlarged more than two and half times its normal size.
The spleen may be infected by blood-borne microbes or local spread of infection Enlargement of the spleen is associated with problems which include;
- Premature destruction of red blood cells
- Sequestration of red cells, white cells and platelets (pancytopenia)
- Valunabirity to traumatic rapture
- Hyperplasia of bone marrow follows as a compensatory response
Causes of splenomegaly
- Bacterial infection like endocarditic, tuberculosis, septicemia, brucellosis, syphilis and typhoid
- Viral infection like hepatitis and AIDS
- Protozoa infection like malaria, leishmaniasis and trypanosomiasis
- Fungal like histoplasmosis
- Inflammatory disorders like SLE, rheumatoid arthritis and sarcoidosis
- Congestion due to portal hypertension, hepatic vein thrombosis, chronic CCF and pericardial effusion
- Hemolytic disorders like sickle cell anemia and spherocytosis
- Infiltrative diseases of the spleen like leukemia and lymphomas
- Iron deficiency anemia and megaloblastic anemia
Signs and symptoms of splenomegaly
- Palpable spleen Fever
- Other signs of underlying disease
Management of splenomegaly
- Investigations helps in identifying the cause such as blood smear, CBC, radiological imaging and culture and biopsy.
- Treat the cause accordingly
- In severe persistent spleenism, splenectomy may be performed
This refers to lack or impairment of spleen function.
- It is due to Trauma
- Surgical removal of the spleen
- Autoplenectomy as in sickle cell due to ischemic atrophy (microvascular occlusion) Splenic atrophy in celiac disease
Signs of hypoplenism
- Recurrent bacterial infection such as streptococci, E-coli, Haemophilus influenza and Neisseria meningitides
- Severe septicaemia Intravascular coagulation Multiorgan failure
- Red cell abnomalities