Index
The lymphatic system is made up of a network of nodes and vessels throughout the body.
Its main function is to drain any tissue fluid that has not passed into the bloodstream, filter debris or the invasion of microorganisms in this fluid, and return the fluid, now known as lymph, to the bloodstream.
Sometimes large substances such as some proteins found in tissue spaces cannot pass through the wall of blood vessels.
It then returns through the lymphatic channels to the bloodstream. Eventually, all of the lymph drains into the venous circulation that carries oxygen-deficient blood to the heart.
Sometimes a lymph node or lymphatic vessel can become inflamed and this is known as lymphadenitis and lymphangitis respectively.
There are several causes of this inflammation that disrupts the normal drainage function of the lymphatic system. Therefore, tissue fluid cannot be passed back into the bloodstream as it normally does.
Fluid accumulates particularly within the lower extremities and causes swelling of the affected part which is known as lymphedema.
If this is permanent and lymphatic drainage in the area is permanently compromised, a condition known as elephantiasis can develop.
Elephantiasis is a condition in which the skin thickens and hardens after excessive swelling associated with the accumulation of lymph (lymphedema).
It is most marked in the lower extremities, but it also commonly affects the scrotum in men, and it can also affect the breasts and arms.
Elephantiasis is commonly caused by lymphatic filariasis.
The terms elephantiasis and lymphatic philiarisis are often used interchangeably, but lymphatic filariasis refers to infection of the lymphatics with the filarial worm, while elephantiasis is the gross deformity caused by lymphedema, often as a result of this infection.
It can be misleading because elephantiasis can occur for other reasons, such as exposure to certain types of soils even without infection.
Since the latter accounts for a smaller number of elephantiasis cases, it often does not receive the same attention as the role of lymphatic filariasis in the development of elephantiasis.
Another common but incorrect term used for elephantiasis is elephantitis. It is often the result of the word elephantiasis being misheard.
Types of elephantiasis
Since most cases are due to lymphatic filariasis, it is important to know the disease, how it is contracted, and the mechanism of the disease process that ultimately leads to elephantiasis.
However, another condition known as podoconiosis can also cause lymphedema and later elephantiasis.
It is not due to an infection but to an abnormal inflammatory reaction to certain types of soil.
Therefore, elephantiasis resulting from lymphatic filariasis is known as filarial elephantiasis, while others are called non-filarial elephantiasis.
Elephantiasis filaria
Lymphatic filariasis occurs when a parasitic worm, or nematode, enters the lymphatic system.
There are three such worms in human infections: Wuchereria bancrofti, Brugia malayi, or Brugia timori.
Of these three, Wuchereria bancrofti is the most common cause accounting for about 90% of lymphatic filariasis cases.
The immature form of the worm, known as the larva, is carried by certain species of mosquitoes: Culex, Aedes, and Anopheles species.
The larva is the infectious form of the nematode worm.
When the mosquito bites a human to feed on blood, the larvae settle on the skin.
It then migrates to the lymphatic system where it resides and grows into the adult worm that is 1 to 4 inches long.
This growth is slow and takes an average of seven years, although there have been cases where it has taken up to forty years.
During this period, however, there are small larvae (microfilariae) that circulate in the bloodstream.
These microfilariae can be ingested by mosquitoes that feed on the infected person and then the mosquito can transmit the disease to another person in a subsequent feeding.
Elephantiasis no filaria
Although several other causes beyond filariasis can cause severe lymphedema, not many can be as severe as a condition known as podoconiosis or have the likelihood of progressing to elephantiasis.
Podoconiosis is seen most frequently in Africa (tropical regions) and to a lesser extent in Central America and northwestern India.
It is an abnormal inflammatory reaction caused by exposure to irritating soil. It is not an infection.
There is evidence to suggest that this reaction is determined by genetic factors and, therefore, not all people exposed to this type of soil will be affected.
Contact with the ground is made by walking barefoot and develops over a period of time.
Disease development
Elephantiasis filaria
Lymphatic filariasis can be asymptomatic, acute, or chronic.
It is a complex disease where the exact mechanism is not fully understood.
The worm appears to secrete toxins and cause changes in the body’s immune response.
Some of these are similar to an allergic reaction that can cause swelling of the lymphatic vessel.
This results in dysfunction of lymphatic drainage beyond the blockage caused by the presence of the worm.
There are also certain types of bacteria that infect the parasite and coexist with it to cause inflammation in the body. Elephantiasis is a result of chronic lymphatic filariasis.
Here the worms secrete toxins that cause excessive dilation of the lymphatic vessels known as lymphangiectasia.
This dilation leads to permanent dysfunction of the lymphatic vessel and severely interrupts drainage. It is further complicated by the backward flow of the lymph.
There is an excessive accumulation of lymphatic and tissue fluid that cannot be drained and the affected area becomes inflamed (lymphedema and hydrocele).
The skin then hardens and the condition is now known as elephantiasis.
Parts of the blood flow to the area are compromised by excessive swelling and some tissues may die and become gangrenous.
Bacteria can also infect the skin (secondary infection) and further complicate the condition.
Elefantiasis no filarial
In podoconiosis, repeated exposure to the irritant soil of bare feet causes recurrent or persistent lymphadenitis and lymphangitis.
Over time, the lymphatics in the area are compromised and the swelling becomes hard and fibrotic.
Elephantiasis is seen in a chronic form, which is preceded by acute episodes.
Hardening and thickening of the skin combined with general swelling of the foot and leg as a result of severe lymphedema leads to elephantiasis.
The disease is almost always limited to the foot and leg and rarely extends above the knee.
Causes
Filarial elephantiasis is caused by the parasitic nematode worm that is transmitted by certain species of mosquitoes.
It is aggravated by the presence of rickettsial-like bacteria that infect, but do not destroy, the worm.
Elephantiasis symptoms are the result of long-term bites made by mosquitoes over a long period of time in certain countries where a particular type of roundworm is known to exist.
This syndrome is caused by an infection with a type of nematode parasite known as a filarial worm.
This parasite is transmitted from one human to another through a female mosquito that eventually develops into an adult worm and resides within the lymphatic system of a human.
Eight different types of filarial worms are known to affect humans that can be divided according to the area of the body affected, and these are:
- Subcutaneous filariasis is caused by infection with oases such as, Onchocerca volvulus, Loa loa, and Mansonella streptocerca, all of which occupy the fatty layer of the skin.
- Lymphatic filariasis is caused by parasites such as Wuchereria bancrofti, Brugia malayi, and Brugia timori, which live within the lymphatic system.
- Another group of filarial worms include: Mansonella streptocerca, Mansonella ozzardi, and Mansonella perstans that occupy the serous cavity that is present in the abdomen.
Podoconiosis is caused by exposure to red clay soil from volcanic deposits on a regular basis as a result of walking barefoot on this type of soil.
The reaction to soil in podoconiosis also appears to be due to genetic factors.
Other causes of non-filarial elephantiasis that can only progress to elephantiasis in a minority of cases include tuberculosis, leishmaniasis, leprosy, sexually transmitted diseases such as lymphogranuloma venereum, leprosy, and repeated streptococcal infections.
These pathogens cause severe lymphatic damage that allows persistent lymphedema and the subsequent development of elephantiasis.
However, these diseases are more likely to affect other organs and cause various other symptoms.
The role of these pathogens in the development of elephantiasis does not receive as much attention as in the case of lymphatic filariasis and podoconiosis to a lesser extent.
Risk factors for filarial and non-filarial elephantiasis vary.
Both types are most common in tropical regions of Africa, Central and South America, and Southeast Asia.
Poor mosquito control and an infected population within an area are other risk factors.
Poverty or cultural practices that lead a person to walk barefoot can be another risk factor for developing podoconiosis.
Farmers who come into contact with irritating soil on a regular basis are also more likely to develop podoconiosis within these high-risk areas.
Life cycle of the filarial parasite
The female mosquito is responsible for the transfer of this disease from human to human, as it feeds on human blood.
The transfer process begins when the mosquito begins to feed on the blood through human skin and these filarial worms enter the system.
Of all worms, those in their third stage of development successfully enter the bite wound and continue to become adults and remain within the human lymphatic system.
Symptoms of elephantiasis
One of the most distinguished elephantiasis symptoms is gross enlargement and great swelling of a particular area of the body as a result of fluid accumulation.
A person’s arms and legs are generally the most affected areas.
A person’s arm or leg can swell many times more than normal, giving it the appearance of elephant skin.
Although the legs, arms, and genitals are the most affected parts, elephantiasis symptoms can also be experienced in other parts of the body.
Symptoms can vary in lymphatic filariasis and podoconiosis before the development of elephantiasis.
Initially there are symptoms of inflammation of the lymph nodes (lymphadenitis), lymphatic vessels (lymphangitis), and swelling due to reduced lymph drainage (lymphedema).
Eventually there is a copious accumulation of fluids (hydrocele) with massive enlargement of the affected part.
The skin in the affected area generally tends to become extremely dry, thickened, and may also become ulcerated and darkened (hyperkeratosis).
Elephantiasis symptoms can start when the person has a high fever, random chills in the body, and a general feeling of being unwell.
Elephantiasis can also affect and damage the male and female external genitalia.
In a male, dilation of the scrotum and the penis that retracts under the thickened skin is considered an important symptom of elephantiasis.
The outer areas of the female genital organs or the vulva can also be adversely affected by the symptoms of elephantiasis.
A thick skin covered tumor mass with infested ulcers may develop between the thighs and, in some cases, may also be accompanied by enlarged lymph nodes in the legs.
In some women, their breasts can also enlarge.
Other underlying damage that occurs in the lymphatic system can leave people susceptible to secondary fungal and bacterial infections that can make the situation worse.
Depending on the cause, specific symptoms are experienced such as:
lymphatic filariasis
Lymphatic filariasis is largely asymptomatic in most cases.
In the acute stages there is fever, pain and tenderness of the affected area with red streaks on the skin (erythema) that correspond to the swollen lymphatic channel.
Inflammation is also common, although in the acute stages this can be temporary.
The scrotum may appear swollen and inflamed as the spermatic cord, epididymis, and testicle are commonly affected in lymphatic filariasis.
Lymph nodes within the affected area are also enlarged. The swollen area is usually soft and smooth in the early stages.
In the chronic form there is a gradual and progressive enlargement of the affected area, often most noticeable in the lower limb and scrotum.
The scrotum enlarges and becomes massive. The skin over the affected areas becomes thick and rough.
Cracks (fissures) begin to form in the skin and bacterial skin infections develop with localized tenderness, pain, warmth, and sometimes pus discharge.
The swelling continues and becomes permanent.
Podoconiosis
The first symptoms associated with acute attacks mainly include burning and itching of the foot and lower leg.
The soles of the feet may be swollen and oozing.
There may be additional symptoms, such as leg pain, heat in the affected area, and fever.
The scrotum and testicles are generally not involved, as is the case with lymphatic filariasis.
These symptoms can be persistent although the intensity can vary due to constant contact with the irritating soil.
As the condition progresses, other changes develop that precede elephantiasis.
The skin thickens, the toes stiffen, making normal walking difficult, and there may be skin outgrowths that resemble massive warts.
Little by little, the inflammation changes from soft to hard and rough.
Diagnosis
Elephantiasis can be diagnosed based on the findings of a clinical examination.
There are several methods for diagnosing lymphatic filariasis and differentiating it from non-filarial causes.
Blood tests not only help with this differentiation, but can be helpful in earlier stages before elephantiasis develops.
These tests can confirm the presence of filarial worms.
Initially, a complete blood count can indicate very high levels of eosinophils.
In the process of diagnosing lymphatic filariasis, it is mandatory to know the history of the vector.
It is believed that the short period of exposure of the vector will not cause a high exposure of microfilaria, so it will not lead to disease.
Whereas in the longer time of exposure of the host with the vector it can culminate in microfilaremia.
Elephantiasis antigen detection
The antigen detection test is selective for lymphatic filariasis.
The test can differentiate microfilarial disease.
Antigen detection is a good diagnostic process, due to the sensitivity of the process.
It can detect microfilmias in its low amount in blood or skin.
The test for the detection of microfilariae is only possible when the adult worm is alive or in active form, when the adult worm dies it becomes undetectable for this test. It is the biggest drawback of this test.
An immunochromatographic test is also a useful test for antigen detection.
It is more advantageous than others because it takes a few minutes to prepare.
A highly sensitive enzyme-linked immunosorbent assay is also useful for diagnostic purposes, especially for Wuchereria bancrofti infection, but it takes longer to complete the analysis.
X-ray screening for elephantiasis
Dead worms cannot be easily detected in the antigen test.
Radiography is effective in identifying the dead worm in tissue.
Although it is sometimes limited due to the detection of dead worms only.
Ultrasound for the diagnosis of elephantiasis
Ultrasound is a useful technique for the diagnosis of live adult filarial worms, especially for the diagnosis of Wuchereria bancrofti in the lymphatic vessels of the scrotum.
Detect the worm by its Brownian-like movement (filarial dance sign).
For the dead and immature worm it is not a useful process as in the case of filarial lymphedema, where the adult worm does not show its presence.
In many cases, scrotal ultrasound is not suitable for patients with Brugia malayi infection, as its presence on the genitals is negligible.
An approach diagnostic study concluded that the ultrasonography method is adequate for the detection of Brugia malayi parasites in the lymphatic vessels of the thigh, epitrochlear region, axilla, and / or popliteal fossa.
Detection of microfilariae in elephantiasis
Microfilariae detection is a widely used technique for many years; still, it is receiving attention from many diagnostic experts. It is a highly consistent method.
In this detection technique, the microfilariae load of the peripheral blood is detected.
This method detects the microfilaria in the initial stage so that some time helps the patient to heal without presenting any clinical symptoms.
It is well established that the presence of lymphodema causes the disappearance of the microfilaria from the systemic circulation.
At night, when the microfilariae population is highest, it is the right time for venous blood collection.
In the microfilariae detection process, the collected blood sample must be filtered through the millepore system, which will be accomplished by identifying the microfilariae load.
In an emergency, diethylcarbamazine can be used to induce microfilariae loading during the day and the blood sample can be drawn during the day, followed by nucleopore filtration for concentration.
Instead of the venous blood sample for the capillary blood test technique, the finger prick technique may be useful, because capillary blood contains more microfilaria (Brugia malayi, Brugia timori, Wuchereria bancrofti) than venous blood.
For the differentiation of microfilariae based on morphology, the staining technique can provide better results.
Diagnosis of skin lesions and elephantiasis
Subcutaneous filariasis can be better detected by skin biopsy, in this specific method microfilariae of Onchocerca volvulus and Mansonella streptocerca are usually detected.
A biopsy is the process of examining highly infected areas, such as the iliac crest or calves.
Skin clippings are selective for microfilar species.
Skin cuts must be free of blood, so it is best to use a needle and a scalpel.
Examination through the microscope is sufficient to differentiate microfilariae according to their morphology, since Onchocerca volvulus can be easily detected due to its specific morphology (long headspace and flexed tail).
For more permanent preparations, tissue culture can be arranged with a Giemsa stain.
Lymphoscintigraphy and diagnosis of elephantiasis
Lymphoscintigraphy is a sensitive technique, where abnormalities in the lymphatic system can be detected early, even before symptoms appear.
In this technique, radiolabeled albumin or dextran is induced.
Radioactive agents provide an image with the aid of a gamma camera to verify structural variation.
These images provide information on the complete functioning of the lymphatic systems, such as lymphatic dilation, dermal flow, and obstruction of the affected limb.
Polymerase chain reaction and elephantiasis diagnosis
The polymerase chain reaction is a technique used for the amplification of deoxyribonucleic acid. Using deoxyribonucleic acid probes it is highly specific and sensitive.
It is the useful technique to detect the deoxyribonucleic acid of the parasite both in humans and in vectors.
It is suitable for the detection of Wuchereria bancrofti.
A modified polymerase chain reaction technique is restriction fragment length polymorphism which can easily differentiate parasites, however it may take a day to complete the process.
Treatment of elephantiasis
The elephantiasis treatment procedure depends on the symptoms of the elephantiasis, which generally involves treating the underlying conditions.
Treatment of elephantiasis involves a combination of medical and surgical measures that depend on the severity of the condition.
Treatment with podoconiosis is highly dependent on hygiene and avoiding contact with the ground, as well as other conservative measures such as compression and elevation of the legs.
Eventually surgery may be necessary.
Filariasis is a complicated disease and cannot be easily treated.
The early stages of infection can cause damage.
Reinfection is a major concern for people living in endemic areas.
Transmission of the parasite by Brugia malayi, Brugia timori, Wuchereria bancrofti, as well as tropical pulmonary eosinophilia and loiasis (Loa loa) should be prevented to reduce filariasis.
Medication
These medications are used to treat filariasis by eradicating the parasitic worm. The main parasite i.e. lymphatic filariasis is treated with the help of diethylcarbamazine.
Diethylcarbamazine is an anthelmintic drug used to kill microfilariae and adult worms.
Side effects are more prominent due to the worm’s immune response to death.
Diethylcarbamazine in a single annual dose of 6mg / kg is highly effective against microfilariae and adult worms as well.
The effect of this drug is maintained for more than a year and the level of microfilariae in the blood is decreasing.
There has been a successful decrease in microfilarial infections as well as a lower prevalence of hydrocele in South India from the mass administration of diethylcarbamazine drugs.
Another interesting treatment of filariasis is the addition of diethylcarbamazine in a dose of 0.1-0.5% concentration in table salt and should be administered for a year.
Albendazole is another drug that is used in conjunction with diethylcarbamazine.
Albendazole is a broad-spectrum anthelmintic drug and works by binding tubulin molecules, thereby killing adult filarial worms and inhibiting microtubule polymerization.
Ivermectin is a broad-spectrum antiparasitic drug that is used in conjunction with albendazole, instead of diethylcarbamazine, in areas where Onchocerciasis or river blindness is endemic.
Ivermectin is a synthetic macrocyclic lactone molecule that is used as a broad spectrum antiparasitic drug.
The mechanism of action of this drug includes killing microfilaria directly by binding and opening glutamate-activated chloride ion channels in nerve and muscle cells.
As a result of this, cells became hyperpolarized and then paralyzed leading to microfilarial death.
The other mechanism of action of ivermectin is believed to potentiate the actions of the inhibitory neurotransmitter gamma aminobutyric acid, which ultimately paralyzes and kills the microfilaria.
However, ivermectin does not kill adult worms, it can sterilize them, thus reducing the possibility of microfilaremia.
Antibiotics can be used to treat bacterial cellulitis that arises secondary to massive lymphedema and elephantiasis.
Terapia anti-wolbachial
It is a treatment that takes advantage of the relationship between the Wolbachia bacteria and the parasite.
Larval development, embryogenesis, and survival are possible due to the symbiotic relationship between the parasite and the Wolbachia bacterium.
Because all filarial nematode species depend on the bacteria for the viability of the adult worm, antibiotics can be used as a new defense against this disease.
Surgery
In many cases, medical treatment and therapies are not enough, in such cases surgery becomes a necessity.
The surgery aims to remove excess tissue and certain lymph nodes and drain any fluid buildup (hydrocele) in the area.
It is not curative and if effective lymphatic drainage cannot be established, the inflammation may recur.
Prevention
Preventive measures to avoid elephantiasis are not only indicated for a person with lymphatic filariasis or podoconiosis, but also for other high-risk contacts who may develop these conditions.
In terms of preventing lymphatic filariasis in endemic areas, a single dose of diethylcarbamazine can be administered to the entire population annually and effective mosquito control measures should be implemented. This reduces the chances of transmission.
Proper footwear is important to prevent podoconiosis.
In both conditions, proper hygiene and prompt medical attention for bacterial infections of the affected area can help prevent the development of elephantiasis, especially in combination with other therapeutic measures.
Bandaging the area while it is still a mild swelling and elevating the legs to drain the fluid is also helpful in slowing the progression of elephantiasis.
The bandage should only be considered when directed by a physician and should be modified and monitored periodically to identify the occurrence of any secondary bacterial infections.
Ultimately, therapeutic measures are needed to treat the underlying filariasis or other infections.
Complications associated with elephantiasis
If left untreated, elephantiasis can get complicated to very dangerous levels, even in the early stages.
There are some complications that can occur like:
- It is a very serious condition in which fluid builds up in the testicles in men who have suffered from elephantiasis. This is a very serious and painful condition that can render a man powerless. Similarly, there is another painful condition in which the male penis and scrotum are affected.
- Elephantiasis can infect the lungs and cause lung damage in the form of eposinophilia. The number of eosinophils can increase in the blood. This is a condition that is commonly characterized by a cough and fever.
- Prolonged elephantiasis can cause kidney failure.
