Filarial Hydrocele

Etiology

Lymphatic filariasis is caused by three species of parasitic worm, Wuchereria bancrofti, Brugia malayi, and B. timori. However, it is Wuchereria bancrofti that is most commonly linked to the chronic disease manifestation of hydrocele.

In the human body, adult worms (male and female) live in lymph nodes and, after mating, produce numerous larvae called microfilariae, which migrate between the lymph system and blood channels to reach the peripheral blood vessels. When female mosquitoes, Culex, Aedes, and Anopheles (depending on the region of the world), ingest a blood meal from an actively infected person, they consume microfilariae with the blood. The larvae grow and molt repeatedly in the mosquito to produce the highly active infective larvae in about 10 to 12 days. The infective larvae then migrate and collect in the mosquito’s proboscis. The next time the mosquito bites a human host, larvae are deposited on the skin and find their way into the bloodstream through the bite wound. They develop further as they migrate through the human body to the lymphatic vessels and lymph nodes, where they develop into adult worms.

Eventually, some adult worms make their way to the scrotal lymph vessels, causing acute filarial lymphangitis, lymphangiectasia, and acute hydrocele. This may produce transient symptoms in the form of pain or nodularity. Repeated cycles of inflammation over time will lead to chronic hydrocele. Thus, a majority of men with lymphatic filariasis will eventually develop symptomatic hydroceles.[2][4][5][6][7][8][9]

Epidemiology

The disease is uncommon in the USA, and most cases are seen in immigrants or travel acquired infections. In tropical regions, mainly in low and middle-income countries, lymphatic filariasis is the most significant risk factor for the development of non-communicating hydrocele. Lymphatic filariasis is caused by infection with the mosquito-borne parasite Wuchereria bancrofti.[1][10]

While males and females are affected by this parasitic infection, only males can develop a scrotal hydrocele due to W. bancrofti’s penchant for residing in the spermatic cord lymphatics, causing scrotal nodules which cause more than 50 percent of infected men to develop chronic hydrocele over time.[2][11][12] Thus, filarial hydrocele is seen in adult males, 20 years and older, that live in over 70 tropical and subtropical countries in Africa, Asia, the Caribbean, Pacific, and South America. It is estimated to affect over 27 million men in these regions.[1][13] 

Overall, 5% of men with scrotal nodules will develop hydrocele that may persist for 18 months or longer.[2] An Egyptian study found that 14 of 16 men infected with the parasite were found to have some detectable fluid in the scrotal sac after treatment, and out of these, at least three developed chronic hydroceles.[14] 

A number of studies report lymphedema and/or hydrocele following mass drug administration for filariasis management, but other studies report no such association. Additionally, studies indicate that population-based and household surveys consistently underestimate the true prevalence of hydrocele and disability from the disease. As personal modesty may be responsible for minor hydroceles to be ignored by patients, especially when data collection is done by surveys. Therefore the reported incidence is dependent mainly on clinical examination and may be imprecise for the true extent of the disease.[15][16]

Pathophysiology

A filarial hydrocele is an accumulation of fluid, due to true hydrocele (fluid), chylocele (lymph), or hematochylocele (blood with lymph), in the scrotum. The term "filaricele" is inclusive of all three and has been suggested as the all-inclusive term in recent years. The hydrocele may be of two types: communicating and non-communicating. Non-communicating hydroceles develop with filarial infections and may present as acute or chronic conditions. In filarial infections, migration of adult worms and then there persistence in the scrotal lymph system result in a hydrocele. Chylocele may result from the rupture of lymphatic vessels inside the scrotal cavity leading to lymph ('lymphocele') or milky (chylocele) fluid collection. This may contain variable amounts of red blood cells (hematochylocele).

Acute hydroceles result from the death of these worms, often after medical therapy. Acute filarial hydrocele can be triggered by post-treatment death and/or disintegration of the worm, the filarial antigen thus produced may lead to acute filarial lymphangitis (AFL). This is followed by temporary clogging of the lymphatics by the inflammatory reaction to disintegrating worms. However, the acute response may resolve over days and weeks.[2][17] The degree to which AFL triggers or hastens the development of hydrocele in filariasis has been investigated by several authors. Norões et al. reported a 22% incidence of acute hydrocele following a single 'scrotal nodule event', either spontaneously or induced by treatment.[17]

Chronic hydroceles, on the other hand, develop due to poor functioning of the lymph system due to adult worms making their way to the scrotal lymphatics and forming scrotal nodules.[18] Depending on the extent and severity of lymphangiectasia and other cofactors such as adult worm burden, and location of adult worm in the scrotal lymphatic system (for instance, in the spermatic cord or the testicular sac area) hydrocele, chylocele and, possibly, lymph scrotum, can develop years after the initial infection. Occasionally chyluria may also be seen.[19]

There is some evidence suggesting that superimposed bacterial infection may play a role in triggering immune response due to the death and disintegration of the parasite. Wolbachia is an intracellular bacteria, in the filarial parasite, that gets released on the death of the parasite W. bancrofti. It is thought that the bacteria release causes an immune response leading to an increase in the patient's blood levels of IL-6, IL-10, and also sTNF-alpha receptors. The exact role this plays in the development of hydrocele is not understood. Recent research has implicated the endosymbiotic bacteria Wolbachia as a possible trigger in the immune reaction following the death of adult worms.[20][21]

History and Physical

A careful history and physical examination should be done. With initial infection by Wuchereria bancrofti often at a young age, and hydrocele development later in life, it is critical to ask about the region a patient lived in and any relevant travel history. History often reveals staggering effects on a patient’s life, including poor sexual function, physical disability, the effect on the ability to work, causing economic loss, and even depression.[18] A full examination, including attention to the lower extremities, is important to evaluate for other manifestations of lymphatic filariasis that may also be present.

Filarial hydroceles can be either acute or chronic. Acute hydroceles present with painful nodules in the scrotal region with or without palpable enlargement of the scrotal sac due to fluid. These are thought to be caused by the death of adult worms and may or may not be related only to treatment.[12] Although, often, there may be a history of diagnosis of filariasis followed by medical treatment. The nodules are caused by an inflammatory response to the disintegrating parasite due to lymphangitis.

Usually, the only indication of a chronic hydrocele is a painless swelling on one or both sides of the scrotal sac. The size of the hydrocele can vary from barely detectable to very large. Patients may report discomfort from the heaviness due to the swollen scrotum. Careful questioning will elicit a history of filariasis years ago and a few previous episodes of painful nodules in the scrotal area that resolved within a week.[22] Most hydrocele patients may report up to two episodes of inflammation per year, on average, of variable severity resulting in scrotal nodules.[19][23] 

Pain may be present if inflammatory lymphangitis is severe. On examination, the genitals may reveal variably sized hydrocele, some may be quite large and disfiguring at diagnosis. Patients may have thickened spermatic cord and may have numerous firm nodules in the epididymis. In long-standing hydroceles, calcification may develop, which may be palpated or visualized by imaging studies.

Evaluation

The evaluation of filarial hydrocele includes laboratory investigations e.g., complete blood count to check for eosinophilia (active filariasis), and peripheral blood examination for microfilariae. However, it is expected that the active infection will not be present by the time chronic hydrocele develops. Urinalysis may be done to check for the presence of chyluria, proteinuria, or hematuria. Rarely microfilariae may be detected in urine samples.

The best and most sensitive method to diagnose lymphatic filariasis is by detecting circulating filarial antigen (CFA) of W. bancrofti DNA in the blood. Circulating filarial antigens can also be detected by ELISA immunoassay or other rapid field tests.[24][25] Fine needle aspiration cytology may detect microfilariae or even adult worms in the lymphatics or hydrocele fluid.[26]

Other serological investigations to check for elevated levels of immunoglobulins and interleukins may be done to determine inflammatory response. Circulating filarial antigens can be detected by ELISA immunoassay with Og4C3 antibodies. In recent years several recombinant antigens, e.g., WbSXP-1, have been developed for use in immunoassays. These antigens detect circulating filarial antibodies to W. bancrofti antigens in the blood. Unlike when testing for the presence of microfilariae, the blood samples can be drawn during the daytime. Since some patients can have an asymptomatic infection, testing can be of additional help to detect and treat patients.[13][27][28]

The mainstay of imaging studies is ultrasonography (US). It can help detect even non-palpable levels of fluid collection in the tunica vaginalis. Lymphatic obstruction can be visualized by the US. The structures examined by ultrasound include visualization of the scrotal lymph vessels, testes size and morphology, epididymis for nodules, spermatic cord for nodularity, and layers of the tunica vaginalis for any fluid.[29] Ultrasound imaging allows the detection of moving adult worms in lymphatic vessels (“filarial dance sign”) and is also used for monitoring the effectiveness of treatment.[22]

Treatment / Management

The World Health Organization (WHO) created the global program to eliminate lymphatic filariasis (GPELF) in 2000 in order to eradicate the widespread filarial infections. A combination of albendazole and diethylcarbamazine (DEC) was distributed in endemic areas via mass drug administration programs. Ivermectin has also been used in combination as a treatment in some countries.[30] While drug treatment is successful for lymphatic filariasis, it is better suited for patients with early infection and to decrease transmission in general. Patients who have already developed filarial hydroceles cannot be effectively and fully managed by medical treatment alone. Surgical management is required for almost all patients with a palpable hydrocele. Additionally, medical treatment can precipitate hydrocele. However, some programs using doxycycline to treat patients with filarial hydrocele found the antibiotic could eliminate some adult worms, thereby bringing some relief. The antibiotic was found to be more successful in the earlier phase of hydrocele development.[8]

Surgery is the mainstay of treatment for filarial hydroceles. However, the surgical management of filarial hydrocele is largely not standardized. No guidelines or standardized protocols are available for the use of antibiotics, surgical techniques, dressings, and perioperative management. The goal of surgery is excision of the hydrocele as well as prevention of recurrence. Surgery for filarial hydrocele may be difficult due to the presence of fibrosis and deformity. During the procedure, damaged lymph vessels should be removed or repaired if possible.[23] (B3)

Several different surgical techniques are utilized in hydrocele repair. In a review of surgical treatments by Lim et al., it is reported that a simple hydrocelectomy can often be utilized that includes excision of the tunica with or without eversion. There is no evidence that one technique is more beneficial than the other.  Other surgical procedures may be added as dictated by the patient’s specific stage or severity of hydrocele and attendant chronic complications like fibrosis. Additional procedures may include reconstruction of the scrotal sac, resection of scrotal skin and may also involve penile reconstruction if the penis is involved.[31] Reconstruction surgery is needed when the skin of the scrotum is thickened, or when the skin has a dripping of lymphatic fluid called “lymph scrotum.” Testicular involvement is seen rarely, and orchiectomy may be needed occasionally depending on testicular damage.[32] (A1)

In a basic surgical approach, an incision is made in the scrotal midline. The hydrocele fluid is drawn out, then the tunica vaginalis is excised. With careful cauterization of blood vessels and inspection for any testicular damage, the wound is closed. Again, other procedures may need to occur depending on the damage to the testis or other tissues, and also the need for possible reconstruction procedures.[33] Selecting a surgical procedure depends on several elements. They may be dictated by the surgeon’s preferences or comfort level or training with the procedure. However, hydrocele size and thickness of the hydrocele sac, both matter when choosing the surgical procedure.[23] (B3)

The hydrocele sac can be excised fully or partially. Total excision of the hydrocele sac has shown better outcomes in terms of reduced hydrocele recurrence, and postoperative infection and complications like hematomas.[18][33] In surgical cases where lymph fistulae were present and contributing to the chronic hydrocele, excising the complete sac, as well as the removal of any lymph fistulae and dilated vessels, lead to better outcomes.[23][23] Programmatic success and outcomes can be improved by training of local practitioners and staff that perform the procedures.(B3)

Access to surgery is important in patients with filarial hydroceles. Some patients not given this option may decide to have their hydroceles drained in an unsterile manner. This sets them up for potential infection and damage to the testes over time.[32] Successful hydrocele repair has allowed patients to return to healthier lives, improved sexual functioning, and a greater likelihood of being employed. Some studies have shown that the overall benefits of surgery are much greater than the costs of the procedures over time.[3][34](B3)

Potential post-surgical complications include hematoma, infection, poor wound healing, and possible reoccurrence of the initial hydrocele.[33](B3)

Differential Diagnosis

It is important to exclude all causes of scrotal enlargement or scrotal mass. A detailed focused history, physical examination, and ultrasonography are helpful diagnostic tools. The differential diagnosis of filarial hydrocele includes all of the following:[29]

• Common hydrocele (non-infectious origin)
• Inguinal hernia
• Spermatocele
• Varicocele
• Epididymal cyst
• Testicular tumors
• Appendix testis

Other conditions that need to be excluded are idiopathic scrotal edema. In the case of painful scrotal enlargements, testicular torsion, infectious epididymo-orchitis, or orchitis should be considered as well.[35]

Prognosis

As mentioned in some of the sections above, filarial hydrocele can take a devastating toll on a person's psychosocial wellbeing. Untreated, the prognosis in general, is poor as the condition impacts multiple aspects of a patient's life. If a chronic hydrocele develops and no therapeutic intervention occurs, a patient can be physically, socially, psychologically, and economically impacted.

Commonly, males with chronic hydrocele experience sexual dysfunction and physical disability due to hydrocele growth and disfigurement. Untreated, the hydrocele creates infection risk as scrotal skin break down, and ulcerations occur. Manifestations such as lymph scrotum result in discharge that leads to frequent infections. These, in turn, can result in scrotal elephantiasis and chronic inflammation of inguinal glands.[8]

Affected men may socially withdraw due to the pain, physical disability, and limits on mobility, making it more difficult to take part in family and community activities, and enable them to perform physical labor. The enlarging size of a hydrocele can make it increasingly a challenge to lift and carry items, walk, and even stand. In addition to economic impact, the disease can reduce the likelihood of marriage and often results in poor sexual functioning.[7]

Complications

Complications of filarial hydrocele, if left untreated, may include infertility, infection risk, scrotal skin break down and ulcerative lesions, physical disability, decreased mobility, greater reliance on others for self-care, loss of employment opportunities and loss of work, social stigma, as well as a negative impact on mental health.[7] 

Various urogenital conditions can result, including inflammation of the penis, scrotum, inguinal lymph nodes, and scrotal elephantiasis.[8] Lower extremity lymphedema is a complication of filarial infection and can be seen in those with filarial hydrocele as well.[31]