Filarial chylous ascites with chylothorax: challenge of diagnosis and management case report

Abstract

Background

Chylous ascites (CA), an uncommon clinical condition, is defined as a milky-appearing, triglyceride-rich peritoneal fluid in the abdominal cavity. It may be due to malignancy or cirrhosis in developed countries or infections such as tuberculosis or filariasis in developing countries. This report presents a female patient with chylous ascites with chylothorax secondary to lymphatic filariasis after the exclusion of other etiologies.

Case presentation

A 33-year-old female, from Damietta, Egypt, was referred to us complaining of abdominal distension and easy fatigability for 5 months. The patient was diagnosed to have elephantiasis of both lower limbs caused by filariasis and treated by ant-filarial therapy for 9 years. Aspirated ascitic fluid was milky in appearance and rich in triglyceride. All other causes of chylous ascites were excluded by ascetic fluid analysis (chemical, microbiological, and pathological). The patient was treated with diethylcarbamazine (DEC), albendazole, pheniramine, and hydrocortisone followed by a therapeutic pleural and ascitic tapping but ascites re-accumulate. With the addition of doxycycline and Somatostatin/ocreotide, the ascites gradually decreased. Three months later, the patient came back with a significant increase in ascites, and paracentesis was done.

Conclusion

Despite rarity, filarial chylous ascites remains a challenge, and the only effective treatment is still repeated aspiration of the accumulated fluid. More work and discussion are needed.

Introduction

Chylous ascites (CA) is defined as a milky-appearing, triglyceride-rich peritoneal fluid in the abdominal cavity. It is an uncommon clinical condition that was first reported in 1912. It is characterized by the accumulation of true chyle from thoracic or intestinal lymph [1]. Various etiologies have been described, and it usually occurs due to trauma, rupture of the lymphatics secondary to obstruction, or an increase in the peritoneal lymphatic pressure. CA is rich in nutrients and immunoglobulins that become biologically unavailable after accumulating in the peritoneal cavity. This can lead to dehydration, electrolyte imbalance, malnutrition, and suppression of the immune system. It can be associated with a high mortality rate that can reach up to 40 to 70%, depending on the underlying etiology. Therefore, prompt diagnosis and treatment are warranted [2].

In Western countries, abdominal malignancy and cirrhosis are considered the main causes of CA. In developing and eastern countries, the majority are secondary to infections, such as tuberculosis and filariasis [3,4,5]. However, a review of 190 patients with CA identified a total of 41 different etiologies. The most common cause was lymphatic anomalies (32%), which are more prevalent in the pediatric population. Malignant diseases were the second common etiology (7%). Cirrhosis and mycobacterial infections were identified as the cause of CA in 11% and 10% of the cases, respectively [6].

Lymphatic filariasis is a common disease in the tropical and subtropical areas of the world. Lymphatic obstruction and the associated complications caused by the adult worms are an important cause of morbidity and cosmetic disfigurement. Most of these patients require shunt surgery to divert lymph flow. We report a patient presented with chylous ascites with chylothorax secondary to lymphatic filariasis after exclusion of other etiologies.

Lymphatic filariasis, commonly known as elephantiasis, is a neglected tropical disease. Infection occurs when filarial parasites are transmitted to humans through mosquitoes. Infection is usually acquired in childhood and causes hidden damage to the lymphatic system.

The painful and profoundly disfiguring visible manifestations of the disease—lymphedema, elephantiasis, and scrotal swelling—occur later in life and can lead to permanent disability. These patients are not only physically disabled, but also suffer mental, social, and financial losses contributing to stigma and poverty (World Health Organization 1 June 2023).

The disease spreads from person to person by mosquito bites. When a mosquito bites a person, who has lymphatic filariasis, microscopic worms circulating in the person’s blood enter and infect the mosquito. When the infected mosquito bites another person, the microscopic worms pass from the mosquito through the skin and travel to the lymph vessels. In the lymph vessels, they grow into adults. An adult worm lives for about 5–7 years. The adult worms mate and release millions of microscopic worms, called microfilariae, into the blood. People with the worms in their blood can spread the infection to others through mosquitoes (Cause and transmission (CDC September 17, 2020)).

Lymphatic filariasis is caused by infection with parasites classified as nematodes (roundworms) of the family Filariodidea. There are 3 types of these thread-like filarial worms:

• Wuchereria bancrofti, which is responsible for 90% of the cases

• Brugia malayi, which causes most of the remainder of the cases

• Brugia timori, which also causes the disease

Adult worms nest in the lymphatic vessels and disrupt the normal function of the lymphatic system. The worms can live for approximately 6–8 years and, during their lifetime, produce millions of microfilariae (immature larvae) that circulate in the blood.

Mosquitoes are infected with microfilariae by ingesting blood when biting an infected host. Microfilariae mature into infective larvae within the mosquito. When infected mosquitoes bite people, mature parasite larvae are deposited on the skin, from where they can enter the body. The larvae then migrate to the lymphatic vessels where they develop into adult worms, thus continuing a cycle of transmission.

Lymphatic filariasis is transmitted by different types of mosquitoes, for example by the Culex mosquito, widespread across urban and semi-urban areas, Anopheles, mainly found in rural areas, and Aedes, mainly in endemic islands in the Pacific (World Health Organization 1 June 2023).

Case report

A 33-year-old female, from Damietta, Egypt, was referred to us complaining of abdominal distension and easy fatigability for 5 months during which she received medications in the form of liver support and diuretics with no response. There is no history suggestive of hepatic, renal, or cardiac diseases. There is also no history of malignancy or surgical operations. The patient was diagnosed to have elephantiasis of both lower limbs caused by filariasis and treated by ant-filarial therapy for 9 years.

On examination, the patient was afebrile, with normal pulse and blood pressure. There was no neck vein distension. She had bilateral thickened skin on both breasts, where breath sound was not audible in the right lower zone, and she had moderate ascites and nonpitting, nonreversible, thickened, and nodular appearance of the skin of both legs up to the inguinal region, more at the left side, classified as elephantiasis (female patient) (Fig. 1).

Fig. 1

Lymphatic filariasis

Laboratory evaluation revealed a hemoglobin level 14.5 gm%, WBC count 4600/cumm, polymorphs 67%, monocyte 12.5%, lymphocytes 20%, and platelets count 190,000. Liver function tests, serum creatinine, and electrolytes were normal except for hypoalbuminemia serum albumin 2.2 mg, CRP 112, and procalcitonin 0.04 ng/mL (negative). The urine examination was normal. HBsAg and anti-HCV Ab were negative, HIV negative, serum amylase and lipase were normal, and tumor markers CEA, CA-125, CA19-9, and AFP were normal.

Ultrasound of the abdomen showed moderate ascites with normal liver and spleen.

According to the Egyptian Club of Ascites (ECA) 2022, algorithmic diagnostic workup for evaluating adult patients with ascites when imaging showed no finding, diagnostic aspiration was done ((R) Sakr et al., Afro-Egypt J Infect Endem Dis 2022;12(2):186–193).

However, most often, the diagnosis of CA is not suspected before performing a diagnostic paracentesis [1].

Cárdenas A., Chopra S. Chylous ascites. American Journal of Gastroenterology. 2002;97(8):1896–1900. https://doi.org/10.1016/S0002-9270(02)04268-5. [PubMed] [CrossRef] [Google Scholar.

Abdominal paracentesis with ascetic fluid examination (physical and laboratory based) should be done in every case of ascites parallel to imaging studies. Ascitic fluid analysis should be done for cell count, total protein, albumin, and cultures in all patients as well as other tests in selected cases. A serum to ascites albumin gradient (SAAG) ≥ 1.1 g/dl has 97% accuracy for diagnosis of ascites due to portal hypertension whether due to cirrhosis, BCS, SOS, or PV thrombosis, < 1.1 = peritoneal disease which is TB or malignant infiltrations [7]. new. Biggins W, Angeli P, Garcia-Tsao G, Ginès P, Ling S, Nadim K et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021, Vol. 74, No. 2.

Aspirated ascitic fluid was milky in appearance (Fig. 2). Chemical analysis of ascetic fluid revealed WBCs 400 cumm with prominent lymphocyte, albumin 0.8 g/dl, LDH 71 units/L, ascitic cholesterol 58 mg/dl, ascitic triglyceride 550 mg/dl, and total protein 726 U/L (up to 40).

Fig. 2

Chylous ascitic fluid

Simultaneous measurement of serum albumin was 1.9 g/dl, and SAAG was calculated to be 1.1.

Microbiological examination of ascetic fluid revealed no growth, negative acid-fast bacilli.

Both adenosine deaminase (ADA) and expert gene for tuberculosis were negative.

Pathological examination showed moderate lymphocytosis, no malignant cells.

Her X-ray chest showed a mild right-sided pleural effusion.

After the exclusion of surgical procedures and infections, she was referred to Damietta Oncology Center to exclude malignancy as a cause of chylous ascites.

At Damietta Oncology Center, bilateral sonomammography revealed breast density matches with American College of Radiology class C (ACRC) bilateral thickened skin, no micro or macro calcifications, normal nipple, no definite masses seen, no solid or cystic masses, no dilated duct, and no pathological axillary LNS seen.

Post contrast CT scan of the chest showed moderate right pleural effusion, no CT evidence of hilar mediastinal lymphadenopathy, nor pericardial effusion, and normal appearance of the great vessels of the thorax.

Post contrast CT scan of the abdomen showed moderate abdominal ascites, normal liver, spleen, both kidneys, IVC, and pelvic organ, and no solid or cystic masses or lymphadenopathy. Abdominal MRI matched with CT scan.

Thoracocenteses were done and investigated which showed as aspirated ascites.

Serologic techniques provide an alternative to microscopic detection of microfilariae for the diagnosis of lymphatic filariasis. Because lymphedema may develop many years after infection, lab tests are often negative with these patients (CDC September 17, 2020).

According to Egyptian Clinical Guidelines for management of Infectious Diseases (First Edition 2017) which diagnosed confirmed cases of filariasis as follows, the presence of microfilaria in nocturnal peripheral blood sample or detection of filarial antibodies by serology or clinically chronic cases which is laboratory negative.

The patient was diagnosed with chylous ascites due to lymphatic filariasis based on the chronic lymphatic filariasis, exclusion of other causes such as postsurgical or malignancy, and ascitic triglyceride 550 mg/dl more than 200.

Inspite the patient was treated 9 years by anti-filarial therapy before being diagnosed with filarial chylous ascites and may keep treating because the adherence with therapy is not confirmed, and while this drug does not kill all of the adult worms, it does prevent infected people from giving the disease to someone else (CDC September 17, 2020).

The patient was treated with diethylcarbamazine (DEC) 300 mg/day in 3 divided doses, albendazole 400 mg/day with pheniramine and hydrocortisone followed by a therapeutic pleural and ascitic tapping. An oral diet of low-fat, high-protein, medium-chain triglycerides, and fat-soluble vitamins was started, and abdominal distention increased.

With the addition of doxycycline 200 mg/day and somatostatin/ocreotide (100 µg) eight hours subcutaneously, the ascites gradually decreased. Somatostatin/ocreotide was given for 3 weeks. Other drugs (doxycycline and albendazole) were continued for 6 weeks. After 6 weeks, the patient improved with minimal ascites (by US), minimal pleural effusion (by chest X-ray), and no fever. Three months later, the patient came back with a significant increase in ascites, and repeated paracentesis was done for 1 year.

During the search for medical treatment, do not forget the management of morbidity and disability prevention (MMDP) in lymphatic filariasis requires a broad strategy involving both secondary and tertiary prevention. Secondary prevention includes simple hygiene measures, such as basic skin care and exercise, to prevent ADL and the progression of lymphedema to elephantiasis. For the management of hydrocoele, surgery may be appropriate. Tertiary prevention includes psychological and socioeconomic support for people with disabling conditions to ensure that they have equal access to rehabilitation services and opportunities for health, education, and income. Activities beyond medical care and rehabilitation include promoting positive attitudes towards people with disabilities, preventing the causes of disabilities, providing education and training, supporting local initiatives, and supporting micro- and macro-income-generating schemes. The activities can also include education of families and communities to help patients with lymphatic filariasis to fulfil their roles in society. Thus, vocational training and appropriate psychological support may be necessary to overcome the depression and economic loss associated with the disease. MMDP must be continued in endemic communities after MDA has stopped and after validation, as chronically affected patients are likely to remain in these communities (World Health Organization 1 June 2023).

The patient consulted at the Egyptian Club of Asities as surgical, intervention radiology and vascular which concluded neither benefits of new imaging as lymphography and lymphoscintigraphy nor surgical intervention.

Discussion

All paragraphs are cited as literatures which are limited in filarial chylous ascites.

Human lymphatic filariasis is caused by infections with W. bancrofti, Brugia malayi, or Brugia timori. These parasites are found in many tropical and subtropical areas of the world. Most infections are asymptomatic, but the living adult worm causes progressive lymphatic vessel dilation and dysfunction. Lymphatic dysfunction may lead to lymphedema of the leg, scrotum, penis, arm, or breast, which can increase in severity as a result of recurrent secondary bacterial infections [8, 9].

The adult worms live in the lymphatics and can cause lymphangiectasia by obstructing lymph flow. Filariasis is the most common cause of acquired lymphedema in the world [7]. The diagnosis is made by identifying microfilariae on a Giemsa-stained thick blood film. Blood must be drawn at night, since the microfilaria circulates at night, when their vector, the mosquito, is most likely to bite. Serologic techniques provide an alternative to microscopic detection of microfilariae for the diagnosis of lymphatic filariasis. Because lymphedema may develop many years after infection, lab tests are often negative in those patients (CDC 2020).

Acording to Egyptian Guidelines of Infectious In Fever Hospital which diagnosed Confirmed case of Filairasis (2018) as follow The presence of microfilaria in nocturnal peripheral blood sample or Detection of filarial antibodies by serology or clinically chronic cases which is laboratory negative.

Diethylcarbamazine is used mainly as a microfilaricide even though it does have macrofilaricidal properties. It is usually effective in treating tropical pulmonary eosinophilia (TPE), and its mechanism of action is thought to involve sensitizing the microfilariae to phagocytosis. For chronic manifestations of lymphatic filariasis, such as lymphedema and hydrocele, specific lymphedema treatment (including hygiene, skin care, physiotherapy, and in some cases, antibiotics) and surgical repair, respectively, are recommended [9]. Doxycycline is a new drug for reducing the microfilaria burden as it depletes the Wolbachia symbionts from W. bancrofti [10]. Somatostatin administration reduced lymphorrhagia from a ruptured thoracic duct [11], and Raimondi et al. [12] described a long-term remission of post-traumatic chyluria following 7 days of intravenous somatostatin infusion. However, the short half-life of somatostatin limits its use to intravenous continuous infusion only. Octreotide is an octapeptide synthetic somatostatin analogue with a circulating half-life of about 2 h [13]. Thus, it can be administered subcutaneously every 8 h with a less pronounced effect on glucose metabolism. The mechanism of action of octreotide is at present unknown. However, evidence for a role of somatostatin in lipid homeostasis has been reported [14]. In dogs, somatostatin administration reduces lymph flow in the thoracic duct and may as well reduce chylomicron synthesis and transport [15]. Nakabayashi et al. [15] reported a relationship between the reduction of lymph flow through the thoracic duct and the dose of somatostatin administered. As there are no specific guidelines as far as the dose and duration of somatostatin/ octreotide are concerned in patients with chylous ascites, we chose the optimum, tolerable, and affordable dose for our patient. Somatostatin / octreotide is a safe and effective therapy for chylous ascites which has successfully been used in patients secondary to pancreatitis, post-liver transplant, malignancy, portal vein thrombosis, and idiopathic causes, improving their quality of life.

The prognosis among patients with chylous ascites (CA) depends on the underlying etiology. CA can be associated with a high mortality rate that can reach up to 40 to 70%. It can be highly morbid [3, 16]. The prognosis of CA cases that are non-surgical is worse than surgical cases [17]. Although malignancies are considered a significant cause of CA, it is associated with improved survival when treated, especially in patients with lymphomas due to the recent introduction of better chemotherapy regimens, and monoclonal antibodies. Prior to the advent of these new protocols in chemotherapy, CA that occurred concurrently with lymphomas usually led to poor prognosis, with a 3-month death rate of 90% [18].

In our case, a definitive diagnostic test was not performed because lymphedema usually develops many years after infection when laboratory tests for filariasis as blood smear at night, serological as IgM, IgG, or PCR for ascitic fluid are most likely to be negative (CDC 2020). However, the correlation between the presentation, laboratory, and imaging studies was done to narrow differentials of chylous ascites in addition to the long history of anti-filarial therapy for years without any evidence of malignancy, surgical procedure, or other infections.

People with lymphedema and elephantiasis are not likely to benefit from DEC treatment because most people with lymphedema are not actively infected with the filarial parasite (CDC 2020), and this is what actually happened in our case with the addition of somatostatin and doxycycline, we got a partial response, but unfortunately, 3 months later, the patient came back with a significant increase in ascites, and repeated paracentesis was done for 2 years about 200 L (200,000 ml) and still alive and generally will and need future paracentesis.

People with lymphedema and hydrocele can benefit from lymphedema management and in the case of hydrocele surgical repair. Even after the adult worms die, lymphedema can develop. You can ask your physician for a referral to see a lymphedema therapist for specialized care. Prevent the lymphedema from getting worse by following several basic principles:

• Carefully wash and dry the swollen area with soap and water every day.

• Elevate the swollen arm or leg during the day and at night to move the fluid.

• Perform exercises to move the fluid and improve lymph flow.

• Disinfect any wounds. Use antibacterial or antifungal cream if necessary.

• Wear shoes adapted to the size of the foot to protect the feet from injury.

Men with hydrocele can undergo surgery to reduce the size of the scrotum (CDC September 17, 2020).

The patient consulted at the Egyptian Club of Asities as surgical, intervention radiology and vascular which concluded neither benefits of new imaging as lymphography and lymphoscintigraphy nor surgical intervention.

As the long-term outcome of our patient or similarly treated patients is not known, we hope for more discussion by experts on how to deal with these cases.

This is a rare case report and no treatment is known; we hope for more discussion by experts on how to deal with these cases.

Conclusion

Despite rarity, filarial chylous ascites remains a challenge, and the only effective treatment is still repeated aspiration of the accumulated fluid. More work and discussion are needed to improve the management of such cases.