|Year : 2012 | Volume
| Issue : 3 | Page : 199-205
|Clinico-laboratory study on filarial lymphoedema
Mohamad A Ebrahim1, Hala A El-Nahas2, Nermen M Nabih2, Husam M Al-Wakeel3
1 Department of Internal Medicine, Faculty of Medicine, Mansoum University Hospitals, Mansoura, Egypt
2 Department of Parasitology, Faculty of Medicine, Mansoum University Hospitals, Mansoura, Egypt
3 Department of Vascular Surgery, Faculty of Medicine, Mansoum University Hospitals, Mansoura, Egypt
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|Date of Web Publication||17-Jul-2012|
| Abstract|| |
Context: Lymphatic filariasis is considered the second leading cause of permanent physical disability in humans next to mood disorder. Aims: To evaluate filarial lymphoedema as a considerable burden to patients and the community. Settings and Design: This study was conducted on 45 patients with filarial lymphoedema among 2,350 patients with lower limb edema and 22 age- and sex-matched controls, from May 2005 to May 2008. Materials and Methods: Subjects were subjected to full history taking, clinical examination, Doppler ultrasound on the affected leg, laboratory tests for filariasis. Statistical Analysis: Data were analyzed using the Statistical Package for Social Scientist (SPSS) for windows 7.5. (SPSS Inc, Chicago, USA). Results: Male to female ratio was approximately 1:1.8. The age group 21-30 years was more affected (42%). The majority of cases of filarial lymphoedema in the present study were diagnosed in advanced irreversible stages. Five patients had hydrocele. Four cases (8.9%) were detected to be microfilaremic, 60% of cases were positive for Immunoglobulin (Ig) G, 4.44% were IgM positive and positive cases for filarial antigenemia were 64.4%. Conclusion: The majority of cases in the present study were detected in advanced irreversible stages with patient disability and serious socioeconomic impact.
Keywords: Acute dermato-lymphangioadenitis, elephantiasis, filarial lymphoedema, hydrocele, microfilaraemia
|How to cite this article:|
Ebrahim MA, El-Nahas HA, Nabih NM, Al-Wakeel HM. Clinico-laboratory study on filarial lymphoedema. Ann Trop Med Public Health 2012;5:199-205
|How to cite this URL:|
Ebrahim MA, El-Nahas HA, Nabih NM, Al-Wakeel HM. Clinico-laboratory study on filarial lymphoedema. Ann Trop Med Public Health [serial online] 2012 [cited 2018 Aug 15];5:199-205. Available from: http://www.atmph.org/text.asp?2012/5/3/199/98618
| Introduction|| |
Human lymphatic filariasis, is caused by the nematode (helminth) Wuchereria bancrofti (about 90% of cases) and Brugia malayi (about 10% of cases) and infection with W. bancrofti occurs with the bite of a mosquito (ie, Culex, Aedes, or Anopheles) carrying the infective third-stage larvae (L3).  Lymphatic filariasis is endemic in approximately 80 countries and more than 1.1 billion people worldwide are estimated to be at risk of infection. 
As regard the geographical distribution and the prevalence of filariasis in Egypt, foci with high levels of endemicity were found in the Nile Delta, especially in the Governorates of Qalyobia, Sharkia, Dakahlia, and Damietta Medicine. 
In 2002, the Egyptian Ministry of Health and Population reported 179 lymphatic filariasis endemic villages distributed in eight Governorates, 6 in the Nile Delta, and 2 in Upper Egypt. A mass drug administration campaign was initiated to cover almost whole of identified endemic villages.  The major pathology in lymphatic filariasis is caused by reactions to degenerating or dead adult worms. 
The disease spectrum of bancroftian filariasis varies widely from an asymptomatic state to a severely debilitating chronic condition. A general classification had been suggested into six groups: (1) Endemic normal; (2) Individuals bearing microfilaremia; (3) Acute manifestations; (4) Chronic manifestations; (5) Tropical pulmonary eosinophilia; and (6) Controversial forms. 
Acute filariasis (Acute Attacks): The first syndrome is known as "filarial fever" or Acute Filarial Lymphangitis (AFL), which is generally mild, self-limiting, and rarely causes residual lymphoedema.  The second syndrome is known as Acute Dermato- Lymphangioadenitis (ADLA) characterized by local symptoms in addition to fever, chills, headache, and weakness. Such symptoms occur in the limbs or scrotum, and are related to bacterial or fungal superinfection. 
Chronic (Obstructive) manifestations: It was identified according to World Health Organization (WHO) criteria for lymphoedema, elephantiasis, hydrocele or chyluria. 
Filariasis is the most common cause of secondary lymphoedema in the world. An estimated 15 million people worldwide have lymphoedema and elephantiasis of the extremities of filarial origin. , Filariasis has serious socioeconomic impact on the society by the significantly lowered productivity and economic loss resulting from its chronicity.  Lymphatic filariasis is considered the second leading cause of permanent physical disability in humans next to mood disorder.  The aim of the work was to evaluate filarial lymphoedema as a considerable burden to the patients and the community.
| Materials and Methods|| |
This study was conducted on 45 patients with filarial lymphoedema out of 2,350 patients with lower limb edema and 22 age and sex-matched controls, from May 2005 to 2008.
Selection of cases
Patients complaining of limb swelling. Some of them were seeking diagnosis and any medical treatment for their condition; others (especially those with elephantiasis) were seeking plastic surgery to decrease the limb size.
Other causes of limb swelling were excluded [hepatic, cardiac, renal, nutritional, DVT, chronic venous insufficiency, hormonal, pregnancy, congenital lymphoedema (onset before 2 years or known familial congenital conditions), post-surgical edema, cancer (especially breast and prostate tumors)].
Subjects were then subjected to (after written consent):
1. Full history was taken with stress on the following Age, residence, occupation, family history of similar condition, travelling and immigration, duration of the condition, symptoms suggesting ADLA attacks.
2. Clinical examination for: a) filarial lesions as Limb lymphoedema and elephantiasis and estimation of the site (unilateral or bilateral limb affection), extension (ankle, knee, thigh), and grade of lymphoedema. Lymphoedema can be graded by the following four-stage system (WHO, 1992):
Grade I: Pitting edema of the limb that is reversible on elevating the limb
Grade II: Pitting/non-pitting edema that is not reversible on elevating the limb, and the skin is normal
Grade III: Non-pitting edema of the limb that is not reversible on elevation, and the skin is thickened
Grade IV: Non-pitting edema with fibrotic and verrucous skin changes (elephantiasis)
- Skin of the limb for thickening, erythema, pigmentary changes, papules, nodules, increased skin folds, superficial varicose veins, scars, chronic ulcers, papillomatous, and elephantoid warty changes
- Signs of ADLA (linear, elevated, hyperaemic, painful cord like swellings in the leg), hyperpigmentation, demarcated edematous inflammatory plaques (with or without ulceration)
- Foot and leg inspection by naked eyes or by magnifying lens for potential entry points (abrasions, fissures, intertrigo, ulcers)
- Inguinal lymphadenopathy
- Scrotum for hydrocele or epididymo-orchitis
3. Doppler ultrasound on the affected leg To exclude deep venous thrombosis and varicosities as a cause of swollen leg, and to detect enlarged lymph nodes.
4. Laboratory tests in the form of:
- Urine examination
- Complete Blood Count (CBC), especially for eosinophilia detection
- Exclusion criteria by performing liver and kidney function tests
- Finger pricking at midnight to perform direct blood smears (for microfilarial detection)
- Ten millilitre of venous blood were withdrawn (at midnight) for microfilarial detection, antibodies and antigen detection
- Concentration techniques for microfilarial detection:
- Knott's concentration technique 
- Membrane filtration technique 
- Detection of antifilarial antibodies: Using Filarias Rapid Screening Kit, CTK Biotech Inc, USA.
- Detection of circulating filarial antigen in serum using Enzyme-Linked Immunosorbent Assay (ELISA) kit (Trop-Ag W. Bancrofti, by TropBio Pty Ltd, Australia).
| Results|| |
[Table 1], revealed that Filarial lymphoedema was present in 45 (1.9 %) out of 2350 patients complaining of lower limb oedem.
[Table 2], summarizes demographic data of patients with filarial lymphoedema, from this table, filarial lymphoedema was common among the age group 21 - 40 years old ( 73.3%) , females were more affected than males (64.4%) and the majority of them were housewives and the majority of males were farmers and Meetghamer villages were the most affected (53.3%).From this table, filarial lymphoedema was common among the age group 21 - 40 years old ( 73.3%), females were more affected than males (64.4%) and the majority of them were housewives and the majority of males were farmers and Meetghamer villages were the most affected (53.3%). [Table 3], summarizes the relation between site, grade, extension of filarial lymphedema, history suggestive of ADLA attacks and associated hydrocele. From this table, the majority presents with unilateral lymphedema (88.9%) of Grade III (62.2%), extending to the knee (77.8%) with associating hydrocele in only 11% of cases. [Figure 1], revealed that microfilaraemia was detected in only four cases (8.9%). [Figure 2], showed antibodies detection in this study where 27 cases (60%) were positive for immunoglobulin (Ig) G, two cases (4.4%) were IgM positive, and 16 cases (35.6%) were negative for antibodies. [Figure 3], revealed that positive cases for filarial antigenaemia were 29 (64.4%) and 16 patients (35.6%) were negative. [Table 4], revealed that there was significant negative trend between grade of lymphedema and antigen titer. [Table 5], showed that, the microfilaraemic group had significantly higher antigen level than the control, whereas the antigenaemia of symptomatic amicrofilaraemic patients had no significant difference than control group. [Table 6], revealed that, there were positive significant correlation between the following; age of patients and grade of lymphedema (P<0.001); age and extension of lymphedema (P=0.003); age and duration of lymphedema (P<0.001), between grade and extension of lymphedema (P=0.008); grade and duration of lymphedema (P<0.001); extension and duration of lymphedema (P=0.001); and between eosinophil count and antigen titer (P=0.019) while negative significant correlations were detected between antigen titer and the following, age (P=0.022); grade of lymphedema (P=0.003); extension of lymphedema (P=0.042); duration of lymphedema (P=0.006) and between esinophil count and grade of lymphedema (P<0.029).
|Table 4: Correlation between grade of lymphoedema and antigen positivity|
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| Discussion|| |
This study included 45 (1.9%) lymphoedema patients from among 2350 patients seen with lower limb edema. Of these patients, 29 (64.4%) were female and 16 (35.6%) were male; male to female ratio was approximately 1:1.8 [Table 1] and [Table 2]. This was in agreement with the findings of many other authors.  However, according to Onapa et al. (2001b), prevalence of limb elephantiasis was considerably higher among males than females.  The difference in male to female ratio may be related to differences in the "preferred" anatomic location of the adult filarial worm between men and women and biologic factors, particularly pregnancy, that further stress the lymphatic system in women. 
In this study, the age of the study group ranged from 16 to 46 years in addition to two children, two males aged 12 and 13 years and the age group 21-30 years were more affected (42%) [Table 2], and this was in accordance with a study by Beuria et al. 
In the present study, 41 patients were from Dakhlia Governorate; most of them were from Meet Ghamr villages (53.3%) [Table 2]. In addition, three patients were from Gharbia Governorate and one from Kafr El-Sheikh Governorate. The extent of infection is parallel with the density of population, poor sanitation, breeding places for the vector, and susceptible population. These conditions prevail in various geographical areas of Egypt.
As regards the occupation of the patients [Table 2], the majority of females were housewife (44.4%), and the majority of males were farmers (24.4%). Richard et al reported in their survey that 49.5% of the lymphoedema patients were farmers. Farmers are more prone to infection due to their prolonged exposure to open spaces, green lands, and small canals, which are the major reservoirs of the mosquito vector.
In the present study, the majority presents with unilateral lymphoedema (88.9%) of Grade III and IV (62.2% and 31.1%, respectively), extending to the knee (77.8%) with associated hydrocele in only 11% of the cases [Table 3]. These results were in accordance with Chandrasena et al who found unilateral lymphoedema in 85.7%.  The majority of cases of filarial lymphoedema in the present study were diagnosed in advanced irreversible stages and according to Feinsod et al.,  unilateral lymphoedema of the extremities, hydrocele and/or elephantiasis can be considered as specific lesions of filariasis. In the present study, [Figure 4] shows changes associated with lymphoedema, starting grade II in which the limb is swollen; however, the skin showed no changes. In grade III, the skin starts to thicken with increased skin folds [Figure 5]. Subsequently, grade IV (elephantiasis) with lymphoedema, extended to the knee, thickened skin, more deep skin folds, and petechial hemorrhage over tibia [Figure 6] and [Figure 7] showed elephantiasis case with huge elephantoid skin mass, multiple areas with hypopigmentation, papillomatous changes, and scarring.
|Figure 4: Unilateral right leg lymphoedema in grade II (irreversible edema with normal skin) with extension to the knee|
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|Figure 5: Unilateral lymphoedema in the start of grade III (start of folding of skin around the ankle|
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|Figure 6: Unilateral lymphoedema starting grade IV, extended to knee, thickened skin, more deep skin folds, and petechial hemorrhage over tibia|
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|Figure 7: Unilateral lymphoedema (grade IV) extended to thigh with huge elephantoid mass (with warty and papillomatous changes), huge skin folding, scarring, and areas of hypopigmentation|
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All cases in this study were positive for enlarged inguinal lymph nodes. The detected lymph nodes were 1-3 nodes, discrete, mobile, not matted, and not or slightly tender. The result was confirmed also by ultrasound examination of the affected lower limb [Figure 8]. The chronic enlargement of lymph nodes in our cases may be due to filarial infection or abrasions, ulcers, fissures, and intertriginous regions or foot affection by bacteria and fungi. Chronic lymphadenopathy is an important clinical manifestation in lymphatic filariasis-endemic areas. 
|Figure 8: Doppler ultrasound of right lower limb revealed enlarged right inguinal lymph node measured 3.2×0.7 cm|
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A major risk factor for development of chronic lymphoedema or elephantiasis is thought to be recurrent episodes of ADLA.  All patients in this study gave a history of painful ADLA attacks affecting their lymphedematous limbs associated with fever, increased swelling, redness, and incapacitation [Table 4], and this was in accordance with Chandrasena et al and Richard et al. ,
In the present work, microfilaraemia was detected in only four cases (8.9%) [Figure 1] by using membrane filtration (nuclepore) technique, and this was expected due to the chronic nature of the cases. This result was higher than reported by Aboul et al, that no microfilaria were detected in the blood of all lymphoedema and elephantiasis patients probably due to low sensitivity of the method used.  On the other hand, it was lower than Albuquerque et al who stated that 15.7% of lymphoedema patients and 26% of the subjects with hydrocele were microfilaraemics.  Probably, that study was performed in high endemic area with high intensity of infection or the use of more blood volumes for concentration.
As regarding antibodies detection in this study, 27 cases (60%) were positive for immunoglobulin (Ig) G, two cases (4.4%) were IgM positive, and 16 cases (35.6%) were negative for antibodies [Figure 2].
As regards antigenaemia in this study, positive cases for filarial antigenaemia were 29 (64.4%) and 16 patients (35.6%) were negative [Figure 3], and there was significant negative trend between grade of lymphoedema and antigen titer [Table 4]. This significant association is relevant to the fact that circulating filarial antigens originate from all stages of filaria, and the presence of microfilaraemia is indicative of the presence of viable adult in the lymphatics and lymph nodes. According to Hassan et al.,  the microfilaraemic group had significantly higher antigen level than the control, whereas the antigenaemia of symptomatic amicrofilaraemic patients had no significant difference than control group [Table 5].
There were positive significant correlation between the following; age of patients and grade of lymphoedema (P<0.001); age and extension of lymphoedema (P=0.003); age and duration of lymphoedema (P<0.001); between grade and extension of lymphoedema (P=0.008); grade and duration of lymphoedema (P<0.001); extension and duration of lymphoedema (P=0.001); and between eosinophil count and antigen titer (P=0.019) [Table 6]. Negative significant correlations were detected between antigen titer and the following, age (P=0.022); grade of lymphoedema (P=0.003); extension of lymphoedema (P=0.042); duration of lymphoedema (P=0.006). Negative correlation was found between eosinophil count and grade of lymphoedema (P<0.029), as shown in [Table 6].
| Conclusion|| |
The majority of cases in the present study were detected in advanced irreversible stages, with patient disability and serious socioeconomic impact.
- All patients presenting with incomplete recovery after acute limb swelling, after excluding deep venous thrombosis, should be submitted for further work-up for diagnosis of filariasis, especially in endemic areas.
- The use of highly sensitive methods to detect circulating filarial antigen to diagnose active infection, which may be common in children, for early diagnosis and treatment.
- Vector control should be included in the transmission control programmes.
- Morbidity control for established cases including health education for prevention and early treatment of ADLA attacks to halt disease progression.
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Mohamad A Ebrahim
Department of Internal Medicine, Islamic University Hospital, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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