The clinical manifestations of lymphatic filariasis vary from one endemic area to another and also differ, to some extent, according to the species of the parasite that is involved (Partono, 1987). In parts of Africa such as Tanzania, the most common clinical form of the disease is hydrocele, while lymphedema and elephantiasis are much less common (Sasa, 1976). In other areas of the world such as India, both hydrocele and lymphedema are seen with almost equivalent frequency (Pani et al., 1991). Some forms of the disease, such as tropical pulmonary eosinophilia (TPE) and chyluria, are restricted in their distribution to certain parts of the world. For example, TPE has been reported most commonly from the Indian subcontinent, Brazil and Malaysia. Several studies have shown that there is a slight preponderance of females with chronic disease (when hydroceles are excluded) (Brabin, 1990). Other reports, especially from Ghana, indicate a male preponderance of the disease (Gyapong et al., 1994).
Differences in clinical presentation between bancroftian and brugian filariasis have also been reported (Partono, 1987; Sasa, 1976). It is recognized that inguinal lymphadenitis is more common in brugian filariasis than in bancroftian filariasis. Lymphangitis also occurs more frequently in brugian filariasis and in some individuals the inflamed lymphatics may stand out as cords. These are painful and prevent movement of the limbs. In the upper limbs, they can easily be palpated ('string sign'). Genital disease (hydrocele and filarial scrotum) is not seen in brugian filariasis.
abnormal patterns of lymphatic flow (Suresh et al., 1997; Dissanyake et al., 1995; Freedman et al., 1994). In parallel studies from Brazil using ultrasound examination of scrotal lymphatics, microfilaria-positive asymptomatic men demonstrated lymphangiectasia (Noroes et al., 1996a).
Although reversibility with treatment has not yet been demonstrated, it is clear that the 'asymptomatic microfilaremic state' is not as benign as initially believed, although the majority of individuals appear to remain asymptomatic for years, with relatively few progressing to the acute and chronic stages.
In areas where W. bancrofti or B. malayi are endemic, the overwhelming majority of infected individuals have few overt clinical manifestations of filariasis, despite the presence of large numbers of circulating microfilariae in the peripheral blood. The prevalence of microfilaremia increases with age during childhood and usually reaches a plateau between 20 and 30 years of age. During the childbearing years, the prevalence tends to be higher among men than among women (Brabin, 1990).
A growing body of evidence indicates that, although they may be clinically asymptomatic, virtually all persons with W. bancrofti or B. malayi microfilaremia have some degree of subclinical disease. First, it was recognized that many (ca. 40%) of these microfilaremic individuals have hematuria and/or proteinuria that reflect low-grade renal damage. The hematuria may be macroscopic, but is most often microscopic and may be accidentally discovered during routine urine examination (Dreyer et al., 1992). These renal abnormalities appear to be associated with the presence of microfilariae rather than adult worms, because clearing microfilariae from the blood results in complete reversal of these renal abnormalities (Dreyer et al., 1992). Second, and even more dramatic, were the observations on microfilariemic individuals using lymphoscintigraphy to visualize the functional anatomy of lymphatic vessels. Although clinically asymptomatic, they had markedly abnormal, dilated and tortuous lymphatics and markedly
The acute clinical manifestations of filariasis are characterized by recurrent attacks of fever associated with inflammation of the lymph nodes (adenitis) and/or lymph vessels (lymphangitis), termed adenolymphangitis (ADL).
In bancroftian filariasis, recurrent attacks of fever associated with lymphadenitis are less frequently seen than in brugian filariasis (Partono, 1987). In addition to the lymph nodes in the inguinal, axillary and epitrochlear regions, the lymphatic system of the male genitalia is frequently affected, leading to funiculitis, epi-didymitis or orchitis, or to a combination of these (Pani et al., 1995). In brugian filariasis, the affected lymph nodes are mostly situated in the inguinal and axillary regions, with inflammation along the course of the distal lymphatic vessels (Partono, 1987; Pani et al., 1990).
The acute clinical course of filariasis may last for several days or up to 4-6 weeks with a fulminant episode. The diagnostic criteria for the identification of acute filarial attacks have been codified (World Health Organization, 1992) and require pain, tenderness and local warmth, with either lymphadenitis/lymphangitis/ cellulitis (Shenoy et al., 1995) (for lungs and breasts) or epididymo-orchitis (for the scrotum). The presence of scars at typical locations, e.g. over the inguinal and epitrochlear lymph nodes, supports the diagnosis of filariasis (Figure 18a.1). In patients with filarial disease, acute attacks of ADL may involve the limb, breast or male external genitalia.
These acute episodes are characterized by local pain, tenderness, warmth and lymphadenitis and/or lymphangitis. Other commonly associated findings include fever, edema, constitutional complaints and localized or ulcerated abscesses, especially in areas where Brugia is endemic.
In endemic areas, there are two distinct types of acute ADL episodes: ADL secondary to bacterial or fungal infection, and ADL caused directly by the parasite infection itself.
The most common presentation is that of a cordlike structure associated with retrograde lymphangitis in the lower or upper limbs. In the scrotal area or the breast, it may present as a painful palpable nodule. Funiculo-epididymo-orchitis is the usual presenting feature of acute attacks of ADL involving the male genitalia. Acute hydro-cele may also be present. The systemic reactions are mild, and distal edema is rare. Recurrence of these attacks at the same site is common (Addiss and Dreyer, 2000; Pani et al., 1990).
Acute Attack Secondary Bacterial or Fungal Infection: Reticular Lymphangitis
This is the most common form of ADL. It is usually recognized as a syndrome with a clinical picture that can include high fever, chills, myalgia and headache. Edematous inflammatory plaques clearly demarcated from normal skin are seen. Occasionally, vesicles, ulcers and hyperpigmenta-tion may also be noted (Dreyer and Piessesns, 1999). There is often a history of trauma, burns, radiation, insect bites, punctiform lesions or chemical injury. Entry lesions, especially in the interdigital area, are common (Dreyer and Piessesns, 2000).
It is now generally agreed that it is possible to distinguish the two forms of acute attacks. The first type, the so-called 'filarial' fever, is characterized by lymphadenitis and retrograde lymphangitis in the absence of any injury or entry site for bacterial infections. The second form is usually diagnosed as cellulitis and is almost always associated with a visible site of entry for bacteria, edematous infiltration of the surrounding subcutaneous tissues, or even formation of abscesses, which may in turn ulcerate and lead to scarring. In contrast to bacterial infections, the ulcer in filariasis is relatively clean and produces a serosanguinous fluid. Lymphedema is quite often present in these fulminant episodes. Usually, the edema subsides after each episodic attack, but with repeated attacks the edema persists, leading to chronic lymphedema. Typically, each attack of fever and lymphadenitis lasts for several days and usually subsides spontaneously following bed rest.
Repeated episodes of ADL have been shown to be important in the progression of the disease, and data exist showing a direct relationship between the number of acute attacks and the grade of lymphedema (Pani et al., 1990). The frequency of acute attacks is generally higher in bancroftian as compared with brugian filariasis (Pani et al., 1990; Dreyer and Piessesns, 2000).
The chronic signs of filariasis rarely develop before the age of 15 years, and only a small proportion of the filaria-infected population is affected; however, immigrants from areas where filariasis is not endemic tend to develop elephantiasis more often and much sooner (sometimes
Fig. 18a.3 Elephantiasis of lower extremities in Wuchereria bancrofti infection and sometimes the arm below the elbow are characteristically involved. Lymphedema can be graded as follows (World Health Organization, 1992): grade 1, pitting edema of the limb that is reversible on elevating the limb; grade 2, pitting/ non-pitting edema that is not reversible on elevating the limb, and skin is normal; grade 3, non-pitting edema of the limb that is not reversible on elevation, and the skin is thickened; grade 4, non-pitting edema with fibrotic and verrucous skin changes (elephantiasis).
In brugian filariasis, the leg below the knee is characteristically affected, and sometimes the arm below the elbow. Genital involvement has not been reported, except in areas where brugian filariasis occurs together with W. bancrofti (Pani et al., 1990). Lymphoscintigraphic studies have shown that lymphedema is not always the result of occlusion of lymphatic channels but can also occur when there is extensive collateralization.
Secondary skin changes, such as skin-fold thickening, hyperkaratosis, hypo- or hyper-trichosis, pachydermia, pigmentary changes, chronic ulceration, epidermal and subepidermal nodules and clinical intertrigo may also be seen in chronic filarial infections (Burri et al., 1996).
Male Genital Disease (Seen only in Bancroftian Filariasis)
within 1-2 years) than do the indigenous populations of endemic areas (Partono, 1987).
In bancroftian filariasis, the occurrence of the major signs of chronic disease—hydrocele (Figure 18a.2), chyluria, lymphedema and elephantiasis (Figure 18a.3)—may differ from one area to another. The most common are hydrocele and swelling of the testis, followed by elephantiasis of the entire lower limb, the scrotum, the entire arm, the vulva and the breast, in descending order of frequency (Shenoy et al., 1995).
Lymphedema of the Limbs
Swelling of the limbs is most common. In ban-croftian filariasis the entire limb may be affected, but in brugian filariasis the leg below the knee
Hydroceles result as a consequence of the accumulation of fluid in the tunica vaginalis. The fluid that accumulates is usually clear and the presence of microfilariae in the hydrocele fluid can occasionally be demonstrated. Transillumination is characteristic and quite often very helpful to identify fluid. Hydroceles should be differentiated from inguinal-scrotal swellings and hernias.
Hydroceles are seen only in areas where there is bancroftian filariasis. This is the most common clinical manifestation in many endemic communities, with 40-50% of the males affected. The prevalence of hydrocele in endemic communities is generally underestimated, and it is not uncommon for small hydroceles to be missed. Repeated episodes of ADL involving the testicular lymphatics (epididymo-orchitis) may precede the development of hydrocele; however, hydroceles can also develop silently, and recent ultrasound studies have shown that lymphangiectasia of the scrotal lymphatics is common in patients with hydroceles (Noroes et al., 1996b).
This is characterized by swelling of the scrotum with or without thickened scrotal or penile skin, which may have a characteristic 'peau d'orange' appearance. In long-standing cases, verrucous lesions and lymphorrhea are common. The genitals may be grossly deformed; terms such as 'ramshorn penis' have been used to describe the gross distortion of the penis seen in this condition.
In this condition, lymph oozes out to the exterior directly from dilated ruptured lymphatic vessels. The dermis may be normal. This frequently occurs in the scrotal wall.
The patient with chyluria often complains of passing milky urine. Chyluria is more frequently observed after a hyperlipidemic meal and may, in many cases, be associated with blood in the urine (hematochyluria). Patients may have a spontaneous regression of their symptoms. The diagnosis of chyluria is confirmed by the presence of lymphocytes in the urine. The level of communication between the lymphatics and the genitourinary system can occur anywhere along the genitourinary tract (from the kidney to the urethra) but is usually at the level of the renal pelvis. Chyluria should be differentiated from pyuria and phosphaturia. In these conditions, white blood cells are absent and a sediment rather than an emulsion seen.
Tropical Pulmonary Eosinophilia (TPE)
The usual presenting features of TPE are cough, dyspnea and wheezing similar to bronchial asthma
(Udwadia, 1975; Spry and Kumaraswami, 1982). Chest radiographs may show diffuse mottling. In some areas, it is associated with paroxysmal nocturnal cough, breathlessness and wheezing, occasionally accompanied by a radiologic picture of diffuse patchy infiltration of the lungs. In other areas, it is associated with lymphadenopathy and sometimes hepatosplenomegaly (so-called 'occult filariasis'; Beaver, 1990). Microfilariae are almost never present in the blood, but remnants of microfilariae surrounded by aggregates of eosi-nophils are sometimes found in the spleen, liver, lymph nodes or lungs (Udwadia, 1975). The total eosinophil count is greater than 3000/^l. Increased levels of IgE and antifilarial antibodies are commonly found (Ottesen and Nutman, 1992).
TPE is characterized by immunologic hyper-responsiveness of the human hosts to the parasite, especially the microfilariae (Ottesen et al., 1979). Although microfilariae are not found in the circulation, lung biopsies have shown the presence of dead or dying microfilariae in the lung tissue (Webb et al., 1960). Bronchoalveolar lavage studies have shown increased numbers of eosinophils in the lavage fluid (Pinkston et al., 1987). The eosinophils are 'activated' and have been shown to release oxygen radicals and other proinflammatory molecules (Rom et al., 1990). Treatment with diethylcarbamazine citrate (DEC) leads to a rapid regression of the clinical symptoms and also to a decrease in the number of eosinophils. Similar syndromes may occur in the presence of intestinal worm infections, with a clinical picture that is difficult to distinguish from that of TPE apart from its inability to be cured by DEC, but which responds to anthelminthics such as albendazole and ivermectin (Vijayan, 1991; Rocha et al., 1995).
Painless lumps in the breasts, testicles or subcutaneous tissues and a 'coin' lesion in the lung can reflect granulomatous reactions around adult or developing adult worms of human or animal filarial parasites. They should be regarded as filarial infections in an unusual location or in an abnormal host.
Chronic adenopathy is a common but non-specific feature of filarial disease (Englehorn and Wellman, 1945), occurring in infected persons of all ages. It is more commonly seen in B. malayi infections. Enlargement of the lymph node is usually painless and may be the only clinical sign in individuals who are asymptomatic and microfilaria-positive. The lymph nodes most commonly involved are in the inguinal, epitrochlear, axillary and, rarely, other areas such as the submandibular (Figuerdo-Silva et al, 1994).
Clinical Manifestations in Expatriates and Transmigrants
The clinical manifestations in individuals who move from filarial-non-endemic areas to filarial-endemic areas are characterized by the rapid appearance of signs and symptoms that are not commonly seen in endemic populations. They rapidly develop inflammatory pathology, including lymphadenitis, hepatomegaly and splenomegaly. Such manifestations were initially seen in soldiers who were posted in filarial-endemic areas in south-east Asia (Wartmann, 1947; King, 1944; Huntington et al., 1944; Hodge et al., 1945; Galliard, 1957) and in humans experimentally infected with filarial parasites (reviewed in Nutman, 1991). Similar manifestations were reported among transmigrants in Indonesia, where populations were relocated from non-endemic areas to areas endemic for filariasis (Partono, 1987). In travelers, acute lymphedema accompanied by massive eosinophilia can be seen (Moore et al., 1996), as can mass lesions that, on biopsy, show filarial parasites (McCarthy et al., 1996). All of these conditions tend to respond rapidly to specific treatment and, more importantly, can be reversed when the individuals return to their non-endemic environment. This is probably because these syndromes are associated with the stages of the parasites (L3s, L4s, early adults) that are very sensitive to DEC (Ottesen, 1985).
Lymphedema and elephantiasis of filariasis are often difficult to differentiate clinically from other conditions that may evoke similar changes secondary to damaged lymphatics. Elephantiasis is characterized by hyperplasia and fibrosis of the subcutaneous tissue and thickening of the skin; however, in barefoot farming communities, skin thickening is quite common. Other conditions that cause compression of the lymphatic vessels may reduce lymph flow and produce subsequent lymphedema or even elephantiasis of the affected part of the body, distal to the compression. These include tumors and fibrotic tissue formation as a result of burns, irradiation or surgical lymphadenectomy. Onchocerciasis may also cause elephantiasis. In Africa, elephantiasis with a physicochemical etiology (absorption of silicate particles through the skin, known as podoconio-sis) has been reported in certain areas where filariasis is not endemic (Price and Bailey, 1984).
Was this article helpful?