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Of all the individuals with lymphatic filariasis less than half appear clinically asymptomatic, though they have microfilariae circulating in their blood and yet all have hidden damage to their lymphatic (as evidenced by lymphoscintigraphy) and/or renal systems (microscopic heamaturia and/or proteinuria). It is clear that this state of asymptomatic microfilaraemia is associated with a highly down-regulated immune system, but it is as yet unclear how, when or even whether these individuals will progress to develop one of the more overt clinical manifestations of filarial disease.
A second asymptomatic 'presentation' exists in individuals previously termed 'endemic normals'; their infections are defined not by microfilaraemia but by the presence of parasite antigen in the blood (which will disappear after appropriate treatment). It has only recently been possible to recognize this group of patients, and both their clinical features and sequelae of infection remain to be defined.
Other syndromes of uncertain relationship to lymphatic filariasis:
A variety of syndromes co-existing with filariasis are found in filarial endemic regions, and because they show some evidence of therapeutic response to DEC, they have been suggested as possible manifestations of lymphatic filariasis. These include arthritis (typically monoarticular), endomyocardial fibrosis, tenosynovitis, thrombophlebitis, glomerulonephritis, lateral popliteal nerve palsy, and others. While future studies may strengthen our knowledge of the clinical presentation, such syndromes at present cannot confidently be attributed to filarial infection.
Recently, a 'new' filarial syndrome has been described as one of clinical and immunologic hyper-responsiveness found in expatriate visitors to regions endemic for loiasis. This clinical syndrome is, of course, not new, nor is it limited to loiasis (tropical eye worm), as similar clinical descriptions of patients with onchocerciasis, lymphatic filariasis, and other filarial infections also have been recorded previously. Instead of developing the commonly described chronic clinical manifestations of their filarial infections, individuals who have grown up outside endemic regions and then moved to these regions and acquired a filarial infection manifest prominent signs and symptoms of inflammatory (including allergic) reactions to the mature or maturing parasites. In loiasis, these manifestations have included primarily Calabar swellings, hives, rashes and occasionally asthma; and in bancroftian filariasis (when military personnel or other migrants to endemic areas have acquired these infections), symptoms have usually been lymphangitis, lymphadenitis, genital pain (from inflammation of the associated lymphatics), along with hives, rashes and other 'allergic-like' manifestations, including blood eosinophilia. The reason for these different clinical presentations lies almost certainly in the different immunoregulatory responses to filarial antigens between those with long (including prenatal) exposure to these antigens and those meeting them for the first time.
There are chronic, acute and 'asymptomatic' presentations of lymphatic filarial disease, as well as a number of syndromes associated with these infections that may or may or not be caused by the parasites.
Chronic manifestations: Hydrocoele, even though found only with W. bancrofti infections (i.e., not Brugia infections) is the most common clinical manifestation of lymphatic filariasis. It is uncommon in childhood but is seen more frequently post-puberty and with a progressive increase in prevalence with age. In some endemic communities 40-60% of all adult males have hydrocoele. It often develops in the absence of overt inflammatory reactions, and, indeed, many patients with hydrocoele also have microfilariae circulating in the blood. Though the mechanism of the fluid accumulation in the tunica vaginalis is still unknown, direct ultrasonographic evidence indicates that in bancroftian filariasis the scrotal lymphatics are the preferred site for localization of the adult worms, and their presence may stimulate not only the proliferation of lymphatic endothelium but also a transudation of 'hydrocoele fluid' whose chemical constituents are similar to those of serum. The localization of adult worms in the lymphatics of the spermatic cord leads to a thickening of the cord that is palpable on physical examination of most patients. The hydrocoeles can become massive but still occur without lymphoedema or elephantiasis developing in the penis and scrotum, since the lymphatic drainage of these tissues is separate and more superficial.
While lymphoedema, too, can develop in the absence of overt inflammatory reactions and in the early stages be associated with microfilaraemia, the development of elephantiasis (either of the limbs or the genitals) is most frequently associated with a history of recurrent inflammatory episodes. In such individuals the early pitting oedema gives rise to a later brawny oedema with hardening of the tissues. Still later, hyper-pigmentation and hyper-keratosis develop, often with wart-like protuberances which, on histological section, reveal dilated loops of lymphatic vessels within the nodular lesions. Patients with chronic lymphoedema or elephantiasis rarely are microfilaraemic. Very important in the progression of these lesions is the fact that the redundant skin folds, cracks and fissures of the skin provide havens for bacteria and fungi to thrive and intermittently penetrate the epidermis to lead to either local or systemic infections. Sometimes the skin over the nodular protuberances breaks down, causing the dilated lymphatic within to rupture and discharge its lymph fluid directly into the environment, at the same time serving as a causeway for penetration of bacterial or fungal organisms directly into the lymphatic system.
Chyluria, another of the chronic filarial syndromes, is caused by the intermittent discharge of intestinal lymph (chyle) into the renal pelvis and subsequently into the urine. The mechanisms underlying this discharge have not been well defined, though the clinical course is known to be intermittent, sometimes remitting after treatment with DEC, sometimes after lymphangiography (owing to the scelerosing effects of the injected contrast material) or sometimes spontaneously. Nutritional compromise can, however, be severe in patients with chronic chyluria; special low-fat, high-protein diets supplemented with fluids that minimize the intake and subsequent loss of medium-chain triglycerides when possible can be helpful.
There are 4 distinct acute manifestations of lymphatic filariasis, each with a different set of causal mechanisms and pathogenic implications.
Most important are the acute inflammatory episodes of the limbs or scrotum that are related to bacterial or fungal superinfection of tissues with already-compromised lymphatic function. In the past these were termed 'filarial fevers' and more recently 'adenolymphangitis' (ADL); it has been suggested, however, that a better description would be 'DLA' (dermatolymphangioadenitis) to indicate that they start peripherally, have features of cellulitis and drain centrally towards lymph nodes.
Confused with this picture in the past was another (second) type of 'filarial fever' in which the inflammation was initiated in the lymph node (commonly the inquinal node) with 'retrograde' extension down the lymphatic tract and an accompanying 'cold' oedema. Here the inflammation appears to be immune-mediated in response to an adult worm dying or being killed in the lymphatic tract. Such immune-mediated reactions are now recognized to be much less frequent (10-20%) than the episodes of inflammation initiated by dermal infection.
A third acute filarial syndrome is tropical pulmonary eosinophilia, caused by an immunologic hyper-responsiveness to filarial infection. It is characterized by extremely high levels of peripheral blood eosinophilia, asthma-like symptoms, restrictive (and often obstructive) lung disease, very high levels of specific anti-filarial antibodies and an excellent therapeutic response to appropriate anti-filarial treatment (DEC). It occurs with a frequency of less than 1% of all filariasis cases, but it is a severe condition that can lead to chronic interstitial fibrosis and pulmonary failure.
The fourth (and least commonly recognized) form of acute inflammatory reaction caused by filarial infection is that seen early after infection particularly in expatriates exposed to, and acquiring, the infection for the first time, as when military missions have been sent to filariasis-endemic areas. Lymphangitis occurs around developing larval and early adult stages in these individuals, and an extensive set of biopsies of such lesions has indicated clearly their acute, eosinophilic inflammatory nature and their association with the presence of immature filarial worms.