Pathogenesis and Treatment of Chronic Symptoms with Emphasis on Chyluria and Elephantiasis
Identifieur interne : 004657 ( Pmc/Corpus ); précédent : 004656; suivant : 004658Pathogenesis and Treatment of Chronic Symptoms with Emphasis on Chyluria and Elephantiasis
Auteurs : Isao TadaSource :
- Tropical Medicine and Health [ 1348-8945 ] ; 2011.
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DOI: 10.2149/tmh.39-1-suppl_2-47
PubMed: 22028601
PubMed Central: 3153157
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pathogenesis and Treatment of Chronic Symptoms with Emphasis on Chyluria and Elephantiasis</title><author><name sortKey="Tada, Isao" sort="Tada, Isao" uniqKey="Tada I" first="Isao" last="Tada">Isao Tada</name><affiliation><nlm:aff id="aff1">Professor Emeritus, Kyushu University</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22028601</idno><idno type="pmc">3153157</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153157</idno><idno type="RBID">PMC:3153157</idno><idno type="doi">10.2149/tmh.39-1-suppl_2-47</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">004657</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004657</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pathogenesis and Treatment of Chronic Symptoms with Emphasis on Chyluria and Elephantiasis</title><author><name sortKey="Tada, Isao" sort="Tada, Isao" uniqKey="Tada I" first="Isao" last="Tada">Isao Tada</name><affiliation><nlm:aff id="aff1">Professor Emeritus, Kyushu University</nlm:aff></affiliation></author></analytic><series><title level="j">Tropical Medicine and Health</title><idno type="ISSN">1348-8945</idno><idno type="eISSN">1349-4147</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Amaral, F" uniqKey="Amaral F">F Amaral</name></author><author><name sortKey="Dreyer, G" uniqKey="Dreyer G">G Dreyer</name></author><author><name sortKey="Figueredo Silva, J" uniqKey="Figueredo Silva J">J Figueredo-Silva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsushita, T" uniqKey="Matsushita T">T Matsushita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsushita, T" uniqKey="Matsushita T">T Matsushita</name></author><author><name sortKey="Yoshinaga, F" uniqKey="Yoshinaga F">F Yoshinaga</name></author><author><name sortKey="Chyosa, H" uniqKey="Chyosa H">H Chyosa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mochizuki, D" uniqKey="Mochizuki D">D Mochizuki</name></author><author><name sortKey="Inoue, S" uniqKey="Inoue S">S Inoue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mochizuki, D" uniqKey="Mochizuki D">D Mochizuki</name></author><author><name sortKey="Kasahara, S" uniqKey="Kasahara S">S Kasahara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mochizuki, D" uniqKey="Mochizuki D">D Mochizuki</name></author><author><name sortKey="Kasahara, S" uniqKey="Kasahara S">S Kasahara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bun, Jc" uniqKey="Bun J">JC Bun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamasaki, T" uniqKey="Yamasaki T">T Yamasaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayashi, I" uniqKey="Hayashi I">I Hayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kume, H" uniqKey="Kume H">H Kume</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcdonald, Df" uniqKey="Mcdonald D">DF McDonald</name></author><author><name sortKey="Huggins, C" uniqKey="Huggins C">C Huggins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirahama, T" uniqKey="Shirahama T">T Shirahama</name></author><author><name sortKey="Ohi, Y" uniqKey="Ohi Y">Y Ohi</name></author><author><name sortKey="Saita, H" uniqKey="Saita H">H Saita</name></author><author><name sortKey="Okamoto, K" uniqKey="Okamoto K">K Okamoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okamoto, K" uniqKey="Okamoto K">K Okamoto</name></author><author><name sortKey="Ohi, Y" uniqKey="Ohi Y">Y Ohi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sabnis, Rb" uniqKey="Sabnis R">RB Sabnis</name></author><author><name sortKey="Punekar, Sv" uniqKey="Punekar S">SV Punekar</name></author><author><name sortKey="Desai, Rm" uniqKey="Desai R">RM Desai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katamine, D" uniqKey="Katamine D">D Katamine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katamine, D" uniqKey="Katamine D">D Katamine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katamine, D" uniqKey="Katamine D">D Katamine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okamoto, K" uniqKey="Okamoto K">K Okamoto</name></author><author><name sortKey="Asechi, S" uniqKey="Asechi S">S Asechi</name></author><author><name sortKey="Nagata, K" uniqKey="Nagata K">K Nagata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Torres, L" uniqKey="Torres L">L Torres</name></author><author><name sortKey="Estrada, J" uniqKey="Estrada J">J Estrada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Hhy" uniqKey="Yu H">HHY Yu</name></author><author><name sortKey="Ngan, H" uniqKey="Ngan H">H Ngan</name></author><author><name sortKey="Leong, Ch" uniqKey="Leong C">CH Leong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kalanjavara, Dk" uniqKey="Kalanjavara D">DK Kalanjavara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Otsuji, Y" uniqKey="Otsuji Y">Y Otsuji</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Trop Med Health</journal-id><journal-id journal-id-type="publisher-id">TMH</journal-id><journal-title-group><journal-title>Tropical Medicine and Health</journal-title></journal-title-group><issn pub-type="ppub">1348-8945</issn><issn pub-type="epub">1349-4147</issn><publisher><publisher-name>The Japanese Society of Tropical Medicine</publisher-name><publisher-loc>Nagasaki, Japan</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22028601</article-id><article-id pub-id-type="pmc">3153157</article-id><article-id pub-id-type="publisher-id">tmh-39-1-suppl_2-47</article-id><article-id pub-id-type="doi">10.2149/tmh.39-1-suppl_2-47</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Pathogenesis and Treatment of Chronic Symptoms with Emphasis on Chyluria and Elephantiasis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tada</surname><given-names>Isao</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1"></xref></contrib></contrib-group><aff id="aff1">Professor Emeritus, Kyushu University</aff><author-notes><corresp id="cor1">Professor Emeritus, Kyushu University, M.D., Ph. D. E-mail: <email>isaotad@nifty.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>3</month><year>2011</year></pub-date><volume>39</volume><issue>1 Suppl 2</issue><fpage>47</fpage><lpage>50</lpage><permissions><copyright-statement>© 2011 Japanese Society of Tropical Medicine</copyright-statement><copyright-year>2011</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions></article-meta></front><body><sec sec-type=""><title>1 Pathogenesis</title><sec><title>1.1 Pathogenesis of elephantiasis, and historical controversy as to on the role of bacterial infection</title><p>Elephantiasis occurs in the chronic stage of lymphatic filariasis due to the obstruction of lymphatic vessels by filariae. After invasion into lymph vessels, third stage larvae grow to maturity in the lymphatic system, mainly in and around the genitourinary system. Amaral <italic>et al.</italic> (1994) [<xref ref-type="bibr" rid="B1">1</xref>] observed actively moving adult worms in dilated and tortuous lymphatic vessels by ultrasonography. The subsequent blockage leads to lymphedema of the legs, arms, mammae, and other peripheral parts of the body. This situation causes hyperplasia of the connective tissues of the subcutis. The secondary and recurrent bacterial or fungal infections act to form the rough appearance of limbs and other parts of the body like elephant hide.</p><p>Historically, elephantiasis, or elephantiasis arabicum, was well known, but the etiology was enigmatic. Prior to the development of elephantiasis, lymphangitis, erysipelaslike skin changes and filarial fever occur. These early symptoms were called “kusafurui” or “baku” in Japan, “mumu” in Samoa and “wanganga” in Fiji. The acute symptoms led scientists to suspect various etiologies for elephantiasis. Matsushita <italic>et al.</italic> (1914) [<xref ref-type="bibr" rid="B2">2</xref>] mentioned in their review that Manson (1883) suggested filariasis as the cause of elephantiasis because of the similarity in the geographic distribution. They also introduced the work by Moncorvo (1886) who concluded streptococcal infection as the cause, and that by Innes (1886) who proposed the existence of two types of elephantiasis, one originating from filariasis and the other from erysipelas. In this way, no concrete causative mechanism was shown even in the early 1900s.</p><p>In Japan, Matsushita <italic>et al.</italic> (1911) [<xref ref-type="bibr" rid="B3">3</xref>] reported the result of their first survey performed in 1908 at Tanegashima Is., Kagoshima prefecture. They found streptococci from the skin and blood in 19 out of 26 elephantiasis cases. Later they examined some 4,500 patients and concluded that streptococci were responsible for the symptoms. The reason: they found very few microfilaremia in the elephantiasis cases but noted a rather high microfilaremia rate in the nonsymptomatic persons. They even concluded that microfilariae were harmless to humans. Based on this hypothesis, they developed vaccine for elephantiasis and examined its protective activity. Matsushita and his colleagues reviewed all the results (1914) [<xref ref-type="bibr" rid="B2">2</xref>].</p><p>Mochizuki and his colleagues criticized Matsushita’s conclusion, which, based on the clinical and parasitological evidence, completely overruled the involvement of filariasis. From 1911, Mochizuki’s group adopted night blood surveys and examined inhabitants of endemic areas such as Amakusa in Kumamoto prefecture. Detailed clinical and epidemiological analyses were reported in their papers (1912, 1913a 1913b) [<xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref>]. At the 10th annual meeting of the Society of Internal Medicine, very interesting and heated discussions unfolded between the two groups, bacteriologists vs. clinicians, on the etiology of erysipelas-like fever/elephantiasis. It is now recognized that the basic cause of elephantiasis is filariasis and that bacterial and fungal infections are involved in the aggravation of the disease.</p><p>In the recent global elimination program of lymphatic filariasis conducted since 2000, as proposed by WHO, we are adopting morbidity control of lymphedema/elephantiasis using sterilizing techniques to suppress bacterial infections on the affected skin. This morbidity control program is reminiscent of the old but serious discussions on the etiology of filarial fever/elephantiasis.</p><p>Later, in order to clarify the causative mechanism in the erysipelas-like change, Bun (1921) [<xref ref-type="bibr" rid="B7">7</xref>] experimented by injecting <italic>Dirofilaria</italic> extract and streptococci into human and rabbit skin. He concluded that both parasite and bacterial components were necessary to cause the skin inflammation. Yamasaki (1953) [<xref ref-type="bibr" rid="B8">8</xref>] considered that proteinase-like components of filaria were responsible for the skin inflammation, based on his experiment using <italic>Dirofilaria</italic> extract.</p></sec><sec><title>1.2 Pathogenesis of chyluria</title><p>In the chronic stage of <italic>Wuchereria bancrofti</italic> infection, chyluria or hemato-chyluria was commonly seen in endemic areas in Japan. Chyluria is essentially urine with the appearance of milk (chyle) due to the inclusion of fat, protein and coagulated fibrin. Hemato-chyluria is chyluria contaminated with blood. Clinically, chyluria is devastating for patients, because of the loss of protein and fat leading to fatigue, pain resulting from urethral obstruction with coagulated fibrin or protein, and mental suffering due to urine colored like milk.</p><p>Studies on this symptom have been conducted by various groups, particularly urologists. Hayashi (1921) [<xref ref-type="bibr" rid="B9">9</xref>] summarized the process of chyluria as follows based on pathological observations: First, congestion of lymphatic fluid and dilatation of vessels occur as a result of occlusion of the filarial parasite in a peripheral lymphatic vessel. Then the bacteria play a role to cause local inflammation and further promote congestion/dilatation of vessels (Fig. <xref ref-type="fig" rid="F1">1</xref>). The fluid is gradually concentrated into a sticky state. Thus the ductus thoracicus is also affected showing dilatation and blockage of the lymphatic passage. Eventually, the fluid backflows into urine through renal fistulas formed by the structural deformity of lymphatics. Chyluria thus appears clinically. Based on this hypothesis, Kume (1929) [<xref ref-type="bibr" rid="B10">10</xref>] experimentally ligated the ductus thoracicus of 25 dogs at the anastomotic portion of the ductus with the left subclavicular vein. This experiment successfully revealed chyluria in 6 dogs. However, the experiment done on rabbits was unsuccessful.</p><p>Later, various urologists intensively investigated the radiological findings of chyluria cases using retrograde pyelography. By this technique, they revealed marked pyelolymphatic connections in chyluria patients (Fig. <xref ref-type="fig" rid="F2">2</xref>). The backflow of the lymph disappeared when chyluria was cured by the injection of sodium iodide into the renal pelvis. Actually, all these mechanisms of chyluria were investigated by researchers of Nagasaki University Hospital. As stated in the following section 7.2.2(2), a unique surgical technique was proposed by Prof. Katamine, Nagasaki Univ., in 1952.</p></sec></sec><sec sec-type=""><title>2 Treatment</title><sec><title>2.1 Treatment of scrotal and penile elephantiasis</title><p>As a result of the lymphatic occlusion by filarial parasites, elephantiasis occurs in genital organs such as the scrotum, penis, labium, and clitoris. In man in Japanese endemic areas, scrotal elephantiasis cases were not uncommon and the patients needed surgical treatment. In the early stage, swelling of the scrotum is mainly associated with hydrocele. This lesion can be rather easily treated by aspiration of liquid using a syringe fitted with a thick needle. Several hundred ml to (in rare cases) several liters of the liquid are seen in each hydrocele. However, in the chronic stage, elephantoid change occurs on the skin of the scrotum and penis, the latter becoming buried in the growth of elephantiasis of the scrotum. In the attempt to reconstruct surgically the affected scrotum or penis, various operations were reported historically. One of such early works is that of McDonald and Huggins (1950) [<xref ref-type="bibr" rid="B11">11</xref>].</p><p>In Japan, Shirahama <italic>et al.</italic> (1982) [<xref ref-type="bibr" rid="B12">12</xref>] reported reconstruction surgery for a huge penile-scrotal elephantiasis case. A 51-year-old man from Tokunoshima Is., an endemic focus in Kagoshima prefecture, was suffering from a penilescrotal elephantiasis of 60 cm in length, 42-75 cm in circumference, and 12.5 kg in weight. By retrograde urethrography they found the glans and urethra in the huge elephantoid tissue. They successfully reconstructed the penis and scrotum (penoscroto-plasty) after the excision of excess tissues.</p></sec><sec><title>2.2 Chyluria</title><sec><title>(1) Renal pelvic instillation therapy</title><p>The purpose of this therapy is to cauterize and obstruct the fistulas between the renal calices or pelvis and the renal lymphatics (Okamoto and Ohi, 1983) [<xref ref-type="bibr" rid="B13">13</xref>]. Thus various trials of renal pelvic instillation were performed; with 50% glucose, 10-25% bromide and 0.1-0.5% silver nitrate. Okamoto and Ohi (1983) [<xref ref-type="bibr" rid="B13">13</xref>] applied the instillation to chyluria patients with increasing concentrations of silver nitrate solution (0.1% up to 0.5%). In their treatment of 217 cases conducted between 1952 and 1973, 129 (59.4%) experienced cessation of chyle excretion and 23 (10.6%) showed improvement, but 65 (30.0%) were unchanged. Two years later 22 (48.9%) out of 45 cases examined showed no recurrence. More recently Sabnis <italic>et al.</italic> (1992) [<xref ref-type="bibr" rid="B14">14</xref>] reported their study using this method.</p></sec><sec><title>(2) Surgical treatment of chyluria</title><p>Katamine (1952a, b) [<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>] reviewed various previous reports on the origin of chyluria and, as mentioned above, concluded that lymphatic fluid causing excretion of chyle flows reversely from larger lymphatic vessels to the renal pelvis. Based on this hypothesis, he surgically blocked the surrounding lymphatic vessels connected to the affected kidneys in 5 chyluria patients. The first case who underwent the operation was a 21-year-old male mineworker who had been experiencing continuous chyluria for 2 weeks. The lymphatic vessels connected to the affected kidney were cut and blocked. After the operation the patient did not excrete chyle anymore and on the 5th day after operation, only clear urine was seen even after provocation with 50 g fat. The second case was a 45-year-old female with intermittent hematuria since the age of 7 years. A pencil-sized lymph vessel leading to the affected right kidney was blocked together with net-like lymphatics. Approximately 3 days after the operation, the patient showed hematuria but without protein or fat. The hematuria was gradually reduced and eventually no macroscopic hematuria was seen. At 15 days postoperation, the provocation with 50 g fat induced no chyluria at all. The third case, a 21-year-old male carpenter, suffered chyluria 7 months after operation. However, urological examination showed that the chyle was flowing from the opposite ureter of the un-operated kidney. Likewise, the fourth case, a 36-year-old female farmer experienced chyluria 7 days after operation. In this case too, the un-operated kidney was found to be affected by the reverse flow of lymphatic fluid. Summarizing all these first surgical trials, complete blockade of lymphatic vessels leading to the kidney was remarkably effective for the treatment of chyluria/hematochyluria. Katamine (1962) [<xref ref-type="bibr" rid="B17">17</xref>] named this surgical treatment the interruption of renal pedicle lymphatics. This method was widely applied to chyluria patients mainly by Okamoto and his colleagues in Japan. They reported the results of 70 operated cases (1964) [<xref ref-type="bibr" rid="B18">18</xref>]. Later they summarized the work performed in the endemic areas of southern Kyushu in their paper (Okamoto and Ohi, 1983) [<xref ref-type="bibr" rid="B13">13</xref>]. According to this report, 375 (97.9%) of 383 patients showed complete cessation of chyluria immediately after the operation, while only 0.8% showed no improvement. Two years later no recurrences were seen in 119 (74.4%) of 160 cases examined. Among 41 cases with recurrence of chyluria, 13 cases (8.1%) were found to excrete chyle from the contralateral kidney. Considering the presence of active transmission, or reinfection, of filariasis in those days, it can be concluded that this treatment was very successful. According to Okamoto and Ohi (1983) [<xref ref-type="bibr" rid="B13">13</xref>], the purpose of this operation was to isolate the affected kidney and upper ureter from adjacent tissues by ligation of the renal pedicle lymphatics that accompany the renal vessels.</p><p>The surgical treatment was then successfully adopted by foreign surgeons like Torres and Estrada (1962) [<xref ref-type="bibr" rid="B19">19</xref>], YU <italic>et al.</italic> (1978) [<xref ref-type="bibr" rid="B20">20</xref>] and Karanjavala <italic>et al.</italic> (1979) [<xref ref-type="bibr" rid="B21">21</xref>].</p></sec></sec></sec></body><back><ack><title>Acknowledgement</title><p>This paper is revised from Asian Parasitology Vol. 3 Filariasis in Asia and Western Pacific Islands, 127-130 by The Federation of Asian Parasitologists in 2004.</p></ack><ref-list><title>References</title><ref id="B1"><label>1</label><mixed-citation publication-type="journal" publisher-type="journal"><person-group person-group-type="author"><name><surname>Amaral</surname><given-names>F</given-names></name><name><surname>Dreyer</surname><given-names>G</given-names></name><name><surname>Figueredo-Silva</surname><given-names>J</given-names></name><etal>, et al</etal></person-group> <article-title>Live adult worms detected by ultrasonography in human Bancroftian filariasis</article-title>. <source>Am J Trop Med Hyg</source><year>1994</year>; <volume>50</volume>(6): <fpage>753</fpage>-<lpage>757</lpage><pub-id pub-id-type="pmid">8024070</pub-id></mixed-citation></ref><ref id="B2"><label>2</label><mixed-citation publication-type="journal" publisher-type="journal"><person-group person-group-type="author"><name><surname>Matsushita</surname><given-names>T</given-names></name><etal>, et al</etal></person-group> <article-title>Recent review on filariasis and elephantiasis. 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Private publication commemorating Dr. Otsuji’s 30 years of work for filariasis research and control, 1994 (in Japanese).</mixed-citation></ref></ref-list></back><floats-group><fig id="F1" orientation="portrait" position="float"><label>Fig. 1.</label><caption><p>Congestion and dilatation of pelvic lymphatics seen in a chyluria case. [Reproduced from Otsuji [<xref ref-type="bibr" rid="B22">22</xref>]]</p></caption><graphic xlink:href="tmh-39-1-suppl_2-47-g001"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Fig. 2.</label><caption><p>Pyelo-lymphatic connection shown as backflow of contrast medium in retrograde pyelography. [Reproduced from Otsuji [<xref ref-type="bibr" rid="B22">22</xref>]]</p></caption><graphic xlink:href="tmh-39-1-suppl_2-47-g002"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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