THE DIAGNOSIS OF LYMPHATIC OBSTRUCTION OF FILARIAL ORIGIN!^/ By HUGH W. ACTON, LIEUTENANT-COLONEL,
Director, Calcutta School of Tropical Medicine and Hygiene, and S. SUNDAR RAO, l.m.p., Filariasis Research Worker, Calcutta School of Tropical Medicine and Hygiene.
The necessity for a paper dealing with the clinical aspect of the diagnosis of filarial obstruction seems very great owing to the
12 numerous
THE INDIAN MEDICAL GAZETTE. errors
seen
in textbooks and papers
tropical diseases which deal with this subject. Nowadays there are so many experts claiming special knowledge about a particular disease, on an experience limited to a single expedition involving a few months' duration in the country where the disease is endemic, that one has ceased to be surprised at seeing such persons indulging in wide generalisations about tropical diseases, and betraying an appalling amount of ignorance about local conditions as their visits generally coincide with the most healthy season of the year. Facts which are of commonplace knowledge to the dwellers in these places are often ignored and many of these have never been properly appreciated; an excellent example is provided by Stephens in his article on Filaria bancrofti in Byam and Archibald's book on the Practice of Medicine in the Tropics, Vol. 3, page 1903. After devoting 34 pages to discussing the disease, he comes to the summary of the evion
"
dence and commences What is the evidence that Filaria bancrofti is the cause of these various diseased conditions of the lymphatic system? It is unfortunately by no means conclusive, but such as it is may be considered under three heads":?
(a) Geographical?and here he
appears two cases
to
of be completely puzzled about chyluria occurring in persons who have never been out of England, and ends up the section. This almost complete agreement in geographical distribution does not, of course, furnish proof of cause and effect." (b) Epidemiological. This is based on the microfilaria! rate, chiefly deduced from MansonBahr's monograph on filariasis (1912)?as seen in Fiji, and other evidences of its association with elephantiasis and he states again there is apparently no definite relationship between the microfilaria rate and the elephantiasis and in different abscess rates, respectively, "
"
countries."
(c) Pathological. Stephens acknowledges the existence of adults and microfilarise in the lymph vessels and glands producing inflammatory changes "resulting in a block in the flow of It is to such blocks that the various lymph. conditions are usually attributed, but that this explanation is true seems to be far from clear." " to sum up then there He finally states be a prima facie case that Filaria to appears bancrofti is responsible for those various pathological conditions, but the question cannot be regarded as settled, much further work on the
subject being required." We will now proceed to deal with these various points mentioned by Stephens. Lymphatic obstruction is not always due to In Filaria bancrofti. Europe there are cases of elephantiasis nostra, and hydrocele, which have never been attributed to
[Jan.,
1931.
filarial infection in spite of their external resemblances to filarial elephantiasis and hydrocele. Even chyluria need not in all cases be due to this filaria, as any lymphatic obstruction in this area, i.e., in the juxta-aortic glands, will give rise to chyluria. Acton and Sundar Rao (1929) hove already shown that in filarial lymphatic obstruction part of the obstruction is clue to the toxins of the Filaria bancrojti and a large share due to septic infection by the staphylococcus and streptococcus. In Europe these cases are due either to mechanical causes such as obstruction from growth, pressure, and removal of the lymphatic glands, or as the result of a septic inflammation in the lymphatic The next point we showed was that the area. of lymphatic glandular obstruction varied type according to the possibilities of intense or light infections (Acton and Sundar Rao, 1930). Thus the type seen in hyper-endemic areas is different from that in the endemic areas, and the types seen in endemic areas are different from types in areas of low endemicity. Other fallacious ideas about the instances of the immunity of Europeans, the rate of incidence in the different sexes, etc., are based on impressions and not on facts as seen locally. The microfilaria rate amongst the apparently healthy individuals and those cases showing signs of filarial obstruction has been evidently very puzzling to Stephens in summing up this evidence. The microfilaria is in a sheath, is born in the lymphatics and has no power of penetrating through the tissues. Naturally when lymphatic obstruction is present the
microfilaria cannot get into the blood stream the rule as regards the microfilaria rate is as follows:?Persons with microfilariae in their peripheral blood usually have little or no symptoms and only 5 per cent, show evidence of lymphatic obstruction. Of persons showing evidences of lymphatic obstruction only 5 per cent, show microfilaria) in their blood. This rule is exclusive of the chyluria cases who generally show microfilariae in the blood; any one having a great deal of personal experience with the pathological manifestations of filariasis will soon appreciate the reason for this anomaly, as it is obvious why microfilariae cannot easily be found in the blood when obstruction is present. A microfilaria rate above 5 per cent, in cases of elephantiasis would make us suspicious of these figures as regards errors of chance sampling, etc. Our statement is based on the combined experience of both of us extending ten years; one of us (S. over a period of S. R.) has devoted the whole of his time to this subject and studied the disease under different conditions of endemicity. ?so
Pathologically.?A fallacious notion about the oedema produced in elephantiasis appears to be prevalent amongst some professors in medical institutions, who teach that the oedema and swelling produced in this disease does not
MAP INDIA of INDIA MAP of SHOWING SHOWING of DISTRIBUTION INFECTION FILARIAL INFECTION DISTRIBUTION ofFILARIAL
on examination of thick blood (based (based on examination of thick blood smears) smears)
Areas filarial infection with filarial infection Areaswith
Areas with no filarial infection Areas with no filarial infection Areas not surveyed Areas not surveyed
hi m
Blank
of India, Published under the direction of Colonel Sir S. G. Burrard, k.c.s.i., r.e., 1915. Reprinted in 1927 General of 1927 with with additions additions r.e., f.r.s., India, 1915. Reprinted in f.r.s., Surveyor General of this this map can be India Offices, and corrections from extra-departmental information. Heliozincographed at the Survey of Offices, Calcutta. of India Calcutta. Copies Copies of map can be 8 annas. Calcutta. Price, Wood Street, Calcutta. Price, 8 annas. obtained from the Map Record and Issue Office, 13, "Wood
Plate I.
Fig.
Fig.
1.?Cutis verticis gyrata.
3.?Von Recklinghausen's disease.
Fig. 2.?Diffuse fibro-neuroma.
Fig. 4.?Diffuse fibromatosis.
Jan., 1931.]
DIAGNOSIS OF FILARIAL OBSTRUCTION: ACTON & SUNDAR RAO. 13
on pressure like cedema due to other conditions such as renal insufficiency. It is true that the elephantoid skin does not pit on pressure, but it takes a large number of years for this dense fibrous tissue to be laid down in the deeper tissues, to make this statement to be of The pathology any value in clinical diagnosis. has been fully described by us in a paper, " entitled Kataphylaxia?a phenomenon usually seen in acute filariasis." We may state definitely that the Filaria bancrofti is responsible for most of the lymphatic obstruction seen in endemic and hyper-endemic areas. On the other hand we would hesitate to make such a diagnosis by a casual glance at a person who has lived in a non-infected area or who shows hypertrophies of the skin in regions such as the scalp, buttocks or lips, etc. The commonest errors in diagnosis we have seen made are due to confusing with filarial lymphangitis with giant urticaria, because the arm is swollen, dermatolysis, and pathological changes due to hypopituitarism. Examples of these mistakes can be seen in textbooks, and in papers written hy
pit
experts.
Ignorance of the tropical conditions and a limited experience of this infection is accountable for most of the mistakes. We propose to discuss what we consider to be fundamental differences between the obstruction produced in filariasis and the other lesions which have been mistaken for it. We will restrict our discussion to the types of lymphatic obstruction seen on the limbs, breast and genitalia.
Conditions necessary for filarial obstruction. We shall first deal with filarial obstruction, and refer to lesions mistaken for filariasis in the latter part of the paper. In previous contributions (1929 and 1930) we have emphasised the existence in India of hyper-endemic, moderate and low-endemic regions and have referred to the different kinds of filarial maniThe accompanying festations in these areas. map (Map 1) illustrates the distribution of the intensity of the infection in this country. A word of explanation regarding the construction of the map may not be out of place. Blood smears were obtained from jails, hospitals, educational institutions and from the public and in many cases they were supplemented by personal study in the field. The statistics may be taken as representative of the areas. Looking at the map it is seen that the distribution is fairly heavy along the low-lying coastal plains and river basins, while hilly tracts and regions far in the interior show comparative freedom of infection. have been divided into hyperendemic, endemic, and areas of low endemicity according to microfilaria rates of 20 per cent, and over, over 10 per cent, and under 20 per cent, and under 10 per cent, respectively in the These
areas
population.
A regional division may be found to repeat itself even locally. We have pointed out in an earlier paper (1930) how in the same area one locality may be under hyper-endemic conditions and another be completely free from the infection. The interesting instance of the low rate of Culex infection in the Civil Surgeon's quarters situated on the outskirts of Cuttack town, and the heavy Culex infective rate in the crowded city was cited in support of such a classification. Thus an individual may stay in a hyperendemic town for a number of years, actually residing in a ward of the area which has only a low endemicity. Under such conditions it may take several years to bring about an obstruction of the superficial inguinal glands. On the other hand, in the crowded parts of the same town, which, on account of the density of the population and of the associated insanitary conditions, gives rise to heavy breeding of Culex jatigans, heavier infection results and obstruction takes place fairly early in life. This time factor is a very important one in diagnosis as the patient must have been resident sufficiently long in the particular area in order to develop elephantiasis and lymphatic obstruction, which may vary from 8 to 20 or more years. As has been shown by us (1930) in a heavy endemic area there must also be the synchronisation of the season of the breeding of Culex Jatigans with the period of transmission. The rarity of filarial infection and disease amongst Europeans is sometimes cited as evi-
dence of a racial factor having something to do with their apparent immunity against the a infection. Such supposition conveniently ignores the fact that, as a class, Europeans in the tropics invariably live in less crowded areas in houses with sanitary drainage and usually take precautions against mosquito bites by using fans and mosquito-nets. It is therefore not strange to* find a very low rate of infection amongst the European population. Our work at Calcutta with regard to the race factor and immunity brings out conclusively that all nationalities, including Europeans living under identical conditions, are equally susceptible to the infection (1930). The intermediary host?Culex jatigans? being nocturnal in its habits generally bites the limbs, especially the lower limbs as being
the most convenient part to attack, and inflicts its bite, thus transmitting the filarial embryos. The head, face and other regions of the body are not usually selected as they are not so easily accessible and so bites on these areas are rarely observed. Naturally obstruction of the limbs, breasts and genitalia are the most common types of lymphatic obstruction seen in this disease. When we find swellings in places like the buttock, face, scalp, etc., we may
THE INDIAN MEDICAL GAZETTE.
14
This fluid containing microfilariae may be obtained from the lymph that oozes from the skin (lymphorrhcea) in cases of lymph-scrotum, lymph-varix of the extremities, or it may be obtained from the tappings of the dilated lymphatics. Microfilaria? are often found in this fluid, although entirely absent from the general circulation. On the other hand they fluid as the are rarely present in hydrocele lymphatic vessels are usually intact.
safely conclude from our knowledge of the disposition of the lymphatic drainage of these
that the cause of obstruction cannot be have discussed We filariasis. fully the mechanism of the lymphatics in relation to filariasis in our other papers (1930 and 1930a) and so do not repeat it here. areas
Pathological findings. AYlien obstruction in the lymphatics develops the microfilaria} are lodged beyond the obstruction and cannot reach the general circulation. For this reason in cases of advanced obstruction the microfilaria) are practically always absent from the blood (vide Table I). The adult filaria? are lodged in the dilated lymphatics below the gland which is enlarged and obstructed as the result of continued filarial irritation. Such cases have been recorded in the course of our work at the Calcutta School of Tropical Medicine (Sundar Rao, 1930). This is further supported by our observations on the eosinophil reaction in persons showing microfilariae compared with those in whom elephantoid conditions have developed to an advanced stage (vide Table II). The lower figures in the obstructive cases indicate that the toxins and parasite products do not enter the. general circulation in these' cases.
Previous
Table I.
of elephantiasis. Percentage.
microfilariae.
per-
2,456
363
14.7
Cases with ele-
932
53
5.7
Normal
These facts are of great importance in the clinical examination and diagnosis of filarial diseases, and a recognition of them would prevent classifying any swelling as due to filarial disease, and also prevent overlooking cases who are definitely suffering from filarial disease.
Total
showing
history.
The most important point to bear in mind in the diagnosis of filarial disease is the previous history of the patient. When he comes from a hyper-endemic area we should examine for as such clinical signs enlarged epitrochlear and superficial inguinal glands, whether painful and tender, peri-adenitis, lymph-varices, fugitive swellings, filarial lymphangitis, filarial abscesses and the development of elephantiasis of the legs, arms and breasts. Patients coming from endemic areas where these hyper-endemic conditions do not exist generally only show slight enlargement of these glands, evidences of development of moderate elephantoid swellings of the legs and genitalia, less frequently of the breasts or arms. Those that come from areas where the filarial endemicity is low may show chyluria, chylocele and lymph-varix as the more commoner manifestation of filarial obstruction.
Showing the incidence of microfilariae in the blood of normal 'persons compared with cases
Total examined.
1931.
[Jan.,
Lesions mistaken for those produced F. bancrofti.
sons.
We have so far of filarial
phantiasis.
types
surveyed briefly the manifestations, and
by
the
different we will
Table II.
Showing 1
2
3
4
5
with a r i se
0
0
13
11
10
In cases with filarial eases without microfil a r i ? in the peripheral blood.
3
11
26
17
12
Percentage.
the
6
eosinophilic, 10 I 11
12
rate. 13
14
15
16
17
18
19
20
3
5
1
3
1
0
0
0
100
01000000
100
Total.
I
In cases microfil
10
12
only. 19
dis-j
One other interesting fact in this connection is that we have frequently found microfilariae in the lymph below the obstruction, whereas the peripheral blood contains no microfilariae.
consider certain pathological lesions which commonly mistaken for filarial obstruction and why these errors have occurred in the
now
are
diagnosis.
Plate II.
Fig. 1.?Diffuse fibromatosis of the right leg and (aged 11 months).
Fig. 3.?Von Recklinghausen's disease.
scrotum
back Fig. 2.?Fibro-lipoma of the back.
Fig. 4.?Hypopituitarism.
Plate III.
Fig. 1.?Early
case
of hypopituitarism.
Fig. 2.?Raynaud's disease.
/#?y
Fig. 3.?Elephantiasis nostra.
Fig. 4.?Macrogymnastia.
Jan., 1931.]
DIAGNOSIS OF FILARIAL OBSTRUCTION: ACTON & SUNDAR RAO. 15
(i) Diffuse fibromatosis (derrnatolysis) is fairly common pathological condition in the tropics and is often mistaken for filarial obstruction. This diffuse fibromatosis is really a late and rare stage of the lesions produced in the syndrome known as von Recklinghausen's disease. The apparent hypertrophy of the skin a
is due to a diffuse fibromatosis of this area and has been unfortunately named dermatolysis in most textbooks on dermatology. The lesion is not due to a dissolution of the skin, but to the formation of soft fibromatous growth formed by an overgrowth of the perineural sheaths of the nerve fibres supplying the subcutaneous tissues and corium, so that the skin hangs in large pendulous folds. This fibromatosis may attack the scalp, when it is spoken of as cutis verticis gyrata, an example of this is depicted in Plate I, fig. 1. Lieut.-Col. Harnett, i.m.s., kindly sent us the case depicted in Plate I, fig. 2?a pendulous growth springing from the back of the scalp; microscopically it was seen to be a diffuse fibroma from the neurilemmal sheath of the nerves. The fibromatosis may attack the face when the skin hangs in long pendulous folds from the eyebrows, cheeks, etc. Plate I, fig. 3, depicts such a case in a beggar woman aged about 40. The folds had been increasing in size from the age of 20, her son aged 18 was also suffering from the von Recklinghausen's syndrome. In the woman, no neurofibromata were felt along the course of the nerves, but she had multiple fibromata and pigment patches. She informed us that she could only see when the pendulous folds of skin hanging from the eyebrows were lifted up by the hand; otherwise she merely saw the ground in front of her feet through a small slit. This diffuse fibromatosis may involve the skin of the buttock (see Plate I, fig. 4). We are indebted to Dr. M. Umar for permission to use his plate published in the Indian Medical Gazette, 1927. Recently we had a case of a child of 11 months with diffuse fibromatosis of the right leg and scrotum (Plate II, fig. 1). We are indebted to Major J. C. John, i.m.s., Civil Surgeon, Cuttack, for this photograph, Plate II, fig. 2, illustrating a large fibro-lipoma of the back. Major-General Coppinger, d.s.o., (Plate II, fig. i.m.s., kindly sent us this case 3) to include in our collection of these rare lesions. These lesions have been depicted in textbooks on tropical medicine as elephantiasis of "the scalp, face, buttock or leg.
(u)
Giant urticaria
(angio-neurotic
oedema
Quincke's disease).?One of us (H. W. A., 1925) questioned the correctness of the existing or
views regarding giant urticaria as a neurosis and suggested that it was due to a toxin but had no connection with the toxins in filariasis. The study of the pathogenesis of giant urticaria which was then in progress has been continued and we are now in a position to state definitely that giant urticaria is not in any way
related to filariasis. This affection generally attacks the limbs, more especially the left arm, and also the face. Almost invariably the history reveals the fact that the patient has only lived for a very short time in an endemic area ?a period rarely sufficiently long for the filarial infection to induce the amount of obstruction necessary to bring about this swelling of the limb. This fact is sufficient before we commence our clinical examination to eliminate the possibility of the swelling being due to Filaria bancrofti. Added to this, the eosinophile reaction in giant urticaria is high?generally over 16 per cent, and sometimes as high as 60 per cent.?in contra-distinction to the correspondingly low percentage found in filarial obstruction. The attack when infrequent can usually be traceable to some article of diet which is rarely eaten by the patient, such as pork, or it may occur when meat like beef is taken after an interval of several years. We sometimes for see such cases amongst tea planters who several years have lived on chicken, mutton, etc., and when they return to Calcutta and eat beef develop an idiosyncrasy towards it. More often we find that the food producing the lesions is some common article like milk, eggs, chicken, etc., which is eaten daily and causes a persistent swelling of the limb. These patients are usually recommended by their medical adviser to live on a light diet containing only these articles; this naturally greatly increases the oedema. Such erroneous advice would not be given if the different food proteins were tested on their forearm by the dermal -tests, where it would be found that the offending food produces a marked urticarial wheel. Sometimes these cases react to all the common food proteins and in these cases one usually discovers signs of intestinal stasis due to a chronic amoebic or bacillary colitis.
(Hi) Cases of hypopituitarism, where generally the arms, abdomen or buttocks are affected, are. commonly mistaken for UTariasis. Plate II, fig. 4, is a photograph of such a case. Hypopituitarism is produced by a dysfunction of the pituitary secretion as a result of which adiposity of the tissues takes place. This may manifest itself in early life by a stunting of the growth with or without adiposity, or come on later in life with the development of marked adiposity. The Litter condition is of interest to us here. Very frequently the posterior lobe is also involved so that there is a lack of pressor substances circulating in the blood; the vascular tone is not maintained and static oedema results. In time elephantiasis is produced by the growth of fibrous tissue as the result of this oedema (see Plate III, fig. 1).
(iv) Elephantiasis nostra is a condition brought about by streptococcal infections in puerperal sepsis, starting from a cervical tear, and extending along the lymphatics of the broad ligament to the pelvic lymphatic glands
THE INDIAN MEDICAL GAZETTE.
16
unilateral or bilateral solid oedema of both legs (white leg). Unilateral oedema of the leg may occur after suppuration of the deep iliac glands from septic conditions arising in the feet. Recently we had an interesting case of Raynaud's disease where attacks of secondary infection occurred in the toes and gradually proceeded up the leg producing an elephantoid condition of this limb (Plate III, fig. 2). Such cases can be diagnosed more easily in countries where Filaria bancrofti is In the tropics when examining not present. such a case the chances of attributing filarial origin to this condition are great if the history of the case is not taken into account. Moreover in hyper-endemic areas it is possible to get both filariasis and hypopituitarism existing side by side. Elephantiasis nostra may also affect the face and lips producing (Plate III, fig. 3) a lesion unknown in filarial infection. (v) Traumatic cases.?It may happen that after the removal of the lymphatic glands, as for instance during an attack of plague, or as a result of injury a permanent mechanical obstruction is produced, giving rise to elephantoid swellings of limbs. The history of the case will help in the correct diagnosis of the disease. (vi) Cases of macrogymnastia (Plate III, fig. 4) may be mistaken for elephantiasis of the breast. A careful examination with the history however reveals its true nature.
causing
one or
Summary. (1) In India, filarial
infections commonly occur along the coast and the course of the great rivers, except the Indus. (2) The prevalence of this infection in these areas are determined by three factors: (a) A wet bulb temperature between 80?? mean 82?F. with very little variation between the day and night. (i>) Suitable Culex breeding places and the breeding coinciding with the infective season, (c) Density of the population amongst whom are persons carrying microfilariae in their blood. (3) The number of months during which all these factors coincide determines whether the of low or is hyper-endemic, endemic area
endemicity.
(4) The type of lymphatic obstruction seen in these different areas varies considerably, the rough rule being that obstruction of the inguinals, epitrochlear and axillary glands are seen in hvper-endemic areas, of the iliacs and deep inguinals in epidemic areas, and of the juxta-aortic in areas of low endemicity. (5) This knowledge can only be gained by a careful study of this disease in all these areas and not by paying flying visits during the cold weather. (6) Continuous infection and reinfection over a long period of time is necessary before lymphatic obstruction can occur. Thus in
[Jan.,
1931.
hyper-endemic areas this latent period is about 8?10 years, in endemic areas from 15 to 20 years, and in areas of low endemicity over 25 This period is shortened when superyears. imposed septic infection is present as well. (7) The apparent immunity of the European is due to the fact that he rarely lives continuously in an infected region for so long a time; the site of his residence and the precautions taken against mosquitoes are all against heavy infection. (8) The microfilaria is a sheathed embryo, has no power to penetrate the tissues when lymphatic obstruction is present, and cannot blood?unless it comes enter the peripheral from a non-obstructed area. (9) Hence the rule holds good that when lymphatic obstruction occurs microfilarise are rarely seen in the peripheral blood, and conversely when microfilariae are seen in the peripheral blood, lymphatic obstruction is rarely seen
in these
cases.
(10) In chyluria, owing to the close anastomosis of the lymphatics in the region of the juxta-aortic glands complete obstruction is not possible, so that microfilariae are usually found in the peripheral blood. (11) In giant urticaria, the percentage and total number of eosinophils is greater than when microfilariae are found in the blood. The eosinophile percentage is much lower in lymphatic obstruction than when microfilariae are present in the circulating blood.
(12) A knowledge of clinical medicine is as important as laboratory experience, as it prevents including dermatolysis, giant urticaria and hypopituitarism along with lesions due to Filarici bancrofti. (13) There are many instances of lymphatic
obstruction which Filaria bancrofti;
are
not due to toxins of the
chyluria, hydroceles, lymphvarices, enlarged glands, or even elephantiasis of the limbs may be due to trauma or septic
infections in non-filarial
areas.
(14) The oedema produced by filariasis pits
readily on dropsy, renal as
pressure as that due to or cardiac disease.
epidemic
(15) Filarial lymphatic obstruction is
pro-
by two causes: the toxins of the Filaria bancrofti acting on the lymphatic vessels and glands and superimposed septic infection as the result of a lowering of the local defense mechanism, i.e., kataphylaxia. (16) There is a definite type of lymphatic obstruction which is helminthic in origin and can be proved to be so on definite?geographical, epidemiological and pathological?evidence as due to the Filaria bancrofti. (17) A knowledge of the lymphatics is essential in understanding the mechanism of this duced
obstruction in filarial and non-filarial lesions, thus preventing gross clinical mistakes.
Jan., 1931.]
RAT-GUARDS FOR SHIPS:
BILDERBECK,
References.
Acton, H. W. (1925). Giant Urticaria. Indian Med. Gaz., May, Vol. LX, p. 197. Acton, H. W., and Sundar Rao, S. (1929). Kataphylaxia." A Phenomenon usually seen in Acute Filariasis. Indian Med. Gaz., November, Vol. LXIV, "(
p. 601.
Acton, H. W., and Sundar Rao, S. (1930). Factors which Determine the Differences in the Types of Lesions Produced by Filaria bancrofti in India. Indian Med. Gaz., November, Vol. LXV, p. 620. Acton, H. W., and Sundar Rao, S. (1930a). Causation of Lymph-scrotum. Indian Med. Gaz., October, Vol. LXV, p. 541. Sundar Rao, S. (1930). Records of Finding of Adult Filaria bancrofti in India. Indian Med. Gaz., September, Vol. LXV, p. 481.
,
YOUNG & OTTO.
17
Director, Calcutta School of Tropical Medicine and Hygiene, and S. SUNDAR RAO, l.m.p., Filariasis Research Worker, Calcutta School of Tropical Medicine and Hygiene.
The necessity for a paper dealing with the clinical aspect of the diagnosis of filarial obstruction seems very great owing to the
12 numerous
THE INDIAN MEDICAL GAZETTE. errors
seen
in textbooks and papers
tropical diseases which deal with this subject. Nowadays there are so many experts claiming special knowledge about a particular disease, on an experience limited to a single expedition involving a few months' duration in the country where the disease is endemic, that one has ceased to be surprised at seeing such persons indulging in wide generalisations about tropical diseases, and betraying an appalling amount of ignorance about local conditions as their visits generally coincide with the most healthy season of the year. Facts which are of commonplace knowledge to the dwellers in these places are often ignored and many of these have never been properly appreciated; an excellent example is provided by Stephens in his article on Filaria bancrofti in Byam and Archibald's book on the Practice of Medicine in the Tropics, Vol. 3, page 1903. After devoting 34 pages to discussing the disease, he comes to the summary of the evion
"
dence and commences What is the evidence that Filaria bancrofti is the cause of these various diseased conditions of the lymphatic system? It is unfortunately by no means conclusive, but such as it is may be considered under three heads":?
(a) Geographical?and here he
appears two cases
to
of be completely puzzled about chyluria occurring in persons who have never been out of England, and ends up the section. This almost complete agreement in geographical distribution does not, of course, furnish proof of cause and effect." (b) Epidemiological. This is based on the microfilaria! rate, chiefly deduced from MansonBahr's monograph on filariasis (1912)?as seen in Fiji, and other evidences of its association with elephantiasis and he states again there is apparently no definite relationship between the microfilaria rate and the elephantiasis and in different abscess rates, respectively, "
"
countries."
(c) Pathological. Stephens acknowledges the existence of adults and microfilarise in the lymph vessels and glands producing inflammatory changes "resulting in a block in the flow of It is to such blocks that the various lymph. conditions are usually attributed, but that this explanation is true seems to be far from clear." " to sum up then there He finally states be a prima facie case that Filaria to appears bancrofti is responsible for those various pathological conditions, but the question cannot be regarded as settled, much further work on the
subject being required." We will now proceed to deal with these various points mentioned by Stephens. Lymphatic obstruction is not always due to In Filaria bancrofti. Europe there are cases of elephantiasis nostra, and hydrocele, which have never been attributed to
[Jan.,
1931.
filarial infection in spite of their external resemblances to filarial elephantiasis and hydrocele. Even chyluria need not in all cases be due to this filaria, as any lymphatic obstruction in this area, i.e., in the juxta-aortic glands, will give rise to chyluria. Acton and Sundar Rao (1929) hove already shown that in filarial lymphatic obstruction part of the obstruction is clue to the toxins of the Filaria bancrojti and a large share due to septic infection by the staphylococcus and streptococcus. In Europe these cases are due either to mechanical causes such as obstruction from growth, pressure, and removal of the lymphatic glands, or as the result of a septic inflammation in the lymphatic The next point we showed was that the area. of lymphatic glandular obstruction varied type according to the possibilities of intense or light infections (Acton and Sundar Rao, 1930). Thus the type seen in hyper-endemic areas is different from that in the endemic areas, and the types seen in endemic areas are different from types in areas of low endemicity. Other fallacious ideas about the instances of the immunity of Europeans, the rate of incidence in the different sexes, etc., are based on impressions and not on facts as seen locally. The microfilaria rate amongst the apparently healthy individuals and those cases showing signs of filarial obstruction has been evidently very puzzling to Stephens in summing up this evidence. The microfilaria is in a sheath, is born in the lymphatics and has no power of penetrating through the tissues. Naturally when lymphatic obstruction is present the
microfilaria cannot get into the blood stream the rule as regards the microfilaria rate is as follows:?Persons with microfilariae in their peripheral blood usually have little or no symptoms and only 5 per cent, show evidence of lymphatic obstruction. Of persons showing evidences of lymphatic obstruction only 5 per cent, show microfilaria) in their blood. This rule is exclusive of the chyluria cases who generally show microfilariae in the blood; any one having a great deal of personal experience with the pathological manifestations of filariasis will soon appreciate the reason for this anomaly, as it is obvious why microfilariae cannot easily be found in the blood when obstruction is present. A microfilaria rate above 5 per cent, in cases of elephantiasis would make us suspicious of these figures as regards errors of chance sampling, etc. Our statement is based on the combined experience of both of us extending ten years; one of us (S. over a period of S. R.) has devoted the whole of his time to this subject and studied the disease under different conditions of endemicity. ?so
Pathologically.?A fallacious notion about the oedema produced in elephantiasis appears to be prevalent amongst some professors in medical institutions, who teach that the oedema and swelling produced in this disease does not
MAP INDIA of INDIA MAP of SHOWING SHOWING of DISTRIBUTION INFECTION FILARIAL INFECTION DISTRIBUTION ofFILARIAL
on examination of thick blood (based (based on examination of thick blood smears) smears)
Areas filarial infection with filarial infection Areaswith
Areas with no filarial infection Areas with no filarial infection Areas not surveyed Areas not surveyed
hi m
Blank
of India, Published under the direction of Colonel Sir S. G. Burrard, k.c.s.i., r.e., 1915. Reprinted in 1927 General of 1927 with with additions additions r.e., f.r.s., India, 1915. Reprinted in f.r.s., Surveyor General of this this map can be India Offices, and corrections from extra-departmental information. Heliozincographed at the Survey of Offices, Calcutta. of India Calcutta. Copies Copies of map can be 8 annas. Calcutta. Price, Wood Street, Calcutta. Price, 8 annas. obtained from the Map Record and Issue Office, 13, "Wood
Plate I.
Fig.
Fig.
1.?Cutis verticis gyrata.
3.?Von Recklinghausen's disease.
Fig. 2.?Diffuse fibro-neuroma.
Fig. 4.?Diffuse fibromatosis.
Jan., 1931.]
DIAGNOSIS OF FILARIAL OBSTRUCTION: ACTON & SUNDAR RAO. 13
on pressure like cedema due to other conditions such as renal insufficiency. It is true that the elephantoid skin does not pit on pressure, but it takes a large number of years for this dense fibrous tissue to be laid down in the deeper tissues, to make this statement to be of The pathology any value in clinical diagnosis. has been fully described by us in a paper, " entitled Kataphylaxia?a phenomenon usually seen in acute filariasis." We may state definitely that the Filaria bancrofti is responsible for most of the lymphatic obstruction seen in endemic and hyper-endemic areas. On the other hand we would hesitate to make such a diagnosis by a casual glance at a person who has lived in a non-infected area or who shows hypertrophies of the skin in regions such as the scalp, buttocks or lips, etc. The commonest errors in diagnosis we have seen made are due to confusing with filarial lymphangitis with giant urticaria, because the arm is swollen, dermatolysis, and pathological changes due to hypopituitarism. Examples of these mistakes can be seen in textbooks, and in papers written hy
pit
experts.
Ignorance of the tropical conditions and a limited experience of this infection is accountable for most of the mistakes. We propose to discuss what we consider to be fundamental differences between the obstruction produced in filariasis and the other lesions which have been mistaken for it. We will restrict our discussion to the types of lymphatic obstruction seen on the limbs, breast and genitalia.
Conditions necessary for filarial obstruction. We shall first deal with filarial obstruction, and refer to lesions mistaken for filariasis in the latter part of the paper. In previous contributions (1929 and 1930) we have emphasised the existence in India of hyper-endemic, moderate and low-endemic regions and have referred to the different kinds of filarial maniThe accompanying festations in these areas. map (Map 1) illustrates the distribution of the intensity of the infection in this country. A word of explanation regarding the construction of the map may not be out of place. Blood smears were obtained from jails, hospitals, educational institutions and from the public and in many cases they were supplemented by personal study in the field. The statistics may be taken as representative of the areas. Looking at the map it is seen that the distribution is fairly heavy along the low-lying coastal plains and river basins, while hilly tracts and regions far in the interior show comparative freedom of infection. have been divided into hyperendemic, endemic, and areas of low endemicity according to microfilaria rates of 20 per cent, and over, over 10 per cent, and under 20 per cent, and under 10 per cent, respectively in the These
areas
population.
A regional division may be found to repeat itself even locally. We have pointed out in an earlier paper (1930) how in the same area one locality may be under hyper-endemic conditions and another be completely free from the infection. The interesting instance of the low rate of Culex infection in the Civil Surgeon's quarters situated on the outskirts of Cuttack town, and the heavy Culex infective rate in the crowded city was cited in support of such a classification. Thus an individual may stay in a hyperendemic town for a number of years, actually residing in a ward of the area which has only a low endemicity. Under such conditions it may take several years to bring about an obstruction of the superficial inguinal glands. On the other hand, in the crowded parts of the same town, which, on account of the density of the population and of the associated insanitary conditions, gives rise to heavy breeding of Culex jatigans, heavier infection results and obstruction takes place fairly early in life. This time factor is a very important one in diagnosis as the patient must have been resident sufficiently long in the particular area in order to develop elephantiasis and lymphatic obstruction, which may vary from 8 to 20 or more years. As has been shown by us (1930) in a heavy endemic area there must also be the synchronisation of the season of the breeding of Culex Jatigans with the period of transmission. The rarity of filarial infection and disease amongst Europeans is sometimes cited as evi-
dence of a racial factor having something to do with their apparent immunity against the a infection. Such supposition conveniently ignores the fact that, as a class, Europeans in the tropics invariably live in less crowded areas in houses with sanitary drainage and usually take precautions against mosquito bites by using fans and mosquito-nets. It is therefore not strange to* find a very low rate of infection amongst the European population. Our work at Calcutta with regard to the race factor and immunity brings out conclusively that all nationalities, including Europeans living under identical conditions, are equally susceptible to the infection (1930). The intermediary host?Culex jatigans? being nocturnal in its habits generally bites the limbs, especially the lower limbs as being
the most convenient part to attack, and inflicts its bite, thus transmitting the filarial embryos. The head, face and other regions of the body are not usually selected as they are not so easily accessible and so bites on these areas are rarely observed. Naturally obstruction of the limbs, breasts and genitalia are the most common types of lymphatic obstruction seen in this disease. When we find swellings in places like the buttock, face, scalp, etc., we may
THE INDIAN MEDICAL GAZETTE.
14
This fluid containing microfilariae may be obtained from the lymph that oozes from the skin (lymphorrhcea) in cases of lymph-scrotum, lymph-varix of the extremities, or it may be obtained from the tappings of the dilated lymphatics. Microfilaria? are often found in this fluid, although entirely absent from the general circulation. On the other hand they fluid as the are rarely present in hydrocele lymphatic vessels are usually intact.
safely conclude from our knowledge of the disposition of the lymphatic drainage of these
that the cause of obstruction cannot be have discussed We filariasis. fully the mechanism of the lymphatics in relation to filariasis in our other papers (1930 and 1930a) and so do not repeat it here. areas
Pathological findings. AYlien obstruction in the lymphatics develops the microfilaria} are lodged beyond the obstruction and cannot reach the general circulation. For this reason in cases of advanced obstruction the microfilaria) are practically always absent from the blood (vide Table I). The adult filaria? are lodged in the dilated lymphatics below the gland which is enlarged and obstructed as the result of continued filarial irritation. Such cases have been recorded in the course of our work at the Calcutta School of Tropical Medicine (Sundar Rao, 1930). This is further supported by our observations on the eosinophil reaction in persons showing microfilariae compared with those in whom elephantoid conditions have developed to an advanced stage (vide Table II). The lower figures in the obstructive cases indicate that the toxins and parasite products do not enter the. general circulation in these' cases.
Previous
Table I.
of elephantiasis. Percentage.
microfilariae.
per-
2,456
363
14.7
Cases with ele-
932
53
5.7
Normal
These facts are of great importance in the clinical examination and diagnosis of filarial diseases, and a recognition of them would prevent classifying any swelling as due to filarial disease, and also prevent overlooking cases who are definitely suffering from filarial disease.
Total
showing
history.
The most important point to bear in mind in the diagnosis of filarial disease is the previous history of the patient. When he comes from a hyper-endemic area we should examine for as such clinical signs enlarged epitrochlear and superficial inguinal glands, whether painful and tender, peri-adenitis, lymph-varices, fugitive swellings, filarial lymphangitis, filarial abscesses and the development of elephantiasis of the legs, arms and breasts. Patients coming from endemic areas where these hyper-endemic conditions do not exist generally only show slight enlargement of these glands, evidences of development of moderate elephantoid swellings of the legs and genitalia, less frequently of the breasts or arms. Those that come from areas where the filarial endemicity is low may show chyluria, chylocele and lymph-varix as the more commoner manifestation of filarial obstruction.
Showing the incidence of microfilariae in the blood of normal 'persons compared with cases
Total examined.
1931.
[Jan.,
Lesions mistaken for those produced F. bancrofti.
sons.
We have so far of filarial
phantiasis.
types
surveyed briefly the manifestations, and
by
the
different we will
Table II.
Showing 1
2
3
4
5
with a r i se
0
0
13
11
10
In cases with filarial eases without microfil a r i ? in the peripheral blood.
3
11
26
17
12
Percentage.
the
6
eosinophilic, 10 I 11
12
rate. 13
14
15
16
17
18
19
20
3
5
1
3
1
0
0
0
100
01000000
100
Total.
I
In cases microfil
10
12
only. 19
dis-j
One other interesting fact in this connection is that we have frequently found microfilariae in the lymph below the obstruction, whereas the peripheral blood contains no microfilariae.
consider certain pathological lesions which commonly mistaken for filarial obstruction and why these errors have occurred in the
now
are
diagnosis.
Plate II.
Fig. 1.?Diffuse fibromatosis of the right leg and (aged 11 months).
Fig. 3.?Von Recklinghausen's disease.
scrotum
back Fig. 2.?Fibro-lipoma of the back.
Fig. 4.?Hypopituitarism.
Plate III.
Fig. 1.?Early
case
of hypopituitarism.
Fig. 2.?Raynaud's disease.
/#?y
Fig. 3.?Elephantiasis nostra.
Fig. 4.?Macrogymnastia.
Jan., 1931.]
DIAGNOSIS OF FILARIAL OBSTRUCTION: ACTON & SUNDAR RAO. 15
(i) Diffuse fibromatosis (derrnatolysis) is fairly common pathological condition in the tropics and is often mistaken for filarial obstruction. This diffuse fibromatosis is really a late and rare stage of the lesions produced in the syndrome known as von Recklinghausen's disease. The apparent hypertrophy of the skin a
is due to a diffuse fibromatosis of this area and has been unfortunately named dermatolysis in most textbooks on dermatology. The lesion is not due to a dissolution of the skin, but to the formation of soft fibromatous growth formed by an overgrowth of the perineural sheaths of the nerve fibres supplying the subcutaneous tissues and corium, so that the skin hangs in large pendulous folds. This fibromatosis may attack the scalp, when it is spoken of as cutis verticis gyrata, an example of this is depicted in Plate I, fig. 1. Lieut.-Col. Harnett, i.m.s., kindly sent us the case depicted in Plate I, fig. 2?a pendulous growth springing from the back of the scalp; microscopically it was seen to be a diffuse fibroma from the neurilemmal sheath of the nerves. The fibromatosis may attack the face when the skin hangs in long pendulous folds from the eyebrows, cheeks, etc. Plate I, fig. 3, depicts such a case in a beggar woman aged about 40. The folds had been increasing in size from the age of 20, her son aged 18 was also suffering from the von Recklinghausen's syndrome. In the woman, no neurofibromata were felt along the course of the nerves, but she had multiple fibromata and pigment patches. She informed us that she could only see when the pendulous folds of skin hanging from the eyebrows were lifted up by the hand; otherwise she merely saw the ground in front of her feet through a small slit. This diffuse fibromatosis may involve the skin of the buttock (see Plate I, fig. 4). We are indebted to Dr. M. Umar for permission to use his plate published in the Indian Medical Gazette, 1927. Recently we had a case of a child of 11 months with diffuse fibromatosis of the right leg and scrotum (Plate II, fig. 1). We are indebted to Major J. C. John, i.m.s., Civil Surgeon, Cuttack, for this photograph, Plate II, fig. 2, illustrating a large fibro-lipoma of the back. Major-General Coppinger, d.s.o., (Plate II, fig. i.m.s., kindly sent us this case 3) to include in our collection of these rare lesions. These lesions have been depicted in textbooks on tropical medicine as elephantiasis of "the scalp, face, buttock or leg.
(u)
Giant urticaria
(angio-neurotic
oedema
Quincke's disease).?One of us (H. W. A., 1925) questioned the correctness of the existing or
views regarding giant urticaria as a neurosis and suggested that it was due to a toxin but had no connection with the toxins in filariasis. The study of the pathogenesis of giant urticaria which was then in progress has been continued and we are now in a position to state definitely that giant urticaria is not in any way
related to filariasis. This affection generally attacks the limbs, more especially the left arm, and also the face. Almost invariably the history reveals the fact that the patient has only lived for a very short time in an endemic area ?a period rarely sufficiently long for the filarial infection to induce the amount of obstruction necessary to bring about this swelling of the limb. This fact is sufficient before we commence our clinical examination to eliminate the possibility of the swelling being due to Filaria bancrofti. Added to this, the eosinophile reaction in giant urticaria is high?generally over 16 per cent, and sometimes as high as 60 per cent.?in contra-distinction to the correspondingly low percentage found in filarial obstruction. The attack when infrequent can usually be traceable to some article of diet which is rarely eaten by the patient, such as pork, or it may occur when meat like beef is taken after an interval of several years. We sometimes for see such cases amongst tea planters who several years have lived on chicken, mutton, etc., and when they return to Calcutta and eat beef develop an idiosyncrasy towards it. More often we find that the food producing the lesions is some common article like milk, eggs, chicken, etc., which is eaten daily and causes a persistent swelling of the limb. These patients are usually recommended by their medical adviser to live on a light diet containing only these articles; this naturally greatly increases the oedema. Such erroneous advice would not be given if the different food proteins were tested on their forearm by the dermal -tests, where it would be found that the offending food produces a marked urticarial wheel. Sometimes these cases react to all the common food proteins and in these cases one usually discovers signs of intestinal stasis due to a chronic amoebic or bacillary colitis.
(Hi) Cases of hypopituitarism, where generally the arms, abdomen or buttocks are affected, are. commonly mistaken for UTariasis. Plate II, fig. 4, is a photograph of such a case. Hypopituitarism is produced by a dysfunction of the pituitary secretion as a result of which adiposity of the tissues takes place. This may manifest itself in early life by a stunting of the growth with or without adiposity, or come on later in life with the development of marked adiposity. The Litter condition is of interest to us here. Very frequently the posterior lobe is also involved so that there is a lack of pressor substances circulating in the blood; the vascular tone is not maintained and static oedema results. In time elephantiasis is produced by the growth of fibrous tissue as the result of this oedema (see Plate III, fig. 1).
(iv) Elephantiasis nostra is a condition brought about by streptococcal infections in puerperal sepsis, starting from a cervical tear, and extending along the lymphatics of the broad ligament to the pelvic lymphatic glands
THE INDIAN MEDICAL GAZETTE.
16
unilateral or bilateral solid oedema of both legs (white leg). Unilateral oedema of the leg may occur after suppuration of the deep iliac glands from septic conditions arising in the feet. Recently we had an interesting case of Raynaud's disease where attacks of secondary infection occurred in the toes and gradually proceeded up the leg producing an elephantoid condition of this limb (Plate III, fig. 2). Such cases can be diagnosed more easily in countries where Filaria bancrofti is In the tropics when examining not present. such a case the chances of attributing filarial origin to this condition are great if the history of the case is not taken into account. Moreover in hyper-endemic areas it is possible to get both filariasis and hypopituitarism existing side by side. Elephantiasis nostra may also affect the face and lips producing (Plate III, fig. 3) a lesion unknown in filarial infection. (v) Traumatic cases.?It may happen that after the removal of the lymphatic glands, as for instance during an attack of plague, or as a result of injury a permanent mechanical obstruction is produced, giving rise to elephantoid swellings of limbs. The history of the case will help in the correct diagnosis of the disease. (vi) Cases of macrogymnastia (Plate III, fig. 4) may be mistaken for elephantiasis of the breast. A careful examination with the history however reveals its true nature.
causing
one or
Summary. (1) In India, filarial
infections commonly occur along the coast and the course of the great rivers, except the Indus. (2) The prevalence of this infection in these areas are determined by three factors: (a) A wet bulb temperature between 80?? mean 82?F. with very little variation between the day and night. (i>) Suitable Culex breeding places and the breeding coinciding with the infective season, (c) Density of the population amongst whom are persons carrying microfilariae in their blood. (3) The number of months during which all these factors coincide determines whether the of low or is hyper-endemic, endemic area
endemicity.
(4) The type of lymphatic obstruction seen in these different areas varies considerably, the rough rule being that obstruction of the inguinals, epitrochlear and axillary glands are seen in hvper-endemic areas, of the iliacs and deep inguinals in epidemic areas, and of the juxta-aortic in areas of low endemicity. (5) This knowledge can only be gained by a careful study of this disease in all these areas and not by paying flying visits during the cold weather. (6) Continuous infection and reinfection over a long period of time is necessary before lymphatic obstruction can occur. Thus in
[Jan.,
1931.
hyper-endemic areas this latent period is about 8?10 years, in endemic areas from 15 to 20 years, and in areas of low endemicity over 25 This period is shortened when superyears. imposed septic infection is present as well. (7) The apparent immunity of the European is due to the fact that he rarely lives continuously in an infected region for so long a time; the site of his residence and the precautions taken against mosquitoes are all against heavy infection. (8) The microfilaria is a sheathed embryo, has no power to penetrate the tissues when lymphatic obstruction is present, and cannot blood?unless it comes enter the peripheral from a non-obstructed area. (9) Hence the rule holds good that when lymphatic obstruction occurs microfilarise are rarely seen in the peripheral blood, and conversely when microfilariae are seen in the peripheral blood, lymphatic obstruction is rarely seen
in these
cases.
(10) In chyluria, owing to the close anastomosis of the lymphatics in the region of the juxta-aortic glands complete obstruction is not possible, so that microfilariae are usually found in the peripheral blood. (11) In giant urticaria, the percentage and total number of eosinophils is greater than when microfilariae are found in the blood. The eosinophile percentage is much lower in lymphatic obstruction than when microfilariae are present in the circulating blood.
(12) A knowledge of clinical medicine is as important as laboratory experience, as it prevents including dermatolysis, giant urticaria and hypopituitarism along with lesions due to Filarici bancrofti. (13) There are many instances of lymphatic
obstruction which Filaria bancrofti;
are
not due to toxins of the
chyluria, hydroceles, lymphvarices, enlarged glands, or even elephantiasis of the limbs may be due to trauma or septic
infections in non-filarial
areas.
(14) The oedema produced by filariasis pits
readily on dropsy, renal as
pressure as that due to or cardiac disease.
epidemic
(15) Filarial lymphatic obstruction is
pro-
by two causes: the toxins of the Filaria bancrofti acting on the lymphatic vessels and glands and superimposed septic infection as the result of a lowering of the local defense mechanism, i.e., kataphylaxia. (16) There is a definite type of lymphatic obstruction which is helminthic in origin and can be proved to be so on definite?geographical, epidemiological and pathological?evidence as due to the Filaria bancrofti. (17) A knowledge of the lymphatics is essential in understanding the mechanism of this duced
obstruction in filarial and non-filarial lesions, thus preventing gross clinical mistakes.
Jan., 1931.]
RAT-GUARDS FOR SHIPS:
BILDERBECK,
References.
Acton, H. W. (1925). Giant Urticaria. Indian Med. Gaz., May, Vol. LX, p. 197. Acton, H. W., and Sundar Rao, S. (1929). Kataphylaxia." A Phenomenon usually seen in Acute Filariasis. Indian Med. Gaz., November, Vol. LXIV, "(
p. 601.
Acton, H. W., and Sundar Rao, S. (1930). Factors which Determine the Differences in the Types of Lesions Produced by Filaria bancrofti in India. Indian Med. Gaz., November, Vol. LXV, p. 620. Acton, H. W., and Sundar Rao, S. (1930a). Causation of Lymph-scrotum. Indian Med. Gaz., October, Vol. LXV, p. 541. Sundar Rao, S. (1930). Records of Finding of Adult Filaria bancrofti in India. Indian Med. Gaz., September, Vol. LXV, p. 481.
,
YOUNG & OTTO.
17
