- Email: [email protected]
Bilharzial appendicitis in Schistosoma haematobium infestations. A preliminary report
385 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE.
Vol. XXX. No. 3. November, 1936.
B I L H A R Z I A L A P P E N D I C I T I S IN SCHISTOSOMA HAEMATOBIUM INFESTATIONS. A PRELIMINARY
REPORT.*
BY
A. C. LOVETT-CAMPBELL, 2Viedical O~icer, Colonial Medical Service, West Africa, AND
A. W. ROSE, Pathologist, Colonial Medical Service, West Africa.
The purpose of this paper is threefold ; firstly, to record the frequency with which Sckistosoma haematobium ova and grosser bilharzial lesions implicated a series of thirty appendices, removed at operation from Africans inhabiting a hyperendemic area of Northern Nigeria; secondly, to discuss certain points in the symptomatology of these cases ; and lastly, to describe serially and in some detail the histological changes evident in what are judged to be early, intermediate and late phases of tissue reaction to local ova infiltration within the appendix. A series of photomicrographs illustrates these changes, and serves to amplify the descriptive histopathology of the condition. In preparing this paper, access to selective literature disclosed the thoroughness with which regional distribution of schistosome ova throughout abdominal viscera had previously been investigated by early workers, notably FAIRLEY (1919), MADDEN (1922), and DEW (1923). While thus disclaiming precedence for our observations, we desire to stress certain facts emerging from our recent investigations, which hitherto appear to have received scarcely adequate mention. For example, in our * This paper is published by the permission of Sir WALTERJOHNSON, C.M.G., Director of Medical and Sanitary Services, Nigeria. The pathological data, observations, and illustrations are incorporated in a thesis accepted for the degree of M.D. of the University of Edinburgh. Permission to publish them is gratefully acknowledged. The writers wish to express their gratitude to Dr. N. HAMILTONFAIRLEYfor helpful criticism and encouragement. They also wish to thank Mr. J. KNIGHT, of the Medical Research Institute, Lagos, for unstinted pains taken with the preparation of certain of the photomicrographs.
886
BILHARZIAL APPENDICITIS.
series of cases, the notable frequency of appendicial lesions* arising exclusively f r o m S. haematobium infestations, deserves particular emphasis, i n a s m u c h as only scant reference to isolated instances of this nature appear in m o s t u p - t o - d a t e text-books. Only four patients had unmistakable appendicular colic and, in each of these, the implicated appendices had characteristic bilharzial lesions of macroscopic degree serving to demonstrate, b e y o n d all reasonable doubt, that occasionally a c u t e appendicitis--clinically indistinguishable f r o m its more familiar surgical c o u n t e r p a r t s - - c a n , and does in fact, arise f r o m uncomplicated S. haematobium infestations. Thirdly, in contrast with the above, a majority group, c o m p r i s i n g sixteen individuals with ova-infested appendices, and fifteen individuals with negative appendices, gave histories, in which the p r e d o m i n a t i n g s y m p t o m s were diffuse abdominal colic, associated with mucoid diarrhoea. Indeed, the p r e d o m i n a n c e of these s y m p t o m s suggested extensive colonic involvement, while a c c o m p a n y i n g appendicial lesions present in just over half the n u m b e r - - b e i n g of m i n o r degree, were, clinically, either masked or actually the cause of no local s y m p t o m s . T h a t the prevailing lesions in this group were colonic, lacks pathological confirmation, as none of our cases came to autopsy. But it has long been observed that mucoid diarrhoea o c c u r s in association with S. haematobium infections, and that terminal spined ova occasionally appear in the stools of these patients, while autopsies confirm the frequency of colonic and rectal lesions. O u r first patient was operated u p o n f o r acute appendicitis.
Case History. Early in March, 1935, an African male, aged 30, was admitted to hospital with a history of recurring, low abdominal pain, diarrhoea and vomiting, of three years duration. Attacks were frequent, usually occurring about every 10 days, and subsiding gradually, after 3 or 4 days. Vomiting always ceased early. Symptoms almost similar to the above were actually witnessed while the patient came under observation in hospital. Closer examination disclosed definite tenderness, more or less constant, over the appendix area, unaccompanied by local rigidity. On digital pressure, marked gurgling of the caecum could be elicited. Faeces and urine were free from ova. Red blood ceils were present in both. Cysts of Entamoeba histolytica were also detected in the faeces. Classified as a dysenteric, this patient was given one week's treatment with emetine and yatren. As no noticeable abatement of symptoms resulted, appendicectomy was performed. At operation a large free appendix was removed. Its extremity was bulbous and tense. The serous coat was injected. Slender, easily divided bands encircled a distended caecum, and ballooned the distal saceulations of the ascending colon. The patient made an uneventful recovery, with immediate and complete cessation of symptoms. The pathological comments read as follows .--"" The appendix shows a condition of subaeute inflammation, and infiltration with round cells and eosinophils, associated with the presence of schistosome ova in the submucosa. Curiously enough, these appear to be S. haematobium, rather than S. mansoni. The condition is an interesting one;" The term " lesion '! is employedhere in a wide sense to include the deposit of ova with 9r without tissue reaction resulting therefrom.
A. C. LOVETT-CAMPBELL AND A. W. ROSE.
~.~7
D u r i n g the subsequent 6 months, thirty-four more appendicectomies ,aTere carried out. Each case was investigated clinically, with a view to establishing a possible relationship between s y m p t o m s and the pathological changes encountered. All patients at the time of admission to hospital were excreting haematobium ova in their urines. Four appendices had gross macroscopic lesions. T o g e t h e r with the histories given, these four specimens provide convincing proof that acute appendicitis, clinically indistinguishable from its pyogenic forms, occasionally arises in bilharziasis. This is contrary to the view of BA~SOUM (1934) that bilharziasis does not cause or predispose to appendicitis. T h i r t y other cases in the series, including sixteen with infested appendices, manifested characteristic dysenteric s y m p t o m s - - a b d o m i n a l colic and profuse mucoid diarrhoea. T h e constancy of these s y m p t o m s in so m a n y cases, irrespective of whether appendicular infestation with ova was proved to exist or not, favours the conclusion that their seat of origin is the colon, not the appendix ; that only in the presence of gross bitharzial lesions of the appendix, do symptoms referable to that organ overshadow associated colonic symptoms. As regards the discovery of ova within the lumen of the appendix, it is conceivable in certain instances that ova may gravitate accidentally there from the caecum, and thus come to lie between the glandular crypts. Below, an account is given of four cases, previously mentioned as having gross lesions of the appendix. Case 1 .--;'¢Iale aged 25. ClinicaL--Symptoms commenced 9 years ago, since when he experienced four severe
bouts of abdominal pain. Vomiting preceded each attack, and pain was relieved by lying face downwards. The onset was always gradual. The pain attained great severity, and subsided at the end of 2 days. It was ahYays most marked over the appendix region, the patient adding that in this area the abdomen became " like a stick " (rigidity). Diarrhoea and looseness of the bowels were frequent, but lately he has tended to be constipated. Pathological.--The appendix was distorted and kinked 2 cm. from the tip by a fibrous mmour, 1.4 × 1 × 1 cm. in size, which occupied half of the circumference of the appendicular wall on the side remote from the mesocolic attachment. The mucosa was intact but pressed upon by the tumour, the lumen being distorted and crescentic in shape, with the concavity towards the tumour. The mucosa showed the presence of congestion and catarrh, and the lumen contained a plug of amorphous matter coated with a layer of mucus, desquamated epithelial cells, and erythrocytes. There was intense infiltration of the mucosa with round cells and eosinophil polymorphs. The tumour was composed of chronic inflammatory reaction surrounding numerous ova of S. haematobium, which had apparently been deposited in the submucosa, at a point remote from the mesocolic attachment. The circular muscle coat was thickened, and showed hyaline Change, and had been ruptured. The ruptured ends were plainly seen, separated by the inflammatory mass. Three-quarters of the tumour lay peripheral to the muscle coat. The surface of the tumour was smooth, except for the presence of minute greyish tubercles 1 to 2 ram. in size, which were very slightly raised above the surface. The structure of the tumour varied slightly in different parts ; broadly speaking it tended to E
~3~
BILHARZIAL APPENDICITIS.
be more cellular within the muscle coats, i.e., in the usual situation of the submucosa, and more fibrous outside these coats at the periphery of the tumour. This favoured the inference that the latter was Of longer standing than the former. T h e serous coat was seen stretched out over the surface of the tumour for a short distance, and then merged into it. T h e structure of the inflammatory mass was as follows : Whorls of fibrous tissue surrounding single or multiple ova were embedded in a matrix of cellular and vascular granulation tissue, abundantly infiltrated with wandering cells, round cells, and eosinophil polymorphs. T h e fibrous whorls differed from each other, and the difference was believed to be due to their respective ages. Five types were seen : - (1) A dense concentration of e0sinophils and wandering cells around the ovum, with outside this a layer of cells resembling fibroblasts. (2) Similar to (1) but the eosinophils had undergone degenerative change although the nuclei were still visible. T h e fibroblasts were ranged radially t o the central mass like the spokes of a wheel, and a concentric wall of fibrosis limited the structure. (3) T h e granular dtbris was no longer apparent, but foreign body giant cells were commonly found. Phagocytosis of the ova could be seen. (4) Similar to the above but very little remained of the ova, and fibrosis was more marked. (5) A concentric fibrous scar alone remained.
Case 2.
Male aged 20.
ClinicaL--Abdominal trouble commenced 6 years ago, characterized b y colicky pain and mucoid diarrhoea. Mild attacks occurred at intervals of 4 months, were gradual i t onset, and continued for at least a day. N o vomiting occurred. No early haernaturia had been noticed. PathologicaL--Two cm. from the base of the appendix there was an irregular swelling 2 × 1 era. in size formed by a localized increase in the appendicular wall. T h e peritoneal surface was smooth and glistening, but minute greyish tubercles could be seen in the substance of the tumour. T h e tip of the appendix was also distorted by a small fleshy beaklike tumour showing the presence of tubercles. A smaller pedunculated mass was found at the junction of the middle and distal thirds and resembled a smooth wart. T h e lumen was filled with a plug of mucus and catarrhal epithelial cells. Th e mucosa was abundantly infiltrated with round cells and eosinophil polymorphs. T h e germinal centres of the l y m p h nodes were prominent. T h e longitudinal muscle coat and subserous coats were much thickened by the presence of granulation tissue heavily infiltrated with eosinophilic polymorphs. S. haematobium ova were present. T h e tissue was vascular. Here and there were pseudo-tubercles of early type; T h e circular muscle coat was split by pseudo-tuberculous reaction. T h e submucosa also contained ova, and here the reaction was of the giant cell type with phagocytosis of the ova. T h e subserous coat was thickened to such an extent that it equalled in breadth the rest of the appendicular wall. Case 3.
Male aged 16.
ClinicaL--Abdominal trouble commenced 3 years ago with severe attacks of colic that occurred every 3 months. Vomiting preceded their onset while during attacks pronounced mueoid diarrhoea was a feature. Pain commenced in the epigastrium and spread to the right iliac fossa. Relief was obtained by pressure over this area. Haematuria , present from childhood, still recurred, usually at intervals of 3 months. PathologicaL--The appendix proper was fairly normal in appearance, but present at its distal extremity was a dense band of adhesions about 2 era. long containing a leash of vessels. This band of tissue connected the tip Of the appendix with a solid 0val tumour 1½ × 1 era. in size. T h e adhesions were twisted on themselves. Th e surface of the turnout was nodular owing to the presence of large numbers of minute greyish tubercle-like elevations. (a) T h e appendix p r o p e r . - - T h e lumen contained erythrocytes and catarrhal epithelial cells. T h e mueosa was congested and infiltrated with round ceils and eosinophil polymorphs
"t
FIe-. 1.
Fie.. 2.
FIe;. 5.
FIG. 3.
FIG. 4.
FIG. 6.
FIGS. 1-4 . - - A p p e n d i c e s from Cases 1-4. FIG. 5.--Calcified ova in the submucosa. N o t e in this case the absence of specific tissue reaction. × 27. FIG. 6 . - - S i m i l a r to Fig. 5, b u t showing o v u m lying between the glandular crypts.
To face page
338.
× 93.
FIG. 7.
Fro. 8.
FIG. 9. FIG. 7.--Pseudo-tuberculous granulation ussue.
FIG. 10 Note the presence of several ova.
× 93.
Fro. 8.--Concentric whorls of fibrosis in relation to very numerous degenerate ova.
× 93.
FIG. 9.--Pseudo-tuberculous tissue demonstrating the presence of cellular infiltration, calcified ova, and multinucleate giant cells. × 60. THE EVOLUTION OF THE PSEUDO-TUBERCLE
(FIGS. 10-14).
FIC. 10.--Ovum surrounded by concentration of eosinophil polyrnorph cells.
× 175.
F m . 11
FIG. 12.
FIG. 13.
Fra. l l . - - G r a n u l a r
FIG. 14.
d e g m e r a t i o n of cells around central ovum. Note the spindle cells arrangad radially around the central mass. × 95. FIG. 1 2 . - - M u l t i n u c l e a t e giant cell.
x 360.
FIg. 13.--Phagocytosis of calcified o v u m by mu!tinucleate giant cell. FIG. 1 4 . - - F i b r o u s scar.
× 360.
× 360.
A, C. LOVETT-CAMPBELL
AND A. W. ROSE.
~9'
and contained a few S. haematobium ova. The submucosa contained clumps of ova numbering 1 to 10 but there was no characteristic reaction. They were situated remote from the mesocolic attachment. The serous coat was thickened and infiltrated with ova. (b) The tumour.--This consisted of a solid mass of pseudo-tubercles surrounding myriads of ova which were mainly calcified. The tubercles were of an advanced type although giant cells were commonly present. (c) The adhesions.---These presented a similar picture to that shown by the tumour. Case 4. Male aged 37. Clinical.--Symptoms commenced 5 years ago with mid-abdominal colic. Attacks alternated with periods of freedom. He recollected four pronounced attacks in 5 years. Each continued for about 3 days. The pain commenced low down above the middle of the right inguinal ligament, and compelled him to lie still. There was no vomiting, but diarrhoea and the passage of blood and sometimes mucus in slight amount occurred. There had been haematuria in childhood. Operation 14th Sept., 1935.--The appendix was difficult to locate, lying retrocaecally buried in adhesions. The caecum was fixed and immobile. The appendix was enlarged and tortuous. The serous coat was much injected. Pathologieal.--The lumen contained a catarrhal plug. The mucous membrane was slightly thickened with marked cellular infiltration. The submucosa, also slightly thickened in parts, was infiltrated with round cells, eosinophils, and fibroblasts. S. haematobium ova were scattered about it singly and in pairs. The muscular coat appeared thickened. The serous coat was definitely thickened in parts and was very vascular. Fairly numerous ova were present in its substance. Many of the smaller vessels in the serous coat were cuffed with lymphoeytes. The serous coat at one point was thickened to form a fleshy adhesion binding down the kinked tip of the appendix to the main body of the organ. PATHOLOGICAL TECHNIQUE AND OBSERVATIONS. T h e s p e c i m e n s n u m b e r i n g thirty-five in all were fixed in 10 per cent. formolzsaline. A s e a r c h i n g m a c r o s c o p i c and m i c r o s c o p i c e x a m i n a t i o n was carried o u t in each case, and particular attention was paid to the following points. .Macroscopic.--Measurements i n c l u d i n g length, average diameter~ a n d thickness of the wall ; abnormalities o f c o n f o r m a t i o n i n c l u d i n g kinking, nodules, or callosities ; the p r e s e n c e of adhesions and congestion of the surface vessels i search o f surface vessels and also the vessels of the m e s o a p p e n d i x for adult helminths. T h e a p p e n d i x was s u b s e q u e n t l y o p e n e d u p ' d o w n its length, and the presence or absence of concretions, foreign bodies, adult helminths, b l o o d and m u c u s recorded. T h e m u c o s a w~s e x a m i n e d for evidence of hyperplasia, congestion, o e d e m a , p o l y p o i d g r o w t h s , and u l c e r a t i o n ; the state of configuration and the p a t e n c y of the l u m e n was o b s e r v e d . Microscopic.--The o r g a n was t h e n e x a m i n e d microscopically as follows : - (1) S c r a p i n g s t a k e n f r o m the m u c o u s and s u b m u c o u s coats t o g e t h e r with a p o r t i o n of the c o n t e n t s of the l u m e n triturated in n o r m a l saline. (2) P o r t i o n s of the c o m p l e t e c i r c u m f e r e n c e of the a p p e n d i c u l a r wall at the base, centre and tip, finely divided and digested in 4 per cent. K O H at 56 ° C. (3) Paraffin sections of the c o m p l e t e c i r c u m f e r e n c e of the a p p e n d i c u l a r wall at t h e level of the base, centre and tip. N o serial section m e t h o d was employed.
~40
BILHAR IAL APPENDICITIS.
Any obvious macroscopic lesion was dealt with in a similar manner. In addition, in all cases failing to reveal ova by these methods, the entire remains o f the appendix were digested and the deposit re-examined. In this way twenty out of thirty-five specimens revealed the presence of S. haematobium ova (including four cases in which gross macroscopic lesions were present) and the number of ova present was found to vary considerably in each case. The number on the whole was greatest in those cases showing macroscopic lesions, but that this was not invariably so will be shown later. It was found, as one would expect, that when scanty the ova could be detected by digestive methods more readily than in paraffin sections and scrapings. No S. mansoni ova were ever encountered. The accompanying table summarizes the results.
Positive by different methods of examination. Scrapings, section, and digestion 13 (65 per cent.) Section and digestion only 4 (20 ) Digestion only 3 (15 ,, Total 20 cases.
Negative for S. haematobium ova by all methods. Total 15 cases.
It will be noted that the specimens can now be divided into two groups. Group 1.mTwenty cases revealing the presence of S. haematobium ova, four of which showed gross macroscopic pathology directly due to the presence of the ova. Group 2.--Fifteen cases showing no evidence of the presence of bilharzia ova.
In view of the fact that only one completely normal appendix was encountered, it will be convenient to contrast in tabular form, and discuss the findings in these two groups.
Pathology.
Abnormality of conformation Congestion Adhesions Adult Enterobius vo-micularis Concretions Eosinophilia Catarrh
Group 1. 20 bilharzia positive cases.
Group 2. 15 bilharzia negative cases.
Present.
Absent.
Present.
Absent.
12 12 9 11 5 20 13
8 8 11 9 15 0 7
7 10 5 7
8 5 10 8 14 2 7
1
13 8
A. C. LOVETT-CAMPBELL AND A. V¢. ROSE.
,~4~[
In assessing the value of the findings contrasted above it is necessary to bear in mind the difference in the total number of cases in the two groups, and the fact that the former group contains four cases in which the pathological findings could be shown to be directly due to bilharziasis. It then becomes apparent that almost as many cases in Group 2 show abnormalities of conformation, congestion, adhesions, catarrh, eosinophilia, etc., as those of Group 1. Concretions may be quoted as a possible exception to this rule, and in several cases they were multiple, o f small size, and quartz-like in appearance, owing their origin, it may be, to inspissated mucus associated with catarrh of the mucosa. It is not conclusive, therefore, except where typical macroscopic lesions are present, that the abnormalities mentioned above are necessarily due to the presence of the ova. Attention is drawn to the large number of cases in both groups in which adult Enterobius vermicularis was found (eighteen cases).
Site of bilharzia ova. Submucosa Submucosa
and mucosa
5 cases 7 cases Unknown
Submucosa and Serous coat All c o a t s i n c l u d i n g m u s c u l a r 3 cases
1 case 4 cases
It will be seen that the ova were more commonly found in the submucous coat then elsewhere, but that no coat was exempt. FaIRLEY draws attention to the rarity with which ova were found in the muscular coat of the intestine in his experimental work on monkeys, and it is of interest to note, therefore, that in our series, ova and inflammatory reaction were sometimes seen actually in the substance of both muscle coats separating the muscular fibres. In all the cases showing macroscopic pathology, ova were demonstrable in the serous or subserous coats, and in only one case where these coats were invaded by ova was macroscopic pathology absent. The ova were found singly or in clumps up to about twenty in number, and were usually situated at some point remote from the mesocolic attachment. The ova were usually found in the tissues, and not in the blood vessels. Occasionally they all appeared to be healthy, and the contained miracidia could be plainly seen ; but more often some, or all of them, were degenerate or calcified. They were usually demonstrated throughout the length of the organ, and had no orderly arrangement, so that on section they might be cut in any plane. When in the mucosa they were always seen to lie between the glandular crypts, and in this situation the spine was usually directed towards the lumen.
~4~
BILHARZIAL APPEb.rDICITIS.
The Number of Bilharzia Ova. T h e number of ova appeared to vary in each case but no accurate count was made. The figures given are merely a rough estimate. Very numerous, 3 cases. Numerous, 7 cases. Fairly numerous, 5 cases. Scanty, 5 cases. It is believed that the presence of gross pathology did not entirely depend on the number or concentration of ova present (although doubtless these are factors of some importance), and as evidence of this we find that cases showing very numerous ova did not always present gross pathological lesions ; furthermore, two of the cases showing gross lesions were not remarkable for the frequency with which ova were encountered.
Tissue Reaction. No reaction at all could be seen in seven cases harbouring ova. In seven other cases there was some evidence of non-specific fibrosis, or young fibroblastic reaction in the region of the ova. In the remaining six cases reaction was observed which, from a careful study of the sections, is believed to be typical of the condition under discussion. In tWO of these six cases, the lesions were judged to be early ones, and in the other cases all stages or only late stages were seen. It has been possible collectively to build up what is believed to be the pathological process at work, and amply to confirm the earlier records of FAIRLEY and DEw. This process is illustrated step by step in the accompanying photomicrographs. The earliest changes were found most characteristically in the serous and subserous coats, where in response to the deposition of ova a peculiar type of granulation tissue is laid down. The latter consists of a fibrous stroma abundantly infiltrated with polymorphonuclear eosinophils and a lesser number of round cells and wandering cells. Very numerous capillaries course through its substance. In consequence of this the serous coat becomes enormously thickened and may equal in breadth the remainder of the appendicular wall. There is great concentration of the eoSinophils in the immediate vicinity of the ova, which at this stage are either quite healthy or only slightly degenerate. The capillaries may show lymphocytic " cuffing " and there may be hyperplasia of the endothelium of their walls. In places the reaction may have progressed to the formation around the ova of a characteristic structure, the pseudo-tubercle. The macroscopic appearances at this stage may consist of a localized thickening or bulging of the external surface of the appendix, or they may take the form of fleshy adhesions. The serous coat may be smooth except for the presence in its substance of slightly raised greyish nodules very similar in appearance and size to miliary tubercles. These are in reality pseudo-tubercles and are formed in the following manner.
A. C. LOVETT-CAMPBELL
AND A. W. ROSE.
343
The eosinophils which are concentrated immediately around the ova commence to degenerate. Very soon mononuclear cells, wandering cells, and fibroblasts range themselves around the degenerate central mass in a radial manner like the spokes of a wheel. Multinucleated giant cells, similar to those found in tuberculous tissues, make their appearance, and a confining wall of hard fibrous tissue is laid down at the extreme periphery. By this time the central eosinophils have entirely degenerated, and have been converted into a granular mass with only a few pyknotic remains of the nuclei left to indicate its origin. Probably the ova themselves are by now completely degenerate and possibly calcified. In a typical example the resemblance to a caseous tubercle may be striking. The giant cells appear to act as scavengers, and are often seen surrounding or engulfing the calcified remains of ova. T h e cells of the central zone which are ranged round the central mass like the spokes of a wheel are mainly elongate, and correspond in position, and somewhat in appearance, to the endothelioid cells of the true tubercle. Occasionally they are seen giving off protoplasmic filaments which connect them with each other and the granular nlass which they surround. Sometimes they are aggregated into a mass in which it is difficult to distinguish their individual outlines. It is tempting to believe, that this is a step in the formation of the multinueleate giant cell which is so commonly encountered. The nuclei of the latter were never seen in the process of division. Sections stained by van Gieson's method showed very little deposition of collagen fibrils in the central zone although dense concentric fibres were continually present at the periphery. In lesions of longest standing fibrosis progresses and all that eventually remains of the pseudo-tubercle, is a dense concentric fibrous scar. Between the individual tubercles fibrous granulation tissue is present infiltrated with eosinophils, fibroblasts, plasma cells, mononuclear cells, and occasional ova. Capillaries are numerous but do not seem to enter the pseudotubercles. It is common to find the whole appendicular wall involved in the more advanced cases in which pseudo-tubercles at all stages are seen, but the mucosa as a rule is not invaded by fibrous reaction. It may be pressed upon and the lumen distorted. As a rule the mueosa in these cases is hyperplastic, and the nuclei of the epithelial cells are frequently seen in a state of mitotic division. The mucus cells are actively secreting, and the lymph nodes contain active germinal centres. SUMMARY.
1. Appendicectomy was performed on thirty-five individuals inhabiting a hyperendemic area of bilharziasis in Northern Nigeria. Ova of S. haematobium were present in the urines of all patients.
344
BILHARZIAL APPENDICITIS.
2. Twenty (57 per cent.) of the thirty-five appendices examined showed terminal spined ova. 3. Four (20 per cent.) of the twenty affected appendices had gross macroscopic lesions which were held accountable for the severe appendicular symptoms described. Clinical and pathological details of these four cases are given. 4. Pathological technique and observations are recorded in detail. The histopathology is described and discussed. 5. A constructive account of the pathological process is given, and the stages illustrated by a series of photomicrographs. CONCLUSIONS. Bilharziasis causes its own type of appendicitis, the symptoms of which occasionally become urgent enough to warrant surgical intervention. The gross pathology encountered bears this out. We are only in agreement with BARSOUM when he states that bilharziasis " does not cause or predispose to appendicitis " if this is taken to indicate purely pyogenic inflammations. Acute symptoms clinically indistinguishable from pyogenic appendicitis are in fact occasionally met with. The lesions responsible in such instances result from ova infestation of the appendix upon which gross tissue changes have followed. Such gross bilharzial lesions of the appendix are infrequent : only when present do they cause appendicial symptoms that overshadow the commoner clinical manifestation of bilharzial dysentery. REFERENCES. BaRSOUM,H. (1934). The bilharzial appendix, ft. trop. Med. (Hyg.), xxxvii (24), 387. DEW, H.R. (1923). Observations on the pathology of schistosomiasis (S. haematobium and S. mansoni) in the human subject, ft. Path. Bact., xxvi, 27. FAIRLEY, N. HAMILTON. (1920). A comparative study of experimental bilharziasis in monkeys contrasted with the hitherto described lesions in man. Ibid., xxiii, 289. MADDEN,F.C. (1922). The Surgery of Egypt, 2nd Ed. Cairo : Nile Mission Press.
Vol. XXX. No. 3. November, 1936.
B I L H A R Z I A L A P P E N D I C I T I S IN SCHISTOSOMA HAEMATOBIUM INFESTATIONS. A PRELIMINARY
REPORT.*
BY
A. C. LOVETT-CAMPBELL, 2Viedical O~icer, Colonial Medical Service, West Africa, AND
A. W. ROSE, Pathologist, Colonial Medical Service, West Africa.
The purpose of this paper is threefold ; firstly, to record the frequency with which Sckistosoma haematobium ova and grosser bilharzial lesions implicated a series of thirty appendices, removed at operation from Africans inhabiting a hyperendemic area of Northern Nigeria; secondly, to discuss certain points in the symptomatology of these cases ; and lastly, to describe serially and in some detail the histological changes evident in what are judged to be early, intermediate and late phases of tissue reaction to local ova infiltration within the appendix. A series of photomicrographs illustrates these changes, and serves to amplify the descriptive histopathology of the condition. In preparing this paper, access to selective literature disclosed the thoroughness with which regional distribution of schistosome ova throughout abdominal viscera had previously been investigated by early workers, notably FAIRLEY (1919), MADDEN (1922), and DEW (1923). While thus disclaiming precedence for our observations, we desire to stress certain facts emerging from our recent investigations, which hitherto appear to have received scarcely adequate mention. For example, in our * This paper is published by the permission of Sir WALTERJOHNSON, C.M.G., Director of Medical and Sanitary Services, Nigeria. The pathological data, observations, and illustrations are incorporated in a thesis accepted for the degree of M.D. of the University of Edinburgh. Permission to publish them is gratefully acknowledged. The writers wish to express their gratitude to Dr. N. HAMILTONFAIRLEYfor helpful criticism and encouragement. They also wish to thank Mr. J. KNIGHT, of the Medical Research Institute, Lagos, for unstinted pains taken with the preparation of certain of the photomicrographs.
886
BILHARZIAL APPENDICITIS.
series of cases, the notable frequency of appendicial lesions* arising exclusively f r o m S. haematobium infestations, deserves particular emphasis, i n a s m u c h as only scant reference to isolated instances of this nature appear in m o s t u p - t o - d a t e text-books. Only four patients had unmistakable appendicular colic and, in each of these, the implicated appendices had characteristic bilharzial lesions of macroscopic degree serving to demonstrate, b e y o n d all reasonable doubt, that occasionally a c u t e appendicitis--clinically indistinguishable f r o m its more familiar surgical c o u n t e r p a r t s - - c a n , and does in fact, arise f r o m uncomplicated S. haematobium infestations. Thirdly, in contrast with the above, a majority group, c o m p r i s i n g sixteen individuals with ova-infested appendices, and fifteen individuals with negative appendices, gave histories, in which the p r e d o m i n a t i n g s y m p t o m s were diffuse abdominal colic, associated with mucoid diarrhoea. Indeed, the p r e d o m i n a n c e of these s y m p t o m s suggested extensive colonic involvement, while a c c o m p a n y i n g appendicial lesions present in just over half the n u m b e r - - b e i n g of m i n o r degree, were, clinically, either masked or actually the cause of no local s y m p t o m s . T h a t the prevailing lesions in this group were colonic, lacks pathological confirmation, as none of our cases came to autopsy. But it has long been observed that mucoid diarrhoea o c c u r s in association with S. haematobium infections, and that terminal spined ova occasionally appear in the stools of these patients, while autopsies confirm the frequency of colonic and rectal lesions. O u r first patient was operated u p o n f o r acute appendicitis.
Case History. Early in March, 1935, an African male, aged 30, was admitted to hospital with a history of recurring, low abdominal pain, diarrhoea and vomiting, of three years duration. Attacks were frequent, usually occurring about every 10 days, and subsiding gradually, after 3 or 4 days. Vomiting always ceased early. Symptoms almost similar to the above were actually witnessed while the patient came under observation in hospital. Closer examination disclosed definite tenderness, more or less constant, over the appendix area, unaccompanied by local rigidity. On digital pressure, marked gurgling of the caecum could be elicited. Faeces and urine were free from ova. Red blood ceils were present in both. Cysts of Entamoeba histolytica were also detected in the faeces. Classified as a dysenteric, this patient was given one week's treatment with emetine and yatren. As no noticeable abatement of symptoms resulted, appendicectomy was performed. At operation a large free appendix was removed. Its extremity was bulbous and tense. The serous coat was injected. Slender, easily divided bands encircled a distended caecum, and ballooned the distal saceulations of the ascending colon. The patient made an uneventful recovery, with immediate and complete cessation of symptoms. The pathological comments read as follows .--"" The appendix shows a condition of subaeute inflammation, and infiltration with round cells and eosinophils, associated with the presence of schistosome ova in the submucosa. Curiously enough, these appear to be S. haematobium, rather than S. mansoni. The condition is an interesting one;" The term " lesion '! is employedhere in a wide sense to include the deposit of ova with 9r without tissue reaction resulting therefrom.
A. C. LOVETT-CAMPBELL AND A. W. ROSE.
~.~7
D u r i n g the subsequent 6 months, thirty-four more appendicectomies ,aTere carried out. Each case was investigated clinically, with a view to establishing a possible relationship between s y m p t o m s and the pathological changes encountered. All patients at the time of admission to hospital were excreting haematobium ova in their urines. Four appendices had gross macroscopic lesions. T o g e t h e r with the histories given, these four specimens provide convincing proof that acute appendicitis, clinically indistinguishable from its pyogenic forms, occasionally arises in bilharziasis. This is contrary to the view of BA~SOUM (1934) that bilharziasis does not cause or predispose to appendicitis. T h i r t y other cases in the series, including sixteen with infested appendices, manifested characteristic dysenteric s y m p t o m s - - a b d o m i n a l colic and profuse mucoid diarrhoea. T h e constancy of these s y m p t o m s in so m a n y cases, irrespective of whether appendicular infestation with ova was proved to exist or not, favours the conclusion that their seat of origin is the colon, not the appendix ; that only in the presence of gross bitharzial lesions of the appendix, do symptoms referable to that organ overshadow associated colonic symptoms. As regards the discovery of ova within the lumen of the appendix, it is conceivable in certain instances that ova may gravitate accidentally there from the caecum, and thus come to lie between the glandular crypts. Below, an account is given of four cases, previously mentioned as having gross lesions of the appendix. Case 1 .--;'¢Iale aged 25. ClinicaL--Symptoms commenced 9 years ago, since when he experienced four severe
bouts of abdominal pain. Vomiting preceded each attack, and pain was relieved by lying face downwards. The onset was always gradual. The pain attained great severity, and subsided at the end of 2 days. It was ahYays most marked over the appendix region, the patient adding that in this area the abdomen became " like a stick " (rigidity). Diarrhoea and looseness of the bowels were frequent, but lately he has tended to be constipated. Pathological.--The appendix was distorted and kinked 2 cm. from the tip by a fibrous mmour, 1.4 × 1 × 1 cm. in size, which occupied half of the circumference of the appendicular wall on the side remote from the mesocolic attachment. The mucosa was intact but pressed upon by the tumour, the lumen being distorted and crescentic in shape, with the concavity towards the tumour. The mucosa showed the presence of congestion and catarrh, and the lumen contained a plug of amorphous matter coated with a layer of mucus, desquamated epithelial cells, and erythrocytes. There was intense infiltration of the mucosa with round cells and eosinophil polymorphs. The tumour was composed of chronic inflammatory reaction surrounding numerous ova of S. haematobium, which had apparently been deposited in the submucosa, at a point remote from the mesocolic attachment. The circular muscle coat was thickened, and showed hyaline Change, and had been ruptured. The ruptured ends were plainly seen, separated by the inflammatory mass. Three-quarters of the tumour lay peripheral to the muscle coat. The surface of the tumour was smooth, except for the presence of minute greyish tubercles 1 to 2 ram. in size, which were very slightly raised above the surface. The structure of the tumour varied slightly in different parts ; broadly speaking it tended to E
~3~
BILHARZIAL APPENDICITIS.
be more cellular within the muscle coats, i.e., in the usual situation of the submucosa, and more fibrous outside these coats at the periphery of the tumour. This favoured the inference that the latter was Of longer standing than the former. T h e serous coat was seen stretched out over the surface of the tumour for a short distance, and then merged into it. T h e structure of the inflammatory mass was as follows : Whorls of fibrous tissue surrounding single or multiple ova were embedded in a matrix of cellular and vascular granulation tissue, abundantly infiltrated with wandering cells, round cells, and eosinophil polymorphs. T h e fibrous whorls differed from each other, and the difference was believed to be due to their respective ages. Five types were seen : - (1) A dense concentration of e0sinophils and wandering cells around the ovum, with outside this a layer of cells resembling fibroblasts. (2) Similar to (1) but the eosinophils had undergone degenerative change although the nuclei were still visible. T h e fibroblasts were ranged radially t o the central mass like the spokes of a wheel, and a concentric wall of fibrosis limited the structure. (3) T h e granular dtbris was no longer apparent, but foreign body giant cells were commonly found. Phagocytosis of the ova could be seen. (4) Similar to the above but very little remained of the ova, and fibrosis was more marked. (5) A concentric fibrous scar alone remained.
Case 2.
Male aged 20.
ClinicaL--Abdominal trouble commenced 6 years ago, characterized b y colicky pain and mucoid diarrhoea. Mild attacks occurred at intervals of 4 months, were gradual i t onset, and continued for at least a day. N o vomiting occurred. No early haernaturia had been noticed. PathologicaL--Two cm. from the base of the appendix there was an irregular swelling 2 × 1 era. in size formed by a localized increase in the appendicular wall. T h e peritoneal surface was smooth and glistening, but minute greyish tubercles could be seen in the substance of the tumour. T h e tip of the appendix was also distorted by a small fleshy beaklike tumour showing the presence of tubercles. A smaller pedunculated mass was found at the junction of the middle and distal thirds and resembled a smooth wart. T h e lumen was filled with a plug of mucus and catarrhal epithelial cells. Th e mucosa was abundantly infiltrated with round cells and eosinophil polymorphs. T h e germinal centres of the l y m p h nodes were prominent. T h e longitudinal muscle coat and subserous coats were much thickened by the presence of granulation tissue heavily infiltrated with eosinophilic polymorphs. S. haematobium ova were present. T h e tissue was vascular. Here and there were pseudo-tubercles of early type; T h e circular muscle coat was split by pseudo-tuberculous reaction. T h e submucosa also contained ova, and here the reaction was of the giant cell type with phagocytosis of the ova. T h e subserous coat was thickened to such an extent that it equalled in breadth the rest of the appendicular wall. Case 3.
Male aged 16.
ClinicaL--Abdominal trouble commenced 3 years ago with severe attacks of colic that occurred every 3 months. Vomiting preceded their onset while during attacks pronounced mueoid diarrhoea was a feature. Pain commenced in the epigastrium and spread to the right iliac fossa. Relief was obtained by pressure over this area. Haematuria , present from childhood, still recurred, usually at intervals of 3 months. PathologicaL--The appendix proper was fairly normal in appearance, but present at its distal extremity was a dense band of adhesions about 2 era. long containing a leash of vessels. This band of tissue connected the tip Of the appendix with a solid 0val tumour 1½ × 1 era. in size. T h e adhesions were twisted on themselves. Th e surface of the turnout was nodular owing to the presence of large numbers of minute greyish tubercle-like elevations. (a) T h e appendix p r o p e r . - - T h e lumen contained erythrocytes and catarrhal epithelial cells. T h e mueosa was congested and infiltrated with round ceils and eosinophil polymorphs
"t
FIe-. 1.
Fie.. 2.
FIe;. 5.
FIG. 3.
FIG. 4.
FIG. 6.
FIGS. 1-4 . - - A p p e n d i c e s from Cases 1-4. FIG. 5.--Calcified ova in the submucosa. N o t e in this case the absence of specific tissue reaction. × 27. FIG. 6 . - - S i m i l a r to Fig. 5, b u t showing o v u m lying between the glandular crypts.
To face page
338.
× 93.
FIG. 7.
Fro. 8.
FIG. 9. FIG. 7.--Pseudo-tuberculous granulation ussue.
FIG. 10 Note the presence of several ova.
× 93.
Fro. 8.--Concentric whorls of fibrosis in relation to very numerous degenerate ova.
× 93.
FIG. 9.--Pseudo-tuberculous tissue demonstrating the presence of cellular infiltration, calcified ova, and multinucleate giant cells. × 60. THE EVOLUTION OF THE PSEUDO-TUBERCLE
(FIGS. 10-14).
FIC. 10.--Ovum surrounded by concentration of eosinophil polyrnorph cells.
× 175.
F m . 11
FIG. 12.
FIG. 13.
Fra. l l . - - G r a n u l a r
FIG. 14.
d e g m e r a t i o n of cells around central ovum. Note the spindle cells arrangad radially around the central mass. × 95. FIG. 1 2 . - - M u l t i n u c l e a t e giant cell.
x 360.
FIg. 13.--Phagocytosis of calcified o v u m by mu!tinucleate giant cell. FIG. 1 4 . - - F i b r o u s scar.
× 360.
× 360.
A, C. LOVETT-CAMPBELL
AND A. W. ROSE.
~9'
and contained a few S. haematobium ova. The submucosa contained clumps of ova numbering 1 to 10 but there was no characteristic reaction. They were situated remote from the mesocolic attachment. The serous coat was thickened and infiltrated with ova. (b) The tumour.--This consisted of a solid mass of pseudo-tubercles surrounding myriads of ova which were mainly calcified. The tubercles were of an advanced type although giant cells were commonly present. (c) The adhesions.---These presented a similar picture to that shown by the tumour. Case 4. Male aged 37. Clinical.--Symptoms commenced 5 years ago with mid-abdominal colic. Attacks alternated with periods of freedom. He recollected four pronounced attacks in 5 years. Each continued for about 3 days. The pain commenced low down above the middle of the right inguinal ligament, and compelled him to lie still. There was no vomiting, but diarrhoea and the passage of blood and sometimes mucus in slight amount occurred. There had been haematuria in childhood. Operation 14th Sept., 1935.--The appendix was difficult to locate, lying retrocaecally buried in adhesions. The caecum was fixed and immobile. The appendix was enlarged and tortuous. The serous coat was much injected. Pathologieal.--The lumen contained a catarrhal plug. The mucous membrane was slightly thickened with marked cellular infiltration. The submucosa, also slightly thickened in parts, was infiltrated with round cells, eosinophils, and fibroblasts. S. haematobium ova were scattered about it singly and in pairs. The muscular coat appeared thickened. The serous coat was definitely thickened in parts and was very vascular. Fairly numerous ova were present in its substance. Many of the smaller vessels in the serous coat were cuffed with lymphoeytes. The serous coat at one point was thickened to form a fleshy adhesion binding down the kinked tip of the appendix to the main body of the organ. PATHOLOGICAL TECHNIQUE AND OBSERVATIONS. T h e s p e c i m e n s n u m b e r i n g thirty-five in all were fixed in 10 per cent. formolzsaline. A s e a r c h i n g m a c r o s c o p i c and m i c r o s c o p i c e x a m i n a t i o n was carried o u t in each case, and particular attention was paid to the following points. .Macroscopic.--Measurements i n c l u d i n g length, average diameter~ a n d thickness of the wall ; abnormalities o f c o n f o r m a t i o n i n c l u d i n g kinking, nodules, or callosities ; the p r e s e n c e of adhesions and congestion of the surface vessels i search o f surface vessels and also the vessels of the m e s o a p p e n d i x for adult helminths. T h e a p p e n d i x was s u b s e q u e n t l y o p e n e d u p ' d o w n its length, and the presence or absence of concretions, foreign bodies, adult helminths, b l o o d and m u c u s recorded. T h e m u c o s a w~s e x a m i n e d for evidence of hyperplasia, congestion, o e d e m a , p o l y p o i d g r o w t h s , and u l c e r a t i o n ; the state of configuration and the p a t e n c y of the l u m e n was o b s e r v e d . Microscopic.--The o r g a n was t h e n e x a m i n e d microscopically as follows : - (1) S c r a p i n g s t a k e n f r o m the m u c o u s and s u b m u c o u s coats t o g e t h e r with a p o r t i o n of the c o n t e n t s of the l u m e n triturated in n o r m a l saline. (2) P o r t i o n s of the c o m p l e t e c i r c u m f e r e n c e of the a p p e n d i c u l a r wall at the base, centre and tip, finely divided and digested in 4 per cent. K O H at 56 ° C. (3) Paraffin sections of the c o m p l e t e c i r c u m f e r e n c e of the a p p e n d i c u l a r wall at t h e level of the base, centre and tip. N o serial section m e t h o d was employed.
~40
BILHAR IAL APPENDICITIS.
Any obvious macroscopic lesion was dealt with in a similar manner. In addition, in all cases failing to reveal ova by these methods, the entire remains o f the appendix were digested and the deposit re-examined. In this way twenty out of thirty-five specimens revealed the presence of S. haematobium ova (including four cases in which gross macroscopic lesions were present) and the number of ova present was found to vary considerably in each case. The number on the whole was greatest in those cases showing macroscopic lesions, but that this was not invariably so will be shown later. It was found, as one would expect, that when scanty the ova could be detected by digestive methods more readily than in paraffin sections and scrapings. No S. mansoni ova were ever encountered. The accompanying table summarizes the results.
Positive by different methods of examination. Scrapings, section, and digestion 13 (65 per cent.) Section and digestion only 4 (20 ) Digestion only 3 (15 ,, Total 20 cases.
Negative for S. haematobium ova by all methods. Total 15 cases.
It will be noted that the specimens can now be divided into two groups. Group 1.mTwenty cases revealing the presence of S. haematobium ova, four of which showed gross macroscopic pathology directly due to the presence of the ova. Group 2.--Fifteen cases showing no evidence of the presence of bilharzia ova.
In view of the fact that only one completely normal appendix was encountered, it will be convenient to contrast in tabular form, and discuss the findings in these two groups.
Pathology.
Abnormality of conformation Congestion Adhesions Adult Enterobius vo-micularis Concretions Eosinophilia Catarrh
Group 1. 20 bilharzia positive cases.
Group 2. 15 bilharzia negative cases.
Present.
Absent.
Present.
Absent.
12 12 9 11 5 20 13
8 8 11 9 15 0 7
7 10 5 7
8 5 10 8 14 2 7
1
13 8
A. C. LOVETT-CAMPBELL AND A. V¢. ROSE.
,~4~[
In assessing the value of the findings contrasted above it is necessary to bear in mind the difference in the total number of cases in the two groups, and the fact that the former group contains four cases in which the pathological findings could be shown to be directly due to bilharziasis. It then becomes apparent that almost as many cases in Group 2 show abnormalities of conformation, congestion, adhesions, catarrh, eosinophilia, etc., as those of Group 1. Concretions may be quoted as a possible exception to this rule, and in several cases they were multiple, o f small size, and quartz-like in appearance, owing their origin, it may be, to inspissated mucus associated with catarrh of the mucosa. It is not conclusive, therefore, except where typical macroscopic lesions are present, that the abnormalities mentioned above are necessarily due to the presence of the ova. Attention is drawn to the large number of cases in both groups in which adult Enterobius vermicularis was found (eighteen cases).
Site of bilharzia ova. Submucosa Submucosa
and mucosa
5 cases 7 cases Unknown
Submucosa and Serous coat All c o a t s i n c l u d i n g m u s c u l a r 3 cases
1 case 4 cases
It will be seen that the ova were more commonly found in the submucous coat then elsewhere, but that no coat was exempt. FaIRLEY draws attention to the rarity with which ova were found in the muscular coat of the intestine in his experimental work on monkeys, and it is of interest to note, therefore, that in our series, ova and inflammatory reaction were sometimes seen actually in the substance of both muscle coats separating the muscular fibres. In all the cases showing macroscopic pathology, ova were demonstrable in the serous or subserous coats, and in only one case where these coats were invaded by ova was macroscopic pathology absent. The ova were found singly or in clumps up to about twenty in number, and were usually situated at some point remote from the mesocolic attachment. The ova were usually found in the tissues, and not in the blood vessels. Occasionally they all appeared to be healthy, and the contained miracidia could be plainly seen ; but more often some, or all of them, were degenerate or calcified. They were usually demonstrated throughout the length of the organ, and had no orderly arrangement, so that on section they might be cut in any plane. When in the mucosa they were always seen to lie between the glandular crypts, and in this situation the spine was usually directed towards the lumen.
~4~
BILHARZIAL APPEb.rDICITIS.
The Number of Bilharzia Ova. T h e number of ova appeared to vary in each case but no accurate count was made. The figures given are merely a rough estimate. Very numerous, 3 cases. Numerous, 7 cases. Fairly numerous, 5 cases. Scanty, 5 cases. It is believed that the presence of gross pathology did not entirely depend on the number or concentration of ova present (although doubtless these are factors of some importance), and as evidence of this we find that cases showing very numerous ova did not always present gross pathological lesions ; furthermore, two of the cases showing gross lesions were not remarkable for the frequency with which ova were encountered.
Tissue Reaction. No reaction at all could be seen in seven cases harbouring ova. In seven other cases there was some evidence of non-specific fibrosis, or young fibroblastic reaction in the region of the ova. In the remaining six cases reaction was observed which, from a careful study of the sections, is believed to be typical of the condition under discussion. In tWO of these six cases, the lesions were judged to be early ones, and in the other cases all stages or only late stages were seen. It has been possible collectively to build up what is believed to be the pathological process at work, and amply to confirm the earlier records of FAIRLEY and DEw. This process is illustrated step by step in the accompanying photomicrographs. The earliest changes were found most characteristically in the serous and subserous coats, where in response to the deposition of ova a peculiar type of granulation tissue is laid down. The latter consists of a fibrous stroma abundantly infiltrated with polymorphonuclear eosinophils and a lesser number of round cells and wandering cells. Very numerous capillaries course through its substance. In consequence of this the serous coat becomes enormously thickened and may equal in breadth the remainder of the appendicular wall. There is great concentration of the eoSinophils in the immediate vicinity of the ova, which at this stage are either quite healthy or only slightly degenerate. The capillaries may show lymphocytic " cuffing " and there may be hyperplasia of the endothelium of their walls. In places the reaction may have progressed to the formation around the ova of a characteristic structure, the pseudo-tubercle. The macroscopic appearances at this stage may consist of a localized thickening or bulging of the external surface of the appendix, or they may take the form of fleshy adhesions. The serous coat may be smooth except for the presence in its substance of slightly raised greyish nodules very similar in appearance and size to miliary tubercles. These are in reality pseudo-tubercles and are formed in the following manner.
A. C. LOVETT-CAMPBELL
AND A. W. ROSE.
343
The eosinophils which are concentrated immediately around the ova commence to degenerate. Very soon mononuclear cells, wandering cells, and fibroblasts range themselves around the degenerate central mass in a radial manner like the spokes of a wheel. Multinucleated giant cells, similar to those found in tuberculous tissues, make their appearance, and a confining wall of hard fibrous tissue is laid down at the extreme periphery. By this time the central eosinophils have entirely degenerated, and have been converted into a granular mass with only a few pyknotic remains of the nuclei left to indicate its origin. Probably the ova themselves are by now completely degenerate and possibly calcified. In a typical example the resemblance to a caseous tubercle may be striking. The giant cells appear to act as scavengers, and are often seen surrounding or engulfing the calcified remains of ova. T h e cells of the central zone which are ranged round the central mass like the spokes of a wheel are mainly elongate, and correspond in position, and somewhat in appearance, to the endothelioid cells of the true tubercle. Occasionally they are seen giving off protoplasmic filaments which connect them with each other and the granular nlass which they surround. Sometimes they are aggregated into a mass in which it is difficult to distinguish their individual outlines. It is tempting to believe, that this is a step in the formation of the multinueleate giant cell which is so commonly encountered. The nuclei of the latter were never seen in the process of division. Sections stained by van Gieson's method showed very little deposition of collagen fibrils in the central zone although dense concentric fibres were continually present at the periphery. In lesions of longest standing fibrosis progresses and all that eventually remains of the pseudo-tubercle, is a dense concentric fibrous scar. Between the individual tubercles fibrous granulation tissue is present infiltrated with eosinophils, fibroblasts, plasma cells, mononuclear cells, and occasional ova. Capillaries are numerous but do not seem to enter the pseudotubercles. It is common to find the whole appendicular wall involved in the more advanced cases in which pseudo-tubercles at all stages are seen, but the mucosa as a rule is not invaded by fibrous reaction. It may be pressed upon and the lumen distorted. As a rule the mueosa in these cases is hyperplastic, and the nuclei of the epithelial cells are frequently seen in a state of mitotic division. The mucus cells are actively secreting, and the lymph nodes contain active germinal centres. SUMMARY.
1. Appendicectomy was performed on thirty-five individuals inhabiting a hyperendemic area of bilharziasis in Northern Nigeria. Ova of S. haematobium were present in the urines of all patients.
344
BILHARZIAL APPENDICITIS.
2. Twenty (57 per cent.) of the thirty-five appendices examined showed terminal spined ova. 3. Four (20 per cent.) of the twenty affected appendices had gross macroscopic lesions which were held accountable for the severe appendicular symptoms described. Clinical and pathological details of these four cases are given. 4. Pathological technique and observations are recorded in detail. The histopathology is described and discussed. 5. A constructive account of the pathological process is given, and the stages illustrated by a series of photomicrographs. CONCLUSIONS. Bilharziasis causes its own type of appendicitis, the symptoms of which occasionally become urgent enough to warrant surgical intervention. The gross pathology encountered bears this out. We are only in agreement with BARSOUM when he states that bilharziasis " does not cause or predispose to appendicitis " if this is taken to indicate purely pyogenic inflammations. Acute symptoms clinically indistinguishable from pyogenic appendicitis are in fact occasionally met with. The lesions responsible in such instances result from ova infestation of the appendix upon which gross tissue changes have followed. Such gross bilharzial lesions of the appendix are infrequent : only when present do they cause appendicial symptoms that overshadow the commoner clinical manifestation of bilharzial dysentery. REFERENCES. BaRSOUM,H. (1934). The bilharzial appendix, ft. trop. Med. (Hyg.), xxxvii (24), 387. DEW, H.R. (1923). Observations on the pathology of schistosomiasis (S. haematobium and S. mansoni) in the human subject, ft. Path. Bact., xxvi, 27. FAIRLEY, N. HAMILTON. (1920). A comparative study of experimental bilharziasis in monkeys contrasted with the hitherto described lesions in man. Ibid., xxiii, 289. MADDEN,F.C. (1922). The Surgery of Egypt, 2nd Ed. Cairo : Nile Mission Press.