J Clin Pathol 1987;40:424-428

Appendicular schistosomiasis: a cause of clinical acuteappendicitis?MB SATTI, DM TAMIMI, MO AL SOHAIBANI, A AL QUORAIN

From the Department ofPathology, King Faisal University, Dammam, Saudi Arabia

SUMMARY The role of schistosomes in the pathogenesis of acute appendicitis in an endemic area-was investigated. Of 1600 appendicectomies received in our laboratory, 26 showed appendicealschistosomiasis, which prompted what we believe to be the first detailed histopathological evalu-ation of all appendices with schistosomal infestation, without prior knowledge of the clinical andoperative diagnoses. The results suggest that there are two types of schistosomal appendicitis, eachwith distinct clinicopathological features and different pathogenetic mechanisms. They could becalled obstructive and granulomatous schistosomal acute appendicitis, respectively.

Schistosomiasis of the appendix is a recognised phe-nomenon, the appendix being regarded as one of theectopic sites for haematobium species. In a necropsystudy of 96 patients Lima' found appendiceal diseasein four with "ectopic lesions" due to Schistosomamansoni infestation. As far as we know there has beenno previous detailed study on the role of schis-tosomiasis in the pathogenesis of acute appendicitis,even from endemic areas. In another necropsy studySmith2 reported that Schistosoma haematobium eggsprefer the appendix, but the problem was notaddressed by Abdel Wahab in his work on schis-tosomiasis in Egypt.3 In this paper we examine therole of schistosomes in the pathogenesis of acuteappendicitis.

Material and methods

The material for this study was retrieved from the filesof the pathology department of King Fahd Hospital,Al-Khobar, during 1982-1985. Of all the cases ofacute appendicitis coming to surgery in that period,those showing schistosomal ova in the appendicealwall were included in this study. Without priorknowledge of their clinical data or diagnoses, adetailed histopathological evaluation was performedon stained paraffin sections. Where necessary, sec-tions were recut from retrieved paraffin blocks andstained with haematoxylin and eosin to investigateany correlation between presence of the ova and clin-ical presentation.

Histopathological critera recorded included thepresence or absence of the following: active granu-

Accepted for publication 27 October 1986

lomatous inflammation with eosinophilic necrosisaround ova; tissue eosinophilia; purulent exudate inlumen, or wall, or both; fibrosis without a purulentexudate or active granulomas; and faecoliths. Weconsidered that the appendix showed pathologicalevidence of recent symptomatic inflammation if therewere active granulomas with tissue necrosis (fig 1) ora purulent exudate in lumen or wall, or both. The firstgroup were called schistosomal granulomatous acuteappendicitis and the second, schistosomal obstructiveacute appendicitis. Appendices that showed neitheractive granulomas nor a purulent exudate, but onlyschistosomal ova occasionally accompanied byfibrosis and calcification (fig 2), were considered toshow no pathological evidence of recent symptomaticinflammation.The patients' charts were reviewed for information

on age, sex, symptoms and duration, signs, -clinicaldiagnosis, operative findings and the white cellcounts, including the neutrophil and eosinophilcounts.

Results

Of 16000 surgical specimens, 1600 were appen-dicectomies. On histopathological review, 1400 (87%)showed transmural acute appendicitis. In all, 26 casesof appendiceal schistosomiasis were found. Of these,19 showed pathological evidence of recent symptom-atic inflammation. Eleven of these qualified for inclu-sion in the group with schistosomal obstrucive acuteappendicitis and eight for inclusion in the group withschistosomal granulomatous acute appendicitis. Theremaining seven did not show pathological evidenceof recent symptomatic inflammation. Severe fibrosis

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Appendicular schistosomiasis

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Fig 1 Appendix with active granulomatous reaction andtissue necrosis. (Haematoxylin and eosin.) x 375.

of the wall with numerous calcified ova was thepathological hall mark of this group. Interestingly,fibrosis and calcification of ova were consistentlypresent in the wall of appendices that showed puru-lent exudation (fig 3), which was not a conspicuousfeature of appendices with active granulomas andeosinophils in the wall.

Table I summarises the clinicopathological cor-

relation between these patients. Of the 21 patientswith clinically diagnosed acute appendicitis, 19 hadhistopathological evidence of recent symptomaticinflammation, accounting for the symptoms andsigns. The remaining two showed no pathological evi-dence of recent symptomatic inflammation. The threepatients with clinically diagnosed chronic appen-dicitis showed no pathological evidence of recentsymptomatic inflammation. In one of these threepatients the appendix had been removed during cho-lecystectomy because of chronic cholecystitis. Twopatients had clinically diagnosed ureteric obstruction,and their appendices were removed. No pathologicalevidence of recent symptomatic inflammation was

found in either case.Table 2 shows the information on age, sex, and

Fig 2 Appendix with schistosomal ova andfibrosis in wall.Note absence ofgranulomas and purulent exudation. (Hae-matoxylin and eosin.) x 125.

white cell counts of patients with schistosomalobstructive appendicitis. Table 3 shows that per-taining to patients with schistosomal granulomatousacute appendicitis, and table 4 that of patients withappendices without pathological evidence of recentsymptomatic inflammation.

Discussion

Acute appendicitis is a common clinical problem.Surgically removed appendices comprise 10% ofmaterial coming to our surgical pathology labora-

Table I Summary of clinicopathological correlation ofpatients with appendiceal schistosomiasis

Pathological diagnosis

No of Recent symptomatic Not inflamedClinical diagnosis patients inflammation

Acute appendicitis 21 19 2Chronic

appendicitis 3 3Incidental removal

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Fig 3 Appendix with fibrosis and calcification in wall inpresence ofpurulent exudation. (Haematoxylin and eosin.)x 320.

Satti, Tamimi, al-Sohaibani, al-Quoraintory. About 87% of these appendices showed evi-dence of transmural acute appendicitis. Obstructionfollowed by infection from faecal contaminants isthought to be an important pathogenetic mechanismnin acute appendicitis.4 Objective evidence of such an

obstruction, however, is found only in a proportionof cases, further emphasising the existence of the non-obstructive form of acute appendicitis.Of the 19 appendices with schistosomal and histo-

pathological evidence of recent symptomaticinflammation, 11 showed suppuration in addition tosevere fibrosis of a portion of the wall, induced by thenumerous calcified ova inside it. No active granu-

lomas or tissue eosinophilia were noted. As no fae-coliths were found, the schistosomal fibrosis was

probably the cause of the obstruction that led to bac-terial infection from faecal contaminants: we suggestthat this be termed schistosomal obstructive acuteappendicitis.

These appendices were all from male patients, withan age range between 25 and 45 years and a median of39 years. Leucocytosis with an absolute neutrophiliawas a notable feature, in keeping with bacterial infec-tion. Blood eosinophilia was occassionally noted. Allof these 11 patients had the typical symptoms andsigns of acute appendicitis.The remaining eight appendices with schis-

tosomiasis showed active granulomatous inflam-mation around viable ova, with tissue necrosis and a

tissue eosinophilia. No obstruction was noted, andneutrophil exudation was not a feature. All of thesepatients presented with typical symptoms and signs of

Table 2 Schistosomal obstructive acute appendicitis

White cell count AbsoluteCase No Age Sex x 109/l Neurophil % neutrophils x 109/l Eosinophil %

1 43 M 12 5 91 11-4 02 38 M 8-9 57 51 103 42 M 11-8 70 8-3 44 39 M 13 75 98 35 45 M 9-3 64 6-0 26 29 M 113 65 74 37 40 M 134 50 67 58 34 M 12-8 77 9-9 69 36 M 113 88 99 010 25 M 6-4 60 3-8 1711 40 M 8-7 73 6-4 1

Table 3 Schistosomal granulomatous acute appendicitis

White cell count AbsoluteCase No Age Sex x 109/l Neutrophil % neutrophils x IO9/l Eosinophil %

1 27 M 6-8 52 3-5 72 30 M 9-3 70 6-5 33 23 M 4-7 29 1-4 24 25 M 7-0 45 3 2 25 17 M 12-2 65 7-9 16 30 M 8-6 59 5-1 37 18 M 6-5 55 3-6 t08 19 M 7-1 68 4-8 13

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Table 4 Appendices without pathological evidence of recent symptomatic acute inflammation

White cell count AbsoluteCase No Age Sex Clinical diagnosis x 109/l Neutrophil % neutrophils x 109/l

1 35 M Acute appendicitis 6-8 65 4-42 18 M Acute appendicitis 5-6 54 3-03 40 M Chronic appendicitis 6-6 50 3-34 30 M Chronic appendicitis 3-3 48 1-65 45 M Cholecystectomy 5 3 63 3-36 26 M Ureteric obstruction 6-3 64 4-07 25 M Ureteric obstruction 7-2 64 4-6

Table 5 Two disease states of schistosomal acute appendicitis

Feature Granulomatus Obstructive

Sex Male MaleAge range (years) 17-30 25-45Median 23 39

Total white cells Normal or mild leucocytosis LeucocytosisNeutrophils (blood) Normal IncreasedGranulomas with tissue necrosis Present AbsentTissue eosinophils Numerous Relatively fewPurulent exudate Absent PresentFibrosis and calcification of wall Absent PresentFaecolith Absent AbsentPathogenesis Immunological Bacterial: follows fibrotic obstructionTime of occurrence after infestation Early (weeks) Late (months to years)

acute appendicitis; we suggest that this be termedschistosomal granulomatous acute appendicitis.These patients were all men, but of a relatively youn-ger age, 17 to 30 years and a median of 23 years. Theirtotal white cell counts were either normal or low-highin contrast to patients in the group with obstructiveappendicitis who, except one, had total white cellcounts above 8-7 x 109/l. Absolute neutrophilia wasnoted in most of the patients with schistosomalobstructive acute appendicitis. Blood eosinophiliawas noted in some cases, and was not an importantdifferentiating feature between the two disease states.Granulomatous tissue destruction is probably the

direct cause of symptoms and signs in patients withschistosomal granulomatous acute appendicitis. Thegranuloma formation is most likely a host immu-nological reaction to a product of the ova, the socalled soluble egg antigen (SEA).5 It has been specu-lated that granuloma formation reaches its maximalsize several weeks after onset of egg laying and there-after decreases around eggs newly deposited in tis-sues. This phenomenon was originally calledendogenous desensitisation.6 7 In support of this the-ory of an immunological reaction to recently depos-ited eggs, one of the appendices with activegranulomatous inflammation that we studied showeda viable schistosomal worm in a venous channel of theappendiceal wall, probably indicating recent ova lay-ing (fig 4). The relatively younger age of patients withschistosomal granulomatous acute appendicitis fur-ther supports this theory, indicating a probably recentinfection with schistosomes.

Granulomatous inflammation of the appendix hasbeen reported to be the direct cause of symptoms andsigns of acute appendicitis. Fourteen of 19 patientswith isolated Crohn's disease of the appendix had ahistory of less than 72 hours and a clinical dignosis ofacute appendicitis.8 In another series9 22 of thereviewed 31 cases with primary Crohn's disease of theappendix had a preoperative diagnosis of acuteappendicitis. In a third series'0 six of 12 patients withCrohn's disease of the appendix had a disease historyof one to three days. Vague right lower abdominalpain due to granulomatous appendicitis, presumablysecondary to yersinial infection was reported in threecases." Tuberculosis'2 -14 and sarcoidosis'5 werealso reported to offset the appendix and producesymptoms and signs of acute appendicitis. In all ofthese cases and in schistosomal granulomatous acuteappendicitis it was the granulomatous destruction oftissue that was the direct cause of pain in the absenceof purulent exudation.The data presented suggest that schistosomes could

cause acute appendicitis via either one of two patho-genetic pathways. The recently deposited ova mightinduce an immunological granulomatous reactionleading to tissue destruction and thus directly leadingto acute appendicitis (schistosomal granulomatousacute appendicitis). This occurs in younger patientsduring the early phase of egg laying in the appendix.Neutrophil leucocytosis is not a characteristic feature.Schistosomes could also result in acute appendicitisvia an indirect pathway. Excessive fibrosis, the resultof long standing inflammation and calcified ova in the

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428 Satti, Tamimi, al-Sohaibani, al-Quorainwall, could lead to obstruction followed by bacterialinfection, which occurs in other forms of obstructiveacute appendicitis.The presence of schistosomal ova in the wall of the

appendix is not always symptomatic. Appendiceswith schistosomal ova but without pathological evi-dence of recent symptomatic inflammation wereremoved in seven instances (table 4). In three patientsthis occurred during either exploration for uretericobstruction (two patients) or cholescystectomy (onepatient). There were no symptoms or signs referrableto the appendix. In two instances the indication forremoval was vague symptoms referred to as chronicappendicitis. Two other patients had a clinical diag-nosis of probable acute appendicitis, which was notconfirmed at operation or histologically. In all sevenpatients the total white cell counts were normal, witha normal neutrophil count but an occasionaleosinophilia. They were all men with an age range of18 to 45 years and a median of 30 years. These fibroticappendices containing the calcified schistosomal ovawere asymptomatic. If left alone, they are probablythe precursor lesion of schistosomal obstructive acuteappendicitis, which occurred in an older age group(median 39 years).

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Fig 4 Appendix with viable schistosomal worm in venouschannel in wall. (Haematoxylin and eosin.) x 125.

In conclusion, we believe that schistosomal acuteappendicitis is a definite clinicopathological entity. Itoccurs in about 1[5% of all cases of an appendicitislike syndrome presenting to surgeons practising inendemic areas. The mere presence of schistosomalova in the appendix without a purulent or granu-lomatous inflammatory reaction is, on the whole,asymptomatic, but the resulting fibrosis may laterproduce the obstructive form of schistosomal acuteappendicitis. Schistosomal acute appendicitis exists astwo disease states that differ in some of their clinicaland histopathological features, as well as in theirpathogenic mechanisms (table 5).

We thank Mr Andrew Archibald for his help with thehalf tones, and Mrs Lolita Galdones-Santos for hersecretarial help.

References

1 Lima JPR. Study of the so called ectopic lesions in schistosomamansoni infections. I: General incidence. Revista Do InstitutoDe Medicina Tropical de Sao Paulo 1962; 8(4):167-72.

2 Smith JH, Kamel IA, Elwi A, Von Lichtenberg F. A quantitativepost-mortem analysis of urinary schistosomiasis in Egypt. I.Pathology and pathogenesis. Am J Trop Med Hyg1974:23:1054-71.

3 Abdel Wahab MP. Schistosomiasis in Egypt. Florida: CRC, 1982.4 Rosai J. Ackerman's surgicalpathology volume . 6th Ed. St Louis:

CV Mosby Company, 1981.5 Pelley RP, Pelley RJ. In: Van den Bossche, ed. Schistosoma man-

soni soluble egg antigen. Biochemistry of parasites and hostparasite relationships. Amsterdam: Biomedical Press, 1976:283.

6 Domingo EO, Warren KS. Endogenous desensitization: changinghost granulomatous response to schistosome eggs at differentstages of infection with Schistosoma mansoni. Am J Pathol1968;52:369-79.

7 Colley DG, Heiny SE, Bartholomew RK, Cook JA. Immuneresponses during human schistosomiasis mansoni. Regulatoryeffects of patients' sera on human lymphocytes blastogenicresponses to schistosome antigen preparation. Am J Trop MedHyg 1977;26:917-25.

8 Allen DC, Biggart JD. Granulomatous disease of the vermiformappendix. J Clin Pathol 1983;36:632-8.

9 Yang SS, Gibson P, McCaughey RS, Arcari FA, Bertnstein J.Primary Crohn's disease of the appendix. Report of 14 casesand review of the literature. Ann Surg 1979;189:334-9.

10 Lindhagen T, Ekelund G, Leandoer L, Hildell J, Lindstrom C,Wenckert A. Crohn's disease confined to the appendix. Dis-eases of the colon and rectum 1982;25:805-8.

11 Payan HM, Gilbert EF, Hafez R. Granulomatous appendicitis.Dis Colon Rectum 1981;24:432-6.

12 Koster H, Kasman LP. Tuberculosis of the appendix. Arch Surg1934;28:1 149-65.

13 Kini MG. Primary tuberculosis appendicitis. Indian J Surg1942;4:34-47.

14 Morrison H, Mixter CG, Schlesinger MJ, Ober WB. Tuberculosislocalized in the vermiform appendix. N Engl J Med1952;246:329-31.

15 Clarke L, Pollett W, Chittal S, Ra Mu. Sarcoidosis with in-volvement of the appendix. Arch Intern Med 1983;143:1603-4

Requests for reprints to: Dr MB Satti, Department of Pa-thology, College of Medicine and Medical Sciences, KingFaisal University, PO Box 2114, Dammam 31451, Kingdomof Saudi Arabia.

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