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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 2  |  Page : 258-261
Acute eosinophilic appendicitis and the significance of eosinophil - Edema lesion

1 Department of Pathology, Medical College, Calicut - 673 008, India
2 Jubilee Mission Medical College & Research Institute, Thrissur-680 005, Kerala, India
3 Department of Pathology, Christian Medical College, Vellore, India

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Date of Web Publication12-Jun-2010


Eight cases of a histological entity that we name 'acute eosinophilic appendicitis' (AEA) are described and compared with classical acute appendicitis and appendices, which turned out to be normal after emergency appendicectomy. These 8 cases formed part of a dataset of 128 emergency appendicectomies, which also included 78 cases of classical acute appendicitis and 42 cases of normal appendix. The clinical and pathological variables were compared between these three. Acute eosinophilic appendicitis is characterized by acute presentation and a grossly inflamed appendix, but with absence of neutrophils in the muscle layer. The histological hallmark of the entity is eosinophil infiltration of the muscularis propria with accompanying edema separating muscle fibers (the Eosinophil - Edema lesion). The duration and prevalence of symptoms, the male female ratio and the gross maximum circumference of the appendix in these 8 cases resembled classical acute appendicitis rather than those cases in which the morphology of the appendix was normal. The Eosinophil-Edema lesion was also seen in many cases of classical appendicitis in non-suppurative areas where neutrophils were sparse or absent. We hypothesize that this lesion is an allergic response and is probably an early event in the evolution of acute phlegmonous appendicitis. Acute eosinophilic appendicitis may merely be those cases that do not proceed on to suppuration.

Keywords: Appendicitis, eosinophils, eosinophil-edema lesion

How to cite this article:
Aravindan K P, Vijayaraghavan D, Manipadam MT. Acute eosinophilic appendicitis and the significance of eosinophil - Edema lesion. Indian J Pathol Microbiol 2010;53:258-61

How to cite this URL:
Aravindan K P, Vijayaraghavan D, Manipadam MT. Acute eosinophilic appendicitis and the significance of eosinophil - Edema lesion. Indian J Pathol Microbiol [serial online] 2010 [cited 2022 Jan 18];53:258-61. Available from: https://www.ijpmonline.org/text.asp?2010/53/2/258/64343

   Introduction Top

Acute appendicitis at its most fundamental level is a condition when the cause of acute abdominal pain and signs like fever, vomiting and right iliac fossa tenderness can be traced to the appendix. There can be no doubt about the cause when the surgeon encounters a red and swollen appendix during emergency laparotomy done for suspected appendicitis. But it is well known that this gross appearance may not be present always. For this reason, pathologists have always grappled with the problem of how to define acute appendicitis in specimens of the vermiform appendix.

Suppuration or the presence of neutrophils has long been the defining feature of acute appendicitis. The textbook view is that the diagnosis of classic suppurative appendicitis (phlegmonous appendicitis) should be made only in the presence of neutrophils in the muscularis propria. [1] The significance of mucosal neutrophils in the absence of muscle involvement has been contentious. Some investigators have considered more than 10 neutrophils/5 HPF found in the mucosa to be evidence of early appendicitis. [2] On the other hand, Pieper et al [3] found inflammation limited to the mucosa in appendices removed incidentally and suggested that the condition is not responsible for actual complaints.

We describe cases presenting clinically like classic acute appendicitis, in which an inflamed and edematous appendix does not show neutrophils in the muscle layer, but marked eosinophil infiltration instead. We choose to name this entity 'acute eosinophilic appendicitis' (AEA).

   Materials and Methods Top

The eight cases of AEA is part of a dataset of 128 cases of consecutive emergency appendicectomies in which an accurate history regarding duration of pain could be obtained by personal interview. Cases in which the whole appendix was gangrenous and in which the muscle layer could not be made out were excluded because the inflammatory cell components were not countable. The patients were personally interviewed before discharge from the hospital (by authors 2 and 3) and a detailed history (including the exact interval between onset of pain and the time of surgery) and relevant investigations were obtained. Of the 128 cases, 78 were histologically classic acute phlegmonous appendicitis (APA). In 42 cases the histology of the appendix was normal.

During gross examination, the length and the circumference at the point of maximum thickness were measured. After formalin fixation, three cross-sections were taken representing the base, middle and tip. Sections were routinely processed and stained with hematoxylin and eosin. In cases of acute eosinophilic appendicitis, the entire appendix was sectioned to exclude areas of neutrophil infiltration.

The clinical and morphological variables were compared between the groups by Chi-square test (Yates correction or Fishers exact test applied wherever appropriate) for qualitative variables and Students t-test or Kruskall Wallis test as appropriate for quantitative variables. EPIINFO 2000 statistical package was used.

   Results Top

The comparison of clinical variables between cases of APA, AEA and normal appendix are shown in [Table 1]. None of the cases of AEA had a history of atopy.

The normal appendix had intact mucosa with lymphoid follicles and a thin muscle layer. In contrast, the grossly inflamed appendix showed congestion and widened submucosa. Varying degrees of edema ranging from massive to mild was responsible for the submucosal widening. The muscle fibers showed separation by edema fluid and exudate in inflamed appendices. Normal appendices showed marked lymphoid hyperplasia in some cases, but the muscle layer was compact.

The exudate seen in the muscle layer of grossly inflamed appendices was composed of a mixture of neutrophils and eosinophils (APA) or eosinophils alone (AEA). In AEA, the appendix was swollen and hyperemic as in most cases of phlegmonous appendicitis. But surface exudate was absent in all cases. There was no mucosal ulceration. Occasional neutrophils were seen in the lamina propria in some cases, but did not exceed 10 cells/5 HPF in any case. Eosinophil infiltration of the muscle layer was accompanied by edema and muscle fiber separation in all cases of AEA. This lesion is best seen in the circular muscle coat [Figure 1]. This Eosinophil-Edema lesion (E-E lesion) was the defining feature of these cases and consists of Eosinophils lying scattered in edematous areas amidst the muscle [Figure 2]. Some of the eosinophils were partially degranulated. There were increased eosinophils in the submucosa also in these cases. However, the lamina propria did not contain an abundance of eosinophils and their numbers were similar to that seen in normal appendices.

There were two cases with pinworms in the lumen of the appendix. There was no significant eosinophil infiltration in either and they were classified as normal appendices.

The E-E lesion was also seen focally in areas away from acute inflammation in many cases of APA [Figure 3]. There were five cases of focal acute appendicitis in which only one of the three sections showed suppuration. The E-E lesion was seen in the other sections of all these cases and in these sections the appearances were indistinguishable from AEA.

   Discussion Top

Eosinophils as the sole infiltrate in the muscle layer in appendicitis have been described before. Stephenson and Snoddy chose to call these 'subacute appendicitis' though the clinical correlation needed to justify this term was not mentioned in their study. [4] Jona et al[5] observed two cases in children very similar to our cases, presenting clinically as acute appendicitis but containing only transmural eosinophil infiltration. They remark in the discussion that they have seen several such cases in adults also. They chose to include them in the spectrum of eosinophilic gastroenteritis rather than consider it as a variant of primary appendicitis. [5] Aravindan [6] in a study of 120 appendicectomies found that mural eosinophil infiltration is a consistent finding in acute appendicitis. He also described cases similar to what Jona et al 5 described, in which eosinophil infiltrate was the sole finding. He suggested that eosinophil infiltrate seen in acute appendicitis is an early event linked possibly to type I hypersensitivity. [6] This was in contrast to what was believed earlier - that infiltration of eosinophils is evidence of subacute or chronic inflammation. [4],[7]

The cases of AEA that we have described share clinical and morphological features with classic acute appendicitis in contrast to those cases in which the surgically removed appendix is of normal histology. The circumference of the appendix is greatly increased in APA and AEA when compared to normal. The duration of symptoms is slightly less in AEA compared to phlegmonous appendicitis, but this was not statistically significant [Table 1]. The absolute blood eosinophil counts are also higher in APA and AEA when compared to normal, but they still fall below the upper limit of normal. This is in contrast to eosinophilic gastroenteritis in which peripheral eosinophilia is frequently present. [8]

The term eosinophil-edema lesion may at first glance appear unwarranted or grandiose, but we feel it is justified. It is a distinct lesion seen only in patients having acute symptoms and grossly inflamed appendices. It helps to differentiate these cases from grossly uninflamed appendices in which variable number of eosinophils may be seen in the muscular layer. Eosinophils admixed with lymphocytes and unaccompanied by edema may be seen in cases of resolving appendicitis. [9] These cases are to be differentiated from cases of acute presentation, which is characterized by the E-E lesion. Furthermore, we have demonstrated that the Eosinophil-Edema lesion, which is the hallmark of AEA is seen also in many cases of classic phlegmonous appendicitis as well as in all cases of focal acute appendicitis in areas where the neutrophils are sparse or absent. It seems reasonable to hypothesize that AEA falls within the spectrum of acute appendicitis and that the E-E lesion is an early event in its evolution. Acute eosinophilic appendicitis may merely represent those cases that do not proceed on to suppuration.

Enterobius vermicularis is an incidental finding in few appendicectomy specimens and can be seen in acute appendicitis as well as in elective appendicectomies of normal histology. The presence of pinworms is not associated with particularly high eosinophil infiltration of the muscular layer. [10] This has also been our experience. There were only two cases with pinworms in the lumen in our dataset. Neither showed significant eosinophil infiltration of the muscle layer and was classified as otherwise normal. It can be argued that pinworms or other parasites in the gut, not seen in the sections may be causing the E-E lesion. This argument may be difficult to falsify, but seems unlikely for two reasons. Firstly, if pinworms within the appendix do not provoke an eosinophil response in the wall, why should it be supposed that those outside would do so? More importantly, the E-E lesion is a regular feature in classical acute appendicitis, provided it is actively searched for in areas of the muscle layer with relatively less or absent neutrophil infiltration. Obviously, all of these cases cannot be due to parasites.

The dogma of obstructive etiology for acute appendicitis has persisted for a long time. Contrary to popular belief, the best evidence indicates that obstruction is unlikely to be the primary cause, at least in the majority of cases. [11] Alternative theories merit serious consideration.

Eosinophils are normal constituents of the appendix in the lamina propria and submucosa, but not in the muscularis propria. Finding of a pure eosinophil infiltrate amidst inflammatory edema in the muscle layer makes one suspect allergy as a cause for the acute onset disease. The analogy with anaphylaxis and acute asthma is inescapable with this histological picture.

Strachan [12] first proposed in 1989 that a decrease in the prevalence of childhood infection might explain the increase in Th2-mediated diseases like asthma and it has subsequently come to be called the hygiene hypothesis. This theory now enjoys wide support. [13] It is interesting that Barker et al [14] have invoked the hygiene hypothesis for acute appendicitis even earlier.

We believe that in a setting of reduced childhood exposure to infections including helminths, there is a heightened Th2 response to many antigens in the gastrointestinal tract. Alternatively, decrease in helminth-specific IgE may leave open more sites on mast cell membranes for allergen specific IgE. Resultant local allergic reactions may be the cause of E-E lesion. The appendix, unlike the rest of the bowel is particularly vulnerable to ischemia due to its small size and any significant edema can compromise the blood supply and cause damage to the mucosal barrier. The entry of microorganisms as a result may be the cause of neutrophilic inflammation and APA. Acute eosinophilic appendicitis may represent those cases in which widespread E-E lesions occur to produce symptoms and signs of acute appendicitis but does not proceed on to suppuration prior to surgery.

   References Top

1.Liu C, Crawford JM. The Gastrinitestinal tract. In: Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease. 7 th edition. Philadelphia PA: Elsevier inc.; 2004. p. 797-875.  Back to cited text no. 1      
2.Barcia JJ, Reissenweber N. Neutrophil count in the normal appendix and early appendicitis: Diagnostic index of real acute inflammation. Ann Diagn Pathol 2002;6:352-6.  Back to cited text no. 2      
3.Pieper R, Kager L, Nδsman P. Clinical significance of mucosal inflammation of the vermiform appendix. Ann Surg 1983;197:368-74.  Back to cited text no. 3      
4.Stephenson J, Snoddy WT. Appendiceal lesions. Observation in 4,000 appendectomies. Arch Surg 1961;83:661-6.  Back to cited text no. 4      
5.Jona JZ, Belin RP, Burke JA. Eosinophilic infiltration of the gastrointestinal tract in children. Am J Dis Child 1976;130:1136-9.  Back to cited text no. 5      
6.Aravindan KP. Eosinophils in acute appendicitis; Possible significance. Indian J Pathol Microbiol 1997;40:491-8.  Back to cited text no. 6  [PUBMED]  Medknow Journal  
7.Crabbe MM, Norwood SH, Robertson HD, Silva JS. Recurrent and chronic appendicitis. Surg Gynecol Obstet 1986;163:11-3.  Back to cited text no. 7      
8.Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR. Eosinophilic gastroenteritis: A clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut 1990;31:54-8.  Back to cited text no. 8      
9.Ciani S, Chuaqui B. Histological features of resolving acute, non-complicated phlegmonous appendicitis. Pathol Res Pract 2000;196:89-93.  Back to cited text no. 9      
10.Stĕrba J, Vlcek M. Appendiceal enterobiasis--its incidence and relationships to appendicitis. Folia Parasitol (Praha) 1984;31:311-8.  Back to cited text no. 10      
11.Carr NJ. The pathology of acute appendicitis. Ann Diagn Pathol 2000;4:46-58.  Back to cited text no. 11      
12.Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299:1259-60.  Back to cited text no. 12      
13.Weiss ST. Eat dirt--the hygiene hypothesis and allergic diseases. N Engl J Med 2002;347:930-1.  Back to cited text no. 13      
14.Barker DJ, Osmond C, Golding J, Wadsworth ME. Acute appendicitis and bathrooms in three samples of British children. Br Med J (Clin Res Ed) 1988;296:956-8.  Back to cited text no. 14      

Correspondence Address:
K P Aravindan
Medical College, Calicut - 673 008
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.64343

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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