Histopathological surprises: When eosinophils invade the appendix

INTRODUCTION

Globally, acute appendicitis remains one of the leading causes of surgical emergencies. Acute appendicitis typically results from blockage of the appendix lumen, often by a fecolith, leading to bacterial growth and reduced blood flow that causes inflammation and tissue damage.^[1] While surgery (appendectomy) remains the standard treatment, uncomplicated appendicitis (UA) without perforation may be managed with antibiotics.^[2] In contrast, acute eosinophilic appendicitis (AEA) is a rare form thought to arise from an allergic reaction rather than infection or obstruction, characterized by eosinophil infiltration in the appendix. Its symptoms often mimic classic appendicitis, and diagnosis is usually confirmed after surgical removal through histological examination. Identifying AEA is important to prevent misdiagnosis and inappropriate antibiotic treatment.

Here, we report a rare case of appendicitis that was diagnosed as UA through clinical symptoms and radiological findings. The patient underwent a laparoscopic appendectomy, and by histopathological investigation, she was diagnosed to have AEA.

CASE REPORT

A 63-year-old woman presented with complaints of pain in the right lower abdominal quadrant and nausea for 2 days. The pain was continuous, but there was no fever, vomiting, or difficulty in defecation. She had similar complaints in the past. She was a known case of hypertension on medication and coronary artery disease. Local examination revealed a soft abdomen with no tenderness. Her blood test results were as follows: Hemoglobin level, 13.3 g/dL; and white blood cell count 14,160 cells/cu mm (differential count: neutrophils, 73.9%; lymphocytes, 20.8%; and eosinophils, 1.7%). Contrast-enhanced computed tomography (CT) abdomen showed a dilated and fluid-filled appendix with mild periappendiceal fat stranding. There was no evidence of perforation, abscess, or tumor [Figure 1].

Close

Figure 1:

A 63-year-old woman presented with pain in the right iliac fossa. Computed tomography image shows dilated appendix (red arrow) with mild periappendiceal fat stranding.

Export to PPT

Based on the clinical and radiological findings, she was diagnosed with UA and was taken up for laparoscopic appendectomy for further evaluation. On the table, the appendix was grossly inflamed and edematous. Tip was adherent to the cecum, forming a small pocket of pus. Intraoperatively, the adhesions were released between the appendix and the surrounding bowel. The mesoappendix was ligated, and the appendix was retrieved and sent for histopathological examination.

Histopathological examination showed appendiceal mucosa with erosion and acute inflammatory infiltrate composed of predominantly eosinophils along with some neutrophils and lymphocytes extending to the muscularis propria with many congested blood vessels. Deep in the muscularis propria, there was extensive eosinophilic infiltration, >20 eosinophils per high-power field [Figure 2a and b]. There was no evidence of edema (as present in eosinophil-edema lesion), granuloma formation or parasites or malignancy. Special stains were not used since intraluminal parasites or their larval forms were not found in Hematoxylin and Eosin (H&E) staining. Histopathological examination ultimately revealed AEA. The peripheral blood shows normal levels of eosinophils (1.7%) which also aligns with AEA, unlike in eosinophilic gastroenteritis (EGE), where there is peripheral eosinophilia. Postoperatively, her abdominal pain subsided, and orals were allowed on the same day after surgery. She was discharged 2 days after surgery with a course of antibiotic T. CIPLOXTZ for 7 days along with pain medications. At the follow-up visit on post-operative day 8, she reported no gastrointestinal complaints and had finished the prescribed antibiotics.

Close

Figure 2:

A 63-year-old woman presented with pain in the right iliac fossa and was diagnosed as appendicitis and underwent appendectomy. (a) Histopathological investigation shows acute inflammatory infiltrate composed of predominantly eosinophils (red circle shows the eosinophils) along with some neutrophils and lymphocytes seen in lamina propria Hematoxylin and Eosin (H&E) ×40. (b) Histopathological investigation shows >20 eosinophils (all the red circles show the collection of eosinophils) in one high-power field in muscularis propria H&E ×400.

Export to PPT

DISCUSSION

AEA presents acutely with a visibly inflamed appendix and on histopathological examination will reveal eosinophil infiltration into the muscularis propria with accompanying edema separating muscle fibers (eosinophil-edema lesion).^[2] Eosinophil-rich, edematous areas are frequently observed in classical appendicitis, especially where neutrophils are minimal or absent.^[2] This pattern suggests that an allergic reaction may occur early in appendicitis, possibly representing an initial phase before the condition develops into the more typical, pus-forming stage. AEA may simply be cases that halt at this early, non-suppurative stage. Unlike the typical appendicitis, AEA lacks the presence of neutrophils in the muscle layer.^[3] Although our case has neutrophils in the muscularis propria, the histological hallmark of the entity, the eosinophil-edema lesion is present.^[2] Eosinophilic appendicitis can closely resemble acute appendicitis in terms of clinical presentation, laboratory parameters, and imaging appearances, which complicates pre-operative distinction between the two conditions, as in our case, where the clinical symptoms and CT findings denoted acute appendicitis, but the histopathological examination proved otherwise.

Confirming eosinophilic appendicitis relies heavily on histopathological evaluation with the presence of eosinophil infiltration in the appendiceal wall, with no signs of granulomas or parasitic organisms.^[1] It is also essential to rule out other possible sources of eosinophilia, such as malignancy. It is a rare condition with a reported incidence of 0.03–1.2%.^[3] It can occur as a single disease or as component of a systemic eosinophilic disorder, such as EGE or esophagitis.^[1] Eosinophilic enteritis may affect the gastric antrum or intestinal and may present with chronic gastrointestinal complaints such as vomiting, abdominal pain, diarrhea, blood in stools, anemia, or as polypoid lesions and fibrosis causing obstruction, intussusception, and gastrointestinal hemorrhage.^[2,4]

Unlike EGE, where oral corticosteroids are the standard treatment, there is currently no well-defined therapy for AEA.^[3] In cases of EGE, peripheral eosinophilia is commonly observed, whereas it is typically absent in AEA. Parasitic appendicitis, commonly by Enterobius vermicularis, can also be seen in the H&E staining. Special stains like periodic acid-Schiff with diastase can be used for further confirmation.

Because diagnosing AEA before surgery is challenging, performing an appendectomy is often necessary to obtain a definitive diagnosis through histopathological examination.^[3] After surgery, it is important to closely monitor patients for any further developments in relation to EGE.

CONCLUSION

AEA is often misdiagnosed as UA due to overlapping symptoms and imaging, and it typically resists antibiotic treatment. Histopathology, showing eosinophil infiltration of the muscularis propria, is the only way to differentiate it. When antibiotics fail, AEA should be considered. While no standard treatment exists, surgical removal is common, and careful post-operative follow-up is crucial as AEA may be associated with EGE.