A brief overview of the S. japonicum life cycle
The complete life cycle of schistosomal trematodes was first described by Pirajá da Silva in 1908 [
21]. Oncomelania hupensis robertsoni, a subspecies of an aquatic gastropod mollusk, a very small freshwater snail serves as an intermediate host and a unique vector for
S. japonicum, while humans serve as a definitive host in the transmission of Schistosomiasis. The eggs from feces and urine of infected individuals hatch and release miracidium into freshwater. They undergo developmental changes from sporocysts to cercaria. When humans come in contact with infested waters, cercaria loses the tail and become schistosomula that mature into sexually dimorphic adult worms. Adult worms mate in the hepatic parenchyma and move against the flow of blood to their final niche in the mesenteric circulation, where they begin egg production (> 32 days). Egg depositions occur intravascularly in the small venous tributaries of mesenteric and vesical plexus; eventually, they get migrated to the lumen of respective viscera aided by the peristaltic movement [
22].
Relation with intestinal schistosomiasis and age
S. japonicum eggs are the main pathogenic factor that gets deposited intravascularly in the portal venous system, as well as the small venous tributaries of the mesenteric or vesical plexuses. It has been well established that in the middle and late stages of the disease, the eggs often remain in clusters causing continuous erosion to the intestinal wall invading every layer of the rectum and sigmoid colon base forming long-segment circumferential interrupted mural calcifications [
23]. Moreover, the presence of discontinuous to continuous calcifications extending along ascending colon and cecum could be attributed to the deposition of eggs from mesenteric plexus. Many of the patients that have been exposed to
S. japonicum parasite, if not treated for a longer period of time, are liable to progress into SAA in later life years owing to gradual deposition of eggs in the appendicular sub-mucosal and sub-serosal layers.
In our study, some cases also showed one or more types of these calcifications on different MPR views suggesting single focus depositions are point calcifications, and surrounding sheet-like continuous and uniform hyper densities-linear calcifications, as well as annular hyper densities-orbital type calcifications occurring as a result of varying degrees of egg depositions at multiple foci on the surrounding layers of the appendix, out of which orbital calcifications are most common. In our study, it was also observed that the average age of the SAA patients who showed colon calcifications was 66.38 years. So, high age (> 53 years) with positive infection status for many years appears to be a major predisposing factor that could have contributed to a higher incidence of these vivid appendicular wall calcifications.
Petechial hemorrhages, granulomas in the lamina propria and submucosa and tram track/curvilinear calcifications are the most common lesions observed radiologically in intestinal schistosomiasis, similarly found in 90% cases of our study [
24,
25]. However, secondary conditions such as Crohn’s disease, ulcerative colitis present with colon calcifications that are visualized as skip lesions, small bowel wall thickening, halos which are confined mostly to terminal ileum and cecum [
26]. Intestinal tuberculosis shows circumferential wall thickening of terminal ileum and cecum, asymmetric thickening of the ileocecal valve along with mesenteric lymphadenopathy [
27].
Radiological analysis of the study
Plain CT is the preferred imaging modality for the detection of AA with high sensitivity (94–98%) and specificity up to 97% [
28]. Dilated appendix with distended lumen (> 6 mm diameter), thickened and enhancing wall, thickening of the cecal apex (up to 80%): cecal bar sign, arrowhead sign, periappendiceal inflammation, including adjacent fat stranding and thickening of the lateroconal fascia or mesoappendix are mostly confirmatory features on NCCT and CCT [
29]. Though the SAA group showed the highest positivity rate for these particular indicators, there were no significant differences. They are more common in young patients of either SAA or NSA because both groups manifested as the appendicular pathology. In our study, the SAA group showed appendiceal dilation > 13.6 mm and up to 22 mm along with various peculiar signs of complicated appendicitis suggesting ASA and AGA types are more frequent than simple appendicitis (SA).
Pathophysiological correlation of radiological features
The role of schistosomiasis and the exact association in the development of appendicitis still remains uncertain and controversial [
30] but we believe that it depends upon a series of changes triggered by two pathophysiological mechanisms after intestinal schistosomiasis infection that can be recognized as primary, secondary radiographic features, and its associated complications.
The first mechanism is the Schistosomal obstructive acute appendicitis-suppurative type. The basic structure of appendiceal orifice in the caecum and colon is similar, eggs deposited in the mesenteric plexuses eventually get migrated into the inferior mesenteric vein and superior hemorrhoidal vein leading to the tardy blood supply and decreased peristalsis of the appendix over time. At the same time, the peripheral intravenous eggs can get lodged into the appendicular lumen causing sluggish movements that can form appendicolith or fecalith and cause non-expulsion. Moreover, eggs can also get deposited in the appendiceal wall, submucosa, and muscular layer causing passive obstruction owing to fibrosis around eggs. Its primary structure is in the appendix wall but not on appendix lumen which is visualized as higher density peripheral to lumen—a point calcification resultant of such aggravated mechanism. It can also be further complicated by a bacterial infection with subsequent formation of a phlegmon or polyp, and sometimes with other conditions like intestinal tuberculosis, ileocecal intussusceptions, intestinal obstruction [
31]. This mechanism pathologically presents with no tissue eosinophils or granulomas and is more often seen in the late stages of infection. It is always necessary to carefully evaluate for all the direct and indirect signs of acute appendicitis like effusions > 2.6 mm, fluid collections and peri appendiceal streak shadows (surrounding in-homogeneous appearance), inflammatory fat stranding, pneumatosis on CT [
32].
The second mechanism is the acute Schistosomal appendicitis- granulomatous type, believed to be a result of immunological inflammatory and granulomatous reactions to newly deposited eggs [
33] that are released in tandem along the submucosal layers of the appendix. Moreover, long-term deposition of eggs in the appendix wall is progressive increasing the granulomatous reaction and can form a kind of continuous homogeneous orbital calcification similar to that of the colon. When the underfilling of appendix lumen occurs, the calcification along the opposite sides of lumen shows as linear calcification because of partial volume effect and other restrictions. Even if the appendix collapses, it may appear as a line, but it is difficult to track the appendix when full. At the same time, 7 cases from the SAA group in which orbital calcifications has not been demonstrated, the degree of calcifications could directly be dependent on the quantity and duration of deposition of the eggs into the appendiceal cavity [
34]. This mechanism presents pathologically with tissue necrosis, granulomas and eosinophilia, on the contrary, is more often seen in the early stages of infection.
The nidus for these granulomatous lesions is the parasite eggs with their multiple antigens that are recognized by the host. Peri appendiceal reactive nodal prominence, appendicular enlargement, and thickening, mucosal changes are precursors to perforation formation which can be recognized as a focal wall defect along with signs of suppurative type SAA [
31]. Because such a vivid effect on the appendix is still uncommon in the endemic areas, it has been widely reported that the disease is progressing rapidly with higher perforation rates spontaneously, causing high mortality and morbidity [
33].
Thus, we can infer that acute cases are at higher risk of perforation, granuloma, and abscess formation, while long-standing cases are most prone to the development of luminal fibrosis, appendicolith, and phlegmon formation. A simultaneous increase in age also precipitates the risk of progression into spontaneous perforations and peri-appendiceal abscess, the prognosis is poor [
35]. A diameter greater than 13 mm appears to be a reliable feature in assessing appendicolith, fibrosis and abscess formation; while diameter greater than 18 mm can estimate the risk of eventual perforation in chronic cases. Calculating the radiological appendicitis severity index (APSI) [
32] helps in differentiating SA, ASA, and AGA. There is a risk of misdiagnosis of SAA when the related signs are not analyzed in all anatomical planes.
Chronic infection can also result in scarring of mesenteric or vesicular blood vessels leading to portal hypertension, portocaval shunting [
36] along with capsular calcifications extending towards the center of the liver with “turtleback appearance” due to massive fibrosis can also be observed in most cases [
37] which are typical for hepatic schistosomiasis. There were no liver calcifications observed in the NSA group. Calcified eggs in the lymph nodes, the inflammatory tissues of mesocolon [
15] and descending duodenum [
38] appear as punctuate calcifications. There has been a well-established relation between Schistosomiasis and colorectal/rectosigmoid cancer [
39]. It is still unknown that how many patients with hepatic or intestinal schistosomiasis are liable to develop into SAA, so, it is often very useful to look for these ancillary signs by exploring the adjacent abdominal viscera, especially liver and colon.
Limitations of the study
SAA is a very rare entity that presents an acute emergency situation involving multiple complex pathophysiological mechanisms, so the sample size is slightly inadequate to analyze vivid patterns. Color doppler ultrasound is still the preliminary investigation of choice for diagnosing AA in a tertiary care level hospital. Contrast CT, fluoroscopy and MRI provides better diagnostic information; availability, technique, and expertise are major contributors for non-preference. Moreover, especially during, poor clinical conditions, perforations, and risk of side-effects to contrast materials are contraindications. We endeavor to integrate advanced modalities like Dual CT, MSCT with contrast studies, curved planar reformation (CPR) and CT virtual colonoscopy (CTVC), gastro intestinal fluoroscopy and selective angiography in our future projects aiming to completely understand the development and progression of SAA.