Article, Gastroenterology

Anisakiasis presenting to the ED: clinical manifestations, time course, hematologic tests, computed tomographic findings, and treatment

a b s t r a c t

Background: The prevalence of anisakiasis is rare in the United States and Europe compared with that in Japan, with few reports of its presentation in the emergency department (ED). This study describes the clinical, hema- tologic, computed tomographic (CT) characteristics, and treatment in gastric and small intestinal anisakiasis pa- tients in the ED.

Methods: We retrospectively reviewed the data of 83 consecutive anisakiasis presentations in our ED between 2003 and 2012. Gastric anisakiasis was endoscopically diagnosed with the Anisakis polypide. Small intestinal anisakiasis was diagnosed based on both hematologic (Anisakis antibody) and CT findings.

Results: Of the 83 cases, 39 had gastric anisakiasis and 44 had small intestinal anisakiasis based on our diagnostic criteria. Although all patients had abdominal pain, the gastric anisakiasis group developed symptoms significant- ly earlier (peaking within 6 hours) than the small intestinal anisakiasis group (peaking within 48 hours), and fewer patients with gastric anisakiasis needed admission therapy (5% vs 57%, P b .01). All patients in the gastric and 40 (91%) in the small intestinal anisakiasis group had a history of raw seafood ingestion. Computed tomo- graphic findings revealed edematous wall thickening in all patients, and ascites and phlegmon of the mesenteric fat were more frequently observed in the small intestinal anisakiasis group.

Conclusions: In the ED, early and accurate diagnosis of anisakiasis is important to treat and explain to the patient, and diagnosis can be facilitated by a history of raw seafood ingestion, evaluation of the time-to-symptom devel- opment, and classic CT findings.

(C) 2014

Introduction

Anisakiasis, which was first described in the Netherlands in the 1960s, is a fish-borne parasitic disease caused by the consumption of raw or undercooked seafood contaminated by third-stage larvae of the Anisakidae family, particularly Anisakis simplex [1]. The larvae can pene- trate the gastrointestinal tract and cause gastric or small intestinal anisakiasis. Every year, approximately 20 000 cases of anisakiasis are re- ported worldwide, with more than 90% from Japan and most of the other cases from Spain, the Netherlands, and Germany, depending on the habits of fish consumption; however, anisakiasis remains a rare disease

? Conflict of interest statement: All authors declare no conflicts of interest.

?? Funding: None.

? Previous presentation: This manuscript was presented in part at the 33rd International

Symposium on Intensive Care and Emergency Medicine in Brussels, Belgium; March 19, 2013.

* Corresponding author. Department of Emergency Medicine, Hiroshima City Hospital, Hiroshima, Japan. Tel.: +81 82 221 2291; fax: +81 82 223 5514.

E-mail address: [email protected] (T. Takabayashi).

1 7-33 Motomachi, Naka-ku, Hiroshima-shi, Hiroshima 730-8518, Japan.

2 9-1 Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan.

3 54 Kawara-machi, Seigoin, Sakyo-ku, Kyoto 606-8507, Japan.

[1-3]. Although the prevalence of anisakiasis is rare in the United States and European Union, particularly in inland areas, compared with that in Japan [2,3], the incidence is expected to increase, given the growing pop- ularity of Japanese cuisine, such as sushi or sashimi.

Although the clinical symptom of anisakiasis is abdominal pain, this clinical finding is nonspecific, and the patient may be misdiagnosed or may unnecessarily undergo surgery for different ailments, including ap- pendicitis, ileus, and peritonitis [2,4,5]. In the emergency department (ED), we examine several patients with acute abdominal pain; there- fore, we should consider anisakiasis when the cause of abdominal pain cannot be determined by initial assessment [2,6,7]. However, few case reports have described the precise clinical manifestations, time course, hematologic test results, and Computed tomographic findings of patients with anisakiasis; and this information would aid in the early and definitive diagnosis of anisakiasis in emergency settings. In addi- tion, previous case series reports comparing gastric anisakiasis with small intestinal anisakiasis have tended to have a small sample size [7-9].

We analyzed a large single-center case series of patients with gastric and small intestinal asnisakiasis to describe the specific clinical manifesta- tions, time courses, hematologic test results, CT findings, and treatment.

http://dx.doi.org/10.1016/j.ajem.2014.09.010

0735-6757/(C) 2014

computed tomographic imaging“>Methods

Study design and setting

A retrospective single-center case series study was conducted in the ED of St Luke’s Hospital in Tokyo, Japan, near the Tsukiji market (a fa- mous seafood market in Tokyo). Every year, more than 40 000 patients visit the ED of the hospital. There are many patients who visit the ED with the chief complaint of abdominal pain, and we often observe anisakiasis. We selected out patients diagnosed with “anisakiasis,” “gastric anisakiasis,” and “small intestinal anisakiasis” using an ED diag- nosis from July 22, 2003, to July 22, 2012; and the author retrospectively reviewed the data of these consecutive patients and is responsible for extracting all data. At the time of data collection, there was no established protocol in the ED for the emergency physicians to follow, but all patients with gastric anisakiasis underwent endoscopic examina- tions in the ED. Because of acute and severe abdominal pain, all the pa- tients were obtained blood and imaging studies to rule out appendicitis, acute pancreatitis, and digestive tract perforation, etc.

Definitions and data sources

Gastric anisakiasis was diagnosed with the endoscopically proven Anisakis polypide, and small intestinal anisakiasis was diagnosed with a hematologically positive Anisakis antibody (immunoglobulin G and immunoglobulin A) and CT diagnostic imaging by an ED physician. Clin- ical information, including age, sex, onset and duration of abdominal pain, blood test results, and diagnostic CT Imaging results, was obtained from the hospital charts.

Computed tomographic imaging

All patients underwent 64-slice CT (Toshiba Aquilion ONE, Toshiba Aquilion, Toshiba Medical Systems Corporation, Otawara, Japan, and GE BrightSpeed, GE Healthcare Japan Corporation, Tokyo, Japan) at the discretion of the patient and attendant physicians in the ED. All images were evaluated by a radiologist.

Computed tomographic evaluation

Previous reports have revealed that the radiologic features of gastric and intestinal anisakiasis included the following findings: the presence of submucosal edema of the stomach and intestine (edematous wall thickening), fat infiltration of the mesentery around the involved stom- ach and intestine, dilatation, fluid collection in the involved stomach and intestine, abdominal lymphadenopathy, and the presence of ascites [2,10-12].

Because edematous wall thickening, fat infiltration of the mesentery around the involved stomach and intestine, and the presence of ascites in CT findings are frequently observed in patients with gastric and intes- tinal anisakiasis [10], we evaluated the frequency of these CT findings in the patients in this study.

Statistical analysis

We classified the participants into a gastric anisakiasis group and a small intestinal anisakiasis group. Descriptive analyses were conducted with the use of frequency tabulations. We determined the medians and interquartile ranges for all variables. An unpaired t test or Mann- Whitney test was conducted for unpaired comparisons. ?2 test or Fisher exact test was used to examine the differences between categorical var- iables. All analyses were conducted with JMP software version 10.0.0 (SAS Institute, Inc, Cary, NC). The authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the contents of the manuscript.

Ethical considerations

The study protocol was in accordance with the guidelines for epide- miological studies issued by the Ministry of Health, Labour and Welfare of Japan. The Research Ethic Committees of St Luke’s Hospital approved the research protocol.

Results

Patient characteristics

In total, 83 patients who were diagnosed with anisakiasis over the study period were retrospectively analyzed. Of these, 39 (47%) had gas- tric anisakiasis and 44 (53%) had small intestinal anisakiasis (Fig. 1). The characteristics of the 2 patient groups are shown in Table 1. The gastric anisakiasis group comprised more female patients. Patients in the small intestinal anisakiasis group were older and Serum C-reactive protein levels higher. All patients had abdominal pain. All patients in the gastric anisakiasis group and 40 (91%) in the small intestinal anisakiasis group had a history of raw or undercooked seafood ingestion.

Computed tomographic imaging

All of the patients underwent 64-slice CT imaging according to the discretion of the patient and the attendant physicians in the ED. Edem- atous wall thickening was observed in all patients with abdominal pain. Ascites and phlegmon of the mesenteric fat were more frequently ob- served in the small intestinal anisakiasis group (Table 2 and Fig. 2).

Symptom development

The patients with gastric anisakiasis developed symptoms signifi- cantly earlier than those with small intestinal anisakiasis. The symp- toms developed within 48 hours and peaked within 6 hours in the gastric anisakiasis group, whereas the symptoms peaked within 48 hours and persisted for a maximum of 5 days in the small intestinal anisakiasis group (Table 3 and Fig. 3).

Treatment

All patients diagnosed with gastric anisakiasis were treated by endo- scopically removing the Anisakis larvae. They received a conservative treatment, including Fluid replacement therapy and pain control. We did not routinely use antibiotics, proton pump inhibitors, and histamine blockers. Although more than half of the patients with small intestinal anisakiasis received treatment on admission (25/44, 57%), few with gas- tric anisakiasis (2/39, 5%) needed admission therapy, and inpatient days of the small intestinal anisakiasis group were longer (Table 1). In this study, no patient underwent emergency surgery.

Fig. 1. The number of patients with gastric and small intestinal anisakiasis.

Table 1

Patient characteristics

Overall

Gastric anisakiasis

Small intestinal anisakiasis

P

n = 83

n = 39

n = 44

Female, n (%)

25 (30)

17 (44)

8 (18)

.01

Age, y (median [IQR])

46 (36-57)

41 (32-49)

50 (40-59)

b.01

Blood test

WBC, cells per microliter (median [IQR])

9950 (7900-12 025)

9800 (8800-11 175)

10 050 (7625-13 675)

.66

CRP, milligrams per deciliter (median [IQR])

1.7 (0.4-5.0)

0.5 (0.1-1.7)

2.9 (1.0-6.4)

b.01

Abdominal pain, n (%)

83 (100)

39 (100)

44 (100)

1.00

History of raw or undercooked seafood ingestion, n (%)

79 (95)

39 (100)

40 (91)

.05

Admission rate, n (%)

27 (33)

2 (5)

25 (57)

b.01

Inpatient day, d (median [IQR])

6 (4.5-7.5)

2.5 (2.3-2.8)

6.0 (5.0-8.0)

.04

Abbreviations: IQR, interquartile range; WBC, white blood cell; CRP, C-reactive protein.

Discussion

Key results

This is the first large-scale study to demonstrate differences in clini- cal manifestations, time courses, hematologic test results, CT findings, and treatment between patients with gastric and small intestinal anisakiasis. All patients had abdominal pain; however, the patients in the gastric anisakiasis group developed symptoms significantly earlier (peaking within 6 hours) than those in the small intestinal anisakiasis group (peaking within 48 hours). Not all patients in the small intestinal anisakiasis group had a history of raw or undercooked seafood inges- tion. With regard to CT findings, edematous wall thickening was ob- served in all patients, whereas ascites and phlegmon of the mesenteric fat were more frequently observed in the patients in the small intestinal anisakiasis group.

As previously described, the pathologic characteristics of anisakiasis consist of a combination of 2 different mechanisms: direct tissue dam- age and Allergic reactions to the Anisakis larvae. Direct tissue damage due to the invasion of Anisakis larvae involves the development of eosin- ophilic granulomas or perforations. A pathologic examination of the resected Small intestine from a patient with small intestinal anisakiaisis who underwent surgery for a suspected acute abdomen showed transmural edema, congestion, and diffuse infiltration of neutrophils and eosinophils [2,13]. Because a gastric or intestinal endoscopic biopsy is not painful, the pain of anisakiasis may be caused by an allergic reac- tion rather than by direct tissue damage. These pathophysiologic find- ings are directly reflected by edematous wall thickening, ascites, and phlegmon of the mesenteric fat on CT findings. The difference in the de- velopment of symptoms between patients with gastric anisakiasis and small intestinal gastric anisakiasis may simply reflect the time for the Anisakis larvae to cause these Pathologic changes.

A blood test for the Anisakis antibody is not routinely performed without a typical clinical history. However, it is surprising that approx- imately 9% patients in the small intestinal anisakiasis group had no

Table 2

Computed tomography results of patients with gastric and small intestinal anisakiasis

Gastric anisakiasis

n = 39

Small intestinal anisakiasis

n = 44

P

Edematous wall thickening, n (%)

39 (100)

44 (100)

1.00

Ascites, n (%)

12 (44)

40 (91)

b.01

Around the liver, n (%)

2 (7)

24 (55)

b.01

Around the Douglas pouch, n (%)

11 (41)

39 (89)

b.01

Phlegmon of mesentery fat, n (%)

0 (0)

32 (73)

b.01

Gastric anisakiasis was diagnosed with an endoscopically proven Anisakis polypide, and small intestinal anisakiasis was diagnosed with a hematologically positive Anisakis anti- body and CT.

history of raw or undercooked seafood ingestion in this study. Small in- testinal anisakiasis takes more time to develop symptoms compared with gastric anisakiasis; thus, the patients may have forgotten that they ate raw or uncooked seafood, and it may be difficult to identify the causal food. Moreover, the clinical diagnosis of small intestinal anisakiasis is usually difficult because of atypical Clinical histories with a long interval from raw or undercooked seafood ingestion. It has been reported that several patients are clinically diagnosed with other abdominal diseases before CT findings suggest the possibility of anisakiasis [10]. Classic CT findings of small intestinal anisakiasis are useful for ED physicians to be able to make clinically underrecognized diagnosis of small intestinal anisakiasis. In our data, although more than half of the patients with small intestinal anisakiasis had admission therapy, almost all with gastric anisakiasis did not. On the other hand, if we make an early and accurate diagnosis of small intestinal anisakiasis, we could take conservative strategy without unnecessary operation. Based on these data, I also believe that it is important to make an early and accurate diagnosis of anisakiasis while the patient is in the ED.

Limitations

This study had several limitations. First, this study was a single- center case series; however, there have only been small-scale case series comparing gastric and intestinal anisakiasis thus far [7-10]. Second, al- though the definitions of gastric and intestinal anisakiasis in this study were consistent with those used in other studies [7,10], they could be considered lenient because we did not perform endoscopies, blood tests, or CTs in all patients with abdominal pain. Third, our study was retrospectively performed; therefore, it had inherent design flaws. Fi- nally, there may have been patient selection bias in our study because the hematologic Anisakis antibody test was only performed on those pa- tients with suspected small intestinal anisakiasis. Patients who were not suspected of having small intestinal anisakiasis by CT scan may have been missed in this study.

Generalizability

Although the prevalence of anisakiasis is rare in the United States and European Union, particularly in inland areas, compared with that in Japan [2,3], the incidence is expected to increase, given the growing popularity of Japanese cuisine, such as sushi or sashimi. Several cases of anisakiasis are reported worldwide annually [1]. As outlined above, the symptoms of anisakiasis are vague, and the patient may be misdiagnosed or undergo unnecessary surgical interventions [2,4,5]. In the ED, we examine several patients with acute abdominal pain every day; thus, the clinical diagnosis of anisakiasis is sometime difficult in emergency settings. In particular, the clinical diagnosis of small intesti- nal anisakiasis is more difficult than that of gastric anisakiasis. Our study demonstrated that approximately 9% patients with small intestinal anisakiasis had no history of raw or undercooked seafood ingestion

Fig. 2. Computed tomography findings (contrast-enhanced abdominal scan). All patients underwent 64-slice CT at the discretion of the patient and attendant physicians in the ED. We observed edematous wall thickening (?), mesenteric phlegmon (?), and ascites (->). A, Gastric anisakiasis (male, 37 years old) with edematous thickening of the gastric mucosal wall. B, Small intestinal anisakiasis (male, 69 years old) with limited edematous wall thickening of the intestinal tract, mesenteric phlegmom, and ascites.

and had prolonged clinical manifestations, which confounded the diag- nosis. Furthermore, the antigen test is not routinely performed for pa- tients with abdominal pain in emergency settings; therefore, there is a need for specific CT findings of small intestinal anisakiasis in that set- ting, and Radiographic diagnoses can be improved with the aid of multi- slice CT.

When we clinically diagnosed gastric anisakiasis, we decided to per- form endoscopy to confirm and remove the Anisakis larvae; this is a highly recommended therapy for gastric anisakiasis [1,14]. However, there is no established treatment for small intestinal anisakiasis, and small intestinal anisakiasis is typically treated in a conservative manner and is cured without surgery [15,16]. In practice, all patients with small intestinal anisakiasis were conservatively treated, including fluid re- placement therapy and pain control and cured without surgery in this study. We did not routinely use antibiotics, proton pump inhibitors, and histamine blockers. However, the Anisakis larvae can damage the digestive tract and occasionally other organs, causing erosive and/or Hemorrhagic lesions, ascites, perforation, granulomas, and masses [1,6,11]. In addition, some reports have shown that conservative thera- py failed in patients with small intestinal anisakiasis, and they underwent surgery for ischemia and perforation of small intestine. Thus, we should carefully observe patients with small intestinal

anisakiasis. In our study, 2 (5%) patients in the gastric anisakiasis group and 25 (57%) in the small intestinal anisakiasis group were ad- mitted to our hospital for Conservative therapy. We were unable to treat patients for small intestinal anisakiasis by an endoscopic removal of the Anisakis larvae; thus, these patients tended to develop ileus, thereby explaining why the admission rate and inpatient days of the small intestinal anisakiasis group were greater than those of the gastric anisakiasis group. The early and accurate diagnosis of anisakiasis in the ED helps us design a treatment plan and explain it to the patient.

Table 3

Symptom development

Development of symptoms, h (median [IQR])

Gastric anisakiasis Small intestinal P

anisakiasis

n= 39 n= 44

7 (4-12) 36 (12-48) b.01

Fig. 3. Symptom development. This figure indicates that the symptoms of gastric anisakiasis developed earlier than those of small intestinal anisakiasis. Gastric anisakiasis typically developed in 48 hours and peaked within 6 hours, whereas the small intestinal anisakiasis peaked within 48 hours and persisted for a maximum of 5 days.

Conclusion

When the cause of abdominal pain cannot be determined by an ini- tial assessment, anisakiasis should be considered, particularly if the pa- tient has a history of raw or undercooked seafood ingestion. In the ED, early and accurate diagnosis is important to determine a treatment plan and explain it to the patient. Diagnosis can be facilitated by a histo- ry of raw or undercooked seafood ingestion, evaluation of the time-to- symptom development, and classic CT findings.

References

  1. Pravettoni V, Primavesi L, Piantanida M. Anisakis simplex: current knowledge. Eur Ann Allergy Clin Immunol 2012;44(4):150-6.
  2. Kojima G, Usuki S, Mizokami K, Tanabe M, Machi J. Intestinal anisakiasis as a rare cause of Small bowel obstruction. Am J Emerg Med 2013;31(9):1422e1-2.
  3. Bucci C, Gallotta S, Morra I, Fortunato A, Ciacci C, Iovino P. Anisakis, just think about it in an emergency! Int J Infect Dis 2013;17(11):e1071-2.
  4. Mattiucci S, Fazii P, De Rosa A, Paoletti M, Megna AS, Glielmo A, et al. Anisakiasis and gastroallergic reactions associated with Anisakis pegreffi infection. Italy Emerg Infect Dis 2013;19(3):496-9.
  5. Pampiglione S, Rivasi F, Criscuolo M, De Benedittis A, Gentile A, Russo S, et al. Human anisakiasis in Italy: a report of eleven new cases. Pathol Res Pract 2002;198(6): 429-34.
  6. Valle J, Lopera E, Sanchez ME, Lerma R, Ruiz JL. Spontaneous splenic rupture and Anisakis appendicitis presenting as abdominal pain: a case report. J Med Case Rep 2012;6:114.
  7. Repiso Ortega A, Alcantara Torres M, Gonzalez de Frutos C, de Artaza Varasa T, Rodriguez R, Valle Munoz J, et al. Gastrointestinal anisakiasis. Study of a series of 25 patients. Gastroenterol Hepatol 2003;26(6):341-6.
  8. Gonzalez Quijada S, Gonzalez Escudero R, Arias Garcia L, Gil Martin AR, Vicente Serrano J, Corral Fernandez E. Anisakiasis gastrointestinal manifesta- tions: description of 42 cases. Rev Clin Esp 2005;205(7):311-5.
  9. Bouree P, Paugam A, Petithory JC. Anisakidosis: report of 25 cases and review of the literature. Comp Immunol Microbiol Infect Dis 1995;18(2):75-84.
  10. Shibata E, Ueda T, Akaike G, Saida Y. CT findings of gastric and intestinal anisakiasis. Abdom Imaging 2014;39:257-61.
  11. Lee JS, Kim BS, Kim SH, Park JK, Choi G, Hwang IK, et al. Acute invasive small- bowel Anisakiasis: clinical and CT findings in 19 patients. Abdom Imaging 2014:1-7.
  12. Ozcan HN, Avcu S, Pauwels W, Mortele KJ, De Backer AI. Acute intestinal anisakiasis: CT findings. Acta Gastroenterol Belg 2012;75(3):364-5.
  13. Caramello P, Vitali A, Canta F, Caldana A, Santi F, Caputo A, et al. Intestinal local- ization of anisakiasis manifested as acute abdomen. Clin Microbiol Infect 2003; 9(7):734-7.
  14. Sugimachi K, Inokuchi K, Ooiwa T, Fujino T, Ishii Y. Acute gastric anisakiasis. Analysis

    of 178 cases. JAMA 1985;253(7):1012-3.

    Matsui T, Iida M, Murakami M, Kimura Y, Fujishima M, Yao Y, et al. Intestinal anisakiasis: clinical and radiologic features. Radiology 1985;157(2):299-302.

  15. Takano Y, Gmi K, Endo T, Suzuki R, Hayashi M, Nakanishi T, et al. Small intestinal obstruction caused by anisakiasis. Case Rep Infect Dis 2013;2013:401937.