해외 증례(Japan) Autoimmune Gastritis with a Long-term Course of Type B gastritis: A Report of Two Cases

관리자
2023-08-23
조회수 68

Intern Med. 2023 Mar 15;62(6):855-863. doi: 10.2169/internalmedicine.0195-22. 


2개의 증례보고 입니다. 과거에 H. pylori induced atrophic gastritis (type B gastritis)의 분명한 내시경적 소견을 보이고 있었고, 수년이 지난 후 AIG가 확인된 환자에서 eradication therapy 없이 active H. pylori infection이 확인되지 않은 cases 입니다. 이러한 현상은 severe atrophy가 진행 되면서 spontaneous 하게 H. pylori의 현증 감염이 사라지는 것으로, H. pylori infection과 AIG사이의 연관성, H. pylori가 spontaneous하게 사라진 과정에서 AIG의 발생, 그리고 AIG cases에서 H. pylori infection의 유병률이 매우 낮게 나타나는 이유 등에서 유용한 data가 될 수 있겠습니다. 

 

<Case 1>

78/Female, Hypertension, Dyslipidemia

[2003년]

- GC of body: diffuse redness, enlarged folds, cloudy white mucus adhesion

- Gastric angle: xanthoma

- Antrum: partially discolored changes

[2008년 (Prominent atrophic changes)]

- Gastric fold: shrunk

- Kimura-Takemoto classification: type O3

- Antrum: extensive coarse and discolored atrophic changes

[2012년]

- Gastric fold: shrunk (more)

- GC of body: mild redness remained

[2019년]

- Kimura-Takemoto classification: type O4 (Op) (severe atrophic mucosa encompassed the entire area of the corpus)

- Antrum: severe atrophic changes

* H. pylori evaluation

- Anti-H. pylori antibody titer: 3U/mL  (cut-off value: 10U/mL)

- Monoclonal stool antigen test: negative

- Histological evaluation: no signs of active gastritis (neutrophilic infiltration)

- Giemsa stain: negative

* Serological biomarkers

- PG I: 14.0 ng/mL, PG I/II: 1.8, Gastrin: 978 pg/mL (standard cut-off titer, 200 pg/mL)

- Anti-parietal cell antibody (APCA): positive (1:160), Anti-intrinsic factor antibody: negative

[2020년]

- Endoscopic examination: (Fig. 1J-L) 

Figure 1. Temporal changes in endoscopic findings of Case 1 from 2003 to 2020. The number in parentheses indicates the patient’s age at that time. A, D, G, J (upper row): Images from the upper corpus to the angular portion. B, E, H, K (middle row): Images from the lower corpus to the angular portion. C, F, I, L (lower row): Images of the antrum. The progression of atrophic gastritis followed the pattern of type B gastritis.

Figure 2. Endoscopic findings of Case 1 in 2003. A: Typical findings of H. pylori-infected gastric mucosa at the greater curvature in the fornix. B: Predominant atrophic changes at the lesser curvature side of the corpus.


[2020년]

* Histolopathologic examination: 

- Deeper part of the lamina propria mucosa: Dense lymphocytic infiltration with eosinophils (Fig. 3A)

- Chromogranin A: Remarkable hyperplasia of enterochromaffin-like (ECL) cells (Fig. 3B)

- Antrum: Chronic inflammation (slightly), Intestinal metaplastic changes (some parts) (Fig. 3C, D)

Figure 3. Histopathological findings of Case 1 in 2020. A: The biopsy specimen obtained from the greater curvature of the middle corpus [Hematoxylin and Eosin (H&E) staining, original magnification ×100]. Severe atrophic changes with mucous gland metaplasia, intestinal metaplasia, and lymphoplasmacytic infiltration in the deeper part of the lamina propria mucosa, including eosinophilic cells. B: The same specimen as A (immunohistochemical staining for chromogranin A, original magnification ×100). Enterochromaffin-like cell hyperplasia with linear, tubular, and micronodular patterns. C, D: The biopsy specimen obtained from the antrum (H&E staining, original magnification ×100). Pyloric glands were relatively well-preserved in specimen C. Intestinal metaplasia changes were prominent in specimen D. 


[2021년]

* Serological examination

- Gastrin: 2,615 pg/mL, APCA: positive (1:160)

- Anti-H. pylori antibody titer: <3 U/ mL 

- Serological biomarkers for other autoimmune diseases (anti-thyroglobulin antibody [TgAb], anti-thyroid peroxidase antibody [TPOAb], anti-thyroid-stimulating hormone receptor antibody [TRAb], anti-SSA antibody, antiSSB antibody, anti-glutamic acid decarboxylase antibody [GADAb], and antinuclear antibodies [ANAs]) : all negative


[2022년]

* Serological examination

- No findings of iron-deficiency anemia or pernicious anemia

- Mild anemia with vitamin B12 deficiency 

(hemoglobin: 11.3 g/dL, mean corpuscular volume: 95.8 fL, vitamin B12: 138 pg/mL [lower limit of the reference value: 180 pg/mL])

* Endoscopic examination

- Visibility of submucosal vessels: More conspicuous in the entire area of the corpus

- Upper corpus & fornix: Sticky adherent dense mucus with white-yellowish color 

* Histopathological examination

- Severe atrophic changes with chronic inflammation in the deeper part of the lamina propria and ECL hyperplasia 

Figure 4. Endoscopic findings of Case 1 in 2022. A: Severe atrophic changes with marked vascular visibility all over the corporal area. B: Sticky adherent dense mucus in the upper corpus and fornix. C: Severe atrophic changes all around the antrum. D: Findings on narrow-band imaging (NBI) of the antrum. Many patchy grey plaques had spread all around. 


<Case 2>

76/Female, Dyslipidemia, DM

[2014년]

- Complete atrophic changes partially remained in the greater curvature of the corpus (Fig. 5A, B)

[2019년]

 - Discoloration and marked vascular visibility had extended to encompass the entire area of the corpus (Fig. 5D, E) 

- Remained in the antrum (Fig. 5F), it was difficult to recognize the finding of “reverse atrophy” on endoscopy

Figure 5. Endoscopic findings of Case 2 in 2014 (A-C), May 2019 (D-F), and October 2020 (G-I). The number in parentheses indicates the patient’s age at that time. A, B, D, E, G: Images from the corpus to the angular portion. C, F, I: Images of the antrum. In 2014, the antral mucosa was slightly coarse, although the discoloration was not so noticeable. In 2019 and 2020, the antral mucosa showed coarse and discolored atrophic changes with patchy redness. H: Close-up image by narrow-band imaging (NBI) of the greater curvature in the upper corpus. The surface mucosa showed irregular and uneven changes. 


* Histopathological examination 

- Upper & lower corpus: Moderate to severe atrophic changes, relatively aligned structure of the oxyntic glands was partially preserved, and several parietal cells could also be clearly distinguished at both sites (Fig. 6A, B)

- Chromogranin A: Obvious hyperplasia of the ECL cells (Fig. 6C) 

Figure 6. Histopathological findings of Case 2 in May 2019 (A-C) and October 2020 (D-F). A: The biopsy specimen obtained from the greater curvature of the lower corpus [Hematoxylin and Eosin (H&E) staining, original magnification ×200]. The relatively aligned structure of the oxyntic glands, including several parietal cells, partially remained. B: The biopsy specimen obtained from the greater curvature of the upper corpus (H&E staining, original magnification ×200). Several parietal cells were closely aligned in the glandular tubules. C: The same specimen as B (immunohistochemical staining for chromogranin A, original magnification ×100). Enterochromaffin-like (ECL) cell hyperplasia with linear, tubular, and micronodular patterns. D: The biopsy specimen obtained from the greater curvature of the lower corpus (H&E staining, original magnification ×200). The atrophic changes with mucous gland metaplasia were conspicuous. E: The biopsy specimen obtained from the greater curvature of the upper corpus (H&E staining, original magnification ×200). Clearly identifiable parietal cells were rarely observed. F: The same specimen as E (immunohistochemical staining for chromogranin A, original magnification ×100). ECL cell hyperplasia with linear, tubular, and micronodular patterns. 

- Antrum: Mild glandular atrophy & chronic inflammation, intestinal metaplastic changes (some parts) (Fig. 7A, B)

Figure 7. Histopathological findings of Case 2 in May 2019. A, B: The biopsy specimen obtained from the antrum (Hematoxylin and Eosin staining, original magnification ×100). Atrophic changes of the pyloric glands were relatively mild, but intestinal metaplastic changes were recognized in some parts. 

* Serologic examination

- PG I level: 22.0 ng/mL, PG I/II ratio 1.8

- Gastrin: 1,275 pg/mL

- APCA: positive (1: 80), AIFA: negative


[2020년 10월]

* Histopathological examination

- Similar to those from the previous year (Fig. 5G-I) 

- Glandular structure in the oxyntic mucosa became more non-uniform, with obvious mucous gland metaplasia. 

- Parietal cells were not as clearly recognized as they had been previously, and there were very few cells especially in the upper corpus (Fig. 6D, E) 

* Serological examination

- Gastrin: 1,172 pg/mL

- APCA: positive (1:320) 


[H. pylori infection status]

[1996년] Anti-H. pylori antibody titer: 6.5 EV (Determiner H. pylori, standard cut-off titer 1.7 EV)

[1998년] Histological examination: H. pylori specific immunostaining: positive

[2016년] 

- Anti-H. pylori antibody titer: 6.1 U/mL (E-Plate EIKEN H. pylori Ab II)

- UBT: 0.5‰ (negative reference value <2.5‰) 

[2018년] 

- Anti-H. pylori antibody titer: <3 U/mL

- Culture of H. pylori (gastric corporal biopsy specimens): negative 

[2019년]

- Histological examination (corpus, antrum: biopsy specimens): No signs of active gastritis

- Giemsa staining: negative

- Serological biomarkers for other autoimmune diseases (TgAb, TPOAb, TRAb, anti-SSA antibody, anti-SSB antibody, GADAb, and ANAs): all negative  


* H. pylori infection과 AIG의 상관관계는 아직도 논란이 많습니다. 이번 cases 처럼, 오랜시간 H. pylori gastritis가 선행되었다가 사라지면서 AIG가 나타나기도 하며, 동반되어 존재하고 있었을 수도 있고, active infection 상태가 burn-out 되어 없어지면서 AIG가 나타날 수도 있습니다. 

* H. pylori infection이 AIG를 억제시키고 있다가, H. pylori가 사라지거나 eradication 한 뒤에 AIG가 나타나고 빠르게 corporal atrophy를 진행시켰을 수도 있는데, 이러한 관점으로 본다면 H. pylori infection과 관계없이 어떤 다른 선천적인 autoimmune fators에 의해 AIG는 발생한다고 할 수 있으나 동반된 다른 autoimmune diseases는 없었습니다. 

* H. pylori gastritis를 가진 환자에서 어느 시점에 잠복되어 있던 AIG가 나타나는 것일 수도 있고, H. pylori gastritis 상태에서 나중에 AIG로 전환될 수도 있다고 생각됩니다.

* Severe한 corporal atrophy가 관찰된다면 serological markers를 확인하고, histological examination을 할 때는 전형적인 AIG의 양상을 보이지 않는 다고 하더라도, ECL cell identification을 고려하는 것이 좋을 것 같습니다. 

* AIG가 진단이 되면, 주의깊은 long-term surveillance가 필요합니다. 


 In conclusion, we experienced two cases of AIG with a long-term course of type B gastritis. These two cases had evidence of prior H. pylori infection, and their courses showed spontaneous disappearance. Further investigations are needed to determine whether or not there are many other such atypical cases, and whether or not this type of AIG is truly associated with H. pylori infection. In addition, it is important to accurately assess the H. pylori infection status, including previous or hidden infections, even if the patient is negative for infection at the time of the AIG diagnosis.

 

Abstract: Autoimmune gastritis (AIG) typically exhibits the characteristics of type A gastritis and has been classified as a separate disease from type B gastritis that corresponds to Helicobacter pylori gastritis. However, many reports have suggested the involvement of H. pylori infection in the pathogenesis of AIG. In our two cases, the patients’ previous gastritis exhibited a clear pattern in which H. pylori gastritis had progressed over many years, but ultimately transitioned to AIG with a spontaneous disappearance. These findings suggest that some cases of AIG might originate from long-standing H. pylori gastritis.

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대한자가면역성위염연구회

주소 : 경기도 용인시 기흥구 중부대로 579, 508-23호 (구갈동, 강남대프라자)

대표전화 : 070-8080-0453  이메일 : autogastritis@gmail.com 


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