| < Presentation of Case >
A 39-year-old man had been diagnosed as having focal segmental glomerulosclerosis (FSGS) for 15 years and started peritoneal dialysis (PD) since six years earlier before this admission. Four episodes of bacterial peritonitis due to methicillin-sensitive Staphyllococus aureus occurred to him without complications and his general condition and ultrafiltration and urea clearance had been maintained in good condition over the past six years. Three months prior to this admission, he started to experienced abdominal fullness and pain, nausea, occasional vomiting and indigestion. The PD catheter was patent at that time but he experienced less efficient ultrafiltration when using the PD dialysate of the same concentration. He was treated as a non-specific functional GI disorder initially, however, the symptoms persisted and he lost two kilograms of weight in three months. At PD clinic, there were no symptoms or signs suggestive of heart or liver failure. The dialysate fluid was blood-tinged exudate in character (data not shown) and the culture result was negative for bacteria, fungi and acid-fast bacilli. (See laboratory tests for dialysate). Cytology of the dialysate was negative. Since he failed to achieve adequate ultrafiltration and urea clearance, PD was shifted to hemodialysis two weeks prior to admission. However, his abdominal symptoms gradually worsened and he was admitted for diagnostic and therapeutic paracenteses.
Upon admission, the physical examination revealed a well-developed man with chronic ill-looking. His heart rate was 82 bpm, temperature was 37.1 ℃, blood pressure was 130/72 mmHg. There was neither pale conjunctiva nor icteric sclera. The heart beat was regular without murmurs. Auscultation of the lung fields was normal. On examination of the abdomen, hyperactive bowel sounds and mildly distended abdomen were detected. There was shifting dullness, but no hepatosplenomegaly or peritoneal sign was observed. Mild lower leg edema was noted.
< Laboratory and Image Study >
1. CBC and differential count
|
Day after admission |
WBC
K/μL |
Hgb
g/dL |
Hct
% |
Plt
K/μL |
Band
% |
Seg
% |
Eos
% |
Lym
% |
PD clinic-1 |
5.98 |
13.3 |
38.5 |
440 |
0 |
68 |
0.2 |
2.2 |
PD clinic-2 |
6.98 |
11.3 |
33.5 |
430 |
0 |
70 |
0.3 |
2.5 |
Admission day 1 |
7.54 |
10.6 |
30.8 |
462 |
0 |
70 |
0.5 |
2.4 |
Admission day 5 |
7.48 |
11.0 |
33.1 |
440 |
0 |
N/A |
N/A |
N/A |
Admission day 15 |
7.53 |
11.8 |
34.7 |
460 |
0 |
N/A |
N/A |
N/A |
N/A: not applicable, PD clinic-1 indicates condition patient had no subjectively complaint, PD clinic-2 indicates this event.
2. Biochemistry
|
Day after admission |
BUN
mg/dl |
Cre
mg/dl |
Na
mmol/l |
K
mmol/l |
Ca mg/dl |
P
mg/dl |
GOT
U/l |
CRP
mg/dl |
Albumin
g/dl |
PD clinic-1 |
65 |
6.5 |
137 |
4.2 |
10.3 |
3.5 |
30 |
0.5 |
4.2 |
PD clinic-2 |
85 |
6.5 |
137 |
4.1 |
10.1 |
3.9 |
29 |
2.5 |
3.8 |
Admission day 1 |
89 |
7.3 |
138 |
4.6 |
9.8 |
5.5 |
N/A |
8.2 |
3.6 |
Admission day 5 |
72 |
7.0 |
140 |
4.3 |
9.9 |
4.9 |
N/A |
N/A |
N/A |
Admission day 15 |
77 |
7.8 |
138 |
4.6 |
10.0 |
4.5 |
30 |
4.3 |
3.6 |
3. Tests for Dialysate
|
Day after admission |
appearance |
WBC count
(/mm3) |
PMN
% |
Lym
% |
Gram stain |
Bacteria culture |
Fungus culture |
PD clinic-1 |
clear |
40 |
8 |
30 |
- |
N/A |
N/A |
PD clinic-2 |
Slightly reddish |
38 |
10 |
26 |
- |
N/A |
N/A |
Admission day 1 |
Slightly reddish |
54 |
10 |
28 |
- |
- |
- |
Admission day 5 |
Slightly reddish |
50 |
12 |
26 |
- |
N/A |
N/A |
Admission day 7 |
Slightly reddish |
48 |
10 |
26 |
- |
N/A |
N/A |
4. Ascites study (aspirated from loculated ascites): Exudate in character, negative for bacterial, fungal and mycobacterial cultures. WBC: 100/ul; neutrophils, 7%; lymphocytes, 30%; monocyte/macrophage, 50%.
5. Computed tomography (CT) of the abdomen: Moderate to massive multi-loculated ascites is noted, without abscess formation. Relatively thicken intestinal wall and peritoneum was noted. No tumor or lymphadenopathy. Partial small bowel adhension is noted. Atrophic kidney, bilateral. Suspected bilateral simple cysts of both kidneys.
6. Peritoneum biopsy: Prominent fibrosis with inflammatory cells infiltration. No evidence of malignancy.
< Course and Treatment >
After admission, CT of the abdomen was performed, which revealed moderate to massive multi-loculated fluid accumulation without abscess. In addition, thickened intestinal wall and peritoneum as well as partial dorsal fixation of the small bowel were noted. There was no tumor or lymphadenopathy. Based on the history, clinical symptoms, thickening of the intestinal wall and visceral peritoneum, local adhesion of the intestines, and negative studies for microbiological cultures, encapsulating peritoneal sclerosis (EPS) was suspected. Laparoscopy was arranged and biopsy of the thickened peritoneum, lyses the adhesion and drainage the loculated ascites were performed. The pathology demonstrated thickened and fibrotic peritoneum. A diagnosis of EPS of unknown etiology was made. After surgery, even though the adhesion was not completely relieved, patient subjectively felt improved in GI symptoms. An arteriovenous fistula was created to prepare for future permanent hemodialysis. Immunosuppressive therapy using prednisolone (30 mg/day) and tamoxifen (10 mg/day) was instituted. This patient was discharged with improvement of GI symptoms. Prednisolone was tapered in the following two months but tamoxifen was continued. The patient tolerated hemodialysis well and did not experience recurrent GI symptoms.
< Analysis >
Encapulating peritoneal sclerosis (EPS) 又名sclerosing peritonitis或sclerosing encapsulating peritonitis，可以原發或次發於腹膜透析的病患，不過不管原發或次發，發生率都相當低。在PD病患，EPS被定義為一種臨床症候群 (clinical syndrome)，其臨床特點為在接受或已沒有接受PD治療的病患中，當病患出現持續、間歇性或反覆性腸道阻塞，有時並伴隨帶血之腹水。症狀最主要是因為小腸被增厚且纖維化的腹膜所包裹所造成。由於目前尚不清楚此症候群發生的原因，因此並無標準治療方法，且方法也有限，因此造成此症候群的死亡率頗高。根據不同研究，EPS在PD病患的發生率約為0.5%至2.8%。雖然發生率低，但接受PD治療的時間越長，發生EPS的可能性就隨之增加，可從5年內的0.4%增加到15年的17%。至於男女之間的發生率，目前並無定論。目前所有關於EPS的研究都是屬於回溯性的，因此很難去釐清因果關係，但有些危險因子被報告，如使用chlorhexidine消毒PD導管、較多腹膜炎次數、high peritoneal membrane transport特性，使用beta-blocker及接受長期PD治療的病患等(見Table 1 & 2)。不過如同之前所述，EPS的致病因果關係目前仍不清楚，因此有一些所謂的危險因子需要進一步確認，如EPS也是會出現在從未發生過腹膜炎的病患及83%接受PD治療超過15年的病患，沒有產生EPS。
由於EPS的症狀不具特異性，且無法以檢驗方法診斷，因此EPS主要靠臨床醫師的高度警覺來診斷。EPS的初期表現是不具特異性的腸胃道症狀及脫水(ultrafiltration, UF)效果變差，不具特異性的腸胃道症狀有可能被診斷為functional GI disorder而錯失早期診斷機會。一般PD初期的UF下降主要是由於腹膜的通透性增加所致，但EPS導致的UF變差是以腹膜的通透性下降所致，而造成腹膜的通透性下降是源於腹膜的逐漸纖維化。因為腹膜的逐漸纖維化而變厚、腸道變厚、沾黏進而引起噁心、嘔吐、腹瀉或便秘、腹脹及完全或部分腸道阻塞，接者體重減輕及營養不良。實驗室方面檢查則可見不具特異性的C-reactive protein升高。影像學檢查如超音波或abdomen CT，或可幫助EPS的診斷，但僅止於幫助確定腸道沾黏或阻塞，而無法判定病因是EPS。以abdomen CT來說，典型的發現如腹膜增厚(早期不一定會見到)、局部液體蓄積(loculated fluid accumulation)、腹膜鈣化、小腸壁增厚及與後部沾黏(posterior tethering)。其中以腹膜鈣化、小腸壁增厚及與後部沾黏(posterior tethering)和較嚴重的腸胃道症狀有關。但是要注意的是，即使影像學檢查正常也不能完全排除EPS的可能。最後也是最直接的診斷就是以手術方法直接檢視，則可見腹膜增厚、纖維化及病變的腹膜包裹部分小腸。病理切片則可見增厚腹膜的methothelium cells被collagen取代，增加微血管新生、在更嚴重的情形可見腸壁纖維化、longitudinal肌及myenteric plexus都被纖維組織取代。不過單憑組織病理的結果也不具特異性，且有時與UF failure或感染性腹膜炎難以區分，因此臨床上診斷EPS是需要靠諸多證據包括病史、臨床症狀、影像學及組織病理學結合，才可能辦到的。
治療分為內科及外科治療，在內科治療方面，類固醇是被使用最多的治療藥物，包括低劑量的prednisolone (10 – 40 mg/d)或methylprednisolone 脈衝式治療(pulse therapy) (0.5 – 1 g/d)都有人使用。文獻提出的EPS治療建議為，若在保守治療後，病患的反應不理想(或改善有限)時，就要考慮類固醇治療，而治療的成功率，則從38%到100%都有被報告過。由於曾有EPS病患在腎臟移植後使用免疫抑制藥物，進而發現免疫抑制藥物能減緩甚至改善EPS的症狀，因此如azathioprine、cyclosporin及tamoxifen就開始被使用於EPS。不過並非所有的免疫抑制藥物都有效，如mycophenolate mofetil (MMF)、tacrolimus及sirolimus就被認為是可能無效的。至於為何免疫抑制藥物能治療EPS，目前並不清楚。外科治療方面，雖然EPS病患會有較高的術前、術後手術死亡率，但至少一半以上的病患，對內科治療的反應不佳，最終還是得接受手術以解除症狀。造成高手術死亡率多起因於anatomic leak之後所產生的敗血症。所以目前EPS的手術治療，多僅限於清除沾黏及切除cocoon (cocoon: 在EPS末期，因全部或局部小腸被增厚的纖維組織包裹所形成)。另外也有報告指出若在術前即給予類固醇及免疫抑制藥物，術後發炎及沾黏會較輕微，且治療效果也較好。
由於EPS是相當難處理及治療的症候群，因此預防發生成了最重要的課題。不過如前所述，EPS目前仍無確定的病因，因此在預防上只能依據臨床建議。在所有PD病患都需做到的預防措施，包括: 1)、預防腹膜炎； 2)、及早診斷及治療腹膜炎； 3)、在嚴重腹膜炎時要提早移除PD catheter，以減低腹膜的受損； 4)、使用biocompatible dialysate (bicarbonate buffers及non-glucose osmotic agents； 5)、避免及減低腹膜接觸可能傷害腹膜的藥物及化學物質。其他爭議性較大的，如在接受腹膜透析4至8年後，就改成血液透析或在EPS早期徵象確定時馬上停止等，不過這必需因病人而異。本病例接受PD治療，雖有2次PD腹膜炎的病史，但不易確定導致EPS產生的原因，由於診斷還算早，且病患腸道沾黏不是太嚴重，因此在經過手術處理後及藥物治療後，情況已穩定並且在門診持續追蹤中。由於曾有報告指出接受PD治療的時間越長，發生EPS的機會就越高，而國內目前大力推廣PD，是否會對未來國人EPS的發生率產生影響，值得注意。
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Case Discussion
繼續教育考題