Collagenous gastritis

: A 54-year-old woman presented with nausea, vomiting and weight loss associated with impaired gastric emptying necessitating institution of paren teral nutrition. Subsequent studies revealed an unusual gastric mucosa! inflam matory nrocess characterized by unique subepithelial collagenous deposits. Collagenous gastritis appears to be a distinct, possibly immune-mediated, chronic disorder, pathologically reminiscent of collagenous sprue and collagenous colitis.


I N 1970, WEINSTEIN ET AL ( I ) DESCRIBED
a unique form of sprue -collagenous sprue -characterized clinically by refractory malabsorption and histopathologically by subepithelial collagen deposition in small in testinal biopsies. Simila r histological features in the small intes-tine were noted in two earlier reports by Schein (2) and Hourihane (3). ln 1976. two reports independently described previously unrecognized histopathological featu res in colorectal biopsies from patients with chronic watery diarrhea ( 4 ,5 ). Thick subepi thelial collagenous de- Medicine  Receiuedfor publication August 8,1989. Accepted October 6,1989 CAN J GASTROENTEROL VOL 3 No 5 N OVEMU~R./DECEMBER 1989 posi ts were seen and Lindstrom (5), in one of these reports, proposed the label collagenous colitis because of apparent pathological similarities to collagenous sprue. Since 1976, more than 50 patients with this disorder have been described and reviewed; in at least one patient both the small and large bowel were involved with the same process (7). In the present report, a 54-year-old woman with a distinct form of gastri tis is described. Clinical fea tures suggested a progressive, possibly immune-mediated disorder, while gastri c biopsies were cha racte rized histopathologicall y by trichrome-positive, subepithelial collagenous deposits reminiscent of previously described changes in the small and large intestine of patients with collagenous sprue or collagenous colitis ( 1-7).

CASE PRESENTATION
A 54-year-old woman born in Scotland was initially seen in March 1979 with a three year history of anorexia, intermittent vomiting and weight loss of 14 kg. She d id not use alcohol, salicylates or other medications. Past history included a psychiatric admission in 1972 fo r depression; at that time, nausea and vomiting were apparently present. Examination revealed a weight of 38 kg and generalized muscle wasting. Gastroscopy  was initially attempted prior to referral but rescheduled because of retained food residue; it was reported to show 'severe gastritis' with diffuse mucosa! friability. As symptoms persisted despite treatment with antacids, cimetidine and metoclopramide, she was referred for evaluation.
Investigations included a normal hemoglobin of 123 g/L and white cell count of 10,300/mm 3 with a normal differential. Platelets, prothrombin time, activated partial thromboplastin time and fibrinogen were normal. Erythrocyte sed-imencation rate was 3 mm/h (normal up to 20). Serum electrolytes, urea, creatinine, fasting and 2 h postprandial glucose, bilirubin, alkaline phosphatase, transaminases, uric acid, amylase, gastrin, ferritin, folic acid, vitamin B 12, thyroxine and urinalysis were normal. Parietal cell antibodies, antinuclear antibodies and rheumatoid factor were negative. Syphilis serology was negative. Adrenocorticotrophic hormone-stimulated cortisols were normal. Total protein was reduced to 45 g/L (normal 60 to 77) and serum albumin was reduced to 27 g/L (normal 36 to 48). lmmunoelectrophoresis and immunoglobulin quantitations (lgG, lgM, lgA, lgE) were normal. Sig· moidoscopy and biopsy were normal. Chest x-ray, oral cholecystogram, intra· venous pyelogram and barium x-rays of the upper and lower gastrointestinal tracts were normal. Abdominal ultrasound, bone, liver and gallium whole body scans as well as bone marrow aspiration were normal, with no evidence of neoplasia.
In hospital, attempts to introduce food and enteral nutrition supplements led to abdominal distension with severe nausea and vomiting. A succussion splash was detected and abdominal x-rays revealed gastric dilation. Because of continuing nutritional deterioration, total parenteral nutrition was initiated. The patient's hospital course was subsequent· ly complicated by bilateral aspiration pneumonia and hypoxemic respiratory failure with a pleural effusion. Pseudomonas aeruginosa was cultured, requiring intensive treatment with oxygen, physiotherapy and antibiotics. Sputum cyto· logies and thoracentesis of pleural fluid were negative for malignant cells and tu· berculosis cultures were negative. Repeat endoscopies by two gastroenterologists confirmed the presence of patchy erythematous gastric mucosa without ulceration; mucosa! vasculature appeared normal. Air insufflation of the stomach resulted in multiple freely bleeding petechial hemorrhages and marked mucosa! friability. The duodenum was normal.
Multiple mucosa! biopsies from the gastric fundus, body and antrum revealed an 'acute gastritis' with polymorphonuclear leukocytes but no evidence of neoplasia. A search in the biopsy sections for candid a and other organisms including spirochetes, Campylobacter pylori, cryptosporidium and cytomegalovirus was negative. Cultures of the gastric aspirate revealed P aeruginosa but no candida. Small bowel b iopsies were normal. A gastrograffin swallow suggested impaired gastric emptying, but repeat bar· ium studies of the upper and lower gas· trointestinal tract were normal. A two week therapeutic trial of carbenoxalone resulted in hyperkalemia; cimetidine, metoclopramide and antacids were re·  instituted. Respiratory and nutritional status improved with an increase in weight to 47 kg. Nausea and vomiting abated permitting oral intake but this was variable ranging from 600 to 1800 kcal/day.
The patient was discharged in May 1979 but required readmission in August 1979 because of deterioratil)g respiratory status, redevelopment of nausea and vomiting, and weight loss to 36 kg. Repeated blood tests revealed continuing hypoproteinemia and hypoalbuminemia, with the appearance on peripheral blood smears of Howell-Jolly bodies. Parenteral nutrition was reinstituted. Liver-spleen scan revealed no splenic activity. Bone marrow biopsy was normal. Chest x-ray and bronchograms suggested bronchitis and early bronchiectasis. Pulmonary function studies were consistent with airflow obstruction. Lymphangiogram of the lower limbs, inguinal, iliac and periaortic lymph nodes was normal. Pentagastrin-stimulated gastric analysis revealed no titratable acid, and a repeat barium study suggested slight narrowing of the gastric antrum. Gastroscopy revealed only hyperemia with diffuse mucosa! friability; biopsies revealed no neoplastic cells. Persisting pulmonary sepsis required continuing antimicrobial therapy and parenteral nutrition was reinitiated.
Because of persistent nausea and inability to eat, an exploratory laparotomy was done in October 1979. The stom-ach appeared pale and prominent rugal folds with a 'gritty texture' were described. An atrophic spleen was resected and showed fibrosis. Liver biopsy revealed some bile stasis consistent with cholestasis associated with parenteral nutrition. Full thickness gastric biopsies were done. Oral intake continued to deteriorate and was estimated to be 500 to 600 kcaVday and prednisone 10 mg bid was started . During admission eye pain developed and filamentary keratopathy was observed. Tear secretion was absent on a Schirmer's test and a diagnosis of Sjogren's syndrome was made. Respiratory deterioration continued; the course was complicated by a fatal pulmonary embolism. Autopsy: Autopsy revealed buccal mucosa! subepithelial inflammation consisting predominantly of lymphocytes. In addition, salivary gland lobules showed atrophy with a lymphocytic inflammatory change. Extensive bronchiectasis was present in both lower lobes of the lungs. Although the gastrointestinal mucosa was severely autolyzed, full thickness gastric biopsies from the laparotomy were reviewed; these confirmed the presence of gastritis with increased lamina propria lymphocytes and plasma cells. Glands were reduced in number and numerous polymorphonuclear leukocytes were noted in the surface epithelium and lamina propria. No neoplastic cells were present and amyloid stains were negative. A prominent extracellular sub-CAN J GASTROENTEROL VOL 3 N O 5 N OVEMBER/DECEMBER 1989 epithelial band of eosinophilic material was observed with entrapped cells; this material was trichrome-positive, typical of collagen and si milar to features in collagenous sprue ( 1) and collagenous colitis (5). Endoscopic biopsies prior to laparotomy: These included six gastric biopsies from body and antrum in March 1979. and one gastric body biopsy in September 1979. Of these, one gastric antral biopsy done in March 1979 showed a focal area of su bepithelial collagen deposition. No deposits were identified in the other six gastric biopsies, two biopsies from the small intestine and one rectal biopsy.

DISCUSSION
This report illustrates a unique gastric mucosa! inflammatory process characterized histopathologically by the presence of dense subepithelial collagenous deposits. C linically, the patient had markedly impaired gastric emptying and achlorhydria. These histopathological changes in gastric biopsies are similar to those reported in the subepithelial regions of small and large bowel mucosa! biopsies from patients with collagenous sprue (I) and collagenous colitis (5). The entity described here appears to be distinct from other previously described forms of gastritis and is labelled collagenous gastritis.
This entity shares some apparently common clinical features with those al-FREEMAN er al ready observed in patients with collagenous sprue and collagenou s colitis. As in the p resent case. most patie n ts described with small o r large in testinal involvem ent are fe m ale w ith a m ean age of m o re than SO years (6)(7)(8). T he cl in ical course o f these disorde rs appears to be chronic with persistent o r intermitten t sym pto m s. In collage no us sprue, refractory m a labsorption is usua lly present ( L) and pare nteral n u trition may be required to pe rmit survival, w hile in collagenous colitis, ch ronic watery d iarrhea is evident. A ltho ugh th ere a re som e a necdotal reports of successfu l d rug treatme n t of collage nous sprue (9) and collage nous colitis ( 10-12), patient n umbers in most series are small and duration of follow-u p is usu ally li m ited. An imm u ne-med iated pathogenesis has been suggested for both collage nous sp rue and collagenous coli-ACKNOWLEDGEMEN TS, The autho rs acknowledge the excellent secretarial assistance of Mrs Wendy Semko and Mrs Cec Taerg.
In th e present patien t, clinical and pathological features typical of Sjogren 's syndrome appeared. S he a lso developed features of functiona l hyposplen ism . H owell-Jo lly bodies appeared in perip h eral blood smears associated with an absence of sple n ic radionuclide uptake; at laparotomy, fibrosis of the spleen was discovered. Lymphoreticular dysfunction with hyposplenism and splenic atroph y o r fibrosis may accompany several gastroin testinal disorders including celiac sprue and dermatitis herpetiformis, intestinal lymphoma, mesenteric lymph node cavitation syndrome and infla mmatory bowel d isease ( l 7-21). Studies in this patient excluded each of these collagenous colitis with involvement of e ntities; in retrospect, reduced splenic fun ction p robably con tributed to the contin u ing respiratory sepsis.
T his report describes a new form of gastric r:nucosal inflammato ry disease, collageno us gastritis, in a m idd le-aged fe m ale w ith defective gastric e mptying and achlorhyd ria; associated disorders in th is patien t incl uded h yposple nism w ith splen ic fib rosis, progressively deteriora ti ng respiratory sepsis with bronch iectasis and development of Sjogen's synd rome. A n immu ne-med iated pathogenesis is suspected, possib ly resu lting in a ltered fu nction of la m ina propria fibroblasts, cells though t to be importan t in collagen production a nd deposition in the ep ithelial base me n t membrane region of the gastrointestinal tract. Treatment of collagenous gastritis is, at this time, unk nown .