Acute pancreatitis, mesenteric adenopathies, and

1130-0108/2008/100/12/779-787 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS Copyright © 2008 ARÁN EDICIONES, S. L.

CLINICOPATHOLOGICAL CONFERENCE

REV ESP ENFERM DIG (Madrid) Vol. 100. N.° 12, pp. 779-787, 2008

Acute pancreatitis, mesenteric adenopathies, and diarrhea Y. Sánchez, C. Garfia, G. López Alonso1, C. Yela, M. Amo, C. Arribas, F. Cruz Vigo2 and J. A. Solís Herruzo

Services of Digestive Diseases, 1Pathology, and 2General Surgery A. University Hospital 12 de Octubre. Madrid, Spain

Sánchez Y, Garfia C, López Alonso G, Yela C, Amo M, Arribas C, Cruz Vigo F, Solís Herruzo JA. Acute pancreatitis, mesenteric adenopathies, and diarrhea. Rev Esp Enferm Dig 2008; 100: 779-787.

CASE REPORT

Dr. Cristina Garfia. A 34-year-old woman with Down’s syndrome and adequate motor, cognitive, and adaptive development presented to our hospital’s emergency room because of poorly-defined, continuous severe epigastralgia for 24 hours, with no reductions or exacerbations, radiating to the back, and associated with nausea, bile vomiting, and asthenia. Her personal history included no allergies or toxic habits, and the patient had undergone laparotomy for the excision of a left ovarian “chocolate cyst” three years before. The questioning on organ systems revealed intermittent dyspeptic symptoms since young age with no mention to specific triggering factors, which consisted of postprandial fullness, heartburn, non-specific epigastric discomfort, and flatulence. She also reported intermittent, self-limited fluid diarrhea episodes with no pathological products, alternating with normal intestinal rhythm. Received: 12-07-08. Accepted: 18-08-08.

Correspondence: Cristina Garfia. Servicio de Medicina del Aparato Digestivo. Hospital Universitario 12 de Octubre. 28041 Madrid, Spain. e-mail: [email protected]

Physical exploration revealed the phenotypical manifestations of trisomy 21; heart and lung auscultation was normal; the abdomen was soft and tender to deep palpation in the epigastrium, with no defense reaction or other peritoneal irritation signs; palpation revealed no masses or organomegalies; bowel sounds were normal. The remaining exploration was uneventful. The CBC and coagulation tests performed in the emergency room were normal, but biochemistry revealed elevated amylase levels (660 IU/l). The patient was admitted with a diagnosis of acute pancreatitis. The patient had a favorable clinical course. At 48 hours after admission she was asymptomatic, tolerated fluid ingestion, and lacked Ranson’s criteria for severity. During admission the following lab tests were performed: CBC, coagulation, renal and liver function, and lipids, which were all normal. Serum amylase was 624 IU/l and lipase was 8,859 IU/l. Serum iron was 43 µg/dl, but ferritin and transferrin levels were normal. C-reactive protein (CRP) was 0.50 mg/dl. Two coprocultures showed the standard saprophytic bacterial flora, and no Clostridium difficile toxins were identified. In order to establish the cause of acute pancreatitis and the presence of potential complications, the patient underwent the following exams: abdominal ultrasonography, which was normal; abdomino-pelvic computerized tomography (CT), which showed minimal attenuation of the pancreatic fat-acinar pattern with normal contrast uptake and no fluid collections or increased density in peripancreatic fat. This exam also found numerous mesenteric adenopathies of uncertain significance, which were not associated with retroperitoneal adenopathies or hepatosplenomegalia. Cholangio-MRI confirmed the presence of adenopathies, all of them smaller than 1 cm, with normal bile and pancreatic ducts. Despite a favorable outcome, lack of complaints, and normal imaging results, blood amylase and lipase levels remained high.

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Table I. Evolution over weeks or months Test Hb (g/dl) Htc (%) MCV (fl) Platelets/mcl WBCs/mcl Neutrophils (%) Lymphocytes (%) Glucose (mg/dl) Creatinin (mg/dl) Amylase (UI/l) Lipase (UI/l) Total prot. (g/dl) Albumin (g/dl) Bilirubin (mg/dl) GOT (IU/l) GPT (IU/l) GGT (IU/l) Alkaline P. (IU/l) LDH (IU/l) Ca (mg/dl) Na (mEq/l) K (mEq/l) Cl (mEq/l) Coagulation CRP ESR (1st. tour) Iron (μg/dl) Ferritin (ng/ml) Transferrin (mg/dl) TIBC (μg/dl) Abdominal pain Diarrhea

ER

4 days

26 days

13.6 40.4 91.1 434,000 7,200 79 15.5 110 0.7 660 – 8.12 4.02 0.3 31 38 13 171 126 8.6 140 3.8 106 Normal –

13.2 38 90.2 496,000 4,500 59 25 94 1.13 624 8,859 6.7 3.5 0.29 30 16 12 194 132 8.7 140 4.67 104 Normal 0.5 48 43 103 246 347 Asymptomatic Intermittent

11.5 35.1 94 433,000 4,500 62 24.2 78 0.91 557 8,910 7.3 3.71 0.22 29 39 14 150 128 8.8 142 4.48 107 Normal – 60 – – – – Asymptomatic Intermittent

– – – – Severe No

Dr. Yuramí Sánchez. This is a 34-year-old patient who was admitted for mild acute pancreatitis with a favorable outcome from a clinical standpoint, albeit elevated blood amylase and lipase levels persisted for at least 26 days. Radiographic studies ruled out biliary lithiasis as the cause of pancreatitis, with the former condition representing, together with excessive alcohol drinking, 75-85% of acute pancreatitis causes (1). The patient reported a very limited incidental use of alcoholic beverages on social grounds, always in small amounts. Among metabolic causes, hypertriglyceridemia is most common and may originate pancreatitis in 1.3 to 3.8% of cases (2). Hypercalcemia of any etiology results in acute pancreatitis rarely, hence its occurrence in patients with chronic hypercalcemia suggests other factors; for instance, in hyperparathyroidism acute pancreatitis occurs in fewer than 1.5% of cases (3,4). In this patient normal triglyceride and calcium levels rule out these metabolic causes. The use of some drugs (antibiotics, diuretics, sulfasalazine, immunosuppresants, neuropsychiatric agents, etc.) has been thought to increase the risk for acute pancreatitis; however, this is fairly uncommon and most series report an incidence of such cases around 1-3% (3,4). This etiology may also be excluded in this patient since she usually received no medication. Therefore, with the available data,

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we should include her pancreatitis within the idiopathic group. Imaging techniques ruled out all sorts of complications or pseudocysts that might have explained the persistently increased blood amylase and lipase levels. However, both CT and cholangio-MRI showed multiple mesenteric adenopathies smaller than 1 cm (Fig. 1), whose significance could not be established with these techniques. In this patient adenopathies seemed limited to the mesentery as neither CT nor MRI identified involved lymph nodes in other anatomical sites. Physical exploration also found no palpable peripheral adenopathies.

Fig. 1. Abdominal CT scan showing mesenteric adenopathies (arrows).

The differential diagnosis of mesenteric adenopathies should include those that develop during inflammatory conditions, infectious diseases, and tumors (5,6). Mesenteric adenopathies may be secondary to any inflammatory process, both abdominal (appendicitis, diverticulitis, cholecystitis, pancreatitis, abdominal perforation) and systemic. In appendicitis adenopathies usually develop on the right iliac fossa mesentery. When caused by diverticulitis, adenopathies are usually found close to the inflamed colon. Adenopathies secondary to pancreatitis are commonly retroperitoneal or peripancreatic. Only severe pancreatitis -which was not the case with our patient -- may be associated with mesenteric adenopathies. In Crohn’s disease mesenteric adenopathies are a fairly common finding (7,8). These adenopathies may be found either at the mesenteric root or the peripheral mesentery, or in the right lower quadrant of the abdomen. They are commonly reported as large, prominent, though rarely massive adenopathies. Their density increases following the injection of a radiographic contrast. In collagenoses, including lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, adenopathies -even mesenteric ones -- are common (9-11); however, peREV ESP ENFERM DIG 2008; 100 (12): 779-787

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ripheral and retroperitoneal adenopathies are nearly always present. Other conditions where mesenteric adenopathies are common include primary biliary cirrhosis (12), amyloidosis, mastocytosis (13), Schönlein-Henoch purpura (14), familial Mediterranean fever (15), and celiac disease, but in all these conditions adenopathies accompany their characteristic manifestations. Another inflammatory cause of mesenteric adenopathies is mesenteric panniculitis. This disease also manifests with abdominal pain, nausea, vomiting, fever, and weight loss. Radiographically, mesenteric fat density is highly attenuated because of inflammation and fibrosis (16,17). In our patient CT scans revealed no mesenteric changes resembling those of mesenteric panniculitis. Sarcoidosis is a multisystemic granulomatous condition of unknown etiology that is relatively common in adults younger than 40 years, and preferentially involves the lungs and thoracic lymph system (18,19); it also may affect abdominal lymph ducts (20). Between 30% and 50% of patients with sarcoidosis are asymptomatic, and a diagnosis is incidentally reached when a chest film is available (21). This is a diagnosis of exclusion that requires the presence of: a) compatible clinical or radiographic manifestations; b) non-caseating epithelioid granulomas in histological samples; and c) no other causes potentially leading to similar clinical-radiographic manifestations (22). This patient had no respiratory complaints, and also lacked general symptoms, joint pain, erythema nodosum, fever, ocular discomfort, etc.; however, as previously discussed, the disease may be subclinical. Chest radiograms and CT scans revealed no abnormal changes. While transbronchial biopsy and bronchoalveolar lavage have a high diagnostic value (18,21,22), I presume this patient underwent no such tests because CT scans were normal and there were no symptoms to justify these procedures. Even though I feel sarcoidosis may be excluded in this case as the cause for mesenteric adenopathies, I would like to know whether angiotensin converting enzyme (ACE) activity was measured, as this parameter is above normal in 40-80% of patients with sarcoidosis, most often with levels above twice the upper normal limit (18,19,21). Dr. C. Garfia. ACE levels were measured and found to be normal (23.9 U/l). Indeed, no lung biopsy or bronchoalveolar lavage was performed. Dr. Y. Sánchez. Thank you. While normal ACE levels do not rule out sarcoidosis, as these may be normal in 20-50% of patients, this result, together with those previously discussed, does allow to exclude such disease and prompts consideration of infection and tumor-related alternatives. Infectious causes of mesenteric adenopathies include tuberculosis. The incidence of this disease has increased of late in Spain, likely in relation to immigrants from areas where the condition is common. According to WHO, Spain has the second highest incidence of tuberculosis (after Portugal) in the European Union, with more than 20 cases/100,000 inhabitants (23). Tuberculous adenopathies usually have specific characteristics - primary lung tuberculosis is commonly associated REV ESP ENFERM DIG 2008; 100 (12): 779-787

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with unilateral paratracheal and subclavicular adenopathies; milliary tuberculosis shows a uniform, diffuse radiographic pattern with adenopathies 10 to 30 mm in size, at times in clusters or calcified (24,25). Abdominal adenopathies are preferentially found on the mesentery rather than the peritoneum. In 60% of patients they exhibit central attenuation from central necrosis (26). Following the intravenous injection of a contrast medium images are peripherally enhanced (25). A similar, cavitated radiographic aspect has been described for Whipple’s disease caused by Tropheryma whippelii (27), and celiac disease (28,29). In primary intestinal tuberculosis adenopathies may be limited to the mesentery. Our patient had no respiratory symptoms, and her adenopathies lacked tuberculous radiographic characteristics, hence this etiology seems extremely unlikely; however, before ruling out tuberculosis we would like to know whether a sputum microbiological study, Mantoux test, chest PA and lateral radiographic study, or chest CT scan were performed. Dr. C. Garfia. The sputum could not be analyzed since she had no respiratory symptoms or expectoration. A radiologist reported her chest radiograms were normal, and dual-contrast thoracic CT revealed no parenchymal changes or mediastinal adenopathies. The Mantoux test was negative. Dr. Y. Sánchez. Well, as tuberculous etiology seems unlikely for these mesenteric adenopathies, we should consider other infectious causes. These include infection with Yersinia enterocolitica. This infection typically exhibits a thickened wall in the terminal ileum plus mesenteric adenopathies (30). Symptoms may be mistaken for acute appendicitis, and intestinal lesions for those of Crohn’s disease. Infection with the human immunodeficiency virus (HIV) may originate mesenteric lymphadenopathies in 1015% of cases. At times this is due to viral infection itself; on other occasions they arise from opportunistic infection or complicating neoplasms (31). In the former instance adenopathies are small or moderate in size, and never massive. Most common opportunistic infections in these patients include the Mycobacterium avium complex, when CD4 cell levels are lower than 50/ml. Mesenteric adenopathies, usually massive and in conglomerates, are found in 42% of patients with this superimposed infection (30,32). The characteristics of our patient’s adenopathies strongly differed from those seen in Mycobacterium avium infection. Mesenteric adenitis is another common cause of mesenteric adenopathies particularly in children, albeit imaging techniques are now showing that this condition may be not rare in adults (26). This is a benign, usually viral inflammatory condition of uncertain etiology (33,34) that manifests with mesenteric adenopathies, at times associated with intestinal inflammation. These patients usually suffer from acute, chronic or recurrent abdominal pain, most commonly in the right iliac fossa, usually accompanied by nausea, vomiting, diarrhea, fever, and leucocytosis; the condition is commonly and not surprisingly mistaken for acute

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appendicitis (26,35). I do not know whether any studies were performed to exclude the aforementioned abdominal infections. If not, these diseases should not be overlooked (Table II).

Table II. Diseases causing mesenteric adenopathies Infectious

Immunological

Hematological

Mesenteric adenitis Tuberculosis Yersinia enterocolitica Y. pseudotuberculosis Mycoses Whipple’s disease Mononucleosis Cytomegalovirus Rubella Syphilis Toxoplasmosis AIDS

Lupus erythematosus Rheumatoid arthritis Dermatomyositis Sarcoidosis Mesenteric panniculitis Crohn’s disease Primary biliary cirrhosis Amyloidosis Mastocytosis Schönlein-Henoch purpura Celiac disease

Hodgkin’s lymphoma Non-Hodgkin lymphoma Chronic lymphoid leukemia T-cell lymphoblastic lymphoma T-cell acute lymphoblastic leukemia Metastases

The third group of mesenteric adenopathies I must consider is that related to tumors, primarily those arising from lymphoproliferative conditions (36). Hodgkin’s disease usually begins in mediastinal or cervical lymph nodes, whence it extends to nodes in other areas, including the retroperitoneum and spleen. The disease then spreads through the blood and involves other organs such as the liver, lungs, and bone marrow. This patient had no supradiaphragmatic adenopathies, B symptoms (fever, night sweating, weight loss) or liver/spleen involvement signs. More rarely the disease may present with only infradiaphragmatic affectation in 30% of cases, albeit adenopathies are retroperitoneal rather than mesenteric in such patients (25,37). A definitive diagnosis with Hodgkin’s disease is reached when the histological study of adenopathies reveals Reed-Sternberg cells (37). As I suppose no biopsies were obtained from this patient’s mesenteric adenopathies, I would like to know whether she underwent 67Ga abdominal scintigraphy or 18F-deoxyglucose positron-emission tomography (PET). Both exams are useful in revealing the lymphomatous nature of adenopathies (38). Dr. C. Garfia. The patient had a 67Ga scintigram, which showed no changes suggestive of lymphoma. Dr. Y. Sánchez. These results make it even more unlikely that these mesenteric adenopathies arise from either Hodgkin’s or non-Hodgkin lymphoma. Nonetheless, in contrast with Hodgkin’s disease, initial manifestations may be extranodal in non-Hodgkin lymphomas (37). Adenopathies are initially scarce and small, but they increase in size and number as the disease progresses, and tend to cluster into big soft-tissue masses that displace neighboring structures. On CT scans they exhibit soft-tissue density, but a higher-density peripheral ring may be

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seen on occasion. Such radiographic changes were also not found in our patient. Other tumors frequently resulting in mesenteric adenopathies include breast (39), lung, pancreas, gastrointestinal (40,41), and bladder carcinomas, as well as melanoma and sarcoma, including Kaposi’s sarcoma (42). Breast and lung tumors rarely induce mesenteric adenopathies without previously affecting mediastinal, lung hilar, or axillary locations. Gastrointestinal and colonic tumors are very commonly associated with mesenteric adenopathies. Pancreas carcinoma also originates mesenteric adenopathies; however, initial adenopathies arise in peripancreatic and retroperitoneal areas. Kaposi’s sarcoma gives rise to big adenopathies, 3 to 5 cm in size, that tend to come together into huge masses and are usually associated with intestinal compromise. The presence of adenopathies in only one territory obliges to explore neighboring organs, as they may be the only manifestation of neoplastic disease (24,43,44). In this patient with only mesenteric adenopathies gastrointestinal exploration is mandatory. Tumors in this location, particularly lymphomas, may give rise to such adenopathies (45). Lymphoma types most commonly involving the gut include: a) marginal zone B-cell (MALT) lymphoma; b) diffuse large B-cell lymphoma (high-grade MALT lymphoma); c) other lymphomas (lymphoplasmacytic, mantle-cell, Burkitt’s, T-cell lymphomas, associated with bowel disease or otherwise). MALT lymphomas usually manifest with various clinical pictures including diarrhea, intestinal malabsorption, abdominal pain, general symptoms, and/or bowel obstruction. These tumors, initially restricted to the gut wall, spread to mesenteric lymph nodes and then to farther locations; nearly 13% of patients have subdiaphragmatic adenopathies at the time of diagnosis (46). Intestinal T-cell lymphomas are rarer, but often develop in patients with celiac disease (47). Because of this, I would like to know whether any radiological or endoscopic studies of the gastrointestinal tract were carried out. Furthermore, such studies would help us rule out or support some of the discussed diagnoses (tuberculosis, yersiniosis, inflammatory bowel disease, celiac disease, etc.). Dr. C. Garfia. Yes, they were. A follow-through showed that intestinal loops were somewhat dilated, but their diameter still remained within the normal range. Normal limits were exceeded only in the ileum. However, fold characteristics were normal (Fig. 2). A colonoscopy was also performed, which revealed no abnormal changes. Gastroscopy showed chronic gastritis with antral predominance, and duodenal villous atrophy. This led to carry out a capsule endoscopy of the small bowel, which confirmed mild villous atrophy in the duodenum and proximal jejunum, but no masses, infiltration areas, ulcers, or strictures (Fig. 3). Dr. Y. Sánchez. Obviously, these studies suggest that the patient may well suffer from an intestinal condition with villous atrophy. While such atrophy is a histological REV ESP ENFERM DIG 2008; 100 (12): 779-787

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Fig. 2. Intestinal follow-through. Note mildly increased loop width and fold thickness.

Fig. 3. Images obtained with capsule endoscopy, which revealed mild villous atrophy in the duodenum and proximal jejunum.

lesion of celiac disease, this association is not exclusive. Indeed, this histological change may be found in parasitoses, bacterial overgrowth, eosinophilic enteritis, tropical sprue, malnutrition, hypogammaglobulinemia, acute REV ESP ENFERM DIG 2008; 100 (12): 779-787

viral gastroenteritis, and cow milk intolerance, among others. An adequate interpretation of histological findings requires further histological parameters including gland crypt status, epithelial characteristics, and type of inflammatory infiltration. In celiac disease there is a shortening or flattening of intestinal villi together with gland crypt hyperplasia and lamina propria infiltration, mainly with (CD4+) lymphocytes and plasma cells (47,48). These lesions that result from exposure to gluten-containing food are common among Europeans and their descendants in non-European countries, with an incidence of up to 1 in 100-300 inhabitants (49-51). The risk for this disease is particularly high among the firstand second-degree relatives of patients with celiac disease, in patients with type-I diabetes mellitus, in subjects with thyroiditis or other autoimmune diseases (52), and in individuals with Down syndrome, as in our case. In the latter setting it has a prevalence of 3 to 12%, and the risk for celiac disease in these patients is estimated around five-fold that of the general population (51,53). As celiac disease is relatively common in our context (54), and subclinical, oligosymptomatic, or extradigestive in most adults, I will first discuss the possibility that this patient may have this disease. To this end I need to know the results of the following tests: fecal fat, anti-transglutaminase antibodies, and intestinal biopsy. Dr. C. Garfia. Fecal fat was normal (1 g/24 hours), as was fecal chymotrypsin (27.1 U/g); blood levels following the oral administration of 25 g of D-xylose were

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24.7 mg% and 31 mg% at 60 and 120 min, respectively, and urinary excretion at 5 hours was 14% (3.5 g), all of them within normal ranges. Blood immunoglobulin levels were normal (IgG, 1270 mg/dl; IgA, 484 mg/dl; IgM, 62 mg/dl), and non-organ-specific antibodies (ANA, AML, AMA, ALKM) were negative. In contrast, IgA anti-gliadin antibody levels were 45.6 IU/l, and IgA antitransglutaminase antibody levels were 581.7 IU/l (both elevated). Regarding histological findings in biopsies obtained during gastroscopy, these were reported as follows: duodenal mucosa biopsy that shows architectural changes consisting of total villous atrophy, gland crypt hyperplasia, and lymphoplasmacytic infiltration of the lamina propria (Fig. 4). The gastric (antrum, fundus) mucosa sample exhibited normal glands with scarce neutrophilic infiltration, with no lymphoid infiltrates in follicles, and no bacilli identifiable with Giemsa stain. These histological studies concluded that there was total villous atrophy in the duodenum, and superficial antral gastritis with no evidence of Helicobacter pylori.

Fig. 4. Distal duodenal mucosal biopsy showing full intestinal villous atrophy, gland crypt hyperplasia, and lamina propria infiltration.

Dr. Y. Sánchez. All these findings suggest that our patient may have adult celiac disease with few symptoms till recently, which would account for the diarrhea episodes in her medical history, as well as for her epigastric discomfort. Normal fecal fat may be explained, even in the presence of celiac disease, by inadequate fecal sampling or insufficient fat ingestion. Nevertheless, intestinal fat absorption is normal in some cases, in which malabsorption for other nutrients may be seen. Anyway, normal fat excretion in the feces does not exclude celiac disease. The D-xylose test provided results on the lower limit of normality, since urinary excretion should be higher than 4 g (> 16%) and blood levels at 60 minutes

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should exceed 20 mg/dl. Diagnostic reliability is not very high for this test either, as it may be normal in up to 20% of patients with untreated celiac disease (55). The sensitivity and specificity of IgA anti-transglutaminase antibodies in the diagnosis of celiac disease are pretty high, above 95% in the presence of total villous atrophy (56), as is the case with this patient. On these grounds, gluten withdrawal from the diet and patient monitoring are recommended. The diagnosis with celiac disease would be reinforced should abdominal complaints, anti-transglutaminase antibody levels, and histological lesions improve within days or weeks after gluten-free diet onset (51,57). However, histological normalization usually requires longer than one year or may never result (58,59); however, the height of epithelial cells in the villous stump increases within weeks after gluten withdrawal. CT and MRI may provide data with a high diagnostic value -- for example, splenic atrophy, ascites, and lymphadenopathies (60-62). The latter are seen in 43% of cases (63) and are extremely suggestive of this disease when cavitated (28,29,64), albeit this rare finding has been reported in fewer than 50 cases. Histologically, adenopathies are cavitated, contain a chylous-creamy material, and are surrounded by a thin peripheral ring made up of fibrosis and lymph-node remnants (65). This finding provides recognition that adenopathies are not secondary to a lymphoma complicating celiac disease. The relationship of mesenteric adenopathies to celiac disease is demonstrated when their size and number decrease following gluten withdrawal (62). Therefore, I would like to know whether this patient had gluten withdrawn from her diet, and how she responded. Dr. C. Garfia. In view of the available data we also considered celiac disease, and consequently withdrew gluten-containing food from her diet. Pain subsided completely, as did digestive complaints, and blood amylase and lipase levels decreased and reached 266 IU/l and 1724 IU/l, respectively, after 6 months. IgA anti-gliadin and IgA anti-transglutaminase antibodies paralleled this (21.8 IU/ml and 368.5 IU/ml, respectively). Dr. Y. Sánchez. The response of this patient to gluten deprivation supports the notion that she has celiac disease, even though antibody levels after 6 months should be lower. Overall, when gluten withdrawal is complete, blood antibody levels return to normal within 3 to 6 months (59,60). Therefore, it is highly likely that the patient complies inadequately with her diet, and still eats gluten-containing food maybe involuntarily (forgetfulness or neglect), as occurs in many non-responders (66). During dietary restriction blood amylase and lipase levels decreased, which suggests that pancreatitis was also related to celiac disease. Several studies report the presence of hyperamylasemia and hyperlipasemia in celiac disease, and their progressive improvement when on a gluten-free diet (67). Blood pancreatic enzymes decreased but did not return to normal in the reported case. Incomplete reversal may also be associated with REV ESP ENFERM DIG 2008; 100 (12): 779-787

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poor diet compliance; however, despite stringent compliance, such reversal may be slow and take up to one or two years (67). These elevations of pancreatic enzymes may be accounted for by autoimmune pancreatitis associated with celiac disease (68). Approximately 20% of patients with celiac disease have some sort of autoimmune condition associated (52,69), with type-I diabetes mellitus, hypothyroidism, lupus erythematosus, and atrophic gastritis being most common. No clear criteria exist for the diagnosis of autoimmune pancreatitis, but pancreatic ducts usually have an irregular, narrow lumen, and blood IgG -- particularly IgG4 -- levels are severely high (70,71). Our patient showed no relevant changes in her pancreatic ducts on cholangio-MRI, and electrophoresis revealed no marked increase in IgG. While the latter test’s diagnostic value has been questioned, other changes have been found in celiac disease that may account for pancreatic disturbances (69). For instance: macroamylasemia with or without macrolipasemia (72-74), duodenal inflammation, a stenotic papilla of Vater, or inadequate pancreozymin production may be responsible for these changes in celiac disease (73,75,76). While gluten intolerance plays a pivotal role in the development of bowel lesions in celiac disease, strong genetic predisposition is certainly an issue here (47,77). In this respect 80%-95% of celiac patients have been found to carry HLA-DQ2 (α1*501, β1*02), with HLA-DQ8 (α1*0301, β1*0302) in the rest (47,53,78,79). Hence, I would like to know whether this patient underwent genetic tests. Dr. C. Garfia. Yes, she did, and these tests revealed that she is homozygotic for HLA DQ2. Dr. Y. Sánchez. That is, this genetic study also supports a diagnosis with celiac disease. While this HLA-DQ2 is fairly common among the European population (25-30%) with no celiac disease, it is well known that HLA DQ2 in both chromosomes multiplies the risk for celiac disease by five versus heterozygotes (79,80). Although mesenteric adenopathies may be found in celiac disease, as discussed above, this is a rare finding, and adenopathies regress with dietary management; thus, I would like to know their outcome following gluten restriction. Dr. C. Garfia. At 6 months after starting on a glutenfree diet a new CT scan revealed the persistence of the reported adenopathies. One was 1.7 x 0.9 cm, and a second one was 1.9 x 1.2 cm in size, and both looked like conglomerates of smaller adenopathies; still, no adenopathies were seen in other areas. Dr. Y. Sánchez. This finding makes close monitoring mandatory with regular tomographic follow-up. Dr. C. Garfia. Even though no diagnostic test had found evidence supporting other disorders, particularly tuberculosis or lymphoma, the persistence of mesenteric adenopathies prompted a diagnostic laparoscopy including a biopsy of these adenopathies. Adenopathies were REV ESP ENFERM DIG 2008; 100 (12): 779-787

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seen to be small in size, and their histological characteristics were non-specific. FINAL DIAGNOSIS

Adult celiac disease, acute pancreatitis, and non-specific mesenteric adenopathies. REFERENCES 1. 2.

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