Dr. Bailey.
Cristina Garfia.
A 34-year-old woman with Down's syndrome but adequate development of her motor, cognitive and adaptive capacities went to the hospital's emergency department due to intense epigastric pain radiating to 24 hours of continuous, poorly defined asthenia.
Her personal history included no allergies or toxic habits and she had only had a laparotomy three years before to remove a "chocolate cyst" in her left ovary.
In the anamnesis by organs and devices, he pointed out that since his youth he had dyspeptic symptoms intermittently, without needing triggers, consisting of postprandial fullness, heartburn, nonspecific epigastric discomfort and flatulence.
He also reported intermittent and self-limiting episodes of liquid diarrhea without pathological products that alternated with phases of normal intestinal rhythm.
Physical examination revealed the typical phenotypic changes of trisomy 21; normal cardiopulmonary resuscitation; abdominal examination revealed no palpable abdominal mass or deep auscultation findings in peritoneal epigastrium or other signs of diffuse abdominal irritation.
The rest of the examination showed no abnormalities.
Laboratory tests showed that the blood count and coagulation study performed in the Emergency Department were normal, but the biochemical analysis of blood showed that the amylase value was high (660 IU/l).
She was admitted with a diagnosis of acute pancreatitis.
The clinical evolution of the patient was favorable.
48 hours after admission, the patient was asymptomatic, tolerated fluid intake and had no Ranson criteria of severity both at admission and 48 hours later.
During admission, the following analytical studies were performed: blood count, coagulation, renal and hepatic function and lipids, all normal.
Serum amylase was 624 IU/l and lipase 8.859 IU/l.
The sideremia was 43 μg/dl but ferritin and transferrin were normal.
C-reactive protein (CRP) was 0.50 mg/dl. Two coprocultives showed normal bacterial flora saprophytic and no Clostridium difficile toxin was detected.
In order to determine the cause of acute pancreatitis and recognize the existence of complications, the patient was subjected to the following examinations: abdominal ultrasound, normal; computerized axial tomography (CAT), normal pancreatic fat mass without contrast uptake, peripelvic fat mass.
This exploration also found the existence of numerous adenopathies with uncertain significance, which were not accompanied by retroperitoneal adenopathy or hepatomegaly.
A nuclear magnetic resonance was also performed which confirmed the presence of lymphadenopathies, all of them smaller than 1 cm, but the biliary and pancreatic ducts were normal.
Despite the good evolution of the patient, being asymptomatic and the results of imaging tests, the rates of amylase and lipase in blood remained high.
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Dr. Bailey.
Yuramí Sánchez.
A 34-year-old female patient was admitted for mild acute pancreatitis with favorable clinical manifestations, although elevated rates of amylase and lipase were observed for at least 26 days.
Studies allowed ruling out gallstones as a cause of pancreatitis, which together with alcohol consumption constitute the 75th percentile of causes of acute pancreatitis (1).
The patient reported very occasional alcohol consumption due to social reasons and in very few cases.
Among the metabolic causes, hypertriglyceridemia is the most frequent, and it can cause pancreatitis in 1.3 to ̄s cases (2).
Hypercalcemia of any etiology produces acute pancreatitis very infrequently, so that its incidence in patients with chronic hypercalcemia leads us to think that it is a consequence of other factors, for example in the case of acute pancreatitis 1, less hyperparathyroidism.
In this patient, normal rates of triglycerides and calcium allow us to rule out these metabolic causes.
It has been reported that the use of some drugs (antibiotics, diuretics, anaphylaxis) is common and most cases refer to quite rare series of neuropsychiatric agents, etc.), which may increase the risk of acute pancreatitis.
This etiology can also be ruled out in this patient, since the patient did not usually consume any drug.
Therefore, with the available data, the nature of pancreatitis should initially be included in the group of idiopathic pancreatitis.
Imaging techniques ruled out any complications or pseudocysts that could explain the persistent increase in blood amylase and lipase.
However, both CT and magnetic resonance cholangiography showed that there were multiple mesenteric adenopathies smaller than 1 cm in size, whose significance could not be determined with these techniques.
In this patient, adenopathies appeared to be limited to the mesentery, since neither CT nor magnetic resonance imaging could recognize that they existed elsewhere in the body.
Neither did the physical examination reveal palpable peripheral adenopathies.
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In the differential diagnosis of mesentery adenopathies, those appearing in the course of inflammatory, infectious and tumoral diseases must be considered (5,6).
Adenopathy affecting the mesentery may be secondary to any inflammatory process, such as abdominal colitis, diverticulitis, pancreatitis, and systemic perforation.
In the case of meningitis, adenopathies are located in the mesentery of the right iliac fossa.
When the cause of adenopathies is an immediate diverticulum, its location is usually in the vicinity of the inflamed colon.
If adenopathies are secondary to pancreatitis, their location is usually retroperitoneal or peripancreatic.
Only severe forms of pancreatitis, which was not the case of the patient mentioned above, can be accompanied by lymphadenopathies.
In Crohn's disease, mesenteric adenopathies are a very common finding (7.8).
These lymph nodes can be found both at the root of the mesentery and in its periphery or in the lower right quadrant of the abdomen.
They are often described as large, prominent lymph nodes, although they are rarely massive.
After injection of radiological contrast, its density increases.
Rheumatoid arthritis, including lupus erythematosus, peripheral and systemic lupus, is common among patients with rheumatoid arthritis. It is rare for those with adenopathies, even those with adenopathies (9-11), but it is very rare that they do not accompany them
Other circumstances in which familial adenopathy is usually found are celiac disease (12), although primary biliary cirrhosis is characterized by amyloidosis, mastocytosis (13), and Schchönlein-H purpura (14).
Another inflammatory cause of adenopathy is mental retardation.
This disease also presents with abdominal pain, nausea, vomiting, fever and weight loss.
Radiologically, it is observed that the fat mass originates a great attenuation of its density due to inflammation and fibrosis (16,17).
The CT scan of the patient did not reveal any mesenteric change that reminded the patient of the “pan mental disorder”.
Sarcoidosis is a granulomatous, multisystemic disease of unknown etiology, relatively common in adults under 40 years of age, which preferentially affects the lungs and the thoracic lymphoid apparatus (18.19), but can also compromise the abdominal lymph
Between 30% and 50% of patients with sarcoidosis are asymptomatic and the diagnosis is reached by chance on performing a chest X-ray (21).
Diagnosis is made by exclusion and requires the presence of: a) compatible clinical or radiological manifestations; b) atypical epithelioid granulomas (noncase type 22), histological samples; and c) exclusion of other causes.
The patient we discussed here had no respiratory symptoms, and there were no general symptoms, arthralgia, erythema nodosum, fever, eye discomfort, etc., although, as I mentioned above, the disease may occur.
Neither chest X-ray nor CT showed abnormal changes.
Although transbronchial lung biopsy and bronchoalveolar lavage have a great diagnostic value (18.21,22), I suppose that in this patient they were not performed due to lack of symptoms that justify it and to be the normal TAC.
Although I believe that sarcoidosis can be excluded in this patient as the cause of the enlarged lymph nodes21 most of them, with their first wishes to know if in this patient was determined the activity of the enzyme converter of angiotensin (ECA), 4019).
Dr. Bailey.
C. Garfia.
ACE levels were determined which were normal (23.9 U/l).
Indeed, lung biopsy or bronchoalveolar lavage were not performed.
Dr. Bailey.
Y. Sanchez.
Thank you, although the normality of this test does not exclude sarcoidosis, since it can be normal in 20-50% of patients, this data together with all the above, I believe that they allow us to reject this infectious disease and force us to consider the tumor options.
Tuberculosis stands out among the infectious causes of adenopathy.
It is a disease that has increased in recent years in Spain, probably in relation to the arrival of puppies from areas where the disease is very common.
According to WHO data, Spain is the second country in the European Union with the highest incidence of tuberculosis (after Portugal), with more than 20 cases/100,000 inhabitants (23).
Tuberculous lymph nodes usually have particular characteristics, since when pulmonary tuberculosis is primary, adenopathies are usually unilateral and the affected lymph nodes are the paratracheal and subclavicular conglomerates with diffuse calcified pattern 10
Abdominal lymph nodes are preferentially located in the mesentery rather than in the retroperitoneum.
In 60% of cases central attenuation was caused by central necrosis (26).
After intravenous contrast injection, a peripheral enhancement of the image occurs (25).
A similar cavitated radiological aspect has been described in Whipple disease caused by Tropheryma whippelii (27) and celiac disease (28.29).
When tuberculosis is primary intestinal, adenopathies may be limited to the mesentery.
The patient we discussed lacked respiratory symptoms and the lymphadenopathies did not present the radiological characteristics of tuberculosis, so this etiology seems extremely unlikely. However, before we rule out tuberculosis, we would like a post-mortem CT scan.
Dr. Bailey.
C. Garfia.
The sputum could not be analyzed because it lacked respiratory symptoms and expectoration.
The chest X-ray was reported as normal by the radiologist and the double-contrast chest CT showed no parenchymal alterations or mediastinal adenopathies.
The Mantoux test was negative.
Dr. Bailey.
Y. Sanchez.
Well, since the tuberculous etiology of adenopathies affecting the mesentery is unlikely, other infectious causes must be considered.
Yersinia enterocolitica infection is one of them.
The thickening of the wall of the terminal ileum accompanied by mesenteric adenopathies (30) is characteristic of this infection.
Symptoms can be confused with those caused by acute colitis and intestinal lesions with Crohns disease.
Human immunodeficiency virus (HIV) infection can also cause lymphoadenopathies in 10-15% of cases.
Sometimes this is due to the viral infection itself, in others it is caused by opportunistic infections or complications (31).
In the first case, the size of the lymph nodes is small or medium, but not massive.
Among the most frequent opportunistic infections in these patients is caused by the Mycobacterium avium complex; this occurs when the CD4 rate is less than 50/ml.
Forty-two percent (42%) of patients with this type of infection had lymphadenopathy, usually massive and conglomerated masses (30.32).
The characteristics of the adenopathies originated in the patient were very different from those reported by Mycobacterium avium.
Metastatic adenitis is another common cause of adenopathies preferentially affecting children. However, imaging techniques have shown that they are not uncommon in adults (26).
It is a benign inflammation of unknown etiology, usually viral, 34), in which there are adenopathies every month, sometimes accompanied by intestinal inflammation.
These patients usually complain of acute, chronic or recurrent abdominal pain, preferably located in the right iliac fossa, frequently accompanied by nausea, vomiting, diarrhea, fever and leukocytosis, so it is not rare to have acute confusion (26.35).
I don't know if studies were done to rule out the abdominal infections I mentioned.
If not, these diseases should not be forgotten.
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The third group of lymphadenopathies that should be considered is the malignant lymphoproliferative disorders.
Hodgkin's disease usually begins in the lymph nodes of the mediastinum or neck and from them extends to other ganglionic areas, including the retroperitoneum and the spleen.
Later on, the disease spreads by pathogenic pathway and involves several organs, such as the liver, lung or bone marrow.
The patient reported here had no supradiaphragmatic lymphadenopathies, symptoms B (fever, night sweats, weight loss) or signs of liver or splenic involvement.
Although rarer, the disease may present with exclusive infradiaphragmatic involvement in 30% of cases, although in these cases the adenoids are retroperitoneal and non-mesophilic (25,37).
The definitive diagnosis of Hodgkin's disease is made when the presence of Reed-Sternberg cells is demonstrated in the histological study of adenopathies.
As I suppose that PET adenopathies in this patient were not biopsied, I would like to know if an abdominal 67Ga scintigraphy or an 18F- positron emission tomography (PET) were performed.
Both examinations are very useful to recognize the lymphomatous character of adenopathy.
Dr. Bailey.
C. Garfia.
In this patient, an abdominal scintigraphy with 67Ga showed no changes suggestive of lymphoma.
Dr. Bailey.
Y. Sanchez.
With these results, it is even more unlikely that adenopathies affecting the mesentery were due to both Hodgkin and non-Hodgkin lymphomas.
However, in the latter, and contrary to what occurs in Hodgkin's disease, the first manifestations can be extrauterine, including those resulting from involvement of the gastrointestinal tract and lymph nodes.
Initially, adenopathies are small and scarce, but as the disease progresses, their size and number increase and tend to involve large masses of soft tissue displacing neighboring structures.
At CT, its density is characteristic of blade tissues, but sometimes there is a peripheral ring of higher density.
Neither are these radiographic changes found in this patient.
Other tumors that frequently cause adenopathies are breast cancer (39), lung, pancreas, gastrointestinal (40.41) and gallbladder, melanoma and sarcomas, including Kaposi's (42).
Breast and lung tumors rarely cause adenopathies affecting the mediastinum, pulmonary hilium or armpits.
Gastrointestinal and colonic diseases are frequently associated with adenopathies affecting the mesentery.
Pancreatic carcinoma also causes adenopathies of this location; however, the first adenopathies to appear are peripancreatic and retroperitoneal.
Kaposi's sarcoma originates large adenopathies of 3 to 5 cm, which tend to accumulate large masses and are usually accompanied by intestinal involvement.
The presence of lymph nodes located in a single territory requires exploring organs as they can be the only manifestation of a disease (24.43.44).
In the case of this patient with exclusively mesenteric adenopathies, the study of the digestive tract is mandatory.
Tumors of this location, especially lymphomas, can originate this type of adenopathy.
The types of lymphomas most frequently affecting the digestive system are: (a) B-cell lymphoma of the marginal area of the lymphatic tissue associated with the mucosa (MALT lymphoma); (b) diffuse large B-cell lymphoma (lymphoma).
MALT lymphomas usually manifest with various clinical pictures including diarrhea, intestinal malabsorption, abdominal pain, general symptoms or intestinal obstruction.
These tumors, which initially are limited to the wall of the digestive tract, extend to the mesenteric ganglia and later to more distant ganglionic groups: approximately 13% of cases present adenopathy (46).
Intestinal T-cell lymphomas are rarer, but in many cases they develop in patients with celiac disease (47).
For this reason, I would like to know if endoscopic studies of the digestive tract were performed.
These studies would also help to rule out or support some of the aforementioned diagnoses (tuberculosis, inflammatory bowel disease, celiac disease, etc.).
Dr. Bailey.
C. Garfia.
They did.
The radiological study of the intestinal transit showed that the intestinal loops were somewhat identical, but their diameter was still within normal limits.
Only in the ileum exceeded these limits.
However, the characteristics of the folds were normal.
Pathway was also performed, which revealed no abnormal change.
A gastroscopy revealed an endoscopic image of chronic gastritis predominantly antral and veilous duodenal.
For this reason, a study of the intestine with capsule endoscopy was also carried out, which confirmed the existence of veils and vesicular and proximal strictures, but not masses, duodenum zones, ulcers or ulcers.
1.
Dr. Bailey.
Y. Sanchez.
Evidently, these studies suggest that the patient may suffer from an intestinal disease that manifests as a vesicular disease.
Although this form is part of the spectrum of histological lesions that occur in celiac disease, it is not the only disease in which intestinal villi exist.
In fact, this change can be found in parasitosis, bacterial overgrowth, eosinophilic enteritis, tropical spurt, malnutrition, hypogammaglobulinemia, acute viral gastroenteritis, intolerance to other cow's milk.
For a correct interpretation of the histological results it is necessary to have more histological data, including the status of glandular crypts, the characteristics of the epithelium and the type of inflammatory infiltrate.
In celiac disease there is a flattening or flattening of intestinal villi while hyperplasia of glandular cells and cryopreservation of lamina propria lymphocytes (47.48).
These lesions, determined by exposure to gluten-containing foods, are common among Europeans and their descendants in other countries, where they can occur in 1 per 100-300 inhabitants (49-51).
The risk of this disease is especially high among first- and second-degree relatives of patients with celiac disease, in patients with type I diabetes mellitus, in whom thyroiditis or other autoimmune diseases of Down occur (52).
In this latter situation its prevalence is 3 to 12% and it is estimated that the risk of these patients to suffer celiac disease is about five times higher than the general population (51.53).
Because celiac disease is relatively common (54) in our environment and because it occurs in adults in most cases subclinically, oligosymptomatic or with non-gastrointestinal manifestation, I will begin to analyze this disease.
To do so, please do not know the results of the determination of fecal fats, anti-transglutaminase antibodies and intestinal biopsy.
Dr. Bailey.
C. Garfia.
Faecal fats were measured, but these were normal (1 g/24 hours), as well as faecal chymotrypsin levels (27.1 U/g); blood rates after oral administration of 25 g of D-120 %, respectively
Blood immunoglobulin levels were normal (IgG, 1270 mg/dl, IgA, 484 mg/dl, IgM, 62 mg/dl) and non-organ specific antibodies (ANMA, ALKM, AML) were negative.
In contrast, the antigliadin-IgA antibodies were 45.6 IU/l and the antitransglutaminase-IgA antibodies of 58 IU/l (high emboli).
In relation to the histological findings of biopsies taken during gastroscopy, they were described as: biopsy of the duodenal mucosa that shows an architectural alteration constituted by total lymphocytic vesicles in the villi, hyperplasia of the cryptic lamina.
The gastric mucosa biopsy (antral, fundic) showed a normal glandular population, with low neutrophil infiltration, without lymphoid infiltrate in follicles or bacilli recognizable with Giemsa staining.
These histological studies concluded that there was a total duodenal mucosa with villi and antral superficial gastritis, with no evidence of Helicobacter pylori.
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Dr. Bailey.
Y. Sanchez.
All these findings suggest that the patient could have an adult celiac disease until then little symptomatic, but that would justify the episodes of diarrhea appearing in the medical history, as well as epigastric discomfort.
Normality of fat could be explained, even celiac disease, if stool collection was not correct or fat intake was insufficient.
However, there are cases in which intestinal absorption of fats is normal but absorption of other nutrients is defective.
In any case, normal faecal fat excretion does not exclude celiac disease.
The D-xylosa test also did not provide results that were within the low limits of normality, since its urinary excretion should be higher than 4 g (> 16%) and its normal celiac disease blood concentration at 60 minutes exceeds the normal celiac disease.
The sensitivity and specificity of antitransglutaminase-IgA antibodies in the diagnosis of celiac disease are very high, above 95% when there is total hair loss (56), as was the case of celiac disease.
For this reason, it is justified to withdraw gluten-containing foods from the diet and observe the evolution of the patient.
The diagnosis of celiac disease would be reinforced if abdominal symptoms, transglutaminase antibody rates and histological lesions improved within a few days or weeks after complete withdrawal of gluten from the diet (51.57).
Histological normalization, however, usually requires more than a year or it is possible that never occurs (58.59), although the height of the epithelial cells of the stump of the first weeks of gluten withdrawal increases during the first weeks.
CT and magnetic resonance imaging can provide data of great diagnostic value, for example, ascites and lymphadenopathies (60-62).
The latter are found in 43% of the cases (63) and are highly suggestive of this disease when cavitated (28.29.64), although it is a rare finding in this disease, described in less than 50 occasions.
Histologically, when adenopathies are located, they are occupied by a chylous-chromous and surrounded by a peripheral ring composed of fibrosis and cavitated remnants (65).
Its finding allows us to recognize that the cause of adenopathies is not a lymphoma involving celiac disease.
The relationship between adenopathy and celiac disease is demonstrated when its number and size decreases when gluten is removed from the diet (62).
Therefore, I would like to know if gluten was removed from the diet in this patient and, in this case, what was the response.
Dr. Bailey.
C. Garfia.
With the data available, we also thought about celiac disease and, consequently, we removed from his diet foods containing gluten.
The evolution of the patient was complete disappearance of pain and digestive discomfort and a decrease in blood amylase and lipase rates, which had fallen to 266 IU/ IU, respectively, at 6 months.
A similar course followed antigliadin-IgA antibodies (21.8 IU/ml) and antitransglutaminase-IgA antibodies8.5 IU/ml).
Dr. Bailey.
Y. Sanchez.
The response of this patient to gluten deprivation supports that celiac disease, although after six months of gluten suppression, the rates of these antibodies should be even lower.
In general, when dietary gluten restriction is complete, these antibodies return to normal in blood within 3-6 months.
Therefore, it is very likely that the patient was not doing the diet correctly and would continue to take gluten-containing foods even if it was involuntary (forgotten or neglected diet) as happens in many patients (66
During dietary restriction, blood amylase and lipase levels decreased, suggesting that pancreatic disease was also related to celiac disease.
There are several studies reporting hypercholesterolemia and hyperlipasemia in celiac disease and their progressive improvement with diet (67).
In the case reported here, there was a decrease but no normalization of pancreatic enzymes in blood.
Incomplete regression of these changes could also be related to poor compliance with dietary restrictions; however, sometimes, despite the fact that the diet itself (6 or 2 years, normalization for a decrease can be very slow and requires up to one year).
These elevations in pancreatic enzymes could be justified by the existence of autoimmune pancreatitis associated with celiac disease.
Approximately 20% of celiac patients have some associated autoimmune disease (52.69), the most frequent are type I diabetes mellitus, hypothyroidism, lupus erythematosus and atrophic gastritis.
There are no clear criteria for the diagnosis of autoimmune pancreatitis, but it is common for the pancreatic ducts to have an irregular, narrow caliber and that the blood rates of IgG, especially IgG4, are very high (70.71).
The patient we discussed showed no significant changes in pancreatic ducts appreciable by magnetic resonance cholangiography and electrophoresis did not show a marked increase in IgG.
Although the diagnostic value of this last test has been questioned, other alterations that could justify pancreatic alterations have been found in celiac disease (69).
For example, macrophage anemia, with or without macrolipasemia (72-74), duodenal inflammation, papillary stenosis of Vater or low production of pancreozimine in these celiac disease could be responsible.76
Although gluten intolerance plays a decisive role in the development of intestinal lesions of celiac disease, there is undoubtedly a strong genetic predisposition (47.77).
In this sense, it has been found that 80-95% of celiac patients have HLA-DQ2 (α1*501, β1*02) and HLA-DQ8 (α18.7*037.501), respectively.
Therefore, I would like to know if this genetic study was performed in this patient.
Dr. Bailey.
C. Garfia.
The patient was found to be homozygous for HLA DQ2.
Dr. Bailey.
Y. Sanchez.
That is, this genetic study also supports the diagnosis of celiac disease.
Although HLA-DQ2 is quite common in the European population (25-30%) without celiac disease, it is known that when HLA DQ2 appears in both chromosomes, the risk of heterozygous disease is multiplied in the 579.
Although, as we have said before, in celiac disease we can find dietary adenopathies removed after the diet is rare and usually disappear with restriction, so we would like the evolution of gluten.
Dr. Bailey.
C. Garfia.
Six months after starting a gluten-free diet, a new CT scan was performed, which showed the persistence of the described adenopathies.
One of them was 1.7 x 0.9 cm and the other 1.9 x 1.2 cm that seemed to correspond more than single lymph nodes to clusters of other smaller adenopathies, but lymph nodes were still not visible in other areas.
Dr. Bailey.
Y. Sanchez.
This finding requires close monitoring of this patient, with periodic controls.
Dr. Bailey.
C. Garfia.
Indeed, although no evidence of other processes, mainly tuberculosis or lymphoma, was found in any of the diagnostic tests performed, given the persistence of adenopathies month, a diagnostic laparoscopy was performed with biopsy of the adenopathies.
Small adenopathies with nonspecific histological characteristics were observed.
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Final diagnosis
Adult celiac disease, acute pancreatitis and nonspecific mesodermal adenopathies.
