By Prof Dr: Fawzy Megahed 8-2-2015 65-year-old man with recurrent pancreatitis, rash, and diarrhea: Diagnostic dilemma By Prof Dr: Fawzy Megahed 8-2-2015

PRESENTATION The patient, a 65-year-old white man, endured several episodes of acute pancreatitis before presenting for this current admission.

On the night before discharge, after a 5-day hospitalization for his most recent occurrence, he developed diarrhea.

Testing for Clostridium difficile toxin was negative, and the diarrhea was attributed to a bowel regimen prescribed for constipation during his stay.

At home, the patient continued to have loose stools every few hours and cramping abdominal pain that was different from the discomfort provoked by pancreatitis.

Loperamide provided no relief.

After 5 days of profuse nonbloody diarrhea, joint pain, and dysphagia, he was readmitted. Upon questioning, he denied having any sick contacts.

Two years earlier, the patient underwent cholecystectomy during hospitalization for presumed gallstone pancreatitis.

At that time, abdominal computed tomography (CT) disclosed a small cystic lesion at the head of the pancreas, a finding that raised concerns for an intraductal papillary mucinous neoplasm.

The cyst could not be sampled with fine needle aspiration during endoscopic ultrasound. Further monitoring was recommended.

The patient suffered 2 more episodes of acute pancreatitis, requiring 2 more hospitalizations.

cholangiopancreatography (MRCP) during these admissions Magnetic resonance cholangiopancreatography (MRCP) during these admissions showed the same lesion.

Since he had already undergone cholecystectomy and did not drink alcohol, the cause of his recurrent pancreatitis was unclear.

Other possible etiologies, including medications, hypertriglyceridemia, hypercalcemia, and autoimmune pancreatitis, were ruled out.

Once again, it was feared that his cyst was a tumor obstructing the pancreatic duct, thus causing pancreatitis. He was referred to a surgeon for consultation on further work-up, including possible surgery.

The surgeon advised MRCP while the patient was asymptomatic The surgeon advised MRCP while the patient was asymptomatic. This indicated that the lesion had resolved and likely had represented a pseudocyst.

ASSESSMENT The patient was thin and exhausted on physical examination, but his vital signs were normal.

His oral mucosa was dry, and he had large, easily scrapeable, white exudates on the posterior pharynx.

He had a distended abdomen With diffuse tenderness that was most pronounced in the epigastrium. No rigidity or rebound tenderness was noted.

Tympanic bowel sounds were present Tympanic bowel sounds were present. Edema in his lower legs, present on his previous admission, was likely the result of the large amounts of fluids administered during that stay.

Laboratory testing identified leukocytosis, anemia, hypokalemia and hypoalbuminemia. Amylase and lipase levels were normal.

Stool testing was negative for occult blood but showed fecal leukocytes.

A stool culture showed normal flora.

Investigations for C. difficile, shiga toxin, Giardia species, Cryptosporidium species, Cyclospora cayetanensis, Cystoisospora belli, ova and parasites, and rotavirus were all negative.

Spot fecal fat testing demonstrated normal contents

Abdominal radiographs revealed air-fluid levels in the right mid-abdomen with no free air.

Abdominal CT disclosed 3 pancreatic pseudocysts with ascites and pleural effusion.

Culture of a sample retrieved with a throat swab grew Candida species, and the patient was treated with nystatin. An HIV test was negative.

The patient was given intravenous fluids and a regimen of ciprofloxacin and metronidazole.

Overnight, he developed tender erythematous nodules on the lateral left leg

Ciprofloxacin was stopped because it can cause cutaneous reactions.

Biopsies showed enzymatic fat necrosis consistent with panniculitis

Because diarrhea continued, a colonoscopy was performed.

This showed severe patchy colitis with erosions and clean-based ulcers in the left colon, cecum, and proximal ascending colon; rectal mucosa was normal.

Biopsy samples were taken from the affected areas

DIAGNOSIS

Because infection is the most likely cause of acute diarrhea, C Because infection is the most likely cause of acute diarrhea, C. difficile was a likely culprit in this patient. However, his negative workup for infectious causes and continued diarrhea despite empiric antibiotic therapy made us consider other etiologies.

Steatorrhea from pancreatic insufficiency was in the differential diagnosis, but the acute onset and the lack of a relationship between diarrhea and meals made this unlikely.

The finding of positive fecal leukocytes in the absence of infection suggested Crohn’s disease.

lesions were initially thought to be evidence of erythema In addition, his skin lesions were initially thought to be evidence of erythema nodosum, which is associated with the illness. However, biopsy proved them to be pancreatic panniculitis.

Nonetheless, colon biopsies demonstrated chronic colitis with areas of activity and noncontinuous ulceration consistent with Crohn’s disease

This idiopathic disorder can cause inflammation throughout the gastrointestinal tract. Characteristic symptoms are abdominal pain or diarrhea with or without blood.

The disease has a bimodal age distribution, with peaks at ages 20-30 years and at ages older than 60 years.

Aside from erythema nodosum, various other extraintestinal manifestations have been described, including arthritis.

Medications used to treat Crohn’s disease can make a patient vulnerable to pancreatitis, as can gallstones and Alcohol.

Pancreatitis without an obvious cause has been diagnosed in patients with Crohn’s disease, though an explanation for this relationship has yet to be identified.

The inflammatory process triggered in the walls of the gastrointestinal tract does not appear to be responsible, as only 3 patients have been found to have granulomas, pathognomonic for Crohn’s disease, in the pancreas.

Many people with both Crohn’s disease and pancreatitis have had duodenal disease. One proposed mechanism for this concurrence is that reflux of duodenal contents into the pancreatic duct activates zymogens.

with our patient, pancreatitis also exists without duodenal Then again, as with our patient, pancreatitis also exists without duodenal involvement.

Our patient’s case is unique in that the diagnosis of Crohn’s disease came after multiple bouts of pancreatitis, circumstances reported in only a few other cases.

Histologic findings suggested that our patient had subclinical Crohn’s disease for some time. Pancreatic panniculitis, a rare complication of pancreatitis, occurs in pancreatic cancer as well

Theoretically, release of pancreatic enzymes into the bloodstream spurs fat necrosis.

Yet normal serum pancreatic enzyme levels have been reported in some patients

Pancreatic panniculitis can be difficult to differentiate from erythema nodosum.

Distinguishing features of pancreatic panniculitis include the presence of lobular rather than septal panniculitis and extensive ghost cell change; ghost cells are not seen in erythema nodosum.

Moreover, dense neutrophilic infiltrate and extensive hemorrhage are not characteristic of erythema nodosum.

Management involves suppressing the body’s normal immune response

In patients with moderate to severe Crohn’s disease, steroids are often required to induce remission.

Then remission can be maintained with immunomodulators, although anti-tumor necrosis factor drugs can be used to induce and maintain remission.

Our patient was placed on methylprednisolone for 2 days Our patient was placed on methylprednisolone for 2 days. His symptoms improved, and he was transitioned to oral prednisone upon discharge.

Several weeks later, he started a mesalamine regimen and was tapered off steroid therapy. One year later, he remains symptom-free and is tolerating a normal diet.

Management of pancreatic panniculitis is generally supportive Management of pancreatic panniculitis is generally supportive. Nodules may ulcerate, but they tend to regress spontaneously.

Treatment of the causative etiology of pancreatitis, such as cholecystectomy for gallstone pancreatitis, can resolve the condition. Our patient’s lesions were almost gone by the time he was discharged.

Between 10-30% of recurrent acute pancreatitis is idiopathic Between 10-30% of recurrent acute pancreatitis is idiopathic. It is important to consider Crohn’s disease in patients with repeated bouts, particularly if clinical symptoms arise; our patient, for example, developed diarrhea.

Conversely, it is important to consider pancreatitis as a cause of abdominal pain in patients with Crohn’s disease.

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