AIDS TREATMENT UPDATE, Issue 28 - April 1995
David Campbell-Morrison

Diseases of the pancreas or gall bladder can give rise to pancreatitis. This is a syndrome in which the pancreas becomes inflamed and the digestive enzymes leak into the abdominal cavity. There, the enzymes can start to cause severe inflammation and damage to the surrounding es can be perfectly harmless, but the condition becomes a cause for concern if the levels rise beyond a certain point. At the other end of the spectrum, there have been a number of deaths caused directly by ddI-related pancreatitis.

The risk of developing pancreatitis from ddI seems to be related to three factors. Individuals are at increased risk if:

- they have other risk factors for pancreatitis apart from taking ddI - they have a CD4 count below 50 - they are taking higher doses of ddI. The Alpha trial found no difference in efficacy between doses of 200 mg/day and 750 mg/day, but 4.5% of people taking the higher dose developed pancreatitis, compared with only 0.6% of the lower dose group.

The risk of developing ddI-related pancreatitis is increased in people who are also receiving intravenous or oral ganciclovir as treatment or maintenance therapy for CMV.

Symptoms and diagnosis

The physical symptoms of pancreatitis include nausea, vomiting and sometimes pain (which can be very severe) in the epigastric region below where the ribs join in the centre of the chest. The abdomen may be very tender and painful to the touch.

Tests which are used to confirm the diagnosis blood tests which detect the presence of pancreatic enzymes in the blood, and X-rays or ultrasound or CT scans to see if there is an enlargement of the pancreas and gall bladder.

In cases of chronic pancreatitis where further tests are needed to identify physical damage to the pancreas, a procedure called ERCP may be used. A fibreoptic endoscope is passed into the intestine through the mouth and then hooked into the bile duct so that the changes in the pancreas and gall bladder can be seen. This procedure needs a highly skilled operator and carries some risk of damaging the pancreas and of introducing infections. In the course of ERCP, it is also possible to take samples of tissue to examine in the laboratory to check for infections or cancer.

Treatment

There are two aspects to the treatment of pancreatitis:

- minimising the disruption caused by the failure of the pancreas to work properly - minimising the damage caused by the release of pancreatic enzymes into areas where they are not normally found.

One complication of pancreatitis is that the released enzymes can damage the cells that produce insulin; this effectively makes the individual temporarily diabetic and causes swings in glucose levels in the blood which in themselves can cause coma and death. The person with pancreatitis may also become dehydrated because of vomiting and the leaking of fluids out of body tissues. This may have to be corrected by giving fluid intravenously, since often nothing can be given by mouth.

Enzyme inhibitors such as aprotinin may be given to stop the released enzymes eating the pancreatic gland and surrounding tissue, but their value is debatable.

Pain control

The pain caused by pancreatitis may be severe and is difficult to relieve. Some commonly used painkillers such as morphine, codeine and the opiates are not recommended as they may actually worsen the problem. Pethidine is a safe alternative. A pain control regime may include anti-inflammatory drugs such as naproxen or aspirin in high dose. In cases of severe pain a technique which destroys the nerves to the pancreas may be useful.

It may be helpful for people with chronic relapsing/recurrent pancreatitis to be in regular contact with their GP so that adequate pain relief can be given quickly during an attack. Casualty departments which may not have access to medical notes can be wary of people demanding strong painkillers, labelling them as addicts working the system, and may only give them minimal pain relief.

Chronic pancreatitis

In some people, the initial attack of pancreatitis may cause physical damage to the pancreas that results in long-term problems and relapses. This is called chronic pancreatitis, and is a problem that is not confined to people with HIV. At present, medical treatment is limited to treating the symptoms. However, there are lifestyle changes that may help to reduce the number and severity of recurrences.

Ideally, all alcoholic drinks should be avoided. Any drugs which cause pancreatitis should be avoided. In chronic pancreatitis the reduction in pancreatic enzymes can cause difficulties with digesting food, especially fat. Doctors may prescribe digestive enzyme supplements, such as Creon, which may help. Dr Mick Connolly, a gastroenterologist at the Chelsea and Westminster Hospital, told AIDS Treatment Update that these supplements also seem to be effective in reducing pain. In severe cases where there is extensive damage to the pancreas, it may help to reduce dietary fat as meals rich in fat may cause an attack.

As certain opportunistic infections can cause pancreatitis, it is worth having thorough and exhaustive tests for any that are present so that they can be treated and prophylaxis taken afterwards to prevent recurrence.

Rarely, surgery may also be undertaken in cases of chronic pancreatitis. It is usually limited to cases when there are readily identifiable physical problems that can be corrected.

Doctors at Manchester Royal Infirmary have been studying the use of anti-oxidant vitamins to treat pancreatitis. In 1991 they reported the results of a small, 28-person placebo-controlled trial which concluded that sufferers of recurrent pancreatitis who took high doses of anti-oxidants were less likely to suffer a relapse. The level of discomfort and pain they suffered was also reduced when compared with a group receiving a placebo. Six participants had an attack whilst on placebo, compared with only one recipient of anti-oxidants. Most of the participants in this trial had pancreatitis caused by heavy use of alcohol.

Past studies at the hospital suggested that the optimum daily doses were 600 g of selenium, 9000 international units (i.u.) of beta carotene, 540 mg of vitamin C and 270 i.u.of vitamin E - combined in a single tablet which is marketed as Selenium CE - plus 2 g of methionine (an amino acid that is an active component of garlic). After six months on this regime, the dose could be cut in half with no recurrence of symptoms.

"It never seemed to go away"

At its worst, recurrent pancreatitis can make life a misery. Here, a reader recounts his experience:

In 1992 my clinic started offering ddI on an open-label basis to people they thought might benefit from it. Because it was still experimental I had to sign some kind of disclaimer. The ddI came in the form of vile-tasting sachets that you took twice a day.

I had only been on it for 2 months when one day I started throwing up violently. At first I thought it was just indigestion and I went to bed, but it didn't seem to get any better. What happened next is a bit of a blank because I was in so much pain, but I remember coming to in a hospital bed and lots of people round me looking very concerned. I was on heavy painkillers and a main-line giving me intravenous fluids because of the dehydration. They told my partner it was very serious and I might die. I was taken off ddI immediately.

I was hospitalised for about 2 weeks and spent the next 6 weeks recovering at home, eating only liquidised food and baby food. Then just a couple of weeks later the pancreatitis was back, and then two months later I had another milder attack. You can't eat or drink anything because you vomit it up, and when everything's been vomited up you start to puke up this vile brown liquid. I had a tube up my nose into my stomach draining off the bile. In all I had two major attacks of pancreatitis and seven hospitalisations during one year.

Then it seemed to go away for a while. I didn't have an attack for a year. They said this was the typical healing process. But then I did have another attack, although not as bad. I got a second opinion and they said that I still had acute pancreatitis - there was none of the scar tissue that you see when it's healed and turned into chronic pancreatitis.

I consulted all kinds of people but it never seemed to go away. The general view seems to be that once you've got pancreatitis you've just got to suffer with it. Even prominent gastroenterologists and HIV experts said that there was very little they could do about it. I was given Creon to give my pancreas a rest but it had no effect on the symptoms at all.

I kept having these dreadful attacks, having to go into hospital or day-care and take painkillers. One time I remember lying on the floor in Casualty screaming 'Get me pethidine!'. I kept trying to get some idea about whether I could do anything to help, like giving up fatty foods, but the doctors and dieticians couldn't make any suggestion except to avoid alcohol, and I don't drink anyway. I went through all the drugs I take, eliminating the ones that could cause pancreatitis. I was so depressed by it at one point that I asked for Prozac but they couldn't give it to me because pancreatitis is on its huge list of possible side-effects.

Eventually a friend of mine put me onto Manchester Royal Infirmary where they had been testing quite high doses of antioxidants. It does seem to have worked for me - I haven't had the severe attacks since.

9504
ATU2803

Copyright © 1995 - AIDS Treatment Update. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. NAM Publications 16a Clapham Common Southside, London, England SW4 7AB; TEL: 01-71-627-3200 (from outside the UK: +44-171-627-3200); FAX: 01-71-627-3101 (from outside the UK: +44=171-627-3101)  info@nam.org.uk  http://www.nam.org.uk