Diarrhoea in an immunosuppressed patient

This patient was brought down from the haematology ward with diarrhoea.  The patient was immunosuppressed following a  donor bone marrow transplant for myeloma. 
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WHAT IS THE LIKELY DIAGNOSIS?
a) Graft versus host disease
b) An opportunistic infective colitis
c) Checkpoint inhibitor colitis

explanation

This is a case of acute Graft-versus-host disease (GVHD). Checkpoint inhibitor colitis gives a severe looking colitis whilst superficial ulceration is what should make you consider an opportunistic infective colitis.  In the case of GVHD, there is usually very little to see. 

I knew that GVHD was due to T cells from the stem-cell donor which attack tissues in the recipient. However, I hadn't realised that it's the main cause of death after a stem cell transplant!   This is bad news! 

The most common tissues affected by acute GVHD are the skin (widespread rash even appearing on the palms of the hands), liver (transaminitis) and the gastrointestinal tract.  The horrendous secretory diarrhoea, classically developing in the weeks following a stem cell transplantation, is the most severe complication and linked with the 40% mortality rate of acute GVHD. 

There are a few take-home messages for endoscopists. 

■ First, is that the mucosa may appear entirely normal but that samples nevertheless have to be taken as the diagnosis is clinical (of course) and histological (apoptosis of epithelial cells with loss of crypts). 

■Secondly, endoscopic appearances are variable ranging from oedema (as in my video) to small intramucosal haemorrhages to erosions and ulceration. 

There is something called the 'Freiburg Classification' which basically orders this into a 4-level scale:
1 Normal mucosa
2 Patchy erythema 
3 Aphthous ulcers and/or focal erosions
4 Confluent ulceration 

■ Thirdly, 10 biopsies from the distal colon have the greatest chance of yielding the diagnosis. I take 3-4 biopsies from the rectum and sigmoid and if possible also the descending colon.  

■ Fourth, because of the horrendous diarrhoea, there is no need to subject the poor patient to a phosphate enema before the flexible sigmoidoscopy. 

■ Fifth, these patients often have low platelet counts and deranged clotting. Personally, I place an 11mm clip on each biopsy site to avoid the need for platelet transfusions and the need to correct the INR. However, this is a personal preference and for example the ASGE recommend bringing the platelet count up to above >50 × 109/L before biopsy (>20 for an endoscopy without biopsies). 

■ Sixth, consider the possibility of superimposed infection, particularly if there is superficial ulceration as both CMV and HSV causes ulceration. Biopsies for viral cultures have to be placed in viral transport medium. Of course, the ward team should also have sent stool for viral PCR (adenovirus, astrovirus, rotavirus, noro-virus can all cause watery diarrhoea) as well as for bacterial pathogens such as C.diff and C. septicum as well as for parasites such as Giardia and Cryptosporidia

Recently, I've had five referrals for GVHD. All patients were on high dose steroids (eg. 80mg of prednisolone) and in none of them did it seem to make any difference to their symptoms!  All of the patients felt awful with abdominal pain, profuse diarrhoea and swollen limbs (from hypoalbuminaemia).  Sadly, 2 out of 5 died within weeks of their flexible sigmoidoscopy.