Introduction

Various regimens are available to treat severe skin graft versus host disease (GVHD) with more novel therapy available such as extracorporeal photophoresis (ECP) and mesenchymal stem cell infusions (MSC) in recent years.  We report our experience in the management of skin GVHD in intestinal transplant patients.

Materials and Methods

Retrospective study by review of clinical casenotes and electronic data base of intestinal transplant recipients with skin GVHD from 1993 to 2016.

Results

12/94  patients had skin GVHD  from 1993 to 2016; age range 10mths to 9yrs.  Data from 11 of these patients were obtained; underlying diagnosis were NEC (n=3),  Megacystis microcolon-intestinal  hypoperistalsis syndrome (MMIH; n=3), Gastroschisis (n=2), Microvillus inclusion disease (n=2) and  malrotation & volvulus (n=1).  Five had combined liver and small bowel, 3 isolated small bowel, 2 multivisceral and 1 modified multivisceral transplants. 

Mean time from transplant skin GVHD onset was 3mths (mode 4mths); seven had Grade 4, two Grade 3 and two Grade 1 skin GVHD.  5 patients had mucositis, 4 ocular GVHD, 4 haemolytic anaemia (bone marrow GVHD), 1 liver GVHD and one had neurological involvement (immune mediated Myasthenia gravis). 

Chimerism studies 4mths post-transplant for our cohort showed mostly CD3+ donor cell mixed chimerism (range 6-67%, mode 17%) with an almost absent donor B cell lineage (range 0-41%, mode 0).  This was the trend throughout, particularly for Grade 3-4 skin GVHD.

8 patients had intravenous steroids at diagnosis; 4 had combination Infliximab and Basiliximab therapy, 1 had Infliximab alone, 2 Dacluzimab, 2 Campath, 1 Methotrexate, 5 ECPand 7 MSC.  ECP and MSC became available at our centre from 2010; average time of referral for these were 1month from 2014 onwards as compared to 7mths from 2010 to 2013.

Although 4 patients initially had resolution of their skin GVHD and 5 had chronic skin GVHD, four patients (all Grade 4 GVHD) eventually died as a result of their skin GVHD

Discussion

Skin was the primary organ with GVHD in our cohort of patients.  Mixed chimersm studies from them showed higher than expected CD3+ activated donor cells at 4mths and thereafter.  This may reflect a correlation persistence of disease activity in GVHD.

Our initial experience of steroid refractory skin GVHD were with a combination of interleukin 2 receptor antagonists (Basiliximab and Daclulizimab) and TNFα (Infliximab) which were ineffective.  Second line therapy with ECP and MSC had more success with clinical improvements, particularly when patients were referred earlier as seen from 2014 onwards. 

Conclusion

Skin GHVD in intestinal transplant population can progress rapidly, is associated with high mortality and should be treated aggressively. ECP and MSC should form second line treatment options in children with steroid refractory GVHD.