Graft vs Host Disease Flashcards
What is graft vs host disease?
A multiorgan disease due to foreign haematopoeitc stem cell transplants
What are the clinical features of ACUTE GVHD?
Occurs 4 - 6 weeks post HSCT
80% have skin involvement:
- morbilliform eruption
- prediliction for acral areas
- +/- pruritis
- +/- bullae
- +/- folliculotropic
- +/- purpura (in the context of thrombocytopaenia)
GIT - nausea / vomiting / diarrhoea
Liver - cholestasis > transaminitis
Features of Chronic GVHD
40% have skin invovlement
- many different phenotypes!
- Lichen planus like
- Morphea like
- Lichen sclerosus like
- Fascitits
- Pokiloderma
- Psorisiform
- KP like
- SLE like
- vitiligo
- calcinosis cutis
- alopecia
- premature graying
- joint contractures
- patterent hyperpigmentation
- nail ridging, thinning, brittleness, onycholysis
- ulcers
- xerostomia
What is the pathogenesis of acute GVHD?
Activation of host antigen presenting cells
–> donor T cells proliferate in response to these
–> destruction of target tissues (skin, gut, liver) via cytotoxic T cells, NK cells and cytokines
What is the pathogenesis of chronic GVHD?
Not well understood
Thought to be alloreactive T cells +/- B cells
what are the major RFs for GVHD?
Most important is HLA compatibility between the host and the donor
True or False
40% of HLA identical host and donors develop GVHD, verus 70% in they are HLA mismatched.
True
What is the histology of acute GVHD?
Lichenoid reaction pattern
Keratinocyte necrosis
Basal layer vaculolation
Lymphocytic infiltrates
Microvesicles and subepidermal bullae
What are the histological features of chronic GVHD?
Very variable - also lichenoid inflammation often with sclerosis
How is GVHD staged?
Skin staging:
* < 25% BSA = grade 1
* 25 - 50% BSA = grade 2
* >50% BSA = grade 3
* generalised or bullae formation = grade 4
What is the DDx for GVHD?
Acute:
- engraftement syndrome
- viral illness
- drug eruption
Chronic:
- broad… depends on the phenotype
What is the treatment for GVHD?
General measures
- moisturise
- avoid irritants
- SUN PROTECTION
Skin directed therapies:
- topical CS
- topical calcinurin inhibitors
Systemic agents: (directed by haem)
- oral CS
- Systemic immunosupressants: Ruxilitinib (JAK), MMF, AZA, Calcinurin inhibiotr
What is the incidence of GVHD?
25 - 80%
Rook
What are the risk factor for GVHD?
HLA mistmatch
Unrelated donor
Gender mismatch (esp multiparous female donor to a male recpipient)
Type of transplant (peripheral stem cells are at higher risk than BM which are higher risk than cord blood
Older age (>40)
The pre-conditioning regimen (total body irradiation)
Lack of post transplant conditioning wiht cyclophosphamide
CMV / EBV mismatch
Histology of aGVHD
Lichenoid reaction pattern
Linerar arrangement of lymphocytes along the basement membrane zone
Satelite cell necrosis consisting of apoptotic keratinocytes with tightly asssociated lymphocytes
Interface vaculoar change
Hist difference for aGVHD and durg reaction
Can be indistinguishable from lichenoid drug eruption
In early stages - scattered eosinophils are found in both
If there are a high number of eosinophils (16 per 10 high power feilds - this favours durg)
non- lichenoid pattern - favours drug
What are the histological grades of aGVHD?
1: Basal cell vacuolation with or without mononuclear cell infiltration
2: Solitary epidermal cell necrosis, surrounded by mononuclear cells
3: Regional epidermal cell necorsis with bullae
4: complete dermal and epidermal seperation
Histological changes of cGVHD?
Depend on the type of skin involvement
Lichenoid cGVHD:
- hyperkeratosis, hypergranulosis, acanthosis, saw tooth rete ridges, interface dermatitis and dyskeratotic keratinocytes.
- Periadnexal, perieccrine inflammation may be evident
Sclerotic lesions of GVHD:
- atrophy
- oedema
- homogenisation of collagen in the superficial dermis
Morpheform:
- thickend dermal collagen fibre bundles
- loss of adnexal structures
- no epidermal change
What histo changes are evident?
Atrophy of the epidermis
Homogenisaiton of dermal collagen
Some oedema
Typical time frame of aGVHD?
2 - 4 weeks post transplant (rook), 4 -6 weeks (bolognia)
What are the cutaneous features of aGVHD?
Red blanching macules
- palms, soles or ears
- can appear photoagravated - affects neck, upper back and face
THen becomes more confluent with a morbilliofrm appearance
More severe cases
- Erythroderma
- Bullae
- nikolsky positive epidermal skin loss
Oral
- xerostomia
- redness
- ulceration
Pruritis ++
Rook
Complications of aGVHD
Weight Loss
Dehyrdration
Electorlyte disturbance
Secondary infection
Thermodysregulation, Electorlyte disturbance (and all other complications of erythroderma)
Rook
DDx for aGVHD?
Cutanoues durg reaction
- morbilliform
- lichenoid
- SJS / TEN
Chemotherapy induced mucosisit
Engraftment syndrome
Viral illness
Rook
Prognosis of aGVHD?
Mortalitiy depends of grade:
1: 27%
2: 43%
3: 68%
4: 92%
Investigations for aGVHD?
4 mm skin biopsy of lesional skin
- for histology
- for DIF (to exclude ddx)
FBC
UEC
LFTs
Blood cultures + Septic screen if fevers / unwell
aGVHD management
Topical
- Emolliants
- TCS
- topical calcinurin inhibiotrs
Adjuncts
- antihistamines
Systemic:
- optimisation of prophylactic GVHD therapy (guided by haematology)
- for grade 2 - 4: oral corticosteroids or IV methyl prednisolone
Steroid refractory (no response in 7 days)
- ECP
- MMF
- mTOR inhibitors
- anti IL -22
What are the cutaneous featuers of cGVHD?
Mucous membranes:
- Oral: Xerostomia, ulceration, Wickam striae, dental caries
- genital: LS, ulceration, dryness, itch, stenosis, fusion
- Ocular: dryness, keratoconjunctiva sicca
Pruritis
Xerosis
Skin tightening / thickening
LP like
SLE like
Morphea like
Sceledermoid like
Dyspigmentation and vitiligo
Pokilodermatous
Esosinic fascitis like
ecxematous
papulosquamous
PRP like
Nail:
- dystrohpy
- pterygium
- anonychia
Hair:
- alopecia (scarring or non-scarring)
What are the key extracutanoues features of GVHD?
Liver
GIT
Lung
MSK
Neuro
Chronic GVHD Managment
Treatment ladder, progress through the ladder for more sever disease
Emolliants / lubricants
TCS
UVA1 / PUVA
Oral corticosteroids - 1mg/kg/day
Ciclosporin
Ruxolitinib
Imatinib
