This document provides information about graft-versus-host disease (GVHD), including its classification, pathophysiology, clinical features, histopathology, differential diagnosis, and management. GVHD is a complication of allogeneic hematopoietic stem cell transplantation where donor T cells attack the recipient's organs. It can be acute (occurring within 100 days of transplant) or chronic (after 100 days). The main organs affected are the skin, liver, and gastrointestinal tract. Risk factors include HLA mismatch and donor/recipient gender combinations. Management involves immunosuppression with corticosteroids, calcineurin inhibitors, or other agents depending on the severity.

1. GRAFT VS HOST DISEASE
PRESENTER - DR. VIKAS PURUSHOTTAM
MODERATOR – DR. RAM SINGH MEENA SIR

2. CONTENTS
• Introduction
• Classification
• Pathophysiology
• Clinical features
• Histopathology
• Differential diagnosis
• Management

3. INTRODUCTION
• Graft‐versus‐host disease (GvHD) is a multiorgan disease process
• Results from the action of donor‐derived immunocompetent T lymphocytes
against antigens expressed on the cells of the immunocompromised recipient
host.
• GvHD is a major complication of allogeneic haematopoietic stem
cell transplantation, with an incidence of 25–80%

4. • PRIMARY DISORDERS TREATED WITH ALLOGENIC
HEMATOPOIETIC STEM CELL TRANSPLANTATION
• Leukemia
• Lymphoma
• Bone marrow failure
• Immunodeficiencies
• Myeloproliferative disorders
• Hematologic disorders
• Metabolic disorders
• Autoimmune diseases

5. MAIN ORGANS AFFECTED ARE –
1. Skin (1st and m/c)
2. Liver
3. Git tract
RISK FACTORS-
1. HLA incompatibility
2. Patient age (elderly > adult > pediatric)
3. Female donor (especially miltiparous) / male recipient
4. Stem cell source (peripheral blood>bone marrow>cord blood)
5. T cell replete graft
6. Unrelated donor
7. Donor leukocyte infusion

6. GvHD
Acute
≤ 100 days
post - HSCT
Classic
Acute GvHD
> 100 Days
post HSCT
Persistent Recurrent Delayed
Chronic
Overlap
syndrome
Classic
Chronic GvHD

7. HSCT conditioning by
chemotherapy or radiotherapy
causes tissue damage
in the host
release of numerous
inflammatory cytokines
cytokine storm
TISSUE INJURY PHASE
Activation of host antigen
presenting cells ( APCs)
Donor T cells proliferate
In response to contact with
activated APCs
Alloreactive T cells expand to
form cytotoxic effector T cells
release more inflammatory
cytokines
Tissue injury –skin , liver , GIT
DONOR T CELL PRIMING
PHASE EFFECTOR PHASE

8. ACUTE GvHD- clinical features
• Most commonly occur 4-6 weeks post
HSCT
• Pruritis or burning sensation precede the
skin lesions
• Erythematous blanching macules
develop on the palms, soles or ears.
• Photo aggravated in distribution
affecting neck ,upper back and face or it
may be folliculocentric

9. • Lesions become more confluent with a
morbilliform appearance.
• In severe cases, there may be
generalized erythroderma , bullae
• Extensive Nikolsky sign positive
• Epidermal skin loss with a TEN like
picture .

10. GASTROINTESTINAL
• Abdominal pain
• Anorexia
• Ileus
• Vomiting
• Secretory diarrhoea
LIVER
pale urine , dark coloured stools, upper quadrant tenderness
• Pericholangitis
• Cholestatic hyperbilirubinemia
• Endothelithiasis

11. ACUTE GvHD staging
STAGE SKIN RASH GIT - DIARRHEA( ml/day ) LIVER - BILIRUBIN mg/dl
1 < 25% BSA ≥ 500 or persistent anorexia,
nausea, vomiting
2- 3
2 25%- 50 % BSA ≥ 1000 3-6
3 > 50 % BSA ≥ 1500 6- 15
4 Generalised Erythroderma with bulla
or desquamation
≥ 2000 or severe abdominal
pain with or without ileus
≥15
GRADE SKIN RASH GIT LIVER
I Stage 1-2 None None
II Stage 1-3 Stage 1 Stage 1
III Stage 2-3 Stage 2-3 Stage 2-3
IV Stage1- 4 stage 2-4 Stage 4-4
GLUCKSBERG SCORE AND GRADING FOR ACTE GvHD

13. • Hallmark change,
although not
pathognomonic, is
satellite cell necrosis
consisting of apoptotic
keratinocytes with
tightly associated
lymphocytes seen in
the epidermis and
associated interface
vacuolar change.

14. HISTOLOGICAL
SEVERITY
DESCRIPTION
Grade I Basal cell vacuolation with or
without mononuclear cell
infiltration
Grade II Solitary epidermal cell necrosis
surrounded by mononuclear cells
Grade III Regional epidermal cell necrosis
with bulla
Grade IV Complete dermal and epidermal
separation

15. DIFFERENTIAL DIAGNOSIS
• Drug eruption
• Eruption of lymphocyte recovery
• Rash of engraftment syndrome
• Transient acantholytic dermatosis
• Toxic epidermal necrolysis (for stage IV disease)
• Toxic erythema of chemotherapy
• Viral exanthem

16. MANAGEMENT
• Skin sloughing –skin care, Rx infection, fluid management
• Prophylactic use of cyclosporine, methotrexate and prednisolone (combination of these
agents) has reduced the incidence of acute GvHD
• Grade1 skin involvement(without hepatic and GI symptoms) – high potency topical steroids
and emollients
• Topical tacrolimus in refractory cases
• More severe skin involvement with internal organ involvement – systemic corticosteroids
• Grade2 – oral prednisolone 1mg/kg
• Grade 3-4 – iv methylprednisolone 2mg/kg

17. SYSTEMIC TREATMENT FOR ACUTE CUTANEOUS GVHD
FIRST LINE
• Corticosteroids (IV methylprednisolone 2mg/kg/day)
• Tacrolimus (usually on prophylactic treatment)
• Cyclosporine (usually on prophylactic treatment)
SECOND LINE
• Mycophenolate mofetil (2 – 3 g/day)
• Etanercept(0.4mg/kg upto max of 25mg per dose s.c twice a week)
• Infliximab(10mg/kg iv once a week)
• Pentostatin (1.5 mg/m2 /d for 3 days)

18. OTHER SALVAGE THERAPY
• Extracorporeal photopheresis
• Mesenchymal stem cell therapy
• Alemtuzumab
• PUVA
• Narrowband UVB
FUTURE TREATMENTS/TRIALS
• Anti-thymocyte globulin (if not given during preconditioning)
• T‐regulatory adoptive immunotherapy strategies

19. PATHOGENESIS OF CHRONIC GvHD
• TWO THEORIES-
• 1.autoimmune model-
• decrease immune tolerance - allow activation and proliferation of
donor T cells directly at self antigen shared between host and
donor
• 2. chronic donor t cell activation – and role of B cells

20. CHRONIC GvHD
• CUTANEOUS FEATURES-
1. Sclerotic –
• sclerodermoid , deep sclerosis/ eosinophilic fascitis like
• Lichen sclerosus like
• Morphoeoform
2. Lichenoid
3. Epidermal – eczematoid, papulosquamous , prp like

21. erythematous–violaceous lichenoid papules &plaques
manifest in early disease, predominantly over the
dorsal aspects of the hands, forearms and trunk,
LICHEN PLANUS LIKE LICHEN SCLEROSUS LIKE
Shiny wrinkled porcelain white atrophic plaques
m/c seen over upper back

22. Localised or generalised areas of sclerosis
MORPHE LIKE
Diffuse dermal involvement may result in ‘pipe- stem’
appearance of extremities with
Marked reduction in limb volume
Overlying shiny hidebound skin
Loss of hair

23. EOSINOPHILIC FASCIITIS-LIKE
Rippled appearance & irregular ,nodular
texture indicative of involvement of
subcutaneous tissue
SCLERODERMA LIKE POIKILODERMATOUS LIKE

24. • Fibrosis of subcutaneous fat
with cellulite-like appearance
Groove’s sign is the result of
increased fibrosis around tendons

25. OTHER ATYPICAL MANIFESTATIONS
• Psoriasiform
• Eczematous/dyshidrotic
• Keratotic follicular papules
• Pityriasis rosea-like lesions
• Erythema multiforme- like lesions
• SCLE like eruption
• Psoriasiform like
• Vitiligo like

26. ORAL CAVITY
• Lichen planus like
• Mucocele
• Erythema
• Gingivitis
• Hyperkeratotic plaques
• Mucosal atrophy
• Restriction of oral opening
from sclerosis
• Ulcer
• Xerostomia

27. NAIL
• Longitudnal ridging or
splitting
• Brittleness
• Partial or complete
anonychia
• Onycholysis
• pterygium
HAIR
• Scarring alopecia
• Loss of body hair
GENITAL MUCOSA
• Lichen planus-like features
• Lichen sclerosis-like
features
• Vaginal scarring or
clitoral/labial agglutination
(female)
• Phimosis or
urethral/meatus scarring
or stenosis (male)

28. occular
Keratoconjunctivitis sicca
Blepharitis
Photophobia
Cicatricial conjunctivitis
GIT
Esophageal web -Strictures or stenosis in the upper to mid third of the
esophagus
Pancreas- exocrine insufficiency
HEART
Cardiac effusion
Cardiomyopathy
Conduction defect

29. • RESPIRATORY SYSTEM
• Bronchiolitis obliterans diagnosed with lung biopsy
• Air trapping and+ bronchiectasis on chest CT
• Pleural effusion
• MUSCULOSKELETON
• Arthralgia,Arthritis ,Edema , Myalgia
• Myositis /polymyositis
• OTHERS
▫ Peripheral neuropathy , nephrotic syndrome
▫ Thrombocytopenia ,Eosinophilia ,Hypo/hypergammaglobinemia
,Lymphopenia
▫ Elevated transaminases ,Elevated total bilirubin ,Elevated ALP

30. COMPLICATIONS
• Skin erosions and ulceration due to chronic GVHD - Secondary infection
• Sclerotic changes – functional disability and joint contracture
• HCT survivors are at increased risk for melanoma and nonmelanoma skin cancers
due to previous exposure to ionizing radiation, immunosuppressive treatment

31. DIFFERENTIAL DIAGNOSIS
EPIDERMAL INVOLVEMENT
• Drug eruption
• Demodex folliculitis
• Eczematous drug eruption
• Lichen planus
• Pityriasis lichenoides chronica
• Pityrosporum folliculitis
• Psoriasis
SCLEROTIC INVOLVEMENT
• Eosinophilic fasciitis
• Lichen sclerosus
• Morphea
• Nephrogenic systemic brosis
• Radiation dermatitis
• Systemic sclerosis

32. CHRONIC GVHD-MANAGEMENT
• Nonsclerotic lichen planus like and other papulosquamous chronic GVHD
features – topical steroids
• Topical emollients
• Topical pimercrolimus 0.1%
• Treatment with prednisolone and azathioprine for atleast 9-12 months –
generalized chronic GVHD

33. First line
• Corticosteroids, e.g. prednisolone 1
mg/kg oral or IV
• Oral calcineurin inhibitors – ciclosporin as
a steroid sparing
Second line
• Extracorporeal photopheresis
• Imatinib
• Sirolimus
• Pentostatin
• Rituximab
Third line
• Mycophenolate mofetil
• Pulsed high‐dose corticosteroids
• Methotrexate
Others
• Hydroxychloroquine, clofazemine,
cyclophosphamide,
alemtuzumab, anti‐TNF antibodies,
thalidomide, alefacept, retinoids,
azathioprine, mesenchymal stem cells

34. THANK YOU