Skin nontumor

Lichenoid and interface reaction patterns

Graft versus host disease

Editor-in-Chief: Debra L. Zynger, M.D.
Omar P. Sangueza, M.D.

Last author update: 23 April 2019
Last staff update: 30 June 2023 (update in progress)

Copyright: 2002-2023,, Inc.

PubMed Search: Graft versus host disease skin pathology

Omar P. Sangueza, M.D.
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Cite this page: Aljarbou O, Sangueza OP. Graft versus host disease. website. Accessed September 27th, 2023.
Definition / general
Essential features
  • GVHD most commonly occurs after allogeneic hematopoietic stem cell transplantation
  • Dyskeratotic keratinocytes involving the adnexal epithelium can differentiate between GVHD and drug eruption in difficult cases
    • GVHD and drug reactions cannot always be distinguished on histologic grounds; therefore, strong clinical correlation is essential in all cases
  • GVHD: graft versus host disease
  • GVH: graft versus host reaction or disease
ICD coding
  • ICD-10:
    • D89.81 - graft versus host disease
    • D89.810 - acute graft versus host disease
    • D89.811 - chronic graft versus host disease
    • D89.812 - acute on chronic graft versus host disease
    • D89.813 - graft versus host disease, unspecified
  • 3 phases of acute GVHD (Biol Blood Marrow Transplant 1999;5:347):
    • Phase 1: damage to host tissues by inflammation from the preparative chemo or radiotherapy regimen
    • Phase 2: recipient and donor antigen presenting cells as well as inflammatory cytokines triggering the activation of donor derived T cells, which expand and differentiate into effector cells
    • Phase 3: activated donor T cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions, perforin-granzyme B and the additional production of cytokines, such as TNFα
      • TNFα is produced mainly by monocytes and macrophages and secondarily by T lymphocytes and natural killer cells
Clinical features
  • Revised National Institute of Health (NIH) criteria now define classic acute GVHD as occurring within 100 days following hematopoietic stem cell transplantation (Br J Haematol 2012;158:30)
  • Late onset acute GVHD occurs after 100 days and affects mainly the skin, gastrointestinal tract and liver (Br J Haematol 2012;158:30)
  • Chronic GVHD occurs 100 days after hematopoietic stem cell transplantation, representing 50% of all cases and causing late mortality in up to 25% of patients (An Bras Dermatol 2016;91:336)
  • Clinical manifestations of GVHD after hematopoietic stem cell transplantation include fever, cutaneous rash, severe gastrointestinal manifestations and impaired liver function (An Bras Dermatol 2016;91:336)
  • Cutaneous GVHD manifests as erythematous maculopapular rash that can begin anywhere in the body but often starts with palm and sole involvement (An Bras Dermatol 2016;91:336)
  • Early lesions are usually centered on a hair follicle, a clue for diagnosis (Arch Dermatol 1988;124:688)
  • If the rash is severe, vesicles, bullae and erythroderma can develop; generalized desquamation also emerges (Adv Dermatol 2001;17:115)
  • Lichenoid chronic GVHD patients present with violaceous or erythematous papules and plaques, including a fine scale on top that can coalesce (An Bras Dermatol 2016;91:336)
Prognostic factors
Case reports
  • Glucocorticoids in combination with other agents such as antithymocyte globulin, tacrolimus or monoclonal antibodies (Semin Hematol 2006;43:32)
  • Topical immunosuppressive therapies for chronic GVHD are linked to less toxicity compared with systemic treatment (An Bras Dermatol 2016;91:336)
  • Topical calcineurin inhibitors are of special interest on anatomical sites such as the face or intertriginous areas where potent topical steroids should be used with caution (Br J Dermatol 2011;165:18)
  • Psoralens plus ultraviolet A light (PUVA) or narrow band ultraviolet B phototherapy are the treatment choices for sclerotic chronic GVHD lesions (An Bras Dermatol 2016;91:336)
Clinical images

Images hosted on other servers:

Plaques and papules

Maculopapular rash

Skin rash

Microscopic (histologic) description
  • Vacuolar degeneration of the basal cell layer, dyskeratotic keratinocytes and mild, mononuclear, superficial, perivascular infiltrate (An Bras Dermatol 2016;91:336)
  • Epithelial damage occurs, initially at the tips of rete ridges and hair follicles (An Bras Dermatol 2016;91:336)
  • These damaged cells are often accompanied by 2 or more lymphocytes, producing the picture known as satellite cell necrosis (lymphocyte associated apoptosis) (J Am Acad Dermatol 1996;35:187)
  • Chronic GVHD has 2 stages: lichenoid and sclerodermatous
  • Infiltrate in GVHD developing after solid organ transplantation is usually brisk in comparison to the more sparse inflammation following bone marrow transplantation (J Cutan Pathol 2004;31:179)
  • Psoriasiform GVHD is similar to psoriasis; in addition, there is vacuolar interface dermatitis with keratinocyte necrosis within epidermis and adnexal epithelia and lymphocyte satellitosis (Am J Dermatopathol 2018;40:511)
Microscopic (histologic) images

Contributed by Ohoud Aljarbou, M.D.

Acute GVHD with sparse inflammation and abundant dyskeratotic keratinocytes

Dense perivascular and interstitial eosinophilic infiltrate

Acute GVHD with vacuolar interface reaction and abundant dyskeratotic keratinocytes

Focal formation of subepidermal blister

Psoriasiform GVHD with regular acanthosis and parakeratosis

Immunohistochemistry & special stains
  • Not applicable
Sample pathology report
  • Skin, biopsy:
    • Interface dermatitis (see comment)
    • Comment: In the context of the clinical history, the morphologic findings are compatible with graft versus host disease (add differential diagnoses if applicable).
Differential diagnosis
  • The most important distinguishing feature between GVHD and the diagnoses below is the clinical history of bone marrow or solid organ transplant
  • Drug eruption:
  • Lupus erythematosus:
    • Vacuolar interface reaction, superficial and deep perivascular and periadnexal inflammation
  • Dermatomyositis:
    • Vacuolar interface reaction, mild superficial perivascular inflammation and abundant dermal mucin deposition
  • Psoriasis vulgaris:
    • Lacks vacuolar interface inflammation and satellite cell keratinocyte necrosis within the epidermis and adnexal epithelia
    • The presence of these features in addition to the classic findings of psoriasis could suggest the possibility of psoriasiform GVHD (Am J Dermatopathol 2018;40:511)
  • Lichen planus:
    • Denser infiltrate
  • Morphea or scleroderma:
    • Usually not associated with poikilodermatous surface changes
Board review style question #1
Which of the following histopathological features can help to differentiate graft versus host disease from other interface dermatitis?

  1. Vacuolar interface reaction, mild perivascular inflammation and abundant dermal mucin deposition
  2. Vacuolar interface reaction, perivascular and interstitial dense eosinophilic infiltrate
  3. Vacuolar interface reaction, sparse superficial perivascular inflammation and dyskeratotic keratinocytes involving the adnexal epithelium
  4. Vacuolar interface reaction, superficial and deep perivascular and periadnexal inflammation
Board review style answer #1
C. Vacuolar interface reaction, sparse superficial perivascular inflammation and dyskeratotic keratinocytes involving the adnexal epithelium. The presence of dyskeratotic keratinocytes involving the adnexal epithelium can help to differentiate between graft versus host disease and other interface dermatitis, such as lupus erythematosus (vacuolar interface reaction, superficial and deep perivascular and periadnexal inflammation), dermatomyositis (vacuolar interface reaction, mild superficial perivascular inflammation and abundant dermal mucin deposition) and drug eruption (vacuolar interface reaction, superficial and deep perivascular and periadnexal inflammation).

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Reference: Graft versus host disease
Board review style question #2
A 15 year old boy, day 47 post bone marrow transplantation, presented with abrupt onset of diffuse erythematous papular eruption. Which of the following is the most likely diagnosis?

  1. Discoid lupus erythematosus
  2. Graft versus host disease
  3. Pityriasis lichenoides chronica
  4. Viral exanthema
Board review style answer #2
B. Graft versus host disease. The given clinical history along with the pathological findings support the diagnosis of graft versus host disease.

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Reference: Graft versus host disease
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