Difference between revisions of "Graft-versus-host disease"

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'''Graft-versus-host disease''', abbreviated as '''GVHD''', is a rare thingy seen mostly in tertiary care centres.  It is a complication of hematopoietic stem cell transplantation.
'''Graft-versus-host disease''', abbreviated as '''GVHD''', is a rare thingy seen mostly in tertiary care centres.  It is a complication of [[hematopoietic stem cell transplantation]].


===General===
==General==
*Complication of hematopoietic stem cell transplantation, i.e. bone marrow transplantation (BMT).
*Complication of hematopoietic stem cell transplantation, i.e. bone marrow transplantation (BMT).
**Affects skin, liver (bile ducts), gastrointestinal tract.<ref name=pmid15792120>{{cite journal |author=Niino D, Nakashima M, Kondo H, ''et al.'' |title=Correlation of donor-derived keratinocytes and severity of graft-versus-host disease (GVHD) in epidermis |journal=Pathol. Res. Pract. |volume=200 |issue=11-12 |pages=775–81 |year=2005 |pmid=15792120 |doi= |url=}}</ref><ref>{{cite journal |author=van Dijk  AM, Kessler FL, Verdonck LF, ''et al.'' |title=Primary human keratinocytes as targets in predicting acute graft-versus-host disease following HLA-identical bone marrow transplantation |journal=Br. J. Haematol. |volume=111 |issue=3 |pages=791–6 |year=2000 |month=December |pmid=11122139 |doi= |url=}}</ref>
*The histology of GVHD in the intestine is the same as rejection in bowel transplantation.<ref>GT. 14 January 2011.</ref>
*The histology of GVHD in the intestine is the same as rejection in bowel transplantation.<ref>GT. 14 January 2011.</ref>


Clinical:
Clinical:
*May present as diarrhea.
*May present as diarrhea.
*Main DDx (clinical): infection.
*Main DDx (clinical): infection and certain drugs, especially mycophenolate
 
==Microscopic==
===Microscopic (skin)===
Features:<ref name=stanford>{{cite web |url=http://surgpathcriteria.stanford.edu/transplant/skinacutegvhd/printable.html |title=Acute Graft versus Host Disease of the Skin |last1= |first1= |last2= |first2= |date= |work= |publisher= |accessdate=January 17, 2011}}</ref>
#Keratinocyte [[apoptosis]].
#*Intensely eosinophilic on [[H&E]].
#Epidermotropic lymphocytic infiltrate = lymphocytes in the epidermis.
#Vacuolar degeneration of basal and suprabasal cells in the epidermis.
 
Note:
*Apoptotic cells should not be confused with dyskeratotic cells.<ref>{{cite web |url=http://dermatology.acvsc.org.au/dermatology_assets/documents/proc2007/acvs%20dermatology%20chapter%20proceedings%202007%20-%20nimmo%20-%20dyskeratotic,%20apoptotic%20or%20acantholytic%20keratinocytes.pdf |title=Dyskeratotic, apoptotic or acantholytic keratinocytes? How to differentiate these on histology and what meaning does this have to the disease in question |author=Judith S. Nimmo |date= |work= |publisher= |accessdate=17 January 2011}}</ref>
 
====Grading<ref name=stanford/>====
*Grade I: Only vacuolar changes, no apoptosis, no lymphocytes; '''not treated'''.
*Grade II: Only scattered apoptotic cells.
*Grade III: Focal separation/cleft formation at the dermal-epidermal junction.
*Grade IV: Extensive necrosis with degeneration of epidermis.
 
Notes:
*Same scheme applies to esophagus... it has the same structure.
*Originally described in NEJM.<ref name=pmid235092>{{cite journal |author=Thomas ED, Storb R, Clift RA, ''et al.'' |title=Bone-marrow transplantation (second of two parts) |journal=N. Engl. J. Med. |volume=292 |issue=17 |pages=895–902 |year=1975 |month=April |pmid=235092 |doi=10.1056/NEJM197504242921706 |url=}}</ref>


===Microscopic (intestine)===
===Microscopic (intestine)===
Line 16: Line 38:


Notes:
Notes:
*Neutrophils should not be present.
*Neutrophils may be present.


Images:
DDx:
*[http://www.nature.com/modpathol/journal/v24/n1/fig_tab/modpathol2010163f1.html#figure-title GVHD grade 1-4 (nature.com)].
*Drug effect (mycophenolate mofetil) - cannot be distinguished from GVHD.


====Grading<ref name=pmid20953169/>====
====Grading<ref name=pmid20953169/>====
Line 30: Line 52:
Notes:
Notes:
*Low-grade rejection is a diagnosis that requires a careful examination, i.e. it is subtle.
*Low-grade rejection is a diagnosis that requires a careful examination, i.e. it is subtle.
===Microscopic (liver)===
:See: ''[[Vanishing bile duct syndrome]]''.
===Images===
<gallery>
Image: apoptotic gastropathy intermed mag.jpg | Consistent with gastric GvHD (need to exclude mycophenolate as an alternative cause) - intermed mag. (WC)
Image: apoptotic gastropathy high mag.jpg | Consistent with gastric GvHD - high mag. (WC)
Image: Colonic graft-versus-host disease (high magnification).jpg | Colonic GvHD - high mag. (WC)
Image: Skin graft versus host disease high mag 1.jpg | Skin GvHD - high mag. (WC)
Image: Skin graft versus host disease high mag 1.jpg | Skin GvHD - high mag. (WC)
</gallery>
*[https://www.nature.com/articles/modpathol2010163/figures/1 GVHD grade 1-4 (nature.com)].<ref name=pmid20953169/>


==See also==
==See also==
*[[Hematopoietic stem cell transplantation]].
*[[Small bowel]].
*[[Small bowel]].
*[[Colon]].
*[[Colon]].

Latest revision as of 19:03, 11 February 2021

Graft-versus-host disease, abbreviated as GVHD, is a rare thingy seen mostly in tertiary care centres. It is a complication of hematopoietic stem cell transplantation.

General

  • Complication of hematopoietic stem cell transplantation, i.e. bone marrow transplantation (BMT).
    • Affects skin, liver (bile ducts), gastrointestinal tract.[1][2]
  • The histology of GVHD in the intestine is the same as rejection in bowel transplantation.[3]

Clinical:

  • May present as diarrhea.
  • Main DDx (clinical): infection and certain drugs, especially mycophenolate

Microscopic

Microscopic (skin)

Features:[4]

  1. Keratinocyte apoptosis.
    • Intensely eosinophilic on H&E.
  2. Epidermotropic lymphocytic infiltrate = lymphocytes in the epidermis.
  3. Vacuolar degeneration of basal and suprabasal cells in the epidermis.

Note:

  • Apoptotic cells should not be confused with dyskeratotic cells.[5]

Grading[4]

  • Grade I: Only vacuolar changes, no apoptosis, no lymphocytes; not treated.
  • Grade II: Only scattered apoptotic cells.
  • Grade III: Focal separation/cleft formation at the dermal-epidermal junction.
  • Grade IV: Extensive necrosis with degeneration of epidermis.

Notes:

  • Same scheme applies to esophagus... it has the same structure.
  • Originally described in NEJM.[6]

Microscopic (intestine)

Features:[7]

  • Isolated epithelial cell apoptosis - key feature.
  • +/-Crypt destruction (focal or extensive).
  • +/-Loss of epithelium (denudation).

Notes:

  • Neutrophils may be present.

DDx:

  • Drug effect (mycophenolate mofetil) - cannot be distinguished from GVHD.

Grading[7]

  • Grade 1 = isolated epithelial cell apoptosis.
    • No crypt loss/destruction.
  • Grade 2 = individual crypts are lost/scatter destruction of single crypts.
  • Grade 3 = foci several adjacent crypts lost.
  • Grade 4 = large number of adjacent crypts lost/loss of epithelium.

Notes:

  • Low-grade rejection is a diagnosis that requires a careful examination, i.e. it is subtle.

Microscopic (liver)

See: Vanishing bile duct syndrome.

Images

  • Consistent with gastric GvHD (need to exclude mycophenolate as an alternative cause) - intermed mag. (WC)

  • Consistent with gastric GvHD - high mag. (WC)

  • Colonic GvHD - high mag. (WC)

  • Skin GvHD - high mag. (WC)

  • Skin GvHD - high mag. (WC)

See also

References

  1. ↑ Niino D, Nakashima M, Kondo H, et al. (2005). "Correlation of donor-derived keratinocytes and severity of graft-versus-host disease (GVHD) in epidermis". Pathol. Res. Pract. 200 (11-12): 775–81. PMID 15792120.
  2. ↑ van Dijk AM, Kessler FL, Verdonck LF, et al. (December 2000). "Primary human keratinocytes as targets in predicting acute graft-versus-host disease following HLA-identical bone marrow transplantation". Br. J. Haematol. 111 (3): 791–6. PMID 11122139.
  3. ↑ GT. 14 January 2011.
  4. ↑ 4.0 4.1 "Acute Graft versus Host Disease of the Skin". http://surgpathcriteria.stanford.edu/transplant/skinacutegvhd/printable.html. Retrieved January 17, 2011.
  5. ↑ Judith S. Nimmo. "Dyskeratotic, apoptotic or acantholytic keratinocytes? How to differentiate these on histology and what meaning does this have to the disease in question". http://dermatology.acvsc.org.au/dermatology_assets/documents/proc2007/acvs%20dermatology%20chapter%20proceedings%202007%20-%20nimmo%20-%20dyskeratotic,%20apoptotic%20or%20acantholytic%20keratinocytes.pdf. Retrieved 17 January 2011.
  6. ↑ Thomas ED, Storb R, Clift RA, et al. (April 1975). "Bone-marrow transplantation (second of two parts)". N. Engl. J. Med. 292 (17): 895–902. doi:10.1056/NEJM197504242921706. PMID 235092.
  7. ↑ 7.0 7.1 7.2 Cogbill CH, Drobyski WR, Komorowski RA (January 2011). "Gastrointestinal pathology of autologous graft-versus-host disease following hematopoietic stem cell transplantation: a clinicopathological study of 17 cases". Mod. Pathol. 24 (1): 117–25. doi:10.1038/modpathol.2010.163. PMID 20953169. http://www.nature.com/modpathol/journal/v24/n1/full/modpathol2010163a.htm.
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