Table of ContentsView AllTable of ContentsSelf-ChecksDiagnostic CriteriaPhysical ExaminationLabs and TestsDifferential DiagnosesGradingNext in Graft-Versus-Host Disease GuideHow Graft-Versus-Host Disease (GvHD) Is Treated
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View All
Table of Contents
Self-Checks
Diagnostic Criteria
Physical Examination
Labs and Tests
Differential Diagnoses
Grading
Next in Graft-Versus-Host Disease Guide
Graft-versus-host disease (GvHD)is a complication of abone marroworstem cell transplantin which cells from a donor attack the tissues of the recipient. GvHD can be classified as being either acute (occurring within 100 days of the transplant) or chronic (occurring 100 days or more after the transplant).
The diagnosis of GvHD is often complex and may require multiple tests and procedures. Although GvHD can sometimes be diagnosed based on symptoms alone, other cases are not so straightforward. In cases like these, there is a strict set of criteria that governs the diagnosis of GvHD.
Once diagnosed, additional tests may be performed to grade the severity of the complication and direct the appropriate course of treatment.
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There are no home tests or self-exams available to diagnose GvHD. With that said, recognizing the signs and symptoms of GvHD can help you seek timely diagnosis and treatment. If left untreated, GvHD can cause profound tissue damage, doubling the risk of high-grade disease and early death.
Acute GvHDtypically starts with the sudden outbreak of a red, inflamed rash on the palms, soles, face, ears, and shoulders. The rash can often become widespread and precede the onset of gastrointestinal or liver symptoms.3
Chronic GvHDalso tends to start with a burning rash on the same parts of the body, although it can be more severe and cause blistering, peeling, and thehardening of the skin. Gastrointestinal and liver symptoms can also develop, in addition to symptoms affecting other organ systems, including the eyes, lungs, joints, muscles, genitals, and nervous system.
Chronic GvHD represents the broadening of theautoimmune-like attack on normal tissues. Symptoms not only tend to be more diverse than acute GvHD but often more severe.
Acute GvHDMaculopapular rashGreenish, watery diarrheaAbdominal crampsBloatingHematochezia (blood in stools)Mouth painDry mouthChanges in tasteHepatomegaly (enlarged liver)Persistent fatigueDark-colored urineChalky stoolsChronic GvHDMaculopapular rash with bullae (a large blister) and peelingScleroderma-like symptomsChanges in skin colorGreenish, watery stoolsBloody stoolsNausea and vomitingDysphagia (difficulty swallowing)Weight lossOral lichen planusGingivitisMouth soresAcute hepatitis withjaundiceDry eyesBlurred visionBlepharitis (eyelid inflammation)Asthma-like symptomsJoint pain and stiffnessMuscle painParesthesia (prickly sensations)Neuralgia (nerve pain)
Acute GvHDMaculopapular rashGreenish, watery diarrheaAbdominal crampsBloatingHematochezia (blood in stools)Mouth painDry mouthChanges in tasteHepatomegaly (enlarged liver)Persistent fatigueDark-colored urineChalky stools
Chronic GvHDMaculopapular rash with bullae (a large blister) and peelingScleroderma-like symptomsChanges in skin colorGreenish, watery stoolsBloody stoolsNausea and vomitingDysphagia (difficulty swallowing)Weight lossOral lichen planusGingivitisMouth soresAcute hepatitis withjaundiceDry eyesBlurred visionBlepharitis (eyelid inflammation)Asthma-like symptomsJoint pain and stiffnessMuscle painParesthesia (prickly sensations)Neuralgia (nerve pain)
GvHD can differ from one person to the next. Acute and chronic symptoms can sometimes overlap or develop in different patterns. Because of this, you should never wait to speak to a doctor if an abnormal symptom occurs, however mild.
What Is Graft-Versus-Host Disease?
The symptoms of GvHD may seem “obvious” enough to render an immediate diagnosis—particularly if they occur within the first 100 days—but it’s not always that simple.
GvHD can be challenging to diagnose because many of the symptoms occur with other conditions or diseases, none of which have anything to do with GvHD. If treated presumptively without meeting specific diagnostic criteria, a person with GvHD may be exposed to therapies that are not only unnecessary but can mask the true cause of the symptoms.
Not everyone with symptoms of GvHD requires confirmatory testing. In some cases, the type and/or burden of symptoms is enough to render a definitive diagnosis without the need for further investigation.
Where Do Stem Cells Come From?
Not everyone with symptoms of GvHD requires confirmatory testing. Some symptoms are characteristic enough to render a diagnosis on their own.
The NIH allows for the diagnosis of acute GvHD if a classic rash, abdominal cramps with diarrhea, and increasedbilirubinlevels occur within the first 100 days of an allogeneic transplant.
The NIH also allows for the diagnosis of chronic GvHD based on whether the symptoms are “diagnostic” or “distinctive.” Diagnostic symptoms are those regarded as defining features of chronic GvHD and do not require additional testing. Distinctive symptoms are those that only suggest chronic GvHD and do require additional testing.
Unless the symptoms of GvHD are considered diagnostic under the NIH guidelines, additional testing must be performed to confirm the findings.
Among the tests commonly used to confirm GvHD:
Doctors will often perform confirmatory tests irrespective of whether a symptom is diagnostic or distinctive as they can aid in the grading of GvHD.
Engraftment in a Stem Cell Transplant
Because the symptoms of GvHD can mimic those of other diseases or conditions, the doctor will explore other causes as part of thedifferential diagnosis. By excluding all other possible explanations, the doctor can render a diagnosis with greater confidence, especially if the other findings are borderline or inconclusive.
Among the conditions that may be investigated are:
GvHD is graded to classify the severity of the condition. This helps direct the appropriate course of treatment and helps predict the likely outcome of treatment (referred to as theprognosis).
There are different classifications used to grade and acute GvHD, each of which uses different measures and grading scales.
Acute GvHD
In the United States, a system called the modified Seattle Glucksberg criteria is recommended for the standardized grading of acute GvHD. The other commonly used classification model is the International Bone Marrow Transplant Registry (IBMTR) grading system.
Under the Seattle Glucksberg system, grades 1 and 2 are regarded as low-grade GvHD with better outcomes, while grades 3 and 4 are considered high-grade GvHD with generally poorer outcomes.
The IBMTR grading systemclassifies GvHD based on the cumulative involvement of skin, gastrointestinal, and liver symptoms. Together, these symptoms are assigned a grade of A, B, C, or D, with A being the least severe and D being life-threatening.
Chronic GvHD
Under the NIH grading system, chronic GvHD is classified as being either mild, moderate, or severe based on the number of organ systems with a score of 1 or more. Mild GvHD is referred to as low-grade disease, while moderate to severe GvHD are considered intermediate- and high-grade disease, respectively.
NIH Severity Scoring for Chronic GvHDMild diseaseThere is one or more organ sites with a score of 1Moderate diseaseThere are three or more organ sites with a score of 1,orThere is at least one organ site with a score of 2,orThe lung score is 1Severe diseaseThere is at least one organ site with a score of 3,orThe lung score is either 2 or 3Once the grade had been established, there are guidelines to direct the first-, second-, and subsequent-lines of treatment for both acute and chronic GvHD.
Once the grade had been established, there are guidelines to direct the first-, second-, and subsequent-lines of treatment for both acute and chronic GvHD.
8 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Wolfe D, Lawitschka A.Chapter 44: Chronic graft-versus-host disease. In: The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition.Bacigalupo A, Milone G, Cupri A, Severino A, et al.Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.Haematologica.2017;102(12):17157. doi:10.3324/haematol.2017.171157Pidala J, Vogelsang G, Martin P, et al.Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study.Haematologica.2012;97(3):451-8. doi:10.3324/haematol.2011.055186Jagasia MH, Greinix HT, Arora M, et al.National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant.2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001Lee SJ.Classification systems for chronic graft-versus-host disease.Blood. 2017;129(1):30-7. doi:10.1182/blood-2016-07-686642Dignan FL, Clark A, Amrolia P, et al.Diagnosis and management of acute graft-versus-host disease.Br J Haematol. 2012;158(1):30-45. doi:10.1111/j.1365-2141.2012.09129.xChoi SW, Levine JE, Ferrara JL.Pathogenesis and management of graft-versus-host disease.Immunol Allergy Clin North Am. 2010;30(1):75-101. doi:10.1016/j.iac.2009.10.001Arora M, Klein JP, Weisdorf DJ, et al.Chronic GVHD risk score: A Center for International Blood and Marrow Transplant Research analysis.Blood. 2011;117(24):6714-20. doi:10.1182/blood-2010-12-323824
8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Wolfe D, Lawitschka A.Chapter 44: Chronic graft-versus-host disease. In: The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition.Bacigalupo A, Milone G, Cupri A, Severino A, et al.Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.Haematologica.2017;102(12):17157. doi:10.3324/haematol.2017.171157Pidala J, Vogelsang G, Martin P, et al.Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study.Haematologica.2012;97(3):451-8. doi:10.3324/haematol.2011.055186Jagasia MH, Greinix HT, Arora M, et al.National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant.2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001Lee SJ.Classification systems for chronic graft-versus-host disease.Blood. 2017;129(1):30-7. doi:10.1182/blood-2016-07-686642Dignan FL, Clark A, Amrolia P, et al.Diagnosis and management of acute graft-versus-host disease.Br J Haematol. 2012;158(1):30-45. doi:10.1111/j.1365-2141.2012.09129.xChoi SW, Levine JE, Ferrara JL.Pathogenesis and management of graft-versus-host disease.Immunol Allergy Clin North Am. 2010;30(1):75-101. doi:10.1016/j.iac.2009.10.001Arora M, Klein JP, Weisdorf DJ, et al.Chronic GVHD risk score: A Center for International Blood and Marrow Transplant Research analysis.Blood. 2011;117(24):6714-20. doi:10.1182/blood-2010-12-323824
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Wolfe D, Lawitschka A.Chapter 44: Chronic graft-versus-host disease. In: The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition.Bacigalupo A, Milone G, Cupri A, Severino A, et al.Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.Haematologica.2017;102(12):17157. doi:10.3324/haematol.2017.171157Pidala J, Vogelsang G, Martin P, et al.Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study.Haematologica.2012;97(3):451-8. doi:10.3324/haematol.2011.055186Jagasia MH, Greinix HT, Arora M, et al.National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant.2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001Lee SJ.Classification systems for chronic graft-versus-host disease.Blood. 2017;129(1):30-7. doi:10.1182/blood-2016-07-686642Dignan FL, Clark A, Amrolia P, et al.Diagnosis and management of acute graft-versus-host disease.Br J Haematol. 2012;158(1):30-45. doi:10.1111/j.1365-2141.2012.09129.xChoi SW, Levine JE, Ferrara JL.Pathogenesis and management of graft-versus-host disease.Immunol Allergy Clin North Am. 2010;30(1):75-101. doi:10.1016/j.iac.2009.10.001Arora M, Klein JP, Weisdorf DJ, et al.Chronic GVHD risk score: A Center for International Blood and Marrow Transplant Research analysis.Blood. 2011;117(24):6714-20. doi:10.1182/blood-2010-12-323824
Wolfe D, Lawitschka A.Chapter 44: Chronic graft-versus-host disease. In: The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition.
Bacigalupo A, Milone G, Cupri A, Severino A, et al.Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.Haematologica.2017;102(12):17157. doi:10.3324/haematol.2017.171157
Pidala J, Vogelsang G, Martin P, et al.Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study.Haematologica.2012;97(3):451-8. doi:10.3324/haematol.2011.055186
Jagasia MH, Greinix HT, Arora M, et al.National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant.2015;21(3):389-401.e1. doi:10.1016/j.bbmt.2014.12.001
Lee SJ.Classification systems for chronic graft-versus-host disease.Blood. 2017;129(1):30-7. doi:10.1182/blood-2016-07-686642
Dignan FL, Clark A, Amrolia P, et al.Diagnosis and management of acute graft-versus-host disease.Br J Haematol. 2012;158(1):30-45. doi:10.1111/j.1365-2141.2012.09129.x
Choi SW, Levine JE, Ferrara JL.Pathogenesis and management of graft-versus-host disease.Immunol Allergy Clin North Am. 2010;30(1):75-101. doi:10.1016/j.iac.2009.10.001
Arora M, Klein JP, Weisdorf DJ, et al.Chronic GVHD risk score: A Center for International Blood and Marrow Transplant Research analysis.Blood. 2011;117(24):6714-20. doi:10.1182/blood-2010-12-323824
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What Is Graft-Versus-Host Disease?Causes and Risk Factors of Graft-Versus-Host DiseaseHow Graft-Versus-Host Disease (GvHD) Is DiagnosedHow Graft-Versus-Host Disease (GvHD) Is TreatedCoping With Graft-Versus-Host-Disease
Causes and Risk Factors of Graft-Versus-Host Disease
How Graft-Versus-Host Disease (GvHD) Is Diagnosed
How Graft-Versus-Host Disease (GvHD) Is Treated
Coping With Graft-Versus-Host-Disease
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