Graft-versus-host disease (GvHD) is a
syndrome
A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
, characterized by inflammation in different organs. GvHD is commonly associated with
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce a ...
s and
stem cell transplants.
White blood cell
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. This should not be confused with a
transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipien ...
, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donor's immune system's white blood cells reject the recipient. The underlying principle (
alloimmunity
Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility ...
) is the same, but the details and course may differ.
GvHD can also occur after a
blood transfusion
Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
, known as ''Transfusion-associated graft-versus-host disease'' or
TA-GvHD if the
blood products used have not been
gamma irradiated or treated with an approved
leukocyte
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
reduction system. In contrast to organ/tissue transplant associated GvHD, the incidence of TA-GvHD is increased with HLA matching (first-degree or close relatives).
Types

In the clinical setting, graft-versus-host disease is divided into
acute and
chronic forms, and scored or graded on the basis of the tissue affected and the severity of the reaction.
In the classical sense, acute graft-versus-host disease is characterized by selective damage to the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
(rash),
mucosa
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
, and the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
. Newer research indicates that other graft-versus-host disease target organs include the immune system (the
hematopoietic system
The haematopoietic system ( spelled hematopoietic system in American English) is the system in the body involved in the creation of the cells of blood.
Structure Stem cells
Haematopoietic stem cells (HSCs) reside in the medulla of the bone ( ...
, e.g., the
bone marrow
Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
and the
thymus
The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...
) itself, and the
lung
The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s in the form of immune-mediated
pneumonitis
Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris (e.g., animal dander), aspiration, herbicide ...
.
Biomarkers can be used to identify specific causes of GvHD, such as
elafin in the skin.
Chronic graft-versus-host disease also attacks the above organs, but over its long-term course can also cause damage to the
connective tissue
Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...
and
exocrine glands.
Mucosal damage to the
vagina
In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
can result in severe
pain
Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and
scarring
A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a nat ...
, and appears in both acute and chronic GvHD. This can result in an inability to have
sexual intercourse
Sexual intercourse (also coitus or copulation) is a sexual activity typically involving the insertion of the Erection, erect male Human penis, penis inside the female vagina and followed by Pelvic thrust, thrusting motions for sexual pleasure ...
.
Acute
The ''acute'' or ''fulminant'' form of the disease (aGvHD) is normally observed within the first 10 to 100 days post-transplant,
and is a major challenge to transplants owing to associated morbidity and mortality.
About one-third to one-half of
allogeneic transplant recipients will develop acute GvHD.
It is less common in younger patients and in those with closer
human leukocyte antigens (HLA) matches between donor and the patient.
The first signs are usually a rash, burning, and redness of the skin on the palms and soles. This can spread over the entire body. Other symptoms can include nausea, vomiting, stomach cramps, diarrhea (watery and sometimes bloody), loss of appetite, jaundice, abdominal pain, and weight loss.
Acute GvHD of the
GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting.
This is typically diagnosed via intestinal biopsy. Liver GvHD is measured by the bilirubin level in acute patients.
Skin GvHD results in a diffuse
red maculopapular rash,
sometimes in a lacy pattern.
Acute GvHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GvHD usually have a poor prognosis. If the GvHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections
as a result of the immunosuppression and may die of infection. However, a 2016 study found that the prognosis for patients with grade IV GvHD has improved in recent years.
Chronic
The ''chronic'' form of graft-versus-host disease (cGvHD) normally begins 90 to 600 days post-transplant.
The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.
The first symptom of cGvHD is commonly a rash on the palms of the hands or the soles of the feet, and the rash can spread and is usually itchy and dry. In severe cases, the skin may blister and peel, like a bad sunburn. A fever may also develop. Other symptoms of chronic GVHD can include:
* Decreased appetite
* Diarrhea
* Abdominal cramps
* Weight loss
* Yellowing of the skin and eyes (jaundice)
* Enlarged liver
* Bloated abdomen
* Pain in the upper right part of the abdomen
* Increased levels of liver enzymes in the blood (seen on blood tests)
* Skin that feels tight
* Dry, burning eyes
* Dryness or painful sores in the mouth
* Burning sensations when eating acidic foods
* Bacterial infections
* Blockages in the smaller airways of the lungs
In the
oral cavity
A mouth also referred to as the oral is the body orifice through which many animals ingest food and vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also the first part of the alime ...
, chronic graft-versus-host disease manifests as
lichen planus
Lichen planus (LP) is a chronic inflammatory and autoimmune disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, but is named for its appearance. It is characterized by polygonal, flat-topped, violaceous p ...
with a higher risk of
malignant transformation
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor.
Causes
There are ...
to oral
squamous cell carcinoma
Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
in comparison to the classical oral lichen planus.
Oral cancer
Oral cancer, also known as oral cavity cancer, tongue cancer or mouth cancer, is a cancer of the lining of the lips, mouth, or upper throat. In the mouth, it most commonly starts as a painless red or white patch, that thickens, gets ulcerated ...
associated with graft-versus-host disease may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-hematopoietic stem cell transplantation patients.
Causes

Three criteria, known as the Billingham criteria, must be met in order for GvHD to occur.
* An
immuno-competent graft is administered, with viable and functional immune cells.
* The recipient is immunologically different from the donor –
histo-incompatible.
* The recipient is
immunocompromised
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
and therefore cannot destroy or inactivate the transplanted cells. In particular, it involves an inability of the recipient's
cell-mediated immunity to destroy or inactivate viable
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...
s from the donor.
[ ]
After bone marrow transplantation,
T cell
T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s present in the
graft, either as contaminants or intentionally introduced into the host, attack the
tissues of the transplant recipient after perceiving host tissues as antigenically foreign. The T cells produce an excess of
cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s, including
TNF-α and
interferon-gamma
Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...
(IFNγ). A wide range of host
antigens
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
An ...
can initiate graft-versus-host disease, among them the
human leukocyte antigens (HLA). However, graft-versus-host disease can occur even when HLA-identical siblings are the donors.
HLA-identical siblings or HLA-identical unrelated donors often have genetically different
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s (called
minor histocompatibility antigens) that can be presented by
major histocompatibility complex
The major histocompatibility complex (MHC) is a large Locus (genetics), locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for Cell (biology), cell surface proteins essential for the adaptive immune system. The ...
(MHC) molecules to the donor's T-cells, which see these antigens as foreign and so mount an immune response.
Antigens most responsible for graft loss are
HLA-DR (first six months),
HLA-B (first two years), and
HLA-A
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the ''HLA-A'' locus (genetics), locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one o ...
(long-term survival).
While donor T-cells are undesirable as effector cells of graft-versus-host disease, they are valuable for engraftment by preventing the recipient's residual
immune system
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
from rejecting the bone marrow graft (
host-versus-graft). In addition, as bone marrow transplantation is frequently used to treat
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
, mainly
leukemia
Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
s, donor T-cells have proven to have a valuable graft-versus-
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
effect.
A great deal of current research on
allogeneic bone marrow transplantation involves attempts to separate the undesirable graft-vs-host disease aspects of T-cell physiology from the desirable
graft-versus-tumor effect.
Transfusion-associated GvHD
This type of GvHD is associated with
transfusion of un-irradiated blood to immunocompromised recipients. It can also occur in situations in which the blood donor is
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mos ...
and the recipient is
heterozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mos ...
for an
HLA haplotype
A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together from a single parent.
Many organisms contain genetic material (DNA) which is inherited from two parents. Normally these organisms have their DNA orga ...
. It is associated with higher mortality (80–90%) due to involvement of bone marrow lymphoid tissue, however the clinical manifestations are similar to GVHD resulting from bone marrow transplantation. Transfusion-associated GvHD is rare in modern medicine. It is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells (including lymphocytes) within.
Thymus transplantation
Thymus transplantation may be said to be able to cause a special type of GvHD because the recipient's
thymocyte
A thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood.
Thymopoiesis describes the process which turns thy ...
s would use the donor thymus cells as models when going through the
negative selection to recognize self-antigens, and could therefore still mistake own structures in the rest of the body for being non-self. This is a rather indirect GvHD because it is not directly cells in the graft itself that causes it but cells in the graft that make the recipient's T cells act like donor T cells. It can be seen as a multiple-organ autoimmunity in
xenotransplantation experiments of the thymus between different species. Autoimmune disease is a frequent complication after human allogeneic thymus transplantation, found in 42% of subjects over one year post-transplantation. However, this is partially explained by the fact that the indication itself, that is, complete
DiGeorge syndrome
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent ...
, increases the risk of autoimmune disease.
Thymoma-associated multiorgan autoimmunity (TAMA)
A GvHD-like disease called
thymoma-associated multiorgan autoimmunity (TAMA) can occur in patients with thymoma. In these patients rather than a donor being a source of pathogenic T cells, the patient's own malignant thymus produces self-directed T cells. This is because the malignant thymus is incapable of appropriately educating developing thymocytes to eliminate self-reactive T cells. The result is a disease virtually indistinguishable from GvHD.
Mechanism
The pathophysiology of GvHD includes three phases:
# The afferent phase: activation of APC (
antigen presenting cells)
# The efferent phase: activation, proliferation, differentiation and migration of effector cells
# The effector phase: target tissue destruction
Activation of APC occurs in the first stage of GvHD. Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, especially intestinal mucosa. This allows the microbial products to enter and stimulate pro-inflammatory cytokines such as
IL-1 and
TNF-α. These proinflammatory cytokines increase the expression of MHC and adhesion molecules on APCs, thereby increasing the ability of APC to present antigen.
The second phase is characterized by the activation of effector cells. Activation of donor T-cells further enhances the expression of MHC and adhesion molecules, chemokines and the expansion of CD8 + and CD4 + T-cells and guest B-cells. In the final phase, these effector cells migrate to target organs and mediate tissue damage, resulting in multiorgan failure.
Prevention
*
DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
-based tissue typing allows for more precise HLA matching between donors and transplant patients, which has been proven to reduce the incidence and severity of GvHD and to increase long-term survival.
* The T-cells of umbilical cord blood (UCB) have an inherent immunological immaturity, and the use of UCB stem cells in unrelated donor transplants has a reduced incidence and severity of GvHD.
*
Methotrexate,
cyclosporin and
tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...
are common drugs used for GvHD prophylaxis.
Further research is necessary to evaluate whether mesenchymal stromal cells can also be used for the prophylaxis.
* Graft-versus-host disease can largely be avoided by performing a T-cell-depleted bone marrow transplant. However, these types of transplants come at a cost of diminished graft-versus-tumor effect, greater risk of engraftment failure, or cancer relapse, and general
immunodeficiency
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that aff ...
, resulting in a patient more susceptible to
viral,
bacterial, and
fungal
A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...
infection
An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
. In a multi-center study, disease-free survival at three years was not different between T cell-depleted and T cell-replete transplants.
Treatment
Glucocorticoids
Intravenously administered
glucocorticoids, such as
prednisone
Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
, are the standard of care in acute GvHD
and chronic GVHD. The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect..While glucocorticoids remain the first line of treatment for acute GVHD, only about 50% of patients respond to treatment, otherwise having steroid-refractory GVHD (SR-GVHD).
An increasing number of recent treatment options for SR-GVHD have been investigated, such as extracorporeal photopheresis (ECP), mesenchymal stem cell (MSCs), fecal microbial transplantation (FMT), and the medication Ruxolitinib.
Steroid-sparing immunosuppression/immunomodulation
Cyclosporine and
tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...
are
calcineurin inhibitors. The substances are structurally different but have the same mechanism of action. Cyclosporine binds to the cytosolic protein peptidyl-prolyl cis-trans isomerase A (known as cyclophilin), while tacrolimus binds to the cytosolic protein peptidyl-prolyl cis-trans isomerase FKBP12. These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus. Standard prophylaxis involves the use of cyclosporine for six months with methotrexate. Cyclosporin levels should be maintained above 200 ng/ml.
Other substances that have been studied for GvHD treatment include, for example:
sirolimus,
pentostatin,
etanercept, and
alemtuzumab.
In August 2017, the
US FDA approved
ibrutinib to treat chronic GvHD after failure of one or more other systemic treatments.
Axatilimab (Niktimvo) was approved for medical use in the United States in August 2024.
Cell therapy
Remestemcel (Ryoncil) was approved for medical use in the United States in December 2024.
Non-pharmacological treatment
Given the complex systemic condition and immunosuppression of the chronic GVHD patients, non-drug therapies are a significant advancement, and may be preferred whenever possible. Examples are
photobiomodulation
Low-level laser therapy (LLLT), cold laser therapy or photobiomodulation (PBM) is a medical treatment approach that applies low-level (low- power) lasers or light-emitting diodes (LEDs) to the surface of the body. Whereas high-power lasers are ...
for GVHD-related
oral mucosal ulcers, and electrostimulation for GVHD-related
xerostomia.
Clinical research
There are a large number of clinical trials either ongoing or recently completed in the investigation of graft-versus-host disease treatment and prevention.
On 17 May 2012, Osiris Therapeutics announced that Canadian health regulators approved
Prochymal, its drug for acute graft-versus-host disease in children who have failed to respond to steroid treatment. Prochymal is the first
stem cell drug to be approved for a systemic disease.
In January 2016,
Mesoblast released results of a phase 2 clinical trial on 241 children with acute Graft-versus-host disease, that was not responsive to steroids.
The trial was of a mesenchymal stem cell therapy known as
remestemcel-L or MSC-100-IV. Survival rate was 82% (vs 39% of controls) for those who showed some improvement after one month, and in the long term 72% (vs 18% of controls) for those that showed little effect after one month.
[
]
HIV elimination
Graft-versus-host disease has been implicated in eliminating several cases of HIV, including The Berlin Patient and six others in Spain.
See also
* Graft-versus-tumor effect
Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells (T lymphocytes) that can be beneficial for the recipient by eliminating residual malignant cells. GvT might ...
* Immunosuppression
* Transplant rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipien ...
References
Further reading
* Ferrara JLM, Deeg HJ, Burakoff SJ. ''Graft-Vs.-Host Disease: Immunology, Pathophysiology, and Treatment.'' Marcel Dekker, 1990
* Polsdorfer, JR ''Gale Encyclopedia of Medicine: Graft-vs.-host disease''
External links
{{DEFAULTSORT:Graft-Versus-Host Disease
Immune system disorders
Transplantation medicine
Noninfectious immunodeficiency-related cutaneous conditions
Complications of surgical and medical care