Chronic Graft-versus-Host Disease
Rheumatologic Manifestations of Chronic Graft-versus-Host Disease
Our featured expert reviews important similarities and differences between complex primary rheumatologic diseases and chronic graft-versus-host disease (cGVHD) with rheumatologic manifestations. In both cases, a multidisciplinary approach may be valuable.
Deputy Division Head
"While it can be somewhat academic to distinguish the rheumatologic manifestations of cGVHD from a primary rheumatologic disorder, it is an important distinction because the treatment may be different.”
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be lifesaving, cGVHD is a potential complication of allo-HSCT that weighs heavily on transplant physicians. GVHD occurs when donor immune cells react against the patient's body through a process involving histocompatibility differences to cause tissue injury, inflammation, and fibrosis. Historically, the timing of these manifestations (ie, ≥100 days post transplant) was the major defining feature of cGVHD, but, today, we think of cGVHD much more so in the context of the organs that it affects. cGVHD is truly a multisystem disease. It can affect the eyes, skin, mucus membranes, gastrointestinal tract, liver, heart, lungs, and other organs.
cGVHD can resemble autoimmune or immunologic disorders clinically, and autoantibodies may be present. Antinuclear antibodies are among the most commonly seen autoantibodies in patients with clinical manifestations of cGVHD. Symptoms such as dry eye may also be common in both cGVHD and certain rheumatologic disorders. The involvement of the salivary and lacrimal glands in cGVHD can result in Sjögren's syndrome–like manifestations, including the hyposecretion of saliva and tears. Other manifestations of cGVHD may resemble scleroderma or, less commonly, polymyositis.
The American College of Rheumatology and the European Alliance of Associations for Rheumatology have developed diagnostic criteria for rheumatologic disorders that exclude a history of allo-HSCT with manifestations of cGVHD. For example, scleroderma-like changes in cGVHD would be considered distinct from scleroderma according to these criteria. Some differences in presentation also distinguish the two. Scleroderma is very commonly associated with Raynaud's phenomenon as opposed to cGVHD, which rarely ever manifests with Raynaud's phenomenon. Of course, the history of allo-HSCT is the crucial deciding factor.
While it can be somewhat academic to distinguish the rheumatologic manifestations of cGVHD from a primary rheumatologic disorder, it is an important distinction because the treatment may be different. Targeted agents that are used for rheumatologic disease are not necessarily used for cGVHD, and vice versa, despite some shared biology. There is not a single standard therapy for steroid-refractory cGVHD, but we have 3 drugs that have been approved by the US Food and Drug Administration for this indication (ie, ruxolitinib, belumosudil, and ibrutinib). Some of the agents that are approved in cGVHD have not been adequately studied in primary rheumatologic diseases. Ultimately, it is possible that there might be some application in rheumatologic diseases, but this would need to be evaluated in clinical trials.
There is a final point that connects cGVHD with complex multisystem rheumatologic disorders, and that is the importance of multispecialty care. A specialist who performs the transplant may not necessarily be an expert in all of the manifestations of cGVHD, such as ocular and pulmonary manifestations. So, it may be beneficial for patients with cGVHD to visit a clinic that has teams of physicians from multiple specialties with expertise in the various manifestations of cGVHD for their assessment and treatment.
EULAR recommendations: EULAR/ACR collaborative projects. EULAR. Accessed August 8, 2023. https://www.eular.org/recommendations-eular-acr
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