Undifferentiated spondyloarthritis following allogeneic stem cell transplantation
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Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT.
We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation.
Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s).
KeywordsPsoriasis Stem Cell Transplantation Rheumatic Disease Thrombotic Thrombocytopenic Purpura Allogeneic Stem Cell Transplantation
stem cell transplant.
Both autologous and allogeneic stem cell transplantation (SCT) have become standard therapeutic modalities for lymphoid proliferative and certain autoimmune/rheumatic disorders [1, 2]. With modified protocols to ensure less profound depletion of T cells, better control of systemic disease prior to transplantation, antiviral prophylaxis after transplantation, and slower tapering of corticosteroids both morbidity and mortality complications following SCT have significantly declined in recent years . The development, however, of de novo rheumatic disorders is being increasingly recognized following either autologous or allogeneic SCT procedures [4, 5, 6]. The purpose of this report is to describe a patient in whom undifferentiated spondyloarthritis developed following allogeneic SCT.
Some rheumatic diseases appear to be directly related to SCT itself, while others may be associated to the therapy used (Additional File 1). Wagener et al. first brought into attention the development of musculoskeletal complaints following allogeneic but not autologous bone marrow transplantation . Oligoarthritis occurring in 18/33 and avascular bone necrosis in 8/33 patients were noted. Since then several case reports or small series have appeared describing the development of a variety of rheumatic disorders including rheumatoid arthritis, HLA-B27 related spondyloarthritis, psoriatic arthritis, vasculitides syndromes including ANCA-associated small vessel vasculitis, eosinophilic fasciitis, ANA positivity, and antiphospholipid syndrome [7, 8, 9, 10, 11, 12]. Gouty and acute inflammatory arthritis following the use of recombinant granulocyte colony-stimulating factor therapy has also been described in SCT patients [13, 14]. Immune-mediated thyroid disease and cytopenias including Evans syndrome, hemolytic anemia, and thrombotic thrombocytopenic purpura (TTP)-like syndromes constitute another group of disorders seen in SCT [12, 15].
A literature search along with consultation of leading hematologists was performed to find the current level of science in stem cell transplantation. Through our work, we found that a few other authors have noticed the phenomenon of autoimmune disease transmission after stem cell transplantation.
Our patient exhibits clinical manifestations associated with undifferentiated spondyloarthropathy . HLA-B27 was not detected, but the presence of oligoarthritis, unilateral sacroiliitis, dactylitis, and enthesitis and a positive family history of psoriasis fulfill classification criteria for spondyloarthritis-most likely undifferentiated spondyloarthritis.
We present an interesting patient who has undergone stem cell transplantation for the treatment of pre-B lymphocytic leukemia and was in remission. However, his development of a de novo rheumatic disease was recognized by us and the incidence is increasing according to recent medical literature. We reviewed current theories regarding the reasons behind autoimmune disease transfer between donor and recipient and postulate that our patient fits into the current science.
One could consider the development of de novo autoimmune disease as a possible side effect of stem cell transplantation. These serious secondary effects of stem cell transplantation must be taken into account as tertiary centers continue using SCT as a modality for the treatment of rheumatic and hematologic disease.
The exact pathophysiology of both rheumatic and immune-mediated disorders is not fully understood. It is quite likely, however, that multiple factors including genetic predisposition, environmental factors such as CMV infection, drug exposure, abnormal reconstitution of the immune system, and direct transfer of pathogenic hematopoietic stem cells from the donor that could generate autoreactive clones in allogeneic transplants-possibly the case in our patient, might participate. Inflammatory cytokines, chemokines and adhesion molecules, particularly interleukin-8 and drugs used during SCT such as cyclosporine A or tacrolimus may also play an important role in inducing vascular endothelial damage leading to TTP-like syndromes.
Our patient revealed a clinical picture consistent with undifferentiated spondyloarthritis which developed following allogeneic SCT. The exact incidence as well as the pathophysiology of this complication is unknown, but larger studies are needed to develop preventive measures.
Patient has given authors consent for the use of these clinical images for publication.
The authors would like to thank Professor Elmongy in the LSU Health Sciences Center Section of Hematology/Oncology for technical guidance.
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