Bone Marrow Transplantation (2000) 26, 673–675 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt Case report First manifestations of seronegative spondylarthropathy following autologous stem cell transplantation in HLA-B27-positive patients B Koch2, N Kranzho¨fer1, M Pfreundschuh1,2, HW Pees1 and L Tru¨mper1 1Dr Mildred-Scheel Unit for Blood Stem Cell Transplantation and 2Saarland University Rheumatology Center, Department of Internal Medicine I, Saarland University, Homburg, Germany Summary: usually disappear after recovery and restoration of physical fitness and are therefore probably related to immobilization Two male patients with non-Hodgkin’s lymphoma and/or medication such as drugs used in conditioning regi- (NHL, follicular NHL, diffuse large B cell NHL, both mens, steroids or total body irradiation. We describe three in 2nd complete remission) and one female patient with patients who presented with rheumatic symptoms after acute myeloid leukemia in 1st complete remission autologous SCT. These were shown to be primary manifes- developed arthralgias and enthesopathy following auto- tations of an HLA-B27-associated rheumatic disorder. logous stem cell transplantation. In 2/3 patients, sacro- iliitis could be demonstrated on X-ray. In both patients, the rheumatic symptoms were classified as manifes- Case reports tations of a spondylarthropathy. All three patients were subsequently shown to be HLA-B27-positive. The During regular follow-up at our transplant unit, arthralgias patients were successfully treated with non-steroidal were observed in 3/140 consecutive patients following anti-inflammatory drugs. The differential diagnosis of autologous PBSCT. All three were shown to be HLA-B27- joint pain following autologous stem cell transplantation positive. Details of the patients are listed in Table 1. 114 should include HLA-B27-associated spondylarthropath- autologous transplant patients and 26 allogeneic transplant ies in addition to the more commonly seen bone and patients were included in this series. 78 were male and 62 joint pain due to immobilization and medication. Bone female. The median age at transplant was 40 years. The list Marrow Transplantation (2000) 26, 673–675. of diagnoses included NHL (n = 59), ALL (n = 6), AML Keywords: autologous stem cell transplantation; HLA- (n = 20), CML (n = 9), MDS (n = 1), HD (n = 20), multiple B27; spondylarthropathy; enthesopathy; non-Hodgkin’s myeloma (n = 8) and solid tumors (n = 17). 105 patients lymphoma; late effects received peripheral blood stem cells and 35 bone marrow as the stem cell source. The data were retrieved from our data base (Stemsoft, Vancouver, BC, Canada). All trans- plants were registered with the EBMT-G. Joint pain is a common finding in patients after bone mar- row or stem cell transplantation. Following allogeneic bone marrow (BMT) or blood stem cell transplantation (SCT), Case 1 rheumatic manifestations such as arthralgias and arthritis A 39-year-old male with relapsed follicular NHL achieved have been reported previously. These are thought to be due a 2nd complete remission (CR) following treatment with to avascular necrosis of the bone or are interpreted as an two cycles of the Dexa-BEAM regimen (dexamethasone, early clinical sign of imminent chronic graft-versus-host- carmustine, etoposide, cytosine arabinoside, and 1–3 disease, respectively. During the course of chronic graft- melphalan8) and abdominal bath irradiation with 20 Gy. versus-host disease characteristics similar to several auto- The patient underwent conditioning with the BEAM-regi- immune diseases such as scleroderma, Sjo¨gren’s syndrome, men9 and received 2.5 × 106 CD34-positive cells/kg body 3–6 and polymyositis may be seen. In the follow-up of auto- weight. Hematological recovery was uneventful logous SCT autoimmune events such as thyroiditis, throm- (neutrophils Ͼ1000 on day 12, platelets Ͼ20 000 on day bocytopenic purpura, and hemolytic anemia have been 19). Neutropenic fever and slight pulmonary infiltrates in 7 described, and in the early post-transplant period, joint and the second week after transplant resolved with standard bone pain are relatively common events. However, these broad spectrum antibiotics. Serology for common infec- tions and blood cultures was negative. No other infectious complications occured during the first month. After a period Correspondence: Dr L Tru¨mper, Department of Internal Medicine I, Dr Mildred Scheel Unit for Stem Cell Transplantation, Saarland University, of 3 months, he developed arthralgias in the knee-joints and D–66421 Homburg, Germany wrists and heel pain, and 3 months later low back pain and Received 5 November 1999; accepted 20 May 2000 tenderness of the sacroiliac joints. X-rays revealed minimal Spondylarthropathy in HLA-B27-positive patients B Koch et al 674 Table 1 Characterization of patients with rheumatic symptoms fol- of pain in his heels and in his shoulder joints worsened by lowing autologous stem cell transplantation exercise and receives regular medication with NSAID. Case 1 2 3 Case 3 Sex Male Male Female A 29-year-old female was diagnosed with acute myeloid Diagnosis NHL, NHL, DLBC AML, FAB follicular M4 leukemia (FAB M4 subtype) in 1984. After induction ther- Source of stem cells Peripheral Peripheral BM apy with HAM she was transplanted in 1st CR after con- Cond/HD-CT BEAM BEAM TBI/Cy ditioning with total body irradiation and cyclophosphamide. Status at SCT Second CR Second CR First CR In 1985 she acquired an infection with Yersinia enterocoli- Age at SCT (years) 40 39 29 Current hematological status Third relapsea CR CR tica proven by stool culture. A few months later, she Onset of rheumatic +3 months +4 months +1 year developed low back pain, arthralgias in the knee-joints, symptoms after SCT ankles, wrists, heel pain and tenderness of the sacroiliac Enteritic infection −−Yersinia joints. Grade III sacroiliitis and a heel spur on the right enterocolitica were demonstrated by X-ray examination 6 years after Arthralgias +++ Joint swelling −−−onset of the rheumatic symptoms. Bone scans with tech- Low back pain +−+netium 99m showed increased uptake in the knee joints, Enthesopathy +++wrists, ankles, and in the right heel. The patient responded X-ray: sacroiliitisb grade II ND grade III to treatment with NSAID. She is in continuous 1st CR of X-ray: heel spur + ND + (right) Bone scan-technetium 99m heels + ND right heel + the hematological disease 15.5 years following SCT. How- HLA-B27 +++ever, she still needs treatment with NSAIDs to relieve Response to NSAID +++her symptoms. Time from SCT (years) 4.5 4 15.5 Current rheumatic symptoms + (+) + Discussion SCT = stem cell transplantation; cond/HD-CT = conditioning/high dose- chemotherapy; BEAM = carmustine, etoposide, cytosine arabinoside, mel- phalan; TBI/Cy = total body irradiation/high-dose cyclophosphamide; According to the preliminary criteria proposed by the Euro- CR = complete remission; NSAID = non-steroidal antirheumatic drugs; pean Spondylarthropathy Study Group10 the rheumatic ND = not done. symptoms in two of the three patients described here could a At age 43 years. be classified as classical features of a spondylarthropathy. bGrading based on European Spondylarthropathy Study Group prelimi- nary criteria. In the third patient (case 2) the symptoms could be classi- fied as features of an incomplete undifferentiated spondyl- arthropathy fitting into the ARMOR classification of spon- dylarthropathias.11 In all three patients the rheumatic bilateral grade II sacroiliitis and heel spurs 6 months after symptoms evolved in the early post-transplant period. One transplant with bone scintigraphy activity at the heels and of the three patients presented with a pulmonary infiltrate at the wrists. He received non-steroidal-anti-inflammatory during the early post-transplant period (case 1), the second drugs (NSAID). After treatment for 4.5 years he is still patient suffered from an enteritic infection with Yersinia complaining of pain in the knees and heels. A Schober test enterocolitica before the onset of rheumatic symptoms of the lumbar spine revealed a 3 cm increase in distance (case 3), while the third patient did not report any enteritic, after maximal forward bending, and chest expansion was genito-urinary or other infection (case 2). None of the 2 cm compatible with restricted spine flexibility. Continu- patients had experienced symptoms of a rheumatic disease ous treatment with NSAID for symptomatic relief is neces- before the transplant. After autologous PBSCT, develop- sary and recently, treatment with azulfidine had to be ment of a polyarthritis has been described secondary to a started. Four years after PBSCT, the patient’s low grade CMV infection.12 However, in our cases no evidence for NHL relapsed. a CMV infection was found. Whether the immunological changes associated with autologous SCT favor the manifes- Case 2 tation of rheumatic symptoms in HLA-B27-positive indi- viduals is not clear. Since HLA-typing had not been per- A 39-year-old male was diagnosed with relapsed high- formed regularly in our autologous transplant group, the grade non-Hodgkin’s lymphoma (diffuse large B cell lym- incidence of rheumatic symptoms in HLA-B27-positive phoma of the mediastinum according to the REAL patients cannot be judged with certainty. In our patient classification) in 1995. After treatment with two cycles of group, the prevalence of HLA-B27-associated rheumatic Dexa-BEAM, he achieved a 2nd CR and was subsequently disease was 2.1%, which