Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation

Grotz, Wolfgang; Breitenfeldt, Marie K; Braune, Stefan; Allmann, K.-H.; Krause, Thomas; Rump, J. A.; Schollmeyer, P.

doi:10.1007/s001470000285

Cited by 57 publications

(93 citation statements)

References 16 publications

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“…Lucas and associates 11 studied 26 renal transplant patients who had isolated musculoskeletal pain owing to cyclosporine use and suggested that the interaction between cyclosporine and glucocorticoids, and the toxicity of cyclosporine metabolites, may contribute to CIPS. Grotz and colleagues 10 hypothesized that calcineurin inhibitor-induced vascular disturbance might lead to an increased permeability of bone marrow vessels with consecutive bone marrow edema. However, bone marrow edema is a nonspecific change of CIPS because it can also occur in osteonecrosis, a joint disorder caused by wear and tear, osteoporosis, ischemia, and tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The relation between calcineurin inhibitors and bone pain was first reported by Bouteiller and associates in 1989, 9 and it was named calcineurininhibitor-induced pain syndrome by Grotz and colleagues in 2001. 10 The prevalence of CIPS is 1% to 17%, mostly occurring in renal transplant recipients. [10][11][12][13][14][15] The mechanism of CIPS is unknown because it is a rare syndrome, and there is a lack of systematic study about it.…”

Section: Introductionmentioning

confidence: 99%

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Immunosuppressant-Related Hip Pain After Orthotopic Liver Transplant

He²,

Fu³

et al. 2012

Exp Clin Transplant

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Objectives: Immunosuppressant-related hip pain can greatly affect a patient's mobility and increase the number of total hip arthroplasties. We investigated risk factors and causes of hip pain after orthotopic liver transplant. Materials and Methods:The medical records of 175 adult orthotopic liver transplant patients, who were followed-up for more than 2 years, were retrospectively reviewed. Data collected from the records included primary disease, medications, biochemical results, Child-Turcotte-Pugh score, death, rejection, and complications related to liver transplant. Results: A total of 11 patients (6.3%) complained of hip pain, which was diagnosed as calcineurininhibitor-induced pain syndrome in 4 patients (2.3%), osteonecrosis of the femoral head in 3 patients (1.7%), and osteoporosis in 2 patients (1.1%). The incidence of calcineurin-inhibitorinduced pain syndrome was related to the dosage of tacrolimus (P > .05) but independent of methylprednisolone use. The occurrence of osteonecrosis of the femoral head was independent of the dosage and early withdrawal of methylprednisolone (P > .05). Patients with methylprednisolone withdrawal within 6 months had significantly longer survival than those using methylprednisolone for more than 6 months (50 ± 15 vs 41 ± 18 mo; P = .007). Conclusions: Calcineurin-inhibitor-induced pain syndrome and osteonecrosis of the femoral head are main causes of hip pain in adult orthotopic liver transplant patients. Osteonecrosis of the femoral head was not common, but the incidence of hip pain owing to calcineurin-inhibitor-induced pain syndrome was relatively high in orthotopic liver transplant patients. Early withdrawal of methylprednisolone could benefit the patients' survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunosuppressant-Related Hip Pain After Orthotopic Liver Transplant

He²,

Fu³

et al. 2012

Exp Clin Transplant

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“…Bone scintigraphy shows increased joint and bone uptake, accentuated at the tarsus. 1 This syndrome was initially recognized in the setting of organ transplantation 1 and then also reported in patients following hematopoietic SCT (HSCT). [2][3][4][5] However, the clinical aspects of CIPS in HSCT remain unclear.…”

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confidence: 99%

“…In contrast, CIPS often occurs at a late stage (X6 weeks) in solid organ transplantation. 1 The reason for this discrepancy is unclear. Patients with hematological diseases have received many neurotoxic drugs, such as chemotherapeutic agents, before HSCT and they also receive many drugs during their HSCT, which may either contribute to or predispose the patients to this complication including the timing of onset.…”

mentioning

confidence: 99%

“…The pathogenesis of CIPS remains unclear, but vascular disturbance of bone perfusion and permeability or facilitation of pronociceptive processes by interrupting glial function and by inhibition of nuclear factor-activated T-cells has been postulated. 1,7 A recent report also showed that some patients with human herpes virus 6 (HHV-6) reactivation manifested CIPS-like symptoms. 8 As HHV-6 was measured in only one patient (case 5) and was negative, the association between CIPS and HHV-6 reactivation is unclear.…”

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confidence: 99%

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Clinical features of calcineurin inhibitor-induced pain syndrome after allo-SCT

Kakihana

Ohashi

Murata

et al. 2011

Bone Marrow Transplant

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Bone infarction of the hip after hand allotransplantation: A case report

et al. 2018

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Vascularized composite allotransplantation represents as an emerging field in reconstructive surgery. However, some complications can be associated with the procedure. The authors describe a case of bone infarctions of the bilateral hip joints following the first hand allotransplantation in Taiwan. A 45‐year‐old man who experienced a traumatic amputation of the distal third of his forearm received a hand transplantation from a brain‐dead donor. Immunosuppression included antithymocyte globulins, and bolus methylprednisolone (Solu‐Medrol) was used for the induction. The maintenance therapy protocol included systemic tacrolimus, mycophenolate mofetil, and prednisone. The patient discontinued the systemic steroid 15 months after surgery. Two episodes of acute rejections were observed at 105 and 810 days after surgery. These signs disappeared after pulse therapy with Solu‐Medrol, titration with tacrolimus, and topical immunosuppressive creams (tacrolimus and clobetasol). However, the patient felt pain in both hips after long periods of standing 30 months after the transplantation. A pelvic radiograph and magnetic resonance imaging revealed avascular necrosis (AVN) in both hip joints. Because of the progressive worsening of the pain, the patient underwent a decompression surgery on the left hip involving a fibula bone graft. The patient underwent a right hip hemi‐arthroplasty with a bipolar prosthesis 3 months later. The patient remained in good health without major complications. These findings indicate that systemic steroids and tacrolimus might be the major predisposing factors for the induction of AVN after hand allotransplantation.

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Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation

Abstract: Bone pain after trans-

Cited by 57 publications

References 16 publications

Immunosuppressant-Related Hip Pain After Orthotopic Liver Transplant

Immunosuppressant-Related Hip Pain After Orthotopic Liver Transplant

Clinical features of calcineurin inhibitor-induced pain syndrome after allo-SCT

Bone infarction of the hip after hand allotransplantation: A case report

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