Calcineurin-inhibitor induced pain syndrome (CIPS)

Case Discussion

The patient presented with bilateral knee and ankle pain. She is an organ transplant recipient and had been taking tacrolimus for a few months as immunosuppression.

Calcineurin inhibitor-induced pain syndrome (CIPS) is an acute pain syndrome that can occur in transplant patients secondary to the use of immunosuppressive calcineurin inhibitors ¹. CIPS classically presents, as in this case, as symmetric lower limb/joint pain. The pain usually starts in the more distal joints and progresses proximally ². In this patient's case, the pain started in the ankles and progressed to the knees.

The onset of symptoms may range from a few weeks up to 14 months post-transplant surgery ¹. Although the pain is reversible, symptoms may last for as long as 18 months ². Features on MRI include low T1 and high T2 signal intensity in affected bones due to subchondral and periarticular edema ². Bone scintigraphy shows bilateral uptake within the distal periarticular femur and medial tibial plateau. In the ankles, there is increased uptake, particularly within the calcaneus and talus bilaterally on the anterior views and posteriorly within the calcaneus. Increased uptake is indicative of augmented perfusion, vascularity and metabolism ³. Treatment includes a dose reduction of calcineurin inhibitors, switching to a different class of immunosuppressant and calcium channel blockers ². Symptoms usually resolve over a few months on treatment ³.

Post-imaging the patient's dose of tacrolimus was reduced. After this medication change, the pain improved over the following months.