**Introduction/Hypothesis**
Tacrolimus, calcineurin inhibitor similar to Cyclosporine, is commonly used as an immunosuppressive therapy for organ transplant rejection prophylaxis. It has been reported to cause various adverse effects such as nephrotoxicity, neurotoxicity, infectious complications, and disturbance in lipid metabolism. It has been reported to lead to ascites and pleural effusions. However, pericardial effusion is a side effect rarely seen or noted to be induced by tacrolimus. We present a case of a patient with recurrent pericardial effusion associated with chronic treatment with tacrolimus.

**Methods**
A 75-year-old Jamaican male initially presented to the hospital after he was seen by cardiology for an abnormal echocardiogram as a follow up for incidental moderate effusion noticed on prior high-resolution CT of the chest. The echo revealed a significantly large pericardial effusion, ejection fraction of 56-60%, and moderate pulmonary hypertension (right ventricular pressure = 53 mmHg). His medical history involved a renal transplant in 2002 (daughter was a donor) and on tacrolimus, mycophenolate mofetil, and prednisone. The patient had been prescribed tacrolimus to take 0.5 mg daily, but instead took 1.5 mg in morning and 2mg in evening. The patient was negative for COVID upon arrival to the Emergency department.  He underwent an emergent pericardiocentesis, which yielded 750 cc of serosanguinous fluid; this was followed by a pericardial sub-xyphoid window and drain placement that was removed a few days later.  Fluid analysis (AFB stain, Gram stain, and fungal and viral cultures and tissue culture) was negative.  Pericardial biopsy was notable for benign fibroadipose tissue consistent with pericardium. Cytology was normal for mesothelial cells and negative for malignant cells.  The patient’s nephrologist chose to reduce frequency of the tacrolimus from 0.5 mg twice daily to once daily.  The patient was discharged a few days later. He was re-admitted about 3 months later with complaints of fatigue, anorexia, poor oral intake, and was found to have abdominal distention and bilateral peripheral edema.  CT of the abdomen and pelvis showed anasarca changes with moderate ascites.  A follow up echo noted a normal EF (= 56-60%) and a moderate to large pericardial effusion anterior to heart with concerns for cardiac tamponade.  The tacrolimus was discontinued for a couple days which resulted in improved creatinine from 1.55 to 1.32 with baseline 1.3-1.4. However, tacrolimus was restarted with Cr at baseline and within the next couple days the creatinine increased to 1.59. He underwent a right thoracoscopy and Video-Assisted Thoracoscopic Surgery with pericardial window, which recovered serous fluid. Repeat fluid analysis (AFB stain, Gram stain, and fungal and virus cultures) was negative, with similar benign fibroadipose tissue noted on biopsy, as before. The cytology of the yellow pleural fluid and amber pericardial fluid was negative for malignant cells, but positive for mesothelial cells, macrophages, and lymphocytes. His post-thoracoscopy chest tube was later removed.  Rheumatology was consulted for additional help with diagnosis and management.  His ANA comprehensive panel with reflex to titer and patter (including SCL-70, SM Ab, SM/RNP), CRP, ESR, Rheumatoid Factor, anti-CCP Ab IgG, and CK were all negative, essentially ruling out Sjӧgren’s syndrome, inflammatory pericarditis, and rheumatoid arthritis.  He subjectively improved and was later discharged.

**Results**
Not applicable to the Case Study

**Conclusion**
Classically, Tacrolimus (similar to Sirolimus) has been known to cause various undesired clinical effects, including nephrotoxicity, neurotoxicity, infections (due to its immunosuppressive properties), along with pleural effusion and ascites. Usually, these adverse effects occur early in the course of treatment (immediately or days to weeks after its initiation). However, this case, with evaluations that ruled out malignancy, infections, and autoimmune processes, suggests that tacrolimus, seemed to be the cause of the patient’s pericardial and pleural effusions and occurred in the setting of chronic use of the medication. The fact that the patient was prescribed 0.5 mg daily, but rather took 1.5 mg in the morning and 2 mg in evening, may have led to the chronic toxicity building up over time.  In patients on tacrolimus therapy, if no other causes for a pericardial effusion is found, in addition to drainage of the effusion, stopping or reducing the dosage of offending drug, or switching to an alternative immunosuppressive regimen should be considered.



Tacrolimus-Induced Pericarditis/Pericardial effusion Following Kidney Transplant