Introduction:
Pseudo pseudo Meigs syndrome (PPMS), also known as Tjalma syndrome, is a rare condition, that is seen in patients with systemic lupus erythematosus (SLE), with abnormal renal function. It usually presents with pleural effusion, ascites and an elevated CA 125 without evidence of an ovarian tumor. It has also been reported with the use of the disease modifying drug, leflunomide. Although it is a condition seen mostly associated with SLE, it can be seen with mixed connective tissue disorder (MCTD). We present a case of a 67-year-old female with PPMS after administration of leflunomide therapy for her undifferentiated connective tissue disorder. Interestingly, this patient did not have ascites and had a normal renal function. The patient’s pleural effusion resolved and CA 125 normalized after stopping leflunomide. There has been a reported case of PPMS with normal renal function, and a reported case of PPMS without the ascites component in a patient with SLE and lupus nephritis. Here we discuss the role of Leflunomide as a probable cause of this variant of PPMS in our patient.

Case Presentation:
A 67-year-old female with PMHx of undifferentiated connective tissue disorder, hypertension, hyperlipidemia, and coronary artery disease presented with shortness of breath and was found to have bilateral pleural effusion and pericardial effusion without tamponade. Examination of the patient revealed no fever (temp of 97.8 F), vitals were stable (BP 135/65mmHg; HR 73/min; RR 16/min) with an oxygen saturation of 96% on room air. Patient’s medications included olmesartan, amlodipine, bisoprolol, atorvastatin, oxycodone, leflunomide, hydroxychloroquine, omeprazole, duloxetine and cevemilline. Initial labs showed a normal WBC, normal albumin, iron deficiency anemia (total iron 19 and % saturation 6), an elevated CRP 15.4 (normal <0.9), and elevated ferritin of 501 (normal 11-307). Echocardiogram showed a normal ejection fraction with moderate aortic regurgitation and pericardial effusion without tamponade. Chest x-ray showed bilateral pleural effusions that was confirmed by a CT of the chest which also showed moderate pericardial effusion. Pertinent rheumatologic labs revealed normal complement levels, negative dsDNA, AMA, SSA, SSB and scleroderma antibodies, and a positive ANA and anti-histone antibodies. A CA 125 was elevated at 136 (normal <35). A CT of the abdomen and pelvis failed to reveal any ovarian or pelvic masses. There was no ascites. The patient had a thoracentesis which showed a transudative tap (pleural fluid protein <3, serum protein 6.1, pleural LDH 84, serum LDH 203). Patient’s shortness of breath improved after the thoracentesis and she was discharged home to follow up on all results. However, within the next two weeks, the patient had a recurrence of shortness of breath and pleural effusions. Follow up labs two weeks later showed an increase in CA 125 levels to 217 and a ferritin of 1372. Repeat right sided thoracentesis was performed which was still transudative (pleural fluid protein <3, serum protein 6.1, pleural LDH 125, serum LDH 381). At this time cardiothoracic surgery was consulted and patient underwent right Video-assisted thoracoscopic surgery with Talc pleurodesis and biopsy of the pleura. Cytology of the pleural fluid was negative for any malignant cells. Pleural biopsy revealed evidence of acute and chronic inflammation with no evidence of malignancy. The T-spot TB test was negative and the pleural fluid adenosine deaminase was 8.9 (normal <9.2U/L).

Final Working Diagnosis:
After ruling out other causes of pleural effusion in the presence of an elevated CA 125, her medications were reevaluated and the cause of her recurrent pleural effusion and elevated CA 125 was thought to be PPMS due to Leflunomide.

Outcome:
The patient’s Leflunomide was discontinued and she was started on Azathioprine. Her CA 125 decreased in two weeks from 217 to 149, and her small left pleural effusion was stable. Two months later, off Leflunomide, patient’s CA 125 was normal at 13 with minimal left pleural effusion and no right pleural effusion on chest Xray.