The TEMPI Syndrome: Telangiectasias, Elevated Erythropoietin and Erythrocytosis, Monoclonal Gammopathy, Perinephric Fluid Collections, and Intrapulmonary Shunting

Abstract 1037

We report a rare and novel syndrome which we have termed TEMPI: telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. In 2010, the index case of a man with unexplained erythrocytosis and perinephric fluid collections was published in the Case Records of the Massachusetts General Hospital in the New England Journal of Medicine. In the case report, we appealed to readers to share insights and similar cases. As a result, two strikingly similar cases were identified: a woman in Antwerp, Belgium and a woman in Los Angeles, California. The patients share five characteristics constituting the TEMPI syndrome.

The three patients had all been healthy until their 3^rd or 4^th decades when they began to manifest symptoms. Telangiectasias developed spontaneously and were most prominent over the trunk, arms, hands, face, and oropharynx; there was no evidence of liver dysfunction. Erythrocytosis was present, with the presenting hematocrit ranging between 58–64% (hemoglobin 19–22 g/dL). The serum erythropoietin level was elevated at diagnosis, and gradually rose to values greater than 5000 mU/ml. Extensive imaging did not reveal a source of erythropoietin production, and evaluations incluing hemoglobin electrophoresis, hemoglobin oxygen affinity, and gene sequencing were negative. An IgG-kappa monoclonal gammopathy was identified, at similar concentrations of approximately 0.7g/dL, without hypercalcemia or lytic bone lesions, and the bone marrow biopsies revealed fewer than 10% plasma cells, consistent with a diagnosis of monoclonal gammopathy of undetermined significance (MGUS). The progressive accumulation of bilateral perinephric fluid collections is a striking and unique feature of the syndrome. There were no intraparenchymal renal cysts; the fluid was localized between the kidney and the renal capsule. Sampling of the fluid revealed a clear, aseptic, serous fluid with low protein, few leukocytes, and no cholesterol or triglycerides. Microscopic intrapulmonary shunting was identified, and slowly progressed with worsening hypoxia and shortness of breath. There was no evidence of pulmonary hypertension on echocardiogram or right heart catheterization. All three patients have suffered spontaneous venous thromboses, and two of the patients suffered spontaneous intracranial hemorrhages without identifiable arterio-venous malformations on MRI/MRA or cerebral angiography.

The pathophysiology underlying the TEMPI syndrome is unknown. The similar characteristics shared by patients of different ages, genders, and geographies suggest an acquired rather than an inherited disorder. The presence of an IgG-kappa paraprotein in all three patients is suggests that the paraprotein might be involved in the pathophysiology of this disease. One of the patients underwent empiric treatment with the proteasome inhibitor bortezomib, with dramatic improvement in her symptoms after six cycles of therapy. The telangiectasias resolved, the level of serum erythropoietin normalized, the monoclonal gammopathy disappeared, the perinephric fluid collections resolved, and the degree of intrapulmonary shunting decreased to the point that she was able to discontinue her supplemental oxygen. Based on her clinical improvement, the decision was made to treat the other patients similarly. We will report in detail the characteristics of this novel syndrome as well as the treatment results. The response of one patient to the treatment of her MGUS suggests that the monoclonal gammopathy is involved in this syndrome by a mechanism that remains to be defined.