TEMPI syndrome: difficult to diagnose, "easy" to treat?

TEMPI syndrome is a rare, acquired disorder with multisystemic manifestations. It is classified as a plasma cell disorder and is characterized by telangiectasias, erythrocytosis, monoclonal gammopathy, perinephric fluid collections and intrapulmonary shunt. Even though TEMPI's pathophysiology remains elusive, it responds to anti-myeloma therapy indicating that the monoclonal protein or clone plays a key role. We present a challenging case of a 73-year-old man with erythrocytosis and deteriorating renal function with nephrotic-range proteinuria in whom after extensive work up, the diagnosis of TEMPI syndrome was made. He was received treatment with daratumumab-bortezomib-cyclophosphamide and dexamethasone (Dara-VCD) and achieved a hematological and clinical response. We also report preliminary data on a multiplex assay for cytokines and growth factors for two patients with TEMPI syndrome and note lower levels for non-specific innate immunity related cytokines. A direct link between renal impairment and TEMPI syndrome is not currently established; cytokine deregulation could potentially be involved in the ischemic changes observed in the renal biopsy of our patient.

Successful Treatment of the TEMPI Syndrome with Pomalidomide Plus Dexamethasone Followed by Autologous Stem Cell Transplantation.

TEMPI syndrome is a rare disease associated with plasma cell neoplasms. Although previous studies have reported that bortezomib is effective as a first-line treatment for TEMPI syndrome, some cases are refractory to this treatment. Pomalidomide, a kind of immunomodulatory drug, is widely used for the treatment of relapsed or refractory multiple myeloma and could be administered without dose modification in patients with renal dysfunction. We present a case of bortezomib-refractory TEMPI syndrome with renal insufficiency that was successfully treated with a combination of pomalidomide and low-dose dexamethasone with minimal adverse effects, followed by autologous hematopoietic stem cell transplantation (ASCT). To the best of our knowledge, this is the first case of TEMPI syndrome that was successfully treated with pomalidomide. Pomalidomide may be suitable for patients who do not respond to a proteasome inhibitor-based treatment. In addition, a subsequent ASCT could also be effective for achieving a further treatment response.

Complete Remission in a TEMPI Syndrome Treated with a Daratumumab, Lenalidomide, and Dexamethasone-Based Regimen: A Case Report.

Introduction: TEMPI syndrome is a rare and acquired condition which is characterized by five classical features: telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. The classical treatment is based on bortezomib which can achieve variable responses. Relapse or refractory disease may occur, so other treatment strategies can be proposed. Case Presentation: We describe the case of a 54-year-old male followed for a refractory TEMPI syndrome who achieved complete remission after a second-line therapy composed of daratumumab-, lenalidomide-, and dexamethasone-based regimen (DLd). He achieved a complete remission with dramatic improvement of his renal function, restitution of a normal blood oxygen, and disappearance of polycythemia. Conclusion: This case highlights the effectiveness of an association of DLd to treat refractory TEMPI syndrome. We also provide arguments for an association between TEMPI syndrome and monoclonal gammopathy of renal significance.

Ocular involvement in TEMPI syndrome.

Purpose: We report the first case of ocular involvement in TEMPI syndrome, a rare disease characterized by telangiectasias, elevated erythropoietin with erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intra-pulmonary shunting. Observations: A 64-year-old Caucasian man with history of TEMPI syndrome presented with subacute bilateral painless vision loss. Ocular examination showed chronic retinal ischemia with microvascular damage, which was likely associated with the chronic systemic hypoxemia, and spontaneous wax and wane of cystoid macular edema, presumedly related to the systemic bortezomib treatment. Conclusions and importance: Our case demonstrates that pathologic retinal vascular changes could be seen in association with TEMPI syndrome and suggests that a comprehensive ophthalmological examination may be beneficial for these patients.

Case Report: TEMPI syndrome: Report of three cases and treatment follow-up.

The TEMPI syndrome is a novel and rare disease with five distinct clinical features: Telangiectasis, Erythrocytosis, Monoclonal gammopathy, Perinephric fluids collection, and Intrapulmonary shunting. Here, we report three cases of TEMPI syndrome and their treatment response. The three patients were presented to our department with polycythemia, abdominal distension, and dyspnea. On admission, all patients manifested telangiectasis, erythrocytosis, monoclonal gammopathy, and intrapulmonary shunting. Patient 1 and 2 manifested perinephric fluids collection. In addition, all patients had skin pigmentation, patient 1 and 2 had polyserosal effusion, two symptoms that had not been associated with TEMPI syndrome before. The three patients showed various response to plasma cell-directed therapy. We demonstrated their treatment response by measuring erythropoietin, hemoglobin, and M protein levels throughout therapy. This report suggested that TEMPI syndrome is a rare yet treatable disease. The diagnosis and treatment of it remain challenging.

Long-Term Complete Clinical and Hematological Response With Bortezomib: The Report of a Case With TEM(P)I Syndrome and a Review of the Literature.

TEMPI syndrome was first defined in 2011 and classified as a plasma cell neoplasm with associated paraneoplastic syndrome in 2016. The pathogenesis of the syndrome is not well understood. Recognition of a combination of telangiectasia, erythrocytosis with a high erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunt is the first step in managing the disease. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other dermatological, renal, and pulmonary disorders. Without early diagnosis significant disability results from the pulmonary damage. The article we present here describes a clinical case of TEMPI-syndrome in a 58-year-old woman, which illustrates the difficulties associated with the timely recognition of this unusual disease. Here, we also review the clinical features of TEMPI syndrome, differential diagnosis and available treatment options, based on current literature. Although limited in number, with the addition of new patients to the literature, TEMPI syndrome is evolving into a well characterized multisystem syndrome. This rare disorder should not be missed, especially if the patient has a putative diagnosis of essential telangiectasia with a monoclonal gammopathy and polistemia. Increasing the awareness of clinicians about the disease and adding new patient data to the literature may contribute to a better understanding of the pathophysiology of the disease and standardization of treatment.

TEMPI Syndrome: Update on Clinical Features, Management, and Pathogenesis.

TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is a rare and newly defined multisystemic disease, which belongs to "monoclonal gammopathy of clinical significances". Due to its rarity, the etiology, pathogenesis, and clinical features of this disease remain largely unknown. Owing to its hidden and diverse clinical manifestations, missed diagnosis and misdiagnosis are common. In recent years, as more patients (including three fatal cases) were identified, some special clinical manifestations other than the typical pentad of TEMPI syndrome have been reported. Meanwhile, several studies attempting to identify the pathogenesis of TEMPI syndrome were conducted. In this review, we summarize the reported clinical characteristics of TEMPI syndrome and discuss the current and potential treatment options for patients with TEMPI syndrome, including those with relapsed/refractory disease. Furthermore, we provide an overview of current knowledge on the pathophysiology of TEMPI syndrome.

The First Case of TEMPI Syndrome in Japan.

TEMPI syndrome, a disease entity comprising telangiectasia, erythrocytosis with high erythropoietin, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting, was first described by Sykes et al. in 2011. To our knowledge, only 15 cases have been reported worldwide, none of which were in Japan. We herein report a 47-year-old man who had intractable ascites for 2 and a half years and was referred to our department for a peritoneovenous shunt. In addition to ascites, he had telangiectasia, high erythropoietin, monoclonal gammopathy, and perinephric fluid collection. Thus, this is the first case of TEMPI syndrome in Japan.