Management of Kaposi sarcoma after solid organ transplantation:A European retrospective study

Background: Systemic therapeutic management of post-transplant Kaposi sarcoma (KS) is mainly based on 3 axes: reduction of immunosuppression, conversion to mammalian target of rapamycin (mTOR) inhibitors, chemotherapy, or a combination of these.Objective: To obtain an overview of clinical strategies about the current treatment of KS.Methods: We conducted a multicenter retrospective cohort study including 145 solid organ transplant recipients diagnosed with KS between 1985 and 2011 to collect data regarding first-line treatment and response at 6 months.Results: Overall, 95%, 28%, and 16% of patients had reduction of immunosuppression, conversion to mTOR inhibitor, and chemotherapy, respectively. Patients treated with chemotherapy or mTOR inhibitor conversion were more likely to have visceral KS. At 6 months, 83% of patients had response, including 40% complete responses.Limitations: The retrospective design of the study.Conclusion: Currently available therapeutic options seem to be effective to control KS in most patients. Tapering down the immunosuppressive regimen remains the cornerstone of KS management.Dermatology-oncolog

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. Results: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Conclusions: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia

APPORT DE L'ELECTROCHIMIOTHERAPIE EN DERMATOLOGIE (ETUDES DE PHASE I-II DANS LA MALADIE DE KAPOSI ET LES METASTASES CUTANEES DE MELANOME)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Two observations raising questions about risk factors of cutaneous necrosis induced by Terlipressin (Glypressin (R))

Introduction: Triglycyl lysine vasopressin (terlipressin, Glypressin (R)) is a potent vasoconstrictive drug which became popular because of its prolonged duration of action, ease of administration and lower incidence of side effects. Ischemic complications are rare but may be life threatening. Observations: Case 1, a 68-year-old man with alcoholic cirrhosis and hepatocellular carcinoma, was admitted due to acute functional renal failure. He was first treated for septic shock with intravenous catecholamines. He then developed hepatorenal syndrome and received terlipressin as intravenous bolus (4 mg/day). Three days later, he presented a diffuse purpuric and necrotic eruption with tongue ischemia. He died from Staphylococcus aureus infection. Case 2, a 74-year-old man with metastatic carcinoma, presented severe renal insufficiency. He developed sepsis and pseudohepatorenal syndrome, which was treated with terlipressin (0.5 mg/h) using an infusion pump. Four days later, he developed an isolated large erythematous and purpuric macular plaque of the scalp near skin metastases. The patient died a few weeks later from tumor progression. In both cases, skin biopsies showed ischemic necrosis caused by thrombosis of superficial dermal capillaries. Conclusion: These cases point to the risk of either widespread or localized necrosis. Although the precise incidence of these events as well as risk factors remain to be determined, hypovolemia, concomitant administration of vasoactive drugs and the mode of administration of terlipressin may influence the occurrence of these complications. Copyright (C) 2009 S. Karger AG, Base

A French National Survey on Clotting Disorders in Mastocytosis.

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.status: publishe

Erratum to: Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

status: publishe