Christian De Gennes

Cardiac Sarcoidosis: A Retrospective Study of 41 Cases

Abstract: This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids. Abbreviations: CS = cardiac sarcoidosis, ECG = electrocardiogram, NYHA = New York Heart Association.

Long-term outcome of 32 patients with chorea and systemic lupus erythematosus or antiphospholipid antibodies.

The aim of this work was to describe chorea during systemic lupus erythematosus or antiphospholipid antibodies and its long‐term outcome.

Hydroxychloroquine-Induced Pigmentation in Patients With Systemic Lupus Erythematosus: A Case-Control Study

IMPORTANCE Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising. OBJECTIVE To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE). DESIGN, SETTING, AND PARTICIPANTS In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ. MAIN OUTCOMES AND MEASURES The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses. RESULTS Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration. CONCLUSIONS AND RELEVANCE Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.

Gastrointestinal manifestations in mastocytosis: A study of 83 patients

BACKGROUND Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in 1 or more organs. Gastrointestinal manifestations of systemic mastocytosis have been previously studied in small cohorts of patients, and no specific histologic description is available. OBJECTIVE We sought to assess the clinical and pathologic features of gastrointestinal manifestations in patients with mastocytosis. METHODS Medical history and gastrointestinal symptoms of patients with mastocytosis (n = 83) were compared with those of matched healthy subjects (n = 83) by means of patient questionnaire. Data were analyzed for epidemiologic, clinical, biological, and genetic factors associated with gastrointestinal symptoms for patients with mastocytosis. A comparative analysis of gastrointestinal histology from patients with mastocytosis (n = 23), control subjects with inflammatory bowel disease (n = 17), and healthy subjects (n = 19) was performed. RESULTS The following gastrointestinal symptoms occurred more frequently and were more severe in patients with mastocytosis than in healthy subjects: bloating (33% vs 7.2%, P < .0001), abdominal pain (27.3% vs 4.8%, P < .0001), nausea (23% vs 8.4%, P = .02), and diarrhea (33.85% vs 1.2%, P < .0001). Patients with mastocytosis had a significantly higher incidence of personal history of duodenal ulcer (P = .02). Wild-type (WT) c-Kit was associated with diarrhea (P = .03). Specific histologic lesions were present in patients with mastocytosis but were not correlated with clinical symptoms. CONCLUSION Gastrointestinal manifestations in patients with mastocytosis are highly prevalent and often severe. Clinical symptoms do not correspond to histologic findings, are nonspecific, and can simulate irritable bowel syndrome.

Blood CD34−c-Kit+ cell rate correlates with aggressive forms of systemic mastocytosis and behaves like a mast cell precursor

Mastocytosis is a heterogeneous disease characterized by the accumulation of mast cells in one or more organs. Our objective was to identify a peripheral mast cell precursor and assess its variation rate in mastocytosis. A peripheral blood phenotypic analysis was performed among 50 patients with mastocytosis who were enrolled in a prospective multicentric French study, and the phenotypic analysis results of the patients were compared with those of healthy donors. The rate of peripheral blood CD34(-)c-Kit(+) cells correlated with the severity of mastocytosis. This cellular population was isolated from healthy donors as well as from patients with systemic mastocytosis. After 30 days of culture, the CD34(-)c-Kit(+) cells gave birth to mature mast cells, indicating that this cellular population constitutes a mast cell circulating precursor. Monitoring peripheral CD34(-)c-Kit(+) cells by flow cytometry could be a useful and low-invasive tool to determine the disease severity and the relapses and to assess treatment efficiency.

Leukocyte telomere length in mastocytosis: Correlations with depression and perceived stress

BACKGROUND Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems. Negative emotionality has been shown to be associated with telomere shortening. Taken together these observations led us to hypothesize that mast cells activity could be involved in both negative emotionality and telomere shortening in mastocytosis. OBJECTIVE To demonstrate a possible relationship between negative emotionality in mastocytosis and leukocytes telomere length. METHODS Leukocyte telomere length and telomerase activity were measured among mastocytosis patients and were correlated with perceived stress and depression assessed by the Beck Depression Inventory revised and the Perceived Stress Scale. RESULTS Mild-severe depression scores were frequent (78.9%) as well as high perceived stress (42.11%). Telomere length was correlated to perceived stress (r=0.77; p=0.0001) but not to depression in our population. Patients displaying Wild-type KIT significantly presented higher perceived stress levels. Patients with the D816VC KIT mutation who had high perceived stress scores displayed significantly shorter telomere but not if they had high depression scores. CONCLUSION These findings suggest that high perceived stress in mastocytosis could accelerate the rate of leukocytes telomere shortening. Since mastocytosis is, by definition, a mast cell mediated disease; these cells could be involved in this phenomenon. Mechanistic causal relationships between these parameters need to be investigated.

Hypertrophic Osteoarthropathy and Follicular Thyroid Cancer: A Rare Paraneoplastic Syndrome

Background: Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. Objectives: Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare - only 2 cases have been described in the literature. Results: We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of 131I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. Conclusion: HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine.

Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

AbstractMastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.

Horst Schleusener, 1933-2015

his inaugural lecture on ‘The Regulation of TSH Synthesis and Secretion’. Together with Jürgen Quabbe and Wolfgang Oelkers, he created a competitive, academic Department of Endocrinology at Steglitz. Thyroid research gained momentum in the 1960s due to innovations in biochemistry and nuclear physics in medicine and immunology. Radioimmunoassays were introduced in thyroid testing and these allowed functional diagnostics for the first time. Schleusener’s first PubMed-listed publication with his colleague F.A. Horster described the ‘biological test for the thyrotropic hormone’ [1] , and paved the way for further research. In 1967, together with K. Schimmelpfennig and F.A. Horster, he received the first Schöller-Junkmann prize, awarded by the German Endocrine Society (DGE). This award was Horst Schleusener passed away on 12 July 2015. From the late 1960s to the 1990s of the last century, he was a leading figure in thyroidology in Germany and Europe. Born, raised and educated in Berlin, a wartime city that then got divided, he studied medicine at the Free University, from which he graduated in 1959. His academic focus on the thyroid came about by serendipity. Once asked by Werner Scherbaum why he had become a thyroidologist, he revealed that Gotthard Schettler, the head of his medical department at the time (later to become director of the Heidelberg University Hospital), advised him to choose the organ that started with an alphabetic alliteration to his surname, i.e. ‘Schilddrüse’ (thyroid). He remained faithful to this organ throughout his professional life. After his internship, he went to work for 18 months with J. Maxwell McKenzie at the Canadian McGill University of Montreal, where he further characterised the long-acting thyroid stimulator. According to his wife Annerose Schleusener, who accompanied him, this must have been one of the happiest periods of his life. After his return to Germany, he established a research group funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF) and others. In 1969, he advanced to the senior position of ‘Oberarzt’ (consultant/senior registrar), and was in the group of physicians under Max Schwab, who developed the structure of internal medicine in the Klinikum Steglitz (now known as Campus Benjamin Franklin) in Berlin. In 1971, his habilitation treatise was approved and he gave Published online: October 28, 2015