M. Pavic

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: A multicenter survival analysis of 53 patients

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

Igg4-related Systemic Disease: Features and Treatment Response in a French Cohort

AbstractIgG4-related systemic disease is now recognized as a systemic disease that may affect various organs. The diagnosis is usually made in patients who present with elevated IgG4 in serum and tissue infiltration of diseased organs by numerous IgG4+ plasma cells, in the absence of validated diagnosis criteria. We report the clinical, laboratory, and histologic characteristics of 25 patients from a French nationwide cohort. We also report the treatment outcome and show that despite the efficacy of corticosteroids, a second-line treatment is frequently necessary. The clinical findings in our patients are not different from the results of previous reports from Eastern countries. Our laboratory and histologic findings, however, suggest, at least in some patients, a more broad polyclonal B cell activation than the skewed IgG4 switch previously reported. These observations strongly suggest the implication of a T-cell dependent B-cell polyclonal activation in IgG4-related systemic disease, probably at least in part under the control of T helper follicular cells.

Late-Onset Combined Immune Deficiency: A Subset of Common Variable Immunodeficiency with Severe T Cell Defect

BACKGROUND Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001). CONCLUSIONS LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.

Sarcoidosis and melanoma: a referral center study of 1,199 cases.

Background: Case reports and small short case series have described patients with sarcoidosis and melanoma. Objectives: To examine the relation between sarcoidosis and melanoma. Methods: Computerized search of all patients seen at our department of dermatology between 1998 and 2007 and review of the literature using a Medline search from 1985 to June 2008. Results: We identified 7 cases in our population of 1,199 melanoma inpatients. Including these cases, 20 cases of sarcoidosis have been described in melanoma patients. Fifteen patients had their sarcoidosis diagnosed after melanoma. In 7 cases, sarcoidosis was related to immunotherapy. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. Conclusion: Our referral center study shows a prevalence of sarcoidosis of 0.58% among melanoma inpatients. Clinicians should be aware of the possibility that sarcoidosis may initially manifest itself in melanoma patients, especially after treatment with immunotherapy, and mimic metastatic disease.

Retrospective study of intravascular large B-cell lymphoma cases diagnosed in Quebec: A retrospective study of 29 case reports

Introduction: Intravascular large B-cell lymphoma (IVL) is an extremely rare malignancy, mainly studied through European and Asian series. Due to the low incidence of this condition, our understanding of the clinical presentation as well as the management of IVL relies on a limited number of patients. We report the largest North American study to date on IVL with 29 cases from Quebec hospital diagnosed between 1990 and 2016. The aim of our study is to describe the clinical presentations, diagnostic and staging procedures, therapeutic management and clinical outcomes of IVL patients in our population and compare the disease phenotype to European and Asian series reported. In our cohort, all patients had stage IV IVL at diagnosis, with a median age of 66.7 years (range 47.2–90.8). Clinical presentation was characterized by constitutional symptoms (100%), poor ECOG-PS (100% ≥ 2), cytopenias (93% anemia), and elevated lactate dehydrogenase (97%) and C-reactive protein (96%). Our cohort presented with mainly cutaneous and neurological symptoms. However, neurological involvement (75.9%) was predominant and no “cutaneous variant” was observed; this differs from European literature, where “classical” IVL is reported with mainly cutaneous involvement. Two of our Caucasian patients presented “Asian variant” IVL; this observation is not unusual, as cases of “classical” IVL have been reported in Asians and “Asian variant” IVL has been reported in Europeans. All patients were classified according to their immunophenotypic features in 3 different subgroups (CD5+ or CD5−CD10+, CD5−CD10−, CD5+CD10−) with no difference in outcome. Finally, 62% of our cohort received anthracycline-based chemotherapy and 53% of them achieved a complete response. After a median follow-up of 328 days, OS at 3 years was 42.7% for the entire cohort and 47.4% for the cases with in vivo diagnosis. Conclusion: Unlike European studies on “classical” IVL, our study showed that the French Canadian presentation of this subtype of IVL is more frequently observed with neurological rather than cutaneous involvement. Finally, an early diagnosis is of primary importance since almost a quarter of patients receive a post-mortem diagnosis. A prompt diagnosis allows the introduction of an early treatment, associated with a CR in 53% of patients.

Sarcoidosis Occurring After Solid Cancer: A Nonfortuitous Association

AbstractThe association between cancer and sarcoidosis is controversial. Some epidemiological studies show an increase of the incidence of cancer in patients with sarcoidosis but only few cases of sarcoidosis following cancer treatment have been reported.We conducted a retrospective case study from internal medicine and oncology departments for patients presenting sarcoidosis after solid cancer treatment. We also performed a literature review to search for patients who developed sarcoidosis after solid cancer. We describe the clinical, biological, and radiological characteristics and outcome of these patients.Twelve patients were included in our study. Various cancers were observed with a predominance of breast cancer. Development of sarcoidosis appeared in the 3 years following cancer and was asymptomatic in half of the patients. The disease was frequently identified after a follow-up positron emission tomography computerized tomography evaluation. Various manifestations were observed but all patients presented lymph node involvement. Half of the patients required systemic therapy. With a median follow-up of 73 months, no patient developed cancer relapse. Review of the literature identified 61 other patients for which the characteristics of both solid cancer and sarcoidosis were similar to those observed in our series.This report demonstrates that sarcoidosis must be considered in the differential diagnosis of patients with a history of malignancy who have developed lymphadenopathy or other lesions on positron emission tomography computerized tomography. Histological confirmation of cancer relapse is mandatory in order to avoid unjustified treatments. This association should be consider as a protective factor against cancer relapse.

Severe IgA-mediated autoimmune haemolytic anaemia in Hodgkin lymphoma: A very rare event

Autoimmune diseases are frequently observed in patients with lymphoma. Amongst 519 patients with a Hodgkin lymphoma, 45 (8.6%) had an associated immune disease, predominantly thyroidal disorders including thyroiditis and Graves’ disease (31 cases); one had autoimmune haemolytic anaemia (AIHA) [1]. Amongst 72 patients with warm antibody (Ab) AIHA, Genty et al. [2] identified one patient with a Hodgkin lymphoma. In a review of 71 patients with Hodgkin lymphoma, Levine et al. [3] found seven patients with a positive direct antiglobulin test (DAT) on red blood cells (RBC), all of whom were male with an extensive pathology. They noted that the presence of a positive DAT in Hodgkin lymphoma patients was related to extensive and symptomatic disease and not to a poor prognosis. AIHA alone [4,5] or associated with an immune thrombocytopoenia [6] may reveal a Hodgkin lymphoma. This report presents an original case of a severe IgAmediated AIHA in a patient with Hodgkin lymphoma in remission, with no relapse after this episode of AIHA. A 21-year-old man presented with asthenia and dyspnea but no other symptom, such as fever, loss of weight, pain, sweating, adenopathy, hepatomegaly or splenomegaly, was reported. At this time, patient physical examination was normal and no treatment was given. Two years before, the patient had received 6 cycles of chemotherapy with adriamycin, bleomycin, vinblastine and dacarbazine and radiotherapy (30 þ 10 Gy) for a Hodgkin lymphoma with thoracic adenopathy and pericarditis (stage II B, nodular sclerosis) and disease remission had followed. Anaemia (haemoglobin 87 g l, haematocrit 25.8%, RBC count 2.46 10 l, macrocytosis 107 fl, reticulocyte count 3346 10 l and schizocyte negative) was observed but without evidence of leucopoenia or thrombocytopoenia. Hyperbilirubinaemia (48 mmol l) was associated with a sharp drop in haptoglobin level to below 0.2 g l. The patient had elevated lactate dehydrogenase level (1007 IU l), but alanine aminotransferase (14 IU l), aspartate aminotransferase (42 IU l), C-reactive protein (less than 5.0 mg l), fibrinogen (2.84 g l) levels, activated cephalin time (32 s vs. 36 s in control), prothrombin time test (73% vs. normal range 70 – 100%) and haemoglobin electrophoresis were all normal. There was no evidence of paroxysmal nocturnal haemoglobinuria clone. Abdominal and thoracic tomography scan of the patient, 2-[18F] fluoro-2-desoxy-D-glucose positron emission tomography and bone marrow biopsy showed no relapse of Hodgkin lymphoma. Haemocultures, urine cytobacteriological tests, viral (Cytomegalovirus, Epstein Barr virus, HIV) and Mycoplasma pneumoniae serologies were negative. No infectious disease was diagnosed. Antinuclear, anti-ssDNA and anti-neutrophil cytoplasmic Ab were negative and serum T3, T4 and thyrotropic hormones levels were normal. A haemolytic anaemia was suspected. Anaemia remained unchanged for 2 days (D) and haemolysis was confirmed, but aetiology was not determined. On D8, because the anaemia was getting

Maladies auto-immunes et cancers. Première partie : cancers au cours des maladies auto-immunes et de leur traitement

The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjögrens syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs.

Axitinib-induced acute pancreatitis: a case report.

Axitinib is an oral second-generation selective inhibitor of vascular endothelial growth factor receptors recently approved for the treatment of advanced renal cell carcinoma. Numerous cases of acute pancreatitis have been reported after treatment with nonselective tyrosine kinase inhibitors such as sorafenib and sunitinib. We present the first report of a patient under axitinib treatment presenting with acute pancreatitis for which no other etiology has been found. The patient was a 29-year-old woman treated for renal cell carcinoma. The patient had no history of chronic illness, gallstone-related disease, or alcohol consumption. She had been previously treated with sunitinib and everolimus. Four months after the onset of axitinib treatment she was hospitalized for acute pancreatitis. Symptoms and blood lipase levels normalized within a few days after axitinib was withheld. We believe that acute pancreatitis should be recognized as a potential axitinib-related adverse event.

Mise au pointMaladies auto-immunes et cancers. Première partie : cancers au cours des maladies auto-immunes et de leur traitementAutoimmune diseases and cancers. First part: Cancers complicating autoimmune diseases and their treatment

The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjögrens syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs.