P. Cathébras

Safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis: Data from the French Autoimmunity and Rituximab registry

Management of nonviral cryoglobulinemia vasculitis has yet to be defined. Rituximab has emerged as a novel and promising therapeutic alternative, but data are scarce. Our objective was to evaluate the safety and efficacy of rituximab in nonviral cryoglobulinemia vasculitis in off‐trial real‐life patients.

The spectrum of type I cryoglobulinemia vasculitis: new insights based on 64 cases.

AbstractType I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.

Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a thrombotic microangiopathy complicating pregnancy and shares many clinical and biological features with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is also a pathological feature of catastrophic antiphospholipid syndrome (CAPS). An association between refractory HELLP syndrome and antiphospholipid syndrome (APS) has been reported in a few cases. We describe a 19-year-old woman with APS and multiorgan failure conforming to a diagnosis of CAPS who developed refractory HELLP syndrome.

Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study

OBJECTIVE We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study. METHODS In this study, 123 patients with MDS and SIADs were analysed. RESULTS Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5). CONCLUSION The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.

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.

Lupus érythémateux disséminé survenant après 65 ans

Resume Propos. – Le lupus erythemateux dissemine revele chez des sujets âges a ete peu etudie (une serie de 21 patients de plus de 65 ans publiee). La prise en charge de cette maladie est-elle modifiee dans cette population ? Methodes. – Dix-sept cas de lupus ayant debute apres 65 ans et hospitalises entre 1988 et 2000 sont rapportes retrospectivement. Les resultats sont compares a ceux de sujets plus jeunes. Resultats. – Le sex-ratio femme/homme est a 1,83. L’âge moyen lors de la survenue du premier signe est de 71,9 ± 3,5 ans. La duree moyenne de suivi est de 3,5 ± 2,4 ans. Les principaux signes initiaux sont une alteration de l’etat general (41 %), des manifestations articulaires (35 %), cutanees (35 %), thromboemboliques (24 %) et des pleuresies (18 %). Le rash malaire est exceptionnel (12 %). La nephropathie n’est jamais revelatrice et rarement severe au cours de l’evolution. Comme pour les atteintes neurologiques, l’etiologie doit etre discutee en tenant compte des comorbidites. Sur le plan hematologique, la lymphopenie (82 % des patients) a une specificite contestable. Les anticorps antinucleaires sont constants, avec des anti-ADN natifs dans 82 % des cas, des anticorps anti-antigenes nucleaires solubles dans 50 %, un anticoagulant circulant dans 59 %. Le pronostic est difficile a estimer sur une petite serie, mais la probabilite de survie a 5 ans est de 83 %. La corticotherapie a entraine 50 % de complications graves. Conclusions. – Cette etude permet surtout d’insister sur les manifestations revelatrices particulieres du lupus erythemateux dissemine chez le sujet âge (alteration de l’etat general, thromboses, signes cutanes atypiques), ainsi que sur les difficultes specifiques du diagnostic differentiel et du traitement.

An unusual cause of spontaneous bleeding in the intensive care unit – mastocytosis: a case report

We report the case of a 39-year old male patient who presented with anaphylactoid shock and diffuse bleeding with prolonged activated partial thromboplastin time at the emergency room. The diagnosis of aggressive mastocytosis was suspected and then confirmed by raised tryptase level and mastocytic infiltration of the bone marrow. The outcome was favorable with supportive measures, antihistamine drugs, and imatinib mesylate.

Acute camptocormia induced by olanzapine: a case report.

IntroductionCamptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder.Case presentationA 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L). Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later.ConclusionsCamptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug-induced rhabdomyolysis, in patients presenting with acute-onset bent spine syndrome. Although rare, the occurrence of camptocormia induced by olanzapine must be considered.

Éruption et syndrome néphrotique, penser à la syphilis

Resume Introduction Parmi les manifestations cliniques de la syphilis secondaire figure la nephropathie, comme en temoigne cette observation. Observation Chez un homme de 63 ans, a l’occasion d’une syphilis secondaire confirmee par les examens serologiques, est survenu un syndrome nephrotique correspondant a une glomerulonephrite extra-membraneuse de type 1 a la biopsie renale. Commentaires La glomerulonephrite extra-membraneuse est une complication immunologique de la syphilis secondaire. D’evolution presque toujours favorable sous traitement, elle est souvent associee a des manifestations pouvant orienter a tort vers une connectivite.

L'hémolyse: une cause d'erreur dans l'interprétation de l'hémoglobine glycosylée

Hemoglobin A1c (HbA1c), measured regularly in the patients with diabetes, is the major form of stable glycated hemoglobin and has to be maintained below 6.5% to prevent or decrease the risk of chronic complications. HbA1c reflects mean blood glucose levels of the previous 3 months. We report the case of a particularly low HbA1c in a diabetic patient despite high plasma glucose levels, that was induced by auto-immune hemolysis related to an Evans syndrome. All hemolytic disorders can be responsible for falsely reassuring HbA1c values. Clinicians must be aware that hematologic status has to be considered for the correct interpretation of HbA1c results.