Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation.

Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n = 12) or was diagnosed simultaneously with (n = 11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAF(V600E) mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.

Non HCV-related infectious cryoglobulinemia vasculitis: Results from the French nationwide CryoVas survey and systematic review of the literature.

In patients with infectious cryoglobulinemia vasculitis (CryoVas) in the absence of hepatitis C virus infection, data on presentation, therapeutic management and outcome are lacking. We conducted a nationwide survey that included patients with HCV-negative CryoVas. We describe here the presentation, therapeutic management and outcome of 18 patients with non-HCV infectious CryoVas and 27 additional patients identified form a systematic review of the literature. We included 18 patients, mean age 57.9±13.5 years. Infectious causes were viral infections in 8 patients [hepatitis B virus (HBV) in 4, and cytomegalovirus, Epstein Barr virus, parvovirus B19 and human immunodeficiency virus in one case each], pyogenic bacterial infection in 6 patients, parasitic infection in 2 patients, and leprosy and candidiasis in one case each. Baseline manifestations were purpura (78%), glomerulonephritis (28%), arthralgia (28%), peripheral neuropathy (22%), skin necrosis (22%), cutaneous ulcers (17%), and myalgia (11%). Cryoglobulinemia was type II in 2/3 of cases. Most cases received specific anti-infectious therapy as first-line therapy, sometimes associated with corticosteroids, achieving sustained remission in the majority of cases. Refractory or relapsing patients, frequently related to HBV infection, showed a complete remission after rituximab in addition to antiviral therapy. In contrast, corticosteroids and/or immunosuppressive agents used in the absence of anti-infectious agents were frequently associated with refractory CryoVas. Viral and pyogenic bacterial infections represent the main causes of non-HCV infectious CryoVas. Antimicrobial therapy is commonly associated with sustained remission. Immunosuppressive agents should be considered only as a second-line option in patients with refractory vasculitis.

Splenic infarction during Plasmodium ovale acute malaria: first case reported.

The splenic complications of acute malaria include two different prognostic and treatment entities: splenic infarction and splenic rupture. This is the first case of splenic infarction during an acute malaria due to Plasmodium ovale in a 34-year-old man. As in the majority other described cases of splenic infarction, the course was spontaneously favourable, suggesting that this complication was relatively benign compared to splenic rupture, which is life-threatening and usually necessitating surgery.

Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease.

PURPOSE: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. PATIENTS AND METHODS: Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). RESULTS: All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. CONCLUSION: Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.

[Respiratory manifestations of giant cell arteritis: 8 cases and review of the literature]. / Atteinte respiratoire de la maladie de Horton: 8 observations et revue de la littérature.

BACKGROUND: Pleural and pulmonary manifestations of giant cell arteritis are rare and not well known. They can be associated to more typical signs of the disease and to an inflammatory biological syndrome which are comprised in the multisystemic manifestations of the disease. They can be inaugural, leading to a late management if unrecognized. METHODS: Retrospective and descriptive study of 8 cases over a 10 year period was conducted. Five females and three males with a 67-year-old average age were included according to the American College of Rheumatology criteria. They illustrated the clinical and/or radiological respiratory manifestations of the disease. RESULTS: Pulmonary manifestation was inaugural in six cases over eight. The time to diagnosis range was 15-60 days. Cough was the most frequent symptom (five cases over eight). Dyspnea with orthopnea was described in one case. Pleural and parenchymal radiological manifestations had no specific characteristics: pleurisy, pleural thickening, nodules of variable size, reticular lesions. Temporal artery biopsy was positive in five cases, atypical in one case and negative in two cases. Bronchial and transbronchial biopsies (in two and one cases respectively) did not find any specific lesion. Clinical and radiological signs disappeared quickly after the introduction of glucocorticoid therapy. CONCLUSION: The knowledge of these different respiratory manifestations during giant cell arteritis (persistent cough, nodules, pleural effusion) is useful for the clinician. It helps him in prescribing non invasive investigations or even a presumptive glucocorticoid therapy, in an often old and weakened patient.

Three related cases of cutaneous anthrax in France: clinical and laboratory aspects.

Anthrax is an acute bacterial infection caused by Bacillus anthracis. The infection is cutaneous in about 95% of human cases and respiratory in about 5%. Approximately 2000 cases of cutaneous anthrax are reported annually worldwide. This disease became exceptional in Europe thanks to strict veterinarian monitoring. The last human cases of anthrax indicated in France were in 1997. We report 3 new related cases of naturally acquired cutaneous anthrax that occurred in France in 2008. The unique features of these cases include the atypical clinical presentation and the contribution of the rapid and specific diagnosis techniques by polymerase chain reaction.In cutaneous forms of anthrax, although the local course is not influenced by the treatment, antibiotic therapy is necessary to control any bacterial distribution. A case of exposure similar to that of a confirmed human case or an exposure identified by epidemiologic inquiry should usually result in chemoprophylaxis. Chemoprophylaxis for the close relations of a patient or for health workers is unnecessary since person-to-person transmission has not been reported.