Myocarditis in monkeypox-infected patients: a case series.

OBJECTIVES: Monkeypox, a zoonotic orthopoxvirus, has spread to many countries in recent months, involving mostly men who have sex with men with multiple partners. Clinical presentation includes skin lesions, systemic signs, and less frequent skin superinfections or anorectal and ophthalmic involvements. We aim to detail cases of myocarditis attributable to monkeypox, an entity that has been poorly described. METHODS: This is a descriptive case series reporting three cases of myocarditis that occurred in patients infected with monkeypox in France in 2022. RESULTS: Patients were adult men with no medical history who had skin lesions with positive polymerase chain reaction for monkeypox virus. A few days after the onset of cutaneous signs, patients developed acute chest pain, elevated cardiac markers, and biological inflammatory syndrome compatible with myocarditis. Two patients presented electrocardiogram abnormalities and decreased ejection fraction associated with kinetic disturbances on transthoracic electrocardiography. The last patient had normal transthoracic electrocardiography and normal electrocardiogram, but cardiac magnetic resonance imaging showed segmental inferolateral acute myocarditis. Patients were hospitalized and received cardioprotective treatment. One received antiviral treatment with tecovirimat. Symptoms and laboratory abnormalities rapidly resolved in all patients. DISCUSSION: These cases suggest an association between monkeypox infections and cardiac inflammatory complications. The development of chest pain in an infected patient should not be underestimated and should lead to prompt investigations for myocarditis. Monkeypox infection should also be included in the differential diagnosis of myocarditis, particularly in at-risk patients such as men who have sex with men with multiple partners in whom complete examination for skin or mucosal lesions should thus be performed.

[Argatroban in heparin-induced thrombocytopenia: A survey of prescribing practices and use in France]. / Argatroban et thrombopénie induite par l'héparine : observatoire des modalités de prescription et d'utilisation en France.

OBJECTIVE: A survey of prescribing practices was carried out in France to ensure that argatroban was used appropriately during the first 18months after it obtained marketing authorization for anticoagulation in adults with heparin-induced thrombocytopenia (HIT). METHODS: This observational study was proposed to public and private hospitals with at least 2 orders of argatroban. All patients who received at least one argatroban injection during the study period had to be included. Their demographic characteristics, the pathology causing heparin treatment, the indication of treatment with argatroban, as well as available real-life clinical and biological monitoring data were retrospectively collected. RESULTS: In the 23 participating centers, the drug was prescribed mainly by the following hospital units: surgery and intensive care (79.3%) (of which 18.3% cardiovascular), nephrology/hemodialysis (14.8%) and internal medicine (5.9%). Among the 169 patients included, with median age of 68 years, 118 (69.8%) had renal impairment (creatinine clearance <90mL/min). The HIT probability scoring and diagnostic tests used differed widely between the centers. The reasons for prescribing the drug were mainly suspected HIT (51.5%), declared confirmed HIT (21.3%) or a history of HIT (14.8%). Seventy-three (73) patients (43.2%) had thrombotic symptoms or a systemic reaction initially. The median initial dose prescribed was 0.5µg/kg/min (ranging from 0.05 to 4.42) and doses >2µg/kg/min were used during hemodialysis. More than half of the patients (58.6%) had no clinical complications. Most of the serious adverse reactions were hemorrhagic (11/12). CONCLUSION: This study illustrates the complexity of treatment for HIT and the need to be familiar with and follow guidelines on the management of HIT, especially for susceptible patients treated in intensive care units.

Management of haemophilia A-inhibitor patients: clinical and regulatory perspectives.

Inhibitors to factor VIII (FVIII) are alloantibodies directed against epitopes able to neutralise FVIII procoagulant activity. They may render FVIII replacement therapy ineffective. They represent the most severe complication of haemophilia A. At least three mechanisms of FVIII neutralisation activity by anti-FVIII antibodies have been described: (1) steric hindrance; (2) recognition of neo-epitopes and (3) catalytic activity. The Nijmegen modification of the Bethesda is the recommended method for inhibitor surveillance. The occurrence of inhibitors is a relatively frequent and early event in previously untreated patients. Conversely, it is rare in previously treated patients. Therapeutic strategies for managing inhibitors include: inhibitor eradication, haemostatic management of bleeding episodes and/or surgery and supportive care. For high responding inhibitors, immune tolerance induction (ITI) is the strategy for achieving antigen-specific tolerance to FVIII. ITI success rate ranges commonly between 60% and 80%. For treatment of patients with high-titre, high-responding inhibitors, 'by-pass' therapy is generally recommended. Activated prothrombin complex concentrates represent the historically primary 'by-pass' treatment. Recombinant factor VIIa has also been widely used as a by-passing agent. Considering the small patient population, it has to be considered that full immunogenicity data cannot be collected premarketing authorisation. Thus, stringent follow-up of patients in the post-authorisation phase is required.

Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A.

Von Willebrand factor (VWF) has been proposed to reduce the immunogenicity of therapeutic factor VIII (FVIII) in patients with hemophilia A. Using FVIII-deficient mice, we compared the immunogenicity of different preparations of plasma-derived (pd) and recombinant (r) FVIII. Treatment of mice with pdFVIII induced significantly lower titers of FVIII inhibitors, as measured by ELISA and in vitro coagulation assays, compared with rFVIII. Furthermore, pre-incubation of rFVIII with excess VWF significantly reduced rFVIII immunogenicity. Our data confirm that pdFVIII induces lower levels of inhibitors than rFVIII, and that VWF is an immuno-chaperone molecule for FVIII.

Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients.

OBJECTIVE: To compare long and short durations of adjunctive cyclophosphamide for the treatment of severe Churg-Strauss syndrome (CSS). METHODS: In this prospective multicenter therapeutic trial, 48 patients with CSS with at least 1 poor-prognosis factor at baseline were treated with glucocorticoids and either 12 or 6 intravenous cyclophosphamide pulses. RESULTS: At 8 years, complete remission rates and severe side effects of therapy were comparable for both groups. The overall difference in relapses was not significant between the 12-pulse and the 6-pulse regimens (P = 0.07), but when considering only the number of mild relapses this difference became statistically significant (P < 0.02). Although the total number of inclusions was not reached, the study was stopped prematurely in response to the superiority of the 12-pulse regimen. CONCLUSION: We concluded that 12 cyclophosphamide pulses were better able to control severe CSS than a 6-pulse regimen. The optimal duration of therapy remains to be determined.

Lymphoplasmacytic lymphoma associated with polyradiculoneuritis and cryoglobulinemia mimicking polyarteritis nodosa.

INTRODUCTION: Systemic vasculitis is sometimes associated with malignant blood disease. CASE: We describe the case of a 77-year-old woman who had extensive livedo racemosa, acute polyradiculoneuritis, and meningeal hemorrhage. The skin biopsy showed evidence of necrotizing angiitis. This vascular involvement resembled polyarteritis nodosa (PAN). Despite corticosteroid and cyclophosphamide treatment, the polyradiculoneuritis worsened and the patient died of acute respiratory failure. Type II cryoglobulinemia was detected late, and the autopsy revealed lymphoplasmacytic lymphoma involving the spleen and infiltrating nerve roots, together with necrotizing angiitis involving small-sized arteries. CONCLUSION: This case shows that necrotizing angiitis involving small arteries may occur with type II cryoglobulinemia.

[Simultaneous hepatitis B virus infection and polyarteritis nodosa. Three cases]. / La périartérite noueuse, complication immédiate d'une hépatite aiguë virale B. Trois observations.

In polyarteritis nodosa (PAN) due to hepatitis B virus (HBV) infection, the insidious nature of the infection makes very difficult to establish the chronology which often remains unknown. PN occurs in the majority of patients during the year following infection. Simultaneous occurrence or occurrence immediately after infection with the HBV is exceptional. We report here three cases of this form of simultaneous HBV infection and PN and describe the particular clinical, virological and evolutive features of the disease.

Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review.

OBJECTIVE: To analyze specific clinical findings, underlying disorders, treatments, outcomes, and prognostic factors for reactive hemophagocytic syndrome (RHS) in systemic disease. METHODS: Data were collected using standardized forms as part of a French national survey. Adult cases without an underlying malignancy, diagnosed on bone marrow or lymph node biopsy, were included. RESULTS: Twenty-six cases (7 men, 19 women, mean age 47.4 +/- 17.7 years) were studied. Systemic diseases included systemic lupus erythematosus (n = 14), rheumatoid arthritis (n = 2), adult onset systemic Still's disease (n = 4), polyarteritis nodosa (n = 2), mixed connective tissue disease (n = 1), pulmonary sarcoidosis (n = 1), systemic sclerosis (n = 1), and Sjögren's syndrome (n = 1). RHS occurred in 2 distinct clinical settings in the course of systemic disease. RHS was associated with an active infection in 15 patients (bacterial infections, 10 cases; viral, 3 cases; tuberculosis, 1 case; and aspergillosis, 1 case) and with the onset of a systemic disease alone in 9 cases. Isolated RHS occurred in 2 cases. The overall mortality rate was 38.5%. Two factors were associated with mortality: corticosteroid treatment at the time of RHS diagnosis, and thrombocytopenia (odds ratio = 28, 95% confidence interval = 13.3-238.9). CONCLUSIONS: When RHS occurs in the course of an active systemic disease (situation only reported in cases of systemic lupus or adult Still's disease), immunosuppressive therapy should be used. In contrast, when RHS is present concomitantly with an active infection, immunosuppressive therapy needs to be lowered and antibiotic therapy should be instituted.