Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.

bronchoalveolar lavage (BAL) specimens from 150 patients (19 HIV-infected and 131 non-HIV-infected patients) were evaluated for identification of Pneumocystis jiroveci (formerly known as Pneumocystis carinii f. sp. hominis) using staining techniques, conventional PCR (mtLSUrRNA gene) and real-time PCR (MSG gene). Test results were compared to Pneumocystis pneumonia (PCP) confirmed by typical clinical findings and response to treatment. Sensitivity and specificity of the techniques were 60 and 100 % for staining (where either one or both techniques were positive), 100 and 87 . 0 % for conventional PCR and 100 and 84 . 9 % for real-time PCR, respectively. The use of a concentration of 10 3 copies of DNA per capillary of BAL as a cut-off (determined by real-time PCR) increased specificity from 84 . 9 to 98 . 6 % without reducing the sensitivity of the technique. This technique is rapid (,3 h) and therefore of major interest in differentiating between asymptomatic carriage and PCP. A BAL specimen with ,10 3 copies per capillary of Pneumocystis-specific DNA is more likely to indicate a chronic carrier state, but in such cases follow-up is required to ensure that the patient is not in the early stage of an active PCP.

The cases of 52 patients with Propionibacterium acnes infection of orthopaedic implants are summarized: 20 patients with definite infection (sepsis, with P. acnes recovered from multiple specimens per patient), 15 with probable infection (sepsis, with P. acnes recovered from one specimen), and 17 with possible infection (signs of prosthetic malfunction or pseudo-osteoarthritis, with P. acnes recovered from one specimen). The patient population consisted of 37 males and 15 females with a mean age of 51.8 years (range 17-88). Besides bone surgery, 21% of these patients had severe coexisting illness. The study population was very heterogeneous and clinical presentation very polymorphic; infections became clinically apparent through sepsis, prosthetic malfunction, or a delay in consolidation. The diagnosis was highly dependent on the quality of the samples taken and the methodology used by the microbiology laboratory to isolate this bacterium. Culture time was long, on average 11.4 days. Treatment involved a combination of antibiotic treatments (67% of cases) and ablation of the material (83% of cases). Although P. acnes is considered to be weakly pathogenic, this bacterium may be responsible for infections in patients with implanted orthopaedic material. Ablation of the arthroplastic or osteosynthetic material is necessary in the majority of cases.

A retrospective study was undertaken to analyse the risk factors for systemic emboli in infective endocarditis. Patients (n = 80; 70% males; mean age 65 years; range 20-91 years) with infective endocarditis, as defined by the Duke criteria and diagnosed using transoesophageal echocardiography during the period January 1995 to March 2001, were included. The average time between the start of the illness and the beginning of antibiotic treatment was 55 days (range 0-405 days). The pathogens identified were streptococci (n = 47), staphylococci (n = 11), enterococci (n = 9), and others (n = 4). In nine cases, blood cultures were sterile. Thirty patients with at least one embolic episode were compared with 50 control patients. According to univariate analysis, the main risk factor for systemic emboli was the size of the vegetation (12.4 mm vs. 7.8 mm; p = 0.0005). The risk of emboli was 57% when the vegetation measured > 10 mm and only 22% when it was < 10 mm (p = 0.003). The mobility of the vegetation was also a risk factor: 48% if the vegetation was mobile; and 9% if fixed (p = 0.003). Sex, age, pathogen, antibiotic treatment, type of valve and the number and position of the vegetations were not found to be risk factors. With multivariate analysis, only mobility was identified as a risk factor. Overall, mobile vegetations > 10 mm in size were associated with an increased risk of embolic episodes in infective endocarditis.

Q fever is a worldwide-occurring zoonosis caused by Coxiella burnetii. Better knowledge of the disease and of evolving diagnostics can enable recognition of unusual manifestations. Reported here are four cases of Q fever osteoarticular infections in adults: two cases of Q fever tenosynovitis, which represent the first two reports of this infection, and two cases of Q fever spondylodiscitis complicated by paravertebral abscess. In addition, the literature is reviewed on the 15 previously reported cases of Q fever osteoarticular infection, six of which were vertebral infections. Osteomyelitis is the usual manifestation Q fever osteoarticular infection. Because its onset is frequently insidious, diagnosis is usually delayed. The main differential diagnosis is mycobacterial infection, based on the histological granulomatous presentation of lesions. Whereas serology is the reference diagnostic method for Q fever, detection of C. burnetii in tissue specimens by PCR and cell culture provides useful additional evidence of infection. Culture-negative osteoarticular samples with granulomatous presentation upon histological examination should raise suspicion of Q fever.