[Show abstract][Hide abstract] ABSTRACT: Objectives
We studied the clinical phenotypes and tolerance to treatments in a series of patients affected by both inflammatory joint diseases and mastocytosis.
This retrospective multicenter study was conducted on behalf of 3 networks, focused on mastocytosis, pediatric and adults’ inflammatory joint diseases respectively. Patients who displayed both mastocytosis and inflammatory joint diseases were included.
Thirty-one patients were included. They had spondyloarthritis (SpA) (16 patients), rheumatoid arthritis (6 patients), juvenile idiopathic arthritis (2 patients), and undifferentiated arthritis (7 patients). The median ages at diagnosis of arthritis rheumatism and mastocytosis were 44 and 40.5 years respectively. Disease-modifying anti-rheumatic drugs (DMARDs) were required in 22 patients, comprising mostly methotrexate (13 patients), salazopyrine (8 patients), anti-tumor-necrosing-factor agents (7 patients) and corticosteroids (9 patients). They were well tolerated. Adverse events occurred in 2/24 patients receiving non-steroidal anti-inflammatory drugs. The prevalence of SpA among the 600 patients included in the mastocytosis cohort was 2.33%, which is significantly higher than the prevalence of SpA in the French population (p< 0.001).
This study suggests that mastocytosis is associated with a higher prevalence of SpA than expected, and that DMARDs, notably anti-TNFα agents, are well tolerated in patients with mastocytosis. Mast cells might be involved in the development of SpA.
Seminars in Arthritis and Rheumatism 12/2014; 44(3). DOI:10.1016/j.semarthrit.2014.05.016 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hidradenitis suppurativa (HS) is a skin disease characterized by recurrent nodules or abscesses and chronic suppurating lesions. In the absence of clear pathophysiology, HS is considered to be an inflammatory disease and has no satisfactory medical treatment. Recently, prolonged antimicrobial treatments were shown to improve or resolve HS lesions. We prospectively studied the microbiology of 102 HS lesions sampled from 82 patients using prolonged bacterial cultures and bacterial metagenomics on 6 samples. Staphylococcus lugdunensis was cultured as a unique or predominant isolate from 58% of HS nodules and abscesses, and a polymicrobial anaerobic microflora comprising strict anaerobes, milleri group streptococci, and actinomycetes was found in 24% of abscesses or nodules and in 87% of chronic suppurating lesions. These data show that bacteria known to cause soft tissue and skin infections are associated with HS lesions. Whether these pathogens are the cause of the lesions or are secondary infectious agents, these findings support targeted antimicrobial treatment of HS.
[Show abstract][Hide abstract] ABSTRACT: Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients.
[Show abstract][Hide abstract] ABSTRACT: Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide "RetroZygo" study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p < 0.0001), frequency of cutaneous localization (87% vs 7%, p < 0.0001), short time before diagnosis (4.5 vs 21 d, p = 0.0002), species involved (Apophysomyces elegans complex and Saksenaea vasiformis), surgical requirement (93.7% vs 47%, p = 0.0006) and better survival (87.5% vs 47.6% at day 90, p = 0.03). We studied 122 cases of posttraumatic mucormycosis through our literature review. Most frequently reported traumas were traffic (37%), domestic accidents (15.1%), or natural disasters (13.4%). Mucormycosis occurred after extensive soft-tissue damage in 47.5% cases, with symptoms occurring a median of 9.5 days after trauma with necrosis being reported in 76.2% cases. Dissemination was found in 9% of patients, and bacterial coinfection in 41%. Nineteen percent of cases occurred in the Middle East or in India where Apophysomyces elegans complex was the predominant species recovered. Awareness of mucormycosis as a cause of posttrauma soft-tissue infection is warranted, especially in cases of soil-contaminated wounds. Survival is higher than in other forms of mucormycosis, but morbidity remains high.
Medicine 11/2014; 93(24):395-404. DOI:10.1097/MD.0000000000000221 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Les infections à Nocardia sont graves. Les présentations cliniques et radiologiques étant multiples et non spécifiques, c’est souvent un terrain prédisposant qui fait suspecter le diagnostic. La confirmation diagnostique est microbiologique et repose sur des techniques de culture et de biologie moléculaire. La sensibilité des souches de Nocardia aux antibiotiques est corrélée à l’espèce responsable de l’infection et son évaluation impose une expertise. Le diagnostic d’espèce, nécessitant formellement le recours à des méthodes moléculaires, est un élément fondamental pour guider la thérapeutique. Une association d’antibiotiques comprenant au moins le cotrimoxazole est proposée en probabiliste en cas de forme grave, disséminée ou chez un patient immunodéprimé. L’amikacine, l’imipénem, le linézolide, la ceftriaxone et le cefotaxime sont les autres antibiotiques pouvant être prescrits en probabiliste. Les résultats microbiologiques (antibiogramme, identification d’espèce) et l’évaluation du terrain permettront de décider du traitement d’entretien (intraveineux ou oral, monothérapie ou association d’antibiotiques) adapté. Le traitement d’entretien est prolongé, de 6 à 12 mois, selon la localisation de l’infection, pour éviter les rechutes dans les formes invasives. Une prophylaxie secondaire peut être proposée, en cas de persistance d’un facteur favorisant. Il n’y a pas d’études comparatives ni prospectives sur lesquelles s’appuyer pour la prise en charge optimale de ces patients. De nouveaux schémas thérapeutiques restent à valider afin d’améliorer le pronostic des nocardioses.
Journal des Anti-Infectieux 11/2014; 16(4). DOI:10.1016/j.antinf.2014.10.001 · 0.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Isavuconazole (ISA) is a novel, broad-spectrum, triazole antifungal available as a water-soluble prodrug in IV and oral formulations for treatment of invasive fungal disease. A Phase 3 trial (NCT00412893) assessed the efficacy and safety of ISA vs voriconazole (VRC) in patients with invasive mold disease (IMD). Neutropenia is linked to significant morbidity and mortality in patients with IMD. We present outcomes in patients with and without neutropenia at baseline from this trial.
Methods: Patients with proven/probable/possible IMD (EORTC/MSG criteria) were randomized 1:1 to receive ISA or VRC for up to 84 days. Dosing regimens were: ISA 200mg IV TID for 2 days, then 200mg QD (IV or PO); VRC 6mg/kg IV BID on Day 1, 4mg/kg IV BID on Day 2, then either 4mg/kg IV BID or 200mg PO BID. The primary endpoint was all-cause mortality through Day 42. Overall success at end-of-treatment (EOT) as determined by an independent data-review committee (DRC), safety, and tolerability were also analyzed. Neutropenia was defined as per EORTC/MSG criteria.
Results: Patient characteristics, efficacy, and safety outcomes are shown in Table 1.
Conclusion: ISA has comparable efficacy to VRC for the primary treatment of IMD in neutropenic and non-neutropenic patients and may be better tolerated.
Table 1.Patient characteristics and outcomes
All treated patients (ITT), n
Proven/probable IMD (mITT), n
% (95% CI)
% (95% CI)
All-cause mortality Day 42
Overall success EOT
AEs, n (%)
Drug-related AEs, n (%)
*ISA–VRC (VRC–ISA for overall success)
ITT, intent-to-treat population (patients who received ≥1 dose of study drug); mITT, modified intent-to-treat population (patients in ITT with proven/probable IMD as assessed by DRC)
IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients.
[Show abstract][Hide abstract] ABSTRACT: Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
International Journal of Antimicrobial Agents 10/2014; 44(4). DOI:10.1016/j.ijantimicag.2014.07.003 · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Isolation rates of Candida glabrata at ≤2 days were 8.9%, and 34.8% at > 2 days; for Cryptococcus neoformans they were 0.9%, and 8.6% respectively (1741 fungemia analysed). An incubation time >2 days supports candins as presumptive treatment for C. glabrata, keeping in mind the risk of Cryptococcus fungemia.
[Show abstract][Hide abstract] ABSTRACT: Background
Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined.
We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization.
MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma.