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International audience; Background: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging.Objective: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort.Methods: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized.Results: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse.Conclusions: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.

Context In 2012, the French Infectious Diseases Society (French acronym SPILF) initiated the “Coordination of epidemic and biological risk” (SPILF-COREB - Emergences [SCE]) group to support the readiness and response of healthcare workers (HCWs) to new alerts. Objective To present the SCE group, its functioning, and the main support it provided for frontline HCWs. Methods A multidisciplinary group of heads of infectious disease departments from reference hospitals was created to build a network of clinical expertise for care, training, and research in the field of epidemic and biological risk (EBR). The network developed a set of standardized operational procedures (SOPs) to guide interventions to manage EBR-suspect patients. Results A working group created the SOP aimed at frontline HCWs taking care of patients. Priority was given to the development of a generic procedure, which was then adapted according to the current alert. Five key steps were identified and hierarchized: detecting, protecting, caring for, alerting, and referring the EBR patient. The interaction between clinicians and those responsible for the protection of the community was crucial. The SOPs validated by the SPILF and its affiliates were disseminated to a wide range of key stakeholders through various media including workshops and the SPILF's website. Conclusion SPILF can easily adapt and timely mobilize the EBR expertise in case of an alert. The present work suggests that sharing and discussing this experience, initiated at the European level, can generate a new collective expertise and needs to be further developed and strengthened.

Presented in part at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 27–30 September 2006, San Francisco, CA, USA, Abstract M-1307; International audience; Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) uptake may be observed in the course of active inva-sive fungal infections. The aim of this study was to assess the role of positron emission tomography with [ 18 F]FDG ([ 18 F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [ 18 F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplanta-tion (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidia-sis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomyco-sis in one case each. An increased uptake of [ 18 F]FDG was observed in all areas previously identified by computed tomography and/ or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [ 18 F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [ 18 F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [ 18 F]FDG-PET was performed to assess the evolution of the disease. [ 18 F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [ 18 F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.

Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.

Autosomal dominant loss of function mutation of signal transducer and activator of transcription 3 (STAT3) gene (STAT3-deficiency) predisposes to recurrent bacterial pneumonia that are complicated in 67% of patients with bronchiectasis, cavitations and Aspergillus infection or colonization in 22% of patients1. We aimed to report the prevalence, describe clinical, mycological, pathological and radiological presentation and both medical and surgical treatment of mold infections in the National French cohort. Methods Referent physicians of STAT3-deficient patients (n= 74 patients) were contacted to know if patients had evidence of colonization or infection with molds. Clinical and mycological information were collected and imaging was centralized. An expert committee reviewed all charts and classified the cases (EC, SP, CT, AD, FL, OL, MOC). Results Eighteen episodes of filamentous fungal infection in ten (13.5%) STAT3-deficient patients were identified. The median age at first episode was 12 years (IQR 10.2–25). Ninety percent of patients had underlying pulmonary disease, bronchiectasis and cavitations, usually multiple. Mold infections were classified as follow: three aspergillomas, six Chronic Pulmonary Aspergillosis (CPA), five Allergic BronchoPulmonary Aspergillosis (ABPA), two mixed forms ABPA and CPA, one Chronic Allergic Sinus Aspergillosis and one Rasamsonia invasive pulmonary infection. According to EORTC/MSG definitions, no cases of invasive aspergillosis were reported. Aspergillus fumigatus was isolated in 13 cases, Rasamsonia argillocea in one case. Aspergillus precipitins were detectable in 86% of cases (12/14). Two-thirds of fungal episodes (12/18) were breakthrough infections (itraconazole prophylaxis in most cases), and half of the cases (9/18) occurred while on immunoglobulin substitutive therapy. First line antifungal therapy was voriconazole only (8/18) or amphotericin B alone or in association (6/18). Five patients required surgery (4 CPA, 1 aspergilloma). One patient died from respiratory failure at 11 years old. Conclusion Mold infections occurred in 13.5% of STAT3-deficient patients from the French cohort, mostly on anatomical modification of the lung. Notably, patients developed aspergilloma, ABPA or CPA, but no invasive aspergillosis. Despite prolonged antifungal treatment and/or surgery half of the patients (5/10) relapsed.

Background: Antibiotics have been shown to improve hidradenitis suppurativa (HS) patients but complete remission is rare using these treatments. Objective: To assess the efficacy and safety of a combination of oral rifampin, moxifloxacin and metronidazole in long-lasting refractory HS. Methods: We retrospectively studied 28 consecutive HS patients including 6, 10 and 12 Hurley stage 1, 2 and 3 patients, respectively. Complete remission, defined as a clearance of all inflammatory lesions including hypertrophic scars, was the main outcome criterion of the study. Results: Complete remission was obtained in 16 patients, including 6/6, 8/10 and 2/12 patients with Hurley stage 1, 2 and 3, respectively (p = 0.0004). The median duration of treatment to obtain complete remission was 2.4 (range 0.9–6.5) and 3.8 months (range 1.6–7.4) in stage 1 and 2 patients, respectively, and 6.2 and 12 months in the 2 stage 3 patients. Main adverse events of the treatments were gastrointestinal disorders (64% of patients) and vaginal candidiasis (35% of females). Reversible tendinopathy and hepatitis occurred in 4 and 1 patient, respectively. Conclusions: Complete remission of refractory HS can be obtained using broad-spectrum antibiotics and Hurley staging is a prognostic factor of response to the treatment.

Abstract 1982 Background: Systemic mastocytosis (SM) is a myeloproliferative disabling disorder for which no consensual curative therapy is currently available. Preliminary experiences in small groups of patients using cladribine (2-CdA) were encouraging, but no long term follow-up to evaluate its efficacy and safety have been reported. Patients and Methods: We studied the efficacy and safety of 2-CdA in 44 patients with mastocytosis enrolled in a compassionate program in France. Characteristics of patients were as follows: 22 male, 22 female, mean age 54y (18-83y), mean duration of disease 13 y (6m-39y). Symptoms of the disease included pigmentosa urticaria (31), Fatigue (35), flushs (24), prurit (24), abdominal pain (21), Ascite (9), diarrhea (23), weight loss (16), Headache (14), Cough (10), splenomegaly (20), Lymph nodes (6), Bone fractures (6), pleural effusions (2), Neuropsychological symptoms (19). Blood cell count showed eosinophils >0.5g/l (10), Hb2N (1/44). Patients were classified as having cutaneous mastocytosis (CM) (n=3) indolent SM (n=19), smoldering (SSM) (n=3), aggressive SM (ASM) (n=12) or SM with an associated clonal hematologic non-MC-lineage (AHNMD) (n=6), mast cell leukemia (n=1). Mean tryptase level was 158 (2.7-1240). All failed previous symptomatic therapy and/or recombinant interferon-a(n=10) or kinase inhibitors (n=7). Treatment consisted in intravenous 2-CdA (1 to 6 cycles of 0.15 mg/kg/d administered in a 2-hour infusion or subcutaneously for 5 d, repeated at 4–12 weeks), the mean number of infusion was 4.1 (1-15) to treat severe SM-related infiltration or symptoms. Results: After a median follow up of 35m (0-96m) 28 pts were alive, 14 were dead (all with ASM/ASM-AHNMD/MCL of mastocytosis progression n=5, Solid neoplasia n=2, hematological malignancy n= 3, septic shok n=4) and 2 were lost of follow up. Safety anlalysis showed 18 acute (pneumonia n=3) but no opportunistic infections except two zoster infections, and one renal tubulopathy. Five solid neoplasia were reported and one AML. Responses were observed for most of the symptoms with improvement of pigmentosa urticaria (n=24/31), fatigue (n=17/35), flushs (14/24), prurit (9/24), abdominal pain (9/21), Ascite (1/9), diarrhea (11/23), weight loss (8/16), Headache (4/14), Cough (5/10), splenomegaly (7/20), Lymph nodes (2/6), pleural effusions (0/2), Neuropsychological symptoms (5/19). Eosinophils count was normalized in 7/10 cases, Hb Conclusion: As a single agent, cladribine is an effective and safe treatment in symptomatic and aggressive SM. Cladribine improves significantly symptoms associated with the disease and may induce regression of mast cell tumoral burden. Its tolerability and efficacy argues for the possibility to use it even in ISM and symptomatic CM. Cladribine is ineffective to improve AHNMD. Further work is warranted to define the optimal regimen with respect to dose and schedule, and the usefulness of maintenance cladribine therapy. Disclosures: Hermine: Lipomed: Research Funding. Off Label Use: Cladribine.