Correction to: A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

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A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

Chronic Granulomatous Disease in Patients Reaching Adulthood: A Nationwide Study in France.

Background: Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD patients diagnosed before age 16, at various adult time points. Method: Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry. Results: Eighty CGD patients (71 males [88.7%], 59 X-linked [73.7%], median age 23.9 years [minimum, 16.6; maximum, 59.9]) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood. Conclusions: Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.

The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a frequent and severe disease of the skin, characterized by recurrent or chronic skinfold suppurative lesions with a high impact on quality of life. Although considered inflammatory, antimicrobial treatments can improve or lead to clinical remission of HS, suggesting triggering microbial factors. Indeed, mixed anaerobic microbiota are associated with a majority of HS lesions. Our aim in this study was to characterize the landscape of anaerobic infections in HS using high-throughput sequencing. METHODS: We sampled and cultured 149 lesions and 175 unaffected control skinfold areas from 65 adult HS patients. The microbiome of 80 anaerobic lesions was compared to that of 88 control samples by 454 high-throughput sequencing after construction of 16S ribosomal RNA gene libraries. RESULTS: Bacterial cultures detected anaerobes in 83% of lesions vs 53% of control samples, combined with milleri group streptococci and actinomycetes in 33% and 26% of cases, respectively. High-throughput sequencing identified 43 taxa associated with HS lesions. Two gram-negative anaerobic rod taxa, Prevotella and Porphyromonas, predominated, contrasting with a reduced abundance of aerobic commensals. These rare taxa of normal skinfold microbiota were associated with lesions independently of gender, duration and familial history of HS, body mass index, and location. Two main additional taxa, Fusobacterium and Parvimonas, correlated with the clinical severity of HS. CONCLUSIONS: In this study we reveal the high prevalence and particular landscape of mixed anaerobic infection in HS, paving the way for rationale targeted antimicrobial treatments.

Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients.

OBJECTIVES: Hidradenitis suppurativa (HS) is an inflammatory skin disease typically localized in the axillae and inguinal and perineal areas. In the absence of standardized medical treatment, severe HS patients present chronic suppurative lesions with polymicrobial anaerobic abscesses. Wide surgery is the cornerstone treatment of severe HS, but surgical indications are limited by the extent of lesions. Intravenous broad-spectrum antibiotics may help control HS, but their efficacy is not documented. This study was designed to assess the efficacy of a 6 week course of ertapenem (1 g daily) and of antibiotic consolidation treatments for 6 months (M6) in severe HS. PATIENTS AND METHODS: Thirty consecutive patients with severe HS were retrospectively included in this study. The clinical severity of HS was assessed using the Sartorius score, which takes into account the number and severity of lesions. RESULTS: The median (IQR) Sartorius score dropped from 49.5 (28-62) at baseline to 19.0 (12-28) after ertapenem (P < 10(-4)). Five patients were lost to follow-up thereafter. At M6 the Sartorius score further decreased for the 16 patients who received continuous consolidation treatments, since 59% of HS areas reached clinical remission at M6 (i.e. absence of any inflammatory symptoms, P < 10(-4)). Nine patients interrupted or received intermittent consolidation treatments due to poor observance or irregular follow-up. Their Sartorius score stopped improving or returned to baseline. No major adverse event occurred. CONCLUSIONS: Ertapenem can dramatically improve severe HS. Consolidation treatments are needed to further improve HS and are mandatory to prevent relapses. Combined with surgery, optimized antibiotic treatments may be promising in severe HS.

Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis.

Mastocytosis (M) is a clonal myeloid-disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a synthetic purine analog cytoreductive treatment, for which efficacy is mostly reported in advanced M. Here we report, with a long-term follow-up period (>10 years) efficacy and safety in 68 adult patients with M (36 [53%] had indolent M and 32 [47%] had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1-9). The overall response rate was 72% (complete remission [R]/major/partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (major/partial R: 56%/36%) and 50% (major/partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10 of 11 mediator release and 6 of 7 mast cell infiltration-related symptoms including urticaria pigmentosa and organomegaly (P < .02). Serum tryptase levels decreased (P = .01). Median durations of response were 3.71 (0.1-8) and 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies.

Bacterial pathogens associated with hidradenitis suppurativa, France.

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.

Prevention of infections during primary immunodeficiency.

Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then, a working group including different specialists systematically debated about chemoprophylaxis, immunotherapy, immunization, and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management of PIDs and improving the outcome of patients with PIDs.

Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency condition with alterations in T cell regulation and function, dendritic and B-cell compartment and represents the most frequent cause of symptomatic primary immunodeficiency. We addressed whether CVID is associated with abnormalities in the polymorphonuclear neutrophil (PMN) compartment, an important component of innate immunity and plays a key role in host defenses against invading microorganisms. We used flow cytometry to examine PMN phenotypic and functional abnormalities in CVID patients, using whole-blood conditions in order to avoid artifacts due to isolation procedures. We demonstrated that PMN from CVID patients displays, at resting state, a decreased expression of CD15, CD11b and CD16b, which might be related to an abnormality in neutrophil maturation. In addition, these neutrophils exhibit a decrease in degranulation, phagocytosis and reactive oxygen species production, as well as an increased death by apoptosis. These PMN abnormalities observed in CVID patients could result in an increased risk for recurrent bacterial infections.

Iatrogenic Cushing's syndrome induced by posaconazole.

Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome. We present a patient with common-variable immunodeficiency who received 7 years of itraconazole therapy for bronchial colonization with Aspergillus in combination with inhaled fluticasone without any Cushingoid symptoms. After a switch to posaconazole, the patient developed Cushingoid symptoms.

[Chronic granulomatous disease: pathogenesis and therapy of associated fungal infections]. / Infections fongiques et granulomatose septique chronique - De la physiopathologie aux nouvelles perspectives thérapeutiques.

Chronic granulomatous disease is a genetic disorder responsible for a defect in the NADPH oxidase of phagocytic cells. It impairs the oxidative burst necessary to the intracellular inactivation of microorganisms and predisposes to an increased risk of infections by various microorganisms, including fungi like Aspergillus spp. and other less frequently encountered or emerging fungal species. Here we review the genetic basis, pathogenesis and clinical presentation associated with fungal infections in chronic granulomatous disease as well as the current prophylaxis and newly available therapies.

Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.

BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.

Adherence to preventive measures after splenectomy in the hospital setting and in the community.

UNLABELLED: Overwhelming post-splenectomy infection (OPSI) remains a long-term risk in asplenic patients, which may be reduced by appropriate preventive measures. Specific guidelines have been developed to lower its incidence. AIMS: To assess the implementation of guidelines by specialized physicians of a university hospital and primary care physicians. METHODS: A retrospective review of splenectomized patients' medical files over a six year period was carried out. Patients' general practitioners were contacted and a questionnaire was sent to them. RESULTS: 154 individuals who underwent splenectomy between 2000 and 2005 were eligible (62 children and 92 adults): 70.8% received pneumococcal vaccine, 44% received vaccine against Haemophilus influenzae type b with a good cover of children population (88.7%), 24% received meningococcal vaccine. Prophylactic antibiotics were prescribed in 74% of patients. Septic events were found in 8.4%, and global mortality was 11.7% during a mean follow-up period of 4.5 years. CONCLUSIONS: Management of the infectious risk in asplenic patient has to be improved: some of the patients are not correctly identified as at risk of OPSI, and vaccination against Neisseria meningitidis is insufficient. Hospital specialists should improve the implementation of guidelines and give better information to general practitioners involved.

[Pregnancy: a high risk factor in influenza infection]. / Faut-il avoir peur de la grippe chez la femme enceinte ?

During pregnancy both mother and foetus are at increased risk of being infected with either pandemic or seasonal influenza viruses, and it is thus legitimate to implement enhanced surveillance for infection particularly with the A/H1N1v and discuss priority vaccine administration. We will review the alterations in immunologic parameters which lead to some degree of cellular immunodeficiency, but also in anatomic changes and pulmonary restrictions which contribute to this suceptibility of pregnant women to severe complications of an influenza infection. We also provide an update on the epidemiological data available for the A/H1N1v infection in this population, and discuss the benefit/risk ratio of treatment with the antiviral medications.