Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.

     

Healthcare-associated mucormycosis

Mucormycosis is a severe emerging invasive fungal infection that occurs as a consequence of environmental exposure. We exhaustively reviewed all the cases of mucormycosis (European Organisation for Research and Treatment of Cancer/Mycoses Study Group 2008 criteria) attributed to healthcare procedures that occurred between 1970 and 2008. A total of 169 cases were studied (29% children, 61% male). Major underlying diseases were solid organ transplantation (24%), diabetes mellitus (22%), and severe prematurity (21%). Skin was the most common localization (57%), followed by gastrointestinal tract (15%). Culture results were available in 75% (92% positive), and results of histological examination were positive in 95%. Rhizopus was the most frequent genus (43%). Infection portal of entry included surgery and presence of medical devices such as catheters or adhesive tape. Outbreaks and clusters were related to adhesive bandages (19 cases), wooden tongue depressors (n = 5), ostomy bags (n = 2), water circuitry damage (n = 2), and adjacent building construction (n = 5). Thorough investigations are mandatory to identify healthcare-associated mucormycosis, notably in neonatology, hematological, and transplantation units.     

Osteoarticular Infections Caused by Non-Aspergillus Filamentous Fungi in Adult and Pediatric Patients: A Systematic Review

Osteoarticular mycoses due to non-Aspergillus moulds are uncommon and challenging infections.A systematic literature review of non-Aspergillus osteoarticular mycoses was performed using PUBMED and EMBASE databases from 1970 to 2013.Among 145 patients were 111 adults (median age 48.5 [16–92 y]) and 34 pediatric patients (median age 7.5 [3–15 y]); 114 (79.7%) were male and 88 (61.9%) were immunocompromised. Osteomyelitis was due to direct inoculation in 54.5%. Trauma and puncture wounds were more frequent in children (73.5% vs 43.5%; P = 0.001). Prior surgery was more frequent in adults (27.7% vs 5.9%; P = 0.025). Vertebral (23.2%) and craniofacial osteomyelitis (13.1%) with neurological deficits predominated in adults. Lower limb osteomyelitis (47.7%) and knee arthritis (67.8%) were predominantly seen in children. Hyalohyphomycosis represented 64.8% of documented infections with Scedosporium apiospermum (33.1%) and Lomentospora prolificans (15.8%) as the most common causes. Combined antifungal therapy and surgery was used in 69% of cases with overall response in 85.8%. Median duration of therapy was 115 days (range 5–730). When voriconazole was used as single agent for treatment of hyalohyphomycosis and phaeohyphomycosis, an overall response rate was achieved in 94.1% of cases.Non-Aspergillus osteoarticular mycoses occur most frequently in children after injury and in adults after surgery. Accurate early diagnosis and long-course therapy (median 6 mo) with a combined medical-surgical approach may result in favorable outcome.     

New insights into hepatosplenic candidosis, a manifestation of chronic disseminated candidosis

Chronic disseminated candidosis, often referred to as hepatosplenic candidosis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients after profound and prolonged neutropenia, which is more often seen in patients with acute haematological malignancies. The incidence of HSC ranges from 3% to 29% in patients suffering from Acute Leukaemia. However, it is now seen less frequently with the widespread use of antifungal agents as prophylaxis or as preemptive therapy. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. The pathogenesis is not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome. In this context, new therapeutic approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This article will focus on the clinical, diagnostic and therapeutic aspects of HSC and provide an accurate review of recent pathophysiological data.     

Diabetes and mucormycosis: a complex interplay

Mucormycosis is a life-threatening invasive fungal infection that arises particularly in diabetic patients with or without other underlying conditions such as haematological malignancies or the need for solid-organ transplantation. Rhino-orbito-cerebral involvement is the primary site of mucormycosis, but the paucity of signs may be a cause of delayed diagnosis. Thus, any case of documented non-bacteriological sinusitis in diabetic patients, even without ketoacidosis, should prompt suspicion of a mucormycosis diagnosis. To optimalize information for clinicians in charge of diabetic patients, this extensive review of the literature was carried out to provide an overview of mucormycosis specificities, epidemiology and pathophysiology in the setting of diabetes.