Acute bacterial skin infections and cellulitis.

PURPOSE OF REVIEW: Acute bacterial skin infections are very common, with various presentations and severity. This review focuses on deep skin infections. We separate acute nonnecrotizing infections of the hypodermis (erysipelas), forms with abscesses or exudates and necrotizing fasciitis. These three types actually differ in risk factors, bacteriology, treatment and prognosis. RECENT FINDINGS: Leg erysipelas/cellulitis occurs in more than one person/1000/year. It remains mainly due to streptococci. Foot intertrigo is an important risk factor. Necrotizing fasciitis is much rarer and usually occurs in patients with chronic diseases. Staphylococci, especially community-acquired methicillin-resistant strains in some areas, play a growing role in the intermediate form of cellulitis with abscesses and exudates. For erysipelas or noncomplicated cellulitis, antibiotic treatment at home, when feasible, is much less expensive and as effective as hospital treatment. Intermediate cases with collections and exudates often require surgical drainage. For necrotizing fasciitis early surgery remains essential in order to decrease the mortality rate. SUMMARY: Antibiotic treatment of deep skin infections must be active on streptococci; the choice of a larger spectrum of activity depends on clinical presentation, risk factors and the burden of methicillin-resistant staphylococci in the environment.

Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells.

Two classes of oncogenic mutations of the c-kit tyrosine kinase have been described: the juxtamembrane domain V560G mutation, which is preferentially found in gastrointestinal stromal tumors (GISTs), and the kinase domain D816V mutation, which is highly representative of systemic mastocytosis (SM). Here we show that both mutations constitutively activate the mammalian target of rapamycin (mTOR) signaling pathway. Surprisingly, the mTOR inhibitor rapamycin induces only apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. In support of this unexpected selectivity, rapamycin inhibits the phosphorylation of 4E-BP1, a downstream substrate of the mTOR pathway, but only in D816V HMC-1 cells. Importantly, D816V mast cells isolated from SM patients or from transgenic mice are sensitive to rapamycin whereas normal human or mouse mast cells are not. Thus, rapamycin inhibition appears specific to the D816V mutation. At present there is no effective cure for SM patients with the D816V mutation. The data presented here provide a rationale to test whether rapamycin could be a possible treatment for SM and other hematologic malignancies with the D816V mutation.