Panton-Valentine Leucocidin of Staphylococcus aureus Induces Oxidative Stress and Neurotransmitter Imbalance in a Retinal Explant Model

PurposeEndophthalmitis models have reported the virulent role of Panton-Valentine leucocidin (PVL) secreted by Staphylococcus aureus on the retina. PVL targets retinal ganglion cells (RGCs), expressing PVL membrane receptor C5aR. Interactions between PVL and retinal cells lead to glial activation, retinal inflammation, and apoptosis. In this study, we explored oxidative stress and retinal neurotransmitters in a rabbit retinal explant model incubated with PVL.MethodsReactive oxygen species (ROS) production in RGCs has been assessed with fluorescent probes and immunohistochemistry. Nuclear magnetic resonance (NMR) spectroscopy quantified retinal concentrations of antioxidant molecules and neurotransmitters, and concentrations of neurotransmitters released in the culture medium. Quantifying the expression of some pro-inflammatory and anti-inflammatory factors was performed using RT-qPCR.ResultsPVL induced a mitochondrial ROS production in RGCs after four hours’ incubation with the toxin. Enzymatic sources of ROS, involving nicotinamide adenine dinucleotide phosphate–oxidase and xanthine oxidase, were also activated after four hours in PVL-treated retinal explants. Retinal antioxidants defenses, that is, glutathione, ascorbate and taurine, decreased after two hours’ incubation with PVL. Glutamate retinal concentrations and glutamate release in the culture medium remained unaltered in PVL-treated retinas. GABA, glycine, and acetylcholine (Ach) retinal concentrations decreased after PVL treatment. Glycine release in the culture medium decreased, whereas Ach release increased after PVL treatment. Expression of proinflammatory and anti-inflammatory cytokines remained unchanged in PVL-treated explants.ConclusionsPVL activates oxidative pathways and alters neurotransmitter retinal concentrations and release, supporting the hypothesis that PVL could induce a neurogenic inflammation in the retina.     

Fibrose systémique néphrogénique

Nephrogenic systemic fibrosis is a recently described entity that occurs in patients with advanced renal failure. Its cause is probably toxic. The patients develop skin thickening, which is usually symmetrical on the limbs and sometimes extend to the trunk. Joint contractures and muscle sclerosis confine the patients to wheelchair. Systemic involvement may occur and includes cardiomyopathy, pulmonary fibrosis and diaphragmatic paralysis. The diagnosis is confirmed by the association of skin fibrosis and a cellular infiltration composed of CD34+ fibrocytes. Prognosis is severe with many deaths, rarely directly related to the disease. An improvement of lesions is possible, especially in case of resolution of the renal insufficiency. Several treatments have been evaluated, but none has shown consistent benefit. The toxic culprit is likely to be the gadolinium ions (Gd⁺⁺⁺), released from some contrast agents used in nuclear magnetic resonance imaging. Evidence of the responsibility of Gd⁺⁺⁺ is based on epidemiologic, biochemical and experimental data. Recommendations have been published for patients with renal insufficiency requiring a nuclear magnetic resonance imaging. If they are followed and efficient, it is likely that nephrogenic systemic sclerosis will disappear.     

The Schnitzler syndrome. Four new cases and review of the literature

The Schnitzler syndrome is characterized by a chronic urticarial eruption with a monoclonal IgM gammopathy. The other signs of the syndrome include intermittent elevated fever, joint and/or bone pain with radiologic evidence of osteosclerosis, palpable lymph nodes, enlarged liver and/or spleen, elevated erythrocyte sedimentation rate, and leukocytosis. The mean delay to diagnosis is more than 5 years, and this syndrome is of concern to internists and many medical specialists. Patients with this syndrome are often initially considered to have lymphoma or adult-onset Still disease, which are the main differential diagnoses. However, hypocomplementic urticarial vasculitis, systemic lupus erythematosus, cryoglobulinemia, acquired C1 inhibitor deficiency, hyper IgD syndrome, chronic infantile neurologic cutaneous and articular (CINCA) syndrome, and Muckle-Wells syndrome should also be excluded, because diagnosis relies on a combination of clinical and biologic signs and there is no specific marker of the disease. The disease pursues a chronic course, and no remissions have yet been reported. Disabling skin rash, fever, and musculoskeletal involvement are the most frequent complications. Severe anemia of chronic disease is another serious complication. The most harmful complication, however, is evolution to an authentic lymphoplasmacytic malignancy, which occurs in at least 15% of patients. This hematologic transformation can occur more than 20 years after the first signs of the disease, thus patients deserve long-term follow-up. Treatment is symptomatic and unsatisfactory. The skin rash is unresponsive to treatment, and nonsteroidal antiinflammatory drugs, antihistamines, dapsone, colchicine, and psoralens and ultraviolet A (PUVA) therapy give inconstant results. Fever, arthralgia, and bone pain often respond to nonsteroidal antiinflammatory drugs. In some patients, these symptoms and/or the presence of severe inflammatory anemia require steroids and/or immunosuppressive treatment, which ameliorate inflammatory symptoms but do not change the course of the skin rash.     

Blaschkolineäre Dermatitis im Erwachsenenalter (Morbus Grosshans-Marot) mit antinukleären Antikörpern

E. Grosshans and L. Marot first described blaschkitis in 1990 as a linear inflammatory dermatitis following lines of Blaschko in an adult patient. We report another case which occurred in a 38-year-old woman who developed an extensive, linear, erythematosquamous dermatitis involving the face, all limbs and the trunk. The patient's serum tested positive for antinuclear antibodies at a dilution of 1:640. The lesions regressed spontaneously within 4 weeks. Blaschkitis is a distinct entity which corresponds neither to a known inflammatory dermatitis in the lines of Blaschko nor to an hamartoma nor to an X-linked disease. Cutaneous antigenic mosaicism, the expression of which might be induced by a viral infection, could trigger this localized inflammatory T-cell response. This hypothesis relates blaschkitis to other cutaneous autoimmune diseases, as does the presence of antinuclear antibodies. We therefore suggest renaming this type of inflammatory dermatitis Grosshans-Marot disease in honour to the dermatologists who first described the entity.