Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.

Hypodermis is the predominant site of Staphylococcus aureus infections that cause cellulitis. Given the importance of macrophages in tissue remodeling, we examined the hypodermal macrophages (HDMs) and their impact on host susceptibility to infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy. HDM homeostasis required the fibroblast-derived growth factor CSF1, ablation of which abrogated HDMs from the hypodermal adventitia. Loss of CCR2- HDMs resulted in accumulation of the extracellular matrix component, hyaluronic acid (HA). HDM-mediated HA clearance required sensing by the HA receptor, LYVE-1. Cell-autonomous IGF1 was required for accessibility of AP-1 transcription factor motifs that controlled LYVE-1 expression. Remarkably, loss of HDMs or IGF1 limited Staphylococcus aureus expansion via HA and conferred protection against cellulitis. Our findings reveal a function for macrophages in the regulation of HA with an impact on infection outcomes, which may be harnessed to limit the establishment of infection in the hypodermal niche.

Specific infiltrate of Hodgkin lymphoma at site of cellulitis mimicking secondary cutaneous involvement.

Hodgkin lymphoma (HL) usually involves the lymph nodes, but concomitant cutaneous manifestations can also occur. The diagnosis of cutaneous involvement by HL must be supported by specific clinical and histopathological findings. We describe the case of a 56-year-old man recently diagnosed with HL of the left axillary nodes who developed cellulitis of the left trunk. Histopathological examination of a skin biopsy specimen revealed the presence of large atypical lymphoid cells with the same immunophenotype of those located in the lymph node affected by HL. Our case adds to the many cutaneous infiltrations by neoplastic cells during the course of an inflammatory skin disease, namely cellulitis.

Peculiar clinical features of cellulitis in peripheral lymphedema.

Although the occurrence of cellulitis in lymphedema (LE) is believed to be an infection-related event, many findings in its clinical course seem to suggest that it is unlikely to be an infection. Therefore, we tried to clarify the specific features of cellulitis in LE. In-hospital courses of cellulitis obtained from medical charts were reviewed in the patients with leg LE (LE; 24 patients, 72admissions), chronic venous insufficiency (CVI; 28 patients, 29 admissions), and leg cellulitis secondary to wound infection without underlying disease (N; 42 patients, 42 admissions). The patients with LE complained of less local pain (peak numerical scale; LE: 1.4 ± 1.7, CVI: 4.1 ± 2.5, N: 3.2 ±2.0, p < 0.0001), showed an abnormally higher peak procalcitonin level (LE: 33.8 ± 34.8 (N = 7), CVI: 2.9 ± 5.8 (N = 8), N: 0.4 ± 0.6(N = 10), p < 0.05), and required fewer antibiotics (LE: 1.1 ± 0.3, CVI: 1.8 ± 0.9, N: 1.5 ± 0.9, p < 0.0001). These findings suggested that the occurrence of cellulitis in LE seems unlikely to be an infection-related type of cellulitis similar to that found in CVI.

Loss of periostin ameliorates adipose tissue inflammation and fibrosis in vivo.

Recent evidence suggests that the accumulation of macrophages as a result of obesity-induced adipose tissue hypoxia is crucial for the regulation of tissue fibrosis, but the molecular mechanisms underlying adipose tissue fibrosis are still unknown. In this study, we revealed that periostin (Postn) is produced at extraordinary levels by adipose tissue after feeding with a high-fat diet (HFD). Postn was secreted at least from macrophages in visceral adipose tissue during the development of obesity, possibly due to hypoxia. Postn-/- mice had lower levels of crown-like structure formation and fibrosis in adipose tissue and were protected from liver steatosis. These mice also showed amelioration in systemic insulin resistance compared with HFD-fed WT littermates. Mice deficient in Postn in their hematopoietic compartment also had lower levels of inflammation in adipose tissue, in parallel with a reduction in ectopic lipid accumulation compared with the controls. Our data indicated that the regulation of Postn in visceral fat could be beneficial for the maintenance of healthy adipose tissue in obesity.

Rutin and meloxicam attenuate paw inflammation in mice: Affecting sorbitol dehydrogenase activity.

Rutin, naturally occurring flavonoid, has reported to cover interesting multiple pharmacological properties. This study evaluated rutin or/and meloxicam effects in paw inflammation induced by formalin in mice. Mice were divided into four groups: I-Formalin group, II-Rutin 60 mg/kg (p.o.), III-Meloxicam 10 mg/kg (p.o.), plus IV-Combined rutin and meloxicam. Therapies were administered once a day for 7 days. The curative effects were assessed on inflammatory, oxidative stress, and apoptosis. Both rutin and/or meloxicam induced marked improvement in paw licking time on the 1st day and by combined treatment only on the 3rd day as well reduction in paw edema% on the 3rd day. Moreover, noticeable progress in liver malondialdehyde content, superoxide dismutase, and sorbitol dehydrogenase activities as well decline in paw interleukin-1ß level and extent of apoptosis. The results spot light on the good influence of combined rutin and meloxicam in formalin-induced mice paw inflammation to a better extent than either rutin or meloxicam lonely.

IMMUNOHISTOCHEMICAL ANALYSIS OF APPENDIX CELL WALL INFILTRATE IN ACUTE PHLEGMONOUS APPENDICITIS.

The purpse of the study was to analyze the content of the mucous infiltrate of cells of the lamina propria of the appendix using immunohistochemical analysis in patients with acute phlegmonous appendicitis. The research included 21 patients with acute phlegmonous appendicitis. The control group consisted of 15 persons lacking the inflammation of the intraperitoneal cavity. Primary monoclonal (MC) antibodies (AB) of the mouse used in the immunohistochemical (IHC) research included the following: Ki-67, CD3, CD4, CD8, CD20, CD45, CD45R0, and CD68 (DAKO, Denmark), as well as EnVision+ System-HRP (DAB) optical system. The research has shown that acute phlegmonous appendicitis is characterized by statistically reliable increased infiltration (p<0.001) by B-lymphocytes (CD20), memory T-cells (CD45R0), Ki-67+ cells, macrophages (CD68), T-lymphocytes (CD3), T-helper cells (CD4), cytotoxic T-lymphocytes (CD8), and CD45 cells of the lamina propria of the appendix when compared with the control group. Development of acute phlegmonous appendicitis is characterized by enhance infiltration of the lamina propria by B-lymphocytes (CD20), macrophages (CD68), memory T-cells, and high proliferation activity of the mononuclear cells (Ki-67 index).

Blood cultures in the evaluation of uncomplicated cellulitis.

PURPOSE: The frequency of bacteremia and the array of microorganisms involved in cellulitis vary greatly among studies. Although current guidelines do not recommend routine blood culture in uncomplicated cellulitis, their implementation in clinical practice remains challenging. We therefore aimed to assess the frequency, determinants and microbiology of bacteremia in hospitalized patients with uncomplicated cellulitis. METHODS: We retrospectively reviewed the medical records of all adult patients admitted at a primary-care hospital with a diagnosis of community-acquired uncomplicated cellulitis during a 4-year period. We looked at the factors associated with blood cultures sampling and at the incidence, determinants and microbiology of bacteremia in this population. RESULTS: Among the 476 patients hospitalized with a diagnosis of cellulitis, 250 (52.5%) had blood cultures. Fever, high C-reactive protein and lymphatic insufficiency were significantly associated with the sampling of blood cultures. Twelve (4.8%) patients had bacteremia. Alcoholism and duration of hospitalization were associated with bacteremia in multivariate analysis. Among the 12 patients with bacteremia, 9 had Streptococcus sp. and 3 had Staphylococcus aureus infection. CONCLUSION: In our study population with uncomplicated cellulitis, representative of unselected population admitted at primary-care hospitals, bacteremia was uncommon and not associated with discriminant patient characteristics, except for alcohol abuse. Episodes of bacteremia were exclusively due to gram-positive cocci susceptible to co-amoxicilin, a common first-line empirical therapy. In accordance with existing guidelines, we do not recommend to collect blood for cultures in uncomplicated cellulitis. Clinicians' awareness of guidelines and of the poor yield of blood cultures could reduce useless investigation.

Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.

Lymphomatoid papulosis type C of the eyelid in a young girl: a case report and review of literature.

PURPOSE: To report an unusual presentation of a case of Lymphomatoid papulosis(LyP) in a young girl. MATERIAL AND METHODS: A 14-year-old female presented with a history of swelling of the left upper eyelid of two weeks duration. There was a history of trivial trauma prior to the swelling. The patient was diagnosed as having pre-septal cellulitis elsewhere and was put on oral antibiotics. The lesion was non-responsive to oral antibiotics. The patient was then referred to our hospital. Ocular examination revealed an elevated lesion measuring 15 mm × 10 mm on the left upper eyelid, associated with pre-septal swelling and induration. Ocular movements were normal. The anterior and posterior segment examination was normal. Incision biopsy was done from the eyelid lesion. Multiple cutaneous lesions were also biopsied. RESULTS: The histopathology examination confirmed the diagnosis of lymphomatoid papulosis type C. Dermatological and systemic evaluation ruled out the other aggressive forms of CD30(+) lymphoid proliferation. CONCLUSION: We report an unusual presentation of lymphomatoid papulosis(LyP) type C in a young girl. Complete systemic work up and histopathological evaluation is mandatory in cases of suspicious lesions, not responding to conservative treatment.

Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.

[THE ROLE OF ANTIHYPOXANTS AND ANTIOXIDANT IN TREATMENT OF ODONTOGENIC OF MAXILLOFACIAL AREA].

The aim of this work is the systematization of the literature data for the most clearly defined directions of study of the effectiveness of antioxidant and antihypoxant drugs in complex treatment of patients with purulent inflammatory diseases of the maxillofacial area. The authors attempt to analyze the results of the use of antioxidant and antihypoxant therapy at pyoinflammatory pro- cesses of different localization. Areas of research of the impact of antioxidant and antihypoxants therapy on physical and biochemical parameters of the maxillofacial area and the organism of the patient as a whole are defined.

[Effectiveness of Reamberin in correction of oxidative stress syndrome in patients with phlegmonous and gangrenous erysipelas against the background of the 2 type diabetes mellitus].

The influence of modern detoxic preparation Reamberin on indicators of oxidative stress syndrome (OSS)--the content of lipoperoxidation products was investigated. It was established that inclusion of Reamberin in the complex of surgical treatment of destructive forms of erysipelas on the background of type 2 DM accelerates the liquidation of OSS.

Diagnostic features of mild cellulitis phlegmon in patients with rheumatoid arthritis treated with tocilizumab: a report of two cases.

Two cases of subcutaneous soft tissue infection in 30 RA patients treated with tocilizumab are reported. In both patients, local redness, swelling, and heat were observed around the affected site. WBC spikes and such local findings were suggested to be clinically useful for the early detection of low-grade subcutaneous infection in RA patients whose disease is tightly controlled with tocilizumab. Of note, the C-reactive protein (CRP) level and temperature lacked clinical utility for such detection.

[Regional lymphotropic antibiotic therapy as a part of comprehensive treatment of children with purulent-inflammatory diseases of maxillofacial region].

126 children (aged 3-14 years) with severe purulent-inflammatory maxillofacial lesions underwent complex treatment: lymhotropic method of antibiotic (cefamabol) therapy was used in 64 of them. Clinical, microbiological and pharmacokinetic investigations have shown the method of lymphotropic regional antibiotic therapy to be effective and feasible to treat purulent-inflammatory maxillofacial lesions in children.

[Experimental substantiation of indirect electrochemical blood oxidation and antioxidant therapy use efficacy in the treatment of festering soft tissues wounds].

In experiment on rats in the treatment of festering soft tissues wounds it was substantiated the inclusion into the scheme of the basic therapy 0.03% solution of sodium hypochlorite and antioxidant Recsod. Introduction of these preparations let to reduce the level of oxidation stress and endogenous intoxication, to eliminate imbalance in the antioxidant erythrocyte system and in the organism as a whole in the acute inflammation phase and to speed up wound healing processes.

Expression of antimicrobial peptides in the normal and involved skin of patients with infective cellulitis.

BACKGROUND: Endogenous antimicrobial peptides participate in the innate defense of skin against a variety of pathogens. The systemic expression of these peptides in normal-appearing skin of patients with infective cellulitis is unknown. METHODS: Study patients were adults with infective cellulitis and signs of systemic inflammation. Skin biopsy and serum specimens were obtained from patients and from control subjects with no active infection. Cathelicidin and human beta-defensin 2 mRNA expression were determined by real-time polymerase chain reaction. RESULTS: Skin biopsy specimens from 11 patients and 4 uninfected control subjects were analyzed. The relative expression level for cathelicidin mRNA was elevated in both the involved and the distal normal-appearing skin of patients with cellulitis, compared with expression in the skin of control subjects (mean ratios, 39.46 vs. 1.32, P=.0059; and 21.41 vs. 1.32, P=.0059). Similarly, the relative expression level of human beta -defensin 2 mRNA was elevated in both the involved skin (mean ratios, 20,844 vs. 11.65; P=.0015) and in distal normal-appearing skin of patients with cellulitis (mean ratios, 201.1 vs. 11.65; P=.0103). DISCUSSION: In response to cutaneous infection there is a local and distal increase in endogenous antimicrobial peptide mRNA in both involved and normal-appearing skin. These observations show, for the first time to our knowledge, that after infection the human body responds by increasing systemic innate immunity.