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.

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.

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.

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.

Langerhans cell histiocytosis with periorbital cellulitis.

PURPOSE: To report a case of Langerhans cell histiocytosis presenting as periorbital cellulitis. DESIGN: Interventional case report. METHODS: A 3-year-old girl presented with periorbital swelling of the right upper lid laterally of two days' duration. A history of recent eye trauma was reported. RESULTS: Computed tomography showed a soft tissue mass that eroded the frontozygomatic suture. The lesion was debulked through a lateral orbitotomy. Electron microscopy disclosed Birbeck granules. Immunohistochemistry stained positively for CD68 and CD1a antigenic determinants. CONCLUSIONS: Although rare, Langerhans cell histiocytosis can cause acute periorbital cellulitis in children. Trauma can induce an inflammatory response, allowing for earlier diagnosis of the orbital lesion.

Carcinoma erysipeloides from prostate cancer presenting as cellulitis.

We report a 72-year-old man with carcinoma erysipeloides presenting as cellulitis of the thigh. Immunohistochemical study of the skin biopsy showed positive staining to prostate-specific antigen, confirming that the tumor originated in the prostate.

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation.

BACKGROUND: Eosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation. OBJECTIVE: Our purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus. METHODS: Family members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines. RESULTS: Three short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients' plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption. CONCLUSION: Eosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking.

[Plasmosorption in the combined treatment of patients with phlegmons of the maxillofacial area in diabetes mellitus]. / Plazmosorbtsiia v kompleksnom lechenii bol'nykh s flegmonami cheliustno-litsevoi oblasti na fone sakharnogo diabeta.

Diabetes mellitus and surgical infection coursing intermittently aggravate each other, and therefore search for methods of treatment permitting a simultaneous impact on the pyoinflammatory process and on diabetes mellitus is a priority. Plasmasorption method used at present at Chair for maxillofacial surgery and dentistry of the Russian State Medical University meets these requirements to a great measure. Clinical and laboratory studies showed that plasmasorption used in multiple-modality treatment helps effectively control a purulent process, reduces intoxication of the body, corrects the development of insulin resistance in patients with maxillofacial phlegmons coursing in the presence of diabetes mellitus. In patients with grave and medium-severe diabetes the same insulin doses injected after plasmasorption reduce blood sugar levels by 1.5-1.7 times on an average, and in slight forms of the condition even normalize them. Secondary healing of postoperative wounds is accelerated in diabetics with maxillofacial phlegmons, and hospital stay of such patients is reduced by 9.5-10 days, on an average.

Haemorrhagic cellulitis: a syndrome associated with tumour necrosis factor-alpha.

A newly defined clinical syndrome, haemorrhagic cellulitis, is described in 12 patients. The syndrome consists of an acute onset of extremely painful erythema affecting dependent areas, followed by dermal haemorrhage and sloughing of the overlying epidermis, and requiring both antibiotics and systemic corticosteroids for complete resolution. The patients usually have demonstrable Gram-negative or Gram-positive infection, of non-cutaneous origin, and underlying systemic disease. Vacuolopathic necrosis of epidermal keratinocytes, and damaged vascular endothelium of the dermal blood vessels can be demonstrated by light and electron microscopy, as well as by lectin studies. Immunocytochemical studies reveal the presence of activated macrophages and T lymphocytes. We believe the syndrome is due to lipopolysaccharide-induced or bacterial mitogen-induced tumour necrosis factor-alpha (TNF-alpha), secreted by previously primed activated macrophages in a second-set response. TNF-alpha characteristically injures endothelial cells and epidermal keratinocytes. It is thought to induce its cytotoxic effects partly via neutrophil degranulation, and partly via DNAase activation, with resultant DNA fragmentation and cell lysis. Corticosteroids have been shown not only to inhibit TNF-alpha secretion by activated macrophages, but also to block its cytotoxicity, thus accounting for the extremely rapid clinical response to this drug in conjunction with adequate and appropriate antibiotic therapy.

[The efficacy of using a helium-neon laser, ascorbic acid and methylene blue in the combined treatment of patients with maxillofacial phlegmons]. / Effektivnost' ispol'zovaniia gelii-neonovogo lazera, askorbinovoi kisloty i metilenovogo sinego v kompleksnom lechenii bol'nykh s flegmonami cheliustno-litsevoi oblasti.

The efficacy of multiple-modality treatment including interstitial He-Ne laser exposure and agents normalizing redox processes due to their antioxidant effect, 5 percent ascorbic acid and 1 percent methylene blue aqueous solution, was assessed in the treatment of 188 patients with maxillofacial phlegmons. The treatment accelerated injured tissue regeneration, this permitting early secondary suturing and shortening the invalidity periods.

Acute pulpal-alveolar cellulitis syndrome. IV. Exacerbations during endodontic treatment. Part 3. A case report.

An asymptomatic abscessed maxillary premolar, which had undergone previous endodontic treatment, was retreated. The initial attempt to remove the silver cone seal was unsuccessful. Early the next morning, the patient appeared with a severe cellulitis exacerbation. The silver cone was now loose: a lateral "blowout." Specific cultures of the silver cone and exudate revealed three aerobic microbes: a Streptococcus sp and two obligate Pseudomonas spp. Anaerobes were shown to be absent with anaerobic subcultures. This case would appear to substantiate the alteration of the tissue oxidation-reduction potential as the major factor in endodontic cellulitis exacerbations, as previously reported.

Acute pulpal-alveolar cellulitis syndrome. IV. Exacerbations during endodontic treatment: a clinical study of specific microbial isolates and their etiologic role. Part 1.

A statement has been made by Sundqvist that it has not been possible to isolate the specific bacteria that is responsible for acute exacerbations during endodontic treatment of existing periapical inflammation. This clinical study presents specific microbial isolates from 34 intact nonvital teeth involved with acute cellulitis exacerbations during endodontic therapy. No obligate anaerobes were isolated. Forty-seven aerobic and facultative microbes were isolated. Streptococci, primarily facultative, were the major group of microbes isolated (80%); alpha hemolytic streptococci and the group D enterococcus were predominant as mixed and pure culture specimens. Gram-negative microbes as strict aerobic and facultative microbes were also reported as specific isolates. The biological role of anaerobes were discussed in primary pulpal-periapical infections. The alteration of the tissue oxidation-reduction potential, (Eh) is proposed as an etiologic factor in cellulitis exacerbations during endodontic treatment. This is further substantiated in the Part 2 report. Attention is drawn to the pathogenic potential of streptococci and other microbes isolated in this study.