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.

Atypical pediatric presentation of alopecic and aseptic nodules of the scalp with features of dissecting cellulitis.

Alopecic and aseptic nodules of the scalp (AANS) and dissecting cellulitis of the scalp (DCS) are rare, closely related conditions of young men that exclusively affect the hair-bearing scalp. We describe a 9-year-old boy who presented with a 6-year history of chronically relapsing, sterile, partially scarring nodules of the scalp and facial skin. Histopathology revealed mixed inflammatory infiltrates consisting of neutrophils, macrophages, lymphocytes, and plasma cells in the deep dermis, consistent with the morphological pattern of suppurative, partly granulomatous dermatitis. The present atypical case is characterized by prepubertal onset and facial involvement which, to our knowledge, has not yet been described before, may be included in the spectrum of "typical" AANS and "typical" DCS.

Histopathology in the Diagnosis of Tinea Capitis: When to Do, How to Interpret?

The diagnosis of tinea capitis is usually made by clinical signs and direct microscopic examination. Early diagnosis of this dermatophytic infection, which may cause permanent hair loss if not treated appropriately, is very crucial. In recent years, the use of dermoscopy has helped with early diagnosis. However, when tinea capitis has an atypical course and develops in adulthood, it can be confused with several diseases, such as psoriasis, seborrheic dermatitis, folliculitis decalvans, acne keloidalis, and dissecting cellulitis. Due to the different treatment approaches and prognoses, it is important to distinguish tinea capitis from invasive dermatoses on the scalp. In this article, histopathological findings of tinea capitis and several advantages and disadvantages of histopathology in the diagnosis of fungal infections are also reviewed and updated.

Retrospective characterisation and outcome of surgical treatment for cervical lymph node abscessation in 15 dogs.

CASE HISTORIES: Medical records of a private referral hospital (Veterinary Emergency Clinic, Toronto, Canada) and a university teaching hospital (Louisiana State University, Baton Rouge, LA, USA) were reviewed, using the search terms lymphadenectomy, lymph node extirpation, cervical lymphadenitis, and lymph node abscessation. Dogs (n = 15) with a diagnosis of cervical lymph node abscessations confirmed through histopathology that underwent surgery for treatment from January 2015-May 2022 were included in the study. Long-term follow-up data was obtained by an in-person visit or telephone interview with each owner. Dogs that met the inclusion criteria were of various breeds with a median age of 6 (min 0.5, max 12) years. All cases presented with cervical swelling and lethargy, with inappetence and fever in 5/15 dogs. The range of duration of clinical signs prior to treatment was 1-3 weeks. Seven dogs were treated with a short course of antibiotics, with or without prednisone, without successful resolution, before referral. CLINICAL FINDINGS: Diagnostic imaging using CT or cervical ultrasound revealed enlargement of unilateral mandibular and retropharyngeal lymph nodes with regional cellulitis and oedema in four dogs, enlargement of unilateral retropharyngeal lymph nodes with regional cellulitis in eight dogs, and a right ventral cervical abscess infiltrating the right medial retropharyngeal lymph nodes with oedema in one dog. Unilateral or bilateral cervical lymph node abscessation was diagnosed by lymphadenectomy and histopathology of affected lymph nodes. Bacterial cultures from samples of excised lymph nodes were positive in six cases. TREATMENT AND OUTCOME: Cervical exploration and lymphadenectomy were performed in all cases. Thirteen dogs received antibiotics along with surgical treatment. Resolution was defined as absence of cervical swelling or enlarged lymph node(s) at the time of long-term follow-up (median 300 (min 240, max 1,072) days). Most patients had resolution of clinical signs following surgical excision of affected lymph nodes. Two dogs had complications including recurrence of clinical signs and development of open wounds following surgery. Their clinical signs resolved following additional administration of antibiotics. CONCLUSIONS AND CLINICAL RELEVANCE: All dogs in this series had lymphadenectomy of abscessed lymph nodes and showed resolution of clinical signs with a favourable outcome. As 13/15 dogs also received antibiotics in conjunction with surgical treatment, appropriate use of antimicrobials may also play a role in treatment of this disease process.

Treatment of dissecting cellulitis of the scalp with tumour necrosis factor inhibitors: a retrospective multicentre study.

Although retinoids are considered as the most effective treatment, management of dissecting cellulitis of the scalp (DCS) is often challenging. A multicentre retrospective study was conducted to evaluate the efficacy of anti-tumour necrosis factor (TNF) agents in treating DCS after failure of other conventional treatments. Twenty-six patients were included. After a mean treatment duration of 19 months (SD 21), the median Physician's Global Assessment score decreased from 3 to 1. The median number of inflammatory nodules and abscesses decreased from 7 to 0.5 and from 1 to 0, respectively. The median Dermatology Life Quality Index and numerical rating scale score for pain severity decreased from 10 to 8 and 6 to 1, respectively. The median treatment satisfaction was 7 out of 10 on the Patient Satisfaction Index. This study confirms the efficacy of anti-TNF agents in treating patients with DCS that is resistant to conventional therapies.

Vascularized Lymph Node Transfer Improved Outcomes of Elderly Patients with Secondary Upper Extremity Lymphedema.

BACKGROUND: Secondary lymphedema is a debilitating morbidity. This study investigated the outcomes of vascularized lymph node transfer (VLNT) in elderly patients with secondary upper extremity lymphedema. METHODS: Between 2008 and 2018, elderly (≥65 years) patients with secondary upper extremity lymphedema who underwent VLNT were retrospectively reviewed. Cheng's Lymphedema Grading, Taiwan Lymphoscintigraphy Staging, and indocyanine green lymphography were used to select the procedures. Outcome measurements included complications, circumferential difference, episodes of cellulitis, and the Lymphedema-Specific Quality of Life questionnaire (LYMQoL). RESULTS: Eleven patients with a mean age of 70.2 ± 5.3 years (range 65-80 years) who underwent VLNT survived and no major complications were encountered. At a mean follow-up of 6.5 ± 3.6 years (range 2-13 years), the mean limb circumferential difference was significantly improved from 25.6 ± 11.5% to 8.3 ± 4.2% (p = 0.016), and the mean episode of cellulitis was statistically reduced from 2.4 ± 1.3 to 0.4 ± 0.9 times/year (p = 0.007). At a follow-up of 24 months, four domains of Function (from 30.6 ± 2.8 to 14.5 ± 2.5), Appearance (from 18.2 ± 1.9 to 8.5 ± 2.1), Symptoms (from 30.4 ± 5.9 to 10.9 ± 1.0) and Mood (from 29.2 ± 4.4 to 10.7 ± 1.0), as well as overall LYMQoL score (from 3.9 ± 1.1 to 7.4 ± 0.5), showed statistical improvement (all p < 0.05). CONCLUSIONS: VLNT for secondary upper extremity lymphedema in elderly patients significantly decreased the limb circumferential difference and frequency of cellulitis and improved quality of life without using compression garments postoperatively.

Wells Syndrome Presenting as Atypical Periorbital Cellulitis.

A 62-year-old man presented with diffuse, painless, left-sided preseptal edema, erythema, and woody induration extending to the left temple. The induration generated an orbital compartment syndrome with markedly elevated intraocular pressure necessitating lateral canthotomy and cantholysis. Although atypical for an infectious etiology, empiric broad-spectrum intravenous antibiotics were initiated with no improvement. A tissue biopsy demonstrated extensive perivascular and interstitial eosinophils with focal flame figures, and the patient was diagnosed with a severe hypersensitivity reaction or eosinophilic cellulitis (Wells syndrome). The disease process remitted rapidly upon initiation of oral prednisone. Wells syndrome is a rare inflammatory eosinophilic dermatosis, most often presenting in the limbs and trunk, with few reports of facial and periorbital involvement. This case highlights the importance of considering Wells syndrome in the differential diagnosis of atypical periorbital cellulitis that is nonresponsive to antibiotics and reviews the clinicopathologic nature of this disease.

Dissecting the Roles of Innate Cells in the Skin and Intractable Skin Diseases.

The skin is not merely a physical barrier but also an active immunological interface, exposed to various external stimuli including microbes. Over the recent years, our laboratory has defined hair follicles as control towers that regulates immune cells residing in the skin. Hair follicles produce chemokines and cytokines that are crucial for the localization and tissue-residency of immune cells including the Langerhans cells, resident memory T cells, and innate lymphoid cells. We also discovered that disruption of the ADAM17-EGF receptor axis and ADAM10-Notch signaling axis leads to dysbiosis on the skin surface and in the hair follicles, respectively. The former leads to microbiome predominance of Staphylococcus aureus and results in atopic skin inflammation, whereas the latter leads to Corynebacterium species predominance that trigger irreversible hair follicle destruction. These findings highlight the distinct mechanisms that regulate the microbiome in different compartments of the skin. In this talk, I will focus on the deeper layers of the skin-the hypodermis (a.k.a subcutaneous tissue), a common site for cellulitis, which we found to be enriched with macrophages. We enabled layer-specific depletion of macrophages, which had prominent effects on the organization of the extracellular matrix, counterintuitively rendering mice highly protected against S. aureus-mediated cellulitis. I will also introduce our ongoing efforts to understand the histology and pathophysiology of Degos disease, an extremely rare and highly fatal disease of unknown etiology.

Lymphangitis Carcinomatosa in Neck Soft Tissue: Computed Tomography Findings With Emphasis on Differentiation From Cellulitis.

OBJECTIVE: Lymphangitis carcinomatosa (LC) is a rare form of metastasis. The purposes of this study were to evaluate computed tomography (CT) findings associated with LC in neck soft tissue and to determine those that were useful in distinguishing LC from cellulitis. METHODS: Contrast-enhanced CT images of 26 patients with pathologically confirmed LC (n = 5) and clinically proven cellulitis (n = 21) were reviewed retrospectively. The following CT findings were evaluated and compared between the 2 groups: subcutaneous fat infiltration, enlargement of muscle, thick irregular enhancement of the superficial cervical fascia, grouping of micronodules, focal intramuscular enhancement, localized fluid collection, and nodular skin thickening. RESULTS: Thick irregular enhancement of the superficial cervical fascia (80.0% vs 0%, P < 0.0005), grouping of micronodules (60.0% vs 0%, P < 0.005), and focal intramuscular enhancement (60.0% vs 4.8%, P < 0.05) were significantly more frequent in LC than in cellulitis. Other findings did not show statistical significance between both groups. CONCLUSIONS: When soft tissue swelling is present in the neck with either thick irregular enhancement of the superficial cervical fascia, grouping of micronodules, or focal intramuscular enhancement, the possibility of LC should be considered especially in patients with underlying malignancy.

Bilateral periorbital leukemia cutis presenting as suspected cellulitis.

Many conditions present with periorbital edema and erythema, mimicking preseptal cellulitis. We report the unique case of a patient with relapsed monoblastic mutant isocitrate dehydrogenase-2 (IDH2) acute myeloid leukemia (AML) who presented with periorbital edema and erythema, unresponsive to antibiotics. Histopathology from punch biopsy was consistent with leukemia cutis. The patient responded rapidly to the initiation of enasidenib, a novel targeted inhibitor of mutant IDH2 enzymes. Our case highlights the importance of considering leukemia cutis in patients with a history of leukemia presenting with periorbital edema and erythema.

A meta-analysis of the efficacy of vascularised lymph node transfer in reducing limb volume and cellulitis episodes in patients with cancer treatment-related lymphoedema.

BACKGROUND: Lymphoedema after cancer treatment is a chronic and disabling complication that presents a significant health care burden during survivorship with limited treatment options. Vascularised lymph node transfer (VLNT) can reconstruct lymphatic flow to reduce limb volumes, but limited higher-order evidence exists to support its effectiveness. AIM: The aim of the study was to systematically review and meta-analyse the effectiveness of VLNT in reducing upper limb (UL) or lower limb (LL) volume and cellulitis episodes in patients with cancer treatment-related lymphoedema (CTRL). METHODS: PubMed, Medline (Ovid) and Embase databases were searched between January 1974 and December 2019. Full-length articles where VLNT was the sole therapeutic procedure for CTRL, reporting volumetric limb, frequency of infection episodes and/or lymphoedema-specific quality-of-life data, were included in a random-effects meta-analysis of circumferential reduction rate (CRR). Methodological quality was assessed using STROBE/CONSORT, and a novel, lymphoedema-specific scoring tool was used to assess lymphoedema-specific methodological reporting. Sensitivity analyses on the site of VLNT harvest and recipient location were performed. RESULTS: Thirty-one studies (581 patients) were eligible for inclusion. VLNT led to significant limb volume reductions in UL (above elbow pooled CRRs [CRRP] = 42.7% [95% confidence interval (CI): 36.5-48.8]; below elbow CRRP = 34.1% [95% CI: 33.0-35.1]) and LL (above knee CRRP = 46.8% [95% CI: 43.2-50.4]; below knee CRRP = 54.6% [95% CI: 39.0-70.2]) CTRL. VLNT flaps from extra-abdominal donor sites were associated with greater volume reductions (CRRP = 49.5% [95% CI: 46.5-52.5]) than those from intra-abdominal donor sites (CRRP = 39.6% [95% CI: 37.2-42.0]) and synchronous autologous breast reconstruction/VLNT flaps (CRRP = 32.7% [95% CI: 11.1-54.4]) (p < 0.05). VLNT was also found to reduce the mean number of cellulitis episodes by 2.1 episodes per year (95% CI: -2.7- -1.4) and increased lymphoedema-specific quality-of-life scores (mean difference in Lymphoedema-Specific Quality of Life (LYMQOL) "overall domain" = +4.26). CONCLUSIONS: VLNT is effective in reducing excess limb volume and cellulitis episodes in both UL and LL lymphoedema after cancer treatment. However, significant heterogeneity exists in outcome reporting, and standardisation of reporting processes is recommended.

Combination of antibiotics, gastric lavage and nasojejunal feeding-an effective alternative for the management of acute phlegmonous gastritis: a case report.

BACKGROUND: Phlegmonous gastritis is a rare bacterial infection of the gastric wall, characterised by purulent inflammation of the gastric mucosa, submucosa and muscularis layers. Phlegmonous gastritis has a high mortality rate, even with correct diagnosis and antimicrobial therapy. CASE PRESENTATION: A 22-year-old man presented for acute epigastric pain associated with aqueous diarrhoea, vomiting and sustained fever. Abdominal computed tomography showed diffuse oedema and thickened gastric wall, increased number and size of abdominal lymph nodes and the absence of pneumoperitoneum. Fibregastroscopy revealed oedematous, ridged and thickened gastric mucosa with abundant purulent secretion, especially in the antrum, consistent with phlegmonous gastritis, which was confirmed by histological evaluation of gastric biopsies. Cultures of the tissue biopsies and purulent secretion were positive for Enterococcus cecorum. He was treated with sensitive antibiotics according to the antibiogram, and importantly, with continuous gastric lavage and individualised nutritional support therapy. He eventually recovered well and was discharged with no abdominal symptoms. CONCLUSIONS: Our case indicates that early diagnosis and immediate treatment are crucial to achieve positive outcomes. The combination of sensitive antibiotics, gastric lavage and early enteral nutrition via nasojejunal feeding might be an effective alternative for the comprehensive treatment of acute phlegmonous gastritis.

Phlegmonous Psoas Muscle Infection Causing Sepsis and Death With Missing Postmortem Computed Tomography Scan Correlation.

ABSTRACT: Infection of the psoas muscle is a rare pathology, which carries a high risk of sepsis and is a potential cause of death. Classic symptoms include back pain and fever and it may be diagnosed premortem on computed tomography or magnetic resonance imaging, where abscess formation may be identified as a discrete rim enhancing and low-attenuation lesion. Infections without abscess formation, such as phlegmonous infection, may be more difficult to identify however, particularly if there is absence of other nonspecific findings, such as gas bubbles. We report a case of Staphylococcus aureus phlegmonous psoas muscle causing sepsis and death with no postmortem computed tomography scan correlation, where clinical history of back pain and an unknown source of sepsis was the only prompt for psoas dissection. This case highlights a potential postmortem computed tomography blind spot in abdominal pathology and we recommend dissecting the psoas muscle if sepsis is suspected but a definitive septic focus is unable to be identified.

Approach to treatment of refractory dissecting cellulitis of the scalp: a systematic review.

BACKGROUND: Dissecting cellulitis is a chronic inflammatory dermatosis that results in disfiguring and painful, purulent lesions. Treatment of patients with disease resistant to standard therapies, including intralesional or topical steroids or antibiotics, can be a dilemma for clinicians. METHODS: We performed a systematic review of the literature in November 2018 to find articles which presented treatment options and outcomes of patients who failed prior treatment with standard therapies. RESULTS: We identified 57 articles of interest, with 53 being case studies or series. Isotretinoin was the most often reported, but the response was limited. Biologics and laser therapy were used less often but demonstrated a better chance of remission. X-ray epilation and surgical excision demonstrated the best remission rates but can be complicated by serious morbidity. CONCLUSION: We propose a regimen for the treatment of recalcitrant cases of dissecting cellulitis. In the future, more robust studies including randomized control trials are needed to identify the preferred treatment options for refractory dissecting cellulitis.

Assessment of quality of life changes in patients with lower extremity lymphedema using an advanced pneumatic compression device at home.

OBJECTIVE: Lymphedema is associated with significant morbidity and healthcare resource usage. Conventional therapy efficacy has been limited, with poor surgical salvage options. Preliminary studies have demonstrated that the use of advanced pneumatic compression devices (APCDs) improves clinical outcomes. However, limited evidence regarding their role in healthcare cost mitigation or health-related quality of life (QOL) is available. METHODS: The present postmarket, multicenter, single-arm, observational clinical trial conducted in the Veterans Affairs Healthcare System evaluated patients with a diagnosis of primary or secondary edema of unilateral or bilateral lower extremities treated with the Flexitouch APCD (Tactile Medical, Minneapolis, Minn) from February 2016 to March 2019. The patients were assessed at baseline and 12, 24, and 52 weeks from enrollment by limb circumference, QOL assessments (short form-36 and Lymphedema Quality of Life), device compliance, cellulitis episodes, and lymphedema-related healthcare use since the previous visit. The primary endpoints of interest were the QOL at baseline compared with at 12 weeks, unscheduled lymphedema-related clinic visits, and hospital admissions at 52 weeks. The secondary endpoints included the change in limb girth and QOL at 52 weeks compared with baseline. RESULTS: A total of 178 patients with lower extremity lymphedema were prospectively enrolled. The present study reports the interim data for the first 74 subjects to complete 52 weeks of APCD treatment. The cohort was predominately male (94.6%), elderly (mean age, 67 years), obese (median body mass index, 32 kg/m2), and most commonly enrolled for the treatment of phlebolymphedema (71.6%) with largely bilateral lower extremity involvement (91.9%). No significant difference was seen in QOL at 12 weeks. However, at 52 weeks, the Lymphedema Quality of Life scores had significantly improved from baseline (6.3 vs 7.4; P < .0001) and the short form-36 had demonstrated significant improvement from baseline in the physical component (38.6 vs 40.8; P = .035), with an effect toward overall improvement in the mental component (49.9 vs 51.3; P = .549). The limb circumference had decreased significantly at 12 weeks compared with baseline (28.5 cm vs 27.7 cm; P = .0005) in the most affected lower extremity, and this reduction had remained stable for the study duration. APCD treatment was associated with a significant reduction in cellulitis episodes (24.3% vs 8.1%; P = .005), lymphedema-related clinic visits (2.2 vs 0.7; P = .02), urgent care visits (1.2 vs 0.3; P = .004), and hospital admissions (0.5 vs 0.1; P = .047) per patient. CONCLUSIONS: The Flexitouch APCD resulted in initial significant limb girth reduction as early as 12 weeks and a steady and sustained improvement in health-related QOL for ≤1 year. The latter was likely reflective of a decrease in cellulitis episodes and fewer associated lymphedema-related clinic and urgent care visits and hospital admissions.

Circulating Secretory Phospholipase A2 Activity following Snakebites and Its Relationship with Envenomation Status and Progression of Local Swelling.

We studied whether circulating secretory phospholipase A2 (sPLA2) activity reliably distinguished patients with snakebite envenomation from those with nonvenomous/dry snakebites, and whether patients with progressive local swelling had persistence of circulating sPLA2 activity despite antivenom treatment. We prospectively enrolled adults presenting to the emergency with a history of snakebite in the past 24 hours. We estimated circulating sPLA2 activity at baseline before antivenom administration and after 48 hours in those with envenomation. We enrolled 52 patients with snakebites (mean age 39.3 ± 12.6 years; 35 [67%] men), and 16 patients with infective cellulitis as controls. Thirty patients had local ± systemic envenomation; 15 were classified as dry/nonvenomous bites; and envenomation status was unclear in seven patients. Baseline sPLA2 activity was significantly higher in snakebite patients than that in those with infective cellulitis (4.64 [3.38-5.91] versus 3.38 [1.69-4.01] nmol/minute/mL; P = 0.005). Among patients with snakebites, sPLA2 activity in the highest quartile was significantly associated with envenomation (12 of 27 versus two of 22; P = 0.010). However, median sPLA2 activity did not differ significantly between patients with envenomation and the rest. Baseline sPLA2 activity was significantly associated with the maximum extent of limb swelling (P = 0.031 for trend). In envenomed patients, circulating sPLA2 activity significantly decreased after 48 hours compared with the baseline (5.49 [3.38-8.86] versus 3.38 [2.53-4.64]; P = 0.003) including those with progressive swelling. Although circulating sPLA2 activity was elevated following snakebites, its sensitivity to diagnose envenomation appears to be limited. Administration of more antivenom after systemic manifestations had reversed might not benefit patients with progressive local swelling.