The effect of histopathologic analysis and tissue cultures on inpatient management of cellulitis: a randomized control trial.

BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124). LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.

Pemetrexed-Induced Pseudocellulitis: A Diagnostic Conundrum.

Pemetrexed, an anti-folate, antineoplastic agent, effectively treats various malignancies such as non-small cell lung cancer (NSCLC) and mesothelioma. Here, we report two cases of recurrent pemetrexed-induced lower extremity erythema and edema, one in a 60-year-old male and the other in a 47-year-old male, who were both treated for recurrent cellulitis on multiple occasions before finally being diagnosed with pemetrexed-induced pseudocellulitis (PIP), a rarely reported adverse effect. This is an important diagnostic pitfall for clinicians to be aware of, as early recognition may minimize patient morbidity and prevent unnecessary hospitalization and antibiotic use for presumed cellulitis.

Misdiagnosis of Uncomplicated Cellulitis: a Systematic Review and Meta-analysis.

BACKGROUND: Cellulitis is a clinical diagnosis with several mimics and no gold standard diagnostic criteria. Misdiagnosis is common. This review aims to quantify the proportion of cellulitis misdiagnosis in primary or unscheduled care settings based on a second clinical assessment and describe the proportion and types of alternative diagnoses. METHODS: Electronic searches of Medline, Embase and Cochrane library (including CENTRAL) using MeSH and other subject terms identified 887 randomised and non-randomised clinical trials, and cohort studies. Included articles assessed the proportion of cellulitis misdiagnosis in primary or unscheduled care settings through a second clinical assessment up to 14 days post initial diagnosis of uncomplicated cellulitis. Studies on infants and patients with (peri-)orbital, purulent and severe or complex cellulitis were excluded. Screening and data extraction was conducted independently in pairs. Risk of bias was assessed using a modified risk of bias tool from Hoy et al. Meta-analyses were undertaken where ≥ 3 studies reported the same outcome. RESULTS: Nine studies conducted in the USA, UK and Canada, including a total of 1600 participants, were eligible for inclusion. Six studies were conducted in the inpatient setting; three were in outpatient clinics. All nine included studies provided estimates of the proportion cellulitis misdiagnosis, with a range from 19 to 83%. The mean proportion misdiagnosed was 41% (95% CI 28 to 56% for random effects model). Heterogeneity between studies was very high both statistically (I2 96%, p-value for heterogeneity < 0.001) and clinically. Of the misdiagnoses, 54% were attributed to three conditions (stasis dermatitis, eczematous dermatitis and edema/lymphedema). DISCUSSION: The proportion of cellulitis misdiagnosis when reviewed within 14 days was substantial though highly variable, with the majority attributable to three diagnoses. This highlights the need for timely clinical reassessment and system initiatives to improve diagnostic accuracy of cellulitis and its most common mimics. TRIAL REGISTRATION: Open Science Framework ( https://osf.io/9zt72 ).

Confusion With Presentations of Calcium Pyrophosphate Dihydrate Disease: A Report of Two Cases Mistaken for Cellulitis.

Both pseudogout and cellulitis are diseases that may mimic one another in clinical practice. We discuss two cases of acute calcium pyrophosphate dihydrate (CPPD) arthritis mistaken for cellulitis in the emergency department. Both patients experienced significant improvement after management was changed to treat CPPD. These cases highlight how it is essential for physicians to consider CPPD as a differential diagnosis for a patient that is presenting with signs of inflammation in any joint.

The utility of augmented teledermatology to improve dermatologist diagnosis of cellulitis: a cross-sectional study.

Dermatology consultation for cases of presumed cellulitis improves diagnostic accuracy and management. However, access to in-person consultation remains limited, a gap that could be filled with teledermatology. Augmented teledermatology may improve outcomes. In this cross-sectional study, 20 dermatologists (60% of whom reported conducting inpatient consults > 1 month per year) reviewed 10 real-life cases representing either cellulitis or pseudocellulitis as diagnosed by in-person dermatology consultation. For each case, respondents recorded their diagnosis, confidence, and management decisions after viewing the history and standard teledermatology photos, the responses to a physician-reported cellulitis questionnaire, and finally thermal images. Overall mean diagnostic accuracy increased from 84 ± 4% with the history and physical to 89 ± 3% when adding a cellulitis questionnaire and thermal images (p = 0.23). Accuracy for cellulitis cases specifically significantly increased from 76 ± 6% to 88 ± 4% when adding a cellulitis questionnaire and thermal images (p = 0.049). Accuracy for pseudocellulitis was consistently ≥ 94%. Augmented teledermatology with a standardized questionnaire and thermal images improved diagnostic accuracy for cases of cellulitis and may increase physician confidence. Dermatologists were able to accurately diagnose regardless of experience with inpatient consults, increasing the pool of potential dermatologists who could diagnose cellulitis remotely.

Distinguishing clinical features for pseudocellulitis in pediatric inpatients: A retrospective study.

The clinical features of 588 pediatric inpatients admitted with a diagnosis of cellulitis were reviewed with attention to diagnostic accuracy of true cellulitis (95.1%) versus pseudocellulitis (4.9%) and utilization of specialist consultations (28.1% infectious disease, 6.1% dermatology). Laboratory abnormalities were unable to distinguish cellulitis from pseudocellulitis, supporting previous studies that routine laboratory evaluation may be unnecessary for this diagnosis. Higher rates of pseudocellulitis were identified in cases involving specialist consultation by both dermatology (44.8% pseudocellulitis, 4.1% true cellulitis, p < .001) and infectious disease (48.3% pseudocellulitis, 27.0% true cellulitis, p = .01). Thus, consultation may improve the diagnostic accuracy of suspected cellulitis among pediatric inpatients.

Comparing skin surface temperature to clinical documentation of skin warmth in emergency department patients diagnosed with cellulitis.

Objective: To compare clinical documentation of skin warmth to patient report and quantitative skin surface temperatures of patients diagnosed with cellulitis in the emergency department (ED). Methods: Adult patients (≥18 years) presenting to the ED with an acute complaint involving visible erythema of the lower extremity were prospectively enrolled. Those diagnosed with cellulitis were included in this analysis. Participant report of skin warmth was recorded and skin surface temperature values were obtained from the affected and corresponding unaffected area of skin using thermal cameras. Average temperature (Tavg) was extracted from each image and the difference in Tavg between the affected and unaffected limb was calculated (Tgradient). Clinical documentation of skin warmth was compared to patient report and measured skin warmth (Tgradient >0°C). Results: Among 126 participants diagnosed with cellulitis, 110 (87%) exhibited objective warmth (Tgradient >0°C) and 58 (53%) of these cases had warmth documented in the physical examination. Of those with objective warmth, 86 (78%) self-reported warmth and 7 (6%) had warmth documented in their history of present illness (HPI) (difference = 72%, 95% confidence interval [CI]: 62%-82%; P < 0.001). A significant difference was observed for Tavg affected when warmth was documented (32.1°C) versus not documented (31.0°C) in the physical examination (difference = 1.1°C, 95% CI: 0.29-1.94; P = 0.0083). No association was found between Tgradient and patient-reported or HPI-documented warmth. Conclusions: The majority of ED-diagnosed cellulitis exhibited objective warmth, yet significant discordance was observed between patient-reported, clinician-documented, and measured warmth. This raises concerns over inadequate documentation practices and/or the poor sensitivity of touch as a reliable means to assess skin surface temperature. Introduction of objective temperature measurement tools could reduce subjectivity in the assessment of warmth in patients with suspected cellulitis.

Acute inflammatory edema as a variant of pseudocellulitis resolved after transcatheter aortic valve implantation.

Acute inflammatory edema is a noninfectious inflammatory condition of the skin that is commonly seen in critically ill patients. It is characterized by edematous, erythematous, and nontender plaques involving the abdomen and thighs, sparing areas of the skin subject to pressure. Risk factors include fluid overload, hypoalbuminemia, and obesity. Differentiating acute inflammatory edema from cellulitis can be challenging. Supportive care is the mainstay therapy for acute inflammatory edema, with interventions primarily focused on lowering the fluid burden. We report an unusual case of a nonobese patient in the outpatient setting with acute inflammatory edema.

Retinoblastoma associated with orbital pseudocellulitis and high-risk retinoblastoma: a study of 32 eyes.

PURPOSE: To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. METHODS: Retrospective study of 32 patients who underwent primary enucleation for RB presenting with orbital pseudocellulitis. RESULTS: All RB patients presented with orbital pseudocellulitis. The mean age at presentation of RB was 30 months (median, 24 months; range, 3-70 months). There were 14 (44%) males and 18 (56%) females. All patients were referred with a diagnosis of RB with orbital pseudocellulitis. Tumor was bilateral in 12 (38%) patients but orbital pseudocellulitis was unilateral in all cases. The pseudocellulitis features included proptosis (n = 9; 28%), eyelid edema (n = 22; 69%), conjunctival congestion (n = 23; 72%), and conjunctival chemosis (n = 15; 47%). Based on clinical features and orbital imaging, all patients were diagnosed to have group E intraocular RB. All patients received intravenous steroids prior to enucleation. On histopathology, tumor necrosis was present in all cases with a mean % necrosis of 60% (median, 60%; range, 10% to 90%). Most tumors (72%) were poorly differentiated. High-risk histopathology features were noted in 23 (72%) cases and adjuvant chemotherapy was advised for all these patients. The most common high-risk histopathology features included post-laminar optic nerve infiltration (34%) and scleral infiltration (22%). Over a mean follow-up period of 34 months (median, 9 months; range, < 1-188 months), there was no event of metastasis or death in any patient. CONCLUSION: RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.

Acute Inflammatory Edema: A Case Report with Histopathological and Immunohistochemical Findings.

Acute inflammatory edema (AIE) is a rare variant of pseudocellulitis characterized by blanchable, erythematous, and edematous plaques mainly on the thighs and abdomen and sparing areas of increased pressure. The condition occurs predominantly in critically ill patients with hypoalbuminemia, those with increased body mass index, and those with evidence of fluid overload. AIE was introduced in 2019; however, its histopathological picture has never been elucidated in the literature. We report a case of AIE in a 64-year-old Thai woman with several comorbidities and illustrate its histopathological and immunohistochemical features for the first time. Treatment with diuretics, fluid restriction, and adjuvant hemodialysis revealed marked improvement after ten days. Our report emphasizes that AIE is a distinct dermatosis with specific characteristics that help differentiate AIE from cellulitis and other pseudocellulitic conditions. Furthermore, our observations support the role of lymphatic alterations in the pathogenesis of the disease.

Clinical and immunologic differences in cellulitis vs. pseudocellulitis.

Introduction: The immunologic mechanisms between cellulitis and pseudocellulitis differ greatly, even though their clinical presentations may overlap.Areas covered: This article discusses cellulitis and common entities within the pseudocellulitis spectrum including acute lymphedema, superficial venous thrombosis, allergic contact dermatitis, lipodermatosclerosis, stasis dermatitis, erythema nodosum, cutaneous gout, and bursitis. The literature search was conducted from PubMed search engine between March and May 2021.Expert commentary: While immunologic differences in cellulitis and the various entities of pseudocellulitis are clear, there is a practice gap in applying these differences to the clinic and hospital setting. Further, existing studies are weakened by the lack of a gold-standard diagnosis in this disease category. Additional work is necessary in developing a gold-standard for the diagnosis and secondly, to project these immunologic differences as biomarkers to differentiate sterile inflammation from a potential life threatening bacterial or fungal infection.

Handheld infrared thermometer to evaluate cellulitis: the HI-TEC study.

OBJECTIVES: Differentiating cellulitis from pseudocellulitis is challenging, and misdiagnosis leads to unnecessary antimicrobial use and increased healthcare expenditure. Clinical diagnosis remains the criterion standard and may involve expert consultation. Our objective was to evaluate the usefulness of a handheld infrared thermometer to improve diagnostic certainty in cases of suspected cellulitis. METHODS: We conducted a cross-sectional study from August 2018 to January 2020 at a tertiary-care hospital in Montreal, Canada. We enrolled adult patients with suspected limb cellulitis. Using the infrared thermometer, we compared the average temperature of the affected area with that of the contralateral limb, and we used Youden's method to determine the optimal temperature difference which best differentiated cellulitis from pseudocellulitis as determined by an independent and blinded infectious diseases specialist. We used bootstrapping to estimate 95% confidence intervals for the sensitivity, specificity, and area under the receiver operating curve. RESULTS: Of 65 patients screened for enrolment, 52 patients were recruited (median age: 64 years, IQR 52-76); 39 of these were diagnosed with cellulitis and 13 were not. The mean temperature difference between affected and unaffected limbs was 2.6°C (95%CI 2.1-3.1°C) for patients with cellulitis and 0.4°C (95%CI -1.2°C to 2.1°C) for patients without (p < 0.001). An average temperature difference between limbs of 0.8°C or more was 95% sensitive (95%CI 74-100%) and 69% specific (95%CI 44-95%) for the diagnosis of cellulitis (c-statistic 0.82). CONCLUSIONS: In this proof-of-concept single-centre study, a handheld infrared thermometer was a useful aid to differentiate cellulitis from pseudocellulitis.

Distinguishing Cellulitis from Its Noninfectious Mimics: Approach to the Red Leg.

Cellulitis is a common clinical diagnosis in the outpatient and inpatient setting; studies have demonstrated a surprisingly high misdiagnosis rate: nearly one-third of cases are other conditions (ie, pseudocellulitis). This high rate of misdiagnosis is thought to contribute to nearly $515 million in avoidable health care spending in the United States each year; leading to the delayed or missed diagnosis of pseudocellulitis and to delays in appropriate treatment. There is a broad differential diagnosis for pseudocellulitis, which includes inflammatory and noninflammatory conditions of the skin. Accurate diagnosis of the specific condition causing pseudocellulitis is crucial to management, which varies greatly.

A case of exemestane induced pseudocellulitis.

Exemestane is an aromatase inhibitor increasingly incorporated into the treatment of hormone sensitive breast cancer. Pseudocellulitis describes an uncomplicated inflammation of the dermis and hypodermis from a noninfectious etiology. It presents with erythema, swelling, warmth and tenderness of the affected skin. We report a case of a 47-year-old Indian woman who presented with 2-day history of redness and swelling of her left lower limb. There were no other symptoms. She was recently switched from tamoxifen to aromasin as adjuvant treatment for her breast cancer. Examination revealed erythema, edema, and warmth over the left lower limb. Laboratory investigations and doppler ultrasound scan were unremarkable. Skin punch biopsy showed dermal inflammatory infiltrate composed of lymphocytes, histiocytes and scattered eosinophils and neutrophils, concentrated in the superficial and deep perivascular regions suggestive of a leukocytoclastic vasculitis. The diagnosis of exemestane induced leukocytoclastic vasculitis presenting as pseudocellulitis was made. She was given a course of systemic and topical steroids with completere solution of lesion within 2 weeks. This is the first reported case of exemestane induced pseudocellulitis to our knowledge. Dermatologists and clinicians should be aware of this peculiar adverse drug reaction to avoid misdiagnosis and prevent unnecessary treatment.

Orbital Pseudocellulitis: A Retinoblastoma-Associated Masquerade Syndrome.

INTRODUCTION: A masquerade syndrome is an atypical presentation of a neoplastic process that mimics an inflammatory condition. In this paper, we focus on orbital pseudocellulitis. CASE SERIES: Our case series includes 5 retinoblastoma patients with orbital pseudocellulitis at presentation. In 3 patients the disease was bilateral, in 1 trilateral, and in 1 unilateral. The eyes with pseudocellulitis were enucleated, while the fellow eyes were treated conservatively, when affected. Four patients responded well to the therapy and showed remission of the tumor. The patient with trilateral retinoblastoma did not respond to therapy and died of disease. DISCUSSION: Differential diagnosis with infectious orbital cellulitis is extremely important. Patients with orbital cellulitis present with fever, sinusitis, leukocytosis, and raised inflammatory markers, while ophthalmoscopic examination is negative and imaging studies show sinus involvement. On the contrary, patients with retinoblastoma do not show systemic inflammation, while ophthalmoscopic examination reveals leukocoria, buphthalmos, and an intraocular tumor mass associated with retinal detachment. Magnetic resonance imaging shows intralesional calcifications and soft tissue edema without sinus involvement. Histology confirms the diagnosis. CONCLUSIONS: Medical history, physical examination, and imaging studies are crucial in the diagnosis of retinoblastoma-associated orbital pseudocellulitis. Retinoblastoma should be excluded in all patients with signs of pre-septal orbital cellulitis through fundoscopy and/or imaging studies.

Gemcitabine-induced pseudocellulitis: a case report and review of the literature.

Gemcitabine is a chemotherapeutic agent used in a wide variety of solid tumours. Known side effects include a dose-limiting myelosuppressive toxicity, mild rash, and radiation-dependent dermatitis. Rarely, localized inflammation in the form of pseudocellulitis has also been observed. We present the case of a 77-year-old woman with a history of a Whipple procedure for pancreatic adenocarcinoma who presented to the emergency department after the start of gemcitabine therapy with increased erythema, swelling, and tenderness in her lower legs. Relevant past medical history included peripheral vascular disease, dyslipidemia, and hypertension. A diagnosis of gemcitabine-induced pseudocellulitis aggravated by venous stasis was confirmed after an extensive workup. This case report and the literature review describe this rare reaction, highlighting the need for increased recognition to avoid unnecessary therapeutic intervention.