Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study.

BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity, however limited data is available examining these characteristics over time. OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. RESULTS: Non-nephrogenic calciphylaxis (p=0.0004) and involvement of the fingers (p=0.0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (p=0.01) and genitalia (p=0.022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (p=0.028), increase in lesion number (p=0.012), and recurrent hospitalizations (p=0.020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and non-nephrogenic calciphylaxis, respectively. LIMITATIONS: Limitations include the retrospective nature and data from a single institution. CONCLUSION: Diagnostic delay, particularly in non-nephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

Serpentine supravenous hyperpigmentation induced by chemotherapy: a systematic review.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

Scoring Assessments in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Epidermal necrolysis, the unifying term for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a severe cutaneous drug reaction associated with high morbidity and mortality. Given the rarity of this disease, large-scale prospective research studies are limited. Significant institutional and geographical variations in treatment practices highlight the need for standardization of clinical assessment scores and prioritization of research outcome measures in epidermal necrolysis. At the present, clinical assessment is typically simplified to total body surface area (BSA) involvement, with little focus on morphology. Validated clinical scoring systems are used as mortality prognostication tools, with SCORTEN being the best-validated tool thus far, although the ABCD-10 has also been recently introduced. These tools are imperfect in that they tend to either overestimate or underestimate mortality in certain populations and are not designed to monitor disease progression. Although mortality is often used as a primary endpoint for epidermal necrolysis studies, this outcome fails to capture more nuanced changes in skin disease such as arrest of disease progression while also lacking a validated skin-directed inclusion criterion to stratify patients based on the severity of skin disease at study entry. In addition to mortality, many studies also use BSA stabilization or time to re-epithelialization as endpoints, although these are not clearly defined morphologically, and inter- and intra-rater reliability are unclear. More specific, validated cutaneous assessment scores are necessary in order advance therapeutic options for epidermal necrolysis. In this review, we summarize the strengths and weaknesses of current clinical assessment practices in epidermal necrolysis and highlight the need for standardized research tools to monitor cutaneous involvement throughout the hospitalization.

Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Diffuse Reflectance Spectroscopy with Infrared Thermography for Accurate Prediction of Cellulitis.

Cellulitis is frequently misdiagnosed owing to its clinical mimickers, collectively known as pseudocellulitis. This study investigated diffuse reflectance spectroscopy (DRS) alone and in combination with infrared thermography (IRT) for the differentiation of cellulitis from pseudocellulitis. A prospective cohort study at an urban academic hospital was conducted from March 2017 to March 2018. Patients presenting to the emergency department with presumed cellulitis were screened for eligibility, and 30 adult patients were enrolled. Dermatology consultation conferred a final diagnosis of cellulitis or pseudocellulitis. DRS measurements yielded a spectral ratio between 556 nm (deoxyhemoglobin peak) and 542 nm (oxyhemoglobin peak), and IRT measurements yielded temperature differentials between the affected and unaffected skin. Of the 30 enrolled patients, 30% were diagnosed with pseudocellulitis. DRS revealed higher spectral ratios in patients with cellulitis (P = 0.005). A single parameter model using logistic regression on DRS measurements alone demonstrated a classification accuracy of 77.0%. A dual parameter model using linear discriminant analysis on DRS and IRT measurements combined demonstrated a 95.2% sensitivity, 77.8% specificity, and 90.0% accuracy for cellulitis prediction. DRS and IRT combined diagnoses cellulitis with an accuracy of 90%. DRS and IRT are inexpensive and noninvasive, and their use may reduce cellulitis misdiagnosis.

Clinical mimickers of calciphylaxis: A retrospective study.

BACKGROUND: Calciphylaxis is an ischemic vasculopathy with high morbidity and mortality. Early and accurate diagnosis is critical to management of calciphylaxis. Clinical mimickers may contribute to delayed or misdiagnosis. OBJECTIVE: To assess the rate and risk factors for misdiagnosis and to identify clinical mimickers of calciphylaxis. METHODS: A retrospective medical record review was conducted of patients with calciphylaxis at a large urban tertiary care hospital between 2006 and 2018. RESULTS: Of 119 patients diagnosed with calciphylaxis, 73.1% were initially misdiagnosed. Of patients not initially misdiagnosed, median time to diagnosis from initial presentation was 4.5 days (interquartile range, 1.0-23.3), compared to 33 days (interquartile range, 13.0-68.8) in patients who were initially misdiagnosed (P = .0002). The most common misdiagnoses were cellulitis (31.0%), unspecified skin infection (8.0%), and peripheral vascular disease (6.9%). Patients who were misdiagnosed frequently received at least 1 course of antibiotics. Patients with end-stage renal disease were less likely to be misdiagnosed than those without this disease (P = .001). LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: Understanding the risk factors for misdiagnosis of calciphylaxis is an opportunity for further education concerning this rare disease.

Assessment of outcomes of calciphylaxis.

BACKGROUND: Calciphylaxis is a rare thrombotic vasculopathy characterized by high morbidity and mortality. There is a paucity of studies examining longitudinal outcomes. OBJECTIVE: To assess mortality, days spent in the hospital, and amputations in patients with calciphylaxis. METHODS: A retrospective medical record review was conducted in 145 patients diagnosed with calciphylaxis at an urban tertiary care hospital from January 2006 to December 2018. RESULTS: Six-month mortality was 37.2%, and 1-year mortality was 44.1%. Patients with nephrogenic calciphylaxis had worse survival than those with nonnephrogenic calciphylaxis (P = .007). This difference in survival disappeared when limiting mortality to deaths due to calciphylaxis. Age (P = .003) and end-stage renal disease (P = .01) were risk factors associated with 1-year mortality. Diabetes mellitus was associated with greater total hospitalization days (coefficient, 1.1; 95% confidence interval, 1.01-1.4); bedside debridement was associated with fewer hospitalization days (coefficient, 0.8; 95% confidence interval, 0.7-0.9). Amputations were not associated with any of the examined risk factors. The use of warfarin followed by a transition to nonwarfarin anticoagulation was associated with decreased hazard of death (P = .01). LIMITATIONS: Retrospective nature. CONCLUSIONS: Calciphylaxis remains a complex, heterogeneous disease. Mortality is lower in patients with nonnephrogenic disease. These findings may be incorporated during discussions regarding the goals of care to facilitate informed shared decision making.

Penile calciphylaxis: A retrospective case-control study.

BACKGROUND: Calciphylaxis is a rare disorder characterized by skin necrosis caused by calcium deposition within vessels, thrombosis, and subsequent tissue ischemia. Penile involvement may rarely occur. OBJECTIVE: To identify risk factors, diagnosis, management, and mortality of patients with penile calciphylaxis. METHODS: A retrospective medical record review was conducted of 16 patients with penile calciphylaxis treated at 2 large urban tertiary care centers between January 2001 and December 2019. A control group of 44 male patients with nonpenile calciphylaxis at the same institution was included. RESULTS: The median survival of patients with penile calciphylaxis was 3.8 months (interquartile range, 27.0 months). Mortality was 50% at 3 months and 62.5% at 6 months for penile calciphylaxis, and 13.6% at 3 months and 29.5% at 6 months for controls (P = .008). Patients with penile calciphylaxis were less likely to be obese (P = .04) but more likely to have hyperparathyroidism (P = .0003) and end-stage renal disease (P = .049). LIMITATIONS: Retrospective study design and small sample size. CONCLUSIONS: This study further defines the disease course of penile calciphylaxis, which has high mortality. Imaging may be used to aid diagnosis. Risk factors include end-stage renal disease, hyperparathyroidism, and normal body mass index.

Laser Plume From Human Papillomavirus-Infected Tissue: A Systematic Review.

BACKGROUND: Laser procedures are becoming more prevalent across multiple medical specialties for a variety of indications. The plumes created by these lasers have raised concern for the dissemination of an infectious material. OBJECTIVE: To review and summarize the information on viral dissemination in laser plumes available in the literature. MATERIALS AND METHODS: Data Sources A systematic review was performed on English and non-English articles using the PubMed and the Cochrane databases. A manual search of bibliographies from relevant articles was also performed to collect additional studies. STUDY SELECTION: Only articles in the English language with full texts available that pertained to viral particles in laser plumes were included. Data Extraction Two authors performed independent article selections using predefined inclusion and exclusion criteria. RESULTS: There have been case reports of possible transmission of human papillomavirus (HPV) by inhalation of laser-produced aerosols. Multiple investigators have attempted to recreate this scenario in the laboratory to qualify this risk. Others have conducted clinical experiments to determine the presence of HPV in laser plumes. CONCLUSION: The current body of the literature suggests that laser surgeons are at a risk for HPV exposure by inhalation of laser-derived aerosols. We offer best practice recommendations for laser operators.