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.

Sweet syndrome with perifollicular involvement because of koebnerization from facial hair plucking.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon skin eruption characterized by fever, leukocytosis, and tender erythematous papules, nodules, and plaques. Histopathologically, SS lesions are characterized by marked superficial papillary edema with a dense neutrophilic infiltrate. SS is known to demonstrate both the Koebner phenomenon and pathergy. The majority of reported cases of these phenomena occur following significant cutaneous injury (e.g., biopsies, burns) rather than minor trauma such as pressure and friction. Here, we present the first known reported case of SS koebnerization secondary to minor grooming-related hair plucking. In addition, this is also the first reported case to our knowledge of SS with perifollicular involvement on histopathology.

Localized bullous pemphigoid after knee replacement surgery.

Bullous pemphigoid (BP) most commonly presents as widespread, itchy, tense blisters in older patients. Localized bullous pemphigoid is a less common form of BP that can be more difficult to diagnose because of its similarity to more common conditions such as allergic contact dermatitis or bullous cellulitis. Prompt recognition of localized BP is important so that appropriate treatment can be started. We present a 57-year-old woman who presented with pruritic tense bullae overlying the surgical scar from a knee replacement 6 months prior on her anterior right knee. This case illustrates the potential for localized BP to be triggered by surgical procedures.

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.

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.

Effects of 5-HT2C receptor modulation and the NA reuptake inhibitor atomoxetine in tests of compulsive and impulsive behaviour.

Drug repositioning has gained strategic value as a reaction to high attrition rates of new drugs as they pass through the clinical development process. The 5-HT2C receptor agonist lorcaserin (Belviq®), and the selective NA reuptake inhibitor atomoxetine (Strattera®) represent two drugs FDA approved for obesity and ADHD respectively. Although both drugs are of differing pharmacological class, each share a property of regulating impulsive behaviours in preclinical studies, and thus represent candidates for consideration in clinical conditions labelled as 'impulsive-compulsive disorders'. The present studies investigated both drugs, as well as the highly selective 5-HT2C agonist CP-809101 in two tests of compulsive action: schedule-induced polydipsia (SIP) and increased perseverative [PSV] (and premature [PREM]) responses emitted during an extended ITI 5-choice task. While lorcaserin (0.06-0.6 mg/kg), CP-809101 (0.1-1 mg/kg) and atomoxetine (0.1-1 mg/kg) each reduced both PREM and PSV measures in the 5-choice task, at equivalent doses only lorcaserin and CP-809101 affected excessive water intake in the SIP task, atomoxetine (0.1-2 mg/kg) was essentially ineffective. Further evidence supporting a role of the 5-HT2C receptor as an important regulator of impulsive-compulsive behaviours, the selective antagonist SB-242084 produced the opposing effects to lorcaserin, i.e promoting both impulsive and compulsive behaviours. The profile of atomoxetine may suggest differences in the nature of compulsive action measured either as non-regulatory drinking in the SIP task, and PSV responses made in a 5-choice task. These studies support the consideration of 5-HT2C receptor agonists, typified by lorcaserin, and atomoxetine as potential treatments for clinical conditions categorised as 'impulsive-compulsive disorders'. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Prognostic implications of normal or minimal urinary findings on long-term renal impairment in adults with Henoch-Schönlein purpura.

BACKGROUND: Renal involvement in adult Henoch-Schönlein purpura is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at diagnosis is unknown. OBJECTIVE: To assess the risk of long-term renal impairment in patients with Henoch-Schönlein purpura who present with normal or minimal urinary abnormalities. METHODS: Retrospective cohort study of adult Henoch-Schönlein purpura patients presenting with normal urinalysis results, microscopic hematuria, or low-grade proteinuria. Patients were followed for development of long-term renal impairment, with adjusting for comorbidities. RESULTS: Forty-seven patients were included, with median follow-up 73.9 months (interquartile range 35 to 98 months). Thirty-nine patients (83.0%) had abnormal urinalysis results, of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 patients (17%) had normal urinalysis results, of whom only 1 (12.5%) developed long-term renal impairment (adjusted hazard ratio 10.58; 95% confidence interval 1.18-94.73). Renal events occurred at a median 36.1 months (interquartile range 17.1 to 61 months) from diagnosis, earlier in patients with comorbidities compared with those with none, and in a constant event rate over time. LIMITATIONS: Small sample size. CONCLUSIONS: Microscopic hematuria and low-grade proteinuria at Henoch-Schönlein purpura diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.

Estimating the health care costs associated with recurrent cellulitis managed in the outpatient setting.

BACKGROUND: Recurrent cellulitis is diagnosed in 22% to 49% of all cellulitis cases, but little is known about the costs associated with these cases. OBJECTIVE: To characterize patients with recurrent cellulitis in the outpatient setting and estimate the associated costs. METHODS: A retrospective chart review was conducted for adult patients who presented to the outpatient facilities at our institution from January 1, 2007, to December 31, 2011, with recurrent cellulitis. Data provided by the Centers for Medicare and Medicaid Services were used. RESULTS: A total of 157 patients were identified; 56% were male, with a mean age of 62.7 years. The mean number of episodes of cellulitis per patient was 3. Antibiotics were prescribed for all patients with a diagnosis of recurrent cellulitis, with 93% treated with oral antibiotics and 17.6% treated with intravenous antibiotics. A total of 1081 laboratory and 175 radiologic imaging tests were ordered. The minimum average cost per cellulitis episode was $586.91; the average cost per visit was $292.50. LIMITATIONS: Retrospective study; use of a single, large academic institution; and utilization of cost estimates that may not adequately reflect the variation of costs across closed-system sites or geographic regions. There was no accounting for the nonfinancial or opportunity costs associated with hospitalization, such as lost days of employment or child care and any long-term morbidities, among others. CONCLUSIONS: Recurrent cellulitis in the outpatient setting costs about $586.91 per episode. Although there is no criterion standard for diagnosis or treatment of cellulitis, our analysis demonstrates the need for more evidence-based management to achieve better outcomes and reduce the significant health care costs.

Effect of Dermatology Consultation on Outcomes for Patients With Presumed Cellulitis: A Randomized Clinical Trial.

Importance: Each year, cellulitis leads to 650 000 hospital admissions and is estimated to cost $3.7 billion in the United States. Previous literature has demonstrated a high misdiagnosis rate for cellulitis, which results in unnecessary antibiotic use and health care cost. Objective: To determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis. Design, Setting, and Participants: This randomized clinical trial was conducted in a large urban tertiary care hospital between October 2012 and January 2017, with 1-month follow-up duration. Patients were randomized to the control group, which received the standard of care (ie, treatment by primary medicine team), or the intervention group, which received dermatology consultation. Medical chart review of demographic information and hospital courses was performed. Adult patients hospitalized with presumed diagnosis of cellulitis were eligible. A total of 1300 patients were screened, 1125 were excluded, and 175 were included. Statistical analysis was employed to identify significant outcome differences between the 2 groups. Interventions: Dermatology consultation within 24 hours of hospitalization. Main Outcomes and Measures: Length of hospital stay and duration of intravenous antibiotic treatment. Results: Of 175 participants, 70 (40%) were women and 105 (60%) were men. The mean age was 58.8 years. Length of hospital stay was not statistically different between the 2 groups. The duration of intravenous antibiotic treatment (<4 days: 86.4% vs 72.5%; absolute difference, 13.9%; 95% CI, 1.9%-25.9%; P = .04) and duration of total antibiotic treatment was significantly lower in patients who had early dermatology consultation (<10 days: 50.6% vs 32.5%; absolute difference, 18.1%; 95% CI, 3.7%-32.5%; P = .01). Clinical improvement at 2 weeks was significantly higher for those in the intervention group (79 [89.3%] vs 59 [68.3%]; absolute difference, 21.0%; 95% CI, 9.3%-32.7%; P < .001). There was no significant difference in 1-month readmission rate between the groups (4 [4.5%] vs 6 [6.9%]; absolute difference, -2.4%; 95% CI, -9.3% to 4.5%; P = .54). In the intervention group, the rate of cellulitis misdiagnosis was 30.7% (27 of 88 participants). Among the entire cohort, 101 (57.7%) patients were treated with courses of antibiotics longer than what is recommended by guidelines. Conclusions and Relevance: Early dermatologic consultation can improve outcomes in patients with suspected cellulitis by identifying alternate diagnoses, treating modifiable risk factors, and decreasing length of antibiotic treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01706913.

Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease: A Case-Control Study.

Importance: Calciphylaxis is a rare skin disease with high morbidity and mortality that frequently affects patients with renal disease. Hypercoagulable conditions are frequently observed in both patients with calciphylaxis and those with chronic kidney disease (CKD), complicating our understanding of which hypercoagulable conditions are specific to calciphylaxis. Objective: To identify hypercoagulable conditions that are risk factors for developing calciphylaxis while controlling for CKD. Design, Setting, and Participants: This was a case-control study, comparing the hypercoagulability status of patients with calciphylaxis and with renal disease with that of a matched control population at 2 large urban academic hospitals in Boston, Massachusetts. Retrospective medical record review of laboratory values was performed to identify patients with hypercoagulable conditions. Case and control patients were further stratified based on both severity of CKD and warfarin. Patients with a dermatologic diagnosis of calciphylaxis between 2006 and 2014 and concomitant CKD were included as cases (n = 38). Three controls (n = 114) per case patient with CKD were included, and were matched by age, sex, and race. Main Outcomes and Measures: The rate of various hypercoagulable states (ie, antithrombin III [ATIII] deficiency, protein C and S deficiency, factor V Leiden mutation, prothrombin gene mutation [G20210A], elevated factor VIII level, lupus anticoagulant, anti-IgG or IgM cardiolipin antibodies, heparin-induced thrombocytopenia antibodies, and elevation of homocysteine) in patients with calciphylaxis compared with their matched controls. Results: Of the calciphylaxis cohort, 28 (58%) were female and 18 (55%) were non-Hispanic white. Among all patients, lupus anticoagulant (13 [48%] positive in cases vs 1 [5%] in controls; P = .001), protein C deficiency (9 [50%] vs 1 [8%]; P = .02), and combined thrombophilias (18 [62%] vs 10 [31%]; P = .02) were found to be significantly associated with calciphylaxis. In a subanalysis of patients with stage 5 CKD, only lupus anticoagulant (12 [53%] vs 9 [0%]; P = .01) and combined thrombophilia (15 [63%] vs 1 [8%]; P = .004) remained significantly associated with calciphylaxis. In a separate subanalysis of warfarin-unexposed patients, only lupus anticoagulant (7 [50%] vs 1 [6%]; P = .01) and protein C deficiency (5 [46%] vs 10 [0%]; P = .04) remained significantly associated with calciphylaxis. Conclusions and Relevance: Presence of lupus anticoagulant and combined thrombophilias are risk factors for the development of calciphylaxis in patients with late-stage renal disease. Clinicians should be aware of these associations in patients with impaired kidney function and may consider increased screening and appropriate anticoagulation treatment to reduce the risk of calciphylaxis development.

Location of skin lesions in Henoch-Schönlein purpura and its association with significant renal involvement.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small vessel IgA-predominant vasculitis. OBJECTIVE: To describe adult patients with HSP and determine if the distribution of skin lesions (ie, purpura above the waist or purpura below the waist only), is a predictor of significant renal involvement at the time of the skin biopsy and the months following. METHODS: A retrospective study on renal function from 72 adult patients with skin-biopsy proven HSP. Longitudinal renal data were analyzed after HSP diagnosis by using baseline renal function for comparison. RESULTS: Statistical analysis adjusted for sex, age, and baseline creatinine revealed a trend between HSP lesions only on the upper and lower extremities and long-term renal involvement (4.767, P = .067). Moreover, in another analysis adjusted for age and baseline creatinine, lesions located only on the upper and lower extremities significantly increased the odds of having long-term significant renal involvement (6.55, P = .049) in men. LIMITATIONS: This retrospective study used patient information that was subject to selection bias. CONCLUSION: In patients with HSP, skin lesion distribution on the extremities might be predictive of significant long-term renal involvement and might be critical for risk stratification and development of personalized diagnostics and therapeutics.

Successful Use of Cyclosporin A for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Three Children.

BACKGROUND/OBJECTIVES: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are medical emergencies. Mainstays of treatment include removal of the offending agent, supportive care, and wound care. The use of immunosuppressive agents such as corticosteroids and intravenous immunoglobulin (IVIg) is controversial. Some case reports and small studies report the successful use of cyclosporin A (CsA) for SJS/TEN in halting disease progression, fostering reepithelialization, and reducing mortality. OBJECTIVE: To report on the efficacy of cyclosporine A in the treatment of SJS/TEN in three pediatric patients. METHODS: We describe three pediatric patients seen at a tertiary care hospital in Boston, Massachusetts, diagnosed with SJS/TEN confirmed by skin biopsy who were successfully treated with CsA with improvements seen in time to cessation of disease progression or new lesion formation, reepithelialization, and duration of hospital stay. RESULTS: The average time cessation of disease progression or new lesion formation after CsA administration was 2.2 days (range 1.5-3 days) and average time to remission or reepithelialization was 13 days (range 10-15 days). The average length of hospital stay was 11.7 days (range 4-19 days). CONCLUSIONS: We describe three pediatric patients treated successfully with CsA and provide evidence for the use of cyclosporine in children with SJS/TEN. These results further support previous observations that CsA use for SJS/TEN produces consistently favorable outcomes. The results in this case series are limited by their observational nature. Additional trials are needed to evaluate the safety and efficacy of CsA use in children.

Multiple Café au Lait Spots in a Group of Fair-Skinned Children without Signs or Symptoms of Neurofibromatosis Type 1.

BACKGROUND: The presence of six or more café au lait (CAL) spots is a criterion for the diagnosis of neurofibromatosis type 1 (NF-1). Children with multiple CAL spots are often referred to dermatologists for NF-1 screening. The objective of this case series is to characterize a subset of fair-complected children with red or blond hair and multiple feathery CAL spots who did not meet the criteria for NF-1 at the time of their last evaluation. METHODS: We conducted a chart review of eight patients seen in our pediatric dermatology clinic who were previously identified as having multiple CAL spots and no other signs or symptoms of NF-1. RESULTS: We describe eight patients ages 2 to 9 years old with multiple, irregular CAL spots with feathery borders and no other signs or symptoms of NF-1. Most of these patients had red or blond hair and were fair complected. All patients were evaluated in our pediatric dermatology clinic, some with a geneticist. The number of CAL spots per patient ranged from 5 to 15 (mean 9.4, median 9). CONCLUSION: A subset of children, many with fair complexions and red or blond hair, has an increased number of feathery CAL spots and appears unlikely to develop NF-1, although genetic testing was not conducted. It is important to recognize the benign nature of CAL spots in these patients so that appropriate screening and follow-up recommendations may be made.

Avoiding Medical Errors in Cutaneous Site Identification: A Best Practices Review.

BACKGROUND: Although the field of dermatology has a relatively low incidence of medical errors, dermatologic surgery is a major area where medical errors occur. OBJECTIVE: The purpose of this article is to catalog the many cutaneous site identification techniques used by practitioners and determine which techniques are most evidence based. MATERIALS AND METHODS: A comprehensive literature review of cutaneous surgical site identification techniques and medical errors in dermatology. RESULTS: Wrong-site surgery often occurs because of an inability to identify the surgical site because of factors such as inadequate documentation from referring physicians, well-healed scars obscuring the biopsy site, and a patient's inability to visualize the surgical site. Practitioners use techniques such as photography, dermabrasion, written descriptions using anatomic landmarks, and site identification protocols for surgical site identification. CONCLUSION: Site identification remains a challenge for dermatologists and is a leading cause of medical errors in this field. Patients are often unreliable in their ability to identify biopsy sites; therefore, practitioners must take a proactive role to ensure that medical errors do not occur. This article provides a thorough description and evaluation of current site identification techniques used in dermatology with the aim to improve quality of care and reduce medical errors.

Light-triggered eradication of Acinetobacter baumannii by means of NO delivery from a porous material with an entrapped metal nitrosyl.

A photoactive manganese nitrosyl, namely [Mn(PaPy(3))(NO)](ClO(4)) ({Mn-NO}), has been loaded into the columnar pores of an MCM-41 host. Strong interaction between the polar nitrosyl and the -OH groups on the host wall leads to excellent entrapment of the NO donor within the porous host. With the aluminosilicate-based host (Al-MCM-41), the loading is further enhanced due to electrostatic interaction of the cationic species with the aluminum sites. The extent of loading has been determined via analytical techniques including N(2) adsorption/desorption isometry. Powder X-ray diffraction studies on the loaded materials afford patterns typical of an ordered mesoporous silicate consisting of a hexagonal array of unidimensional channels (with slight loss of crystallinity). Elemental mapping of the loaded particles confirms the incorporation of {Mn-NO} into the porous MCM-41 structure and attests to the homogeneity of the guest molecule distribution throughout individual particles. When suspensions of the loaded materials in saline solution are exposed to low-power (10-100 mW) visible light, rapid release of NO is observed. With continuous exposure, a steady release of 50-80 µM of NO is attained with 5 mg of material/mL buffer within 5 min, and the NO flux is maintained for a period of ~60 min. Rapid bursts of 5-10 µM NO are noted with short light pulses. Loss of either the nitrosyl or its photoproduct(s) from these materials in biological media is minimal over long periods of time. The NO release profiles suggest potential use of these powdery biocompatible materials as NO donors where the delivery of NO (a strong antibiotic) could be controlled via the exposure of light. Such prediction has been confirmed with the successful eradication of both drug-susceptible and drug-resistant Acinetobacter baumannii in a soft-tissue infection model through light-triggered NO delivery.