Livedoid vasculopathy: A review with focus on terminology and pathogenesis.

Livedoid vasculopathy (LV) is a rare thrombotic vasculopathy of the dermis characterized by painful, relapsing ulcers over the lower extremities. Diagnosis is challenging due to the overlap in clinical appearance and nomenclature with other skin disorders. Treatment selection is complicated by poor understanding of the pathogenesis of LV and lack of robust clinical trials evaluating therapy efficacy. The terminology and pathophysiology of LV are reviewed here, along with its epidemiology, clinical and histologic features, and treatment options. A diagnostic pathway is suggested to guide providers in evaluating for comorbidities, referring to appropriate specialists, and choosing from the available classes of therapy.

Hypertrophic Lichen Planus with Histological Features of Squamous Cell Carcinoma Associated with Immune Checkpoint Blockade Therapy.

Immune checkpoint blockade (ICB) is highly effective for the treatment of metastatic cancers, but its side effects are incompletely understood. The objective of this article is to highlight hypertrophic lichen planus (HLP) with histological features diagnosed as squamous cell carcinoma (SCC), which is a potential cutaneous reaction to ICB. Two patients (75 and 69 years) presented with lesions diagnosed as SCC on biopsy, which developed after 3-9 months on ICB therapy. Biopsies demonstrated endophytic, atypical, or cystic squamous proliferations consistent with cutaneous SCC. However, the clinical presentation including monomorphic nature of the lesions and lichenoid inflammation in the background were consistent with HLP. Patients initially received topical 5-fluorouracil (5-FU) to reduce the hyperkeratotic lesions followed by topical steroids. The eruptions readily responded to this treatment regimen. Dermatologic immune-related adverse events (irAEs) are the most common irAEs associated with ICB therapy. Our findings indicate that HLP resembling SCC on biopsy is a potential side effect of ICB that can be correctly diagnosed on careful clinical exam and is responsive to ICB cessation and topical steroid with or without 5-FU treatment. KEY POINTS: Immune checkpoint blockade is associated with cutaneous immune-related adverse events including lichen planus. Hypertrophic lichen planus can appear as squamous cell carcinoma histologically and clinical context is key for the proper diagnosis. Hypertrophic lichen planus can be safely treated with topical steroids with or without topical 5-fluorouracil in cases with severe hyperkeratotic lesions. Immune checkpoint blockade may be safely continued if clinical presentation is consistent with hypertrophic lichen planus.

The ALT-70 cellulitis model maintains predictive value at 24 and 48 hours after presentation.

BACKGROUND: Cellulitis has many potential mimickers, and its misdiagnosis often leads to unnecessary hospitalizations and higher health care costs. The ALT-70 predictive model offers an objective tool to help differentiate between cellulitis and other clinically similar conditions at the time of initial emergency department (ED) presentation. OBJECTIVE: To evaluate the performance of the ALT-70 predictive model at 24 and 48 hours following ED presentation. METHODS: We performed a retrospective review of our prior cohort and expanded our data collection to include data at 24 and 48 hours after initial ED presentation. We compared classification measures for the ALT-70 at the time of initial ED presentation, 24 hours after presentation, and 48 hours after presentation. RESULTS: There was a statistically significant difference in median ALT-70 score between patients with true cellulitis and those with mimickers of cellulitis at all time points. Sensitivity, specificity, positive predictive value, and negative predictive value of the ALT-70 score was similar across all 3 time points. LIMITATIONS: Single-center design may reduce generalizability. CONCLUSION: At 24 and 48 hours, the ALT-70 performed similarly to the way it performed at the time of initial ED presentation, allowing for its use in a wider array of clinical settings.

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.

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.

A predictive model for diagnosis of lower extremity cellulitis: A cross-sectional study.

BACKGROUND: Cellulitis has many clinical mimickers (pseudocellulitis), which leads to frequent misdiagnosis. OBJECTIVE: To create a model for predicting the likelihood of lower extremity cellulitis. METHODS: A cross-sectional review was performed of all patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at a large hospital between 2010 and 2012. Patients discharged with diagnosis of cellulitis were categorized as having cellulitis, while those given an alternative diagnosis were considered to have pseudocellulitis. Bivariate associations between predictor variables and final diagnosis were assessed to develop a 4-variable model. RESULTS: In total, 79 (30.5%) of 259 patients were misdiagnosed with lower extremity cellulitis. Of the variables associated with true cellulitis, the 4 in the final model were asymmetry (unilateral involvement), leukocytosis (white blood cell count ≥10,000/uL), tachycardia (heart rate ≥90 bpm), and age ≥70 years. We converted these variables into a points system to create the ALT-70 cellulitis score as follows: Asymmetry (3 points), Leukocytosis (1 point), Tachycardia (1 point), and age ≥70 (2 points). With this score, 0-2 points indicate ≥83.3% likelihood of pseudocellulitis, and ≥5 points indicate ≥82.2% likelihood of true cellulitis. LIMITATIONS: Prospective validation of this model is needed before widespread clinical use. CONCLUSION: Asymmetry, leukocytosis, tachycardia, and age ≥70 are predictive of lower extremity cellulitis. This model might facilitate more accurate diagnosis and improve patient care.

Squaric acid sensitization is not required for response in the treatment of alopecia areata.

BACKGROUND: Topical immunotherapy using potent contact allergens, such as squaric acid dibutylester (SADBE), can be used to treat alopecia areata. However, there are conflicting reports regarding the best protocol for its administration, particularly with regard to the necessity of an eczematous response after the initial sensitization treatment. OBJECTIVES: We sought to assess the impact of initial sensitization on subsequent hair regrowth. METHODS: This is a retrospective review of the use of SADBE in the treatment of alopecia areata in 14 patients. RESULTS: Eleven of 14 patients underwent initial sensitization before initiating treatment. Three of these patients had an eczematous reaction after 1 attempt, 5 after ≥2 attempts, and 3 failed to develop a clinical reaction. Four of 14 initiated treatment without a clinical reaction or a previous sensitization. Eleven of 14 patients experienced regrowth, 7 with previous sensitization and 4 without. LIMITATIONS: This observational study is limited by sample size. CONCLUSIONS: SADBE sensitization regimens and reactions vary widely, and the absence of an initial eczematous reaction to sensitization does not predict a failed response with continued SADBE treatment.

A case of eczematid-like purpura of Doucas and Kapetanakis in a child.

Eczematid-like purpura of Doucas and Kapetanakis is a subtype of the pigmented purpuric dermatoses, a group of uncommon dermatoses of unclear etiology characterized by purpura, petechiae, and hyperpigmentation. The Doucas and Kapetanakis subtype is rare in children, and its subtle findings can initially be overlooked and mistaken for other, more common dermatologic disorders in this age group. We present a case eczematid-like purpura of Doucas and Kapetanakis in an 11-year-old boy initially treated as eczema.

Extensive and Progressing Congenital Dermal Melanocytosis Leading to Diagnosis of GM1 Gangliosidosis.

Congenital dermal melanocytosis (CDM) is a birthmark composed of macular blue-grey hyperpigmentation commonly observed in the lumbosacral region of infants. Generally resolving by childhood, it is traditionally considered a benign condition, but it may be a sign of underlying lysosomal storage disease. We report a case of biopsy-confirmed CDM in a 2-month-old girl of Brazilian descent later diagnosed with infantile GM1 gangliosidosis.

The utility of re-excising mildly and moderately dysplastic nevi: a retrospective analysis.

BACKGROUND: The management of dysplastic nevi (DN) is a highly debated and controversial topic within the dermatology community. Clinicians agree that margin-positive severely DN should be removed with a surgical margin, however, there is disagreement surrounding the appropriate management of margin-positive mildly and moderately DN. OBJECTIVE: We sought to evaluate the utility of re-excising margin-positive mildly and moderately DN. METHODS: A retrospective chart review was conducted on all adult patients given the diagnosis of a biopsy-proven DN from 2010 through 2011. The primary outcomes were defined as the presence of melanocytic residuum in re-excisional specimens and a clinically significant change in diagnosis. RESULTS: A total of 1809 mildly and moderately DN were diagnosed from 2010 through 2011. In all, 765 (42.3%) of these lesions were found to have positive surgical margins during biopsy, and 495 (64.7) of the 765 lesions were subsequently re-excised. Melanocytic residuum was present in 18.2% of re-excisional specimens. Re-excision resulted in a clinically significant alteration of the diagnosis in only 1 case (0.2%). LIMITATIONS: Limitations include retrospective design and inability to assess for malignant transformation given limited follow-up. CONCLUSIONS: Re-excising mildly and moderately DN results in a low histopathological yield and rarely results in a clinically significant change in diagnosis. As such, clinical monitoring of margin-positive lesions may be warranted.

Hair and Nail Conditions: Hypertrichosis and Hirsutism.

Hypertrichosis and hirsutism can be signs of underlying conditions, some of which may be life-threatening. They also can result in significant psychosocial distress for patients. Hypertrichosis refers to excessive hair growth beyond normal variation for a patient's age, sex, or race or for a particular body area. Hirsutism refers to an abnormal excess of hair growth solely in androgen-dependent areas of the body in females. The standard for hirsutism assessment is the modified Ferriman-Gallwey (mFG) score. Hirsutism can be idiopathic or associated with endocrine conditions, most commonly polycystic ovary syndrome (PCOS). Evaluation for underlying causes may be indicated depending on the clinical presentation. For premenopausal patients with an abnormal hirsutism score (ie, mFG score of 8 or greater), a serum total testosterone level should be obtained. If the level is normal in patients with moderate to severe hirsutism and/or evidence of a hyperandrogenic endocrine condition, an early morning serum total testosterone level and a free testosterone level should be obtained. An elevated total testosterone level indicates a hyperandrogenic state, and further testing is needed to determine if this is due to PCOS or another endocrine condition. Hair removal options for patients with hirsutism include temporary methods, electrolysis, and laser treatments. Pharmacotherapies include topical creams, combination oral contraceptives, and antiandrogens. Referral to an endocrinologist may be indicated if an underlying endocrine condition is suspected.

Risk Factors Predicting Cellulitis Diagnosis in a Prospective Cohort Undergoing Dermatology Consultation in the Emergency Department.

Cellulitis is an infection of the skin and skin-associated structures with many clinical mimickers known collectively as pseudocellulitis. Dermatology or infectious disease consultation is considered the gold standard for diagnosis. We evaluated a prospective cohort of adult patients presenting to the emergency department (ED) with concern for lower extremity cellulitis who received dermatology consultation with conferral of a final diagnosis. Possible risk factors independently associated with cellulitis diagnosis (P<.1) were included in a logistic regression model for prediction of cellulitis diagnosis. Factors having odds ratios with a confidence interval excluding 1 were identified as significant independent predictors. The study identified factors that should be considered in evaluation of patients with suspected uncomplicated lower extremity cellulitis.

A United States expert consensus to standardise definitions, follow-up, and treatment targets for extra-intestinal manifestations in inflammatory bowel disease.

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic stress disorder, and their comorbid conditions: role in pathogenesis and treatment.

As US military service members return from the wars in Iraq and Afghanistan with elevated rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), attention has been increasingly focused on TBI/PTSD comorbidity, its neurobiological mechanisms, and novel and effective treatment approaches. TBI and PTSD, and their comorbid conditions, present with a spectrum of common clinical features such as sleep disturbance, depression, anxiety, irritability, difficulty in concentrating, fatigue, suicidality, chronic pain, and alterations in arousal. These TBI and PTSD disorders are also thought to be characterized by overlapping neural mechanisms. Both conditions are associated with changes in hippocampal, prefrontal cortical, and limbic region function because of alterations in synaptogenesis, dendritic remodeling, and neurogenesis. Neural changes in TBI and PTSD result from pathophysiological disturbances in metabolic, cytotoxic, inflammatory, and apoptic processes, amongst other mechanisms. Neurotrophins have well-established actions in regulating cell growth and survival, differentiation, apoptosis, and cytoskeleton restructuring. A body of research indicates that dysregulation of neural brain-derived neurotrophic factor (BDNF) is found in conditions of TBI and PTSD. Induction of BDNF and activation of its intracellular receptors can produce neural regeneration, reconnection, and dendritic sprouting, and can improve synaptic efficacy. In this review, we consider treatment approaches that enhance BDNF-related signaling and have the potential to restore neural connectivity. Such treatment approaches could facilitate neuroplastic changes that lead to adaptive neural repair and reverse cognitive and emotional deficits in both TBI and PTSD.

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.