Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management.

Drug-induced hypersensitivity syndrome, also known as drug reaction with eosinophilia and systemic symptoms, is a severe cutaneous adverse reaction characterized by an exanthem, fever, and hematologic and visceral organ involvement. The differential diagnosis includes other cutaneous adverse reactions, infections, inflammatory and autoimmune diseases, and neoplastic disorders. Three sets of diagnostic criteria have been proposed; however, consensus is lacking. The cornerstone of management is immediate discontinuation of the suspected drug culprit. Systemic corticosteroids remain first-line therapy, but the literature on steroid-sparing agents is expanding. Longitudinal evaluation for sequelae is recommended. Adjunctive tests for risk stratification and drug culprit identification remain under investigation. Part II of this continuing medical education activity begins by exploring the differential diagnosis and diagnosis of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms and concludes with an evidence-based overview of evaluation and treatment.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.

Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.

Monkeypox outbreak, vaccination, and treatment implications for the dermatologic patient: Review and interim guidance from the Medical Dermatology Society.

Rapid human-to-human transmission of monkeypox has created a public health emergency requiring prompt, multidisciplinary attention. Dermatologists are at the forefront of diagnosis due to the disease-defining skin lesions. Moreover, patients with pre-existing skin disease and those who are on immunosuppressive medications for skin disease may be at increased risk of severe infection. In this review, a panel of authors with expertise in complex medical dermatology and managing patients on immunosuppression reviews the literature and provides initial guidance for diagnosis and management in dermatology practices. Though there are knowledge gaps due to a lack of controlled studies, we support use of replication-deficit vaccines in all dermatologic patients who meet qualifying risk or exposure criteria. We offer strategies to optimize vaccine efficacy in patients with immunosuppression. We discuss alternative post-exposure treatments and their safety profiles. Finally, we outline supportive care recommendations for cutaneous manifestations of monkeypox. Large scale epidemiologic investigations and clinical trials will ultimately revise and extend our guidance.

Vaccines: Considerations for pediatric dermatology patients on immunosuppressive agents.

Pediatric dermatologists should be aware of immunization schedules and special recommendations for patients on immunosuppressive agents due to the increased risk of vaccine-preventable infections. Prior to initiating immunosuppressive therapy, pediatric dermatologists should review a vaccine history and administer any necessary age-appropriate or catch-up vaccines. Live vaccines are typically contraindicated while on immunosuppressive therapy, while inactivated vaccines are generally safe to administer.

Vaccine considerations for adult dermatology patients on immunosuppressive and immunomodulatory therapies: a clinical review.

Adults with chronic inflammatory skin disease are at increased risk of vaccine-preventable illnesses and infections, likely because of the underlying disease itself and also their treatment with immunosuppressive and immunomodulatory medications. Despite the association between these agents and increased susceptibility to infection, vaccination rates in dermatology patients remain low. Although preventative care such as vaccinations is typically managed by primary care providers, dermatologists serve a critical role in spreading awareness of the specific risks of immunosuppressive and immunomodulatory agents and promoting understanding of individualized vaccine recommendations. In this review, we provide evidence-based information on vaccine recommendations for adult dermatology patients, specific to age and medication use.

Lack of association of biologic therapy for psoriasis with psychiatric illness: An electronic medical records cohort study.

BACKGROUND: Psoriasis and biologic therapies have been associated with psychiatric illnesses. OBJECTIVE: To determine if persons with psoriasis or those exposed to biologics are more likely to develop a psychiatric illness. METHODS: Retrospective electronic medical records cohort study. RESULTS: Individuals with psoriasis were significantly more likely to have a history of several medical (eg, cardiovascular illnesses) and psychiatric (eg, depression, suicide) illnesses than those without psoriasis. Those with psoriasis who were prescribed a biologic therapy were significantly less likely than those with psoriasis not prescribed a biologic agent to receive a psychiatric illness diagnosis (hazard ratio for any psychiatric illness 0.52, 95% confidence interval 0.51-0.53, P < .0001). With respect to any psychiatric illness, this finding was confirmed when comparing biologic therapy versus methotrexate treatment (0.80, 95% confidence interval 0.76-0.84, P < .0001). LIMITATIONS: These findings were likely attributable to treatment selection bias. CONCLUSION: Individuals with psoriasis have an increased risk of several medical and psychiatric illnesses. Individuals with psoriasis prescribed biologic agents are less likely than those not prescribed biologic agents to develop psychiatric illnesses. Most likely because of treatment selection, individuals with psoriasis prescribed biologic therapy are not currently at increased risk of a psychiatric outcome.

Prevalence of clinically significant incidental findings by whole-body fludeoxyglucose F 18 positron emission tomography/computed tomography scanning in moderate-to-severe psoriasis patients participating in clinical trials.

BACKGROUND: There has been an increase in the number of psoriasis treatments being investigated in clinical trials. Patients may have undiagnosed issues at the start of a study which may become identified during follow-up as incident medicinal conditions. The prevalence of incidental findings in patients with moderate-to-severe psoriasis presenting for clinical trials is unknown. OBJECTIVE: Determine the prevalence of incidentalomas and rate of malignancy identified by fludeoxyglucose F 18 (FDG) positron emission tomography/computed tomography (PET/CT) imaging in clinical trial patients with moderate-to-severe psoriasis. METHODS: A cross-sectional secondary analysis of patients with moderate-to-severe psoriasis who underwent FDG PET/CT scans at the baseline visit, before randomization, for 3 phase 4 clinical trials on vascular inflammation in psoriasis. Only patients without active infection, malignancy, or uncontrolled comorbidities were eligible for the clinical trials. RESULTS: A total of 259 healthy patients with moderate-to-severe psoriasis underwent an FDG PET/CT scan as part of the study procedures. In all, 31 patients (11.97%) (95% confidence interval [CI], 8.28-16.56) had clinically significant incidentalomas on the baseline FDG PET/CT scan. Univariate logistic regression demonstrated that with every increase of 10 years of age, there was an approximate 30% increased risk of discovery of an incidentaloma (odds ratio, 1.30; 95% CI, 1.01-1.68). Of those patients with findings suggestive of malignancy (n = 28), 6 were confirmed to have cancer, resulting in a 2.31% (95% CI, 0.9-5.0) prevalence of malignancy. The positive predictive value of a true cancer was 31.58% (range, 21%-54%). LIMITATIONS: Generalizability and lost to follow-up. CONCLUSION: Incidentalomas on FDG PET/CT imaging are common in otherwise healthy, asymptomatic patients with moderate-to-severe psoriasis in clinical trials. Our results can help inform interpretation of clinical trial safety data and emphasize the importance of compliance with cancer screening recommendations.

Patient-reported outcomes of adalimumab, phototherapy, and placebo in the Vascular Inflammation in Psoriasis Trial: A randomized controlled study.

BACKGROUND: There are limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life. OBJECTIVE: To evaluate the impact of adalimumab and phototherapy on health-related quality of life. METHODS: We examined patient-reported outcomes from a multicenter, randomized, placebo-controlled trial (ClinicalTrials.gov no. NCT01553058). The Dermatology Life Quality Index and EQ-5D-3L were evaluated every 4 weeks. RESULTS: We enrolled 97 patients: 30.9% were female, mean age was 43.5 years (standard deviation, 14.0), and median Psoriasis Area and Severity Index score was 16.7 (interquartile range, 13.9-21.6). At week 12, patients being treated with adalimumab (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.02-8.17) and phototherapy (OR, 8.83; 95% CI, 2.47-31.57) were more likely to achieve the minimal clinically important difference in the Dermatology Life Quality Index compared with those receiving placebo. There were higher odds of achieving the minimal clinically important difference for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR, 9.78; 95% CI, 2.99-31.95) and phototherapy versus adalimumab (OR, 4.07; 95% CI, 1.42-11.70). LIMITATIONS: Small sample size, secondary analysis, generalizability. CONCLUSION: Phototherapy and adalimumab both improve skin-related quality of life and overall health-related quality of life compared with placebo in patients with psoriasis; however, patients treated with phototherapy achieved more improvement in overall health-related quality of life compared with patients treated with adalimumab.

Factors Associated With Patient-Initiated Communication After Mohs Micrographic Surgery.

BACKGROUND: Despite extensive counseling, patients commonly call with postoperative concerns after Mohs micrographic surgery (MMS). OBJECTIVE: We sought to determine the incidence, reasons, and patient and surgical characteristics that lead to patient-initiated communication after MMS. MATERIALS AND METHODS: A retrospective chart review of 1,531 patients who underwent MMS during the observational period was conducted. Demographics and perioperative characteristics of patients who initiated communication were compared with a random sample of matched controls. RESULTS: Of the 1,531 patients who underwent MMS, 263 patients (17.2%) initiated 412 communication encounters within 90 days of surgery. Top reasons for patient-initiated communication included wound concerns, bleeding, and postoperative pain. Female patients and those with a larger surgical defect size (cm) were more likely to call postoperatively. Patients who underwent second intention healing, grafts, and interpolation flaps were more likely to initiate communication compared to patients repaired with a linear closure. CONCLUSION: This study identifies the incidence, reasons, and patient and surgical factors predictive of patient-initiated communication after MMS, which may allow for targeted improvements in postoperative counseling, ameliorating patient anxiety, augmenting patient satisfaction, and improved efficiency for the health care team.

Prescribing Patterns Associated With Biologic Therapies for Psoriasis from a United States Medical Records Database

INTRODUCTION: Selecting a systemic therapy for patients with psoriasis is a complex process, based on a variety of factors including psoriasis severity, comorbid health conditions, access to care, and both patient and provider preference. The objective of this study was to use data from electronic health records to understand prescribing patterns associated with biologic therapies for psoriasis and utilization of concomitant non-biologic psoriasis therapies in patients on biologics. METHODS: A retrospective cohort study was performed using OptumInSight's electronic health records database. Patients were classified as having psoriasis if they had 2 diagnosis codes for psoriasis or 1 diagnosis for psoriasis and a subsequent prescription for a systemic psoriasis therapy or phototherapy on a separate day. Only patients with at least 1 prescription for a biologic medication were included. The time between the first and last prescription in each prescription episode was calculated; at least 1 prescription every 180 days was required to be considered continuous therapy. We also identified a subgroup of patients with prescription episodes of at least 12 months duration in which to evaluate concomitant use of topical medications, phototherapy, and other systemic agents in patients receiving prescriptions for biologics. RESULTS: There were 34,714 eligible psoriasis patients. The median time between first and last prescriptions was 3.3 - 7.0 months, depending on the drug and up to 50% of patients that received a prescription for a biologic medication did not receive a second prescription for the same medication. In a subset of patients with prescription episodes of at least 12 months duration, more than 50% continued to receive prescriptions for topical therapies, most commonly topical steroids. DISCUSSION: Recognition of prescribing patterns associated with biologic medications for psoriasis is important to understand healthcare utilization and improve health systems practices for patients and providers.

Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study.

Aims: To determine the risk of venous thromboembolism (VTE) defined as the combined endpoint of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients with psoriatic arthritis (PsA), psoriasis and rheumatoid arthritis (RA) compared with population controls. Methods and results: A cohort study was conducted in a primary care medical record database in the UK with data from 1994-2014 among patients with PsA, RA, or psoriasis. Cox proportional hazards models were used to calculate the relative hazards for DVT, PE, and VTE. An interaction with disease modifying anti-rheumatic drugs (DMARD) was hypothesized a priori and was significant. Patients with PsA (n = 12 084), RA (n = 51 762), psoriasis (n = 194 288) and controls (n = 1 225 571) matched on general practice and start date were identified. Patients with RA (with and without a DMARD prescription) and patients with mild psoriasis had significantly elevated risks of VTE (HR 1.35, 1.29, and 1.07, respectively) after adjusting for traditional risk factors. Severe psoriasis and PsA prescribed a DMARD had an elevated but not statistically significant risk for VTE. Findings were similar for DVT. The age-and-sex-adjusted risk of PE was elevated in RA, severe psoriasis and PsA patients prescribed a DMARD. Conclusion: While systemic inflammation is a risk factor for VTE, the risk of VTE compared with controls is different among patients with three different inflammatory disorders: RA, PsA, and psoriasis.

Psoriasis and the risk of diabetes: A prospective population-based cohort study.

BACKGROUND: Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking. OBJECTIVE: To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis, stratified by categories of directly assessed body surface area (BSA) affected by psoriasis. METHODS: A prospective, population-based, cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were followed prospectively for approximately 4 years. RESULTS: There were 280 incident cases of diabetes in the psoriasis group (3.44%) and 1867 incident cases of diabetes in those without psoriasis (2.44%). After adjustment for age, sex and body mass index, the hazard ratios for development of incident diabetes were 1.21 (95% confidence interval [CI], 1.01-1.44), 1.01 (95% CI, 0.81-1.26), and 1.64 (95% CI, 1.23-2.18) in the groups with 2% or less of their BSA affected, 3% to 10% of their BSA affected, and 10% or more of their BSA affected compared with in the groups without psoriasis, respectively (P = .004 for trend). Worldwide, we estimate an additional 125,650 new diagnoses of T2DM per year in patients with psoriasis as compared with in those without psoriasis. LIMITATIONS: Relatively short-term follow-up and exclusion of prevalence cases, which may have masked associations in patients with less extensive psoriasis. CONCLUSION: Clinicians may measure BSA affected by psoriasis to target diabetes prevention efforts for patients with psoriasis.

Sweet syndrome in patients with and without malignancy: A retrospective analysis of 83 patients from a tertiary academic referral center.

BACKGROUND: Sweet syndrome is a neutrophilic dermatosis that may be categorized into classic, malignancy-associated, and drug-induced subtypes. Few studies have systematically analyzed this rare disorder. OBJECTIVE: To describe the clinicopathologic characteristics and treatment of Sweet syndrome and identify characteristics associated with concurrent malignancy. METHODS: We retrospectively reviewed patients with Sweet syndrome at the University of Pennsylvania from 2005 to 2015. RESULTS: We identified 83 patients (mean age, 57 years; 51% male) with Sweet syndrome: 30% with the classic form, 44% with the malignancy-associated form, 24% with the drug-induced form in the setting of malignancy, and 2% with the drug-induced form. Acute myeloid leukemia was the most common malignancy (in 24 of 83 patients [29%]). Filgrastim was the most common medication (used in 8 of 83 patients [10%]). Leukopenia (P < .001), anemia (P = .002), thrombocytopenia (P < .001), absence of arthralgia (P < .001), and histiocytoid or subcutaneous histopathology (P = .024) were associated with malignancy (χ2 test). LIMITATIONS: This was a retrospective study that represents patients from a single tertiary academic referral center, which may limit its generalizability to other settings. CONCLUSION: When caring for patients with Sweet syndrome, dermatologists should be aware of the potential association of leukopenia, anemia, thrombocytopenia, absence of arthralgia, and histiocytoid or subcutaneous histopathology with malignancy.

Cutaneous sarcoidosis.

PURPOSE OF REVIEW: Cutaneous sarcoidosis occurs in up to 30% of patients with sarcoidosis and skin findings are often the initial presenting symptom. Cutaneous sarcoidosis is a rare skin disease and many aspects of the disease presentation and treatment are not well understood. This review will highlight developments in the epidemiology, clinical presentation, diagnosis and treatment of cutaneous sarcoidosis over the past several years. RECENT FINDINGS: Epidemiological studies from several different populations reaffirm that cutaneous sarcoidosis is more common in women and is often the presenting symptom of systemic sarcoidosis. Recently, more cases are being reported in association with oncologic immune modulators, which will be of great interest as use of those agents increases. Also, ultrasound has shown promise for the imaging of cutaneous granulomas for disease assessment and measuring response to treatment. Finally, the treatment of cutaneous sarcoidosis remains difficult and is based largely on retrospective data with a paucity of large, prospective trials. There have been recently introduced and validated cutaneous scoring tools which show promise and may lead to more high-quality studies going forward. SUMMARY: The recent developments in cutaneous sarcoidosis have identified many new pharmacologic and physical triggers of disease, but the evidence for effective treatment is still lacking. Further research is necessary to improve the care of patients with cutaneous sarcoidosis.