Real-world comorbidities of atopic dermatitis in the US adult ambulatory population.

BACKGROUND: Atopic dermatitis (AD) is a pruritic, inflammatory skin disease associated with various comorbidities. However, comprehensive analyses of real-world comorbidities in adult patients with AD are limited. OBJECTIVE: To characterize the real-world comorbidities associated with adult AD in an ambulatory population. METHODS: We queried the MarketScan Commercial Claims and Encounters database from January 1, 2017 to December 31, 2017. Multivariable logistic regressions were performed to compare comorbidities in adult patients with AD versus age- and sex-matched controls. RESULTS: A total of 39,779 patients with AD and 353,743 controls were identified. Increased odds of psychiatric conditions, including anxiety (odds ratio [OR] 1.44) and mood disorders (OR 1.31), were observed in patients with AD. Patients with AD had higher likelihoods of autoimmune diseases, including vitiligo (OR 4.44) and alopecia areata (OR 6.01). Adult AD was also associated with infections, including impetigo (OR 9.72), methicillin-resistant Staphylococcus aureus (OR 3.92), and cellulitis (OR 2.52). Patients with AD were more likely to have systemic conditions, including lymphoid/hematopoietic malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47). For all the above, P < .001. LIMITATIONS: Retrospective analysis of health care claims data. CONCLUSION: Adult AD is associated with various psychiatric and systemic comorbidities, emphasizing the systemic nature of AD and the need for the collaborative management of these patients.

Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.

BACKGROUND: Increasing evidence has suggested the systemic nature of atopic dermatitis (AD), a common inflammatory skin condition in children. However, comprehensive analyses of real-world comorbidities in pediatric AD are limited. OBJECTIVE: To characterize comorbidity burden in patients with AD aged <18 years old. METHODS: The MarketScan commercial claims database was queried from January 1, 2017, to December 31, 2017. Age- and sex-matched analyses were used to compare patients with AD with general population controls. RESULTS: A total of 86,969 pediatric patients with AD and 116,564 matched controls were identified. Increased anxiety (odds ratio [OR], 1.20) and attention-deficit hyperactivity disorder (OR, 1.11) were noted in patients with AD. In addition to dermatologic/allergic diseases, AD was also associated with infections, including methicillin-resistant Staphylococcus aureus (OR, 3.76), and autoimmune conditions, including vitiligo (OR, 2.98) and alopecia areata (OR, 4.32). Pediatric patients with AD had higher likelihoods of lymphoid/hematologic malignancies (OR, 1.94), ocular disorders (OR, 1.37-2.02), metabolic syndrome (OR, 1.61), and obesity (OR, 1.81). For all the ORs mentioned above, P was <.001. LIMITATIONS: Retrospective analysis of health care claims data. CONCLUSIONS: AD in pediatric patients was associated with a wide range of psychologic and systemic comorbidities. Increased awareness can help minimize its negative effects on the quality of life and prevent long-term health consequences in young patients with AD.

Retrospective case series of increased oral propranolol dosage for infantile hemangiomas.

BACKGROUND: Infantile hemangiomas (IH) are the most common benign tumor of infancy. Although oral propranolol is currently first-line therapy, optimal dosing for treatment of IH remains debated. We sought to identify hemangioma characteristics associated with poor response to standard dosing (2 mg/kg/d) and to assess the therapeutic benefit of higher dosing. METHODS: Retrospective chart review was conducted of 559 patients with IH seen at Johns Hopkins between 2008 and 2018, of whom 245 (44%) were treated with propranolol. Baseline characteristics were compared between patients who received increased propranolol dosing (≥2.5 mg/kg/d) and those who remained on standard dose (2 mg/kg/d). Changes in the Hemangioma Activity Score (HAS) during the increased dosage period were scored by two trained, blinded pediatric dermatologists. RESULTS: Of 245 patients, 204 (83%) received standard 2 mg/kg/d propranolol dosing while 41 (17%) received a higher dose of ≥2.5 mg/kg/d. The most common location of IH in both groups was the face. In the increased dosage group, 85.4% of IH were of mixed or deep morphology with a mean greatest diameter of 4.6 cm. IH requiring increased dosing received longer courses of propranolol (mean of 389 vs. 282 days, P < .001) and underwent higher rates of excision by plastic surgery (26.8% vs. 5.9%, P < .001). Mean change in HAS over the period with dosage ≥2.5 mg/kg/d was minimal (-0.70; P < .001). CONCLUSIONS: Most recalcitrant IH were located on the face, larger in diameter, and of mixed or deep morphology. Patients had little improvement in HAS score with increased propranolol dosing implemented late in the treatment course with over one-fourth ultimately receiving surgical excision.

Prurigo nodularis: Epidemiology and clinical features.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules that favor the extensor surfaces of the extremities and the trunk. In addition to its significant impact on quality of life, many patients with PN are recalcitrant to therapy because there are currently no therapies approved by the US Food and Drug Administration. In the first article of this 2-part continuing medical education series, we describe the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of PN. Furthermore, we quantify the burden of comorbidities in PN by discussing the broad spectrum of systemic diseases and mental health conditions that have been associated with this condition. The second article of this 2-part series focuses on the pathogenesis of PN and provides detailed algorithms for comprehensive work-up and management.

Prurigo nodularis: Pathogenesis and management.

Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. The second article in this 2-part continuing medical education series focuses on reviewing the pathogenesis of prurigo nodularis and exploring management algorithms for this condition. In addition, we discuss some emerging and novel therapies for treating prurigo nodularis. The first article in this 2-part series describes the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of prurigo nodularis.

Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists.

Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is believed to reduce itching by blocking NK1R on the surface of dermal mast cells. However, the effects of aprepitant on human keratinocytes remains unexplored. Methods: Herein, we examine the effects of aprepitant on EGFR stimulation in HaCaT cells using a phosphoproteomic approach including reverse phase protein arrays and Ingenuity Pathway Analysis. Changes in EGFR phosphorylation were visualized using Western blotting and the effect of EGF and aprepitant on the growth of HaCaT cells was determined using the WST-1 Cell Proliferation Assay System. Results: We found that aprepitant increased the phosphorylation of EGFR, as well as 10 of the 23 intracellular proteins phosphorylated by EGF. Analysis of phosphoproteomic data using Ingenuity Pathway Analysis software revealed that 5 of the top 10 pathways activated by EGF and aprepitant are shared. Conclusions: We propose that aprepitant produces its antipruritic effects by partially activating EGFR. Activation of EGFR by aprepitant was also seen in primary human keratinocytes. In addition to itch reduction through partial activation of shared EGFR pathways, aprepitant exerts a dose-dependent cytotoxicity to epithelial cells, which may contribute to its antitumor effects.

Racial Disparities in the Clinical Presentation and Prognosis of Patients with Mycosis Fungoides.

OBJECTIVE: Racial and gender disparities in mycosis fungoides (MF) are understudied. The objective of this study was to test the hypothesis that worse prognosis in blacks with MF is mediated by higher disease stage at diagnosis and by earlier disease onset in black females. METHODS: We conducted retrospective chart review of 337 patients with clinically-suspected MF seen at Johns Hopkins between 2003 and 2018, requiring biopsy-proven disease for study inclusion. Patient demographics, initial stage/percent body surface area (BSA) involvement, pathology type, flow cytometry results, and treatment regimens were recorded. RESULTS: Of 303 patients with confirmed MF, 166 (55%) were white, 107 (35%) black, 10 (3.3%) Middle Eastern, 6 (2.0%) Asian, and 14 (4.6%) Hispanic/other. Blacks were 3 times as likely (95% CI: 1.2, 8.0) to have Stage 2 disease to have Stage 2 disease at diagnosis as compared to whites as whites. In females, blacks were younger at diagnosis (p = 0.003) and at death (p = 0.008) compared to whites. In males, blacks had 4 times the odds of late-stage disease (p = 0.017) and presented with 19% greater BSA involvement on average compared to whites (p < 0.001). CONCLUSIONS: Compared to their white counterparts in this cohort, black males were diagnosed with MF at a higher stage with greater skin involvement while black females were diagnosed and died earlier. Earlier recognition of MF in skin of color and closer follow-up of black females with early-onset, aggressive disease may help to mitigate disparities in outcomes.

Pruritus Associated with Commonly Prescribed Medications in a Tertiary Care Center.

Background: Sparse data are available on rates of drug-induced pruritus, a well-recognized adverse reaction. We sought to assess relative rates of pruritus associated with commonly prescribed medications. Methods: Using the electronic medical record system EPIC, retrospective data were collected on patients seen at Johns Hopkins who received a medication of interest in a five-year period (2013-2018). Sequential criteria were used to identify the subpopulation who presented with a chief complaint of "pruritus" or diagnosis of "itching" within three months of receiving drugs. Results: We identified 9802 patients with pruritus after drug initiation and 1,085,404 patients without. A higher proportion of those with pruritus were female (70%) than those without (58%), p < 0.001. Patients in both groups were most commonly 50 to 79 years old. A higher proportion of patients with pruritus were black (40%) compared to those without (23%), p < 0.001. In this study, the highest rates of pruritus were observed with heparin (1.11%), trimethoprim-sulfamethoxazole (1.06%), and calcium channel blockers (0.92%). Psychiatric/neurologic drugs used to treat pruritus were associated with low rates of itch. Conclusions: Certain cardiovascular and antimicrobial agents are associated with increased frequencies of pruritus. This knowledge may guide providers in clinical selection of commonly used agents to minimize adverse effects associated with reduced compliance.

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

OBJECTIVES: To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. METHODS: Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. RESULTS: Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3). CONCLUSION: Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Baltimore Reading and Eye Disease Study (BREDS): compliance and satisfaction with glasses usage.

PURPOSE: To assess the patterns and predictors of glasses wear in a 2-year school-based study. METHODS: Second and third graders underwent an eye examination at school. Two pairs of glasses were provided if they met prescribing criteria. Replacements were provided as needed. Students received follow-up examinations and completed survey questionnaires during the same and the following academic year. RESULTS: Of the 197 students prescribed glasses who completed year 1 follow-up, 172 (87%), were observed to still be wearing glasses. However, less than two-thirds of students reported wearing glasses as prescribed (eg full-time if prescribed full-time). Most students, 175 (89%), reported being happy with their glasses and 135 (69%) reported improvement in vision. Thirty-nine students (20%) reported being teased about their glasses. Replacement glasses were required by 136 students (66%). Refractive error was not associated with likelihood of requiring replacement. Being observed wearing glasses correlated with parent (OR = 4.2; 95% CI, 1.2-15.0) and teacher reminders (OR = 6.4; 95% CI, 1.5-28.4) in year 2. CONCLUSIONS: Most children continued to wear glasses during follow-up, yet not always as prescribed. A substantial proportion of students required replacements, underscoring the importance of school-based programs developing mechanisms to monitor eyeglasses usage and mechanisms to replace lost or broken pairs.

Topical timolol as adjunct therapy to shorten oral propranolol therapy for infantile hemangiomas.

BACKGROUND/OBJECTIVES: First-line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta-blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off-label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. METHODS: A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. RESULTS: Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2 months duration (P = 0.006) and were a median of 1.7 months younger (P = 0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P = 0.036). CONCLUSIONS: Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta-blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures.