Chronic Pruritus: A Review.

Importance: Chronic pruritus, defined as itch experienced for 6 weeks or longer, affects approximately 22% of people in their lifetime. Approximately 1% of physician visits are for the chief concern of chronic pruritus. Chronic pruritus is associated with adverse outcomes, including impaired sleep and reduced quality of life. Observations: Chronic pruritus can be categorized by etiology into inflammatory, neuropathic, or a combination of inflammatory and neuropathic pruritus. Chronic pruritus is due to inflammation in approximately 60% of patients and may be caused by eczema, psoriasis, or seborrheic dermatitis. Chronic pruritus is due to a neuropathic or mixed etiology in approximately 25% of patients. Neuropathic causes of chronic pruritus include postherpetic neuralgia and notalgia paresthetica and are typically due to localized or generalized nerve dysregulation. Approximately 15% of people with chronic pruritus have other causes including systemic diseases with secondary itch, such as uremic pruritus and cholestatic pruritus, medication-induced pruritus such as pruritus due to immunotherapy, and infectious etiologies such as tinea corporis and scabies. When few primary changes are present, a thorough history, review of symptoms, and laboratory evaluation should be performed, particularly for people with chronic pruritus lasting less than 1 year. Clinicians should consider the following tests: complete blood cell count, complete metabolic panel, and thyroid function testing to evaluate for hematologic malignancy, liver disease, kidney disease, or thyroid disease. First-line treatment for inflammatory chronic pruritus includes topical anti-inflammatory therapies such as hydrocortisone (2.5%), triamcinolone (0.1%), or tacrolimus ointment. Approximately 10% of patients do not respond to topical therapies. In these patients, referral to dermatology and systemic oral or injectable treatments such as dupilumab or methotrexate may be considered. When no underlying systemic disease associated with pruritus is identified, patients are likely to have neuropathic chronic pruritus or mixed etiology such as chronic pruritus of unknown origin. In these patients, neuropathic topical treatments such as menthol, pramoxine, or lidocaine can be used either alone or in combination with immunomodulatory agents such as topical steroids. Other effective therapies for neuropathic pruritus include gabapentin, antidepressants such as sertraline or doxepin, or opioid receptor agonist/antagonists such as naltrexone or butorphanol. Conclusions and Relevance: Chronic pruritus can adversely affect quality of life and can be categorized into inflammatory, neuropathic, or a combined etiology. First-line therapies are topical steroids for inflammatory causes, such as hydrocortisone (2.5%) or triamcinolone (0.1%); topical neuropathic agents for neuropathic causes, such as menthol or pramoxine; and combinations of these therapies for mixed etiologies of chronic pruritus.

INDIVIDUAL ARTICLE: Patient Journey and the Burden of Systemic Comorbidities and Sequalae in Prurigo Nodularis.

BACKGROUND: Prurigo Nodularis (PN) is a relatively rare chronic inflammatory skin disease characterized by firm pruritic nodules. PN is associated with significantly increased rates of many systemic and non-systemic comorbidities. This results in a higher burden of disease and utilization of specialty care compared to non-PN United States (US) adults. Psychiatric comorbidities associated with PN include depression and anxiety. In this article, we describe the burden of comorbidities. sequelae of disease, inflammatory disease signatures, and the impact of PN in African American and Asian patients. Furthermore, we explore challenges in the recognition and diagnosis of PN and describe methods to increase awareness of PN among dermatologists. J Drugs Dermatol. 2023;22:12(Suppl 2):s12-14.

Allergens in Common Brands of Clobetasol.

BACKGROUND: Allergic contact dermatitis (ACD) may occur secondary to topical corticosteroids. This may be due to topical corticosteroids containing potential allergens in their vehicles. Variation of allergenic ingredients among various brands of a product has not been well characterized. OBJECTIVE: This study aimed to assess the frequency of allergenic ingredients in various brands and manufacturers of clobetasol propionate. METHODS: Common brands of clobetasol propionate were identified online on GoodRx website. Then, ingredient lists for these products were obtained from the US Food & Drug Administration’s Online Label Repository via a proprietary name search. A systematic literature review was performed using the ingredient name on Medline (PubMed) database to find reports of ACD confirmed by patch testing. CONCLUSIONS: Forty-nine different ingredients were identified among all 18 products included, with an average of 8.4 ingredients per product; 19 of these ingredients have allergenic potential, while one has protective effects. Two branded foam formulations contained the greatest number of potential allergens (5), while a shampoo formulation contained no potential allergens. Knowing which allergens are present in different products may be helpful when treating a patient with an allergy or suspected allergy to one of these ingredients. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.4651.

A review of the current management and burden of prurigo nodularis in the United States.

Prurigo nodularis (PN) is a chronic neural- and immune-mediated disease that is characterized by intense itch, history of skin scratching, and development of papulonodular lesions. These lesions can develop consequent to a cycle of itching and scratching associated with inflammation and changes in skin cells and nerve fibers (eg, pathogenic skin fibrosis, tissue remodeling, and chronic neuronal sensitization). Diagnosis of PN involves individual evaluation of clinical characteristics to identify disease and symptom severity. In the United States, adult patients with PN (estimated, < 90,000) are more likely to be older (age, 50-60 years); in addition, this disease is detected at higher rates in women and Black individuals relative to other demographic subgroups. Still, the small population of patients with PN exhibits considerably high use of health care resources and experiences considerable symptom burden and negatively impacted quality of life. Further, PN is associated with increased rates of a range of comorbid diseases compared with other inflammatory dermatoses (eg, atopic dermatitis, psoriasis). Adequate treatment must address both the neural and immunological component of the disease; there remains a great unmet need for safe and effective therapies that can reduce the burden of disease.

Neuropathic pain and itch: mechanisms in allergic conjunctivitis.

PURPOSE OF REVIEW: Allergic conjunctivitis is highly prevalent and affects up to one third of the general population. The current understanding of the pathophysiology and therapeutic strategies center around the type 2 inflammatory pathway. However, there is an increasing body of evidence that suggests neurogenic mechanisms also play a role in allergic inflammation, with a substantial proportion of allergic conjunctivitis patients experiencing both ocular itch and pain. RECENT FINDINGS: Unmyelinated C fibres on the ocular surface transmit histaminergic itch and can be directly activated by mast cell mediators. The conjunctival mucosa also contains TRPV1+ (histamine-dependent) and TRPA1+ (histamine-independent) neurons that enhance ocular pain and itch in allergic conjunctivitis. Allergen-complexed IgE also binds directly to FcεRI expressed on peripheral neurons. Environmental aeroallergens can also directly stimulate neuronal nociceptors to release inflammatory substances. Allergic inflammation thus stimulates nerve terminals to release vasoactive and inflammatory neuropeptides, leading to a cyclical neuronal dysregulation that augments mast cell activity. These repetitive cycles lead to both peripheral and central sensitization and neuronal plasticity, resulting in decreased itch/pain thresholds and a heightened itch/pain response. SUMMARY: Neurogenic mechanisms including peripheral and central sensitization may drive chronic ocular itch and pain secondary to allergic inflammation. Research into these pathways may help to identify therapeutic targets in allergic conjunctivitis patients with refractory symptoms.

Modulation of the kappa and mu opioid axis for the treatment of chronic pruritus: A review of basic science and clinical implications.

Introduction: Treating chronic pruritus is challenging for dermatologists due to the lack of therapeutic options. We review the effects of κ-opioid receptor (KOR) and µ-opioid receptor (MOR) in the modulation of itch, summarize evidence supporting the efficacy and safety of opioid receptor-targeting agents in chronic pruritus, and address clinical considerations. Results: Preclinical studies have found neural pathways underlying detection, transmission, and modulation of itch signaling and spotlighted the importance of neuronal KOR and MOR in itch perception. Clinical reports suggest that opioid axis modulation may be the basis for the successful treatment of chronic itch. Several agents (MOR antagonist naltrexone; KOR agonists nalfurafine and difelikefalin; dual-acting KOR agonists/MOR antagonists butorphanol and nalbuphine) have been evaluated for treating chronic pruritus in case series, small studies, and clinical trials; nalbuphine has progressed through preliminary (phase II/III) studies in uremic pruritus and prurigo nodularis. The antipruritic efficacy of these agents has been observed across multiple disorders with disparate etiologies, suggesting the potential utility of this class to provide a unified approach to chronic pruritus treatment. Conclusions: The relative safety of these agents, including a reduced potential for dependence versus MOR-agonist analgesics, should help overcome resistance to the use of opioid receptor-targeting agents in chronic pruritus treatment.

Practical approaches for diagnosis and management of prurigo nodularis: United States expert panel consensus.

BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intensely pruritic, raised, nodular lesions. Because there are currently no United States Food and Drug Administration-approved therapies specifically for PN, management is highly variable, and no consensus exists on treatment regimens. OBJECTIVE: To provide practical guidance to help United States dermatologists diagnose and effectively treat patients with PN. METHODS: We participated in a roundtable discussion to develop consensus recommendations on diagnosis and treatment of PN from a United States perspective. RESULTS: The core findings in PN are the presence of firm, nodular lesions; pruritus lasting at least 6 weeks; and a history or signs, or both, of repeated scratching, picking, or rubbing. The diagnostic workup involves a complete review of systems, considering potential systemic diseases, and assessment of disease severity, including disease burden and pruritus intensity. Treatment should be selected based on a patient's clinical presentation, comorbidities, and response to prior treatments and should address both neural and immunologic components of pruritus. LIMITATIONS: Data on PN are from anecdotal or small clinical trials, and all treatments are currently used off-label. CONCLUSION: An effective treatment approach for patients with PN should be based on clinical judgment and tailored to the individual needs of the patient.

Frequency of Allergenic Ingredients in Antifungal Creams.

BACKGROUND: Allergic contact dermatitis (ACD) may occur secondary to topical antifungals containing potential allergens in their vehicles. Variation of allergenic ingredients among commonly used antifungal creams (AFCs) has not been well characterized. OBJECTIVE: The study goal was to assess the frequency of allergenic ingredients in 4 commonly used topical AFCs. METHODS: Topical AFCs (clotrimazole, ketoconazole, miconazole, and terbinafine) were selected, and the ingredient lists for these products were obtained from the US Food and Drug Administration's Online Label Repository via a proprietary name search. A systematic literature review was performed using the ingredient name on MEDLINE (PubMed) database to identify reports of ACD confirmed by patch testing. RESULTS: Of the 20 ingredients analyzed, 6 had frequent allergenic potential. Propylene glycol was the most common cause of ACD identified in the literature and is an ingredient in ketoconazole 2% and miconazole nitrate 2%. Ketoconazole 2% and miconazole nitrate 2% creams contained the highest number of potential allergens (n = 3) among the 4 creams analyzed. CONCLUSIONS: Of the 4 creams, terbinafine hydrochloride 1% and clotrimazole 1% contained the least number of potential allergenic ingredients. Awareness of the allergenic potential of commonly used AFCs may help health care providers when evaluating patients with ACD.

Facial Personal Protective Equipment: Materials, Resterilization Methods, and Management of Occupation-Related Dermatoses.

BACKGROUND: The coronavirus infectious disease 2019 pandemic has resulted in health care workers donning personal protective equipment (PPE) for extended periods. OBJECTIVES: The aims of the study were to review facial PPE (surgical masks and N95 respirators) ingredients, to identify facial PPE resterilization techniques, and to recommend strategies for prevention and management of facial PPE-related dermatoses. METHODS: Twenty-one facial PPE (11 N95 respirators, 10 surgical masks) were reviewed. Resterilization techniques were identified. Personal protective equipment-induced occupational dermatoses and management strategies were explored. RESULTS: Polypropylene is the most common chemical identified in facial PPE. Most masks contain aluminum at the nosepiece. Two surgical masks released nickel. Facial PPE dermatoses include irritant contact dermatitis, allergic contact dermatitis, acne, and contact urticaria. Strategies for prevention and management of facial PPE occupational dermatoses are discussed. CONCLUSIONS: There are increasing reports of occupational dermatoses associated with facial PPE. This review discusses the components of facial PPE, mask resterilization methods, and strategies for prevention and management of facial PPE dermatoses.

Occupational dermatitis to facial personal protective equipment in health care workers: A systematic review.

BACKGROUND: Prolonged wear of facial protective equipment can lead to occupational dermatoses. OBJECTIVE: To identify important causes of occupational dermatoses from facial protective equipment. METHODS: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using PubMed and Embase databases. Articles were included if they reported occupational dermatoses caused by surgical/procedure masks or N95 respirators, or both. RESULTS: We identified 344 articles, and 16 were suitable for inclusion in this review. Selected articles focused on facial occupational dermatoses in health care workers. Allergic contact dermatitis to the elastic straps, glue, and formaldehyde released from the mask fabric was reported. Irritant contact dermatitis was common on the cheeks and nasal bridge due to pressure and friction. Irritant dermatitis was associated with personal history of atopic dermatitis and prolonged mask wear (>6 hours). Acneiform eruption was reported due to prolonged wear and occlusion. Contact urticaria was rare. LIMITATIONS: Only publications listed in PubMed or Embase were included. Most publications were case reports and retrospective studies. CONCLUSION: This systematic review from members of the American Contact Dermatitis Society highlights cases of occupational dermatitis to facial protective equipment, including potential offending allergens. This work may help in the diagnosis and treatment of health care workers with facial occupational dermatitis.

Allergic Contact Dermatitis Secondary to Moisturizers.

Background: Moisturizers are cosmetic products used routinely to manage various skin conditions. Even though moisturizers are often thought to have minimal or no adverse reactions, allergic contact dermatitis (ACD) to these products can develop in some cases. Methods: We studied ingredients included in 3 of the most commonly used moisturizer brands, identified their presence in standard patch testing series, and evaluated their allergenic potential, categorizing the allergens as frequent or infrequent. The standard patch testing series used as reference were the Thin-layer Rapid Use Epicutaneous patch test (T.R.U.E. test), the North American Contact Dermatitis Group (NACDG) screening standard series, and the American Contact Dermatitis Society (ACDS) core allergen series. Results: Aveeno, Cetaphil, and Cerave products had a total of 12, 14, and 9 potential allergens, respectively, the majority of which were infrequent and not included in standard patch testing series. Conclusion: Being aware of the allergenic potential of commonly used moisturizers may help healthcare providers when evaluating patients with ACD. Further testing is recommended in a targeted manner when suspecting ACD with negative standard patch testing series or when ACD is refractory to treatment.

Pediatric Baseline Patch Test Series: Pediatric Contact Dermatitis Workgroup.

BACKGROUND: Allergic contact dermatitis is a challenging diagnostic problem in children. Although epicutaneous patch testing is the diagnostic standard for confirmation of contact sensitization, it is less used in children by dermatologists treating children, pediatric dermatologists, and pediatricians, when compared with adult practitioners. OBJECTIVE: The aim of the study was to create and evaluate standardization of a pediatric patch test series for children older than 6 years. METHODS: We surveyed dermatologists and allergists conducting epicutaneous patch testing in children attending the 2017 American Contact Dermatitis Society meeting held in Washington, DC. This was followed by discussion of collected data and consensus review by a pediatric contact dermatitis working group at the conference. CONCLUSIONS: A baseline pediatric patch test panel was established through working group consensus.

Evidence supports blind screening for internal malignancy in dermatomyositis: Data from 2 large US dermatology cohorts.

The association between dermatomyositis and internal malignancy is well established, but there is little consensus about the methods of cancer screening that should be utilized.We wished to analyze the prevalence and yield of selected cancer screening modalities in patients with dermatomyositis.We performed a retrospective analysis of 2 large US dermatomyositis cohorts comprising 400 patients.We measured the frequency of selected screening tests used to search for malignancy. Patients with a biopsy-confirmed malignancy were identified. Prespecified clinical and laboratory factors were tested for association with malignancy. For each malignancy we identified the screening test(s) that led to diagnosis and classified these tests as either blind (not guided by suspicious sign/symptom) or triggered (by a suspicious sign or symptom).Forty-eight patients (12.0% of total cohort) with 53 cancers were identified with dermatomyositis-associated malignancy. Twenty-one of these 53 cancers (40%) were diagnosed within 1 year of dermatomyositis symptom onset. In multivariate analysis, older age (P = .0005) was the only significant risk factor for internal malignancy. There was no significant difference in cancer incidence between classic and clinically amyopathic patients. Twenty-seven patients (6.8% of the total cohort) harbored an undiagnosed malignancy at the time of dermatomyositis diagnosis. The majority (59%) of these cancers were asymptomatic and computed tomography (CT) scans were the most common studies to reveal a cancer.This is the largest US cohort studied to examine malignancy prevalence and screening practices in dermatomyositis patients. Our results demonstrate that, while undiagnosed malignancy is present in <10% of US patients at the time of dermatomyositis onset, it is often not associated with a suspicious sign or symptom. Our data suggest that effective malignancy screening of dermatomyositis patients often requires evaluation beyond a history, physical examination, and "age-appropriate" cancer screening-these data may help to inform future guidelines for malignancy screening in this population.