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.

Cicatricial pemphigoid Brunsting-Perry variant masquerading as neutrophil-mediated cicatricial alopecia.

A 72-year-old male presented with scarring alopecia on the scalp vertex, multiple crusted plaques on the hairline, and a history of vesicular eruption on the face. The scalp showed crusted plaques with loss of follicular ostia. No follicular pustules or compound follicles were present. An initial transverse scalp biopsy showed perifollicular neutrophils, lymphocytes, and plasma cells along with dermal fibrosis. Focal epidermal/dermal and follicular/adventitial dermal clefts were apparent but were thought to be secondary to fibrosis, and the biopsy result was interpreted to represent a neutrophil-mediated cicatricial alopecia. Concurrently, direct immunofluorescence (DIF) analysis showed linear junctional deposition of IgG and C3. A repeat scalp biopsy revealed more prominent epidermal/dermal clefts, fibrosis, mixed infiltrate with neutrophils, lymphocytes, histiocytes, and plasma cells, as well as prominent follicular/adventitial dermal clefts with perifollicular neutrophils. Given the combination of clefts, perijunctional neutrophils, and positive DIF findings, it became clear that this eruption represented the Brunsting-Perry variant of cicatricial pemphigoid. Here, we illustrated that a neutrophil-rich form of cicatricial pemphigoid can masquerade as a neutrophil-mediated scarring alopecia. In evaluating a specimen suspected to be a neutrophil-mediated scarring alopecia, one should be alert to the presence of subepidermal and perifollicular clefting, and consider cicatricial pemphigoid.

Idiopathic pure sudomotor failure: A review and two cases.

Idiopathic pure sudomotor failure (IPSF) is a rare disease characterized by acquired impairment in total body sweating despite exposure to heat or exercise. Its etiology is unknown but thought to involve defective cholinergic receptors on eccrine sweat glands. This article reviews the epidemiology, pathophysiology, presentation, and management of IPSF. Additionally, we report two cases of IPSF treated with multimodal therapy, including stacked antihistamine regimens and omalizumab, resulting in symptom improvement. This is the first report of treatment of IPSF with omalizumab, although its benefit is uncertain and requires further study.

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.

Management of common scabies and postscabetic itch in adults: Lessons learned from a single-center retrospective cohort study.

BACKGROUND: Common scabies can be difficult to diagnose and treat. There are limited data on the clinical characteristics of patients who may benefit from combined topical permethrin plus oral ivermectin. Postscabetic itch is common, but there is scant data describing its prognosis and management. OBJECTIVE: This study describes the clinical characteristics and evaluates treatment outcomes of participants with common scabies treated with combined topical permethrin plus oral ivermectin and describes the prognosis and management of postscabetic itch. METHODS: We conducted a single-center retrospective cohort study of participants with common scabies treated with combined topical permethrin plus oral ivermectin therapy and topical permethrin only. Participants previously treated with permethrin and/or ivermectin were excluded. The primary outcome was clinical outcome at follow-up, categorized as cure, worsening, or no change. Secondary outcomes included time from treatment initiation to cure, duration of follow-up after cure, recurrence rate, frequency of postscabetic itch, and duration of postscabetic itch. RESULTS: Of 55 participants treated with combined topical permethrin plus oral ivermectin, 49 (89%) achieved cure, 5 (9%) had no change, and 1 (2%) had worsening disease. Of 48 participants treated with topical permethrin only, 46 (96%) achieved cure, 2 (4%) had no change, and 0 (0%) had worsening disease. Thirty-five participants (34%) experienced postscabetic itch for 52.5 days (interquartile range, 28-135). More participants in the older (mean: 55 years; standard deviation: 21 years; p = .002) combined treatment group experienced postscabetic itch than in the younger (mean: 42 years; standard deviation: 19 years) permethrin-only treatment group (42% vs. 25%; p = .072). CONCLUSION: These findings support the use of combined topical permethrin plus oral ivermectin therapy in treating common scabies, highlight that postscabetic itch can persist for longer than previously reported, and reveal a potential relationship between older age and postscabetic itch.

Expression of programmed cell death ligand 1 and programmed cell death 1 in cutaneous warts.

BACKGROUND: Cutaneous warts have high prevalence and cause significant morbidity. Understanding the mechanisms by which warts evade the immune system could lead to targeted and improved treatments. OBJECTIVE: To determine whether cutaneous warts express programmed cell death ligand 1 (PD-L1) and to characterize the expression of programmed cell death 1 (PD-1) within the immune infiltrate of inflamed lesions. METHODS: In total, 44 biopsies of cutaneous warts were retrieved from the Department of Dermatopathology archives of the University of California, San Francisco. Biopsies were stained with hematoxylin and eosin and PD-L1 monoclonal antibody, and biopsies of inflamed lesions were stained with PD-1 monoclonal antibody. RESULTS: PD-L1 was expressed on keratinocytes in cases of verrucae vulgares (12/30, 40%) and myrmecia (7/14, 50%) and was associated with an interface inflammatory reaction. PD-1 was expressed by the inflammatory infiltrate in verrucae vulgares (21/24, 88%) and myrmecia (5/8, 63%). LIMITATIONS: This was a retrospective observational study conducted at a single institution. CONCLUSION: Many cutaneous warts express PD-L1, suggesting that human papillomavirus might use this pathway to promote immune dysfunction. This discovery helps explain the recalcitrance of warts to current therapies and provides a rationale for investigating anti-PD-1 immunotherapy as a potential treatment for warts.

Cultural competence for the 21st century dermatologist practicing in the United States.

Significant health disparities exist among under-represented minorities in the Unites States, which can partially be accounted for by the quality of patient-physician interaction. A distinguishing factor of this interaction is the ability of the provider to demonstrate cultural competence, or address the social, cultural, and community influences on healthcare behaviors and incorporate these elements into patient care. However, this practice has yet to be universally implemented in our healthcare system. These factors become even more important as the racial, ethnic and cultural distribution of the United States population changes. Multiple studies have suggested that cultural competence of the health care provider and staff leads to improved patient adherence, satisfaction, and ultimately, health outcome. Cultural competence in the workplace also leads to efficient and cost-effective healthcare and better community integration into healthcare systems. The purpose of this review is to help dermatologists understand the benefits of culturally competent care for their patients and themselves and identify methods and resources to achieve this goal.

Frequency and Management of Sleep Disturbance in Adults with Atopic Dermatitis: A Systematic Review.

INTRODUCTION: Intense nocturnal pruritus as well as the complex pathophysiology of atopic dermatitis (AD) can severely affect sleep and become a major factor in negatively impacting quality of life in adults. However, much of the literature on sleep disturbance in AD patients is on the pediatric population, and it is not well studied in adults. Furthermore, limited studies are available to guide effective management of sleep disturbance in AD in general. We review the literature to present the studies that have investigated the relationship between AD and its effect on sleep in adults and provide an approach for clinicians caring for this population. METHODS: A systematic literature search was conducted through the PubMed and EMBASE databases using the search terms "atopic dermatitis" OR "eczema" AND "sleep." The articles generated by the search and their references were reviewed. RESULTS: A high prevalence of sleep disturbance is experienced by adults with AD. The likelihood of sleep disturbance is much higher in patients with AD compared to those without AD. Sleep disturbance appears to worsen with AD severity. Pruritus and scratching appear to be large contributors to sleep disturbance in adult patients with AD. CONCLUSION: It is important that clinicians evaluate the severity of AD and ask general questions about itching, sleep, impact on daily activities, and persistence of disease during each patient visit and follow-up with the complaint of sleep disturbance. Management of sleep disturbance in AD should focus on adequate disease control of AD as well as possible medical interventions to help improve sleep. The pathophysiology of sleep disturbance in AD is extremely complex, and further research is needed to better understand the interplay of the immune system, circadian rhythm, and environmental factors implicated in both AD and sleep.

A decade of burn unit experience with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Clinical pathological diagnosis and risk factor awareness.

Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) is a rare and often fatal spectrum of mucocutaneous diseases usually attributable to severe adverse drug reactions. Burn units are referral centers for patients at the most extreme end of the disease continuum. Our burn center admits a much higher percentage of TEN (>30% BSA) cases than reported in most prior reviews. The purpose of this study was to analyze the diagnostic and prognostic value of variables collected on referred SJS/TEN patients. We retrospectively analyzed 94 patients admitted to our unit with a presumptive SJS/TEN diagnosis made in most cases by the referring center. Most of the diagnoses were clinical. Fifty of the 94 patients underwent biopsy when the clinical diagnosis was questionable. Of the 50 patients who underwent biopsy, 18 (36%) received an alternative diagnosis. Analysis was therefore limited to 76 patients, i.e. 44 patients felt to have firm clinical diagnoses plus 32 patients with diagnoses confirmed by biopsy. Mean age was 54.3 years (17-93) and overall gender ratio was 43 F vs. 33 M (56.6% vs. 43.4%). Mean LOS was 15.2 days (1-48) and overall mortality was 23.7% (18/76). Univariate analysis revealed percent body surface area (%BSA) did not show statistically significant association with mortality. Histopathological correlation for diagnosis is not standardized across institutions worldwide. Due to challenges in the diagnosis of SJS/TEN and the high incidence of error in clinical diagnosis, it is recommended that all patients with presumed SJS/TEN receive skin biopsies with H&E and direct immunofluorescence. We propose a diagnostic approach in order to address this need. Lack of association between %BSA and mortality suggests that all biopsy-proven SJS/TEN cases belong in specialty centers due to the unstable nature of the disease and risk for rapid progression.