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.

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.

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.

Non-tuberculous mycobacterial infections following cosmetic laser procedures: a case report and review of the literature.

Skin infections are not uncommon after cosmetic laser procedures. Infection rates following ablative laser resurfacing procedures are reported to be as high as 7.6%, compared to 1.9% for fractional ablation. An infrequent yet important infectious complication of ablative laser treatment is that caused by non-tuberculous mycobacteria (NTM).

Imiquimod-induced subacute cutaneous lupus erythematosus-like changes.

Imiquimod is a topical immunomodulator used to treat genital warts and cutaneous malignancies that exerts its effects via induction of proinflammatory cytokines through activation of toll-like receptor (TLR) 7. Although subacute cutaneous lupus erythematosus (SCLE) has been reported in association with multiple systemic medications, SCLE in patients treated with topical agents has not been widely reported. We report the case of a 50-year-old woman with local induction of lesions that clinically and histologically resembled SCLE following treatment with topical imiquimod.

Guidelines of care for the management of atopic dermatitis: Section 4. Prevention of disease flares and use of adjunctive therapies and approaches.

Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence.

Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents.

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.

Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.

Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.

Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

Update on the immunological mechanism of action behind phototherapy.

Phototherapy is often used to treat inflammatory skin conditions such as psoriasis and eczema. Much progress has recently been made in understanding the mechanisms underlying the local, cutaneous immune effects induced by phototherapy. Unlike many immunosuppressive drugs used in the management of inflammatory skin disease, phototherapy not only targets effector immune cells but also appears to up-regulate regulatory T cells (Tregs). Additionally, phototherapy reverses epidermal barrier abnormalities common in these diseases, allowing for restoration of cutaneous homeostasis.

Itch as a patient-reported symptom in ambulatory care visits in the United States.

BACKGROUND: European studies have shown that itch is a widespread symptom, yet little is known about its frequency in the United States. OBJECTIVE: We sought to describe ambulatory care visits to clinicians in the United States for which itch was coded as a patient symptom. METHODS: This study uses retrospective data from the National Ambulatory Medical Care Survey from 1999 through 2009. RESULTS: Itch was coded as a symptom for an average of 7 million visits per year or approximately 1% of all outpatient visits, which was nearly 40% of the number of visits for the symptom of low back pain. Patients seen in visits for itch were more likely to be black or Asian than other patients (20% vs 14%). They were also more likely than other patients to receive a new medication (68% vs 36%) and were over twice as likely to receive 2 or more new medications (31% vs 14%). LIMITATIONS: Secondary data sets may not optimally capture patient reports and some of the procedures or medications may have been ordered for reasons other than itch. CONCLUSION: Visits to clinicians for itch represent a sizeable proportion of ambulatory care visits in the United States, and research on the epidemiology, treatments, and causes of itch should be a priority.

Online learning in a dermatology clerkship: piloting the new American Academy of Dermatology Medical Student Core Curriculum.

BACKGROUND: Multiple studies have shown that both current and future primary care providers have insufficient education and training in dermatology. To address the limitations and wide variability in medical student dermatology instruction, the American Academy of Dermatology (AAD) created a standardized, online curriculum for both dermatology learners and educators. OBJECTIVE: We sought to determine the impact of the integration of the AAD online curriculum into a 2-week introductory dermatology clerkship for fourth-year medical students. METHODS: In addition to their clinical duties, we assigned 18 online modules at a rate of 1 to 3 per day. We evaluated knowledge acquisition using a 50-item, multiple-choice pretest and posttest. Postmodule and end-of-course questionnaires contained both closed and open-ended items soliciting students' perceptions about usability and satisfaction. RESULTS: All 51 participants significantly improved in their dermatology knowledge (P < .001). The majority of students found the modules easy to navigate (95%) and worth their time (93%). All respondents supported the continuation of the modules as part of the dermatology clerkship. LIMITATIONS: Without a control group who did not experience the online curriculum, we are unable to isolate the specific impact of the online modules on students' learning. CONCLUSION: This study demonstrates the successful integration of this educational resource into a 2-week, university-based dermatology clerkship. Students' perceptions regarding usability and satisfaction were overwhelmingly positive, suggesting that the online curriculum is highly acceptable to learners. Widespread use of this curriculum may be a significant advancement in standardized dermatology learning for medical students.

Keratitis, ichthyosis, and deafness syndrome: a review of infectious and neoplastic complications.

Keratitis, ichthyosis, and deafness (KID) syndrome is a rare genodermatosis associated with mutations in the connexin 26 gene. Although characterized by this clinical triad, KID syndrome predisposes to a heterogeneous spectrum of cutaneous manifestations and complications, both infectious and neoplastic in nature. Chronic mucocutaneous candidiasis and/or superinfection of skin lesions commonly occur and warrant aggressive therapeutic intervention. Benign neoplasms, namely trichilemmal tumors, have also been reported and can herald malignant growth and invasive disease. Squamous cell carcinoma of both mucosa and skin, especially acral sites, occurs in approximately 15% of patients. The pathogenesis of KID syndrome can be at least partially explained by the role of connexin 26 in intercellular communication and carcinogenesis, but the precise mechanism of disease remains unclear. Treatment strategies, which have ranged from antifungals and antibiotics to systemic retinoids, pose an ongoing challenge given the spectrum of disease. A review of the literature, with a particular focus on infection and malignancy associated with KID syndrome, and updates on the pathogenesis of disease, is discussed.

Pruritus in the older patient: a clinical review.

IMPORTANCE: Pruritus is a common problem among elderly people and, when severe, causes as much discomfort as chronic pain. Little evidence supports pruritus treatment, limiting therapeutic possibilities and resulting in challenging management problems. OBJECTIVES: To present the evidence on the etiology, diagnosis, and treatment of pruritus in the elderly and, using the best available evidence, provide an approach for generalist physicians caring for older patients with pruritus. EVIDENCE REVIEW: PubMed and EMBASE databases were searched (1946-August 2013).The Cochrane Database of Systematic Reviews and the Agency for Healthcare Research and Quality Systematic Review Data Repository were also searched from their inception to August 2013. References from retrieved articles were evaluated. FINDINGS: More than 50% of elderly patients have xerosis (dry skin). Xerosis treatment should be included in the initial therapy for pruritus in all elderly patients. Calcium channel blockers and hydrochlorothiazide are important causes of pruritic skin eruptions in older patients. Neuropathic pruritus is infrequently considered but may cause localized itching (especially in the genital area) and generalized truncal pruritus (especially in patients with diabetes mellitus). Certain skin conditions are more common in elderly patients, including scabies, bullous pemphigoid, transient acantholytic dermatosis, and mycosis fungoides, and should be considered in elderly patients with pruritus. CONCLUSIONS AND RELEVANCE: It is important to evaluate elderly patients for dermatological, systemic, and neurological etiologies of itch. A simple-to-apply diagnostic and therapeutic algorithm can be used. Xerosis, drug reactions, and neuropathy should be considered when evaluating pruritus.

Erosive pustular dermatosis of the scalp: a review with a focus on dapsone therapy.

BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory disorder of unknown origin characterized by pustules, erosions, and crusting in areas of alopecia that tend to be atrophic, actinically damaged, or both. The most common treatments reported include antibiotics and topical anti-inflammatories, which can be ineffective. In the search for effective treatment for EPDS, we share our experience with topical dapsone 5% gel. OBSERVATIONS: We present 4 patients with EPDS, all with classic clinical presentations and histologic findings of EPDS, who had failed a variety of treatments including oral, intralesional, or topical steroids, tacrolimus, and antibiotics. All patients demonstrated rapid improvement or resolution with topical dapsone 5% gel. LIMITATIONS: Our experience and success with topical dapsone for EPDS is observational and not the result of a randomized controlled trial. CONCLUSION: Our observations demonstrate topical dapsone 5% gel to be a novel, safe, and efficacious therapeutic alternative for mild to moderate EPDS.