Secukinumab in adult patients with lichen planus: Efficacy and safety results from the randomised, placebo-controlled, proof-of-concept PRELUDE study.

BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden; representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP), inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a, randomised, double-blind, placebo-controlled, Phase 2 proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomised to eithersecukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W), or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤2 at Week 16. RESULTS: Overall, 111 patients were randomised (n=37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the 3 cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤2 response at Week 16 with SECQ4W vs. placebo in the MLP (37.5% [95% credibility interval (Crl): 20.3-57.2] vs. 23.1% [95% Crl: 6.5-49.2]) and LPP cohorts (37.5% [95% Crl: 20.2-57.3] vs. 30.8% [95% Crl: 10.8-57.6]). In the LPP cohort, a sustained response for IGA ≤2 from Week 16 to Week 32 was achieved with SECQ4W (Week 16: 37.5%; Week 32: 45.8%), and a substantial improvement was observed in IGA ≤2 response in patients of this cohort switching from placebo (Week 16: 30.8%) to SECQ2W after Week 16 (Week 32: 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomised controlled basket trial evaluating interleukin-17A inhibition with secukinumab across 3 subtypes of LP. Secukinumab was well-tolerated and safe, showing different response rates across the 3 subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of interleukin-17A across LP subtypes. The novel IGA score showed significant correlation with patient as well as physician reported outcome measurements. TRIAL REGISTRATION NUMBER: NCT04300296.

Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.

BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with ClinicalTrials.gov: 'Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris' - NCT03342573. RESULTS: At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment-related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. CONCLUSIONS: Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL-17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)-17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti-IL-17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.

A Review of Oral Therapies for the Treatment of Skin Hyperpigmentation.

This review article examines evidence supporting the use of oral therapies in treating idiopathic, actinic, and metabolically induced skin hyperpigmentation. A thorough review of the literature regarding oral treatments for hyperpigmentation was systematically conducted through PubMed. Keywords used in the primary search include "Hyperpigmentation," "Melanosis" or "Melasma," "Lightening," "Oral," and "Therapeutics." The search was limited to the English language, and no timeframe restrictions were implemented. Numerous orally administered therapies have been proposed for the treatment of skin hyperpigmentation. There is an abundant body of literature demonstrating the efficacy of orally administered tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. It is reasonable to expect that the most effective oral therapies will address known underlying causes of hyperpigmentation such as thyroid disease, diabetes, and hormonal imbalance. Improvement due to oral therapy of otherwise unresponsive skin hyperpigmentation or hyperpigmentation of unknown cause is less predictable. This review is limited by the strength of evidence contained within the available studies. Clinical studies investigating the treatments discussed within this article are limited in number, at times lack blinding in the study design, and are based on small sample sizes. Based on existing research, the most promising oral remedies for hyperpigmentation appear to be tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. Additional studies to better establish safety and efficacy are necessary.

How to Sequence Therapies in Mycosis Fungoides.

OPINION STATEMENT: Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.

Epidermolytic hyperkeratosis of the vulva.

Vulvar epidermolytic hyperkeratosis is a benign entity that mimics other malignant and inflammatory vulvar dermatoses clinically and histologically requiring careful clinical pathologic correlation for diagnosis.

Association of antinuclear antibody status with clinical features and malignancy risk in adult-onset dermatomyositis.

BACKGROUND: The clinical significance of antinuclear antibody (ANA) status in adults with dermatomyositis (DM) has yet to be fully defined. OBJECTIVE: We compared the incidence of amyopathic disease, risk of malignancy, and clinical findings in ANA+ and ANA- patients with adult-onset DM. METHODS: This was a retrospective cohort study of patients with ANA+ or ANA- adult-onset DM determined by enzyme-linked immunosorbent assay. RESULTS: Of 231 patients, 140 (61%) were ANA+ and 91 (39%) were ANA-. Compared with the ANA- patients, the ANA+ patients had a lower frequency of dysphagia (15% vs 26% [P = .033]) and heliotrope rash (38% vs 53% [P = .026]). In all, 54 patients (23%) developed malignancy within 3 years of diagnosis of their DM; 11% of the ANA+ patients developed malignancy versus 43% of the ANA- patients (P < .001). There was a strong association between ANA positivity and lower likelihood of malignancy in multivariable analysis (odds ratio, 0.16; P < .001). Conversely, ANA positivity was not associated with amyopathic disease (odds ratio, 0.94; P = .87). LIMITATIONS: The retrospective nature of the study was a limitation. CONCLUSION: In patients with adult-onset DM, ANA negativity is associated with increased likelihood of development of malignancy within 3 years of diagnosis of their DM. Particularly close follow-up and frequent malignancy screening may be warranted in ANA- individuals with DM.

Persistent dermatomal eruption on a leg.

Unilateral linear capillaritis (ULC) is a rare variant of pigmented purpuric dermatoses (PPD) that is characterized by a linear or pseudo-dermatomal eruption on a single extremity. Although clinically distinct from the other PPD, it shares histopathologic features with this group. Herein, we present a man in his 50s who presented with asymptomatic macules and scaly papules on the left lower extremity in a linear distribution. The eruption persisted despite treatment with topical triamcinolone 0.1% and oral rutocide.

Generalized retiform purpura as a presenting sign of diffuse dermal angiomatosis.

A 49-year-old man presented with progressive, painful, ulcerative, retiform purpuric patches on the torso and extremities. Multiple skin biopsies revealed a prominent pan-dermal vascular proliferation but no occlusive vasculopathy or cutaneous vasculitis. Diffuse dermal angiomatosis should be considered in the differential diagnosis of retiform purpura, especially in patients with atherosclerotic disease or underlying hypercoagulable states.

Sarcoidosis: radiographic manifestations in the nails and distal phalanges.

Sarcoidosis is a granulomatous disease which can affect multiple organ systems. Clinical and radiologic manifestations depend on the organ system involved and the chronicity of disease. Nail involvement in sarcoidosis is rare, but is clinically relevant as it indicates chronic systemic disease. Nail abnormalities can be identified radiographically, and when seen in patients with known or suspected sarcoidosis, should prompt careful evaluation of the underlying bone for osseous involvement. We describe a case of sarcoidosis with radiographic findings in the nails and distal phalangeal tufts, which were indicative of nail and osseous sarcoid involvement and strongly supported the presence of chronic systemic disease. Although the nail findings resolved clinically and on radiographs after treatment, the osseous findings showed only minimal improvement. To our knowledge, the radiographic findings of nail sarcoidosis have not been previously addressed in the literature.

Resident rounds: Part III: Multiple myeloma presenting as fulminant retiform purpura.

Retiform purpura secondary to underlying type 1 cryoglobulinemia can be a presenting sign of multiple myeloma. Severe pain may herald microvascular occlusion and impending ulceration. Recognizing the distinctive cutaneous and histopathologic features of this occlusive vasculopathy allows for timely diagnosis and treatment.

Clinical Features of Cutaneous Paraneoplastic Syndromes in Hodgkin Lymphoma.

Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.

Chromoblastomycosis: A Potential Mimic of Squamous Cell Carcinoma in Transplant Recipients.

Chromoblastomycosis (CBM), also known as chromomycosis is a chronic, granulomatous fungal infection of the skin and subcutaneous tissue. It usually occurs by the traumatic inoculation of various dematiaceous fungi and is more common in the developing world. This condition is rare in North America and the developed world. Herein, we present a case of a 75-year-old man who received a bilateral lung transplant 4 months prior and presented for evaluation of a painful, erythematous papule on the elbow which was diagnosed as CBM. This case highlights that immunosuppression used in patients who undergo solid organ transplantation not only increases the risk of opportunistic infections like CBM but can also be confused for cutaneous squamous cell carcinoma as both these entities share many overlapping clinical and histopathologic features and may be a potential source of misdiagnosis.

Comparison of virtual microscopy and glass slide microscopy among dermatology residents during a simulated in-training examination.

BACKGROUND: Virtual microscopy is increasingly being used in dermatopathology educational settings. OBJECTIVE: The objective is to evaluate diagnostic accuracy and attitudes between virtual microscopy and traditional glass slide microscopy among dermatology residents. METHODS: A 48-question dermatopathology examination was administered to 35 dermatology residents at three different dermatology residency training sites during the 2011-2012 academic year with half (n = 24) of the questions using the gold standard of glass slide microscopy and half (n = 24) using whole, scanned virtual slides. Correct number of questions using glass slides and virtual slides was evaluated. Participants were surveyed regarding previous experience with digital slide imaging; quality, ease of use, and speed of slide review; and overall microscopy preferences. RESULTS: Overall, diagnostic accuracy was better with glass slides than virtual slides (p = 0.01). However, no statistically significant difference was found in diagnostic accuracy of first-year trainees (p > 0.99) or trainees with exposure to virtual microscopy greater than two times per month (p = 0.27). There was no overall personal preference for glass slide vs. virtual microscopy. LIMITATIONS: Different cases and questions were used for glass slides and virtual microscopy. CONCLUSIONS: Diagnostic accuracy with virtual microscopy is dependent on year of residency training and prior experience with virtual microscopy.

More Than Skin Deep: Dermatologic Conditions in Athletes.

CONTEXT: Athletes are a unique group of patients whose activities, particularly in high-contact sports such as wrestling and football, place them at high risk of developing skin conditions. The correct diagnosis of sports dermatoses requires familiarity with their clinical characteristics. It is critical that primary care physicians recognize the most common skin disorders to provide prompt treatment and prevent transmission. EVIDENCE ACQUISITION: The Mayo Clinic library obtained articles from 2012 onward related to dermatologic conditions in athletes. STUDY DESIGN: Review article. LEVEL OF EVIDENCE: Level 3. RESULTS: Dermatologic diseases in athletes are often infectious and contagious due to close-contact sports environments. Sports-related dermatoses include bacterial infections, such as impetigo, ecthyma, folliculitis, abscesses, furuncles, carbuncles, erysipelas, and cellulitis; fungal infections, such as tinea and intertrigo; viral infections, such as herpes, verrucae, and molluscum contagiosum; and noninfectious conditions, such as acne, blisters, and contact dermatitis. CONCLUSION: This article aims to address the manifestations of the most common cutaneous diseases in athletes on the first primary care visit. It discusses the appropriate tests and most recent evidence-based treatments for each ailment. It also addresses return-to-play recommendations related to the guidelines and regulations of selected sports organizations in the United States. STRENGTH OF RECOMMENDATION TAXONOMY (SORT): C.

Urticarial vasculitis: A Complication of SMZ-TMP therapy.

Recognize that delayed hypersensitivity reactions to sulfonamides may present as urticated plaques with hyperpigmentation and purpura for which a diagnosis of urticarial vasculitis should be considered.

Leprosy as a Diagnostic Challenge in the United States.

A 63-year-old woman from Central Florida presented to an outside clinic with a 2-year history of a progressive, asymptomatic cutaneous eruption and arthralgias. Her past medical history was significant for reported seronegative rheumatoid arthritis, for which adalimumab, methotrexate, and low-dose prednisone therapy were initiated 5 years prior. The skin eruption occurred shortly after a 4-week hospitalization during which these medications were withheld. At her initial outside evaluation, a biopsy was performed and interpreted as subacute cutaneous lupus erythematosus (SCLE). She was treated with hydroxychloroquine without improvement. A repeat biopsy was reported as consistent with interstitial granulomatous dermatitis (IGD). There was no improvement with potent topical corticosteroids.