Lichen Simplex Chronicus: Clinical Perspectives and Emerging Therapeutic Strategies

Abstract

Lichen simplex chronicus (LSC), also known as neurodermatitis, is a common chronic pruritic dermatosis defined by lichenified plaques resulting from persistent scratching. Though often secondary to underlying dermatologic, systemic, or psychological triggers, LSC represents a distinct clinical entity with significant morbidity. The hallmark itch-scratch cycle contributes not only to visible skin changes but also to substantial sleep disruption, emotional distress, and functional impairment. Psychological stress, anxiety, and depression are frequent comorbidities and can further perpetuate disease chronicity. This review provides a comprehensive summary of the evolving understanding of LSC, from its neuroimmune-driven pathogenesis to the wide spectrum of therapeutic strategies currently available. In addition to topical corticosteroids, novel approaches including immunomodulators, neuromodulators, Janus kinase (JAK) inhibitors, and biologics are being increasingly explored. Procedural therapies such as cryotherapy, fractional laser resurfacing, and botulinum toxin injections, have also emerged as valuable tools, particularly in treatment-refractory cases. Recent insights into type 2 inflammation and dysregulated sensory pathways have informed the rationale for these targeted strategies. In anatomically sensitive areas such as the genital region, where topical agents may be poorly tolerated, systemic treatments may be required. Given this complexity, individualized, multimodal treatment plans are critical to optimizing management and improving quality of life (QoL) in patients with LSC. By synthesizing current data on pathophysiology, diagnosis, and both established and emerging therapies, this review aims to guide clinicians in optimizing care for patients with LSC and addressing its far-reaching psychosocial burden.

Key Points

Lichen simplex chronicus (LSC), also known as neurodermatitis, is a prevalent and underrecognized chronic pruritic condition driven by repeated scratching and influenced by neuroimmune and psychodermatological factors.

While high-potency topical corticosteroids are first-line therapy, alternative approaches including immunomodulators, neuromodulators, and procedural treatments are increasingly utilized in refractory cases.

Effective long-term management requires an individualized, multimodal strategy that addresses both the physical and behavioral components of disease.

Introduction

Lichen simplex chronicus (LSC), also known as neurodermatitis, is a common and burdensome dermatologic condition characterized by localized lichenified plaques resulting from chronic scratching [1, 2]. Despite its high prevalence—affecting up to 12% of the general population—it remains underrepresented in dermatologic literature and underprioritized in clinical practice [2]. With expanding insight into the neuroimmune mechanisms driving chronic pruritus and the use of novel antipruritic therapeutics in clinical trials, a concise, clinically focused update on the diagnosis and management of LSC is both timely and necessary. While recent research has expanded our understanding of chronic itch and its overlap with conditions such as prurigo nodularis (PN) and atopic dermatitis (AD), this review provides a clinically oriented summary of LSC, focusing on its presentation, psychosocial impact, and evolving management to support dermatologists in patient care.

Epidemiology and Clinical Characteristics

Epidemiology

The overall prevalence of LSC in the general population is estimated to be around 12%, predominantly affecting females (2:1), and individuals aged 30–50 years old [2]. Asian and Black patients seem to have higher prevalence. In one study, Asian patients were over 20 times more likely, and Black patients nearly 12 times more likely, to be diagnosed with vulvar LSC than white patients [3]. In addition, USA outpatient data indicates that Black and Asian patients are disproportionately affected by pruritic dermatoses, including LSC, with increased itch-related visits and higher rates of associated diagnoses such as AD, PN, and lichen planus [4, 5]. Elderly patients of Filipino descent are commonly affected by LSC (prevalence: 5.0–6.7%) [6, 7].

The condition is more prevalent in individuals with a personal or family history of atopy, such as AD, allergic rhinitis, and asthma [8]. LSC has also been linked to neurocutaneous comorbidities, frequently occurring in individuals with anxiety and depression [1]. A large cohort study in Taiwan reported that patients with anxiety had a 41-fold greater risk of developing LSC [9].

Description of Symptoms

The primary symptom of LSC is intense, chronic itch, often described as paroxysmal as it is marked by sudden urges to scratch followed by refractory relief periods of 1–5 hours [10]. Scratching tends to worsen at nighttime and is not only habitual but often experienced as highly pleasurable, contributing to the chronicity of the itch-scratch cycle [11, 12]. In a cross-sectional study examining patients with chronic pruritus, those with LSC rated their scratching pleasure among the highest across pruritic dermatoses (mean score 3.4 ± 2.3 in a linear scale ranging from − 5 (not pleasurable at all) to + 5 (extremely pleasurable)), reinforcing the notion that scratching in this condition is rewarding [11]. However, when LSC involves the genital area, this transient relief is often overshadowed by the condition’s significant physical, sexual, and psychological toll, patients commonly report embarrassment, disrupted intimacy, and diminished quality of life [13]. Psychological stress can exacerbate symptoms, and episodes of scratching often occur during periods of emotional distress [2]. While there has historically been stigma surrounding psychogenic contributions to pruritus, growing research in psychodermatology has since underscored the complex neuroimmune interplay in conditions such as LSC. It is important to emphasize that while stress plays a role in the pathophysiology and exacerbation of LSC, the condition itself is a disorder with an established biological basis.

Commonly Affected Areas of the Body

LSC is typically localized to one or a few sites, distinguishing it from conditions such PN or other eczematous dermatoses that present with more generalized involvement [10]. Commonly affected regions are both easily accessible for scratching and some are highly innervated, including the nape of the neck, ankles, scalp, vulva, scrotum, and extensor forearms [10]. Further psychophysical research has shown that scratching is particularly pleasurable on the ankles and back, areas frequently involved in LSC, suggesting a topographical link between itch intensity and reward processing [14].

LSC lesions may demonstrate a three-zone architecture: a central area of flat lichenification, a middle ring of lichenoid papules, and a peripheral zone of mild thickening and hyperpigmentation [12]. Scratching during the refractory period in the context of psychological stress, may result in clear skin sores [10]. Plaques can range in color varying in terms of skin tone, from pink to dark brown, and may evolve into hypopigmented patches with darker borders over time [1].

Impact on Quality of Life

The persistent and intense pruritus of LSC can have a profound psychosocial impact. The itch-scratch cycle not only causes physical discomfort but also leads to visible skin changes that can be socially stigmatizing and interfere with interpersonal relationships. Emotional distress is common, often linked to or exacerbated by underlying psychiatric conditions [15]. In one study, 62% of patients with LSC had at least one psychiatric diagnosis, with major depressive disorder (32%), dysthymia (18%), and generalized anxiety disorder (12%) being most prevalent [15]. Compared with healthy controls, patients with LSC also exhibited significantly higher scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), positively correlated with LSC severity [15]. Furthermore, patients scored higher on the Harm Avoidance dimension and lower on Self-Directedness, in the Temperament and Character Inventory (TCI) [15].

Beyond psychiatric comorbidity, LSC has a moderate impact on quality of life (QoL). In one study, the mean Dermatology Life Quality Index (DLQI) score among patients with LSC was 8.58, with 57.9% of patients reporting moderate impairment (DLQI 6–10) and 25.3% reporting severe impact (DLQI 11–20) [16]. The most affected items were question 1 (symptoms) and domain 1 (symptoms and feelings), highlighting that pruritus is the principal driver of QoL impairment and that itch control is critical to improving patient outcomes [16].

In another cohort of patients with LSC, over 50% reported moderate-to-severe sleep disturbance, with mean itch severity increasing in parallel: patients with moderate disturbance (47.36%) had a mean visual analogue scale (VAS) pruritus severity of 5.46 (on a scale of 0–10), while those with severe disturbance (4.7%) reported a mean VAS of 8.9 [17]. In contrast, those with no sleep disturbance (4.7%) had a mean VAS of 0.18, highlighting the relationship between nocturnal itch and sleep disruption [17].

Consistent with other chronic pruritic conditions, patients with LSC may also experience chronic fatigue, which further compounds psychosocial impairment and reduces functional capacity [18]. These findings highlight the importance of addressing both the physical and psychological components of chronic itch to improve patient outcomes (Fig. 1).

Fig. 1.

Clinical presentations of lichen simplex chronicus (LSC) across Fitzpatrick skin types. a Moderate LSC with well-demarcated plaques, showing moderate lichenification and induration. b Severe LSC with a well-demarcated plaque showing severe lichenification and induration; erythema is obscured by dark pigmentation in this Hispanic patient. c Severe LSC in Black skin with well-demarcated plaques and severe lichenification; erythema is obscured by dark pigmentation. d LSC with mild lichenification at the periphery of the plaques

Pathophysiology

LSC is a chronic, localized pruritic disorder driven by neural sensitization and sustained inflammatory signaling [12]. Its hallmark is the itch-scratch cycle, in which persistent scratching leads to skin barrier disruption, lichenification, and neuroimmune dysregulation [2]. LSC may be of primary etiology, triggered by psychological (e.g. anxiety, depression, obsessive-compulsive disorder) or environmental (e.g. sweat, chemical irritants, yeast) factors [1, 9]. The pruritus may also be secondary to an underlying dermatoses (e.g., AD) or systemic disease or neuropathies (e.g. diabetes mellitus, cholestatic liver diseases, and nerve impingements) [19].

The itch is nonhistaminergic, primarily mediated by protease-activated receptor 2 (PAR2) and type 2 inflammatory (Th2) cytokines such as interleukin-4 (IL-4), IL-13, and IL-31 [1, 20, 21]. IL-31 activates ankyrin-1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) ion channels on C-fibers, transmitting pruritic signals to the spinal cord [22–24]. This elicits a scratch response, damaging the skin barrier and causing an immune cascade via cytokine and peptide release [23, 25]. LSC skin biopsies showed decreased TRPA1 expression in the epidermis compared with healthy skin controls, reflecting peripheral nerve injury from chronic scratching that may contribute to central sensitization [26].

IL-31, IL-31 receptor, and oncostatin M (OSM) receptor in the skin play a significant role in the pruritus associated with lichen amyloidosis, which is considered a variant of LSC in Asian and Hispanic populations [27, 28].

Transient receptor potential vanilloid-3 (TRPV3) is a thermosensitive, calcium-permeable, ion channel expressed on keratinocytes [22]. Both TRPV3 and PAR2 are upregulated in inflamed skin, where they interact synergistically to amplify pruritus [22, 26]. Inhibition of both receptors reduced scratching and inflammatory responses in AD mouse models [29]. Chronic activation of the immune cascade triggered by primary or secondary drivers of itch has been linked to increased expression of inflammatory mediators implicated in LSC including Delta- and Notch-like epidermal growth factor-related receptor (DNER), matrix metalloproteinase-10 (MMP-10), and glial cell line-derived neurotrophic factor (GDNF) [30].

Genetic and neuroimmune factors may contribute to LSC pathogenesis. Variants in the serotonin transporter gene (5-HTT), particularly the short allele of the 5-HTTLPR polymorphism, result in reduced serotonin reuptake and prolonged serotonergic signaling. This genotype is less common in LSC, suggesting enhanced central serotonergic activity may confer a protective effect against itch [31]. Furthermore, LSC has been associated with a distinct pattern of long interspersed element-1 (LINE-1) DNA methylation in keratinocytes, indicating a potential epigenetic biomarker [32].

Psychological distress may amplify the itch-scratch cycle through dysregulation of the hypothalamic–pituitary–adrenal axis and reduced levels of neurotrophins essential for neuronal health, including brain-derived neurotrophic factor (BDNF,) neurotrophin-3 (NT-3), nerve growth factor (NGF), and glial cell line derived neurotrophic factor (GDNF) in the central nervous system [33]. BDNF in particular, has been increasingly linked to chronic itch in translational and epidemiological studies [34, 35].

Emerging evidence suggests that dysbiosis of the skin microbiome may represent another driver of chronic inflammation in LSC [36]. Recent 16S rRNA sequencing of LSC and PN lesions that were not atopic revealed reduced alpha-diversity across 615 species (290 genera, 29 classes, and 13 phyla), with a relative overabundance of Staphylococcus aureus (S. aureus), and a decreased prevalence of commensal organisms (Cutibacterium acnes, Staphylococcus hominis) compared with healthy skin [37]. Notably, the serine protease-like (SplD) gene was significantly elevated on quantitative PCR in LSC lesions across both Korean and USA cohorts (P < 0.05) [37]. The decline in protective species on LSC skin, such as C. acnes, which normally produce short-chain fatty acids that inhibit S. aureus overgrowth, may facilitate bacterial colonization and contribute to persistent cutaneous inflammation [38, 39].

Diagnosis

Diagnostic Methods and Tools

LSC is a clinical diagnosis based on physical exam findings of characteristic solitary lichenified plaques with enhanced markings owing to chronic rubbing and scratching [19]. Collecting a complete medical history is crucial as it provides insights into potential underlying conditions, triggers, and the origin of the itch, whether psychological, environmental, or secondary to other dermatoses [6]. The VAS, developed by Reich et al. [40] may aid in assessing lesion and pruritus severity. A biopsy may be helpful when the diagnosis is uncertain, or lesions fail to respond to standard therapy [2].

Differential Diagnoses

Conditions that may mimic LSC include hypertrophic lichen planus (LP), lichenified psoriasis, psoriasiform dermatitis, contact dermatitis, and mycosis fungoides [2, 10]. In genital areas, lichen sclerosus and LP should be considered as well as vulvar neoplasia [8, 41]. Lichen amyloidosis is another important consideration; it is a localized pruritic dermatosis and a form of primary cutaneous amyloidosis, more commonly seen in Hispanic and Asian populations. It closely resembles LSC both clinically and histologically, except for the presence of amyloid deposits, and is often considered a variant of LSC.

Although AD can present with lichenification, it tends to have a more widespread distribution and is often associated with elevated serum immunoglobulin (Ig)E and a personal or family history of atopy [42]. Contact dermatitis, both allergic and irritant, may present similarly, and patch testing is essential for identifying allergens [2]. Mycosis fungoides should be considered in treatment-refractory cases and can be distinguished histologically by atypical lymphocytes and epidermotropism [43]. In rare cases, squamous cell carcinoma may present as a chronic, nonhealing plaque, and should be considered in the differential diagnosis, particularly in lesions with atypical features or in patients with risk factors for skin cancer [44].

Histopathology

LSC exhibits pronounced epidermal hyperplasia with hyperkeratosis, alongside a thickened granular layer and acanthosis [10, 44, 45]. The rete ridges are typically elongated, and a stratum lucidum may be seen, a feature usually limited to acral sites [2, 10, 45]. Mild spongiosis can be present, particularly in vulvar biopsies where LSC is often superimposed on chronic spongiotic dermatitis [46]. In the superficial dermis, vertical streaks of thickened collagen are commonly noted, accompanied by perivascular and interstitial inflammation [2, 10, 47]. The inflammatory infiltrate is composed predominantly of lymphocytes, histiocytes, and eosinophils [2].

Treatment

Patient Education and Self-Management Strategies

Patients should be counseled to avoid known triggers such as heat, stress, and skin irritants, and to wear loose, breathable cotton-blend clothing [19]. Regular use of emollients is encouraged to maintain hydration and support the skin barrier [12]. Behavioral strategies, including stress management and habit-reversal therapy, are essential for reducing scratching behavior [48]. Cognitive behavioral therapy (CBT) helps patients identify triggers and develop strategies to reduce scratching [49]. Referral to mental health services may be warranted when psychological stressors contribute to disease persistence [48]. Educating patients about the chronic, relapsing nature of LSC and emphasizing the importance of treatment adherence can significantly improve patient outcomes.

Topical Treatments

The first-line treatment for LSC is topical corticosteroids (TCS) applied on thicker plaques during flares to reduce inflammation and pruritus [2, 12]. Initial options include fluocinonide 0.05% or triamcinolone acetonide 0.1% ointment, with escalation to superpotent agents such as clobetasol propionate 0.05% when necessary [19]. These are typically applied in small amounts twice daily for 2–3 weeks, with a follow-up visit around week 3 to assess response and guide tapering [2, 19]. Maintenance therapy involves gradually tapering the potency and frequency of use to 2–3 days per week to minimize adverse effects such as skin atrophy. Midpotency TCS (class III and IV), such as intralesional triamcinolone (10 mg/mL, 1:4 dilution in 1% local anaesthetic) and topical mometasone, are used to maintain remission and prevent flare-ups [12].

To enhance efficacy and reduce scratching, occlusive tape may be used as a behavioral barrier. A recent randomized controlled trial by Lo and Ip (2023) demonstrated that combining 0.1% mometasone furoate with hydrocolloid dressings significantly improved outcomes including Physician Global Assessment (PGA), Eczema Area and Severity Index (EASI), and pruritus scores, compared with mometasone alone [50]. The combination was well tolerated, cost-effective, and showed no adverse events, supporting its use in moderate-to-severe LSC [50].

The combination of aspirin with dichloromethane in topical formulations has demonstrated significant antipruritic effects and good tolerability, making it a nonsteroidal option for localized LSC [51]. Topical salicylic acid, with its keratolytic and antipruritic properties, can also be combined with TCS to enhance steroid delivery and improve symptom control. Ketamine-amitriptyline-lidocaine (KAL) cream has also demonstrated efficacy in chronic pruritic conditions, including LSC, with a significant reduction in itch scores and minimal localized side effects such as mild burning and erythema [52]. In addition, topical acetaminophen gel (2.5–5%) reduced histaminergic and nonhistaminergic itch intensity in a double-blind, vehicle-controlled study for localized itch, representing possible low-cost, emerging topical treatment options [53].

Topical immunomodulators such as tacrolimus and pimecrolimus are effective for long-term management of LSC, particularly on sensitive areas including the face and genitals [12, 54]. These agents reduce the release of itch-promoting inflammatory cytokines from T cells and increase skin immunity [1]. Importantly, they help avoid corticosteroid-induced side effects such as skin atrophy and striae, making them a safer option for chronic use in delicate areas [55]. While generally well tolerated, patients may experience transient burning or irritation at the application site [12, 55].

Tofacitinib, a JAK inhibitor, has been successfully used in topical form off-label for chronic pruritic dermatoses such as LP and lichen planopilaris [56]. A recent case series also demonstrated its efficacy in treating chronic refractory itch across conditions including psoriasis, PN, and LSC [57].

Topical ruxolitinib, a selective JAK1/JAK2 inhibitor approved for AD, may hold promise for LSC as it is currently under investigation for other pruritic lichenoid dermatoses such as lichen sclerosus and lichen planus [58–61].

Crisaborole, a topical phosphodiesterase-4 (PDE4) inhibitor approved for AD, has shown efficacy in steroid-refractory LSC, as evidenced by successful resolution in a recent pediatric case [62]. Roflumilast, a more potent topical PDE4 inhibitor approved for AD, psoriasis, and seborrheic dermatitis, may offer off-label benefit in LSC owing to its strong antipruritic and antiinflammatory effects [63–65]. While no formal studies have yet evaluated its use in LSC specifically, recent case reports have demonstrated its effectiveness in related pruritic dermatoses, including scalp neurodermatitis, lichen sclerosus, and lichen planus [66–68].

A novel topical TRPV3 inhibitor (Kamari 001) was evaluated in a phase 1 trial for the treatment of LSC, with no safety concerns reported and itch reduction observed in female participants [69].

Systemic Treatments

When topical treatments prove inadequate, systemic agents may be considered for LSC management. Gabapentin and pregabalin are prescribed for their efficacy in reducing neuropathic pruritus, though dizziness is a common side effect patients experience [12, 70]. Antidepressants, particularly sedating tricyclics such as doxepin, are frequently used to alleviate nocturnal itching and may also be beneficial in patients with coexisting depression or anxiety [71]. Sedative antihistamines (such as mirtazapine) are employed for the same purpose [72, 73]. Selective serotonin reuptake inhibitors (SSRIs) may reduce compulsive scratching behaviors in patients with underlying obsessive traits or persistent daytime symptoms [71].

Immunosuppressive agents, such as methotrexate and cyclosporine, have shown benefit in chronic pruritic conditions such as PN, and are under investigation for their utility in refractory LSC cases [55, 74]. Dupilumab, a monoclonal antibody targeting interleukin-4 and interleukin-13 pathways, has demonstrated efficacy in reducing pruritus and inflammation in various chronic skin conditions including PN and AD [75, 76]. A case series of three women with vulvar LSC refractory to steroids and immunomodulators found dupilumab led to marked relief of vulvar pruritus and thinning of lichenified skin, with lesions worsening again after drug discontinuation [77]. This supports the consideration of systemic biologic therapy in anatomically sensitive or treatment-refractory cases of LSC, where topical agents are poorly tolerated or insufficient for disease control, particularly in areas such as the genital region where symptom burden is high and steroid use may be limited.

Dupilumab is undergoing phase 3 trials for LSC of the skin and genitals. Nemolizumab, an IL-31 receptor antibody may show promise in relieving the itch-scratch cycle in LSC, as it has a significant antipruritic effect on multiple itchy conditions beyond its effect in atopic eczema and PN [78].

Procedural Therapies

Cryosurgery, which involves freezing and destroying abnormal skin cells, helps alleviate pruritus by flattening the thickened plaques characteristic of LSC and disrupting the itch-scratch cycle by reducing cutaneous nerve endings. A 2022 meta-analysis of clinical studies found that adding liquid nitrogen cryotherapy to conventional topical treatment significantly improved LSC outcomes without increasing adverse effects [79]. Patients receiving adjunctive cryotherapy had higher lesion clearance rates and lower recurrence compared with those on medical therapy alone.

Patients with very thick, recalcitrant plaques may benefit from physically resurfacing the skin. Serial electrobrasion was successfully used to treat a 67-year-old male with refractory lichenified plaques on his lower extremities [80]. The procedure involved lesion cleansing, anesthetization, serial electrosection, curettage, and abrasion to the papillary dermis [80]. After seven treatments over 3 years, the patient experienced significant symptomatic and cosmetic improvement with no bleeding, infection, or hypertrophic scarring [80]. This case supports electrobrasion as a low-risk, cost-effective, nonpharmacologic option for carefully selected patients, though larger studies are needed.

Ablative fractional CO₂ laser (AFXL) is emerging as a therapy to reduce thickness and induce regeneration in lichenified skin. A recent controlled study in 80 women with vulvar LSC compared ultra-pulse fractional CO₂ laser versus topical steroids over 3–6 months [81]. The laser-treated group had superior outcomes, with 82.5% showing marked improvement at 1 month (versus 65% of the steroid group) and a sustained 87.5% overall response at 6 months (versus 52.5% in the steroid group) [81]. Porvén and Losada reported sustained itch relief and cosmetic improvement in two women with refractory LSC (using 10,600-nm AFXL) [82]. One patient achieved full resolution for over a year after two sessions, while the second required further treatment for long-term benefit [82]. This laser-steroid combination may enhance drug penetration and symptom control in treatment-resistant cases. This combination therapy provided rapid symptom relief after one session and significantly enhanced the patients’ QoL [82].

Narrowband UVB (NB-UVB) phototherapy significantly reduces pruritus with minimal side effects. In a retrospective analysis of 26 patients (mostly children) with widespread, refractory LSC, NB-UVB achieved excellent results, with most patients experiencing marked improvement or clearance of lesions and long-lasting itch relief [83].

High-frequency focused ultrasound is a novel device therapy mentioned in recent literature for vulvar LSC. In a prospective study, Wu et al. found that patients with LSC (n = 85) had a cure rate of 48.24% following treatment, with a recurrence rate of 22.35% [83]. The efficacy of the procedure was inversely correlated to patient age and disease duration [84].

Botulinum toxin type A (BoNTA) has also shown promise in the treatment of recalcitrant localized pruritus in LSC. In a clinical trial of 12 patients with LSC, intradermal BoNTA significantly reduced VAS and EASI scores, with most patients reporting reduced urge to scratch and high satisfaction [85]

Conclusions

LSC is a common, yet under-recognized chronic pruritic condition associated with substantial psychological and functional burden. Beyond impairing quality of life, its persistent itch-scratch cycle can lead to sleep disruption, emotional distress, and impaired daily functioning. Recent advances in understanding its neuroimmune pathophysiology have expanded therapeutic options, including topical, systemic, and procedural interventions. While multimodal treatment approaches have been used in practice, they are increasingly gaining recognition owing to increasing awareness of LSC’s complexity and the emergence of targeted therapies. Continued research is essential to optimize long-term management and reduce disease burden.

Funding

This article has no funding source.

Declarations

Conflict of interest

G.Y. is a consultant and advisory Board member for Sanofi, Regeneron, Pfizer, Galderma, Novartis, Eli Lilly, AbbVie, Arcutis, Abbvie, Kiniksa, Trevi, Pierre Fabre, LEO Pharma, Escient, Celldex,Kamari and Vifor ; and has received research support from Abbvie, Pfizer, Sanofi, Regeneron, LEO Pharma, Eli Lilly, Kiniksa, Novartis, Escient, , Galderma and Celldex. G.Y. is an Editorial Board member of the American Journal of Clinical Dermatology. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Availability of data and material

No new datasets were generated or analyzed during the current study. All data discussed are derived from previously published literature and are available within the referenced sources.

Ethics approval

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Consent for publication

The authors obtained consent from patients for their anonymized photos to be published in print and online and with the understanding that this information may be publicly available.

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Author contributions

M.M. was responsible for the primary literature review and drafting of the manuscript. L.F.A. and M.A. contributed to the literature review and assisted with manuscript editing. G.Y. supervised the project, provided critical revisions, and ensured clinical and academic accuracy. All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.