Nail Psoriasis: Clinical Features and Severity Assessment

Abstract

The nail is an important characteristic in the context of psoriasis. Nail psoriasis exhibits several clinical manifestations. Since the development of the Nail Psoriasis Severity Index (NAPSI) score assessment tool for evaluating the severity of nail psoriasis, nail matrix symptoms such as pitting, leukonychia, crumbling, and red spots have been observed in the lunula. Nail bed symptoms include onycholysis, subungual hyperkeratosis, oil spots, and splinter hemorrhage. However, Beau’s lines and nail fold psoriasis, which are not included in this assessment tool, should be considered essential symptoms for indicating the activity of nail psoriasis. Although NAPSI is the most widely used tool for assessing the severity of nail psoriasis, it has uncontrolled limitations. Although other assessment tools have been developed, none have successfully replaced the NAPSI. In clinical trials for nail psoriasis, the NAPSI is used in various forms, such as improvement rates, changes in the mean NAPSI score, and achievement rates of NAPSI 75. Consequently, caution is warranted when interpreting the clinical trial results related to nail psoriasis improvement.

INTRODUCTION

Nail psoriasis is a major clinical manifestation prevalent in the majority of psoriasis patients. Its occurrence varies widely, ranging from 10% to 80% depending on the study¹,². The features of nail psoriasis vary from patient to patient. Notably, nail psoriasis exhibits poor responsiveness to treatment and manifests with a variety of features, each demonstrating differences in treatment response depending on individual nail characteristics. Nail psoriasis causes various types of discomfort and distress, with the extent and severity of discomfort varying based on specific nail changes and individual sensitivity. The common symptoms associated with nail psoriasis include pain, discomfort, impaired functionality, cosmetic concerns, and functional limitations. This discomfort affects the patients’ social and psychological activities.

Due to the anatomical characteristics of the nail unit, the collection of samples and conduct of in-depth research pose challenges, resulting in limited knowledge about the pathophysiology of nail psoriasis. Most studies on nail psoriasis tend to focus on its association with the overall severity of psoriasis or assessment of the effectiveness of medications or treatments.

Another important aspect related to the clinical presentation of nail psoriasis is its association with psoriatic arthritis³. Although the prevalence of nail psoriasis is believed to increase in patients with psoriatic arthritis, its precise frequency in comparison to psoriasis without joint involvement remains uncertain. However, nail psoriasis is often used as a key diagnostic criterion for psoriatic arthritis and is considered a predictive factor of psoriatic arthritis development.

In this article, a detailed examination of the clinical features of nail psoriasis was conducted, meticulously subdividing each clinical symptom for comprehensive exploration. Only a few studies have evaluated the characteristics and treatment responses of nail psoriasis in Koreans; hence, this study aimed to examine and emphasize this aspect. Additionally, the severity assessment tools, especially the Nail Psoriasis Severity Index (NAPSI) method, for nail psoriasis, which have been developed and are currently used in recent clinical trials for psoriasis, were reviewed. Furthermore, it explored the crucial aspects to consider when interpreting the results of clinical trials on nail psoriasis.

CLINICAL FEATURES OF NAIL PSORIASIS

The clinical features of nail psoriasis are typically categorized into nail matrix and nail bed feature⁴. The distinction between nail matrix and nail bed lesions was initially introduced in a study conducted by Rich et al. that proposed the NAPSI assessment tool⁴. The nail matrix features include nail pitting, leukonychia, nail plate crumbling, and red spots in the lunula. The nail bed features include onycholysis, subungual hyperkeratosis, oil spots, and splinter hemorrhage. With the exception pitting and subungual hyperkeratosis, the precise mechanisms shaping the features of nail psoriasis are not clearly understood. Therefore, the rationality of this morphological classification remains uncertain. This classification of nail psoriasis is considered conventional. As mentioned previously, the prevalence of nail psoriasis varies from 10% to 80%. The diverse results in prevalence studies can be attributed to the discrepancies in the definition used for diagnosing the condition.

The variability in the prevalence of nail psoriasis observed in these studies is believed to be related to nail pitting, a prevalent symptom of nail psoriasis. Unlike other clinical features of nail psoriasis, mild pitting may also be present in healthy individuals without skin conditions, and a few pits may be unrelated to disease activity. In psoriasis, pitting is characterized by a diameter larger than 3 mm and is often accompanied by hyperkeratosis of the rim and/or other nail matrix features. The inclusion of ordinary pitting, unrelated to psoriasis, in the severity assessment of nail psoriasis can introduce fluctuations in the NAPSI scores, depending on the evaluator⁵,⁶. Although periungual psoriasis is not officially categorized as nail psoriasis, it is often observed in patients with severe nail psoriasis. Patients with severe nail psoriasis may develop periungual psoriasis due to the close anatomical connection between the nails and periungual skin. The inflammation associated with psoriasis can extend from the nails to the surrounding skin, resulting in periungual psoriasis⁷.

In a study of 200 Korean patients with psoriasis, the prevalence rates of nail psoriasis, pitting, Beau’s line, onycholysis, leukonychia, and subungual hyperkeratosis were 85.5%, 55.6%, 36.8%, 35.7%, 25.7%, and 22.8%, respectively. Additionally, nailfold psoriasis was identified in 21.6% of the participants². Notably, in this study, subungual hyperkeratosis, pitting, and nail fold psoriasis demonstrated the highest correlation with the NAPSI score. Contrary to our expectations, when the correlation was extended to the Psoriasis Area and Severity Index (PASI) score, pitting did not exhibit a significant association with the severity of psoriasis². Only nailfold psoriasis demonstrated a significant correlation with PASI scores.

In a study targeting patients with palmoplantar pustulosis (PPP), among 95 patients, nail psoriasis was confirmed in 66.3%, onycholysis in 54%, pitting in 39.7%, crumbling in 23.8%, and leukonychia in 20.6%, revealing different frequencies compared with those observed in patients with plaque psoriasis⁸. Subungual pustulation was observed in only 7.9% of patients with PPP. This lesion is believed to correspond to periungual psoriasis in plaque psoriasis. Notably, nail crumbling and onycholysis showed the highest correlation with the NAPSI score in PPP. Nail psoriasis symptoms were more prevalent on the fingernails, ranging from approximately 30% to 45%, depending on the site, compared with the 10% to 20% on the toenails.

The presence of nail changes in patients with psoriasis does not necessarily indicate nail psoriasis symptoms, necessitating consideration of other possible nail disorders. Onychomycosis is commonly found in psoriasis patients⁹ and often requires differentiation from subungual hyperkeratosis or leukonychia in nail psoriasis. Conditions like aging or traumatic hypertrophy of the nail plate are usually misdiagnosed as subungual hyperkeratosis. Additionally, the accessory nail of the fifth toe in Asians, representing a separation of the toenails on the smallest toe, can be confused with nail psoriasis.

In a study on fingernail psoriasis treatment with ustekinumab⁵, an analysis of the NAPSI score components, encompassing the presence of nail psoriasis symptoms and changes in the extent of the lesions, revealed that a reduction in the extent of lesions on the nail plate was more frequently observed than the complete disappearance of clinical symptoms in cases of nail psoriasis. This means that although some improvement in nail psoriasis symptoms can be achieved with treatment, achieving total clearance is often challenging.

ASSOCIATIONS OF NAIL PSORIASIS SEVERITY WITH PSORIATIC ARTHRITIS

Compared with the prevalence of nail psoriasis symptoms in patients with psoriasis, studies on the prevalence of nail psoriasis in patients with psoriatic arthritis are notably scarce and challenging due to their limited nature. This limitation arises due to the lower prevalence of psoriatic arthritis (estimated at approximately 10%–30%) compared with psoriasis, making encounters with these patients less common for dermatologists and challenging to study. Additionally, patients with psoriatic arthritis are primarily managed by rheumatologists, posing difficulties in distinguishing the clinical symptoms of nail psoriasis. The initiation of registry studies has facilitated research on clinical presentations at relatively low prevalence rates. Reports from Germany’s psoriasis registry, PsoBEST, and the rheumatoid arthritis registry (RABBIT) indicate that nail psoriasis was observed in 58% and 41% of patients with psoriatic arthritis, respectively¹⁰. The variations in nail psoriasis prevalence between these two registries may be attributed to the differences in the specialties of the physicians who identified and recorded nail psoriasis symptoms. In the Korean population, the prevalence of psoriatic arthritis among patients with psoriasis is notably low (approximately 10%), and the severity of arthritis tends to be mild due to ethnic characteristics. In a previous study involving 200 patients newly diagnosed with psoriasis patients³, the severity of nail psoriasis was compared between patients with and without psoriatic arthritis. The average NAPSI score of patients with psoriatic arthritis was 9.7±12.4, while the average NAPSI score of patients without psoriatic arthritis was 8.9±12.6. However, no significant differences were observed in the NAPSI scores between the two groups. Future registry studies with a larger number of patients are essential to confirm whether the presence of psoriatic arthritis is associated with nail psoriasis severity.

ASSESSMENT OF NAIL PSORIASIS SEVERITY

The primary tool widely used for evaluating the severity of nail psoriasis is the NAPSI⁴. However, the NAPSI score was not developed through consensus among a large group of experts. Instead, it was arbitrarily developed and introduced by two researchers and was subsequently adopted for convenience in later clinical trials of new drugs. This introduces limitations to its accuracy as an assessment tool. The challenges with NAPSI scoring are rooted in the classification of nail psoriasis symptoms and the assessment of the extent of nail involvement.

Beau’s line is an important feature observed in patients with psoriasis but is not initially included in the original NAPSI assessment. Beau’s lines are transverse depressions of grooves across the fingernails or toenails. They are typically caused by a temporary disruption in the growth of the nail plate in the nail matrix. Beau’s lines are often associated with various underlying conditions including severe illness, systemic infection, physical trauma, chemotherapy, medications, nutritional deficiency, hypothyroidism, uncontrolled diabetes, and aging. They are frequently observed in patients with psoriasis, a skin disease. The exact mechanisms underlying the development of Beau’s lines in psoriasis are not fully understood but are thought to be related to the inflammatory process caused by the pathomechanism of psoriasis involving the nail matrix. Although Beau’s lines are found in approximately 40% of patients with nail psoriasis, incorporating Beau’s lines into the NAPSI scoring is challenging due to their ambiguous classification in either the nail bed or nail matrix, leading to the exclusion of this common symptom.

Another significant limitation of NAPSI scoring lies in the evaluation of the extent of involvement, which is solely based on the presence or absence of lesions within the four quadrants of the nail plate. This can result in an overestimation of severity in cases where only one nail pitting exists in each of the four quadrants compared with cases where the entire nail deformity is confined to one or two quadrants, as observed in subungual hyperkeratosis. To address these limitations, various methods for assessing the severity of nail psoriasis have been developed. The modified NAPSI (mNAPSI) introduced the grading of nail psoriasis severity to overcome the problem of assessing the presence of a lesion in a quadrant⁶. The inclusion of Beau’s lines in the assessment of nail psoriasis severity is unique to the research conducted by Baran¹¹. The Nijmegen-Nail Psoriasis Activity Index (N-NAIL) tool is an assessment method for nail psoriasis that incorporates severity grading from the mNAPSI and includes Beau’s lines, as proposed by Baran’s NAPSI¹². The N-NAIL method only assesses the following symptoms to determine the severity of nail psoriasis: onycholysis/oil drop discoloration, pitting, crumbling, Beau’s lines, and subungual hyperkeratosis. The N-NAIL method does not include the evaluation of symptoms such as splinter hemorrhage, leukonychia, and red spots in the lunula. This exclusion is based on the observation that red spots in the lunula are frequently associated with skin conditions other than psoriasis, and leukonychia can be found in healthy individuals¹². Splinter hemorrhage in patients with psoriasis is usually accompanied by subungual hyperkeratosis. Kim et al.⁵ conducted a study on the treatment outcomes of nail psoriasis using both the NAPSI and N-NAIL methods as assessment tools. After 52 weeks of ustekinumab treatment, the N-NAIL method statistically demonstrated more substantial improvements in treatment effects compared with the NAPSI method. The comparisons of each assessment tools are shown in Table 1.

Table 1. Comparisons of major nail psoriasis assessment tools.

	Characteristics	Strength	Weakness
NAPSI	- Twenty nails	- Accumulated clinical data from lots of clinical trials	- Time consuming
	- Four nail bed features		- Inaccurate involve area assessment (quadrant)
	- Four nail matrix features
	- Severity assessment: number of involved quadrant
mNAPSI	- Usually using features from NAPSI	- Less time consuming	- No uniformity from study to study
	- Modified from study to study for convenience	- Familiar with NAPSI experienced assessor	- Should see the definition in every study
N-Nail	- Included important feature: Beau’ line	- Precise than NAPSI	- Not commonly used
	- Severity assessment		- Confounding severity assessment
	- Pitting: number		- Less accumulated clinical data
	- Other features: area

NAPSI: Nail Psoriasis Severity Index, mNAPSI: modified Nail Psoriasis Severity Index, N-Nail: Nijmegen-Nail Psoriasis Activity Index.

APPLICATION OF NAIL PSORIASIS SEVERITY ASSESSMENT TOOLS FOR CLINICAL TRIALS

The significance of tools for assessing the severity of nail psoriasis has grown since the 2000s, with the advent of various biologics for psoriasis treatment. The PASI score, the most commonly used method for assessing the severity of skin psoriasis, is also a subjective evaluation tool similar to the NAPSI assessment tool, leading to the potential differences¹³ among the evaluators¹⁴,¹⁵,¹⁶. Despite its limitations, “PASI 75,” which signifies a 75% improvement in PASI score from before treatment to after treatment, is generally accepted as a common criterion for evaluating symptom improvement in psoriasis. However, NAPSI does not have specific target improvement rates, such as PASI 75 or PASI 90¹⁷.

In previous trials¹⁸ on biologic treatments for nail psoriasis, improvement was expressed as a percentage because a standardized nail psoriasis assessment method was not established. In that study, infliximab showed a 56% decrease in the mean NAPSI after 24 weeks of treatment. In a previous trial of adalimumab for the treatment of psoriasis¹⁹, the therapeutic effect of adalimumab was evaluated using a 50% improvement in the NAPSI score for a single-target nail. Approximately 56.5% of the patients achieved a NAPSI of 50. In the PHOENIX study, a phase 3 clinical trial of ustekinumab, improvement in nail psoriasis was assessed using the percentage improvement and changes in the mean NAPSI score, along with the nail physician’s global assessment (PGA) score¹³. This highlights the difficulty in adequately expressing the degree of improvement in nail psoriasis in clinical trials. Subsequently, clinical trials have adopted various outcome measures to assess the degree of improvement in nail psoriasis. These measures included percentage improvement, changes in the mean NAPSI score, NAPSI 50, NAPSI 75, NAPSI 100, nail PGA, and more²⁰. The lack of uniformity in evaluation methods across studies has made it challenging to compare and interpret clinical trial results for different medications. Owing to the complexity of result comparisons in the network meta-analyses evaluating the efficacy of various biologics for nail psoriasis, the degree of complete resolution of nail psoriasis was used as a benchmark to compare the effectiveness of each agent²¹.

In accordance with the conventional practice of evaluating the clinical improvement of psoriasis using certain criteria such as PASI 75 and PASI 90, some studies have arbitrarily established levels of improvement rates, such as NAPSI 50 and NAPSI 75, to assess the efficacy of the evaluation method without proper validation. However, unlike skin psoriasis, nail psoriasis does not show rapid or complete effects. Therefore, it is necessary to lower the standards for setting improvement rates instead of relying on NAPSI 50 and NAPSI 75 as reference points. In a previous study that examined the effect of ustekinumab on nail psoriasis¹⁷, the NAPSI improvement rates similar to the level of improvement for skin psoriasis, such as PASI 75 and PASI 90, were suggested as NAPSI 40 and NAPSI 70.

Another significant challenge arises when interpreting clinical trial results of nail psoriasis. Unless clinical trials for nail psoriasis were designed solely to confirm the effectiveness of treatment for nail psoriasis²², only the severity of psoriasis in the recruited patients was considered. Participation in the study was not predetermined based on the severity of nail psoriasis itself. One problem is the inability to manage the severity of nail psoriasis in patients recruited for clinical trials. In contrast to typical clinical trials where the participants are recruited based on the severity of psoriasis, the TRANSFIGURE study²², which investigated the treatment effect of secukinumab for nail psoriasis, specifically focused on patients with a NAPSI score of 16 or higher. Only patients with moderate-to-severe nail psoriasis were recruited to demonstrate their effectiveness. This approach enhances the reliability of the results.

TREATMENT OF NAIL PSORIASIS

This review does not extensively explore the treatment of nail psoriasis but rather highlights considerations when contemplating treatment in relation to clinical presentations and assessment methods for nail psoriasis. Recent advances in treatment options are more effective than conventional medications in improving not only skin psoriasis but also nail psoriasis. However, it is often difficult to claim that these treatments can completely resolve all clinical features of nail psoriasis in every patient. As mentioned earlier, results regarding the degree of improvement in nail psoriasis from phase 3 clinical trials for psoriasis often lack control over nail psoriasis severity in the included patients. Moreover, the methods for assessing efficacy vary widely; in some cases, only the improvement of the “target nail” chosen by the investigator is described, rather than assessing the improvement in all nails. Therefore, it is difficult to assume that the improvement observed in NAPSI from previous clinical trial results applies to all patients one is treating without a detailed analysis.

Isolated nail psoriasis is an important consideration in the treatment of nail psoriasis. Isolated nail psoriasis is defined as nail psoriasis with no or limited (<5%) cutaneous findings²³,²⁴. In my personal experience, it can be challenging to distinguish isolated nail psoriasis without skin psoriasis from other nail disorders. Therefore, empirical treatment with biologics for isolated nail psoriasis without a clear diagnosis of psoriatic nail changes should be undertaken with caution owing to the likelihood of failure and high medical costs.

CONCLUSION

Nail psoriasis is the most common clinical symptom in psoriasis patients. It is usually resistant to treatment and can cause significant social discomfort when affecting exposed areas such as the fingernails. The classification of the clinical presentations of nail psoriasis is not perfect, and the precise mechanisms underlying each clinical presentation and their modes of onset are not well understood. However, recognizing how each clinical presentation manifests, where it tends to occur, and the differences in responsiveness to treatment is crucial for improving the overall quality of life of patients. Understanding these aspects is important for physicians.

The NAPSI is commonly used to assess the severity of nail psoriasis in clinical trials due to its familiarity and relative convenience. However, it has limitations in accurately representing the clinical severity of psoriasis. Achieving a consensus among psoriasis researchers, there is a need to develop another assessment method that more accurately reflects the symptoms and severity of nail psoriasis.