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Advances in Rheumatology

, 59:41 | Cite as

The use of ultrasonography in the diagnosis of nail disease among patients with psoriasis and psoriatic arthritis: a systematic review

  • José Alexandre MendonçaEmail author
  • Sibel Zehra Aydin
  • Maria-Antonietta D’Agostino
Open Access
Review

Abstract

Background

Nail involvement has been described as a key clinical feature for both psoriasis (PsO) and psoriatic arthritis (PsA) and is an important risk factor in PsA. Thus, early diagnosis of nail involvement may be essential for better management of PsO and PsA. Ultrasonography is considered a highly promising method to visualize nail disease. The main aim of this review was to evaluate the use of ultrasonography for the diagnosis of nail disease in patients with PsO and PsA by reviewing ultrasound parameters with the best diagnostic accuracy.

Main body of the abstract: A systematic search was performed in MEDLINE via the PubMed and LILACS databases. Conference proceedings of relevant rheumatology scientific meetings were also screened.

Results

After applying eligibility criteria, only 13 articles and 5 abstracts were included in this review. The selected studies showed a huge variability in evaluation methods (and therefore in the results) and were mainly focused on the assessment of nails ultrasound parameters that may differ among patients and healthy controls, especially the morphological aspects in B-mode ultrasonography and vascularization of the nail bed by Doppler ultrasonography. Our research indicated that the evaluation of nail disease in PsO and PsA is still underrepresented in the literature, probably reflecting a restricted use in clinical practice, despite the widespread use of ultrasonography in the management of chronic arthritis.

Short conclusions

Despite the potential relevance of ultrasonography for the diagnosis of nail disease, additional studies are needed to determine which features are more reliable and clinically pertinent to ensure accuracy in the evaluation of nail involvement in PsO and PsA.

Keywords

Psoriasis Psoriatic arthritis Ultrasonography Spectral Doppler Power Doppler Ungueal disease 

Abbreviations

IQR

Interquartile range

LRI

Resistance Index in longitudinal plane

mNAPSI

Modified NAPSI score

NGS

Standard trilaminar appearance of the nail bed

NPD

Presence of power Doppler in the nail bed

NVRI

Nailfold Vessel Resistive Index

OA

Osteoarthritis

PD

Power Doppler

PsA

Psoriatic arthritis

PsO

Psoriasis

RI

Resistive Index

SD

Standard deviation

TRI

Resistive Index in transverse plane

US

Ultrasonography

Background

Psoriasis (PsO) is defined as a chronic, immune-mediated, gene-based disease with an inflammatory background that affects the skin, semi-mucosa, and joints. When joints and surrounding structures are involved, patients are classified as having psoriatic arthritis (PsA) [1, 2, 3, 4]. The prevalence of PsO may range from 0.5 to 11.8% around the world [5, 6, 7, 8, 9], while the prevalence of PsA amongst patients with PsO varies from 5.9 to 48%, according to the patient characteristics and classification criteria used [1, 3, 4, 8]. PsO manifestations may vary; however, plaque PsO (or psoriasis vulgaris) is the most frequent skin phenotype, affecting approximately 90% of patients with PsO [9]. The disease may also affect the scalp, joints, creases, or nails, even in patients without skin lesions [10].

Fifty to 80 % of patients with PsO have concurrent nail lesions [11, 12, 13], which can lead to functional impairment, pain and discomfort, and decreased quality of life and general well-being [14, 15]. Despite its significant prevalence (around 50% of patients), nail manifestations are often neglected in daily clinical practice, probably due to a lack of recognition of its impact on patients or its relevance as an indicator of disease extension [15].

Psoriatic arthritis leads to impairments in a patient’s life, decreasing functional capacity and quality of life, which also increases the burden of disease to society. This burden highlights the need for early diagnosis and timely treatment for all comorbidities. In this sense, nail disease has been reported as a relevant risk factor for PsA [16] and may be employed as an early diagnostic parameter among patients with PsO.

Imaging techniques such as ultrasonography (US) have been increasingly used to diagnose and to monitor clinical features of PsO and PsA [17, 18, 19, 20]. US findings usually include measures of thickness of the nail bed and the ventral and dorsal plates, as well as loss of definition, morphologic changes, and blood flow disturbances [21, 22]. Power Doppler (PD) and spectral Doppler (SD) are US techniques that are used to visualize nail inflammation. PD semiquantitatively shows nail inflammation through the detection of increased flow in blood vessels, whereas SD calculates the resistive index (RI) using systolic and diastolic peak flows of small vessels, which expresses the resistance to blood flow in the nail bed [22, 23]. Despite the relevance of US, discordant data are available on the usefulness of Doppler techniques for the evaluation of nail disease in PsO and PsA. Thus, the aims of this review are (i) to investigate the usefulness of nail US for the diagnosis of nail disease in patients with PsO and PsA; (ii) to gather data about parameters obtained through Doppler techniques (PD and SD) indicating inflammation of the nail bed, including but not limited to RI and vascularization of the nail unit; and (iii) to observe the differences between PsO, PsA, and healthy controls in RI and morphologic changes.

Main text

Methods

A systematic search was performed using MEDLINE via PubMed and LILACS (Latin American and Caribbean Health Sciences Literature) in order to identify studies addressing the use of US in nail assessment in terms of variables relevant in the context of PsO and PsA, to meet the previously mentioned goals. Two search strategies using a combination of controlled vocabulary (MeSH and DeCs keywords, for Pubmed and LILACS, respectively) and text words were adopted, as shown in Table 1. Searches were performed until March 20, 2018.
Table 1

Search strategy

Database

Search Strategy

PubMed

(“Arthritis, Psoriatic”[Mesh] OR “Psoriasis”[Mesh] OR “psoriatic arthritis” OR “psoriasis”) AND (“Ultrasonography”[Mesh] OR “ultrasound” OR “Ultrasonography, Doppler”[Mesh] OR “Doppler” OR “Power doppler” OR “spectral”) AND (“nail” OR “ungueal”)

LILACS

(“Psoríase” or “Psoriasis” or “Arthritis, Psoriatic” or “Artrite Psoriásica”) and (“ultrasonography” or “ultrasound” or “ultrassonografia” or “doppler”) and (“unha” or “nail” or “ungueal”)

Conference proceedings of relevant scientific meetings in rheumatology (European League Against Rheumatism and American College of Rheumatology, as selected by the authors) were also screened. Only studies published during the past 10 years were considered eligible. Language selection was made manually by the reviewers.

After applying the predefined search strategies, the records were screened by two different reviewers using the following inclusion criteria: i) observational or non-therapy interventional studies; ii) patients with PsO and/or PsA; iii) studies assessing the use of US for nail assessment; and iii) papers reported in English, French, Portuguese, and Spanish only. Studies were deemed non-eligible if they consisted of any of the following exclusion criteria: i) clinical trials of any phase or study design or ii) case reports.

Initially, it was planned that in cases of discordance, a third reviewer would be the responsible for the final decision to include a selected article or not. No disagreements were identified in the review process; therefore, this strategy was unnecessary. Data extraction was performed by the reviewers, using a data collection tool specifically designed for this review. Variables abstracted from individual studies were: author, year, study design, sample size, baseline disease (if applicable), primary and secondary aims (if applicable), US assessments performed, nail parameters described, results. Assessment of bias was based on the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data [24, 25]. The risk assessment tool is descriptive and does not provide scores.

Results

A total of 48 records were initially identified. After application of the eligibility criteria, 13 were selected and included in this review. In addition, five abstracts were manually identified in the conference proceedings searched (Fig. 1), which provided the final number of 18 studies analyzed.
Fig. 1

PRISMA flowchart

The main characteristics of the 18 studies included in this review are summarized in Table 2.
Table 2

Studies included in the review

Author

Year

Study Design

Sample characteristicsa

Aim

Ultrasonography assessment

Ultrasonography variables reported for the nail

Risk of bias

Arbault et al [26]

2017

Cross-sectional

27 patients with PsA

To determine the feasibility, reliability, and validity of nail US in PsA as an outcome measure.

• ESAOTE MyLab 70 XVG fitted with a high frequency transducer of 22 mHz. (PRF: 500 Hz, Doppler frequency: 6.3 MHz, Gain: 30%)

• Nail bed thickness

• Nail plate thickness

High

Severity level: NR

Duration (mean): 13.4 ± 9.4 years

Age (mean): age 55 ± 16.2 years

Female:40.74 %

Aydin et al [27]

2017

Cross-sectional

86 patients with PsO and 19 healthy controls

To find the frequency and severity of PD signals in psoriatic nail disease compared with healthy controls to understand whether PD signals are associated with disease.

• Logiq E9 machine (General Electric, Wauwatosa, WI, USA)

• Linear probe at 10–18 MHz

• PD settings: pulse repetition frequency of 800 Hz, a Doppler frequency of 9.1, and low wall filters

• PD changes on the nail bed

Moderate

Severity level: NR

Duration (mean): NR

Age (mean): NR

Female: NR

Fassio et al [28]

2017

Case-control

82 cases (31 PsO, 51 PsA, and 50 controls)

To evaluate the presence of the nail involvement and subclinical alterations using US in PsO and PsA.

• Not informed

• Nail bed thickness

• Nail plate thickness

Moderate

Severity level: NR

Duration (mean): NR

Age (mean): NR

Female: NR

Paramalingam et al [29]

2017

Cross-sectional

10 patients with PsA

To investigate the nail bed changes seen in patients with PsA and OA using US and MRI, and to determine the impact of nail bed changes on quality of life.

• Not informed

• Pitting

• Nail structural abnormalities

• Trilaminar appearance

High

Severity level: NR

Duration (mean): NR

Age (mean): 55.0 (48.0–63.2) years

Female: NR

Acquitter et al [30]

2016

Cross-sectional

37 patients with PsO (18 with nail disease and19 with scalp PsO and/or inverse PsO)

To detect subclinical entheses and nail abnormalities using gray-scale and PD US between patients with nail PsO and those with inverse and scalp PsO.

• IU 22 machine (Philips) and a linear probe at 12.5 MHz (PRF = 500 Hz)

• Nail matrix thickness

• PD signal in nail bed

• Trilaminar appearance

High

Severity level: NR

Duration (mean): (years/SD) 13.28/10.34 Nail psoriasis 17.11/13.14; Inverse and scalp psoriasis

Age (mean): 47.61 (15.88) years Nail psoriasis; 47.11 (12.65) years Inverse and scalp psoriasis

Female: 44.44% Nail psoriasis; 63.15% Inverse and scalp psoriasis

Marina et al [31]

2016

Case-control

23 cases with PsO and 11 controls

To evaluate both the morphologic appearance and blood flow changes in the nail apparatus of patients with PsO compared with disease-free controls using gray-scale and color and PD HRUS.

• Transducer ranging from 8–40 MHz (focal range 0.2–3 cm, image field 16 mm) – nail anatomy

• Hitachi EUB 8500 System with a variable-frequency transducer ranging from 6.5–13 MHz – blood flow

• Doppler (color Doppler: PRF 500–1000 Hz, wall filter 25–50 Hz, PD: PRF 350–700 Hz, wall filter 22–50 Hz; color and PD)

• Esaote US machine with 18 MHz – morphostructural changes

• Ventral nail plate deposits

• Nail plate aspect

• Color Doppler spots

• PD spots

• Nail bed thickness

• Nail plates thickness

• Nailfold vessel RI

High

Severity level: moderate-to-severe chronic plaque psoriasis

Duration (mean): lasting at least 6 months

Age (mean): 52.43±14.28SD years

Female: 21%

Mendonça et al [32]

2015

Case-control

44 cases (PsA and 16 controls (10 healthy controls, 6 OA)

To compare PD and SD US indexes (semiquantitative gray-scale and PD scores) and RI in the nails of patients with PsA and their controls.

• PD and SD techniques with frequency ranging from 6–8 MHz

• RI

High

Severity level: NR

Duration (mean): NR

Age (mean): NR

Female: NR

El Miedany et al [33]

2014

Case-control

126 cases (PsO) and 112 controls

To identify the clinical predictors of arthritis in patients with PsO and to evaluate the use of musculoskeletal US as a predictor for inflammatory structural progression consistent with early PsA in psoriatic patients, using rheumatologic evaluation as the gold standard for diagnosis.

• Multi-frequency linear array 14–21 MHz transducer;

• Gray-scale and PD techniques.

• Trilaminar appearance

Moderate

Severity level: PASI 12.4±10.4

Duration (mean): 4.8±3.1 mo

Age (mean): 35.9±8.7 years

Female: 43.4%

Mendonça et al [34]

2014

Case-control

28 cases (PsA) and 7 controls

To assess the RI in the nail bed in longitudinal and transverse planes and correlate with the presence of PD in the nail bed, change in standard trilaminar appearance of the nail, measure of the nail bed, and clinical measurements.

• Esaote US machine , with 6–18 MHz broadband multifrequency linear transducer

• Doppler frequency ranging from 7.1–14.3 MHz

• RI in the nail bed in longitudinal plane

• RI in the nail bed in transverse plane

• PD in the nail bed

• Trilaminar appearance

• Nail bed thickness

High

Severity level: PASI 6.03±12.27

Duration (mean): 10.05±10.49 mo

Age (mean): 45.3±14.61 years

Female: 54.5% women

Sandobal et al [35]

2014

Case-control

35 cases with PsA, 20 with PsO, 28 healthy subjects, and 27 with RA

To show findings at finger nails level revealed by high-frequency gray-scale US and PD in patients with PsA, and cutaneous PsO compared with RA and control subjects.

• MyLab 25 XVG system with a variable-frequency transducer ranging from 10–18 MHz

• Doppler frequency ranging from 6–8 MHz

• Wortsman typology

• PD signal in nail beds

• Nail thickness

High

Severity level: PASI 3

Duration (mean): 9±1.6 mo

Age (mean): 51±13 years

Female: NR

Aydin et al [36]

2013

Case-control

5 cases with PsO, 13 with PsA and 12 controls

To compare optical coherence tomography US for nail disease assessment in psoriatic disease.

• Logiq E9 machine with a linear probe at 9–14 MHz

• Multiplanar technique

• Gray-scale technique

• Trilaminar appearance

• Pitting

High

Severity level: NR

Duration (mean): NR

Age (mean): NR

Female: NR

Aydin et al [37]

2012

Case-control

86 cases (PsO) and 20 controls

To compare US with the modified NAPSI, to investigate the nail plate, nail matrix, and adjacent tendons in subjects with psoriatic nail disease and to test the hypothesis that nail involvement was specifically linked to extensor tendon enthesopathy.

• Logiq E9 machine with a linear probe at 18–10 MHz

• Gray-scale technique - frequency at 14 MHz, gain at 18 dB, and a dynamic range at 36 dB

• Pitting

• Nail thickness

• Nail matrix

Moderate

Severity level: mNAPSI 15

Duration (mean): 16 mo

Age (mean): NR

Female: 38.4%

Gisondi et al [38]

2012

Case-control

138 cases (PsO) and 83 controls

To estimate nail involvement in patients with chronic plaque PsO using US.

• Voluson I portable US machine (General Electrics, United States) with linear 10–18 MHz probe equipped with a variable-frequency transducer of 18 MHz

• Gray-scale technique

• Thickening of the nail plate

• Sub-nail hyperkeratosis

• Pitting

Moderate

Severity level: NAPSI 18.4 ± 17.5

Duration (mean): 20 ± 12 mo

Age (mean): |NR

Female: 15%

Haddad et al [39]

2012

Case-control

10 PsA cases, 10 PsO cases, and 20 controls

To investigate the association between clinical and ultrasonographic features of psoriatic nail disease and to identify specific nail features associated with PsA.

• 10-MHz linear array transducer

• Doppler signal standardized with a pulse repetition frequency of 400 Hz, a gain of 20 dB, and a low wall

• Loss of definition of the ventral plate

• Hyperechoioc focal involvement of the ventral plate

• Thickening of both the and dorsal and ventral plates

• Nail bed thickness

• Nail matrix thickness

• Nail bed vascularity

• Nail matrix vascularity

High

Severity level: NR

Duration (mean): 21.1 ± 11.7 mo

Age (mean): 54.7 ± 12.6 years

Female: 22.2%

El-Ahmed et al [40]

2011

Case-control

23 PsO cases (16 with nail disease and 7 without) and 23 controls

To evaluate the vascularity in the nails of patients with PsO treated with classic and biologic therapies for comparison with disease-free controls, and to evaluate whether there are differences in nail vascularity among patients with and without nail involvement.

• Echo Doppler examination

• Nailfold vessel RI

High

Severity level: NR

Duration (mean): NR

Age (mean): 42 years

Female: 34.78%

Gutierrez et al [41]

2010

Pictorial essay

30 cases (PsA)

To show the main high-frequency gray-scale US and PD findings in patients with PsA at joint, tendon, enthesis, skin, and nail level.

• MyLab 70 XVG with 6–18 MHz broadband multifrequency linear transducer and Doppler frequency ranging from 7.1 to 14.3 MHz

• Technos “Partner” System with 8–14 MHz multifrequency linear band transducer and Doppler frequency ranging from 8.3–12.5 MHz

• Logiq with 8–15 MHz multifrequency linear transducer

• Hyperechoic definition of the nail plate

• Fusion of nail plate

• Thickening of nail plate

• Nail bed

• Blood flow

High

Severity level: PASI 12.4

Duration (mean): NR

Age (mean): NR

Female: NR

Gutierrez et al [42]

2009

Case-control

20 cases (PsO) and 10 controls

To show the main sonographic findings obtainable with “last-generation” high-frequency transducers and PD technique in patients with PsO.

• MyLab 70 XVG with a variable-frequency transducer ranging from 6–18 MHz

• Only descriptive approach of morphologic characteristics of nail;

• Nail homogeneity

• Trilaminar aspect

• Nail bed

• Blood flow

High

Severity level: NR

Duration (mean): NR

Age (mean): 32-52 years

Female: 65%

Gutierrez et al [43]

2009

Case-control

30 cases (PsO) and 15 controls

To show the potential of the latest sonographic equipment using high-frequency probes and a very sensitive PD technique in depicting both skin and nail changes in patients affected by PsO.

• MyLab 70 XVG system with a variable-frequency transducer ranging from 6–18 MHz and a Doppler frequency ranging from 7–14 MHz

• Gray-scale – to detect mosphostructural changes

• PD to detect abnormal blood flow

• SD to confirm PD signal

• Nail plate

• Nail bed

• Thickening measurement

• Blood flow

High

Severity level: PASI 12.3

Duration (mean): 20 mo

Age (mean): 46 years

Female: 40%

Studies reported as abstracts: Fassio et al (2017) [28], Paramalingam et al (2017) [29], Mendonça et al (2015) [32], Mendonça et al (2014) [34], and Haddad et al (2012) [39]

aCases indicate the number of patients with an actual diagnosis, as compared to healthy controls, and only data for patients is presented; HRUS=high-resolution ultrasonography; MRI Magnetic resonance imaging, NAPSI Nail Psoriasis Severity Index, NR Not Reported, OA Osteoarthritis, OCR Optical coherence tomography, PD Power Doppler, PASI Psoriasis Area Severity Index, PsA Psoriatic arthritis, PsO Psoriasis, RA Rheumatoid arthritis, RI Resistive Index, SD Spectral Doppler, US Ultrasonography

Assessment of bias

The Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data was applied to all of the included studies. In terms of sample frame and sampling, most studies used a clinic-based approach and described how the potential participants were recruited. Sample sizes varied from 10 to 238 patients, and all of them relied upon convenience, without clearly stating a sample size calculation rationale. Study subjects were appropriately described in all included studies, and valid methods to determine the presence of the pathological condition were used and extensively described. The statistical analysis plan was deemed appropriate for the 15 studies [26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40]. Overall, the risk of bias was assessed as moderate to high due to the small sample size of the studies.

Main findings of included studies

After full text analysis of the 18 records included in the review, a wide range of variables and methodologic approaches was identified. Tables 3, 4, and 5 summarize the key features that are relevant to this systematic literature review. Due to the methodologic variability of the included studies (as shown in Table 2), comparability or further data pooling was deemed not feasible. The descriptive data regarding grey-scale features, presence of Doppler vascularity, and RI measurement of nails’ vascularization are presented below.
Table 3

Studies comprising measurements on gray-scalea

Studies

Population

Gray-scale

Result

Arbault et al. (2017) [26]

PsA

Nail bed thickness

Mean (SD): 0.5 mm (0.04)

Nail plate thickness

Mean (SD): 2.0 mm (0.42)

Fassio et al. (2017) [28]

PsO

Nail bed thickness

Mean (SD): 0.25 mm (0.05)

Nail plate thickness

Mean (SD): 0.063 mm (0.011)

Healthy controls had lower nail plate and nail bed thickness.

PsA

Nail bed thickness

Mean (SD): 0.25 mm (0.04)

Nail plate thickness

Mean (SD): 0.065 mm (0.014)

Controls

Nail bed thickness

Mean (SD): 0.22 mm (0.02)

Nail plate thickness

Mean (SD): 0.051 mm (0.006)

Acquitter et al. (2016) [30]

Patients with PsO with nail disease

Nail matrix thickness

Median (SD): 1.94 mm (0.69)

Patients with PsO with nail disease presented with significantly higher nail matrix thickness than patients with scalp PsO and/or inverse PsO (p < 0.01).

Patients with scalp PsO and/or inverse PsO

Nail matrix thickness

Median (SD): 1.77 mm (0.54)

Marina et al. (2016) [31]

PsO

Nail bed thickness

Median (IQR): 1.88 mm

(1.71–2.03)

Nail plate thickness

Median (IQR): 0.86 mm (0.60–1.14)

Healthy controls had a statistically significant lower nail plate thickness than patients with PsO (p < 0.0001). No significant differences were observed in nail bed thickness variability among groups (p = 0.4621).

Controls

Nail bed thickness

Median (IQR): 1.89 mm (1.78–2.00)

Nail plate thickness

Median (IQR): 0.63 mm (0.59–0.67)

Mendonça et al. (2014) [34]

PsA

NGS

Mean (SD): 0.48 mm (0.50)

Healthy controls had lower NGS than patients with PsA.

Controls

NGS

Mean (SD): 0.00 mm (0.00)

Aydin et al. (2012) [37]

PsO

Nail thickness

Median (range): 0.56 mm (0.3–1.9)

Healthy controls had slightly lower NGS than patients with PsO.

Controls

Nail thickness

Median (range): 0.5 mm

(0.3–0.6)

Gisondi et al. (2012) [38]

PsO

Nail plate thickness

70 patients (50%)

Haddad et al. (2012) [39]

PsO

Nail bed thickness

Mean (SD): 16.0 mm (2.9)

Nail matrix thickness

Mean (SD): 17.5 mm (2.9)

Comparing the three groups, patients with PsO and PsA presented with statistically significant higher values of nail bed thickness and nail matrix thickness than controls (p < 0.0001).

Comparing patients with PsO and PsA, patients with PsO presented with a significantly lower nail matrix thickness than patients with PsA (p = 0.002). No statistically significant differences were observed in nail bed thickness among those groups (p = 0.81).

PsA

Nail bed thickness

Mean (SD): 15.9 mm (3.0)

Nail matrix thickness

Mean (SD): 18.8 mm (3.0)

Controls

Nail bed thickness

Mean (SD): 14.1 mm (1.2)

Nail matrix thickness

Mean (SD): 15.8 mm (0.92)

IQR interquartile range, NGS standard trilaminar appearance of the nail, PD power Doppler, PsA psoriatic arthritis, PsO psoriasis, SD standard deviation

aOnly studies with quantitative results regarding nail thickness, trilaminar appearance, presence of PD signal, and nail resistive index were included in this table

Table 4

Studies comprising quantitative results on PDa

Studies

Population

PD

Results

Aydin et al. (2017) [27]

PsO

NPD: 84.6%

Presence of nail bed with PD signal was similar among patients with PsO and healthy controls.

Controls

NPD: 81.6%

Paramalingam et al. (2017) [29]

PsA

NPD: 96.0%

Patients with PsA presented with a slightly higher percentage of nails with PD signal than patients with OA.

OA

NPD: 95.0%

Acquitter et al. (2016) [30]

Patients with PsO with nail disease

NPD: 44.5%

NPD was higher in patients with PsO with nail disease; however, differences among groups were not significant.

Patients with scalp PsO and/or inverse PsO

NPD: 39.0%

Mendonça et al. (2014) [34]

PsA

NPD mean (SD): 0.88 (0.31)

NPD was slightly lower in patients with PsA than controls.

Controls

NPD mean (SD): 1.0 (0.00)

Sandobal et al. (2014) [35]

PsO

Increase PD signal in nail beds: 20.5%

Patients with psoriatic arthropathy showed increased PD signal in nail bed (p = 0.0001).

PsA

Increase PD signal in nail beds: 23.4%

RA

Increase PD signal in nail beds: 2.2%

Controls

Increase PD signal in nail beds: 19.6%

Haddad et al. (2012) [39]

PsO

Nail bed vascularity: 14%

Comparing the three groups, patients with PsO and PsA presented with statistically significantly lower values of nail bed vascularity than controls (p < 0.001).

Comparing patients with PsO and PsA, patients with PsO presented with lower nail bed vascularity than patients with PsA; however, no statistically significant differences were observed (p = 0.44).

PsA

Nail bed vascularity: 18%

Controls

Nail bed vascularity: 20%

NPD presence of power Doppler in the nail bed, OA osteoarthritis, PD power Doppler, PsA psoriatic arthritis, PsO psoriasis, RI Resistive Index, SD standard deviation

aOnly studies with quantitative results regarding nail thickness, trilaminar appearance, presence of PD signal, and nail RI were included in this table

Table 5

Studies comprising quantitative results on spectral Dopplera

Studies

Population

Spectral Doppler

Results

Marina et al. (2016) [31]

PsO

NVRI

Median (IQR):

0.62 (0.55–0.69)

Patients with PsO presented with significantly higher median NVRI measurements than controls (p < 0.0001)

Controls

NVRI

Median (IQR):

0.57 (0.55–0.58)

Mendonça et al. (2014) [34]

PsA

LRI

Mean (SD): 0.50 (0.13)

TRI

Mean (SD): 0.48 (0.09)

RI measurements in both the transverse and longitudinal planes were lower for patients with PsA than controls.

Controls

LRI

Mean (SD): 0.86 (0.41)

TRI

Mean (SD): 0.70 (0.16)

El-Ahmed et al. (2011) [40]

PsO

NVRI

Mean (SD): 0.56 (0.09)

The mean NVRI was significantly higher in PsO than controls (p < 0.001). Patients with PsO with clinical nail disease had also significantly higher NVRI than those without nail disease (p < 0.05).

Patients with PsO with nail disease

NVRI

Mean (SD): 0.58 (0.10)

Patients with PsO without nail disease

NVRI

Mean (SD): 0.52 (0.45)

Controls

NVRI

Mean (SD): 0.42 (0.04)

IQR interquartile range, LRI Resistance Index in longitudinal plane, NGS standard trilaminar appearance of the nail bed, NVRI Nailfold Vessel Resistive Index, PD power Doppler, PsA psoriatic arthritis, PsO psoriasis, RI Resistive Index, SD standard deviation, TRI Resistive Index in transverse plane

aOnly studies with quantitative results regarding nail thickness, trilaminar appearance, presence of PD signal, and nail RI were included in this table

Gray-scale features of the nail by ultrasonography

Twelve studies reviewed gray-scale findings [26, 28, 29, 30, 31, 33, 34, 35, 36, 37, 38, 39]. Three of these studies were only pictorial essays, which were purely descriptive [41, 42, 43]. The terminology that was used by different investigators to describe gray-scale findings widely varied across studies, such as “loss of definition,” “hyperechoic definition,” “fusion,” or “hyperechoic focal involvement of the ventral plate,” all of which are likely to correspond to the loss of trilaminar appearance. The normal nail plate was usually described as “two hyperechoic white bands surrounding an anechoic well defined layer in between” and the lack of visibility of the latter anechoic layer may technically be named using one of these definitions. Although it was impossible to compare studies in the absence of a uniform definition, there were consistently more nail lesions as measured using US in patients with PsA (46–54%) [29, 35] and PsO (48.8–77.8%) [33, 35, 36, 37] compared with healthy controls (10%) [37]. In addition, patients with clinical nail disease were consistently found to have more lesions on US (57/101 [56.4%] vs 6/68 [8.8%]; p < 0.0001) [37] and had more frequent ventral nail plate deposits (median, 17.72 [Q1–Q3 = 10.14–27.83] vs 4.65 [Q1–Q3 = 0.05–16.23]; p = 0.0410) [31]. US results have a good agreement with clinical assessment for nail disease (kappa value = 0.79 for PsA patients and controls; p < 0.001) [33] and also a strong correlation (chi-square test, 10.769 for PsA and osteoarthritis patients; p = 0.001) [29]. However, it was not possible to confirm that US was more sensitive to detect nail disease versus clinical assessment. While there was higher number of nails with US features in the absence of clinical findings, there were also patients with positive clinical nail disease and no US features [36]. Nails with a false negative US test had mainly mild lesions, such as onycholysis or pitting with lower modified nail psoriasis severity index (mNAPSI, a psoriatic nail grading instrument used to assess severity of nail matrix and bed PsO by area of involvement in the nail unit) than those with true (i.e., marked) abnormalities on US (median mNAPSI, 10 [1–56] vs 17 [1–50]; p = 0.03), with a moderate absolute agreement between US and clinical assessment (76.3% with κ = 0.52, p < 0.0001) [37].

The studies also investigated nail thickness using US, reporting an increased thickness of nail plate, bed, and matrix in patients with PsO and/or PsA compared with controls [26, 28, 30, 31, 37, 39] (Table 3). Marina et al. was not able to demonstrate a difference in nail bed thickness between patients with PsO and controls [31]. Comparing 2 groups with PsO, one with nail disease and other with scalp PsO and/or inverse PsO, Acquitter et al. (2016) reported that the former group presented with statistically higher nail matrix thickness than patients in the latter group [30]. It was not possible to identify in the studies a comparison between PsO and PsA patients in terms of nail bed thickness with statistical significant differences.

Presence of vascularity within the nail unit by ultrasonography

Nail bed PD signals were variable in both patients with PsO and PsA across the studies, with a range varying from 20 to 96% [27, 29, 30, 35, 44]. A high frequency of vascularisation was also observed in healthy controls, ranging from 20 to 81.6% [27, 35]. Some studies demonstrated increased blood flow in patients with PsO [31, 39]. Comparing patients with PsO plus nails disease and patients with scalp PsO and/or inverse PsO, a higher frequency of PD signal in the nail bed was found in the first group compared with the second group [30] (Table 4). PD signals were usually scored semiquantitavely on a scale between 0 and 3. Interestingly, PsO was associated with all grades of PD signal severity [31]. On the contrary, Aydin et al. (2017) reported that a diagnosis of PsO was associated with a less frequent severe (grade 3) PD signal on the nail bed than in healthy controls (healthy controls vs PsO, 65.8% vs 34.9%; p = 0.002, 27].

Resistive index measurements

Three studies assessed RI measurements in patients with PsO or PsA compared with controls (Table 5) [31, 34, 40]. According to two of these studies, patients with PsO presented with statistically higher Nailfold Vessel RI (NVRI) measurements than healthy controls [31, 40]. Mendonça et al. (2014) assessed RI measurements in patients with PsA and reported that patients with PsA had lower RI measurements in both the nail bed in transverse and longitudinal planes than controls (PsA, mean of longitudinal plane measurement, 0.50 ± 0.13; mean of transverse plane measurement, 0.48 ± 0.09; controls, mean of longitudinal plane measurement, 0.86 ± 0.41; mean of transverse plane measurement, 0.70 ± 0.16). In addition, RI measurements in the nail bed in the longitudinal plane were correlated with RI measurements in the nail bed in the transverse plane (r = 0.333; p = 0.013) and with duration of medication use (r = 0.578; p = 0.002) and was negatively correlated with the presence of PD in the nail bed (r = − 0.213; p = 0.038). RI measurements in the nail bed in the transverse plane were not correlated with the presence of PD in the nail bed, while the measure of nail bed was correlated with the trilaminar appearance of nail (r = 0.472; p = 0.023, 34].

One study evaluated the sensitivity and specificity of RI measurements in patients with PsA [32]. In this study, patients with PsA presented statistically significant lower RI measurements than controls (p < 0.001), with high sensitivity and specificity for RI measurements in PSA patients (receiver operating characteristic curve = 0.858; p < 0.01). Patients with PsA and no symptoms of nail involvement also had lower RI measurements. Considering a 0.395 cut-off point for RI measurements, the results showed that RI measurements < 0.4 points were associated with 100 and 99% of sensitivity and specificity, respectively, for ungueal inflammatory activity [32].

Discussion

This systematic review was conducted to evaluate the current knowledge about the use of US for the diagnosis of nail disease in patients with PsO and PsA. However, the heterogeneous methodologic approaches did not allow us to perform a comparison of studies.

Although US is a method of diagnosis widely used in clinical practice for several diseases including PsA, real-world data shows that the use of this technique for the diagnosis of nail disease is still scarcely investigated in the literature, probably reflecting that the techniques is not routinely used in patients with PsO and PsA. Enthesitis/enthesopathies, joint synovitis and effusion, bone changes, tenosynovitis, and dactylitis are the main pathologies examined by US in patients with PsO and PsA [21]. The selected studies were mainly focused on the assessment of parameters that can differentiate healthy subjects with and without PsO and patients with PsO and PsA with and without nail disease [28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43].

A lower Doppler signal in the nail bed was found as marker of nail disease in patients with PsO and PsA compared with healthy controls. However the selected studies showed a wide variability for the presence of Doppler signal in the nail unit, mostly due to differences in the US equipment sensitivity or other variables such as Doppler settings, experience of the observer, or room temperature [29, 31, 34, 35, 39].

Some of the secondary outcomes of this review were related to resistance in the nail bed, such as to assess data regarding artifacts that could alter the RI measurement in the nail bed, the use of resistance in the nail bed to characterize inflammation, and differences in RI measurements in the nail bed among patients with PsO and PsA. Four of the included studies reported the RI measurements in the nail bed with conflicting results among patients with PsO and PsA, indicating the need for further evaluation in future studies to better determine how to apply the measure in clinical practice, including potential differences among specific subgroups.

Regarding artifacts that could alter the RI, two studies have shown significant differences when patients with PsO were compared with healthy controls and also when patients with PsO were stratified by the presence of nail disease [31, 40]. El-Ahmed and colleagues (2011) tested whether there were significant differences on NVRI measurements among groups of individuals based on sex, age, family history of PsO, and Psoriasis Area and Severity Index scores and no associations were found [40]. Also not all studies assessing these parameters reached statistical significance. Thus, this aspect of the disease still needs to be further investigated.

Morphologic changes, such as the thickness of nail beds, and nail plate, seem to be important parameters to analyze [28, 31, 34, 35, 37, 38, 39, 41, 42, 43]. In fact, patients with PsA and PsO presented significantly higher nail bed and nail plate thickness than controls [28, 39]; however, no study was able to predict more severe disease or the development of PsA based on this unique parameter [38].

Our review have limitations that need to be addressed, particularly the number of databases assessed and language limits, adopted due to logistic restrictions. Despite these limitations, we consider that the review was able to gather relevant and updated data about the current knowledge about the use of US to assess nail disease in PsO and PsA patients and also highlight areas for further investigation.

Conclusion

In conclusion, a significant variability across studies assessing nail disease using US in patients with PsO and PsA was observed. Samples were very diverse in terms of severity, disease duration and age. The measurement of thickness was the most frequently assessed parameter. Conflicting results exist on the presence of Doppler signals in the nail unit. Further studies are needed for the evaluation of the diagnostic value of this technique.

Notes

Acknowledgments

The authors thank ANOVA Consultoria em Saúde LTDA for providing scientific review support, which was funded by AbbVie in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Authors’ contributions

All authors made substantial contributions to conception and design, as well as acquisition, synthesis, and interpretation of data, and were also involved in writing the manuscript and given final approval of the version to be published.

Funding

ANOVA Consultoria em Saúde provided scientific review support in the development of this manuscript, funded by AbbVie.

Ethics approval and consent to participate

Not applicable once the analysis does not include human subjects.

Consent for publication

All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • José Alexandre Mendonça
    • 1
    Email author
  • Sibel Zehra Aydin
    • 2
  • Maria-Antonietta D’Agostino
    • 3
    • 4
  1. 1.Department of Rheumatology and Postgraduate Program of the Pontifical CatholicUniversity of CampinasSão PauloBrazil
  2. 2.The Ottawa Hospital Research Institute, Division of RheumatologyUniversity of OttawaOttawaCanada
  3. 3.APHP, Hôpital Ambroise Paré, Rheumatology DepartmentBoulogne-BillancourtFrance
  4. 4.INSERM U1173, Laboratoire d’Excellence INFLAMEX, UFR Simone VeilVersailles-Saint-Quentin UniversitySaint-Quentin-en-YvelinesFrance

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