High-Frequency Sonography in the Evaluation of Psoriasis

Image Presentation High-Frequency Sonography in the Evaluation of Psoriasis Nail and Skin Involvement Marwin Gutierrez, MD, Ximena Wortsman, MD, Emilio Filippucci, MD, Rossella De Angelis, MD, Giorgio Filosa, MD, Walter Grassi, MD Objective. The purpose of this study was to show the potential of the latest sonographic equipment using high-frequency probes and a very sensitive power Doppler (PD) technique in depicting both skin and nail changes in patients affected by psoriasis. Methods. The study was conducted in 30 patients with a diagnosis of psoriasis clinically performed by an experienced dermatologist and 15 healthy participants, using a currently available sonography system equipped with a variable-frequency transducer ranging from 6 to 18 MHz and a Doppler frequency ranging from 7 to 14 MHz. Results. The images illustrated in this presentation are representative examples of the ability of sonography to show and characterize even minimal morphostructural and blood flow changes in patients with both psoriatic plaques and onychopathy. Conclusions. This report provides pictorial evidence that high- resolution gray scale sonography with a PD technique is a real-time and noninvasive imaging technique that can be used as an adjunct to the clinical evaluation in assessing psoriatic disease. Key words: high frequency; nail; onychopathy; power Doppler sonography; psoriasis; skin; sonography. Abbreviations PD, power Doppler Received April 18, 2009, from the Cattedra di Reumatologia, Università Politecnica delle Marche (M.G., E.F., R.D.A., W.G.), and Unità di Dermatologia (G.F.), Augusto Murri Hospital, Jesi, Ancona, Italy; and Department of Radiology, Clinica Servet, Santiago, Chile (X.W.). Revision requested May 19, 2009. Revised manuscript accepted for publication June 26, 2009. Address correspondence to Marwin Gutierrez, MD, Cattedra di Reumatologia, Università Politecnica delle Marche, Augusto Murri Hospital, Via dei Colli 52, 60035 Jesi, Ancona, Italy. E-mail: dr.gmarwin@gmail.com Psoriasis is one of the most common immunemediated inflammatory skin diseases, affecting approximately 1% to 3% of the population. 1 The incidence has remarkable variability according to different geographic areas and ethnic groups. 2 Approximately 10% to 55% of patients with psoriasis will have nail involvement, and 10% to 30% will have inflammatory arthritis known as psoriatic arthritis. 3 The diagnosis of psoriasis is routinely based on the clinical history and physical examination, and the severity is determined using the Psoriasis Area and Severity Index, a specific validated method for assessing the extension of psoriatic lesions. 4 Nevertheless, histologic examination is the reference standard for the final diagnosis. 5 Sonography has proved to be a noninvasive imaging technique for studying soft tissue involvement in patients with dermatologic diseases. 6 18 During the past decades, several studies have described the ability of sonography in both quantification of the disease activity and evalua- 2009 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2009; 28:1569 1574 0278-4297/09/$3.50

High-Frequency Sonography in the Evaluation of Psoriasis tion of the effect of different treatments in patients with psoriasis, but only a gray scale technique was used. 19 26 The aim of this study was to show the potential of the latest sonographic equipment using highfrequency probes and a sensitive power Doppler (PD) technique in depicting both skin and nail changes in patients affected by psoriasis. Materials and Methods This study included a total of 30 patients (12 female and 18 male; age range, 39 52 years; median age, 46 years; disease duration, 2 84 months; median disease duration, 20 months) with a diagnosis of psoriasis made by an experienced dermatologist on the basis of clinical findings and 15 healthy participants (7 female and 8 male; age range, 33 54 years; median age, 44 years). The same dermatologist scored the Psoriasis Area and Severity Index (range, 4 18; median, 12.3). All patients and healthy control participants underwent a sonographic examination performed by an experienced sonographer (M.G.) using a MyLab 70 XVG system (Esaote Biomedica, Genoa, Italy) equipped with a variable-frequency transducer ranging from 6 to 18 MHz and a Doppler frequency ranging from 7 to 14 MHz. Within the focal area, the transducer had an axial resolution of 30 µm and a lateral resolution of 60 µm. The fields of view in the depth and lateral directions were 50 and 60 mm, respectively. Both skin and nail lesions were assessed by sonography in all the patients. At least 1 psoriatic plaque was situated in the following anatomic sites: abdomen, anterior and posterior level of the forearm, and anterior level of the lower half of the leg. In the healthy participants, the sonographic scans were performed in the correspondent body areas as references. On the psoriatic plaque, both the center and margins of the lesion and the surrounding normal skin were scanned. The ultrasound transducer was gently placed over the examined area with the transducer directed perpendicular to the surface with gel applied to the skin to provide a correct acoustic interface. The assessment of nail, skin, and lesion thickness was performed by marking the borders with calipers and measuring the distance between the marks. The sonographic examinations were performed with the patient in a supine or prone position (with extended lower limbs) or seated with the forearm in extension over the table according to the location of the psoriatic plaques. The nails were scanned with the patient seated with the hands in a neutral position over the table. Each skin or nail lesion was scanned in the gray scale mode to detect morphostructural changes and subsequently with the PD technique to detect abnormal blood flow. To confirm that the PD signal represented real blood flow and not an artifact, spectral Doppler imaging was used. Particular attention was paid to not compressing the tissues under examination to avoid the blanching of the PD signal due to transducer pressure. The study was conducted according to the Declaration of Helsinki and local regulations. The Institutional Ethics Committee approved the study, and informed consent was obtained from all participants before the sonographic examinations. Results Healthy Skin In normal glabrous skin, the epidermis appears as a thin hyperechoic and continuous line with homogeneous thickness. The dermis is visualized as a less echoic and homogeneous band, whereas the subcutaneous tissue is characteristically hypoechoic (because of adipose tissue lobules) separated by hyperechoic lines generated by fibrous septa of connective tissue (Figure 1). Healthy Nail The components of the nail unit are clearly visible on sonography. The dorsal and ventral plates appear as 2 hyperechoic parallel lines with a virtual hypoechoic space in between. The nail bed appears as a hypoechoic band not clearly distinguishable from the underlying subcutaneous tissue. The bony margin of the distal phalanx appears as a continuous hyperechoic line below the nail bed (Figure 2, A and B). A minimal amount of blood flow may be detectable on PD imaging in some nail beds because of the presence of thin arterial and venous vessels (Figure 2, C and D). 1570 J Ultrasound Med 2009; 28:1569 1574

Gutierrez et al Psoriatic Plaques The key sonographic features of skin and nails in patients with psoriasis are represented in the Table 1. The morphostructural changes verified in the psoriatic skin are easily distinguishable from surrounding healthy skin on sonography in a considerable number of cases. In the gray scale examination, the epidermis and dermis appear thicker compared with the normal surrounding skin. Moreover, a hypoechoic band in the upper lesion dermis can be observed very frequently (Figure 3). In cases with marked thickening of the epidermis, a posterior acoustic shadowing artifact may be visible, hindering the assessment of the underlying dermis (Figure 4). In active psoriatic plaques, PD imaging allows sensitive detection of an increased blood flow signal that may be seen within the dermis (Figure 5). Psoriatic Onychopathy In psoriatic onychopathy, the changes are located in both the nail plates and nail bed. The nail plates may show hyperechoic parts or loss of definition, which can involve only the ventral plate or both plates. In later stages, a wavy or thickened appearance of both plates may be visible (Figure 6, A and B). The thickening of the nail bed can be measured (ie, the distance between the ventral plate and the bone margin of the distal phalanx). These changes can be associated with an increase of blood flow that can be observed with the PD technique (Figure 6C). Figure 2. A and B, Gray scale sonograms of the normal fingernail in longitudinal (A) and transverse (B) views. The dorsal (arrow) and ventral (arrowhead) nail plates appear as bilaminar structures, characterized by 2 hyperechoic parallel lines with a hypoechoic space in between. The nail bed (circle) appears as a hypoechoic area under the plates. The nail bed thickness measurement was 1.6 mm. The dashed line indicates where the measurement was taken; dp, distal phalanx; et, extensor tendon of the finger; mp, middle phalanx; and nm, nail matrix. C and D, Normal amount of blood flow within the nail bed on PD sonograms in longitudinal (C) and transverse (D) views. A B Figure 1. Gray scale sonogram of the normal skin obtained at the anterior forearm level. The epidermis appears as a thin homogeneous hyperechoic line (arrow). The dermis (d) appears as a more echogenic band than the underlying hypoechoic subcutaneous tissue (sc), which contains hyperechoic septa of connective tissue (arrowheads). Epidermal and dermal thickness measurements were 0.22 and 1.1 mm, respectively. Black and dashed lines indicate where the measurements were taken at the epidermal and dermal levels, respectively. C D J Ultrasound Med 2009; 28:1569 1574 1571

High-Frequency Sonography in the Evaluation of Psoriasis Table 1. Main Sonographic Features of Skin and Nails in Patients With Psoriasis Psoriatic Skin Thickening of epidermis Thickening of dermis Hypoechoic band in upper dermis Absence of involvement of subcutaneous tissue Increased blood flow detected on PD sonography Psoriatic Onychopathy Focal hyperechoic deposits in the ventral plate (may be subclinical and correlate with subungual keratosis) without involvement of dorsal plate Loss of definition of both nail plates, adopting a wavy form Thickening of nail bed Increased blood flow in nail bed detected on PD sonography Discussion Within the last decade, there has been an increasing interest in sonography in the assessment of psoriatic disease. In this way, several studies have been conducted, but the totality of these used dated sonographic equipment provided with single- and fixed-frequency probes (with a penetration power of few millimeters) and only the gray scale technique. 19 23 Very high-frequency probes (up to 100 MHz) have also been used in the assessment of psoriatic plaques but only in experimental settings with complex technical methods (ie, application of petrolatum on the skin, fixing with tape, and a long wait time before the sonographic examination) unlikely to be feasible in daily practice. 21 To the best of our knowledge, no previous study aimed at assessing the potential of the latest top-quality sonographic equipment using high- and variable-frequency probes and a very sensitive PD technique in depicting both skin and nail involvement in patients affected by psoriasis has been conducted. Figure 3. Left, Psoriatic plaques at the anterior level of the lower half of the leg. The black bar indicates the exact point where the probe was placed. Right, Gray scale longitudinal sonogram of the same site. The continuous white line indicates the point of separation between the surrounding normal skin and psoriatic plaque. Note the evident increase of the thickness of the epidermis (arrow) and dermis (d) and the presence of a hypoechoic band in the upper dermis (asterisk). Epidermal and dermal thickness measurements were 0.26 and 1.2 mm, respectively, in the normal skin and 0.70 and 2.1 mm in the psoriatic plaque. Black and dashed lines indicate where the measurements were taken at the epidermal and dermal levels respectively. The main gray scale sonographic findings at the psoriatic plaque level are epidermal and dermal thickening as a result of increased keratinocyte proliferation and an abnormal concentration of proinflammatory infiltrating cells. 19,20,22,27 Another common sonographic feature is a hypoechoic band in the upper dermis, which may represent inflammatory edema and vasodilatation within the papillary dermis. 24 In a previous study, El Gammal et al 22 formulated the hypothesis that this hypoechoic band corresponded to the clinically palpable papule. However, it is not specific for psoriasis because it may be also present in other inflammatory conditions, such as contact dermatitis, atopic eczema, and acantoma. 28 Thickening of both the epidermis and dermis is most constant sonographic pathologic finding in psoriatic plaques, 17,28 whereas the hypoechoic band in the upper dermis is particularly detectable in the most active stages of the disease. 28 The reduction of both the epidermal and dermal thickness and principally the disappearance of the hypoechoic band at the superficial dermis level were described as the main gray scale sonographic indicators of effective therapy. 19,20,22,23 Figure 4. Left, Psoriatic plaque at the abdominal level. The black bar indicates the exact point where the probe was placed. Right, Gray scale sonogram of the psoriatic plaque. The epidermal layer at the lesion site appears thickened and inhomogeneous (arrows) compared with the healthy zone (white line). Note the acoustic shadowing (arrowheads) generated by the increased thickness of the epidermis. Epidermal thickness measurements were 0.28 and 0.68 mm in the normal skin and psoriatic plaque, respectively. The black lines indicate were the measurements were taken at the epidermal level; d, dermis; and sc, subcutaneous tissue. 1572 J Ultrasound Med 2009; 28:1569 1574

Gutierrez et al Some authors have suggested normal sonographic values of thickness in the different layers of the skin, 15,27 but because the normal thickness is widely variable according to the anatomic area, it could be more rational to perform a comparison between the lesion area and normal skin in the same area of the same patient. Psoriatic onychopathy is characterized by a variable degree of involvement of both the nail plates and nail bed. Nail plate thickness has not been formally measured in healthy individuals, whereas nail bed thickness (distance from the bone margin of the distal phalanx to the ventral plate in longitudinal sonographic view) has been reported for the right second finger of both healthy individuals and psoriatic patients, and their values were 1.5 mm (confidence interval, 1.33 1.79 mm) and 3.0 mm (confidence interval, 2.0 4.01 mm), respectively. 25 The single involvement of the ventral plate has been described as a subclinical finding, and further investigations of the initial involvement of this segment of the nail are necessary. 25,29 The increased blood flow in psoriatic skin and onychopathy is a consequence of a wide spectrum of dermal microvascularity changes, including elongation, dilatation, and twisting of the capillary loops. 26 Currently, high-resolution sonography with PD technology permits the detection of even marginally increased levels of blood flow. In this way, PD imaging could be a feasible and sensitive tool for assessing disease activity and the response to treatment in patients with psoriasis. We showed that both the skin and nail could be suitable anatomic sites to assess by PD imaging for detecting minimal blood flow changes induced by systemic drug treatment. To the best of our knowledge, only a study focusing the role of highly sensitive PD imaging in the monitoring of psoriatic plaque treatment has been published. 30 Nevertheless, further investi- Figure 6. Psoriatic onychopathy. A and B, Gray scale sonograms obtained in longitudinal (A) and transverse (B) views show thickening and irregular undulation of the nail plates, which became a single and wavy hyperechoic layer (arrows). The nail bed is clearly thickened (circles). The nail bad thickness measurement was 3.3 mm. The dashed lines indicate where the measurement was taken; dp, distal phalanx. C, Left, Power Doppler Sonogram showing marked signals indicating an evident blood flow increase. Right, Psoriatic onychopathy in the same patient. A Figure 5. Power Doppler sonograms of psoriatic plaques located at the anterior aspect of the lower half of the leg (A) and at the abdominal level (B). The epidermis appears thickened and inhomogeneous (arrows). The dermis (d) is also thickened and shows a focal hypoechoic band in the top part (asterisks). Evident PD signals are shown in the dermis as a result of a blood perfusion increase. The white lines indicate the separation between the surrounding normal skin and the psoriatic plaque; sc, subcutaneous tissue. B A B C J Ultrasound Med 2009; 28:1569 1574 1573

High-Frequency Sonography in the Evaluation of Psoriasis gations studying larger series of patients in correlation with histologic data may be useful to support these observations. In conclusion, this presentation provides pictorial evidence that high-resolution gray scale sonography with PD imaging is a real-time and noninvasive imaging technique that can be used as an adjunct to the clinical evaluation in assessing the extension and activity of psoriatic disease. References 1. Nestle FO. Psoriasis. Curr Dir Autoimmun 2008; 10:65 75. 2. Salaffi F, De Angelis R, Grassi W; MArche Pain Prevalence; INvestigation Group (MAPPING) Study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study, I: the MAPPING study. Clin Exp Rheumatol 2005; 23:819 828. 3. Salomon J, Szepietowski JC, Proniewicz A. Psoriatic nails: a prospective clinical study. J Cutan Med Surg 2003; 7:317 321. 4. Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis 2005; 64:1165 1168. 5. Selkin B, Rajadhyaksha M, Gonzalez S, Langley RG. In vivo confocal microscopy in dermatology. Dermatol Clin 2001; 19:369 377, ix x. 6. Serup J. Northeved A. Skin elasticity in psoriasis: in vivo measurement of tensile distensibility, hysteresis and resilient distension with a new method. Comparison with skin thickness as measured with high-frequency ultrasound. J. Dermatol 1985; 12:318 324. 7. Wortsman XC, Holm EA, Wulf HC. Real-time spatial compound ultrasound imaging of skin. Skin Res Technol 2004; 10:23 31. 8. Fornage B, Duvic M. High-frequency sonography of the skin. J Eur Acad Dermatol Venereol 1994; 3:47 55. 9. Jemec GB, Gniadecka M, Ulrich J. Ultrasound in dermatology, part I: high frequency ultrasound. Eur J Dermatol 2003; 10:492 497. 10. Machet L, Ossant F, Bleuzen A, Grégoire JM, Machet MC, Vaillant L. High-resolution ultrasonography: utility in diagnosis, treatment, and monitoring of dermatologic diseases [in French]. J Radiol 2006; 87:1946 1961. 11. Schmid-Wendtner MH, Burgdorf W. Ultrasound scanning in dermatology. Arch Dermatol 2005; 141:217 224. 12. Rallan D, Harland CC. Ultrasound in dermatology: basic principles and applications. Clin Exp Dermatol 2003; 28:632 638. 13. Coatney RW. Ultrasound imaging: principles and applications in rodent research. ILAR J 2001; 42:233 247. 16. Cammarota T, Pinto F, Magliaro A, Sarno A. Current uses of diagnostic high-frequency US in dermatology. Eur J Radiol 1998; 27(suppl 2):S215 S223. 17. Seidenari S. High-frequency sonography combined with image analysis: a noninvasive objective method for skin evaluation and description. Clin Dermatol 1995; 13:349 359. 18. Coates LC, Anderson RR, Fitzgerald O, et al. Clues to the pathogenesis of psoriasis and psoriatic arthritis from imaging: a literature review. J Rheumatol 2008; 35:1438 1442. 19. Gupta AK, Turnbull DH, Harasiewicz KA, et al. The use of high-frequency ultrasound as a method of assessing the severity of a plaque of psoriasis. Arch Dermatol 1996; 132: 658 662. 20. Vaillant L, Berson M, Machet L, Callens A, Pourcelot L, Lorette G. Ultrasound imaging of psoriatic skin: a noninvasive technique to evaluate treatment of psoriasis. Int J Dermatol 1994; 33:786 790. 21. El Gammal S, El Gammal C, Kaspar K, et al. Sonography of the skin at 100 MHz enables in vivo visualization of stratum corneum and viable epidermis in palmar skin and psoriatic plaques. J Invest Dermatol 1999; 113:821 829. 22. El Gammal S, Auer T, Popp C, et al. Psoriasis vulgaris in 50 MHz B-scan ultrasound: characteristic features of stratum corneum, epidermis and dermis. Acta Derm Venereol Suppl (Stockh) 1994; 186:173 176. 23. Serup J. Non-invasive quantification of psoriatic plaque: measurement of skin thickness with 15 MHz pulsed ultrasound. Clin Exp Dermatol 1984; 9:502 508. 24. Olsen LO, Serup J. High-frequency ultrasound scan for noninvasive cross-sectional imaging of psoriasis. Acta Derm Venereol 1993; 73:185 187. 25. Worstman X, Holm E, Gniadecka M. Ultrasonido de alta resolución (15 MHz) en el estudio de la uña psoriatica. Rev Chil Radiol 2004; 10:6 11. 26. Creamer D, Allen MH, Sousa A, Poston R, Barker JN. Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis. Br J Dermatol 1997; 136:859 865. 27. Guastalla P, Guerci VI, Fabretto A, et al. Detection of epidermal thickening in GJB2 carriers with epidermal US. Radiology 2009; 251:280 286. 28. Di Nardo A, Seidenari S, Giannetti A. B-scanning evaluation with image analysis of psoriatic skin. Exp Dermatol 1992; 1:121 125. 29. Wortsman X, Jemec GB. Ultrasound Imaging of nails. Dermatol Clin 2006; 24:323 328. 30. Gutierrez M, Filippucci E, Bertolazzi C, Grassi W. Sonographic monitoring of psoriatic plaque. J Rheumatol 2009; 36:850 851. 14. Fornage BD. Sonography of the skin and subcutaneous tissues. Radiol Med 1993; 85:149 155. 15. Fornage BD, McGavran MH, Duvic M, Waldron CA. Imaging of the skin with 20-MHz US. Radiology 1993; 189:69 76. 1574 J Ultrasound Med 2009; 28:1569 1574