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Ultrasound biomicroscopy in the diagnosis of skin diseases

European Journal of Dermatology. Volume 17, Number 6, 469-75, November-December 2007, Review article

DOI : 10.1684/ejd.2007.0261

Summary

Author(s) : Mohamed Bakr M El- Zawahry, Hala M Abdel El-Hameed El- Cheweikh, ShahiraAbd-El-Rahman Ramadan, Dalia Ahmed Bassiouny, Marwa Mohamed Fawzy , The Department of Dermatology Kasr El-Aini University Hospital, Cairo-University, Cairo, EgyptFax: (+202) 7496759, The Department of Ophthalmology, Kasr El-Aini, University Hospital Cairo University, Cairo, Egypt.

Summary : Ultrasound scanning is becoming an important diagnostic tool in dermatology. The major advantages of this technique are its non invasive non-ionizing nature and its relatively low cost. We aimed to evaluate the accuracy of ultrasound biomicroscopy (UBM) in the diagnosis of eight skin disorders namely, morphea, keloid, lichen planus, chronic eczema, psoriasis, port wine stain, seborrheic keratosis, and photo-aged skin, through correlation of its findings with clinical and pathological assessment. Fifty seven patients with the above diseases were examined by ultrasound biomicroscopy (UBM). Two areas, one of normal skin and the other from lesional skin, were examined for each patient. Skin biopsies were taken from the same lesion examined by UBM. In morphea, the dermal echogenicity was increased and the thickness of morphea plaques correlated significantly with disease severity. Keloids appeared as low echogenic images. In lichen planus and chronic eczema the dermis appeared as sound shadow. In psoriasis, an intermediate zone between the epidermis and dermis (B zone) was detected. Its thickness correlated significantly with the PASI score. Port wine stain lesions appeared hypoechoic. Seborrheic keratosis appeared as a sound shadow. In photo-aged skin a subepidermal low echogenic band (SLEB) was detected. We conclude that UBM is a non-invasive diagnostic tool in dermatology which can be used to give valuable information about disease progress and the effectiveness of therapy.

Keywords : eczema, keloid, lichen planus, morphea, photo-aging, port wine stain, psoriasis, ultrasound biomicroscopy (UBM)

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ARTICLE

Auteur(s) : Mohamed Bakr M El- Zawahry¹, Hala M Abdel El-Hameed El- Cheweikh², ShahiraAbd-El-Rahman Ramadan¹, Dalia Ahmed Bassiouny¹, Marwa Mohamed Fawzy¹

¹The Department of Dermatology Kasr El-Aini University Hospital, Cairo-University, Cairo, EgyptFax: (+202) 7496759
²The Department of Ophthalmology, Kasr El-Aini, University Hospital Cairo University, Cairo, Egypt

accepté le 2 Mai 2007

For a long time, the diagnosis of different dermatological diseases has been carried by brief history taking, inspection of the lesion and occasionally palpation without any further investigatory tools. In the last century, histopathological assessment became the gold standard for most dermatological diagnoses. But, the somewhat invasive nature of skin biopsy and the fact that not all lesions are amenable to definitive histological diagnosis, increased the need for other less invasive techniques. In this respect ultrasound seems to be a very promising tool for diagnosis and follow up of treatment of different of skin diseases [1].Dermatosonography or the use of high frequency ultrasound for the examination of human skin is now a fully developed matured technique offering a wide range of possibilities in clinical dermatology [2].The major advantages of this technique are its non invasive, non-ionizing nature and its relatively low cost when compared to x-ray, CT and scintigraphic scanning techniques [3].Ultrasound was introduced to medicine by Gohr and Wedkind and the neurologist Dussik. The pulse-echo technique, inaugurated by Firestone, was first applied to medical diagnosis by Ludwig and Struthers in 1949 for the detection of gall stones [4]. In the late 1970s, Alexander and Miller used high frequency ultrasound (15 MHz) to generate uni-dimensional scans of the skin [2].Ultrasound imaging is based on the different acoustic properties of different tissues. The equipment consists of an ultrasound probe (hosting transducer), an elaboration, and a visualization system. The probe emits ultrasound waves which are transmitted into the tissues, where they are reflected or refracted following the optical laws. These events occur at interfaces between structures of different acoustic impedance, and the returning echo is analyzed and displayed on the monitor of the machine [5]. The average speed of sound in soft tissues is about 1540 m/sec. Most clinical instruments are set up or calibrated assuming that sound propagates through the body at this speed [6].The frequency of the ultrasound used is a determining factor in both penetration and resolution of the imaging system. The general relationship is that the higher frequencies give higher resolution but lower penetration. The frequencies used for the examination of subcutaneous tumors and regional lymph nodes are in the range of 3-10 MHz (conventional US). In contrast, dermatological ultrasonography is primarily carried out with high frequency scanners of 20-50 MHz [2]. The penalty paid for the increase in resolution is the loss of penetration, the maximum penetration that could be achieved for the 10 MHz system is approximately 50 mm but for the 60 MHz system, the penetration is only 5 mm. This is due to increased losses in the tissues [7].The term Ultrasound biomicroscopy is applied to equipment that uses ultrasound frequencies between 50 and 100 MHz. The superb resolution results in observation of living tissues at microscopic resolution, hence the name ultrasound biomicroscopy (UBM). The UBM examination technique has many similarities to other types of B-scan ultrasound examinations, the main differences are the presence of a moving transducer without a covering membrane, the necessity for a water bath technique, the finer movements required and a relatively, short working distance. Examination of the skin is by the use of a small cup. Fluid is required to produce a coupling medium between the transducer and the skin [8].The typical skin image shows the following layers: an epidermal entrance echo, the dermal layer and the low or nonechogenic subcutaneous tissue with obliquely oriented echogenic lines caused by connective tissue bundles [9]. Epidermal structures are only visible when they are thickened e.g. in psoriasis, where hyperkeratosis is prominent and consequently the epidermal echo is enhanced [3]. The dermis is less echogenic than the epidermal entrance echo and contains many different echoes of various intensities. It is thought that dermal echoes arise as a result of the reflection of the ultrasound waves from the interface collagen fibers and the surrounding intercellular matrix and cells [9].Dermatosonography using high frequency US (15-50 MHz) was used in the study of several skin diseases such as scleroderma [10, 11] keloids and hypertrophic scars [9], eczema, lichen planus [2] and psoriasis [12, 13]. Some neoplasms have been examined using ultrasonography, such as seborrheic keratosis [14] and haemangiomas [3]. It has also been used to assess the degree of photoaging and the efficacy of antiaging therapies [15, 16]. In our study the same skin diseases were examined using UBM (50 MHz), which has a higher resolution and may offer more valuable diagnostic information.

Patients and methods

Patients

The study included 57 patients with 8 different skin disorders, morphea (5 with linear morphea, 4 with generalized morphea), lichen planus, psoriasis, port wine stain (on the face in all cases), keloid (on the chest in all cases), seborrheic keratosis (on the face in all cases except one case where it was on the trunk), chronic eczema (2 cases of generalized eczema, 4 localized eczema) and lastly photo-aged skin. The patients were of both sexes, 33 females and 24 males, with ages ranging from 4 months to 68 years (mean age 38.83 ± 18.15). Descriptive data of all patients are shown in table 1.

Patients were randomly selected from the outpatient clinic of Dermatology, Kasr El-Aini Hospital over a period of 6 months (December 2003 to June 2004).

All the patients were subjected to full history taking, photography of skin lesions and clinical examination including psoriasis area and severity index (PASI) score for psoriasis patients. Examination of two areas by ultrasound biomicroscopy (UBM), one of the normal skin and the other from lesional skin, was done for each patient. The patient was usually in a supine position. It was necessary to remove any air bubble prior to examination by immersing the tip of the probe in saline and massaging the tip very gently with a bent swab. Skin biopsies were taken from the same lesion examined by UBM and were stained with haematoxylin and eosin and examined by light microscopy.

Table 1 Descriptive data of all patients

Skin disease	Number of patients	Age in years (mean age ± SD)	Sex		Duration in years (mean ± SD)
M	F
Morphea	9	11-26 (20.3 ± 5.09)	3	6	1-15 (4.6 ± 4.24)
Keloid	5	26-60 (43 ± 15.9)	1	4	0.75-7 (3.5 ± 2.67)
Psoriasis	10	20-65 (44.5 ± 14.99)	6	4	2-10 (4.9 ± 3.17)
Chronic eczema	6	15-48 (26.5 ± 11.57)	3	3	2-14 (4.8 ± 4.8)
Lichen planus	8	34-68 (52.75 ± 11.25)	3	5	0.1-4 (1.5 ± 1.18)
Seborrheic Keratosis	6	35-60 (55.17 ± 10)	2	4	5-20 (10.8 ± 4.9)
Port wine stain	6	0.3-35 (15.56 ± 11.75)	3	3	0.3-35 (15.56 ± 11.75)
Photoaged skin	7	40-60 (52.14 ± 8.25)	3	4	1-6 (3.9 ±1.69)

Ultrasound biomicroscopy (UBM)

The machine used was the paradigm ultrasound Biomicroscope plus Model P45 (UBM plus), which is a microprocessor-based digital instrument that uses very high frequency ultrasound (50 MHz) to produce a two dimensional section view of the examined tissue in B scan (brightness) mode for diagnostic evaluation, and A-scan that measures the axial length with depth of penetration up to 5 mm. The machine utilizes the central processing unit (CPU) with peripheral devices (monitor, track ball unit, light pen, foot switch) and accessories (e.g. cups). The ultrasound scan images acquired by the UBM transducer are viewed on a high resolution color monitor in real-time. The reflected ultrasound waves are controlled and assembled by the computer and magnified to provide a high resolution B-scan image. The cross-sectional picture can be further enhanced by digital filters to improve image contrast or brightness to identify interesting findings without altering the original scanned file image.

Statistical analysis

The data were coded and entered on an IBM compatible computer using the statistical package SPSS version 11.0. The data were summarized using the mean and standard deviation for quantitative data and percent for qualitative data. Differences between the groups studied were assessed using the student’s t-test. Differences between the groups studied were considered statistically significant at P-values less than 0.05.

Results

UBM examination of normal and lesional skin

UBM was carried out to compare normal and lesional skin in each patient (figure 1). The thickness of epidermis and dermis in lesional as well as normal skin was measured in mm (table 2). A statistically significant difference in epidermal thickness between normal and lesional skin was detected in morphea (p-value < 0.001), psoriasis (p-value, < 0.001) and seborrheic keratosis (p-value 0.020). Some interesting findings were also detected in some skin diseases; in morphea there was increased echogenecity of the dermis in lesional skin compared to normal skin in all cases whereas in keloids and portwine stains there was low echogenecity of the dermis in lesional skin compared to normal skin in all cases. (A hyperechoic structure is one that produces echoes on examination while a hypoechoic structure produces very few echoes.)

The dermal thickness could not be assessed in all cases of eczema, lichen planus and seborrheic keratosis in lesional skin due to the presence of a sound shadow which is failure of the sound beam to pass through an object. This blockade is caused by reflection or absorption of the sound and may be partial or complete.

In psoriasis an intermediate zone between the epidermis and dermis which corresponded to rete ridges and papillary dermis was detected in lesional skin only. This zone was named “B” zone. The thickness of the “B” zone was 0.312 ± 0.120 mm. The “B” zone thickness of lesional skin when correlated with the psoriasis area and severity index (PASI) score showed a significant proportional correlation (correlation coefficient 0.002).

Imaging of photodamaged skin revealed a subepidermal low echogenic band (SLEB). The mean thickness of the SLEB was 0.29 ± 0.118 mm.

In port wine stain patients the whole skin thickness was measured in normal and lesional skin. The mean total thickness of normal skin was 1.62 + 0.589 mm and that of lesional skin was 2.319 ± 0.910 mm and the difference between them was statistically insignificant (p-value = 0.148).

Table 2 Comparison of epidermal thickness in normal and lesional skin in different skin diseases

Skin disease	Epidermal thickness (mm)		P-value	Dermal thickness(mm)		P-value
Normal skin mean ± SD	Lesional skin mean ± SD	Normal skin mean ± SD	Lesional skin mean ± SD
Morphea	0.163 ± 0.12	0.129 ± 0.17	< 0.001	1.01 ± 0.21	1.57 ± 0.152	< 0.001
Keloid	0.119 ± 0.059	0.190 ± 0.254	0.39	1.160 ± 0.142	1.585 ± 0.634	0.182
Psoriasis	0.164 ± 0.019	0.284 ± 0.061	< 0.001	1.150 ± 0.087	0.959 ± 0.296	0.66
Ch. eczema	0.153 ± 0.009	0.480 ± 0.385	0.563	1.161 ± 0.044	Sound shadow	___
Lichen planus	0.22 ± 0.158	0.26 ± 0.073	0.538	1.10 ± 0.98	Sound shadow	___
Seborrheic keratosis	0.166 ± 0.38	0.322 ± 0.132	0.020	1.33 ± 0.169	Sound shadow	___
Photoaged skin	0.248 ± 0.270	0.155 ± 0.023	0.384	1.123 ± 0.201	3.27 ± 5.849	0.349

Correlation of UBM examination with clinical data

In psoriasis the mean epidermal thickness was inversely proportional to the PASI score while the dermal thickness was directly proportional to PASI without statistical significance in lesional skin. The “B” zone thickness of lesional skin when correlated with the PASI score showed a significant directly proportional correlation (correlation coefficient 0.002) (figure 7). When the B zone was correlated with duration, there was an insignificant inversely proportional correlation. In psoriasis the dermal thickness of lesional skin was also inversely proportional to duration but the relation was statistically insignificant (table 3).

Table 3 Correlation of epidermal, dermal, and B zone thickness of normal and lesional skin with, duration and PASI score in psoriasis group

	Epidermal thickness (normal skin)	Epidermal thickness (lesional skin)	B Zone thickness	Dermal thickness (normal skin)	Dermal thickness (lesional skin)
PASI score	0.665	0.688	0.002^a	0.077	0.777
Duration in weeks	0.123	0.651	0.812	0.556	0.892

^aCorrelation coefficient is significant at a level 0.01.

Histopathological examination and correlation with UBM examination

Light microscopical examination of skin biopsies from lesional skin revealed the classic pathological findings in each disease. Table 4 shows the results and corresponding findings in UBM examination of lesional skin.

Table 4 Histopathological and UBM findings

Skin disease	Characteristic Histopathological findings	Corresponding UBM finding
Morphea (figure 2)	• Thin atrophic epidermis • Dense collagen bundles	• Decreased epidermal thickness • Increased dermal thickness, high echogenecity
Keloid	• Collagen bundles arranged in nodular pattern • Irregularly arranged fibroblasts	• Increased dermal thickness • Low echogenecity (multiple interfaces)
Chronic eczema	• Epidermal hyperkeratosis & acanthosis with irregular rete ridges • Superfacial perivascular infiltrate	• Increased epidermal thickness • Sound shadow
Lichen planus (figure 3) Psoriasis (figure 4)	• Irregular epidermal acanthosis, degeneration of basal cells • Band like inflammatory infiltrate in upper dermis • Thickened stratum corneum • Elongated rete ridges, oedematous papillary dermis • Reticular dermis	• Decreased epidermal thickness • Sound shadow • A zone high echgenecity • B zone low echogenecity • C zone high echogenicity
Seb Keratosis Haemangioma (figure 5)	• Hyperkeratosis, acanthosis, papillomatosis, horn cysts • Masses of endothelial cells, • Wide capillary lumina were lined with flat endothelial cells	• Sound shadow • Increased epidermal thickness • Low echogenicity
Photoaged skin (figure 6)	• Thin epidermis with partial loss of rete ridges. • Basophilic degeneration of collagen	• Decreased epidermal thickness • Sub-epidermal low echogenic band(SLEB)

Discussion

In recent years, ultrasound scanning has become an important diagnostic tool in dermatology. It is easy to use, completely safe, and provides important diagnostic information [17]. Technological advances have enabled the application of high-resolution ultrasonic imaging of the skin [18].

In the present study, fifty seven patients with eight different skin disorders were studied by UBM to evaluate the accuracy of this technique through correlation of its findings with the clinical and pathological assessment.

In morphea the mean epidermal thickness of lesional skin was significantly less than that of normal skin (p-value < 0.001). The mean dermal thickness of lesional skin was significantly higher than that of normal skin (p-value < 0.001). These findings go with the pathological features of morphea, which were seen in our study, where the epidermis is flattened and atrophic with loss of rete ridges and the dermis is markedly thickened with dense collagen [19].

Few studies have examined Morphea plaques by ultrasound. Serup in 1984 [10] used 15 MHz pulsed ultrasound and found an increase in thickness locally confined to the plaques, moreover clinically advanced morphea plaques were more thickened than less advanced morphea. Cosnes et al. examined scleroderma plaques and detected a characteristic dense image resembling a flattened ‘yo-yo’ with undulations of the dermis, disorganization, loss of thickness and thickened hyperechoic bands in the hypodermis using 13 MHz ultrasound. It was concluded that those morphological ultrasound diagnostic criteria had a high specificity and a high sensitivity in cases of scleroderma [11]. In all our cases of morphea, similar changes including hyper-echoic dermis and “yo-yo”like images, were found. This can be explained by the accumulation of collagen fibers and intercellular substances creating a greater number of echogenic interfaces and increased echogenicity of the dermis.

In the present study, keloids appeared as low echogenic images. This finding agreed with Jemec et al. [2]. Unlike morphea, keloid and hypertrophic scars, which are also fibrous tissue, give a homogenous low echogenic image. This is due to the fact that in keloids the collagen fibers are tightly packed with only a minimal amount of intercellular substance and few interfaces, whereas in morphea there is more intercellular substance allowing for a greater number of echogenic interfaces [9].

In keloids, the mean epidermal thickness in lesional skin was higher than normal skin, without statistical significance. This finding does not match with the pathological features of keloids, where the epidermal thickness was normal or even thinned out by the underlying lesion. However, in our study, histopathological examination revealed normal-looking epidermis. This may be due to the early onset of lesions and may explain our results. The mean dermal thickness in lesional skin was higher than normal skin without statistical significance; this finding goes with the histopathological features of keloids seen in our study, namely an increased density of collagen bundles [20].

In lichen planus the mean epidermal thickness of lesional skin was higher than normal skin, without statistical significance. This goes with the characteristic histological features of fully developed lichen planus papules (which were found in our study) which show irregular acanthosis of the epidermis and compact hyperkeratosis [21]. The mean dermal thickness of the lesional skin could not be detected in all cases because of sound shadowing. Jemec et al. [2] explained the reduced echogenicity of the upper dermis in lichen planus by infiltration with inflammatory cells. Upon sonographic follow-up, Korting et al. [22] observed increased echogenicity of the dermis after treatment of lichen planus (locally with corticosteroid). This raises the possibility of the usage of UBM for following up during therapy.

In chronic eczema the mean epidermal thickness of lesional skin was higher than that of normal skin, without statistical significance. This matched with the classic histopathology where hyperkeratosis co-exists with areas of parakeratosis [23]. The dermis appeared as shadow, which agrees with Jemec et al. [2], who stated that the reduced echogenicity of the upper dermis observed in chronic eczema was due to infiltration with inflammatory cells. Korting et al. [22], observed increased dermal echogenicity after local treatment with corticosteroids and suggested sonographic monitoring of the therapeutic effect of treatment.

In psoriasis the mean epidermal thickness in lesional skin was significantly higher than that of normal skin (p-value < 0.001). This finding matches with the pathological features of psoriasis which were seen in our study, namely epidermal hyperplasia [24]. The mean dermal thickness in lesional skin was less than that of normal skin, without statistical significance.

On comparing ultrasound images with histological examination, in our study, three zones were detected; an A zone which represents the thickened stratum corneum, a B zone which represents the elongated rete ridges and oedematous papillary dermis and a C zone which represent the reticular dermis. Gupta et al. [13], compared ultrasound images using a high frequency (40 MHz) system with the corresponding histological section and reached the same conclusion mentioned above.

In our study, the B zone thickness of lesional skin when correlated with PASI score showed a significant proportional correlation (correlation coefficient 0.002). This is in agreement with Gupta et al. [13], who reported that the severity of psoriatic plaques correlated best with the width of band B and less well with the width of bands A and C. In our study, when both epidermal and dermal thickness were correlated with PASI score the relation was insignificant. This finding is in agreement with El-Gammal et al. [25], and Hoffmann et al. [12].

In the port wine stain (PWS) group, the mean total thickness of lesional skin was higher than that of normal skin, without statistical significance. In all patients, PWS were hypoechoic. Haedersdal et al. [26], used 20 MHz ultrasonography in conjunction with 3-dimensional surface contour analysis to evaluate the effectiveness of pulsed dye laser treatment of port wine stains. Ultrasonography revealed lower dermal echogenicitiy of pre-operative port wine stains compared to post-operative ones and normal skin. Skin thickness was significantly higher in the port wine stain before treatment than after treatment. Low echogenecity can be explained by the histopathological findings of wide capillary lumina lined by flat endothelial cells, since the closer the molecules, the faster the sound waves move through the medium, so fluids are poorer conductors of ultrasound than solids [6].

In seborrheic keratosis the mean epidermal thickness in lesional skin was significantly higher than that of normal skin (p-value = 0.020). This was in agreement with the classic histology of seborrheic keratosis showing a hyperkeratotic surface and numerous horn cysts [27] as seen in our cases. The dermal thickness of the lesional skin could not be detected because it appeared as shadow, the same observation was noted by Jemec et al. [2], who stated that tumors with marked hyperkeratosis, such as seborrheic keratosis, present with the phenomenon of attenuation of penetrating sound and are thus characterized by a sound shadow.

In photo-aged skin the mean epidermal thickness of lesional skin was less than that of normal skin, without statistical significance. This is in agreement with Heilman and Friedman [28] who detected basophilic degeneration of collagen in the upper dermis separated from atrophic epidermis by a narrow band of normal collagen and elastic tissues, a finding which matched well with our pathological examination.

A Subepidermal Low Echogenic Band (SLEB) was detected in photodamaged skin. Gniadecka and Jemec [29] detected SLEB in photodamaged skin, correlated its thickness with the severity of photodamage and considered it as a measure for the efficacy of anti-aging preparations. The origin of SLEB is multifactorial. The main contributing factors are alternation in skin fiber structure (collagen and elastin) and accumulation of glycosaminogylcans in the subepidermal region resulting in increased water-binding capacity [29].

Serup [30] documented that SLEB is a consistent echostructural finding in aged and photodamaged skin and its thickness reflected the degree of cutaneous aging, severity of photoaging and the efficacy of anti-aging drugs. PUVA-induced photo-aging in psoriatic patients was measured by high frequency ultrasound using skin thickness and SLEB as a parameter for photo-damage, with the conclusion that long-term PUVA treatment in psoriatic patients accelerates thinning of the skin in comparison to age-matched controls and that the occurrence of SLEB in PUVA treated psoriatic patients is a sensitive method to investigate PUVA-induced skin aging [31].

However, in another study, significant inter-individual and circadian variability of SLEB echostructure were observed by Gniadecka et al. [32], who concluded that SLEB therefore does not represent an irreversible structural change and limited the use of this parameter in studies of skin aging, photo-aging and efficacy of medication.

Conclusion and recommendations

The use of high frequency ultrasound (UBM) is a promising diagnostic tool in dermatology. The major advantage of this technique is its non invasive, non ionizing nature. Moreover, it is easy to use, safe and provides important diagnostic information.

– In morphea, the thickness of morphea plaques measured by UBM may serve as a parameter for disease severity.
– In lichen planus, and eczema, UBM can be used to follow up the response to therapy through the changes in echogenicity of the lesions.
– In psoriasis, measuring B zone thickness by UBM can be used to assess the severity and monitor the efficacy of anti psoriasis treatment.
– In port wine stains, UBM can be used to evaluate the effectiveness of pulsed dye laser therapy.
– In photo-damaged skin, measurement of SLEB by UBM can be used as a parameter to assess the severity of photo-damage and the efficacy of anti-aging preparations.

Further studies utilizing high resolution ultrasound UBM may be of great value in the assessment of dermatological diseases [33].

Acknowledgements

Conflict of interest: none. Financial support: none

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