Abstract
Background
Dermoscopy and reflectance confocal microscopy (RCM) as noninvasive tools are gaining increasing importance in the diagnosis of inflammatory skin disorders. The purpose of our study was to calculate and compare the diagnostic accuracy of dermoscopy and RCM in common inflammatory skin diseases.
Materials and Methods
We retrospectively collected clinical, dermoscopic, and RCM images of psoriasis and lichen planuscases from March 2018 to February 2021 in China‐Japan Friendship Hospital. There were 10 experts evaluated dermoscopic and RCM images independently. Sensitivity, specificity, positive predict value, and negative predictive value for each and all investigators were calculated. The diagnostic accuracy was also measured by the area under the curve (AUC) for the Receiver Operator Characteristic (ROC) Curves.
Results
We collected 82 psoriasis and 47 lichen planus cases. Dermoscopy was more sensitive than RCM in the diagnosis of psoriasis, and overall diagnostic accuracy of dermoscopy was also higher than RCM measured by AUC (0.879 vs. 0.835, p = 0.0001). For lichen planus, RCM had higher sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy than dermoscopy (AUC 0.916 vs. 0.813, p<0.0001).
Conclusion
Dermoscopy and RCM play a significant role in assisting the diagnosis of psoriasis and lichens planus. These two noninvasive diagnostic tools have their own advantages and disadvantages for the evaluation of different inflammatory skin diseases, and they can be combined in clinical practice to improve the accuracy of the diagnosis of inflammatory skin diseases.
Keywords: dermoscopy, lichen planus, psoriasis, reflectance confocal microscopy
1. INTRODUCTION
Dermoscopy as a noninvasive technique allows rapid and magnified in vivo observation of the skin with the visualization of morphologic features, particularly vessels and color variegations, which are often difficult to recognize with the naked eye. Reflectance confocal microscopy (RCM) is a noninvasive technique for real‐time imaging of the superficial layers of the skin down to the superficial reticular dermis, with cellular‐level resolution close to conventional histopathology. Recent years, dermoscopy and RCM are gaining increasing importance in the diagnosis of general dermatoses, such as skin infections and infestations, hair and scalp abnormalities, and inflammatory skin disorders. 1 , 2 , 3 , 4
The clinical appearance of inflammatory skin lesion is usually characteristic, so diagnosis is mainly made clinically in a high proportion of patients. However, unusual presentations at times do exist, but the use of skin biopsies to confirm the clinical diagnosis is frequently avoided by the patients due to its cost. In vivo RCM as a reproducible imaging technique can detect epidermis structure, inflammatory infiltration and dilated capillaries in the papillary epidermis without the need for biopsy samples. The correlation between RCM imaging and histopathology has been studied widely in inflammatory skin diseases. 1 , 5 , 6 RCM and dermoscopy has been used to evaluate several inflammatory skin disorders, such as psoriasis, dermatitis, pityriasis rosea, and lichen planus, and has been correlated with conventional histology in several studies. 7 , 8 , 9 , 10 , 11 , 12
The dermoscopic and RCM diagnostic criteria of these inflammatory skin disorders have been evaluated, but there are few studies comparing diagnostic accuracy of dermoscopy and RCM evaluating images of inflammatory skin diseases by experts instead of single diagnostic criteria. Our study aimed to calculate and compare the diagnostic accuracy of each and all investigators in diagnosis of inflammatory skin disorders using dermoscopy and RCM.
2. MATERIALS AND METHODS
We included psoriasis and lichen planus with confirmed histopathologic diagnosis from March 2018 to February 2021 in China‐Japan Friendship Hospital retrospectively, with dermoscopic images and at least 2 RCM images of each depth (epidermis, dermal‐epidermal junction [DEJ], and dermis). We also included other inflammatory skin diseases as control group, such as atopic dermatitis, contact dermatitis, seborrhea, etc. Lesions on the nail and genital areas were excluded. Moreover, we excluded lesions in patients who had received systemic treatments within 6 months or topical treatments within 1 month.
We performed dermoscopic examinations with the FotoFinder Systems (Medicam 800 HD, FotoFinder Systems GmbH, Birbach, Germany) and RCM with VivaScope Systems (VivaScope 1500, USA, Lucid Inc). One expert who would not participate in the process of image assessment collected clinical, dermoscopic and RCM images of lesions meeting the inclusion criteria.
There were 10 experienced experts blinding to the histopathological diagnoses evaluated images independently to make the diagnosis. They evaluated dermoscopic images, and then RCM images which were arranged in a different order after 2 weeks. Investigators were asked to suggest the most likely diagnosis, and to state if the diagnosis was certain. They also needed to point out if the dermoscopic and RCM images were of high quality for making correct diagnosis. Furthermore, the presence of these dermoscopic and RCM features was evaluated: (1) distribution and pattern of blood vessels, (2) Wickham striae, (3) brown/blue gray dots, (4) Munro microabscesses (neutrophils in the stratum corneum), (5) parakeratosis, (6) papillae interface dermatitis (papillary rims were obscured by the presence of a diffuse inflammatory cells infiltrate), and (7) dermal inflammatory cell infiltration.
2.1. Statistical analysis
We calculated sensitivity, specificity, positive predict value (PPV), and negative predict value (NPV) of the dermoscopic and RCM diagnosis of each investigator and for all investigators. The diagnostic accuracy for each inflammatory skin disorder was also calculated and measured by the area under the curve (AUC) for the Receiver Operator Characteristic (ROC) Curves, and the difference in AUCs were compared by Delong test. We also calculated the proportion of cases that investigators judged to be of high image quality and the proportion of cases presented with certain dermoscopy or RCM pattern. Interinvestigator agreement on RCM and dermoscopic image quality and specific criteria of dermoscopy and RCM was assessed by the kappa of Fleiss coefficient. Statistical analyses were performed using SPSS statistics software 26.0 and Medcalc statistical software 19.0. p Values of <0.05 were considered statistically significant.
3. RESULTS
A total of 207 inflammatory dermatoses cases were evaluated: 82 psoriasis (mean age 37.1 ± 15.3), 47 lichen planus (mean age 45.6 ± 10.6), and other 78 inflammatory lesions as control group, including atopic dermatitis, contact dermatitis, and seborrhea (mean age 38.6 ± 15.6). The characteristics of patients and distribution of lesions in different inflammatory dermatoses were listed in Table 1.
TABLE 1.
Characteristics of included inflammatory dermatoses
| Psoriasis | Lichen planus | Control group | |
|---|---|---|---|
| Cases, n (%) | 82 (39.6) | 47 (22.7) | 78 (37.7) |
| Ages (mean ± SD) | 37.1 ± 15.3 | 45.6 ± 10.6 | 38.6 ± 15.6 |
| Sex, n (%) | |||
| Males | 45 (54.9) | 25 (53.2) | 40 (51.3) |
| Females | 37 (45.1) | 22 (46.8) | 38 (48.7) |
| Sites, n (%) | |||
| Scalp | 16 (19.5) | 0 (0) | 0 (0) |
| Face | 0 (0) | 5 (10.6) | 8 (10.2) |
| Trunk | 34 (41.5) | 9 (19.1) | 18 (23.0) |
| Limbs | 32 (39.0) | 33 (70.2) | 52 (66.7) |
Overall diagnostic accuracy measured by AUC for dermoscopic examination was higher than RCM for psoriasis (AUC 0.879 vs. 0.835, p = 0.0001); however, the overall diagnostic accuracy of RCM examination measured by AUC was higher than dermoscopy for lichen planus (AUC 0.916 vs. 0.813, p < 0.0001) (Figure 1).
FIGURE 1.
Overall diagnostic accuracy for psoriasis and lichen planus of dermoscopy and RCM. The area under the curve (AUC) of the receiver operating characteristics (ROC) was shown
3.1. Psoriasis, lichen planus, and reflectance confocal microscopy
Mean sensitivity, specificity, positive predict value (PPV), and negative predict value (NPV) of all 10 investigators of dermoscopic and RCM evaluations for inflammatory lesions were reported in Table 2. Dermoscopy had higher sensitivity (84.5% vs. 76.8%, p = 0.001) and negative predict value (90.0% vs. 86.1%, p = 0.002) than RCM in the diagnosis of psoriasis, but there was no significant difference for specificity and positive predict value between dermoscopy and RCM. For lichen planus, RCM had higher sensitivity (85.7% vs.69.6%, p<0.001), specificity (97.5% vs. 96.1%, p = 0.047) positive predictive value (91.2% vs. 84.4%, p = 0.004) and negative predictive value (95.9% vs.91.5%, p<0.001) than dermoscopy.
TABLE 2.
Mean sensitivity, specificity, positive predict value, and negative predict value for psoriasis and lichen planus of dermoscopy and reflectance confocal microscopy of all the investigators
| Dermoscopy | RCM | p Value | |
|---|---|---|---|
| Psoriasis | |||
| Sensitivity | 84.5 ± 4.4(78.0–90.2) | 76.8 ± 4.5(69.5–82.9) | 0.001 |
| Specificity | 91.2 ± 2.4(86.4–95.2) | 93.4 ± 3.6(88.0–97.6) | 0.115 |
| Positive predict value (PPV) | 86.4 ± 3.3(83.8–92.0) | 88.8 ± 5.4(80.0–97.1) | 0.244 |
| Negative predict value (NPV) | 90.0 ± 2.6(86.3–93.4) | 86.1 ± 2.3(82.5–89.1) | 0.002 |
| Lichen planus | |||
| Sensitivity | 69.6 ± 3.9(66.0–76.6) | 85.7 ± 4.2(78.7–91.5) | <0.001 |
| Specificity | 96.1 ± 1.4(93.8–98.1) | 97.5 ± 1.4(95.6–98.8) | 0.047 |
| Positive predict value (PPV) | 84.4 ± 4.5(77.8–91.2) | 91.2 ± 4.6(85.1–95.5) | 0.004 |
| Negative predict value (NPV) | 91.5 ± 0.9(90.5–93.3) | 95.9 ± 1.2(94.0–97.4) | <0.001 |
RCM: reflectance confocal microscopy.
Regular/diffuse distributed dotted vessels under dermocopy (Figure 2A) were observed in 79.0% (range 72.0–84.1%, SD 4.4) of psoriasis cases, (Table 3) and the interinvestigator agreement was fair (Fleiss Kappa = 0.391) (Table 4). Wickham striae (Figure 2B) and Brown or blue gray dots were found in 65.3% (range 61.7–68.1%, SD 2.7) and 61.0% (range 49.0–72.3%, SD 8.1) in lichen planus, and the interinvestigator agreement was almost perfect (Fleiss Kappa = 0.846) and moderate (Fleiss Kappa = 0.558), respectively. In RCM examination, Munro microabscesses (Figure 2C) were found in 66.1% (range 61.0–70.7%, SD 3.2) of psoriasis cases, and the interinvestigator agreement was almost perfect (Fleiss Kappa = 0.898). Interface dermatitis (Figure 2D) was found in 86.0% (range 76.6‐91.5%, SD 4.6) of lichen planus cases and the interinvestigator agreement was substantial (Fleiss Kappa = 0.799). Dermal inflammatory cell infiltration was found in 74.2% (range 59.8–81.7%, SD 7.2) of psoriasis cases.
FIGURE 2.
Representative dermoscopic and RCM features of inflammatory skin diseases. (A) Psoriasis presented with regularly distributed globular vessels over light red background with white scales on dermoscopy. (B) Lichen planus exhibited Wickham striae over a yellowish background on dermoscopy. (C) Psoriasis revealed neutrophils in the stratum corneum (Munro microabscess) showing notably highly refractile and twinkling particles on RCM. (D) Lichen planus showed papillary rims obscured by the presence of a diffuse inflammatory cells infiltrate and bright melanophages in the dermal‐epidermal junction on RCM.
TABLE 3.
The proportion of dermoscopic and RCM features investigators observed in psoriasis and lichen planus
| Dermoscopy | Mean ± SD | Range | |
|---|---|---|---|
| Psoriasis | Regular/diffuse distributed dotted vessels | 79.0% ± 4.4% | 72.0–84.1% |
| Lichen planus | Wickham striae | 65.3% ± 2.7% | 61.7–68.1% |
| Brown/blue gray dots | 61.0% ± 8.1% | 49.0–72.3% | |
| Dotted/linear vessels | 56.4% ± 7.5% | 44.7–66.0% | |
| RCM | |||
| Psoriasis | Munro microabscesses | 66.1% ± 3.2% | 61.0–70.7% |
| Parakeratosis | 82.8% ± 3.7% | 78.0–86.6% | |
| Dermal inflammatory cell infiltration | 74.2% ± 7.2% | 59.8–81.7% | |
| Lichen planus | Papillae interface dermatitis | 86.0% ± 4.6% | 76.6–91.5% |
RCM: reflectance confocal microscopy.
TABLE 4.
Interinvestigator agreement of image quality and characteristic features
| Interinvestigator agreement | Fleiss Kappa | 95% confidence interval | |
|---|---|---|---|
| Dermoscopy | |||
| Image quality | Fair | 0.243 | 0.242–0.243 |
| Regular/diffuse distributed dotted vessels | Fair | 0.391 | 0.390–0.391 |
| Wickham striae | Almost perfect | 0.846 | 0.845–0.846 |
| Brown/blue gray dots | Moderate | 0.558 | 0.557–0.559 |
| RCM | |||
| Image quality | Fair | 0.269 | 0.268–0.269 |
| Munro microabscess | Almost perfect | 0.898 | 0.897–0.898 |
| Interface dermatitis | Substantial | 0.799 | 0.799–0.800 |
RCM: reflectance confocal microscopy.
Investigators announced to have a high level of confidence in the dermoscopic and RCM diagnosis in a mean of 70.1% (range 63.8–80.2%, SD 5.1) and 64.1% (range 57.0–74.4%, SD 6.2) of all cases, respectively.
The quality of dermoscopic images was considered good for the diagnosis in 71.0% ± 6.4% of all cases for the ten investigators, and the interinvestigator agreement was fair (Fleiss Kappa = 0.243). Moreover, the quality of RCM images was declared to be good for the diagnosis in 63.6% ± 6.0% of all cases, and the interinvestigator agreement was also considered to be fair (Fleiss Kappa = 0. 0.269). The evaluators considered the overall quality of the dermoscopic images as higher than that of RCM (p = 0.017).
4. DISCUSSION
Our study showed good diagnostic accuracy for inflammatory skin diseases of both dermoscopy and RCM. Dermoscopy had higher sensitivity, negative predictive value, and overall diagnostic accuracy by comparison of AUC of ROCs than RCM for diagnosis of psoriasis. The results were possibly due to certain dermoscopic features such as regular/diffuse distributed dotted vessel were easily observed in a majority of psoriatic cases, which is a characteristic dermoscopic feature of psoriasis, and is highly predictive of the correct diagnosis of psoriasis. 10 , 13 , 14 , 15 Regular/diffuse distributed dotted vessel was also observed in the majority of our psoriasis cases, leading to the high diagnostic sensitivity and overall diagnostic accuracy of psoriasis in our study.
However, the imaging depth of RCM could be affected by hyperkeratosis of some psoriatic lesions, since the refraction is significantly increased and light transmitted into the dermis is reduced, resulting in typical RCM features such as papillomatosis, tortuous and dilated vessels in dermis being neglected in some cases. Even enlarged dermal papillae, dilated vessels and dermal inflammatory cell infiltration had been detected, they could be seen in a number of inflammatory diseases with no significant difference. 16 , 17 Munro microabscesses, which is highly specific for the diagnosis of psoriasis, could be observed in 66.1% of our cases with almost perfect consistency among investigators, which contributed significantly to the correct diagnosis of psoriasis. However, it was often observed with higher capillary flow in tortuous capillaries in unstable psoriatic lesions instead of all psoriatic lesions. 18 As a result, RCM had lower sensitivity and overall diagnostic accuracy than dermoscopy for the diagnosis of psoriasis.
For lichen planus, RCM had higher sensitivity, specificity, positive predictive value and negative predictive value than dermoscopy, and AUC comparison suggested that RCM had higher diagnostic accuracy than dermoscopy, since the most characteristic RCM feature of lichen planus was interface dermatitis, which corresponded well with histopathology. Papillary rims were obscured by the presence of a diffuse inflammatory cells infiltrate, arranged in sheet‐like structures in the dermal‐epidermal junction. A dense infiltrate of plump bright cells corresponded to abundant melanophages in the upper dermis histologically. 19 , 20 The above features were easy to distinguish in both longitudinal (pathological) and transverse (RCM) sections, so histopathology and RCM were sensitive to these changes. Interface dermatitis is of great significance in the diagnosis of lichen planus due to its typical appearance and high interobserver consistency. Interface dermatitis was found in a majority of our lichen planus cases with substantial consistency among investigators, and was rarely seen in other inflammatory skin diseases in our cases. As a result, RCM had higher sensitivity, specificity, and over all diagnostic accuracy than dermoscopy in diagnosis for lichen planus in our study.
It is worth noting that other dermatoses such as lupus erythematosus, lichen nitidus, and acute dermatitis can also exhibit similar changes to interface dermatitis observed in lichen planus, while Wickham striae or blue‐gray dots in dermoscopic examination may assist to distinguish lichen planus from the above dermatoses. 21 , 22 , 23 Wickham striae was seen almost exclusively in lichen planus cases with almost perfect consistency among investigators, leading to high specificity and positive predictive value in dermoscopic examination. However, Wickham striae was commonly seen in classical lichen planus but rarely in pigmented lichen planus. Brown or blue gray dots, which were commonly observed in pigmented lichen planus, were found in 61.0% of our lichen planus cases, corresponding to melanophages in dermis, assisting the diagnosis of lesions without typical Wickham striae. Granular pigmentation can be seen in a variety of skin diseases, therefore interface dermatitis under RCM can make up for the insufficient diagnosis of atypical lichen planus under dermoscopy. In progressive lichen planus lesions, dotted or linear blood vessels were radially arranged, corresponding to vertical or horizontal dilated capillaries in the dermal papillae pathologically. By contrast, the vessels in psoriasis is characterized by regular or diffused dotted vessels without pigmented dots and Wickham striae. 24
There are some limitations in our study. First, cases were included retrospectively in our database rather than prospectively, which may cause selection bias. Some typical RCM features may be missed due to incomplete scanning, and some sites of hyperkeratosis may result in low light transmittance into dermis, leading to the underestimation of the diagnostic accuracy of RCM. Second, our study aimed to compare the diagnostic accuracy of dermoscopy and RCM for inflammatory diseases, so we did not conduct detailed analysis and comparison of specific dermoscopic and RCM criteria in our study. Furthermore, there were only 10 investigators assessing dermoscopic and RCM images separately, resulting in a lack of general applicability.
Our study demonstrated that both dermoscopy and RCM are valuable tools in the diagnoses of inflammatory skin diseases. Further studies should concentrate to compare dermoscopy and RCM alone with the combination of the two techniques, especially in those cases difficult to make the clinical diagnoses. Special locations such as nail and genital areas need attention in further studies.
ACKNOWLEDGMENTS
This work was carried out by Zi‐Yi Wang, Wen‐Min Fei, Cheng‐Xu Li and Yong Cui. We gratefully acknowledge their invaluable cooperation in preparing this application note.
Wang ZY, Fei WM, Li CX, Cui Y. Comparison of dermoscopy and reflectance confocal microscopy accuracy for the diagnosis of psoriasis and lichen planus. Skin Res Technol. 2022;28:480–486. 10.1111/srt.13158
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