Dermoscopic, clinical, and histopathological aspects of leprosy and lepra reaction cases: An observational cross-sectional study

Abstract

Context: 

Owing to myriad clinical presentations in leprosy, it becomes a diagnostic challenge. Dermoscopy visualizes skin structures not normally visible to the naked eye, providing additional morphological information.

Aims: 

The aim of this work was to study and evaluate the various dermoscopic patterns of different types of leprosy and lepra reactions and to assess their association with clinical and histopathology.

Materials and Methods: 

A descriptive cross-sectional study was undertaken at dermatology OPD over 1.5 years after ethical approval. Thorough clinical, physical, local examination, and gross photographs were taken. Dermoscopy was taken and the images were analyzed for dermoscopic features. Biopsy from the same lesion was taken.

Results: 

A total of 50 naïve cases of leprosy and lepra reactions with skin phototypes of IV to VI were studied. Males (30) outnumbered females (20). The most common type was Borderline tuberculoid Leprosy (BT) (21,42%). We observed yellowish-brown and white structureless areas histologically corresponding to dermal granulomatous infiltrate, whereas vascular findings predominantly of linear irregular vessels and variable loss of appendageal structures histologically corresponding to perivascular and periappendageal infiltrate respectively were predominant features throughout the spectrum. Appendageal structures were markedly reduced in the tuberculoid pole. We noted reduced pigmentary network towards tuberculoid pole whereas accentuation towards the lepromatous pole.

Follicular plugging, scaling, and shiny white areas were additional features in the lepra reaction.

Conclusion: 

Yellowish brown and white structureless areas, associated vascular findings predominantly of linear irregular vessels, and variable loss of appendageal structures were key features throughout the spectrum. Sunflower-like appearance, rosette-like pattern and milky red background in histoid leprosy, target-like pattern in type 2 lepra reaction were the unique dermoscopic findings from our study.

Introduction

Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae, primarily affecting the peripheral nerves and skin. The clinical presentation of leprosy mainly depends on the ability of the host to induce cell-mediated immunity (CMI) against M. leprae. It is classified by various classifications but the most scientific, widely accepted, and research-oriented is the Ridley Jopling classification.^[1] It is diagnosed by clinical examination, bacteriological examination, and histopathological examination.^[1,2] The myriad clinical presentations make leprosy a diagnostic challenge, which can easily be confused with other infective and non-infective granulomatous dermatoses.

Dermoscopy is a non-invasive imaging modality, which visualizes subtle clinical patterns of skin lesions and subsurface skin structures not normally visible to the naked eye, thus providing additional morphological information during clinical examination of skin lesions.^[3,4] Its utility has now been extended to pigmentary and inflammatory disorders including granulomatous diseases.^[5-7] Here, we aimed to describe various dermoscopic features in the whole spectrum of leprosy and lepra reaction with their association with clinico-histopathological findings.

Materials and Methods

It was a descriptive cross-sectional study, was conducted via consecutive sampling method on 50 naïve cases. Patients who were clinically suspected of having leprosy, attending the out-patient department over 1.5 years from Nov’19 to March’21 were included in the study after ethical approval from Institute ethical committee board. Patients with any age group, gender, and newly suspected clinical cases of leprosy were included in our study. Patients with pure neuritic leprosy and cases not willing to give consent for biopsy were excluded.

After enrolling the patient, detailed history was collected. Thereafter all the patients were studied for clinical, general physical and local examination. Gross photographs were taken using a Canon HD DSLR camera. Dermoscopy of all patients was taken with dermoscope (Dermlite DL4 - 3Gen Inc, 31521 Rancho Viejo Road, San Juan Capistrano, CA, USA) attached to a smartphone with smartphone adaptor and stored. Thereafter, a biopsy from the same lesion was taken and sent for histopathological examination. Subsequent evaluation of dermoscopic features and their association with clinical and histopathology was done by two observers.

Before conducting the study, a literature search was done using PubMed and many other databases with the following keywords: “dermoscopy , structureless areas, histopathology” for leprosy.

We evaluated dermoscopic findings by the following criteria: structureless area, appendageal findings (follicular findings, white dots), vascular findings (pattern and arrangement), xerosis/scaling pattern, abnormalities in pigment network, shiny areas, background finding, and other features if any.^[8,9]

All data were plotted on excel sheets and analyzed by using GraphPad INSTAT software version 3.06, 32 bit for Windows (GraphPad software Inc.11452 EL Camio Real, San Digeo 92130, USA).

Results

A total of 50 naive leprosy cases were studied. The study patients were of Indian ethnicity, with skin phototypes of IV to VI. Men (30) outnumbered women (20). Leprosy was most common in adulthood (21-40 years) noted in 36 (72%) patients. History of migration was noted in 6 (12%) patients and family history of leprosy was positive in 2 (4%) patients. As per Ridley-Jopling’s classification, the most common type was Borderline tuberculoid Leprosy (BT) (21,42%) in our study (depicted in graph-1).

By performing cutaneous and peripheral nerve examinations (including sensory and motor), we compared our suspected clinical spectrum with proven histopathological type and got the almost similar result (*p-value = 0.7633) shown in [Table 1]. So, in most of our cases, we were able to correlate our clinical spectrum with its corresponding histopathological type.

Table 1:: Comparison between clinical and histopathological types of leprosy and lepra reactions

After performing dermoscopic examination, we observed that yellowish-brown and white structureless areas, associated vascular findings predominantly of linear irregular vessels, and variable loss of appendageal structures were predominant features throughout the spectrum summarized in [Table 2].

Table 2:: Shows a summary of common dermoscopic features with associated histopathological findings

In the Tuberculoid pole of leprosy, majority of cases presented clinically with few, well-defined, asymmetrical, hypoesthetic, erythematous annular plaques. On histopathology, granulomatous infiltrate was mainly located in the upper dermis, we found localized yellowish-brown structureless areas in 5 (20.8%) cases and whitish structureless areas in 14 (58.3%) cases. Linear irregular vessels over the periphery of the structureless areas were seen in 4 (16.6%) cases. Appendageal structures were markedly reduced in BT type compared to TT type. In the patch type of hypopigmented lesion, we also noted a patchy area of reduced to absent pigmentary network. An interesting finding of our study was that we also observed lesions over palm and soles area in two patients of BT leprosy as normally these areas are relatively immune privileged sites in leprosy depicted in [Figure 1].

Figure 1:: Involvement of immune privilege sites in borderline tuberculoid leprosy

One of the distinguishing features of our study is, a single biopsy-proven naïve BB case with erythematous punched-out plaque was also included. In histopathology, it showed upper to deep dermal granuloma corresponding dermoscopically to diffuse yellowish-orange structureless area with the interspersed localized white structureless area, whereas periappendageal granuloma to the reduced number of white dots. The additive finding includes patchy areas of the accentuated pigmentary network with normal hair density.

While studying the lepromatous pole, the BL type had multiple discrete well defined erythematous papules to nodules. Histopathologically, due to the presence of loosely formed dermal granulomas, we found diffuse yellowish-brown structureless area in 3 (50%) cases with out of focus vessels in 4 (66.6%), linear irregular vessels in 5 (83.3%) due to perivascular inflammatory infiltrate whereas diffuse erythema in 1 (16.6%) due to dilated capillaries. Majority of our cases had patchy areas of reduced to broken pigmentary network. Shiny white areas were noted in 3 (50%) BL cases corresponding histologically to dermal fibrosis.

In the symmetrical erythematous to skin-colored papular to nodular lesions of LL leprosy where histology showed diffuse granulomatous inflammatory infiltrate, with the presence of Grenz zone, we observed localized white structureless area in 6 (85.7%) cases, followed by yellowish-brown structureless area in 3 (42.8%) with a relative reduction in appendageal structures. Peripheral erythema in 3 (42.8%) due to dilated capillaries and linear irregular vessels in 4 (57.1%) due to perivascular inflammatory infiltrate, whereas out of focus vessels in 3 (42.8%) due to obscuration by loosely formed granulomatous infiltrate was seen.

The interesting part of our study is, we included uncommon types of leprosy. Here we noted that 4 cases of indeterminate leprosy had well to ill-defined hypopigmented, hypoasthetic patches. As there is histologically presence of perivascular and periappendageal lymphohistiocytic infiltrate, dermoscopically we observed a patchy area of reduced pigmentation with the peripheral broken pigmentary network, reduced appendageal findings, and absence of structureless area in all the cases. This could be a useful clue towards the diagnostic possibility for leprosy in the early phase.

The novel finding of our study is that in both our Histoid leprosy cases presented with multiple shiny, dome-shaped nodules, we found that due to whorled arrangement of granulomas, petal-like structure in roundish configuration giving rise to sunflower-like appearance was seen in dermoscopy. This displaces the feeder vessels outwards, leading to crowning (type of linear irregular vessel) of vessels noted in 2 both cases. Apart from this, we also observed out-of-focus vessels in one case and milky red background with localized white structureless area interspersed with whitish chrysalis-like streaks in the other case. Appendageal findings were reduced to absent. An interesting finding of the present study is that follicular plugging gives rise to a rosette-like pattern [Figure 10].

Figure 10:: Interesting dermoscopic observations in histoid leprosy

In a BT leprosy with type 1 lepra reaction who had an erythematous oedematous hypoesthetic plaque, we observed localized white structureless area with diffuse erythema which histologically corresponds to acute inflammation around dermal granuloma and perivascular inflammatory infiltrate leading to dilated capillaries respectively. There were also a reduced number of white dots and hair density.

In 3 cases of LL with type 2 lepra reaction having discrete erythematous shiny papules to nodules, we saw a localized white area with peripheral erythema, associated telangiectasia, and loss of appendageal structures. Interestingly in one case, we noted a target-like pattern as discussed in Figure 4 with central whitish to a violaceous structureless area with superimposed chrysalis-like whitish streaks, surrounding normal skin followed by a peripheral rim of erythema. The central whitish to a violaceous structureless area corresponding histologically to granulomatous infiltrate with perivascular inflammation, chrysalis like whitish streaks due to dermal fibrosis, and intervening normal skin due to associated dermal edema, whereas in 2 cases of BL with type 2 lepra reaction, we observed shiny white areas with telangiectasia and diffuse erythema along with a reduced number of appendageal findings. This may be due to ongoing acute inflammation which obscures the underlying granulomatous findings.

Figure 4:: Type 2 lepra reaction with dermoscopic and histopathological association

We observed structureless area, vascular morphology and arrangement, pink homogenous background, abnormalities in pigment network and white dots were more marked features in polarized mode, whereas widened skin furrow, abnormality in hair density, attenuation of skin creases, scaling, xerosis, and follicular plugging were more marked features in non-polarized mode.

Discussion

Dermoscopy has evolved over the years to assist in the non-invasive diagnosis of several cutaneous granulomatous disorders like leprosy, sarcoidosis, granuloma annulare, lupus vulgaris, leishmaniasis, nodular amyloidosis, and deposition disorders.^[10,11] The dermoscopic appearance of various granulomatous disorders is characterized by the presence of orange or orange-yellowish structureless areas (focal or diffuse), along with vessels that can be linear or branching.^[10,12] The distinct yellowish-orange background seen in dermoscopy is reflective of underlying dermal granulomas and their visualization is enhanced by applying slight pressure on the skin which reduces erythema called a mass effect.^[8,10,12-14]

In the present study as skin phototype was IV to VI, we noted in the majority of our cases, yellowish-brown structureless area instead of the orangish-yellow structureless area as observed by previous studies^[8,12,15,16] except in one of the BB leprosy cases, where we got yellowish-orange structureless area. Our additive finding may be due to their skin phototype which may lead to a subtle brownish tinge. We observed various dermoscopic findings for each type of naïve leprosy case, where we concluded that yellowish-brown structureless areas with vascular findings predominantly consisting of linear irregular vessels with variable loss of appendageal structures, were predominant features throughout the spectrum. Our study found granulomatous features were more pronounced in infiltrated lesions rather than the flat patchy lesions. We noticed more vascularity over facial areas than extrafacial sites as also observed by K. Vinay et al. in his study.^[12] We observed interesting patterns and appearance in histoid and type 2 lepra reactions outlined in [Figures 2 & Figures 3] respectively.

Figure 2:: Dermoscopic and histopathological association in indeterminate leprosy

Figure 3:: Type 1 lepra reaction with dermoscopic and histopathological association

We have compared our dermoscopic observations and corresponding histological features with the previous literature data depicted in [Figures 5,6,7,8-9].

Figure 5:: Comparison of various dermoscopic observations and their corresponding histological features

Figure 6:: Comparison of various dermoscopic observations and their corresponding histological features

Figure 7:: Comparison of various dermoscopic observations and their corresponding histological features

Figure 8:: Comparison of various dermoscopic observations and their corresponding histological features

Figure 9:: Comparison of various dermoscopic observations and their corresponding histological features

We did not observe yellowish dots and globules as well as violaceous to erythematous hue in the background and follicular plugging in tuberculoid pole and BT leprosy with type 1 lepra reaction respectively as observed by P, Vinay et al. and Alpana Mohta et al. their studies.^[12,15] In the case of histoid leprosy, we didn’t observe the yellowish-orange structureless area and whitish-yellow structureless area as noted by Vinay et al. and Ankad BS et al. in their studies.^[12,17]

Out of 50 patients, we observed a whitish structureless area in 48% cases among which histopathologically perineural inflammatory infiltrate was seen in 70%. Future studies may enlighten on this association.

In comparison with previous studies, the unique aspect of our study is an association of dermoscopic findings with its histopathological features in naive cases of all types of leprosy. We have described the key dermoscopic findings of various types of leprosy including uncommon leprosy (indeterminate and histoid) and lepra reaction, highlighting that dermoscopy as a noninvasive modality can improve the diagnostic aspect. Our study will further aid in the diagnosis of leprosy using dermoscopy.

Sunflower like appearance, rosette-like pattern and milky red background in histoid leprosy, target-like pattern in type 2 lepra reaction and yellowish-brown structureless area, out of focus vessels among various types of leprosy spectrum were the unique dermoscopic findings from our study which has yet not been described in prior literature as per our knowledge.[^18-20]

Conclusion

Yellowish-brown and white structureless areas, associated vascular findings predominantly of linear irregular vessels, and variable loss of appendageal structures were key features throughout the spectrum. Sunflower-like appearance, rosette-like pattern, milky red background in histoid leprosy, target-like pattern in type 2 lepra reaction was the unique dermoscopic findings from our study.

Financial support and sponsorship

Thankful to the Indian association of Leprosy (IAL) and Hind kusht nivaran Sangh, Delhi (HKNS) for the grant.

Conflicts of interest

There are no conflicts of interest.