Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 1 Dermoscopic Differentiation of Blister Beetle Dermatitis and Herpes Zoster: an Observational Study Balachandra Suryakant Ankad1, Varsha R. Koti1, Aimilios Lallas2 1 Department of Dermatology, S. Nijalingappa Medical College, Near APMC, Navanagar, Bagalkot, Karnataka, India 2 First Department of Dermatology, School of Medicine, Faculty of Health Sciences, Aristotle University, Thessaloniki, Greece Key words: dermoscopy, blister beetle dermatitis, herpes zoster, bullous disorders Citation: Ankad BS, Koti VR, Lallas A. Dermoscopic differentiation of blister beetle dermatitis and herpes zoster: An observational study. Dermatol Pract Concept. 2022;12(4):e2022180. DOI: https://doi.org/10.5826/dpc.1204a180 Accepted: January 3, 2022; Published: October 2022 Copyright: ©2022 Ankad et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Balachandra Suryakant Ankad, Professor, Department of Dermatology, S. Nijalingappa Medical College, Near APMC, Navanagar, Bagalkot-587102, Karnataka, India. Cell Phone: +91 9980410056. Fax: 08354 235360, E-mail: drbsankad@gmail.com Introduction: Blister beetle dermatitis (BBD) and herpes zoster (HZ) manifest suddenly with vesicular lesions mimicking each other and progress rapidly. But a lack of definite differentiating criteria yearns the need for better investigating modality. Though histopathology persuades the need, is an invasive procedure, commonly deferred. Thus, dermoscopy, a non-invasive rapid diagnostic tool, can help in differentiating. Objectives: To evaluate different dermoscopic patterns of BBD and HZ to differentiate both and to study dermoscopic features in early and late stages of lesions. Methods: An observational cross-section study conducted in southern India. Nine patients with clin- ical features suggestive of BBD and HZ were recruited. Lesions were divided arbitrarily into early and late. Dermoscopic examination was performed with handheld dermoscope. Diagnosis was confirmed by skin biopsy and Tzanck smear wherever necessary. Statistical analysis performed using data in terms of frequencies and percentages. Results: Dermoscopy of early BBD lesions showed multiple discrete and confluent yellowish-white structures, brown dots, roundish white globules, gray structures, ‘targetoid pattern’, brown areas over intense reddish pink background. Late BBD lesions revealed pinkish-white area, reduced gray struc- tures and, dotted and globular vessels. Early HZ lesions showed poly-lobular gray and brown glob- ules, bright pink background, gray globules covered by grayish veil-like structure with gray rim. Late HZ lesions revealed ‘solar eclipse’ pattern and ‘crumpled fabric’ patterns. The dermoscopic findings correlated with histopathology. Conclusions: Dermoscopic patterns show peculiar features consistently pertaining to BBD and HZ, thus help in early diagnosis assisting in accurate treatment in both conditions. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 Introduction Paederus dermatitis, well known as dermatitis linearis or blister beetle dermatitis (BBD) is an irritant contact der- matitis following exposure of an insect belonging to the genus Paederus [1]. Accidental crushing of the beetle over the skin releases hemolymph containing a potent vesicant, paederine [2]. It is characterized with sudden onset of ery- thematous, edematous lesions in linear whiplash appearance over exposed areas or kissing lesions in opposing areas. Herpes zoster (HZ) is a segmental eruption due to re- activation of latent varicella zoster virus from dorsal root ganglion which presents as closely grouped papules, rapidly becoming vesicular and pustular; develop in one or more contiguous dermatomes with sharp cut off at the midline [3]. BBD and HZ manifest suddenly with vesicular lesions and progress rapidly in the disease process. Lesions of both entity are associated with pain and burning sensation and hence they mimic each other morphologically and symptomatically [4,5]. Thus, both lesions should be diagnosed with accuracy. There are no defined criteria to differentiate both conditions clinically. However, histopathology plays an important role to distinguish. Many times, patients may not agree for the same. Dermoscopy is a rapid, non-invasive tool which helps to visualize surface and sub surface features that are not visible to naked eyes [6]. Dermoscopy of BBD is explained in a single case report till date [7] and limited descriptions on dermoscopic patterns in HZ are present in the literature [8,9,10]. Furthermore, there is a hiatus in the dermoscopic distinction between the two. In this study, we evaluated the dermoscopic features of BBD and HZ. Objectives To evaluate different dermoscopic patterns in distinction of BBD and HZ. To evaluate dermoscopic differences at early and late stages of evolution of lesions. Methods This study was conducted in southern India between January 2021 and May 2021. The approval from the institutional re- view board was taken and an informed written consent was obtained from patients. It was an observational cross-section analysis. The patients with clinical features suggestive of BBD and HZ were analyzed for demographic details in terms of age, sex and occupation. Vesicular lesions with classical features without history of previous treatment were included in the inclusion criteria. Exclusion criteria included lesions with super-added infection. Lesions were divided arbitrarily into early and late. Lesions with less and more than 3 days were considered as early and late lesions respectively. Physi- cal examination and hematological investigations were done to assess the systemic involvement. Dermoscopic examination of target lesion was done with handheld dermoscope with 10x magnification using ultrasound gel as interface medium. Care was taken avoid pressure on the lesions. Dermoscopic analysis was done by one of the authors (BSA). Diagnosis was confirmed by skin biopsy and Tzanck smear wherever necessary. Results This study included 9 patients with 6 (66.6%) males and 3 (33.3%) females. Age of patients ranged from 10 years to 70 years (mean age 35 years). Five (55.5%) patients had BBD with erythematous and linear lesions with crusting and vesicles with burning sensation over exposed body parts (Figures 1A, 2A, 3A, and 4A). One patient was followed up (5 days) for the healed lesion (Figure 5A). Biopsy was per- formed in two patients clinically diagnosed with BBD and in Figure 1. (A) Clinical image of early lesion of blister beetle dermatitis involving malar eminence and left eyelids unilaterally. (B) Dermoscopy reveals presence of multiple discrete and confluent yellowish-white structures (star) and brown globules (arrow) indicating excoriation with white scales. Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 3 Figure 2. (A) Clinical image of early lesion of blister beetle dermatitis over nape of neck. (B) Dermoscopy shows gray structure (yellow star), multiple brown dots/ globules (red arrows), and brown areas (green star) with roundish white globules (red star) over the pink background. Few white globules show brown dots (blue circle) in the center in a targetoid pattern. Figure 3. (A) Clinical image of early lesion of blister beetle dermatitis over right shoulder. (B) Dermoscopy of shows brownish structureless area (green star) in center surrounded by confluent gray structures (yel- low star) with gray (yellow circles) and brown dots (red arrow) on pink background. Note the white scales (black arrow) surrounding the brown dots and globules. Figure 4. (A) Clinical image of late lesion of blister beetle dermatitis over peri-orbital region. (B) Dermos- copy reveals multiple confluent gray structures (yellow star), brown areas (green star) and white globules (red star) with brown globules (red arrow). Pinkish-white structureless area (black star) and gray globules (yellow circle) are well appreciated on a pinkish background. 4 Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 HZ lesions were distributed in the ophthalmic branch of trigeminal nerve (Figures 6A and 7A) and thoracic, cervical nerves (Figures 8A and 9A), as closely grouped red papules and vesicles on erythematous background. Four (44.4%) pa- tients with HZ were included in the study. Dermoscopy of Early HZ Lesions Polylobular gray and brown globules over a bright pink background were noted with gray globules were covered by grayish veil-like structure with gray rim. Yellowish-orange structure surrounding the pigment globules, red areas and scales were seen (Figures 6B, 7B and 8B). Dermoscopy of Late HZ Lesions Polylobular gray and brown structures surrounded by er- ythematous zone resembling a ‘solar eclipse’ pattern were observed with multiple brown and gray dots (Figures 9B and  9C). ‘Crumpled fabric’ appearance which describes one patient with HZ. Tzanck smear was performed in two patients clinically suspecting with HZ to see for acantholytic cells and multinucleated giant cells. Dermoscopy of Early BBD Lesions Multiple discrete and confluent yellowish-white structures, brown dots (Figure 1B) with roundish white globules, gray structures and brown areas (Figures 2B and 3B) over in- tense reddish pink background. Few roundish white glob- ules showed brownish pigmentation at its center (Figure 2B). White scales around the brown globules were other features (Figure 3B). Dermoscopy of Late BBD Lesions Similar pattern were observed but for the reduced gray structures in addition to pinkish-white areas (Figure 4B). Few lesions revealed dotted and globular vessels, scales on a pinkish-white background (Figure 5B). Figure 6. (A) Clinical image of herpes zoster involving left ophthalmic branch of trigeminal nerve. (B) Dermoscopy shows poly-lobular gray (yellow circles) and brown (red arrow) globules. Note the gray veil-like structure (yellow star) covering the pigment globules with gray rim (green arrow). Figure 5. (A) Clinical image of healed lesion of blister beetle dermatitis over nape of neck. (B) Dermoscopy reveals dotted (red circles) and globular vessels (green circles) and scales (black arrow) on a pinkish-white background. White globules (green arrow) and multiple gray and brown dots (white circles) are noted. Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 5 Figure 8. (A) Clinical image of herpes zoster involving right trunk in dermatomal involvement without crossing the midline. (B) Dermoscopy shows poly-lobular gray (yellow circle) and brown (red arrows) globules. Gray globules are covered by grayish veil-like structure (yellow star) with gray rim (green ar- row). Yellowish-orange structure (white star) surrounding the pigment globules is well appreciated. Red areas (white arrow) and scales (black arrow) are seen. Note the bright pink background. Figure 7. (A) Clinical image of herpes zoster involving right trigeminal nerve. (B) Dermoscopy shows poly-lobular gray (yellow circle) and brown (red arrows) globules. Gray globules are covered by grayish veil-like structure (yellow star) with gray rim (green arrow). Yellowish-orange structure (white star) sur- rounding the pigment globules is well appreciated. Note the bright pink background. folding of roof of flaccid bullae in late lesions was noted (Figures 9B and 9C) [8]. There was increased intensity of gray structures observed in late HZ lesions when compared to late lesions of BBD. Dermoscopic differentiation between BBD and HZ is depicted in Table 1. Conclusions Dermoscopy being a rapid, non-invasive diagnostic tool, that demonstrates features which correlate well with histopathological changes. Furthermore it also reveals the changes that take place in the different layers of skin by which one can study the disease evolution process. This study is aimed at differentiating BBD from HZ in a dermo- scopic perspective. Clinically BBD manifests as fluid filled and necrotic lesions with pain and burning sensation [11]. The differentials include herpes simplex, HZ or contact irri- tant dermatitis [12]. Dermoscopic analysis of BBD is very sparse in the lit- erature and limited to a single case report. Authors noted 6 Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 Yellowish-white globules indicate spongiotic vesicles with serum within the epidermis and white roundish globules are suggestive of micro-pustules (Figure 10). Gray structure is due to necrotic pigmented epithelium with non-pigmented regenerating epithelium. In contrast, brown dots are due to necrotic keratinocytes with retained melanin. Brown areas represent dried serum and necrotic keratinocytes with re- tained melanin. Scales and pink background correspond to hyperkeratosis and vasodilatation respectively. White glob- ules with brown dots in the centre are suggestive of perifol- licular micropustule. HZ shows ballooning degeneration of necrotic keratino- cytes within intra-epidermal blister and few multinucleated giant cells at the base of blister in histopathology. Dermal small vessel vasculitis is a characteristic feature [14]. brown/black dots on a gray background surrounded by white halo and erythema in a case of BBD [7]. In the present report, the dermoscopic patterns varied on the basis of duration. Early lesions showed yellowish-white structures with roundish white globules and gray structures on intense reddish-pink background. Similar features were noted in late lesions with reduction in the gray structure. Brown dots/areas and scales were observed in both lesions. Interestingly, healed lesion showed vascular elements such as dotted and globular vessels. Histopathology of BBD is characterized by destruction of epidermis with necrosis and separation of keratinocytes with formation of vesicles and infiltration of eosinophils and polymorphs. Perifollicular and inter-follicular inflammatory infiltrate is noted [13]. Table 1. Dermoscopic differences between blister beetle dermatitis and herpes zoster. Dermoscopic features Blister beetle dermatitis Herpes zoster Early lesions • Discrete and confluent yellowish-white structures. • Brown dots with roundish white globules, gray structures and brown areas. • White scales. • Background: intense reddish pink. • Poly-lobular gray and brown globules. • Gray globules covered by grayish veil-like structure with gray rim. • Yellowish-orange structure surrounding the pigment globules and red areas. • Scales present. • Background: bright pink. Late lesions • Decreased amount of gray structures. • Vessel morphology: dotted and globular vessel. • Scales present. • Background: pinkish-white • Increased intensity of gray structures. • ‘Solar eclipse’ pattern • Multiple brown and gray dots. • ‘Crumpled fabric’ appearance. Figure 9. (A) Clinical image of late lesion of herpes zoster involving right shoulder and arm. (B and C) Dermoscopy shows poly-lobular gray (yellow stars) and brown (red arrows) structures surrounded by erythematous zone (black stars). Note the brown and gray dots (yellow arrows) and the ‘crumpled fabric’ appearance (white circle) and ‘solar eclipse’ pattern (yellow box). Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 7 dilated vessels (Figure 11). The brown dots and globules are due to dried serum, necrotic keratinocytes and melanin re- tention. Scaling is due to hyperkeratosis [8,9]. The white linear folds / ‘crumpled fabric’ appearance were due to fold- ing of superficial keratinocytes (roof) due to flaccidity was observed in late lesions of HZ. This was previously reported only in pemphigus vulgaris, pemphigus foliaceous and Hailey-Hailey disease (as ‘crumpled fabric appearance’) [8]. This appearance is expected in older bullous lesions with flaccidity of bullae. Multiple poly-lobular gray globules correlated to the necrotic keratinocytes within the intra-epidermal vesicle. The grayish veil-like structure is due to the non-pigmented epithelium of the basal keratinocytes with overlying ne- crotic pigmented keratinocytes within the vesicular fluid. Gray rim is because of edge of vesicle that is seen verti- cally under dermoscopy. Yellowish-orange structure cor- responds to serum and extra-vasated erythrocytes within the intra-epidermal vesicle. Erythematous background correlates with the increased vascularity and red dots with Figure 10. Schematic histopathological representation of dermoscopy of blister beetle dermatitis. White globules indicate micro-pustules (yellow box), scaling with grayish structures indicates hyperkeratosis and necrosis of pigmented epithelium (green box), brown areas indicate dried serum with necrotic kera- tinocytes with retained melanin (red box). Erythematous background indicates increased vascularity and vasodilation (blue box). Figure 11. Schematic histopathological representation of dermoscopy of herpes zoster. Multiple poly- lobular gray globules indicates acanthosis and necrotic pigmented keratinocytes within intra-epidermal vesicle (yellow box), brown globules depicting serum, necrotic keratinocytes with retained melanin (red box), yellowish orange structure indicates serum with extra-vasated erythrocytes within the intraepider- mal vesicle (green box). Intense erythematous background with red dots indicate increased vascularity and vasculitis in the superficial dermis (blue box). 8 Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 References 1. Padhi T, Mohanty P, Jena S, Sirka CS, Mishra S. Clinico-epide- miological profile of 590 cases of beetle dermatitis in western Orissa. Indian J Dermatol Venereol Leprol. 2007:333-335. DOI: 10.4103/0378-6323.35735. PMID: 17921615. 2. Zargari O, Asadi AK, Fathalikhani F, Panahi M. Paederus der- matitis in northern Iran. a report of 156 cases. Int J Dermatol. 2003;42:608-612. DOI: 10.1046/j.1365-4362.2003.01771.x. 3. Sterling JC. Viral infections. In: Griffiths CEM, Barker J, Bleiker T, Chalmers R, Creamer D, editors. Rook’s textbook of dermatology. 9th edn, Vol 1. West Sussex: John Wiley and Sons: 2016.pp. 25.12. 4. Singh A, Singh AK, Singh D, Varghese A. Blister beetle derma- titis: Few observations helping in diagnosis. Int J Prev Med. 2013;4:241. PMID: 23544177. 5. 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They correlate well with corre- sponding histopathological changes (Table 2). The dermo- scopic patterns observed in our study correlated well with the study by Narkhede et al [8], in evaluation of HZ, but the characterization of lesions into early and late lesions pertain- ing to duration of onset was not depicted. This is required as any intervention with antiviral therapy within 72 hours of onset of rash, reduces the risk of ophthalmic complications, has effect on severity of acute pain, faster healing of lesions and shortens the duration of post herpetic neuralgia [15,16]. As the lesions of BBD and HZ closely simulate each other, the dermoscopic differentiation thus helps in early diagno- sis and management, as the line of management differs in the two and minimizes the morbidity and the social stigma associated with HZ. Limitations of this study include small sample size, histopathology was not done in all the lesions, and study was conducted in a single center. 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Superficial peri-vascular infiltration with vasodilation of dermal vessels. White globules with brown dots in the centre Perifollicular micro-pustule. Herpes zoster Multiple poly-lobular gray globules Necrotic keratinocytes within intra-epidermal vesicle Greyish veil-like structure Pigmented epithelium overlying the vesicle. Grey rim Edge of the vesicle Yellowish orange structure Serum and extra-vasated erythrocytes within the intra- epidermal vesicle Erythematous background Increased vascularity Red dots Dilated vessels and vasculitis Brown dots and globules Dried serum, necrotic keratinocytes and melanin retention Crumpled fabric appearance Roof of flaccid blister Scales Hyperkeratosis Original Article | Dermatol Pract Concept. 2022;12(4):e2022180 9 rove beetles (Paederus alfierii). Beni-Suef Uni J Basic and App Sci. 2013;2:108-113. DOI: 10.1016/j.bjbas.2013.03.002. 14. Xu X, Yun SJ, Erickson L, Chen L. Disease caused by viruses. 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