Dermatology: Practical and Conceptual Case Report | Dermatol Pract Concept 2016;6(2):3 9 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Hypertrophic lichen planus versus prurigo nodularis: a dermoscopic perspective Balachandra S. Ankad1, Savitha L. Beergouder1 1 Department of Dermatology, S. Nijalingappa Medical College, Bagalkot, Karnataka, India Key words: dermoscopy, hypertrophic lichen planus, prurigo nodularis, histopathology, patterns Citation: Ankad BS, Beergouder SL. Hypertrophic lichen planus versus prurigo nodularis: a dermoscopic perspective. Dermatol Pract Concept 2016;6(2):3. doi: 10.5826/dpc.0602a03 Received: September 14, 2015; Accepted: February 3, 2016; Published: April 30, 2016 Copyright: ©2016 Ankad et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Dr. Balachandra S. Ankad, Associate Professor, Department of Dermatology, S. Nijalingappa Medical College, Near APMC, Navanagar, Bagalkot-587103, Karnataka, India. Tel. +91 9980410056; Fax. 08354 235360. E-mail: drbsankad@gmail.com Background: Hypertrophic lichen planus (HLP) classically involves shin and ankles and is charac- terized by hyperkeratotic plaques and nodules. Prurigo nodularis (PN) is a chronic neurodermatitis that presents with intensely pruritic nodules. Histopathology of HLP and PN demonstrate epidermal hyperplasia, hypergranulosis, and compact hyperkeratosis. The dermis shows vertically arranged col- lagen fibers and an increased number of fibroblasts and capillaries in both conditions. Moreover, basal cell degeneration is confined to the tips of rete ridges, and band-like infiltration is conspicuously absent in HLP. Therefore, both conditions mimic each other clinically, which makes diagnosis difficult. Hence, there is a need for a diagnostic technique to differentiate both conditions. Objective: To evaluate dermoscopic patterns in HLP and PN and to study these patterns histopatho- logically. Materials and methods: The study was conducted at S. Nijalingappa Medical College in Bagalkot. It was an observational case series study. Ethical clearance and informed consent was obtained. A Dermlite 3 dermoscope (3Gen, San Juan Capistrano, CA, USA) attached to a Sony Cyber Shot camera DSC-W800 (Sony Electronics Inc., San Diego, California, USA) was employed. Histopathology was done to confirm the diagnosis. Results: There were 10 patients each with HLP and PN. HLP was seen in 8 males and 2 females. PN was observed in 7 females and 3 males. Dermoscopy of HLP demonstrated pearly white areas and peripheral striations (100%), gray-blue globules (60%), comedo-like openings (30%), red dots (40%), red globules (10%), brownish-black globules (30%), and yellowish structures (90%). In PN, red dots (70%), red globules (60%), and pearly white areas with peripheral striations (100%) were observed under dermoscopy. Conclusion: Both HLP and PN demonstrated specific dermoscopic patterns which can be demon- strated on histopathologic findings. The authors propose that these patterns are hallmarks of each condition. Thus, dermoscopy is a good diagnostic tool in the differentiation of HLP and PN. ABSTRACT mailto:drbsankad@gmail.com 10 Case Report | Dermatol Pract Concept 2016;6(2):3 parakeratosis, and hypergranulosis. The papillary dermis shows fibrosis with vertically arranged collagen fibers and increased number of fibroblasts and capillaries [8]. Hence, histopathologic differentiation of both HLP and PN is dif- ficult in a few instances. The authors evaluated the dermo- scopic patterns in both conditions and believe that these patterns were specific to each condition that would help in differentiating two diseases. Materials and methods The study was conducted in the Department of Dermatology in a tertiary hospital attached to S. Nijalingappa Medical Col- lege at Bagalkot in Southern India from October 2014 to July 2015. It was an observational case series study. Ten patients each with clinical signs and symptoms of HLP and PN were subjected to complete history and dermatological examina- tion. Ethical clearance was obtained by the institutional ethical committee. Informed written consent was taken from patients. Demographic data such as age, gender and disease duration were all documented. Dermoscopic examination A DermLite 3 dermoscope (with 10x magnification) with both polarized and non-polarized lights was employed in the study. Sony digital camera (14 Megapixels) was attached to save the images. Initially, ultrasound gel was applied either on the faceplate of the dermoscope or on the skin lesions and then lesions were observed through the eyepiece of the dermoscope. However, only the polarized light version was used in our study to appreciate color patterns in the dermis. Although polarized dermoscopy was employed, ultrasound gel was applied for clarity of images and to lessen distortions associated with light [9]. Introduction Hypertrophic lichen planus (HLP) is the second most com- mon cutaneous variant of lichen planus. It is characterized as extremely pruritic, and thick hyperkeratotic plaques are seen primarily on the shins or dorsal aspect of the foot and may be covered by a fine adherent scale. The lesions are usu- ally symmetrical and tend to be chronic because of repetitive scratching. Later, lesions become hyperkeratotic thickened elevated purplish or reddish plaques and nodules. The average duration of HLP in patients whose lesions had cleared was reported to be 6 years. Chronic venous stasis frequently con- tributes to the development of this condition (Figure 1a) [1,2]. Prurigo nodularis (PN) is a chronic, benign neuroderma- titis of unclear etiology characterized by excoriated, intensely pruritic nodules, which are secondary to an intense itch- scratch cycle (Figure 1b). It was first described by Hardaway in 1880 and named by Hyde and Montgomery in 1909 [2]. It is found on exposed extensor surfaces of the lower extremi- ties. Vigorous scratching or rubbing results in lichenification, neurotic excoriations, and nodulation [3,4]. HLP and PN mimic each other clinically, especially when HLP affects the lower legs [3, 5]. Histopathology of HLP reveals epidermal hyperplasia, acanthosis, hypergranulosis and compact and lamellated hyperkeratosis centered on follicular infundibula and acrosy- ringia. Basal cell damage is usually confined to the tips of rete ridges and may be missed on casual observation [6]. Band- like infiltration is distinctly missing in the dermis [7]. These pitfalls in histopathology of HLP make it difficult to diagnose histopathologically, unlike classical LP. Collagen bundles are oriented vertically in the papillary dermis in association with an increased number of eosinophils [6]. The characteristic histopathology of PN is the presence of thick, compact orthohyperkeratosis, irregular epidermal hyperplasia or pseudoepitheliomatous hyperplasia, focal Figure 1. (a) Hyperkeratotic, thickened, plaques and nodules on the legs in hypertrophic lichen planus. (b) Hyperkeratotic papules, plaques and nodules on the legs and dorsum of feet in prurigo nodularis. [Copyright: ©2016 Ankad et al.] Case Report | Dermatol Pract Concept 2016;6(2):3 11 Results Out of 10 HLP, 8 male and 2 female patients were present between the ages of 26 and 50 years (mean age 38 years). Duration of disease was between 4 months and 48 months. Dermoscopy demonstrated milky white structures at the center and grayish strands which were arranged peripherally. This was referred to as pearly white areas (Wickham’s striae) and peripheral striations (Figures 2-4). Gray-blue globules were present diffusely in the center extending peripherally (Figure 3). Comedo-like openings (CLO) were observed as regular dells filled with keratin on the surface and were situated diffusely over the lesions (Figures 3, 4). Yellowish structures observed were arranged in a lacy network over the lesions (Figure 4). Tiny pigmented areas referred to as brownish-black globules were present at the periphery of the lesions (Figure 3). Red dots and red globules were present at the center and periphery (Figures 3, 4). Histopathology of HLP demonstrated orthokeratosis, hypergranulosis, and elongation of rete ridges (Figure 5a). Dermoscopic patterns with corresponding histopathologic changes are tabulated in Table 1. PN was observed in 7 female and 3 male patients with ages ranging from 20 to 54 years. Mean duration of disease was 4 years (minimum 1 year and maximum 7 years). Histo- pathology of PN showed orthokeratosis and hyperkeratosis, irregular acanthosis and elongated rete ridges (Figure 5b). Dermoscopy of PN demonstrated pearly white structures in the center with peripheral extensions. The pattern is described as “starburst” appearance. These white areas were sur- rounded by peripheral striations (Figure 6). Red dots and red globules (Figures 6, 7) were located diffusely in the center. Dermoscopic patterns and corresponding histopathologic changes are represented in Table 2. Frequencies of each dermoscopic pattern in HLP and PN are shown in Figure 8. All new and old lesions of HLP and both excoriated and hyperkeratotic lesions of PN were examined under der- moscopy. Data was tabulated in a Microsoft Excel® sheet. Proportions and percentages were used for representing the data. Histopathology was carried out in both HLP and PN to confirm the diagnosis by taking a punch biopsy from each type of lesion. Inclusion criteria: 1. Patients with signs and symptoms of HLP and PN. 2. Patients who had not received or stopped treatment for HLP and PN 1 month prior to the study. Exclusion criteria: 1. Patients with secondary infection superseding HLP and PN. 2. Patients who were receiving treatment 1 month prior to the study. Figure 2. Dermoscopy of hypertrophic lichen planus shows pearly white areas (stars), peripheral striations (arrows). [Copyright: ©2016 Ankad et al.] Figure 3. Dermoscopy of hypertrophic lichen planus shows gray- blue globules (hexagons), comedo-like openings (arrows), brownish- black dots (circles) and red globules (stars). [Copyright: ©2016 An- kad et al.] Figure 4. Dermoscopy of hypertrophic lichen planus shows yellowish structure (black arrows), comedo-like openings (white arrows) and peripheral blood vessels (circles). [Copyright: ©2016 Ankad et al.] 12 Case Report | Dermatol Pract Concept 2016;6(2):3 TABLE 1. Proposed dermoscopic patterns corresponding to histopathologic features in hypertrophic lichen planus. [Copyright: ©2016 Ankad et al.] Dermoscopic patterns Corresponding histopathologic changes 1 Pearly white areas (Wickham striae); and peripheral striations Compact orthokeratosis above zones of wedge-shaped hypergranulosis, acanthosis, and dermal fibrosis. 2 Gray-blue globules Dermal melanophages 3 Comedo-like openings Hypergranulosis and hyperkeratosis of dilated infundibulum 4 Red dots Dermal capillaries 5 Red globules Dermal capillaries 6 Brownish-black globules Epidermal melanocytes 7 Yellow structures Spongiosis and vacuolar degeneration of basal cell Figure 5. (a) Histopathology of hypertrophic lichen planus with compact orthokeratosis, hypergranulosis and elonga- tion of rete ridges. (b) Histopathology of prurigo nodularis with orthokeratosis and hyperkeratosis; irregular acanthosis and elongated rete ridges. (hematoxylin & eosin, x4). [Copyright: ©2016 Ankad et al.] Figure 6. Dermoscopy of prurigo nodularis shows pearly white ar- eas (stars), red globules (circle), red areas (white arrows) and pe- ripheral striations (black arrows). [Copyright: ©2016 Ankad et al.] Figure 7. Dermoscopy of prurigo nodularis shows red globules (white arrows) and peripheral striations (black arrows). [Copyright: ©2016 Ankad et al.] Case Report | Dermatol Pract Concept 2016;6(2):3 13 over the whole periphery of the lesion in PN and it was local- ized in the center with peripheral extensions in some areas in HLP. Peripheral extensions were well defined in PN giving a “starburst” appearance. In classic lichen planus, pearly white areas are arranged in annular and arboriform pattern or circular, linear, globular, reticular and radial streaming [2,11]. However, there was no mention of HLP in these studies. Different configurations and arrangements of pearly white areas help to differenti- ate HLP, PN, and classical lichen planus. Pearly white areas correspond histopathologically to compact orthokeratosis above zones of wedge-shaped hypergranulosis and acanthosis Discussion HLP develops during the course of a subacute attack, never- theless, occasionally only hypertrophic or warty lesions are found. The most common site is the lower limbs, especially around the ankles. The development of hypertrophic lesions greatly lengthens the course of the disease, as they may per- sist for many years. HLP must be distinguished from lichen simplex chronicus, PN and lichen, amyloidosis [10]. Dermoscopy of HLP and PN showed pearly white areas, which were more prominent in PN than in HLP. There was a slight difference in the appearance. White areas were spread TABLE 2. Proposed dermoscopic patterns corresponding to histopathologic features in prurigo nodularis. [Copyright: ©2016 Ankad et al.] Dermoscopic patterns Corresponding histopathologic changes 1 White areas and peripheral striations Hyperkeratosis, hypergranulosis, acanthosis and dermal fibrosis 2 Red dots Dilated capillaries 3 Red globules Focal hemorrhages Figure 8. Frequency of dermoscopic patterns in hypertrophic lichen planus and in prurigo nodularis. [Copyright: ©2016 Ankad et al.] 14 Case Report | Dermatol Pract Concept 2016;6(2):3 ogy [20]. Arrangement and configuration of red globules give a clue to the condition. Red dots were seen as red indistinct islands in the confines of pearly white structures in this study. They were observed in both HLP and PN. They were centrally located in PN in a “comma-like” pattern, whereas in HLP they were arranged diffusely in the lesions. In psoriasis, they appear as regular dotted vessels over a light red background, and in pityriasis rosea, arrangement of vessels is patchy on a yellow background. In classic LP, vessels are arranged periph- erally in the confines of white crossing lines and they appear as clear red globules [20]. Red globules are larger than the red dots. These were prominent in PN and were not evidently seen in HLP in this study. These correspond to enlarged blood vessels as well as focal hemorrhage in dermis. Similar findings, in addition to brown-yellowish crusts and scales, were observed by Errichetti et al in excoriated and hyperkeratotic lesions of PN [13]. However, yellow areas and crusts were not demon- strated in this study. Description of dermoscopy of HLP with histopathologic correlation is well documented [21] and simi- lar dermoscopic patterns were observed in the present study. Histopathologic diagnosis of a condition depends on the characteristic features of that condition which may not be observed in all lesions submitted for histopathologic examination [22]. Dermoscopy visualizes the color patterns in the epidermis, dermo-epidermal junction, and papillary dermis; when these patterns are observed consistently in a given disease, they could aid in its diagnosis [23]. Although the same dermoscopic patterns are expected in HLP and PN due to a few similar histopathologic findings, dermoscopy demonstrated some different patterns which are specific in each condition. This is probably because of the few specific histopathologic features which are unique to HLP and PN. Conclusion Dermoscopy is an in vivo diagnostic technique enabling clinicians to visualize subsurface structures with appropriate configuration and color patterns. HLP and PN demonstrate specific dermoscopic patterns that correspond to histopatho- logic findings. Gray-blue globules, CLO and brownish-black globules were specific to HLP. Hence, the authors propose that these patterns are a hallmark of each condition. Thus, dermoscopy is helpful in the differentiation of HLP and PN. Further studies involving large sample size are suggested for studying the validity (sensitivity, specificity) of dermoscopy in making the diagnosis. Acknowledgement The authors wish to acknowledge the help of Dr. Vijay Domble for his assistance with histopathology. [12]. Peripheral striations were more pronounced in PN than in HLP, and this pattern corresponds to dermal fibrosis in histopathology [13]. Other conditions which can be listed in the differential diagnosis of HLP and PN by dermoscopy include nodular scabies, keratoacanthoma, and reactive perforating collage- nosis [14]. CLO filled with yellow keratinous plugs referred to as corn pearls were observed in HLP by Vazquez-Lopez F et al [12]. CLO correspond to dilatation, plugging and hypergranulosis of infundibulum and they are suggestive of transepithelial elimination. In HLP, histopathologic changes, namely, epider- mal hyperplasia, acanthosis, hypergranulosis and compact and lamellated hyperkeratosis, are centered on follicular infun- dibula and acrosyringia [15]. Hence, CLO are very specific to hypertrophic LP and are not observed in PN. CLO are also demonstrated in the early stages of lichen sclerosis and in basal cell carcinoma and seborrheic keratosis [16-18]. Gray-blue globules observed in this study represent mela- nin pigment in the dermis due to melanin incontinence as a result of vacuolar degeneration. The configuration of gray-blue globules and dots is specific for each condition. Gray-blue globules in lichen planus pigmentosus of the scalp appear as a “target” pattern. This suggests that pathology is around the perifollicular area and spares the interfollicular area. In discoid lupus erythematosus of the scalp, the patho- logic process involves perifollicular and interfollicular areas, hence, gray-blue globules follow a “speckled” pattern [19]. Gray-blue globules appear as ovoid and nest-like in basal cell carcinoma [17]. In this study, gray-blue globules in HLP were arranged in diffuse structureless pattern interspersed in pearly white areas indicating presence of melanin incontinence in perifollicular and interfollicular areas. Gray-blue globules were not demonstrated in PN, suggesting absence of melanin incontinence in PN. Yellow structures represent vacuolar degeneration of the basal layer and spongiosis [2]. Yellow structures dem- onstrated in this study appear as a “lacy network” pattern, traversing the pearly white areas. The characteristic situa- tion of CLO along yellow structures confirms the fact that the pathological process in HLP is cornered in and around follicles. Yellow structures were not demonstrated in PN. Nevertheless, brown-yellowish crusts were noted in PN in one study [13]. Melanocytes in the epidermis appear as brownish-black globules in dermoscopy and their arrangement is diffuse, annular or in dotted patterns in classical LP [2]. In HLP, brownish-black globules were diffusely arranged surrounding gray-blue dots. Brownish-black dots were not observed in PN. Red dots correspond to dilated capillaries in histopathol- Case Report | Dermatol Pract Concept 2016;6(2):3 15 observations. Dermatology 2003;207:151–6. PMID: 12920364. DOI: 10.1159/000071785 13. Errichetti E, Piccirillo A, Stinco G. Dermoscopy of prurigo nodularis. J Dermatol 2015;42:632–34. PMID: 25808786. DOI: 10.1111/1346-8138.12844 14. Errichetti E, Stinco G. The practical usefulness of dermosco- py in general dermatology. G Ital Dermatol Venereol. 2015; 150(5):533-46. PMID: 26086412. 15. Busam KJ, Goldblum JR (eds). Dermatopathology: A Volume in a Series: Foundations in Diagnostic Pathology. Philadelphia: Saunders Elsevier, 2010; 11-81. 16. Shim WH, Jwa SW, Song M, et al. Diagnostic usefulness of der- matoscopy in differentiating lichen sclerosus et atrophicus from morphea. J Am Acad Dermatol 2012;66:690-1. PMID: 22421117. DOI: 10.1016/j.jaad.2011.06.042 17. Bowling J. Non-melanocytic lesions. In: Bowling J, (ed.). Diag- nostic Dermoscopy: The Illustrated Guide. West Sussex: Wiley- Blackwell, 2012; 59-91. 18. Braun RP, Rabinovitz HS, Krischer J, et al. Dermoscopy of pigmented seborrheic keratosis: a morphological study. Arch Dermatol 2002; 138:1556-60. PMID: 12472342. DOI: 10.1001/ archderm.138.12.1556 19. Ankad BS, Beergouder SL, Moodalgiri VM. Lichen planopila- ris versus discoid lupus erythematosus: A trichoscopic per- spective. Int J Trichol 2013; 5:204-7. PMID: 24778533. DOI: 10.4103/0974-7753.130409 20. Lallas A, Kyrgidis A, Tzellos TG, Apalla Z, et al. Accuracy of der- moscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br Journal Dermatol 2012; 166:1198- 205. PMID: 22296226. DOI: 10.1111/j.1365-2133.2012.10868.x 21. Ankad BS, Beergouder SL and Sujana L. Dermoscopy of hypertro- phic lichen planus. Austin J Dermatolog 2014; 1(3):1013. http:// austinpublishinggroup.com/dermatology/fulltext/ajd-v1-id1013. php. Accessed on August, 20, 2015 22. Mobini N, Toussaint S, Kamino H. Noninfectious erythematous, papules and squamous diseases. In: Elder DE (ed.). Lever’s Histo- pathology of the Skin, 10th ed. Philadelphia: Lippincott-Williams Wilkins, 2009:169-203. 23. Nischal KC, Khopkar U. Dermoscope. Indian J Dermatol Venereol Leprol 2005; 71:300-3. PMID: 16394450 References 1. Shiohara T, Kano Y. Lichen planus and lichenoid dermatoses. In: Bolognia JL, Jorizzo JL, Schaffer JV (eds.). Dermatology, 3rd ed. New York: Elsevier Saunders, 2012; 183-202. 2. Doshi B, Khopkar U. Histopathology of lichen planus and its variants. In: Khopkar U and Valia A (eds.). Lichen Planus. New Delhi: Jaypee Brothers Medical Publisher (P) LTD, 2013; 123-47. 3. Vaidya DC, Robert A. Schwartz. Prurigo nodularis: a benign der- matosis derived from a persistent pruritus. Acta Dermatovenerol Croat 2008; 16:38-44. PMID: 18358109 4. Lee MR, Shumack S. Prurigo nodularis: A review. Aust J Derma- tol 2005; 46:211-20. PMID: 16197418. DOI: 10.1111/j.1440- 0960.2005.00187.x 5. Berth-Jones J. Eczema, Lichenification, prurigo and erythroderma. In: Burns T, Breathnach SM, Cox N, Griffiths C (eds.). Rook’s Textbook of Dermatology, 8th ed. Oxford: Wiley-Blackwell, 2010; 23.1-51. 6. Weedon D. The lichenoid reaction pattern (interface dermatitis). In: Weedon D (ed.). Weedon’s Skin Pathology, 2nd ed. London: Churchill Livingstone, 2002; 31-74. 7. Mobini N, Toussaint S, Kamino H. Noninfectious erythematous, papular and squamous diseases. In: Elder DE (ed.). Lever’s Histo- pathology of the Skin, 10th ed. Philadelphia: Lippincott Williams and Wilkins, 2010;169-204. 8. Weigelt N, Metze D, Ständer S. Prurigo nodularis: Systematic analysis of 58 histological criteria in 136 patients. J Cutan Pathol 2010; 37: 578-86. PMID: 20002240. DOI: 10.1111/j.1600- 0560.2009.01484.x 9. Bowling J. Introduction to dermoscopy. In: Bowling J (ed.). Diagnostic Dermoscopy: The Illustrated Guide. West Sussex: Wiley-Blackwell, 2012:2-14. 10. Breathnach SM. Lichen planus and lichenoid disorders. In: Burns T, Breathnach SM, Cox N, Griffiths C (eds.). Rook’s Textbook of Dermatology, 8th ed. Oxford: Wiley-Blackwell, 2010; 41.1-28. 11. Gungor S, Topal IO, Goncu EK. Dermoscopic patterns in active and regressive lichen planus and lichen planus variants: a morpho- logical study. Dermatol Pract Concept 2015;5(2):45–53. PMID: 26114051. DOI: 10.5826/dpc.0502a06 12. Vazquez-Lopez F, Manjon-Haces JA, Maldonado-Seral C, et al. Dermoscopic features of plaque psoriasis and lichen planus: new http://www.ncbi.nlm.nih.gov/pubmed/?term=Errichetti%20E%5BAuthor%5D&cauthor=true&cauthor_uid=26086412 http://www.ncbi.nlm.nih.gov/pubmed/?term=Stinco%20G%5BAuthor%5D&cauthor=true&cauthor_uid=26086412 http://www.ncbi.nlm.nih.gov/pubmed/26086412 http://www.ncbi.nlm.nih.gov/pubmed?term=Shim%20WH%5BAuthor%5D&cauthor=true&cauthor_uid=22421117 http://www.ncbi.nlm.nih.gov/pubmed?term=Jwa%20SW%5BAuthor%5D&cauthor=true&cauthor_uid=22421117 http://www.ncbi.nlm.nih.gov/pubmed?term=Song%20M%5BAuthor%5D&cauthor=true&cauthor_uid=22421117 http://www.ncbi.nlm.nih.gov/pubmed?term=Braun%20RP%5BAuthor%5D&cauthor=true&cauthor_uid=12472342 http://www.ncbi.nlm.nih.gov/pubmed?term=Rabinovitz%20HS%5BAuthor%5D&cauthor=true&cauthor_uid=12472342 http://www.ncbi.nlm.nih.gov/pubmed?term=Krischer%20J%5BAuthor%5D&cauthor=true&cauthor_uid=12472342 http://www.ncbi.nlm.nih.gov/pubmed/12472342 http://www.ncbi.nlm.nih.gov/pubmed/12472342 http://austinpublishinggroup.com/dermatology/fulltext/ajd-v1-id1013.php http://austinpublishinggroup.com/dermatology/fulltext/ajd-v1-id1013.php http://austinpublishinggroup.com/dermatology/fulltext/ajd-v1-id1013.php http://www.ncbi.nlm.nih.gov/pubmed?term=Weigelt%20N%5BAuthor%5D&cauthor=true&cauthor_uid=20002240 http://www.ncbi.nlm.nih.gov/pubmed?term=Metze%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20002240 http://www.ncbi.nlm.nih.gov/pubmed?term=St%C3%A4nder%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20002240 http://www.ncbi.nlm.nih.gov/pubmed/20002240 http://www.ncbi.nlm.nih.gov/pubmed/?term=Topal%20IO%5Bauth%5D