Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2023;13(2):e2023124 1 A Case of Xanthoma Disseminatum in a Progressive Form With Bladder Involvement Effectively Treated With 2-Chlorodeoxyadenosine Elçin Akdaş1, Burcu Beksaç2, Esra Adışen1, Özlem Erdem3, Murat Orhan Öztaş1 1 Department of Dermatology, Faculty of Medicine, Gazi University, Ankara, Turkey 2 Department of Dermatovenereology, University of Health Sciences, Gulhane Research and Training Hospital, Ankara, Turkey 3 Department of Pathology, Faculty of Medicine, Gazi University, Ankara, Turkey Key words: xanthoma disseminatum, bladder, 2-chlorodeoxyadenosine, cladribine Citation: Akdaş E, Beksaç E, Adışen E, Erdem Ö, Öztaş MO. A Case of Xanthoma Disseminatum in a Progressive Form With Bladder Involvement Effectively Treated With 2-Chlorodeoxyadenosine. Dermatol Pract Concept. 2023;13(2):e2023124. DOI: https://doi.org/10.5826/dpc.1302a124 Accepted: November 14, 2022; Published: April 2023 Copyright: ©2023 Akdaş 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: Elçin Akdaş, Department of Dermatology, Gazi Medical University, Yenimahalle TR–06500, Ankara, Turkey. Tel: +905469757697 E-mail: mdelcinakdas@gmail.com Introduction Xanthoma disseminatum (XD) is a rare non-Langerhans cell histiocytosis that is difficult to treat [1]. In rare progressive forms of the disease, organ dysfunctions may occur [2]. We report a case of XD with bladder involvement, with an ex- cellent response to 2-chlorodeoxyadenosine. Case Presentation A 47-year-old male patient presented with a 5-year history of numerous skin lesions on the oral mucosa, head, neck, trunk, and upper limbs (Figure 1, A and C). His personal and family history was unremarkable. He denied  any  sys- temic symptoms. Dermatological examination demonstrated numerous symmetrical yellow to brown papules and nod- ules that enlarged into plaques and tumoral lesions, espe- cially in the intertriginous areas. Laboratory tests were normal except for moderate leukocytosis and a slightly el- evated erythrocyte sedimentation rate. Electrocardiography and chest X-ray were also normal. Histopathologic examination revealed diffuse dermal in- filtration by histiocytic cells, foamy cells, and Touton-type giant cells. Immunohistochemical studies showed positive staining for CD68, factor XIIIa, and fascin, and negative staining for S100 (Figure 2, A-C). The patient was diagnosed with XD based on clinicopathological and immunohisto- chemical findings. Abdominal ultrasound examination for possible systemic involvement revealed grade 2 hydronephrosis in the right kidney and an irregular 18 mm echogenic mass behind the bladder that prevented the opening of the right ureter. The mass in the bladder was also confirmed by an abdominopel- vic CT scan. Magnetic resonance imaging of the brain did not find any abnormality and serum protein electrophoresis did not show any M band. 2 Research Letter | Dermatol Pract Concept. 2023;13(2):e2023124 Figure 1. The appearance of lesions before (A,C) and after (B,D) treatment with 2-chlorodeoxyadenosine. Histopathological and immunohistochemical findings of the specimen obtained through transurethral resection of the bladder were also consistent with XD (Figure 2, D and E). We initiated 2-chlorodeoxyadenosine (cladribine) 0.14 mg/ kg/d for five consecutive days, repeated monthly. The treat- ment was well tolerated, and no serious side effects devel- oped. After three cycles of treatment, improvement in skin lesions was remarkably evident, with more flattening and fading, although a complete resolution was not achieved (Figure 1, B and D). Also, the tumoral lesion in the bladder and hydronephrosis also completely regressed in the control CT scan. No new lesions developed during our follow-up of 48 months. Conclusions Xanthoma disseminatum is characterized by erythematous, reddish-brown papules, plaques, and nodules that are typi- cally symmetrical and tend to coalesce in intertriginous areas [1,2]. Histopathologic findings include diffuse dermal infil- tration by histiocytes and Touton giant cells. Immunohisto- chemical evaluation shows histiocytes staining positive with CD68, CD163, factor XIIIa, and fascin, and negative with S-100 and CD1a (Langerin) [3 4]. Although XD is generally considered a benign disease, in extremely rare progressive forms, mechanical mucosal complications and progressive organ dysfunction can cause Research Letter | Dermatol Pract Concept. 2023;13(2):e2023124 3 significant morbidity and mortality [2]. Many treatments including steroids, azathioprine, cyclophosphamide, elec- trocoagulation, or surgical excision, have been tried in XD, but recently the most satisfactory results have been obtained with 2-chlorodeoxyadenosine [5,6]. The excellent response to 2-chlorodeoxyadenosine was remarkable in this case with the progressive form of XD with bladder involvement. We emphasize the need for appropriate treatment with careful evaluation of the disease and close fol- low-up to prevent significant morbidity in progressive disease. Acknowledgements: The patient in this manuscript has given written informed consent to the publication of his case details. References 1. Altman J, Winkelmann R. Xanthoma disseminatum. Arch Dermatol. 1962;86(5):582-596. DOI:10.1001/archderm. 1962. 01590110018003 2. Caputo R, Veraldi S, Grimalt R, et al. The various clinical patterns of xanthoma disseminatum. Dermatology. 1995;190(1):19-24. DOI: 10.1159/000246628. PMID: 7894090. 3. Zelger B, Cerio R, Orchard G, Fritsch P, Wilson-Jones E. His- tologic and immunohistochemical study comparing xan- thoma disseminatum and histiocytosis X. Arch  Dermatol. 1992;128(9):1207-1212. PMID: 1519935. 4. Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr  Blood  Can- cer. 2005;45(3):256-264. DOI: 10.1002/pbc.20246. PMID: 15547923. 5. Khezri F, Gibson LE, Tefferi A. Xanthoma disseminatum: effec- tive therapy with 2-chlorodeoxyadenosine in a case series. Arch Dermatol. 2011;147(4):459-464. DOI: 10.1001/archderma- tol.2010.378. PMID: 21173305. 6. Adışen E, Aladağ P, Özlem E, Gürer M. Cladribine is a prom- ising therapy for xanthoma disseminatum. Clin Exp Derma- tol. 2017;42(6):717-719. DOI: 10.1111/ced.13116. PMID: 28544144. Figure 2. Histopathological appearance of skin and bladder biopsy specimens showing intense dermal infiltration of histiocytes and foamy cells (A and D, respectively) with Tauton giant cells (D, yellow arrow). H&E original magnifications ([(A] × 40; [D] × 100). Immunohisto- chemical examination, the cells in the skin and bladder stained positive for CD68 (B and D, respectively) and negative for CD1a (C and E, respectively). Original magnification x40 for B,C,E and F.