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Necrobiotic xanthogranuloma:response to dapsone

Yu-Hsiang Wei*, Jen-Jung Cheng, Yu-Hsin Wu,Chin-Yin Liu, Chu-Ju Hung, Jeng-Dong Hsu &Yu-Ping Hsiao*Department of Family and Community Medicine, Dermatology,Pathology, Chung Shan Medical University Hospital and Institute ofMedicine, School of Medicine, Chung Shan Medical University andDepartment of Dermatology, Feng Yuan Hospital, Ministry of Health andWelfare, Taichung, Taiwan

To the Editor,Necrobiotic xanthogranuloma (NXG) is a non-Langerhans cell histiocytosis with granulomatousinfiltration of lymphocytes, epithelioid cells, foamcells, giant cells, and cholesterol crystals withinthe necrobiotic areas. To the best of our knowl-edge, this is the first case report on a patient withNXG that describes a successful response todaposone. Here we report a 69-year-old man withrecalcitrant NXG who received daposone 100 mgdaily for 18 months. Subsequently, skin lesionswere dramatically resolved and did not recurafter discontinuing dapsone at 15 months offollow-up.

Case report

A 69-year-old man with type 2 diabetes mellitussuffered multiple annular plaques of various sizesover the extremities for approximately three years.The skin revealed yellowish borders around adepressed atrophic and telangiectatic center over

the forearms (FIG. 1A). The patients face andtrunk were spared. Histological examinationshowed extensive area of necrobiosis surroundedwith non-palisaded, granulomatous infiltrationsin the dermis (FIG. 1B). Bizarre giant cells (star),foamy histiocytes (arrow), and cholesterol cleft(arrowhead) were detected in the dermis(FIG. 1C). There were no lamellar necrosis, nomucin deposits, and no naked epitheliod granu-loma; so necrobiosis lipoidica, granulomaannulare, and sarcoidosis were excluded. Acid-fast, periodic acidSchiff and Grocottsmethenamine silver stains were all negative.Infectious granuloma was also ruled out.

Laboratory investigations, which includedhemogram, renal functions, and lipid profiles,were all within normal limit. No monoclonal gam-mopathy in serum protein immunoelectrophoresisand Bence-Jones proteins in urine were detected.Antinuclear antibody, cryoglobulin, chest X rays,and whole body gallium scan all revealed negativefindings.

Under the impression of NXG withoutparaproteinemia, we proposed further therapeuticoptions to the patient. About 3 years ago, thepatient had received topical steroid with poorresponse in Feng Yuan Hospital, Taichung, Taiwan(Supplementary Fig. S1). Based on the economic

Address correspondence and reprint requests to: Yu-PingHsiao, MD, Chief, Department of Dermatology, Chung ShanMedical University Hospital, No. 110, Sec. 1, Chien-Kuo N. Rd.,Taichung City 402, Taiwan, or email: missyuping@gmail.com.

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Dermatologic Therapy, Vol. 28, 2015, 79Printed in the United States All rights reserved

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DERMATOLOGIC THERAPYISSN 1396-0296

and safety considerations, he refused intravenousimmunoglobulin, chlorambucil, cyclophospha-mide, and chose oral dapsone 100 mg daily andtopical steroid. After a year and a half of dapsonetreatment and follow-up, his skin lesions showedsignificant improvement and did not recur afterdiscontinuing dapsone (FIG. 2A,B).

Discussion

NXG slowly progressed from yellowish to reddishnodules and plaques, which typically affects the

periorbital region. The face, trunk, arms, and upperthighs could also become involved. Few patientswithout periorbital involvement have beendescribed (1). Its prognosis depends on the severityof the disease and the extent of extracutaneousinvolvement. No first-line therapy has been estab-lished for NXG. The recommended therapiesof intralesional and/or systemic corticosteroids(1,2), alkylating agents (such as melphalan (3),chlorambucil (4), or cyclophosphamide (5)),lenalidomide (6), thalidomide (7), and intravenousimmunoglobulin (2) have all shown inconsistentsuccess.

FIG. 1. Clinical and histopathological findings of our patient with necrobiosis xanthogranuloma. (A) Well-circumscribedyellow-pink plaques and nodules are present over the forearms. (B) Histopathological results show palisaded granulomatousinfiltrateswith necrobiosis (hematoxylin and eosin stain,40). (C) Bizarre giant cells, foamyhistiocytes,and cholesterol cleft weredetected in the dermis (hematoxylin and eosin stain, 200).

FIG. 2. Significant regression of necrobiosis xanthogranuloma over the forearms after dapsone. (A) Before treatment. (B) Aftertreatment with dapsone 100 mg daily for a year and a half.

Wei et al.

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Dapsone is originally used as an antibac-terial medication by competing with para-aminobenzote for active site and inhibitingsynthesis of dihydrofolic acid (8). In 1960, dapsoneacted as an anti-inflammatory medication to treatdermatitis herpetiformis, granuloma annulare, orcicatricial pemphigoid (8). Suda et al. investigatedthat dapsone inhibited the production of supe-roxide (O2) by blocking the influx of calcium viachemotactic peptide N-formyl-L-methionyl-Lleucyl-L-phenylalanine and the physiologicagonist C5a, and then reduces tissue damage(9).

Based on good response of dapsone for granu-loma annulare and necrobiosis lipoidica, Meyeret al. used dapsone for NXG, but the result wasunsatisfactory (10). This is the first case report ofNXG with significant remission under dapsonetreatment. Although there is no clear relationshipbetween the efficacies of dapsone and NXG, weproposed dapsone as an economic and alternativechoice for patient with refractory NXG.

In our case, a 69-year-old man with NXG wassuccessfully treated with dapsone and no recur-rence at 15 months follow-up. By far, this patienthas no paraproteinemia or lymphoproliferativedisorders.

References

1. Yang CY, Chung WH, Hui RCY, Kuo TT, Yang CH.Necrobiotic xanthogranuloma with paraproteinemiawithout periorbital involvement a case report. DermatolSinica 2010: 28: 125129.

2. Hallermann C, Tittelbach J, Norgauer J, Ziemer M. Success-ful treatment of necrobiotic xanthogranuloma with intrave-nous immunoglobulin. Arch Dermatol 2010: 146: 957960.

3. Martinez Fernandez M, Rodriguez Prieto MA, Ruiz GonzalezI, Sanchez Sambucety P, Delgado Vicente S. Necrobiotic

xanthogranuloma associated with myeloma. J Eur AcadDermatol Venereol 2004: 18: 328331.

4. Ryan E, Warren LJ, Szabo F. Necrobiotic xanthogranuloma:response to chlorambucil. Australas J Dermatol 2012: 53:e23e25.

5. Meyer S, Szeimies RM, Landthaler M, Hohenleutner S.Cyclophosphamide-dexamethasone pulsed therapy fortreatment of recalcitrant necrobiotic xanthogranulomawith paraproteinemia and ocular involvement. Br JDermatol 2005: 153: 443445.

6. Silapunt S, Chon SY. Generalized necrobiotic xantho-granuloma successfully treated with lenalidomide. J DrugsDermatol 2010: 9: 273276.

7. Efebera Y, Blanchard E, Allam C, Han A, Lee S, Munshi N.Complete response to thalidomide and dexamethasone in apatient with necrobiotic xanthogranuloma associated withmonoclonal gammopathy: a case report and review of theliterature. Clin Lymphoma Myeloma Leuk 2011: 11: 298302.

8. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology:overview and update. J Am Acad Dermatol 2001: 45: 420434.

9. Suda T, Suzuki Y, Matsui T, et al. Dapsone suppresseshuman neutrophil superoxide production and elastaserelease in a calcium-dependent manner. Br J Dermatol2005: 152: 887895.

10. Meyer S, Landthaler M, Hohenleutner S. [Long-term courseof necrobiotic xanthogranuloma with ocular involvement].Hautarzt 2006: 57: 144149, German.

Supporting information

Additional Supporting Information may be foundin the online version of this article at the publish-ers web-site:

Figure S1 Poor response to topical steroid in thepatient with necrobiosis xanthogranuloma threeyears before admission. (A) Three years beforeadmission. (B) At admission.

Dapsone for necrobiotic xanthogranuloma

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