Dermatologic Therapy, Vol. 28, 2015, 7–9 Printed in the United States · All rights reserved
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE 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 of Medicine, School of Medicine, Chung Shan Medical University and ‡Department of Dermatology, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan
To the Editor, Necrobiotic xanthogranuloma (NXG) is a nonLangerhans cell histiocytosis with granulomatous infiltration of lymphocytes, epithelioid cells, foam cells, giant cells, and cholesterol crystals within the necrobiotic areas. To the best of our knowledge, this is the first case report on a patient with NXG that describes a successful response to daposone. Here we report a 69-year-old man with recalcitrant NXG who received daposone 100 mg daily for 18 months. Subsequently, skin lesions were dramatically resolved and did not recur after discontinuing dapsone at 15 months of follow-up.
Case report A 69-year-old man with type 2 diabetes mellitus suffered multiple annular plaques of various sizes over the extremities for approximately three years. The skin revealed yellowish borders around a depressed atrophic and telangiectatic center over Address correspondence and reprint requests to: Yu-Ping Hsiao, MD, Chief, Department of Dermatology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung City 402, Taiwan, or email: [email protected].
the forearms (FIG. 1A). The patient’s face and trunk were spared. Histological examination showed extensive area of necrobiosis surrounded with non-palisaded, granulomatous infiltrations in 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, no mucin deposits, and no naked epitheliod granuloma; so necrobiosis lipoidica, granuloma annulare, and sarcoidosis were excluded. Acidfast, periodic acid–Schiff and Grocott’s methenamine silver stains were all negative. Infectious granuloma was also ruled out. Laboratory investigations, which included hemogram, renal functions, and lipid profiles, were all within normal limit. No monoclonal gammopathy in serum protein immunoelectrophoresis and Bence-Jones proteins in urine were detected. Antinuclear antibody, cryoglobulin, chest X rays, and whole body gallium scan all revealed negative findings. Under the impression of NXG without paraproteinemia, we proposed further therapeutic options to the patient. About 3 years ago, the patient had received topical steroid with poor response in Feng Yuan Hospital, Taichung, Taiwan (Supplementary Fig. S1). Based on the economic
7
Wei et al.
FIG. 1. Clinical and histopathological findings of our patient with necrobiosis xanthogranuloma. (A) Well-circumscribed yellow-pink plaques and nodules are present over the forearms. (B) Histopathological results show palisaded granulomatous infiltrates with necrobiosis (hematoxylin and eosin stain, ×40). (C) Bizarre giant cells, foamy histiocytes, and cholesterol cleft were detected in the dermis (hematoxylin and eosin stain, ×200).
FIG. 2. Significant regression of necrobiosis xanthogranuloma over the forearms after dapsone. (A) Before treatment. (B) After treatment with dapsone 100 mg daily for a year and a half.
and safety considerations, he refused intravenous immunoglobulin, chlorambucil, cyclophosphamide, and chose oral dapsone 100 mg daily and topical steroid. After a year and a half of dapsone treatment and follow-up, his skin lesions showed significant improvement and did not recur after discontinuing dapsone (FIG. 2A,B).
Discussion NXG slowly progressed from yellowish to reddish nodules and plaques, which typically affects the
8
periorbital region. The face, trunk, arms, and upper thighs could also become involved. Few patients without periorbital involvement have been described (1). Its prognosis depends on the severity of the disease and the extent of extracutaneous involvement. No first-line therapy has been established for NXG. The recommended therapies of intralesional and/or systemic corticosteroids (1,2), alkylating agents (such as melphalan (3), chlorambucil (4), or cyclophosphamide (5)), lenalidomide (6), thalidomide (7), and intravenous immunoglobulin (2) have all shown inconsistent success.
Dapsone for necrobiotic xanthogranuloma
Dapsone is originally used as an antibacterial medication by competing with paraaminobenzote for active site and inhibiting synthesis of dihydrofolic acid (8). In 1960, dapsone acted as an anti-inflammatory medication to treat dermatitis herpetiformis, granuloma annulare, or cicatricial pemphigoid (8). Suda et al. investigated that dapsone inhibited the production of superoxide (O2−) by blocking the influx of calcium via chemotactic peptide N-formyl-L-methionylLleucyl-L-phenylalanine and the physiologic agonist C5a, and then reduces tissue damage (9). Based on good response of dapsone for granuloma annulare and necrobiosis lipoidica, Meyer et al. used dapsone for NXG, but the result was unsatisfactory (10). This is the first case report of NXG with significant remission under dapsone treatment. Although there is no clear relationship between the efficacies of dapsone and NXG, we proposed dapsone as an economic and alternative choice for patient with refractory NXG. In our case, a 69-year-old man with NXG was successfully treated with dapsone and no recurrence at 15 months follow-up. By far, this patient has no paraproteinemia or lymphoproliferative disorders.
References 1. Yang CY, Chung WH, Hui RCY, Kuo TT, Yang CH. Necrobiotic xanthogranuloma with paraproteinemia without periorbital involvement – a case report. Dermatol Sinica 2010: 28: 125–129. 2. Hallermann C, Tittelbach J, Norgauer J, Ziemer M. Successful treatment of necrobiotic xanthogranuloma with intravenous immunoglobulin. Arch Dermatol 2010: 146: 957–960. 3. Martinez Fernandez M, Rodriguez Prieto MA, Ruiz Gonzalez I, Sanchez Sambucety P, Delgado Vicente S. Necrobiotic
4.
5.
6.
7.
8.
9.
10.
xanthogranuloma associated with myeloma. J Eur Acad Dermatol Venereol 2004: 18: 328–331. Ryan E, Warren LJ, Szabo F. Necrobiotic xanthogranuloma: response to chlorambucil. Australas J Dermatol 2012: 53: e23–e25. Meyer S, Szeimies RM, Landthaler M, Hohenleutner S. Cyclophosphamide-dexamethasone pulsed therapy for treatment of recalcitrant necrobiotic xanthogranuloma with paraproteinemia and ocular involvement. Br J Dermatol 2005: 153: 443–445. Silapunt S, Chon SY. Generalized necrobiotic xanthogranuloma successfully treated with lenalidomide. J Drugs Dermatol 2010: 9: 273–276. Efebera Y, Blanchard E, Allam C, Han A, Lee S, Munshi N. Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature. Clin Lymphoma Myeloma Leuk 2011: 11: 298– 302. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: overview and update. J Am Acad Dermatol 2001: 45: 420– 434. Suda T, Suzuki Y, Matsui T, et al. Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner. Br J Dermatol 2005: 152: 887–895. Meyer S, Landthaler M, Hohenleutner S. [Long-term course of necrobiotic xanthogranuloma with ocular involvement]. Hautarzt 2006: 57: 144–149, German.
Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: Figure S1 Poor response to topical steroid in the patient with necrobiosis xanthogranuloma three years before admission. (A) Three years before admission. (B) At admission.
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Copyright of Dermatologic Therapy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
© 2014 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY ISSN 1396-0296
THERAPEUTIC HOTLINE 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 of Medicine, School of Medicine, Chung Shan Medical University and ‡Department of Dermatology, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, Taiwan
To the Editor, Necrobiotic xanthogranuloma (NXG) is a nonLangerhans cell histiocytosis with granulomatous infiltration of lymphocytes, epithelioid cells, foam cells, giant cells, and cholesterol crystals within the necrobiotic areas. To the best of our knowledge, this is the first case report on a patient with NXG that describes a successful response to daposone. Here we report a 69-year-old man with recalcitrant NXG who received daposone 100 mg daily for 18 months. Subsequently, skin lesions were dramatically resolved and did not recur after discontinuing dapsone at 15 months of follow-up.
Case report A 69-year-old man with type 2 diabetes mellitus suffered multiple annular plaques of various sizes over the extremities for approximately three years. The skin revealed yellowish borders around a depressed atrophic and telangiectatic center over Address correspondence and reprint requests to: Yu-Ping Hsiao, MD, Chief, Department of Dermatology, Chung Shan Medical University Hospital, No. 110, Sec. 1, Chien-Kuo N. Rd., Taichung City 402, Taiwan, or email: [email protected].
the forearms (FIG. 1A). The patient’s face and trunk were spared. Histological examination showed extensive area of necrobiosis surrounded with non-palisaded, granulomatous infiltrations in 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, no mucin deposits, and no naked epitheliod granuloma; so necrobiosis lipoidica, granuloma annulare, and sarcoidosis were excluded. Acidfast, periodic acid–Schiff and Grocott’s methenamine silver stains were all negative. Infectious granuloma was also ruled out. Laboratory investigations, which included hemogram, renal functions, and lipid profiles, were all within normal limit. No monoclonal gammopathy in serum protein immunoelectrophoresis and Bence-Jones proteins in urine were detected. Antinuclear antibody, cryoglobulin, chest X rays, and whole body gallium scan all revealed negative findings. Under the impression of NXG without paraproteinemia, we proposed further therapeutic options to the patient. About 3 years ago, the patient had received topical steroid with poor response in Feng Yuan Hospital, Taichung, Taiwan (Supplementary Fig. S1). Based on the economic
7
Wei et al.
FIG. 1. Clinical and histopathological findings of our patient with necrobiosis xanthogranuloma. (A) Well-circumscribed yellow-pink plaques and nodules are present over the forearms. (B) Histopathological results show palisaded granulomatous infiltrates with necrobiosis (hematoxylin and eosin stain, ×40). (C) Bizarre giant cells, foamy histiocytes, and cholesterol cleft were detected in the dermis (hematoxylin and eosin stain, ×200).
FIG. 2. Significant regression of necrobiosis xanthogranuloma over the forearms after dapsone. (A) Before treatment. (B) After treatment with dapsone 100 mg daily for a year and a half.
and safety considerations, he refused intravenous immunoglobulin, chlorambucil, cyclophosphamide, and chose oral dapsone 100 mg daily and topical steroid. After a year and a half of dapsone treatment and follow-up, his skin lesions showed significant improvement and did not recur after discontinuing dapsone (FIG. 2A,B).
Discussion NXG slowly progressed from yellowish to reddish nodules and plaques, which typically affects the
8
periorbital region. The face, trunk, arms, and upper thighs could also become involved. Few patients without periorbital involvement have been described (1). Its prognosis depends on the severity of the disease and the extent of extracutaneous involvement. No first-line therapy has been established for NXG. The recommended therapies of intralesional and/or systemic corticosteroids (1,2), alkylating agents (such as melphalan (3), chlorambucil (4), or cyclophosphamide (5)), lenalidomide (6), thalidomide (7), and intravenous immunoglobulin (2) have all shown inconsistent success.
Dapsone for necrobiotic xanthogranuloma
Dapsone is originally used as an antibacterial medication by competing with paraaminobenzote for active site and inhibiting synthesis of dihydrofolic acid (8). In 1960, dapsone acted as an anti-inflammatory medication to treat dermatitis herpetiformis, granuloma annulare, or cicatricial pemphigoid (8). Suda et al. investigated that dapsone inhibited the production of superoxide (O2−) by blocking the influx of calcium via chemotactic peptide N-formyl-L-methionylLleucyl-L-phenylalanine and the physiologic agonist C5a, and then reduces tissue damage (9). Based on good response of dapsone for granuloma annulare and necrobiosis lipoidica, Meyer et al. used dapsone for NXG, but the result was unsatisfactory (10). This is the first case report of NXG with significant remission under dapsone treatment. Although there is no clear relationship between the efficacies of dapsone and NXG, we proposed dapsone as an economic and alternative choice for patient with refractory NXG. In our case, a 69-year-old man with NXG was successfully treated with dapsone and no recurrence at 15 months follow-up. By far, this patient has no paraproteinemia or lymphoproliferative disorders.
References 1. Yang CY, Chung WH, Hui RCY, Kuo TT, Yang CH. Necrobiotic xanthogranuloma with paraproteinemia without periorbital involvement – a case report. Dermatol Sinica 2010: 28: 125–129. 2. Hallermann C, Tittelbach J, Norgauer J, Ziemer M. Successful treatment of necrobiotic xanthogranuloma with intravenous immunoglobulin. Arch Dermatol 2010: 146: 957–960. 3. Martinez Fernandez M, Rodriguez Prieto MA, Ruiz Gonzalez I, Sanchez Sambucety P, Delgado Vicente S. Necrobiotic
4.
5.
6.
7.
8.
9.
10.
xanthogranuloma associated with myeloma. J Eur Acad Dermatol Venereol 2004: 18: 328–331. Ryan E, Warren LJ, Szabo F. Necrobiotic xanthogranuloma: response to chlorambucil. Australas J Dermatol 2012: 53: e23–e25. Meyer S, Szeimies RM, Landthaler M, Hohenleutner S. Cyclophosphamide-dexamethasone pulsed therapy for treatment of recalcitrant necrobiotic xanthogranuloma with paraproteinemia and ocular involvement. Br J Dermatol 2005: 153: 443–445. Silapunt S, Chon SY. Generalized necrobiotic xanthogranuloma successfully treated with lenalidomide. J Drugs Dermatol 2010: 9: 273–276. Efebera Y, Blanchard E, Allam C, Han A, Lee S, Munshi N. Complete response to thalidomide and dexamethasone in a patient with necrobiotic xanthogranuloma associated with monoclonal gammopathy: a case report and review of the literature. Clin Lymphoma Myeloma Leuk 2011: 11: 298– 302. Zhu YI, Stiller MJ. Dapsone and sulfones in dermatology: overview and update. J Am Acad Dermatol 2001: 45: 420– 434. Suda T, Suzuki Y, Matsui T, et al. Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner. Br J Dermatol 2005: 152: 887–895. Meyer S, Landthaler M, Hohenleutner S. [Long-term course of necrobiotic xanthogranuloma with ocular involvement]. Hautarzt 2006: 57: 144–149, German.
Supporting information Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: Figure S1 Poor response to topical steroid in the patient with necrobiosis xanthogranuloma three years before admission. (A) Three years before admission. (B) At admission.
9
Copyright of Dermatologic Therapy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
