- Email: [email protected]
Long-term complete remission of severe pemphigus vulgaris with monoclonal anti-CD20 antibody therapy and immunophenotype correlations
974 Letters
J AM ACAD DERMATOL JUNE 2004
2. Finlayson GR, Sams WM Jr, Smith JG Jr. Erythema ab igne: a histopathological study. J Invest Dermatol 1996;46:104-8. 3. Page EH, Shear NH. Temperature-dependent skin disorders. J Am Acad Dermatol 1988;18:1003-19. 4. Flanagan N, Watson R, Sweeney E, Barnes L. Bullous erythema ab igne [letter]. Br J Dermatol 1996;134:1159-60. 5. Kligman LH, Kligman AM. Reflections on heat. Br J Dermatol 1984;110:369-75. 6. Hurwitz RM, Tisserand ME. Erythema ab igne [letter]. Arch Dermatol 1987;123:21-3. 7. Mok DWH, Blumgart LH. Erythema ab igne in chronic pancreatic pain: a diagnostic sign. J R Soc Med 1984;77:299-301. 8. Butler ML. Erythema ab igne: a sign of pancreatic disease. Am J Gastroenterol 1977;67:77-9. 9. Mucklow ES, Freeman NV. Pancreatic ascites in childhood. Br J Clin Pract 1990;44:248-51. 10. Meffert JJ, Davis BM. Furniture-induced erythema ab igne. J Am Acad Dermatol 1996;34:516-7. 11. Dovretzky I, Silverman NR. Reticular erythema of the lower back. Arch Dermatol 1991;127:405-9. 12. Helm TN, Spigel GT, Helm KF. Erythema ab igne caused by a car heater. Cutis 1997;59:81-2. 13. Dellavalle RP, Gillum P. Erythema ab igne following heating/ cooling blanket use in the intensive care unit. Cutis 2000;66: 136-8. 14. Johnson WC, Butterworth T. Erythema ab igne elastosis. Arch Dermatol 1971;104:128-31. 15. Arrington JH, Lockman DS. Thermal keratoses and squamous cell carcinoma in situ associated with erythema ab igne. Arch Dermatol 1979;115:1226-8. 16. Reed RJ, Leone P. Porokeratosis: a mutant clonal keratosis of the epidermis. Arch Dermatol 1970;101:340-7. 17. Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol 1998;39:882-7. 18. Hewitt JB, Sherif A, Kerr KM, Stankler L. Merkel cell and squamous cell carcinomas arising in erythema ab igne. Br J Dermatol 1993;128:591-2. 19. Jones CS, Tyring SK, Lee PC, Fine JD. Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne. Arch Dermatol 1998;124:110-3. 20. Treves N, Pack GT. The development of cancer in burn scars. Surg Gynecol Obstet 1930;60:749-82. 21. Kaplan RP. Cancer complicating chronic ulcerative and scarifying mucocutaneous disorders. Adv Dermatol 1987;2:19-46. 22. Sahl WJ, Taira JW. Erythema ab igne: Treatment with 5-fluorouracil cream. J Am Acad Dermatol 1992;27:109-10. doi:10.1016/j.jaad.2003.08.007
Long-term complete remission of severe pemphigus vulgaris with monoclonal anti-CD20 antibody therapy and immunophenotype correlations To the Editor: A 39-year-old man presented with denuded areas affecting 70% of the body surface area (Fig 1, A, B, C). The oral, pharyngeal, and anal mucosa showed multiple erosions. Pemphigus vulgaris (PV) had been diagnosed based on histological and immunofluorescence findings. Intercellular substance (ICS) antibodies titer was 1/160. He was being treated with prednisone (2 mg/kg/d) and azathioprine (2.5 mg/kg/d), with side effects such as muscle loss, hyperglycemia, and skin infections secondary to methicillin-resistant Staphylococcus au-
reus. Immunoprecipitation studies were positive for Dsg1 and Dsg3. He received four plasma exchanges. Cyclophosphamide was not administered because of the cutaneous infections and the risk of azoospermia. We administered four infusions of anti-CD20 antibody (375 mg/m2) (rituximab; Mabthera, Roche Products, Dee Why, New South Wales, Australia) intravenously once a week, beginning immediately after the last plasma exchange. Premedication with acetaminophen and diphenhydramine was given. Azathioprine was discontinued before the first rituximab infusion, and the corticosteroid dose was progressively tapered. Periodic analytical determinations were performed (Table I). Lesions healed completely six weeks after the first administration of Rituximab. Forty weeks after Rituximab administration no lesions have been observed, the affected body surface area remains 0% (Fig 1, D, E, F), and the titer of ICS is 1/10. We recently found a correlation between profile of circulating mononuclear cells and clinical stage in PV,1 suggesting a relationship between B-cell activation and IgG autoantibody production in PV. Rituximab is an anti-CD20 monoclonal antibody effective against B-cell lymphomas2 and several autoimmune diseases. Recently, partial remission of PV with plasmapheresis, cyclophosphamide, and rituximab has been described, with considerable side effects (sepsis).3 Rare side effects include neutropenia, interstitial pneumonitis, bronchospasm, and angina pectoris, but generally adverse effects are mild or moderate and most are infusion-associated.4 Rituximab may induce killing of CD20 cells via complement- or antibody-dependent cytotoxicity, structural changes, and apoptosis.5 CD20 antigen seems to be involved in the activation of B-cells from G0 to G1 and in their differentiation.6 This inactivation of B-cells may explain the efficiency of this drug in diseases mediated by autoantibodies. A correlation between the decrease of CD19⫹ levels and the decrease of the area affected was observed, in spite of the persistence of a high titer of ICS antibodies (Table I). However, these antibodies seem not to be pathogenic. Rituximab may selectively destroy B-cell specific clones producing pathogenic PV-IgG autoantibodies (Table I). CD3⫹, CD3-56⫹16⫹ (natural killer cells), CD4⫹, and CD8⫹ cells reached normal levels a few weeks after the first rituximab infusion. These results show the relation between B- and T-cell responses in PV. Although B-cell count was negative after rituximab administration, IgG serum level was normal (Table I). Long-lived plasma cells may secrete antibodies for a long time in absence of detectable memory cells.7 In addition, this pool of mature plasma cells is
Letters 975
J AM ACAD DERMATOL VOLUME 50, NUMBER 6
Fig 1. Before monoclonal CD20 antibody administration seen on the (A) denuded areas on the face, (B) back, (C) arm and forearm. Forty weeks after monoclonal CD20 antibody administration no lesions are observed (D, E, F).
Table I. Immunophenotype profile and immunologic measurements Basal
Cell count Leukocytes count (4,3–10/L) Lymphocytes count (1,5–6/L) % Lymphocytes (20–50%) CD3⫹ cells (933–2491/l) % CD3⫹ cells (63–85%) CD19⫹ cells (65–467/l) % CD19⫹ cells (5–18%) CD4⫹ cells (370–1468/l) % CD4⫹ cells (32–57%) CD8⫹ cells (183–799/l) %CD8⫹ cells (13–34%) CD4⫹/CD8⫹ ratio (0,9–3) CD3⫺56⫹ 16⫹ cells (60–495/l) % CD3⫹56⫹ 16⫹ cells (5–25%) IgG subclasses IgG1 (455–890 mg/dL) IgG2 (200–525 mg/dL) IgG3 (17–100 mg/dL) IgG4 (14–74 mg/dL) Immunoglobulin serum levels IgG (850–1600 mg/dL) IgA (108–325 mg/dL) IgM (70–150 mg/dL) IgD (0–5 UI/mL) Anti-Dsg1 antibodies (NV: ⱕ 20) Anti-Dsg3 antibodies (NV: ⱕ 20) ICS immunofluorescence titer
14300 2450 17.2 ND ND ND ND ND ND ND ND ND ND ND
ⴙ1w
ⴙ4w
ⴙ8w
ⴙ 16 w
ⴙ 28 w
ⴙ 40 w
11400 2530 22 1969 78 236 9 1356 53 575 23 2.3 299 12
8300 2200 23.7 1600 71 299 13.3 1071 47.6 491 21.8 2.1 331 14.7
11930 4032 33.8 3746 92 0 0 2328 57 1435 35 1.6 278 7
10000 2360 23 2224 94 0 0 1370 58 861 36 1.6 132 5.6
10700 2996 28 2752 91 0 0 1802 60 925 31 1.9 242 8
11520 2327 20.2 2017 86 2,8 0.1 1260 54 726 31 1.7 302 13
ND ND ND ND
ND ND ND ND
ND ND ND ND
ND ND ND ND
817 243 5 169
198 29 22 1 77 160 1/160
947 91 76 5 38 115 1/80
791 80 35 4 105 167 1/160
864 74 32 3 40 156 1/320
1310 81 34 4 24 122 1/40
ND, Not done; NV, normal value; w, weeks after rituximab administration.
841 342 7.3 172 1280 109 64 4 7 90 1/40
ND ND ND ND 1480 136 76 4 ND ND 1/10
976 Letters
J AM ACAD DERMATOL JUNE 2004
CD20 antigen negative, and is unaffected by rituximab. Rituximab seems to be effective against severe PV and can lead to long term remission (forty weeks). So, these patients need no immunosuppressive treatment during this time, which lowers the risk of side effects. Agustı´n Espan ˜ a, MDa Marta Ferna´ndez-Galar, MDa Pedro Lloret, MDa Alfonso Sa´nchez-Ibarrola, MDb Carlos Panizo, MDc From the Departments of Dermatologya, Immunologyb, and Hematologyc University Clinic of Navarra, School of Medicine University of Navarra Pamplona, Navarra, Spain Correspondence to: Agustı´n Espan ˜ a, Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, PO Box 4209 Pamplona 31080, Navarra, Spain E-mail: [email protected] REFERENCES 1. Gonzalez A, Espan˜a A, Lopez-Zabalza MJ, Pelacho B, Sa´nchezCarpintero I, Santiago E, et al. Correlation between profile of circulating mononuclear cells and clinical manifestations in patients with pemphigus vulgaris. Autoimmunity 2000;32:115-28. 2. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, et al. Phase I clinical trial using escalating singledose infusion of chimeric anti-CD20 monoclonal antibody (IDECC2B8) in patients with recurrent B-cell lymphoma. Blood 1994;84: 2457-66. 3. Salopek TG, Logsetty S, Tredget EE. Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, lifethreatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol 2002;47:785-8. 4. Voog E, Morschauser F, Solal-Celigny P. Neutropenia in patients treated with rituximab. N Engl J Med 2003;348:2691-4. 5. Cerny T, Borisch B, Introna M, Johnson P, Rose AL. Mechanism of action of rituximab. Anticancer Drugs 2002;13(suppl 2):S3-10. 6. Golay JT, Clark EA, Beverley PCL. The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol 1985;135:3795-801. 7. Slifka MK, Antia R, Whitmire JK, Ahmed R. Humoral immunity due to long-lived plasma cells. Immunity 1998;8:363-72. doi:10.1016/j.jaad.2003.08.021
Concurrent development of eruptive xanthogranulomas and hematologic malignancy: Two case reports To the Editor: Juvenile xanthogranulomas are the most common histiocytosis of the non-Langerhans type.1 Most cases present during the first year of life, although onset in adults has been reported.2 Children with concurrent xanthogranulomas and neurofibromatosis type 1 (NF-1) carry a high risk of developing chronic myelogenous leukemia (CML)3 that is several-fold greater than the risk caused by having NF-1 alone.4,5 Necrobiotic xanthogranuloma
Fig 1. Case 1. Before treatment of CLL, illustrating eruptive xanthogranulomas on upper and lower lips.
Fig 2. Histology showing nodular dermal collection lipidladen foamy histiocytes and multinucleated giant cells. (Hematoxylin-eosin stain; original magnification ⫻10.)
in older individuals is associated with multiple myeloma and other plasma cell dyscrasias.6
CASE PRESENTATIONS Case 1 A 69-year-old man had a 3-month history of asymptomatic orange to red-brown papules (3-10 mm) erupting on the face, trunk, and extremities (Fig 1). Lesional skin histopathology revealed xanthogranuloma (Fig 2); immunohistochemistry was not performed. A progressively worsening leukocytosis led to a diagnosis of chronic lymphocytic leukemia (CLL). Chemotherapy cleared both the leukemia and xanthogranulomas, the latter leaving hyperpigmented macules (Fig 3). Case 2 A 76-year-old man had a 5-month history of widely distributed asymptomatic orange-brown papules (Fig 4). Lesional skin histopathology revealed xanthogranuloma; immunohistochemistry was not performed. Concurrently, he had a 14 kg weight loss while developing recurrent pleural effusions. Complete blood count, plasma cholesterol and triglycerides, bone marrow biopsy, urinary protein electrophoresis, and computed tomography of the chest and abdomen revealed normal findings, but serum protein electrophoresis documented a monoclonal gammopathy.
J AM ACAD DERMATOL JUNE 2004
2. Finlayson GR, Sams WM Jr, Smith JG Jr. Erythema ab igne: a histopathological study. J Invest Dermatol 1996;46:104-8. 3. Page EH, Shear NH. Temperature-dependent skin disorders. J Am Acad Dermatol 1988;18:1003-19. 4. Flanagan N, Watson R, Sweeney E, Barnes L. Bullous erythema ab igne [letter]. Br J Dermatol 1996;134:1159-60. 5. Kligman LH, Kligman AM. Reflections on heat. Br J Dermatol 1984;110:369-75. 6. Hurwitz RM, Tisserand ME. Erythema ab igne [letter]. Arch Dermatol 1987;123:21-3. 7. Mok DWH, Blumgart LH. Erythema ab igne in chronic pancreatic pain: a diagnostic sign. J R Soc Med 1984;77:299-301. 8. Butler ML. Erythema ab igne: a sign of pancreatic disease. Am J Gastroenterol 1977;67:77-9. 9. Mucklow ES, Freeman NV. Pancreatic ascites in childhood. Br J Clin Pract 1990;44:248-51. 10. Meffert JJ, Davis BM. Furniture-induced erythema ab igne. J Am Acad Dermatol 1996;34:516-7. 11. Dovretzky I, Silverman NR. Reticular erythema of the lower back. Arch Dermatol 1991;127:405-9. 12. Helm TN, Spigel GT, Helm KF. Erythema ab igne caused by a car heater. Cutis 1997;59:81-2. 13. Dellavalle RP, Gillum P. Erythema ab igne following heating/ cooling blanket use in the intensive care unit. Cutis 2000;66: 136-8. 14. Johnson WC, Butterworth T. Erythema ab igne elastosis. Arch Dermatol 1971;104:128-31. 15. Arrington JH, Lockman DS. Thermal keratoses and squamous cell carcinoma in situ associated with erythema ab igne. Arch Dermatol 1979;115:1226-8. 16. Reed RJ, Leone P. Porokeratosis: a mutant clonal keratosis of the epidermis. Arch Dermatol 1970;101:340-7. 17. Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol 1998;39:882-7. 18. Hewitt JB, Sherif A, Kerr KM, Stankler L. Merkel cell and squamous cell carcinomas arising in erythema ab igne. Br J Dermatol 1993;128:591-2. 19. Jones CS, Tyring SK, Lee PC, Fine JD. Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne. Arch Dermatol 1998;124:110-3. 20. Treves N, Pack GT. The development of cancer in burn scars. Surg Gynecol Obstet 1930;60:749-82. 21. Kaplan RP. Cancer complicating chronic ulcerative and scarifying mucocutaneous disorders. Adv Dermatol 1987;2:19-46. 22. Sahl WJ, Taira JW. Erythema ab igne: Treatment with 5-fluorouracil cream. J Am Acad Dermatol 1992;27:109-10. doi:10.1016/j.jaad.2003.08.007
Long-term complete remission of severe pemphigus vulgaris with monoclonal anti-CD20 antibody therapy and immunophenotype correlations To the Editor: A 39-year-old man presented with denuded areas affecting 70% of the body surface area (Fig 1, A, B, C). The oral, pharyngeal, and anal mucosa showed multiple erosions. Pemphigus vulgaris (PV) had been diagnosed based on histological and immunofluorescence findings. Intercellular substance (ICS) antibodies titer was 1/160. He was being treated with prednisone (2 mg/kg/d) and azathioprine (2.5 mg/kg/d), with side effects such as muscle loss, hyperglycemia, and skin infections secondary to methicillin-resistant Staphylococcus au-
reus. Immunoprecipitation studies were positive for Dsg1 and Dsg3. He received four plasma exchanges. Cyclophosphamide was not administered because of the cutaneous infections and the risk of azoospermia. We administered four infusions of anti-CD20 antibody (375 mg/m2) (rituximab; Mabthera, Roche Products, Dee Why, New South Wales, Australia) intravenously once a week, beginning immediately after the last plasma exchange. Premedication with acetaminophen and diphenhydramine was given. Azathioprine was discontinued before the first rituximab infusion, and the corticosteroid dose was progressively tapered. Periodic analytical determinations were performed (Table I). Lesions healed completely six weeks after the first administration of Rituximab. Forty weeks after Rituximab administration no lesions have been observed, the affected body surface area remains 0% (Fig 1, D, E, F), and the titer of ICS is 1/10. We recently found a correlation between profile of circulating mononuclear cells and clinical stage in PV,1 suggesting a relationship between B-cell activation and IgG autoantibody production in PV. Rituximab is an anti-CD20 monoclonal antibody effective against B-cell lymphomas2 and several autoimmune diseases. Recently, partial remission of PV with plasmapheresis, cyclophosphamide, and rituximab has been described, with considerable side effects (sepsis).3 Rare side effects include neutropenia, interstitial pneumonitis, bronchospasm, and angina pectoris, but generally adverse effects are mild or moderate and most are infusion-associated.4 Rituximab may induce killing of CD20 cells via complement- or antibody-dependent cytotoxicity, structural changes, and apoptosis.5 CD20 antigen seems to be involved in the activation of B-cells from G0 to G1 and in their differentiation.6 This inactivation of B-cells may explain the efficiency of this drug in diseases mediated by autoantibodies. A correlation between the decrease of CD19⫹ levels and the decrease of the area affected was observed, in spite of the persistence of a high titer of ICS antibodies (Table I). However, these antibodies seem not to be pathogenic. Rituximab may selectively destroy B-cell specific clones producing pathogenic PV-IgG autoantibodies (Table I). CD3⫹, CD3-56⫹16⫹ (natural killer cells), CD4⫹, and CD8⫹ cells reached normal levels a few weeks after the first rituximab infusion. These results show the relation between B- and T-cell responses in PV. Although B-cell count was negative after rituximab administration, IgG serum level was normal (Table I). Long-lived plasma cells may secrete antibodies for a long time in absence of detectable memory cells.7 In addition, this pool of mature plasma cells is
Letters 975
J AM ACAD DERMATOL VOLUME 50, NUMBER 6
Fig 1. Before monoclonal CD20 antibody administration seen on the (A) denuded areas on the face, (B) back, (C) arm and forearm. Forty weeks after monoclonal CD20 antibody administration no lesions are observed (D, E, F).
Table I. Immunophenotype profile and immunologic measurements Basal
Cell count Leukocytes count (4,3–10/L) Lymphocytes count (1,5–6/L) % Lymphocytes (20–50%) CD3⫹ cells (933–2491/l) % CD3⫹ cells (63–85%) CD19⫹ cells (65–467/l) % CD19⫹ cells (5–18%) CD4⫹ cells (370–1468/l) % CD4⫹ cells (32–57%) CD8⫹ cells (183–799/l) %CD8⫹ cells (13–34%) CD4⫹/CD8⫹ ratio (0,9–3) CD3⫺56⫹ 16⫹ cells (60–495/l) % CD3⫹56⫹ 16⫹ cells (5–25%) IgG subclasses IgG1 (455–890 mg/dL) IgG2 (200–525 mg/dL) IgG3 (17–100 mg/dL) IgG4 (14–74 mg/dL) Immunoglobulin serum levels IgG (850–1600 mg/dL) IgA (108–325 mg/dL) IgM (70–150 mg/dL) IgD (0–5 UI/mL) Anti-Dsg1 antibodies (NV: ⱕ 20) Anti-Dsg3 antibodies (NV: ⱕ 20) ICS immunofluorescence titer
14300 2450 17.2 ND ND ND ND ND ND ND ND ND ND ND
ⴙ1w
ⴙ4w
ⴙ8w
ⴙ 16 w
ⴙ 28 w
ⴙ 40 w
11400 2530 22 1969 78 236 9 1356 53 575 23 2.3 299 12
8300 2200 23.7 1600 71 299 13.3 1071 47.6 491 21.8 2.1 331 14.7
11930 4032 33.8 3746 92 0 0 2328 57 1435 35 1.6 278 7
10000 2360 23 2224 94 0 0 1370 58 861 36 1.6 132 5.6
10700 2996 28 2752 91 0 0 1802 60 925 31 1.9 242 8
11520 2327 20.2 2017 86 2,8 0.1 1260 54 726 31 1.7 302 13
ND ND ND ND
ND ND ND ND
ND ND ND ND
ND ND ND ND
817 243 5 169
198 29 22 1 77 160 1/160
947 91 76 5 38 115 1/80
791 80 35 4 105 167 1/160
864 74 32 3 40 156 1/320
1310 81 34 4 24 122 1/40
ND, Not done; NV, normal value; w, weeks after rituximab administration.
841 342 7.3 172 1280 109 64 4 7 90 1/40
ND ND ND ND 1480 136 76 4 ND ND 1/10
976 Letters
J AM ACAD DERMATOL JUNE 2004
CD20 antigen negative, and is unaffected by rituximab. Rituximab seems to be effective against severe PV and can lead to long term remission (forty weeks). So, these patients need no immunosuppressive treatment during this time, which lowers the risk of side effects. Agustı´n Espan ˜ a, MDa Marta Ferna´ndez-Galar, MDa Pedro Lloret, MDa Alfonso Sa´nchez-Ibarrola, MDb Carlos Panizo, MDc From the Departments of Dermatologya, Immunologyb, and Hematologyc University Clinic of Navarra, School of Medicine University of Navarra Pamplona, Navarra, Spain Correspondence to: Agustı´n Espan ˜ a, Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, PO Box 4209 Pamplona 31080, Navarra, Spain E-mail: [email protected] REFERENCES 1. Gonzalez A, Espan˜a A, Lopez-Zabalza MJ, Pelacho B, Sa´nchezCarpintero I, Santiago E, et al. Correlation between profile of circulating mononuclear cells and clinical manifestations in patients with pemphigus vulgaris. Autoimmunity 2000;32:115-28. 2. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, et al. Phase I clinical trial using escalating singledose infusion of chimeric anti-CD20 monoclonal antibody (IDECC2B8) in patients with recurrent B-cell lymphoma. Blood 1994;84: 2457-66. 3. Salopek TG, Logsetty S, Tredget EE. Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, lifethreatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol 2002;47:785-8. 4. Voog E, Morschauser F, Solal-Celigny P. Neutropenia in patients treated with rituximab. N Engl J Med 2003;348:2691-4. 5. Cerny T, Borisch B, Introna M, Johnson P, Rose AL. Mechanism of action of rituximab. Anticancer Drugs 2002;13(suppl 2):S3-10. 6. Golay JT, Clark EA, Beverley PCL. The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol 1985;135:3795-801. 7. Slifka MK, Antia R, Whitmire JK, Ahmed R. Humoral immunity due to long-lived plasma cells. Immunity 1998;8:363-72. doi:10.1016/j.jaad.2003.08.021
Concurrent development of eruptive xanthogranulomas and hematologic malignancy: Two case reports To the Editor: Juvenile xanthogranulomas are the most common histiocytosis of the non-Langerhans type.1 Most cases present during the first year of life, although onset in adults has been reported.2 Children with concurrent xanthogranulomas and neurofibromatosis type 1 (NF-1) carry a high risk of developing chronic myelogenous leukemia (CML)3 that is several-fold greater than the risk caused by having NF-1 alone.4,5 Necrobiotic xanthogranuloma
Fig 1. Case 1. Before treatment of CLL, illustrating eruptive xanthogranulomas on upper and lower lips.
Fig 2. Histology showing nodular dermal collection lipidladen foamy histiocytes and multinucleated giant cells. (Hematoxylin-eosin stain; original magnification ⫻10.)
in older individuals is associated with multiple myeloma and other plasma cell dyscrasias.6
CASE PRESENTATIONS Case 1 A 69-year-old man had a 3-month history of asymptomatic orange to red-brown papules (3-10 mm) erupting on the face, trunk, and extremities (Fig 1). Lesional skin histopathology revealed xanthogranuloma (Fig 2); immunohistochemistry was not performed. A progressively worsening leukocytosis led to a diagnosis of chronic lymphocytic leukemia (CLL). Chemotherapy cleared both the leukemia and xanthogranulomas, the latter leaving hyperpigmented macules (Fig 3). Case 2 A 76-year-old man had a 5-month history of widely distributed asymptomatic orange-brown papules (Fig 4). Lesional skin histopathology revealed xanthogranuloma; immunohistochemistry was not performed. Concurrently, he had a 14 kg weight loss while developing recurrent pleural effusions. Complete blood count, plasma cholesterol and triglycerides, bone marrow biopsy, urinary protein electrophoresis, and computed tomography of the chest and abdomen revealed normal findings, but serum protein electrophoresis documented a monoclonal gammopathy.