- Email: [email protected]
Lichen planus pemphigoides in a 2-year-old girl: Response to treatment with methotrexate
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OCTOBER 2012
hands without distal limb necrosis. Moreover, penile calciphylaxis is a very unusual disease. To our knowledge, only 43 cases of penile calciphylaxis have been identified in the literature. This case demonstrates the clinical diversity of this disease and illustrates an unusual location of calciphylaxis that caused a significant delay in the diagnosis. Maider Pretel Irazabal, MD, MPH,a Laura Marques Idoate Gastearena, Martin, MD,a Miguel Angel b MD, MPH, Tania Labiano Miravalles, MD,b and Nuria Garcıa Fern andez, MD, MPHc Departments of Dermatology,a Pathology,b and Nephrology,c University Clinic of Navarra, School of Medicine, Pamplona, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Laura Marques Martin, MD, Department of Dermatology, University Clinic of Navarra, Av. Pıo XII, n836, 31008, Pamplona, Spain E-mail: [email protected] REFERENCES 1. Angelis M, Wong LL, Myers SA, Wong LM. Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery 1997;122:1083-9. 2. Budisavljevic MN, Cheek D, Ploth DW. Calciphylaxis in chronic renal failure. J Am Soc Nephrol 1996;7:978-82. 3. Kuzela DC, Huffer WE, Conger JD, Winter SD, Hammond WS. Soft tissue calcification in chronic dialysis patients. Am J Pathol 1977;86:403-24. 4. Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial 2002;15:172-86. 5. Hayden MR, Goldsmith D, Sowers JR, Khanna R. Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate. Int Urol Nephrol 2008;40:443-51. http://dx.doi.org/10.1016/j.jaad.2011.12.022
Lichen planus pemphigoides in a 2-year-old girl: Response to treatment with methotrexate To the Editor: Lichen planus (LP) pemphigoides (LPP) is a heterogeneous autoimmune disease characterized by subepidermal blisters occurring in association with LP. It is hypothesized that the lichenoid inflammation in LP, in the absence of adequate immune surveillance, may result in epitope spreading and production of autoantibodies against 180-kd bullous pemphigoid (BP) antigen (BP180).1 Pediatric LPP is rare, with only 14 cases documented in the literature.2-4 We describe a child with the characteristic findings of LPP who was successfully treated with methotrexate. Decreasing levels of
Fig 1. A, Lichen planus (LP) pemphigoides: punch biopsy specimen from initial eruption showing epidermal hyperplasia, hyperkeratosis, Civatte bodies, and bandlike papillary dermal lymphocytic infiltrate with vacuolar change consistent with LP. B, Punch biopsy specimen from edge of blister showing subepidermal detachment, necrotic keratinocytes, numerous melanophages, and perivascular lymphocytic infiltrate in papillary dermis. (Hematoxylineosin stain; original magnifications: A and B, 333.)
serum anti-BP180 autoantibodies correlated with her clinical improvement. A 2-year-old girl presented with a 3-week history of intensely pruritic, violaceous scaly plaques in a widespread distribution. Only her palms, soles, oral mucosa, and nails were not involved. Histopathologic examination of a skin biopsy specimen confirmed the clinical diagnosis of LP (Fig 1, A). She was treated with triamcinolone 0.1% ointment under occlusion with wet wraps, and with oral hydroxyzine, but showed minimal improvement. Two weeks later, she developed numerous tense blisters and large erosions within the violaceous plaques of LP and on previously uninvolved skin (Fig 2, A and B). Biopsy specimens were obtained for histopathology and direct immunofluorescence. Histopathologic examination revealed a subepidermal blister with a dermal mononuclear infiltrate composed of lymphocytes, plasma cells, and numerous melanophages (Fig 1, B). Direct immunofluorescence showed linear deposition of IgG and complement component 3 at
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Fig 2. A and B, Lichen planus pemphigoides (LPP) before treatment. Generalized violaceous plaques, tense bullae, and erosions over face, trunk, and lower extremities. C, LPP 11 months after initiating treatment with methotrexate. Residual hypopigmentation and hyperpigmentation is present.
the dermoepidermal junction. Enzyme-linked immunosorbent assay demonstrated circulating autoantibodies to BP180 at 173 U/mL ( positive: $9 U/mL); autoantibodies to 230-kd BP antigen were negative. A diagnosis of LPP was made and there was a good response to treatment with oral prednisolone 2 mg/kg/d. However, several attempts to taper the dose of prednisolone below 1 mg/kg resulted in a flare of her severe bullous disease. Weekly oral methotrexate 0.5 mg/kg/dose was initiated and, within the first month of treatment, the violaceous plaques resolved with no new bulla formation. Prednisolone was subsequently tapered and discontinued over 8 weeks. Enzyme-linked immunosorbent assay, repeated after 6 and 11 months of treatment, showed a decrease in circulating BP180 autoantibodies to 66 and 42 U/mL, respectively. This corresponded with her clinical improvement (Fig 2, C ). Reported therapies for pediatric LPP include topical and systemic corticosteroids, erythromycin, dapsone, and azathioprine.2 Low-dose methotrexate has not been described as a treatment for LPP. We chose it instead of other immunosuppressive agents because there is greater experience with methotrexate in the treatment of skin diseases in children. In addition, methotrexate has been used to treat both LP and BP. Levels of serum anti-BP180 antibodies, detected by enzyme-linked immunosorbent assay, have been shown to correlate with disease activity in BP5 and, in one report, in LPP.6 We found a similar trend in our patient. We conclude that methotrexate may be useful as a steroid-sparing agent in patients with
severe LPP. In addition, serum anti-BP180 levels may correlate with disease activity in LPP and help guide treatment decisions. The authors thank Dr David Kelly for providing the photomicrographs for this manuscript.
Buu Duong, MD,a Shellie Marks, MD,b Naveed Sami, MD,b and Amy Theos, MDb Department of Pathology and Laboratory Medicine, Tulane University Health Sciences, New Orleans, Louisiana,a and Department of Dermatology, University of Alabama at Birminghamb Funding sources: None. Conflicts of interest: None declared. Correspondence to: Amy Theos, MD, 1940 Elmer J. Bissell Rd, Birmingham, AL 35243 E-mail: [email protected]
REFERENCES 1. Mignogna MD, Fortuna G, Leuci S, Stasio L, Mezza E, Ruoppo E. Lichen planus pemphigoides, a possible example of epitope spreading. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:837-43. 2. Cohen DM, Ben-Amitai D, Feinmesser M, Zvulunov A. Childhood lichen planus pemphigoides: a case report and review of the literature. Pediatr Dermatol 2009;26:569-74. 3. Jensen A, Steiniche T, Veien NK, Deleuran MS. Lichen planus pemphigoides in a 6-year-old child. Acta Paediatr 2009;98:2-3. 4. Ilknur T, Akarsu S, Uzun S, Ozer E, Fetil E. Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella. J Dermatol 2011;38:707-10. 5. Schmidt E, Obe K, Brocker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with disease activity in
J AM ACAD DERMATOL
e156 Letters
OCTOBER 2012
patients with bullous pemphigoid. Arch Dermatol 2000;136:174-8. 6. Barnadas MA, Roe E, Dalmau J, Alomar A, Martinez L, Gelpi C. Lichen planus pemphigoides: detection of anti-BP 180 antibodies by ELISA and immunoblotting tests. J Eur Acad Dermatol Venereol 2010;24:1360-1.
http://dx.doi.org/10.1016/j.jaad.2011.12.024
Sweat gland carcinoma versus metastatic breast carcinoma: A continued struggle among clinicians and dermatopathologists To the Editor: Sweat gland carcinoma (SGC) may be indistinguishable from cutaneous metastases from breast carcinoma. As management and prognosis are very different, differentiation between these two entities is enormously important. However, it remains one of the most challenging issues in dermatology. New developments in immunohistochemistry and radiologic imaging have improved our abilities to make a ‘‘correct’’ diagnosis, but often we are still faced with the uncertainties of modern medicine. A 69-year-old woman presented with a 3-year history of an asymptomatic lump on the scalp. An excisional biopsy specimen showed an invasive adenocarcinoma characterized by small monotonous cells with prominent nucleoli and extensive perineural extension. Immunohistochemistry was
positive for CK7, CK20, estrogen receptor (ER), progesterone receptor (PR), carcinoembryonic antigen (CEA) and focally positive for GCDFP-15 and mucin, negative for HER-2/neu, p63, CK5, and podoplanin (Fig 1). The diagnoses of cutaneous metastasis of breast carcinoma and primary SGC were considered. Mammogram, breast magnetic resonance imaging, and positron emission tomography (PET)-CT scan were all negative, and her only risk factor for breast cancer was postmenopausal hormone replacement therapy. She underwent wide local excision, which unfortunately showed persistent positive medial margins on frozen sections despite multiple attempts to clear them. As the defect size was becoming very large and all the remaining skin was grossly benign, the defect was closed. The right cervical and preauricular sentinel lymph nodes were negative. Given the locally aggressive nature of the tumor, the presence of ER/PR, and the focally positive medial margin on permanent section, she was started on letrozole, an aromatase inhibitor, at 2.5 mg daily with a plan to treat for 5 years. She continues to do well, without any evidence of recurrent or metastatic disease after 3 years of follow-up; therefore a diagnosis of primary SGC was favored in the end. Our case illustrates the difficulty in differentiating SGCs from cutaneous metastases of breast
Fig 1. Scalp adenocarcinoma. Hematoxylin-eosin (H&E) images and selected immunohistochemical images (of CEA and p63 stains) of patient’s scalp adenocarcinoma.
e154 Letters
OCTOBER 2012
hands without distal limb necrosis. Moreover, penile calciphylaxis is a very unusual disease. To our knowledge, only 43 cases of penile calciphylaxis have been identified in the literature. This case demonstrates the clinical diversity of this disease and illustrates an unusual location of calciphylaxis that caused a significant delay in the diagnosis. Maider Pretel Irazabal, MD, MPH,a Laura Marques Idoate Gastearena, Martin, MD,a Miguel Angel b MD, MPH, Tania Labiano Miravalles, MD,b and Nuria Garcıa Fern andez, MD, MPHc Departments of Dermatology,a Pathology,b and Nephrology,c University Clinic of Navarra, School of Medicine, Pamplona, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Laura Marques Martin, MD, Department of Dermatology, University Clinic of Navarra, Av. Pıo XII, n836, 31008, Pamplona, Spain E-mail: [email protected] REFERENCES 1. Angelis M, Wong LL, Myers SA, Wong LM. Calciphylaxis in patients on hemodialysis: a prevalence study. Surgery 1997;122:1083-9. 2. Budisavljevic MN, Cheek D, Ploth DW. Calciphylaxis in chronic renal failure. J Am Soc Nephrol 1996;7:978-82. 3. Kuzela DC, Huffer WE, Conger JD, Winter SD, Hammond WS. Soft tissue calcification in chronic dialysis patients. Am J Pathol 1977;86:403-24. 4. Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. Semin Dial 2002;15:172-86. 5. Hayden MR, Goldsmith D, Sowers JR, Khanna R. Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate. Int Urol Nephrol 2008;40:443-51. http://dx.doi.org/10.1016/j.jaad.2011.12.022
Lichen planus pemphigoides in a 2-year-old girl: Response to treatment with methotrexate To the Editor: Lichen planus (LP) pemphigoides (LPP) is a heterogeneous autoimmune disease characterized by subepidermal blisters occurring in association with LP. It is hypothesized that the lichenoid inflammation in LP, in the absence of adequate immune surveillance, may result in epitope spreading and production of autoantibodies against 180-kd bullous pemphigoid (BP) antigen (BP180).1 Pediatric LPP is rare, with only 14 cases documented in the literature.2-4 We describe a child with the characteristic findings of LPP who was successfully treated with methotrexate. Decreasing levels of
Fig 1. A, Lichen planus (LP) pemphigoides: punch biopsy specimen from initial eruption showing epidermal hyperplasia, hyperkeratosis, Civatte bodies, and bandlike papillary dermal lymphocytic infiltrate with vacuolar change consistent with LP. B, Punch biopsy specimen from edge of blister showing subepidermal detachment, necrotic keratinocytes, numerous melanophages, and perivascular lymphocytic infiltrate in papillary dermis. (Hematoxylineosin stain; original magnifications: A and B, 333.)
serum anti-BP180 autoantibodies correlated with her clinical improvement. A 2-year-old girl presented with a 3-week history of intensely pruritic, violaceous scaly plaques in a widespread distribution. Only her palms, soles, oral mucosa, and nails were not involved. Histopathologic examination of a skin biopsy specimen confirmed the clinical diagnosis of LP (Fig 1, A). She was treated with triamcinolone 0.1% ointment under occlusion with wet wraps, and with oral hydroxyzine, but showed minimal improvement. Two weeks later, she developed numerous tense blisters and large erosions within the violaceous plaques of LP and on previously uninvolved skin (Fig 2, A and B). Biopsy specimens were obtained for histopathology and direct immunofluorescence. Histopathologic examination revealed a subepidermal blister with a dermal mononuclear infiltrate composed of lymphocytes, plasma cells, and numerous melanophages (Fig 1, B). Direct immunofluorescence showed linear deposition of IgG and complement component 3 at
J AM ACAD DERMATOL
Letters e155
VOLUME 67, NUMBER 4
Fig 2. A and B, Lichen planus pemphigoides (LPP) before treatment. Generalized violaceous plaques, tense bullae, and erosions over face, trunk, and lower extremities. C, LPP 11 months after initiating treatment with methotrexate. Residual hypopigmentation and hyperpigmentation is present.
the dermoepidermal junction. Enzyme-linked immunosorbent assay demonstrated circulating autoantibodies to BP180 at 173 U/mL ( positive: $9 U/mL); autoantibodies to 230-kd BP antigen were negative. A diagnosis of LPP was made and there was a good response to treatment with oral prednisolone 2 mg/kg/d. However, several attempts to taper the dose of prednisolone below 1 mg/kg resulted in a flare of her severe bullous disease. Weekly oral methotrexate 0.5 mg/kg/dose was initiated and, within the first month of treatment, the violaceous plaques resolved with no new bulla formation. Prednisolone was subsequently tapered and discontinued over 8 weeks. Enzyme-linked immunosorbent assay, repeated after 6 and 11 months of treatment, showed a decrease in circulating BP180 autoantibodies to 66 and 42 U/mL, respectively. This corresponded with her clinical improvement (Fig 2, C ). Reported therapies for pediatric LPP include topical and systemic corticosteroids, erythromycin, dapsone, and azathioprine.2 Low-dose methotrexate has not been described as a treatment for LPP. We chose it instead of other immunosuppressive agents because there is greater experience with methotrexate in the treatment of skin diseases in children. In addition, methotrexate has been used to treat both LP and BP. Levels of serum anti-BP180 antibodies, detected by enzyme-linked immunosorbent assay, have been shown to correlate with disease activity in BP5 and, in one report, in LPP.6 We found a similar trend in our patient. We conclude that methotrexate may be useful as a steroid-sparing agent in patients with
severe LPP. In addition, serum anti-BP180 levels may correlate with disease activity in LPP and help guide treatment decisions. The authors thank Dr David Kelly for providing the photomicrographs for this manuscript.
Buu Duong, MD,a Shellie Marks, MD,b Naveed Sami, MD,b and Amy Theos, MDb Department of Pathology and Laboratory Medicine, Tulane University Health Sciences, New Orleans, Louisiana,a and Department of Dermatology, University of Alabama at Birminghamb Funding sources: None. Conflicts of interest: None declared. Correspondence to: Amy Theos, MD, 1940 Elmer J. Bissell Rd, Birmingham, AL 35243 E-mail: [email protected]
REFERENCES 1. Mignogna MD, Fortuna G, Leuci S, Stasio L, Mezza E, Ruoppo E. Lichen planus pemphigoides, a possible example of epitope spreading. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:837-43. 2. Cohen DM, Ben-Amitai D, Feinmesser M, Zvulunov A. Childhood lichen planus pemphigoides: a case report and review of the literature. Pediatr Dermatol 2009;26:569-74. 3. Jensen A, Steiniche T, Veien NK, Deleuran MS. Lichen planus pemphigoides in a 6-year-old child. Acta Paediatr 2009;98:2-3. 4. Ilknur T, Akarsu S, Uzun S, Ozer E, Fetil E. Heterogeneous disease: a child case of lichen planus pemphigoides triggered by varicella. J Dermatol 2011;38:707-10. 5. Schmidt E, Obe K, Brocker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with disease activity in
J AM ACAD DERMATOL
e156 Letters
OCTOBER 2012
patients with bullous pemphigoid. Arch Dermatol 2000;136:174-8. 6. Barnadas MA, Roe E, Dalmau J, Alomar A, Martinez L, Gelpi C. Lichen planus pemphigoides: detection of anti-BP 180 antibodies by ELISA and immunoblotting tests. J Eur Acad Dermatol Venereol 2010;24:1360-1.
http://dx.doi.org/10.1016/j.jaad.2011.12.024
Sweat gland carcinoma versus metastatic breast carcinoma: A continued struggle among clinicians and dermatopathologists To the Editor: Sweat gland carcinoma (SGC) may be indistinguishable from cutaneous metastases from breast carcinoma. As management and prognosis are very different, differentiation between these two entities is enormously important. However, it remains one of the most challenging issues in dermatology. New developments in immunohistochemistry and radiologic imaging have improved our abilities to make a ‘‘correct’’ diagnosis, but often we are still faced with the uncertainties of modern medicine. A 69-year-old woman presented with a 3-year history of an asymptomatic lump on the scalp. An excisional biopsy specimen showed an invasive adenocarcinoma characterized by small monotonous cells with prominent nucleoli and extensive perineural extension. Immunohistochemistry was
positive for CK7, CK20, estrogen receptor (ER), progesterone receptor (PR), carcinoembryonic antigen (CEA) and focally positive for GCDFP-15 and mucin, negative for HER-2/neu, p63, CK5, and podoplanin (Fig 1). The diagnoses of cutaneous metastasis of breast carcinoma and primary SGC were considered. Mammogram, breast magnetic resonance imaging, and positron emission tomography (PET)-CT scan were all negative, and her only risk factor for breast cancer was postmenopausal hormone replacement therapy. She underwent wide local excision, which unfortunately showed persistent positive medial margins on frozen sections despite multiple attempts to clear them. As the defect size was becoming very large and all the remaining skin was grossly benign, the defect was closed. The right cervical and preauricular sentinel lymph nodes were negative. Given the locally aggressive nature of the tumor, the presence of ER/PR, and the focally positive medial margin on permanent section, she was started on letrozole, an aromatase inhibitor, at 2.5 mg daily with a plan to treat for 5 years. She continues to do well, without any evidence of recurrent or metastatic disease after 3 years of follow-up; therefore a diagnosis of primary SGC was favored in the end. Our case illustrates the difficulty in differentiating SGCs from cutaneous metastases of breast
Fig 1. Scalp adenocarcinoma. Hematoxylin-eosin (H&E) images and selected immunohistochemical images (of CEA and p63 stains) of patient’s scalp adenocarcinoma.