CASE REPORT – OPEN ACCESS International Journal of Surgery Case Reports 5 (2014) 212–214
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International Journal of Surgery Case Reports journal homepage: www.casereports.com
Dramatic resolution of bullous pemphigoid after surgery for gastric cancer: A case report Keita Noguchi a,∗ , Hideki Kawamura b , Hiroyuki Ishizu b , Kuniaki Okada b a b
Department of General surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan Department of Surgery, Sapporo Kosei Hospital, N3, E8, Chuo-ku, Sapporo 060-0033, Japan
a r t i c l e
i n f o
Article history: Received 9 November 2013 Received in revised form 5 February 2014 Accepted 15 February 2014 Available online 26 February 2014 Keywords: Resolution Bullous pemphigoid Gastric cancer
a b s t r a c t INTRODUCTION: An association between bullous pemphigoid (BP) and internal malignancy has been suggested. However, no reports have documented a dramatic improvement in BP after surgery for gastric cancer. PRESENTATION OF CASE: An 82-year-old Japanese woman was admitted to a local hospital for severe fatigue. On examination, she was diagnosed with BP and gastric cancer. Her BP was resistant to steroid treatment; however, it improved dramatically after surgery for gastric cancer. DISCUSSION: In this case, a strong relationship appeared to exist between BP and gastric cancer. CONCLUSION: This is the first report of a dramatic improvement in BP after surgery for gastric cancer. © 2014 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
1. Introduction Bullous pemphigoid (BP) is an autoimmune skin disease, characterized by large, tense bullae.1 Lesions usually consist of 1- to 3-cm blisters situated on either normal-appearing or inflamed skin. BP is typically a chronic disease characterized by periods of exacerbation and partial remission; pruritus is a common feature. Several reports have noted the incidence of internal malignancies in BP cases; however, few describe BP associated with gastric cancer.2,3 We present a first case of BP with advanced gastric cancer in which BP improved dramatically after gastrectomy.
2. Case presentation An 82-year-old Japanese woman developed a pruritic eruption on her trunk and extremities. Two months later, she reported severe fatigue and was admitted to a local hospital. There, she was diagnosed with BP, characterized by blisters of the trunk and extremities, and found to have gastric cancer. The patient was then transferred to our hospital for treatment of BP and gastric cancer. On admission, she had severe blisters, pigmentation, erythema, and crusts on her trunk and extremities (Fig. 1). A
Abbreviations: BP, bullous pemphigoid; CRP, C-reactive protein. ∗ Corresponding author. Tel.: +81 117067381. E-mail addresses: [email protected] (K. Noguchi), [email protected] (H. Kawamura), [email protected] (H. Ishizu), [email protected] (K. Okada).
skin biopsy was performed. Histologically, subepidermal bulla containing eosinophils were seen on hematoxylin–eosin staining, and linear basement membrane zone deposits of Immunoglobulin G and complement C3c and C3d were seen on direct immunofluorescence (Fig. 2). The pathological diagnosis was BP. Admission laboratory data revealed anemia (hemoglobin 8.4 g/dL) and hypoproteinemia (total protein 5.2 g/dL, albumin 2.1 g/dL). Creactive protein (CRP) was 9.67 mg/dL and carcinoembryonic antigen was slightly positive (5.6 ng/mL). The patient was treated for BP with prednisolone 20 mg/day, but the response was minimal and may have been impaired by the patient’s persistent severe hypoproteinemia, which was caused by effusion from blisters. We considered that if an association existed between BP and gastric cancer, the patient’s BP might improve on treating the gastric cancer. Because the patient was anemic, we felt the tumor needed to be surgically removed. Therefore, a total gastrectomy was performed. Intraoperative findings showed peritoneal dissemination of gastric cancer, and the pathological diagnosis was poorly differentiated adenocarcinoma stage IV (se, P1, H0, INF␥, ly3, v0, according to the 14th edition General Rules for the Gastric Cancer Study in Surgery and Pathology at Japan). On the 9th postoperative day, the patient required reoperation for an abdominal abscess and wound dehiscence. On the 11th day after the first operation, she had leakage of the duodenal stump. This leakage improved with 11 days of conservative treatment. On the 49th day after the first operation, the patient was discharged from our hospital. She had no evidence of BP despite being completely off prednisolone (Fig. 3). She did not hope the postoperative chemotherapy. The patient had no recurrence of BP. However, 5 months after surgery, she died of gastric cancer metastasis to the peritoneum.
http://dx.doi.org/10.1016/j.ijscr.2014.02.008 2210-2612/© 2014 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
CASE REPORT – OPEN ACCESS K. Noguchi et al. / International Journal of Surgery Case Reports 5 (2014) 212–214
Fig. 1. Preoperative skin shows severe blisters, pigmentation, erythema, and crust.
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associated and was observed in 32 of 64 patients with BP. Gastric cancer was the dominant subtype and was found in 14 out of the 32 patients.4 Why BP is associated with malignant tumors is unclear. Recently, it has been suggested that the extracellular domain of BP180 directly binds to laminin 332, which is the major component of the matrix in the basement membrane zone.7,8 The existence of anti-BP180 may then cause significant inhibition of the attachment of BP180 to laminin 332, leading to the disadhesion of epithelial cells, enhanced motility of epithelial cells, and cancer transformation. Some reports have described dramatic improvement in BP after treatment for malignant tumors of the gallbladder, bronchus, colon, reticulum cells, lung, retroperitoneum, parotid, and breast.9–16 However, there have been a few reports that BP improved dramatically after the treatment of cancers. To the best of our knowledge, this was the 10th report of dramatic resolution of BP after treatment of malignant tumors and the 1st report of dramatic resolution of BP after surgery for gastric cancer. 4. Conclusion In this case, BP was strongly associated with gastric cancer, and resection of the cancer improved the patient’s quality of life through dramatic resolution of BP. Conflict of interest The authors declare that they have no competing interests. Funding
Fig. 2. Direct immunofluorescence: linear basement membrane zone deposit of Immunoglobulin G and complement C3c and C3d.
None declared. Ethical approval Written informed consent for publication of this manuscript and any accompanying images was obtained from all patients. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Authors’ contribution KN was involved in the conception of the report, literature review, manuscript preparation, editing, and submission. HK, HI, and KO were responsible for the manuscript critique and review. All authors have read and approved the final manuscript. Acknowledgment None.
Fig. 3. Postoperative skin shows no lesions.
References 3. Discussion The relationship between BP and malignancy is a matter of debate. Studies from the USA and Sweden suggest no relationship between BP and internal malignancy.2,3 However, contradictory findings have been reported from other countries, especially in Asia. For example, in a Japanese report, patients with BP had a higher incidence of malignancy than controls without BP (5.8% vs. 0.61%, respectively).4 Furthermore, a high incidence of malignancy was associated with BP in both a Chinese (5.8%) and a Taiwanese report (15.1%).5,6 Cancer of the digestive organs was the most frequently
1. Yancey KB, Egan CA. Pemphigoid: clinical, histologic, immunopathologic, and therapeutic considerations. J Am Med Assoc 2000;284(3):350–6. 2. Lindelof B, Islam N, Eklund G, Arfors L. Pemphigoid and cancer. Arch Dermatol 1990;126(1):66–8. 3. Stone SP, Schroeter AL. Bullous pemphigoid and associated malignant neoplasms. Arch Dermatol 1975;111(8):991–4. 4. Ogawa H, Sakuma M, Morioka S, Kitamura K, Sasai Y, Imamura S, et al. The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan. J Dermatol Sci 1995;9(2):136–41. 5. Jin P, Shao C, Ye G. Chronic bullous dermatoses in China. Int J Dermatol 1993;32(2):89–92. 6. Chang YT, Liu HN, Wong CK. Bullous pemphigoid – a report of 86 cases from Taiwan. Clin Exp Dermatol 1996;21(1):20–2.
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K. Noguchi et al. / International Journal of Surgery Case Reports 5 (2014) 212–214
7. Parikka M, Kainulainen T, Tasanen K, Bruckner-Tuderman L, Salo T. Altered expression of collagen XVII in ameloblastomas and basal cell carcinomas. J Oral Pathol Med 2001;30(10):589–95. 8. Franzke CW, Has C, Schulte C, Huilaja L, Tasanen K, Aumailley M, et al. C-terminal truncation impairs glycosylation of transmembrane collagen XVII and leads to intracellular accumulation. J Biol Chem 2006;281(40):30260–8. 9. Umekoji A, Tsuruta D, Inoue T, Nishimori T, Ishii M. Bullous pemphigoid as a dermadrome associated with spindle cell carcinoma of the gallbladder. J Dermatol 2010;37(3):251–4. 10. Graham-Brown RA. Bullous pemphigoid with figurate erythema associated with carcinoma of the bronchus. Br J Dermatol 1987;117(3):385–8. 11. Gilmour E, Bhushan M, Griffiths CE. Figurate erythema with bullous pemphigoid: a true paraneoplastic phenomenon? Clin Exp Dermatol 1999;24(6): 446–8.
12. Anhalt GJ, Kim SC, Stanley JR, Korman NJ, Jabs DA, Kory M, et al. Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990;323(25):1729–35. 13. Takeuchi M, Okazaki A, Nakajima N, Saito Y, Nozaki M, Niibe H. A case of lung cancer with bullous pemphigoid. Gan No Rinsho 1986;32(5):529–33. 14. Krunic AL, Kokai D, Bacetic B, Kesic V, Nikolic MM, Petkovic S, et al. Retroperitoneal round-cell liposarcoma associated with paraneoplastic pemphigus presenting as lichen planus pemphigoides-like eruption. Int J Dermatol 1997;36(7):526–9. 15. Cakmak O, Seckin D, Ceken I, Yilmaz I, Akkuzu B, Ozluoglu L. Bullous pemphigoid associated with parotid carcinoma. Otolaryngol Head Neck Surg 2002;127(4):354–6. 16. Iuliano L, Micheletta F, Natoli S. Bullous pemphigoid: an unusual and insidious presentation of breast cancer. Clin Oncol (R Coll Radiol) 2003;15(8):505.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Contents lists available at ScienceDirect
International Journal of Surgery Case Reports journal homepage: www.casereports.com
Dramatic resolution of bullous pemphigoid after surgery for gastric cancer: A case report Keita Noguchi a,∗ , Hideki Kawamura b , Hiroyuki Ishizu b , Kuniaki Okada b a b
Department of General surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan Department of Surgery, Sapporo Kosei Hospital, N3, E8, Chuo-ku, Sapporo 060-0033, Japan
a r t i c l e
i n f o
Article history: Received 9 November 2013 Received in revised form 5 February 2014 Accepted 15 February 2014 Available online 26 February 2014 Keywords: Resolution Bullous pemphigoid Gastric cancer
a b s t r a c t INTRODUCTION: An association between bullous pemphigoid (BP) and internal malignancy has been suggested. However, no reports have documented a dramatic improvement in BP after surgery for gastric cancer. PRESENTATION OF CASE: An 82-year-old Japanese woman was admitted to a local hospital for severe fatigue. On examination, she was diagnosed with BP and gastric cancer. Her BP was resistant to steroid treatment; however, it improved dramatically after surgery for gastric cancer. DISCUSSION: In this case, a strong relationship appeared to exist between BP and gastric cancer. CONCLUSION: This is the first report of a dramatic improvement in BP after surgery for gastric cancer. © 2014 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
1. Introduction Bullous pemphigoid (BP) is an autoimmune skin disease, characterized by large, tense bullae.1 Lesions usually consist of 1- to 3-cm blisters situated on either normal-appearing or inflamed skin. BP is typically a chronic disease characterized by periods of exacerbation and partial remission; pruritus is a common feature. Several reports have noted the incidence of internal malignancies in BP cases; however, few describe BP associated with gastric cancer.2,3 We present a first case of BP with advanced gastric cancer in which BP improved dramatically after gastrectomy.
2. Case presentation An 82-year-old Japanese woman developed a pruritic eruption on her trunk and extremities. Two months later, she reported severe fatigue and was admitted to a local hospital. There, she was diagnosed with BP, characterized by blisters of the trunk and extremities, and found to have gastric cancer. The patient was then transferred to our hospital for treatment of BP and gastric cancer. On admission, she had severe blisters, pigmentation, erythema, and crusts on her trunk and extremities (Fig. 1). A
Abbreviations: BP, bullous pemphigoid; CRP, C-reactive protein. ∗ Corresponding author. Tel.: +81 117067381. E-mail addresses: [email protected] (K. Noguchi), [email protected] (H. Kawamura), [email protected] (H. Ishizu), [email protected] (K. Okada).
skin biopsy was performed. Histologically, subepidermal bulla containing eosinophils were seen on hematoxylin–eosin staining, and linear basement membrane zone deposits of Immunoglobulin G and complement C3c and C3d were seen on direct immunofluorescence (Fig. 2). The pathological diagnosis was BP. Admission laboratory data revealed anemia (hemoglobin 8.4 g/dL) and hypoproteinemia (total protein 5.2 g/dL, albumin 2.1 g/dL). Creactive protein (CRP) was 9.67 mg/dL and carcinoembryonic antigen was slightly positive (5.6 ng/mL). The patient was treated for BP with prednisolone 20 mg/day, but the response was minimal and may have been impaired by the patient’s persistent severe hypoproteinemia, which was caused by effusion from blisters. We considered that if an association existed between BP and gastric cancer, the patient’s BP might improve on treating the gastric cancer. Because the patient was anemic, we felt the tumor needed to be surgically removed. Therefore, a total gastrectomy was performed. Intraoperative findings showed peritoneal dissemination of gastric cancer, and the pathological diagnosis was poorly differentiated adenocarcinoma stage IV (se, P1, H0, INF␥, ly3, v0, according to the 14th edition General Rules for the Gastric Cancer Study in Surgery and Pathology at Japan). On the 9th postoperative day, the patient required reoperation for an abdominal abscess and wound dehiscence. On the 11th day after the first operation, she had leakage of the duodenal stump. This leakage improved with 11 days of conservative treatment. On the 49th day after the first operation, the patient was discharged from our hospital. She had no evidence of BP despite being completely off prednisolone (Fig. 3). She did not hope the postoperative chemotherapy. The patient had no recurrence of BP. However, 5 months after surgery, she died of gastric cancer metastasis to the peritoneum.
http://dx.doi.org/10.1016/j.ijscr.2014.02.008 2210-2612/© 2014 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
CASE REPORT – OPEN ACCESS K. Noguchi et al. / International Journal of Surgery Case Reports 5 (2014) 212–214
Fig. 1. Preoperative skin shows severe blisters, pigmentation, erythema, and crust.
213
associated and was observed in 32 of 64 patients with BP. Gastric cancer was the dominant subtype and was found in 14 out of the 32 patients.4 Why BP is associated with malignant tumors is unclear. Recently, it has been suggested that the extracellular domain of BP180 directly binds to laminin 332, which is the major component of the matrix in the basement membrane zone.7,8 The existence of anti-BP180 may then cause significant inhibition of the attachment of BP180 to laminin 332, leading to the disadhesion of epithelial cells, enhanced motility of epithelial cells, and cancer transformation. Some reports have described dramatic improvement in BP after treatment for malignant tumors of the gallbladder, bronchus, colon, reticulum cells, lung, retroperitoneum, parotid, and breast.9–16 However, there have been a few reports that BP improved dramatically after the treatment of cancers. To the best of our knowledge, this was the 10th report of dramatic resolution of BP after treatment of malignant tumors and the 1st report of dramatic resolution of BP after surgery for gastric cancer. 4. Conclusion In this case, BP was strongly associated with gastric cancer, and resection of the cancer improved the patient’s quality of life through dramatic resolution of BP. Conflict of interest The authors declare that they have no competing interests. Funding
Fig. 2. Direct immunofluorescence: linear basement membrane zone deposit of Immunoglobulin G and complement C3c and C3d.
None declared. Ethical approval Written informed consent for publication of this manuscript and any accompanying images was obtained from all patients. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Authors’ contribution KN was involved in the conception of the report, literature review, manuscript preparation, editing, and submission. HK, HI, and KO were responsible for the manuscript critique and review. All authors have read and approved the final manuscript. Acknowledgment None.
Fig. 3. Postoperative skin shows no lesions.
References 3. Discussion The relationship between BP and malignancy is a matter of debate. Studies from the USA and Sweden suggest no relationship between BP and internal malignancy.2,3 However, contradictory findings have been reported from other countries, especially in Asia. For example, in a Japanese report, patients with BP had a higher incidence of malignancy than controls without BP (5.8% vs. 0.61%, respectively).4 Furthermore, a high incidence of malignancy was associated with BP in both a Chinese (5.8%) and a Taiwanese report (15.1%).5,6 Cancer of the digestive organs was the most frequently
1. Yancey KB, Egan CA. Pemphigoid: clinical, histologic, immunopathologic, and therapeutic considerations. J Am Med Assoc 2000;284(3):350–6. 2. Lindelof B, Islam N, Eklund G, Arfors L. Pemphigoid and cancer. Arch Dermatol 1990;126(1):66–8. 3. Stone SP, Schroeter AL. Bullous pemphigoid and associated malignant neoplasms. Arch Dermatol 1975;111(8):991–4. 4. Ogawa H, Sakuma M, Morioka S, Kitamura K, Sasai Y, Imamura S, et al. The incidence of internal malignancies in pemphigus and bullous pemphigoid in Japan. J Dermatol Sci 1995;9(2):136–41. 5. Jin P, Shao C, Ye G. Chronic bullous dermatoses in China. Int J Dermatol 1993;32(2):89–92. 6. Chang YT, Liu HN, Wong CK. Bullous pemphigoid – a report of 86 cases from Taiwan. Clin Exp Dermatol 1996;21(1):20–2.
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K. Noguchi et al. / International Journal of Surgery Case Reports 5 (2014) 212–214
7. Parikka M, Kainulainen T, Tasanen K, Bruckner-Tuderman L, Salo T. Altered expression of collagen XVII in ameloblastomas and basal cell carcinomas. J Oral Pathol Med 2001;30(10):589–95. 8. Franzke CW, Has C, Schulte C, Huilaja L, Tasanen K, Aumailley M, et al. C-terminal truncation impairs glycosylation of transmembrane collagen XVII and leads to intracellular accumulation. J Biol Chem 2006;281(40):30260–8. 9. Umekoji A, Tsuruta D, Inoue T, Nishimori T, Ishii M. Bullous pemphigoid as a dermadrome associated with spindle cell carcinoma of the gallbladder. J Dermatol 2010;37(3):251–4. 10. Graham-Brown RA. Bullous pemphigoid with figurate erythema associated with carcinoma of the bronchus. Br J Dermatol 1987;117(3):385–8. 11. Gilmour E, Bhushan M, Griffiths CE. Figurate erythema with bullous pemphigoid: a true paraneoplastic phenomenon? Clin Exp Dermatol 1999;24(6): 446–8.
12. Anhalt GJ, Kim SC, Stanley JR, Korman NJ, Jabs DA, Kory M, et al. Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 1990;323(25):1729–35. 13. Takeuchi M, Okazaki A, Nakajima N, Saito Y, Nozaki M, Niibe H. A case of lung cancer with bullous pemphigoid. Gan No Rinsho 1986;32(5):529–33. 14. Krunic AL, Kokai D, Bacetic B, Kesic V, Nikolic MM, Petkovic S, et al. Retroperitoneal round-cell liposarcoma associated with paraneoplastic pemphigus presenting as lichen planus pemphigoides-like eruption. Int J Dermatol 1997;36(7):526–9. 15. Cakmak O, Seckin D, Ceken I, Yilmaz I, Akkuzu B, Ozluoglu L. Bullous pemphigoid associated with parotid carcinoma. Otolaryngol Head Neck Surg 2002;127(4):354–6. 16. Iuliano L, Micheletta F, Natoli S. Bullous pemphigoid: an unusual and insidious presentation of breast cancer. Clin Oncol (R Coll Radiol) 2003;15(8):505.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
