546865 research-articleXXXX
FASXXX10.1177/1938640014546865Foot & Ankle SpecialistFoot & Ankle Specialist
vol. XX / no. X
Foot & Ankle Specialist
〈 Case Report 〉 Bullous Pemphigoid After Bilateral Forefoot Surgery Abstract: The case of a 76-yearold woman who developed blisters on both forefeet within 2 weeks of bilateral forefoot surgery is reported; the diagnosis of bullous pemphigoid was made by histological and immunofluorescence studies. The pathogenesis and management of this autoimmune condition, which occurs mainly in patients older than 70 years and may occasionally be associated with surgical wounds, are reviewed. It is important for foot and ankle specialists to be aware of and consider the diagnosis when a bullous contact dermatitis-like eruption persists at a surgical site. Level of Evidence: Therapeutic Level IV: Case report Keywords: bullae; vesicles; bullous pemphigoid; surgical site; postoperative wound; bilateral forefoot surgery
A
classic vesicular lesion consists of a thin bubble of fluid under the skin; vesicles larger than 1 cm in diameter are termed bullae. The development of vesicles or bullae within days of surgery is usually thought to be due to an infection, friction, trauma or contact allergy.1-3 A red and hot surrounding area suggests a bacterial
Dishan Singh, MBChB, FRCS(Orth) and Amanda Swann, BSc, MSc
infection especially if the vesicles are in adults older than 70 years and is filled with pus (pustules) whilst viral associated with significant morbidity. diseases such as herpes simplex or With our aging population, bullous pemphigoid will increasingly be shingles may present occasionally.1 A encountered by foot and ankle surgeons. friction or tension blister occurs from separation of the epidermis from the dermis, caused by shear forces under an Case Presentation unyielding adhesive tape or dressing A 76-year-old woman presented with either because of inappropriate tight bilateral hallux valgus and overriding application or when a joint or other area second toes, having previously of movement is covered by an undergone a right first metatarsal unyielding dressing.3 Two types of fracture blisters have been identified: osteotomy and proximal clear fluid filled and blood filled. The hemiphalangectomy of the right second clear fluid–filled blisters demonstrate toe a year previously at another partial epidermal separation of the hospital—unfortunately, she had epidermis from the underlying dermis whereas blood-filled With our aging population, bullous blisters have been shown histologically to pemphigoid will increasingly be have complete separation of the dermis encountered by foot and ankle from the epidermis and surgeons.” eventual necrosis of the epidermis often ensues.3 Acute allergic contact dermatitis is characterized by pruritic developed a recurrence soon afterward. papules and vesicles on an erythematous She suffered from chronic asthma with a base which typically develop within a past history of having been on steroids. few days of exposure, in areas that had She was on oral Phyllocontin and been exposed directly to the allergen inhalers. She had no known allergies to (eg, antiseptic solution).4 medication or metallic substances and she did not smoke. We report a case where large bullae On examination, she was found to were due to the autoimmune disease bullous pemphigoid, which is common have a recurrent hallux valgus on the
“
DOI: 10.1177/1938640014546865. From the Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. Address correspondence to: Dishan Singh, MBChB, FRCS(Orth), Consultant Orthopaedic Surgeon, Foot and Ankle Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK; e-mail: [email protected]. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2014 The Author(s)
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
1
2
Mon XXXX
Foot & Ankle Specialist
right and a marked hallux valgus on the left. She bilaterally had evidence of overriding second toes with tight extensors and she had had a hemiphalangectomy on the right. She had normal pulse and sensation. She had some crepitus in the great toe metatarsophalangeal joints and the right second metatarsophalangeal joint demonstrated an irreducible dorsal dislocation. Radiographs of the right foot showed a recurrent hallux valgus with a screw in the first distal metatarsal and evidence of a previous proximal hemiphalangectomy of the second toe. Radiographs of the left foot revealed a hallux valgus associated with degenerative changes in the great toe metatarsophalangeal joint and a dislocated second toe metatarsophalangeal joint. She was counselled for and subsequently underwent bilateral great toe metatarsophalangeal joint fusions as well as soft tissue corrections of the second metatarsophalangeal joints and a proximal interphalangeal joint fusion of the left second toe in September 2012. One dose of prophylactic cefuroxime (Zinacef) was administered and she underwent her bilateral operations under a general anesthesia and thigh tourniquets. Povidone iodine was used for skin preparation. Two stainless steel screws were used to fix the great toe fusions and stainless steel Kirschner wires (k-wires) were used to transfix the second toes. The skin was closed with subcutaneous vicryl (polyglycolic acid, Vicryl) and interrupted nylon stitches. She was prescribed paracetamol, codeine and the antiinflammatory ibuprofen (Brufen, Advil) postoperatively. She was reviewed 13 days postoperative when she complained of mild pain and mild itchiness in her feet. She had developed blisters at the site of the surgery (Figure 1). No ascending lymphangitis was present, she had no lymphadenopathy, and was apyrexial. She was prescribed Flucloxacillin (floxacillin) 500 mg 4 times a day for 7 days. The sutures were removed and at the 3-week review the forefoot redness had reduced but new blisters were present on the lateral part of the feet. A
Figure 1. Both feet, 13 days after bilateral great toe metarsophalangeal fusions and second toe correction. The skin is erythematous and tense; bullae are present near the incision sites but not confined to the incision sites bilaterally.
dermatology consultation was arranged and the k-wires were removed 4 weeks postoperatively by which time she was starting to develop bullae over her thighs and back. The dermatologist saw her 30 days postoperatively and made a clinical diagnosis of bullous pemphigoid, which was subsequently confirmed on skin biopsy. She was started on 80-mg prednisolone daily and an antihistamine. At the 6-week review (Figures 2 and 3), new crops of blisters had appeared centrally but the foot blisters had turned into noninfected erosions with some crusting. Her great toe metatarsophalangeal joint showed evidence of fusion 8 weeks postoperatively and she was asked to discard her postoperative wedge shoes. At the 12-week follow-up (Figure 4), her feet had a reddish brown pigmentation which was more marked at the sites of previous blister formation; she was mobilizing comfortably with athletic shoes and her itchiness had settled. She was discharged but was contacted again at 18-months postoperative for a review. She had 2 recurrences of mild bullous pemphigoid on her thighs and her prednisolone dose had been tailed
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
off to 5 mg daily. The skin on her feet had returned to normal (Figure 5).
Discussion Bullous pemphigoid is an acquired autoimmune disease in which antibodies are directed against components of the basement membrane zone of skin, resulting in crops of itchy, tense, subepidermal vesicles or bullae filled with clear or occasionally blood-stained fluid.5-9 The vesicles may arise from normal-looking or inflamed skin, and may be localized to one area or be widespread over the trunk and limbs. The disease may be acute, but bullous pemphigoid is typically a chronic disease characterized by periods of exacerbation and partial remission.5,9 It typically but not exclusively occurs in people 70 years and older.8,9 The estimated incidence is 7 to 14 cases per million per year; however, the annual incidence is increasing—possibly because of an aging population.6,9 The mortality in patients with bullous pemphigoid is twice that of the general population, either because of complications of the disease itself (infection leading to generalized sepsis,
vol. XX / no. X
Foot & Ankle Specialist
Figure 2. At 6 weeks postoperatively, the Kirschner wires have been removed. New bullae have appeared whilst erosions are crusting over at the sites of the old crop. The incision sites themselves are healing.
for example) or because of the side effects of steroids used in its treatment.8 In most cases of bullous pemphigoid, no clear precipitating factor can be identified. Potential precipitating events that have been reported include exposure to ultraviolet light, radiation therapy, and certain drugs.7,8 Bullous pemphigoid is thought to occur because of an autoimmune attack on components of the basement membrane (particularly a protein known as the BP [bullous pemphigoid] antigen, also called type XVII collagen), which are associated with the hemidesmosomes—structures that ensure the epidermal keratinocyte cells stick to the dermis to make a waterproof seal.9 Following antibody targeting, an influx of inflammatory cells, activated T
lymphocytes, eosinophils, and IgG immunoglobulins leads to proteases attacking the hemidesmosomes leading to a separation along the dermoepidermal junction. The resulting subepidermal bulla has a full thickness of the epidermis as its roof, is relatively resilient to bursting and becomes tense and large. This is in contrast to another immunobullous disease, pemphigus vulgaris, where flaccid intraepidermal bullae develop, which are fragile and can easily rupture. Clinically, the earliest lesions may appear urticarial (like hives). Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently also
involved.5,7-9 Lesions can be found on erythematous or normal-looking skin. Over time, the tense blisters can become hemorrhagic and/or eventually burst, leaving behind erosions that will crust over. Lesions can easily become secondarily infected. When the blisters heal up, they may leave brown marks (postinflammatory pigmentation), which usually disappear within a few months. 9 A dermatologist can often make the diagnosis by examining the skin carefully and can confirm the diagnosis by a punch biopsy of a typical intact blister. The histopathologic examination demonstrates a subepidermal blister with a polymorphous inflammatory infiltrate with an eosinophil predominance. Direct immunofluorescence staining highlights antibodies along the basement membrane that lies between the epidermis and dermis.9 The morbidity caused by bullous pemphigoid should not be underestimated; the widespread bullous lesions are time consuming to manage, may cause itchiness which disturbs sleep and have the potential to cause localised or generalised sepsis.5,7,10,11 The goal of therapy in bullous pemphigoid is to decrease blister formation, promote healing of blisters, and determine the minimal dose of medication necessary to control the disease process.5 Treatment does not have to be delayed for investigations to be performed. The most commonly used medications for bullous pemphigoid are antiinflammatory agents and immunesuppressants.5,10 Systemic corticosteroids are the best established treatment. Recommended initial doses of prednisolone are 20 mg daily in localized or mild disease, 40 mg daily in moderate disease and 50 to 70 mg daily in severe disease.10 The dose is adjusted until the blisters have stopped appearing, which usually takes several weeks. As systemic steroids have many undesirable side effects, other medications are often added to ensure the lowest possible dose.10 For localized disease, very potent topical corticosteroids are worth trying
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
3
4
Mon XXXX
Foot & Ankle Specialist
Figure 3. At 6 weeks postoperatively, new tense dome-shaped vesicles are appearing over the trunks and thighs.
Figure 4. At 12 weeks postoperatively, areas of reddish brown postinflammatory pigmentation are seen in both feet.
first if practical (not suitable in wounds for example). Immunosuppressants are not recommended routinely from the outset but should only be considered if the corticosteroid dose cannot be reduced to an acceptable level.8,10 Most patients affected with bullous pemphigoid require a slowly reducing
dose of medication for 6 to 60 months, after which many patients experience long-term remission of the disease. Although bullous pemphigoid bas been reported in association with a variety of internal malignancies, this may just be coincidental, merely reflecting the age incidence of these 2
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
diseases. Bullous pemphigoid flare or presentation in surgically treated skin is a phenomenon that has infrequently been reported in the literature and has previously been associated with various surgical procedures, colostomy sites, venous access sites, and amputation stumps.2,12-15 It has not been established whether the association is incidental or causal. In some cases, lesions have shown a predilection for, or localized solely to, sites of recent dermatologic trauma; this may controversially represent a form of “koebnerization”. The Koebner or isomorphic phenomenon is the development of novel skin lesions at the sites of trauma in patients suffering from pre-existing dermatoses and it is best documented in psoriasis.8 It has been suggested that surgical trauma to the skin may unmask the BP antigen and result in the development of localized bullae. Although the case reported here is a single case report, it represents the best evidence available that a bullous pemphigoid flare can start in surgically manipulated skin as the bullae developed simultaneously both within the scar and the adjacent skin of both forefeet within 2 weeks after bilateral forefoot surgery before the bullae became more generalized. With hindsight, features of bullous pemphigoid that differentiate this disease from other conditions were present: itchiness, tense bullae, and a distribution that involved both suture areas and nonsuture areas but not the whole area of skin preparation with antiseptic. It is possible that an earlier referral to a dermatologist may have led to earlier resolution of the disease. This case reminds us that the cause of postoperative local blistering may not be straightforward.
Summary The occurrence of bullous pemphigoid after surgery may be a merely coincident event, especially when one considers other possible triggers such as perioperative drug administration. However, our case report where bullous pemphigoid bullae occurred
vol. XX / no. X
Foot & Ankle Specialist
Figure 5. At 18 months, she had well-healed scars and otherwise normal-looking skin.
4. Lachapelle JM. A comparison of the irritant and allergenic properties of antiseptics. Eur J Dermatol. 2014;24:3-9. 5. Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP. Guidelines for the management of bullous pemphigoid. Br J Dermatol. 2002;147:214-221. 6. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180. 7. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet 1999; 354(9179), 667-672. 8. Ruocco E, Wolf R, Caccavale S, Brancaccio G, Ruocco V, Lo Schiavo A. Bullous pemphigoid: associations and management guidelines: facts and controversies. Clin Dermatol. 2013;31:400-412. 9. Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin. 2011;29:427-438. 10. Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):CD002292.
simultaneously in both feet within 2 weeks of bilateral forefoot surgery suggests that surgical trauma may have a causal effect. The localized eruptions can develop into a debilitating pruritic generalized eruption within weeks if no treatment is provided. Therefore, a dermatology consult for clinical and histopathological assessment should be sought as soon as possible in a patient with postoperative tense bullae, particularly if eruptions start to appear outside the area of surgery.
References 1. Nichols RL, Florman S. Clinical presentations of soft-tissue infections and surgical site infections. Clin Infect Dis. 2001;33 (suppl 2): S84-S93. 2. Massa MC, Freeark RJ, Kang JS. Localized bullous pemphigoid occurring in a surgical wound. Dermatol Nurs. 1996;8:101-103. 3. Polatsch DB, Baskies MA, Hommen JP, Egol KA, Koval KJ. Tape blisters that develop after hip fracture surgery: a retrospective series and a review of the literature. Am J Orthop (Belle Mead NJ). 2004;33:452-456.
11. Murrell DF, Daniel BS, Joly P, et al. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 2012;66:479-485. 12. Macfarlane AW, Verbov JL. Traumainduced bullous pemphigoid. Clin Exp Dermatol. 1989;14:245-249. 13. Anderson CK, Mowad CM, Goff ME, Pelle MT. Bullous pemphigoid arising in surgical wounds. Br J Dermatol. 2001;145:670-672. 14. Neville JA, Yosipovitch G. Flare of bullous pemphigoid in surgically treated skin. Cutis. 2005;75:169-170. 15. Orvis AK, Ihnatsenka V, Hatch RL. Bullous lesions on a skin graft donor site. J Am Board Fam Med. 2009;22:89-92.
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
5
FASXXX10.1177/1938640014546865Foot & Ankle SpecialistFoot & Ankle Specialist
vol. XX / no. X
Foot & Ankle Specialist
〈 Case Report 〉 Bullous Pemphigoid After Bilateral Forefoot Surgery Abstract: The case of a 76-yearold woman who developed blisters on both forefeet within 2 weeks of bilateral forefoot surgery is reported; the diagnosis of bullous pemphigoid was made by histological and immunofluorescence studies. The pathogenesis and management of this autoimmune condition, which occurs mainly in patients older than 70 years and may occasionally be associated with surgical wounds, are reviewed. It is important for foot and ankle specialists to be aware of and consider the diagnosis when a bullous contact dermatitis-like eruption persists at a surgical site. Level of Evidence: Therapeutic Level IV: Case report Keywords: bullae; vesicles; bullous pemphigoid; surgical site; postoperative wound; bilateral forefoot surgery
A
classic vesicular lesion consists of a thin bubble of fluid under the skin; vesicles larger than 1 cm in diameter are termed bullae. The development of vesicles or bullae within days of surgery is usually thought to be due to an infection, friction, trauma or contact allergy.1-3 A red and hot surrounding area suggests a bacterial
Dishan Singh, MBChB, FRCS(Orth) and Amanda Swann, BSc, MSc
infection especially if the vesicles are in adults older than 70 years and is filled with pus (pustules) whilst viral associated with significant morbidity. diseases such as herpes simplex or With our aging population, bullous pemphigoid will increasingly be shingles may present occasionally.1 A encountered by foot and ankle surgeons. friction or tension blister occurs from separation of the epidermis from the dermis, caused by shear forces under an Case Presentation unyielding adhesive tape or dressing A 76-year-old woman presented with either because of inappropriate tight bilateral hallux valgus and overriding application or when a joint or other area second toes, having previously of movement is covered by an undergone a right first metatarsal unyielding dressing.3 Two types of fracture blisters have been identified: osteotomy and proximal clear fluid filled and blood filled. The hemiphalangectomy of the right second clear fluid–filled blisters demonstrate toe a year previously at another partial epidermal separation of the hospital—unfortunately, she had epidermis from the underlying dermis whereas blood-filled With our aging population, bullous blisters have been shown histologically to pemphigoid will increasingly be have complete separation of the dermis encountered by foot and ankle from the epidermis and surgeons.” eventual necrosis of the epidermis often ensues.3 Acute allergic contact dermatitis is characterized by pruritic developed a recurrence soon afterward. papules and vesicles on an erythematous She suffered from chronic asthma with a base which typically develop within a past history of having been on steroids. few days of exposure, in areas that had She was on oral Phyllocontin and been exposed directly to the allergen inhalers. She had no known allergies to (eg, antiseptic solution).4 medication or metallic substances and she did not smoke. We report a case where large bullae On examination, she was found to were due to the autoimmune disease bullous pemphigoid, which is common have a recurrent hallux valgus on the
“
DOI: 10.1177/1938640014546865. From the Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. Address correspondence to: Dishan Singh, MBChB, FRCS(Orth), Consultant Orthopaedic Surgeon, Foot and Ankle Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex HA7 4LP, UK; e-mail: [email protected]. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2014 The Author(s)
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
1
2
Mon XXXX
Foot & Ankle Specialist
right and a marked hallux valgus on the left. She bilaterally had evidence of overriding second toes with tight extensors and she had had a hemiphalangectomy on the right. She had normal pulse and sensation. She had some crepitus in the great toe metatarsophalangeal joints and the right second metatarsophalangeal joint demonstrated an irreducible dorsal dislocation. Radiographs of the right foot showed a recurrent hallux valgus with a screw in the first distal metatarsal and evidence of a previous proximal hemiphalangectomy of the second toe. Radiographs of the left foot revealed a hallux valgus associated with degenerative changes in the great toe metatarsophalangeal joint and a dislocated second toe metatarsophalangeal joint. She was counselled for and subsequently underwent bilateral great toe metatarsophalangeal joint fusions as well as soft tissue corrections of the second metatarsophalangeal joints and a proximal interphalangeal joint fusion of the left second toe in September 2012. One dose of prophylactic cefuroxime (Zinacef) was administered and she underwent her bilateral operations under a general anesthesia and thigh tourniquets. Povidone iodine was used for skin preparation. Two stainless steel screws were used to fix the great toe fusions and stainless steel Kirschner wires (k-wires) were used to transfix the second toes. The skin was closed with subcutaneous vicryl (polyglycolic acid, Vicryl) and interrupted nylon stitches. She was prescribed paracetamol, codeine and the antiinflammatory ibuprofen (Brufen, Advil) postoperatively. She was reviewed 13 days postoperative when she complained of mild pain and mild itchiness in her feet. She had developed blisters at the site of the surgery (Figure 1). No ascending lymphangitis was present, she had no lymphadenopathy, and was apyrexial. She was prescribed Flucloxacillin (floxacillin) 500 mg 4 times a day for 7 days. The sutures were removed and at the 3-week review the forefoot redness had reduced but new blisters were present on the lateral part of the feet. A
Figure 1. Both feet, 13 days after bilateral great toe metarsophalangeal fusions and second toe correction. The skin is erythematous and tense; bullae are present near the incision sites but not confined to the incision sites bilaterally.
dermatology consultation was arranged and the k-wires were removed 4 weeks postoperatively by which time she was starting to develop bullae over her thighs and back. The dermatologist saw her 30 days postoperatively and made a clinical diagnosis of bullous pemphigoid, which was subsequently confirmed on skin biopsy. She was started on 80-mg prednisolone daily and an antihistamine. At the 6-week review (Figures 2 and 3), new crops of blisters had appeared centrally but the foot blisters had turned into noninfected erosions with some crusting. Her great toe metatarsophalangeal joint showed evidence of fusion 8 weeks postoperatively and she was asked to discard her postoperative wedge shoes. At the 12-week follow-up (Figure 4), her feet had a reddish brown pigmentation which was more marked at the sites of previous blister formation; she was mobilizing comfortably with athletic shoes and her itchiness had settled. She was discharged but was contacted again at 18-months postoperative for a review. She had 2 recurrences of mild bullous pemphigoid on her thighs and her prednisolone dose had been tailed
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
off to 5 mg daily. The skin on her feet had returned to normal (Figure 5).
Discussion Bullous pemphigoid is an acquired autoimmune disease in which antibodies are directed against components of the basement membrane zone of skin, resulting in crops of itchy, tense, subepidermal vesicles or bullae filled with clear or occasionally blood-stained fluid.5-9 The vesicles may arise from normal-looking or inflamed skin, and may be localized to one area or be widespread over the trunk and limbs. The disease may be acute, but bullous pemphigoid is typically a chronic disease characterized by periods of exacerbation and partial remission.5,9 It typically but not exclusively occurs in people 70 years and older.8,9 The estimated incidence is 7 to 14 cases per million per year; however, the annual incidence is increasing—possibly because of an aging population.6,9 The mortality in patients with bullous pemphigoid is twice that of the general population, either because of complications of the disease itself (infection leading to generalized sepsis,
vol. XX / no. X
Foot & Ankle Specialist
Figure 2. At 6 weeks postoperatively, the Kirschner wires have been removed. New bullae have appeared whilst erosions are crusting over at the sites of the old crop. The incision sites themselves are healing.
for example) or because of the side effects of steroids used in its treatment.8 In most cases of bullous pemphigoid, no clear precipitating factor can be identified. Potential precipitating events that have been reported include exposure to ultraviolet light, radiation therapy, and certain drugs.7,8 Bullous pemphigoid is thought to occur because of an autoimmune attack on components of the basement membrane (particularly a protein known as the BP [bullous pemphigoid] antigen, also called type XVII collagen), which are associated with the hemidesmosomes—structures that ensure the epidermal keratinocyte cells stick to the dermis to make a waterproof seal.9 Following antibody targeting, an influx of inflammatory cells, activated T
lymphocytes, eosinophils, and IgG immunoglobulins leads to proteases attacking the hemidesmosomes leading to a separation along the dermoepidermal junction. The resulting subepidermal bulla has a full thickness of the epidermis as its roof, is relatively resilient to bursting and becomes tense and large. This is in contrast to another immunobullous disease, pemphigus vulgaris, where flaccid intraepidermal bullae develop, which are fragile and can easily rupture. Clinically, the earliest lesions may appear urticarial (like hives). Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently also
involved.5,7-9 Lesions can be found on erythematous or normal-looking skin. Over time, the tense blisters can become hemorrhagic and/or eventually burst, leaving behind erosions that will crust over. Lesions can easily become secondarily infected. When the blisters heal up, they may leave brown marks (postinflammatory pigmentation), which usually disappear within a few months. 9 A dermatologist can often make the diagnosis by examining the skin carefully and can confirm the diagnosis by a punch biopsy of a typical intact blister. The histopathologic examination demonstrates a subepidermal blister with a polymorphous inflammatory infiltrate with an eosinophil predominance. Direct immunofluorescence staining highlights antibodies along the basement membrane that lies between the epidermis and dermis.9 The morbidity caused by bullous pemphigoid should not be underestimated; the widespread bullous lesions are time consuming to manage, may cause itchiness which disturbs sleep and have the potential to cause localised or generalised sepsis.5,7,10,11 The goal of therapy in bullous pemphigoid is to decrease blister formation, promote healing of blisters, and determine the minimal dose of medication necessary to control the disease process.5 Treatment does not have to be delayed for investigations to be performed. The most commonly used medications for bullous pemphigoid are antiinflammatory agents and immunesuppressants.5,10 Systemic corticosteroids are the best established treatment. Recommended initial doses of prednisolone are 20 mg daily in localized or mild disease, 40 mg daily in moderate disease and 50 to 70 mg daily in severe disease.10 The dose is adjusted until the blisters have stopped appearing, which usually takes several weeks. As systemic steroids have many undesirable side effects, other medications are often added to ensure the lowest possible dose.10 For localized disease, very potent topical corticosteroids are worth trying
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
3
4
Mon XXXX
Foot & Ankle Specialist
Figure 3. At 6 weeks postoperatively, new tense dome-shaped vesicles are appearing over the trunks and thighs.
Figure 4. At 12 weeks postoperatively, areas of reddish brown postinflammatory pigmentation are seen in both feet.
first if practical (not suitable in wounds for example). Immunosuppressants are not recommended routinely from the outset but should only be considered if the corticosteroid dose cannot be reduced to an acceptable level.8,10 Most patients affected with bullous pemphigoid require a slowly reducing
dose of medication for 6 to 60 months, after which many patients experience long-term remission of the disease. Although bullous pemphigoid bas been reported in association with a variety of internal malignancies, this may just be coincidental, merely reflecting the age incidence of these 2
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
diseases. Bullous pemphigoid flare or presentation in surgically treated skin is a phenomenon that has infrequently been reported in the literature and has previously been associated with various surgical procedures, colostomy sites, venous access sites, and amputation stumps.2,12-15 It has not been established whether the association is incidental or causal. In some cases, lesions have shown a predilection for, or localized solely to, sites of recent dermatologic trauma; this may controversially represent a form of “koebnerization”. The Koebner or isomorphic phenomenon is the development of novel skin lesions at the sites of trauma in patients suffering from pre-existing dermatoses and it is best documented in psoriasis.8 It has been suggested that surgical trauma to the skin may unmask the BP antigen and result in the development of localized bullae. Although the case reported here is a single case report, it represents the best evidence available that a bullous pemphigoid flare can start in surgically manipulated skin as the bullae developed simultaneously both within the scar and the adjacent skin of both forefeet within 2 weeks after bilateral forefoot surgery before the bullae became more generalized. With hindsight, features of bullous pemphigoid that differentiate this disease from other conditions were present: itchiness, tense bullae, and a distribution that involved both suture areas and nonsuture areas but not the whole area of skin preparation with antiseptic. It is possible that an earlier referral to a dermatologist may have led to earlier resolution of the disease. This case reminds us that the cause of postoperative local blistering may not be straightforward.
Summary The occurrence of bullous pemphigoid after surgery may be a merely coincident event, especially when one considers other possible triggers such as perioperative drug administration. However, our case report where bullous pemphigoid bullae occurred
vol. XX / no. X
Foot & Ankle Specialist
Figure 5. At 18 months, she had well-healed scars and otherwise normal-looking skin.
4. Lachapelle JM. A comparison of the irritant and allergenic properties of antiseptics. Eur J Dermatol. 2014;24:3-9. 5. Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP. Guidelines for the management of bullous pemphigoid. Br J Dermatol. 2002;147:214-221. 6. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180. 7. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet 1999; 354(9179), 667-672. 8. Ruocco E, Wolf R, Caccavale S, Brancaccio G, Ruocco V, Lo Schiavo A. Bullous pemphigoid: associations and management guidelines: facts and controversies. Clin Dermatol. 2013;31:400-412. 9. Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin. 2011;29:427-438. 10. Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for bullous pemphigoid. Cochrane Database Syst Rev. 2010;(10):CD002292.
simultaneously in both feet within 2 weeks of bilateral forefoot surgery suggests that surgical trauma may have a causal effect. The localized eruptions can develop into a debilitating pruritic generalized eruption within weeks if no treatment is provided. Therefore, a dermatology consult for clinical and histopathological assessment should be sought as soon as possible in a patient with postoperative tense bullae, particularly if eruptions start to appear outside the area of surgery.
References 1. Nichols RL, Florman S. Clinical presentations of soft-tissue infections and surgical site infections. Clin Infect Dis. 2001;33 (suppl 2): S84-S93. 2. Massa MC, Freeark RJ, Kang JS. Localized bullous pemphigoid occurring in a surgical wound. Dermatol Nurs. 1996;8:101-103. 3. Polatsch DB, Baskies MA, Hommen JP, Egol KA, Koval KJ. Tape blisters that develop after hip fracture surgery: a retrospective series and a review of the literature. Am J Orthop (Belle Mead NJ). 2004;33:452-456.
11. Murrell DF, Daniel BS, Joly P, et al. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 2012;66:479-485. 12. Macfarlane AW, Verbov JL. Traumainduced bullous pemphigoid. Clin Exp Dermatol. 1989;14:245-249. 13. Anderson CK, Mowad CM, Goff ME, Pelle MT. Bullous pemphigoid arising in surgical wounds. Br J Dermatol. 2001;145:670-672. 14. Neville JA, Yosipovitch G. Flare of bullous pemphigoid in surgically treated skin. Cutis. 2005;75:169-170. 15. Orvis AK, Ihnatsenka V, Hatch RL. Bullous lesions on a skin graft donor site. J Am Board Fam Med. 2009;22:89-92.
Downloaded from fas.sagepub.com at WASHBURN UNIV on January 6, 2015
5
