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Laryngeal epidermolysis bullosa acquisita requiring tracheostomy presenting with an acquired factor VIII coagulopathy
CASE REPORTS JEFFREY M. BUMPOUS, MD Case Report Editor
Laryngeal epidermolysis bullosa acquisita requiring tracheostomy presenting with an acquired factor VIII coagulopathy DAN HURLEY, MD, FACS, JAMES H. BOYD, MD, and CHARLES EBY, MD, St Louis, Missouri
A
patient with an acquired factor VIII inhibitor in conjunction with epidermolysis bullosa acquisita (EBA) of the larynx requiring a tracheostomy for airway control is presented. Coincidental occurrence of these rare autoimmune disorders has not previously been reported. CASE PRESENTATION A 60-year-old female presented with an iliopsoas hematoma as well as vesicles on her pretibial regions and soft palate, with intermittent hoarseness. She was diagnosed with an acquired neutralizing autoantibody against factor VIII. After 4 months of immunosuppression, the factor VIII inhibitor began to remit. On tapering of the treatment, the oral blistering and hoarseness worsened prompting an otolaryngology evaluation. Examination showed blistering and ulceration of the oral cavity and larynx with airway restriction. Biopsy results of the skin vesicles were consistent with EBA. On a follow-up visit, she was noted to have near complete obstruction of her airway, and underwent a tracheotomy. Oral blistering decreased dramatically after 24 months of immunosuppression therapy and the titer of serum antibodies to the dermal side of human salt split skin steadily
From the Departments of Otolaryngology–Head and Neck Surgery (Drs Boyd and Hurley), and Hematology-Oncology (Dr Eby), Saint Louis University Hospital. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, San Antonio, TX, September 13-16, 1998, as a poster presentation. Reprint requests: James H. Boyd, MD, FACS, Department of Otolaryngology–Head and Neck Surgery, St Louis University Hospital, 3635 Vista at Grand Blvd. St Louis, MO. 63110. Otolaryngol Head Neck Surg 2001;125:270-1. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/4/116791 doi:10.1067/mhn.2001.116791 270
declined becoming undetectable at 27 months. Palatal mucosal biopsy results were obtained at 30 months and direct immunoflourescence staining was positive for IgG and complement along the basal lamina indicating that the patient is not in histologic remission. Current plans are to continue oral Cytoxan and periodically obtain mucosal biopsy specimens for immunofluorescent staining. When a histologic remission is obtained, operative release of laryngeal scarring (Fig 1) with subsequent decannulation is planned. DISCUSSION
EBA is a noninherited autoimmune disorder that is distinguished from the other varieties of epidermolysis bullosa by its lack of inheritability and its spontaneous onset later in life. The diagnosis of EBA was based on history and examination until the development of immunofluorescence methods that detect IgG were able to show antibodies and complement binding to the dermal side of split skin beneath the basal lamina. These patients may also have circulating autoantibodies against the EBA antigens: 290 and 145 kd glycoproteins that are identical to the globular regions of type VII procollagen.1 Symptoms of EBA typically include extreme skin fragility over joints and extensor surfaces. Oral mucosal involvement is present in 50% of patients. Head and neck manifestations include oral ulcers, esophageal stricture, and laryngeal involvement.1,2 This case shows severe involvement of the oral cavity and larynx with less severe involvement of the skin. In our experience, the laryngeal involvement does not extend below the cricoid despite mucosal irritation caused by the tracheostomy. The time course of EBA is unclear, however, symptoms can persist for years. Acquired coagulopathy secondary to autoantibodies against factor VIII is also a rare disorder with an incidence of 0.2 to 1 per million.3 Acquired factor VIII inhibitors often present with severe spontaneous bleed-
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ing that can be life threatening. The treatment with immunosuppression is frequently effective; however, remission can take months and the mortality rate approaches 30%.3 Because both of these diseases are autoimmune phenomena, it is possible that they share a common cause that is not yet defined. Although this combination has never been reported, there have been previous reports of acquired factor VIII inhibitors in association with other autoimmune dermatologic disorders such as bullous dermatitis4 and pemphigus vulgaris.5 REFERENCES 1. Clement M, Ratnesar P, Thirumoorthy T, et al. Epidermolysis bullosa acquisita: a case with upper airway obstruction requiring tracheostomy and responding to cyclosporine. Clin Exp Dermatol 1993;18:548-51. 2. Ramadass J, Thenhauelu T. Epidermolysis bullosa and its ENT manifestations. J Laryngol Otol 1978;92:441-6. 3. Kessler C, Garvey M, et al. Acquired hemophilia, 2nd ed. Excerpta Medica 1995;1-8:91-112. 4. Cooke J, Anderson J, Gamble W. Circulating factor VIII anticoagulant in bullous dermatitis. Arch Intern Med 1962;110: 511-5. 5. Ishikawa O, Tamura A, et al. Pemphigus vulgaris associated with acquired hemophilia A due to factor VIII inhibitor. Acta Derm Venereol 1993;73:229-30.
Fig 1. Photo shows the restriction of airway by laryngeal scarring as well as fixation of arytenoids to each other.
Laryngeal epidermolysis bullosa acquisita requiring tracheostomy presenting with an acquired factor VIII coagulopathy DAN HURLEY, MD, FACS, JAMES H. BOYD, MD, and CHARLES EBY, MD, St Louis, Missouri
A
patient with an acquired factor VIII inhibitor in conjunction with epidermolysis bullosa acquisita (EBA) of the larynx requiring a tracheostomy for airway control is presented. Coincidental occurrence of these rare autoimmune disorders has not previously been reported. CASE PRESENTATION A 60-year-old female presented with an iliopsoas hematoma as well as vesicles on her pretibial regions and soft palate, with intermittent hoarseness. She was diagnosed with an acquired neutralizing autoantibody against factor VIII. After 4 months of immunosuppression, the factor VIII inhibitor began to remit. On tapering of the treatment, the oral blistering and hoarseness worsened prompting an otolaryngology evaluation. Examination showed blistering and ulceration of the oral cavity and larynx with airway restriction. Biopsy results of the skin vesicles were consistent with EBA. On a follow-up visit, she was noted to have near complete obstruction of her airway, and underwent a tracheotomy. Oral blistering decreased dramatically after 24 months of immunosuppression therapy and the titer of serum antibodies to the dermal side of human salt split skin steadily
From the Departments of Otolaryngology–Head and Neck Surgery (Drs Boyd and Hurley), and Hematology-Oncology (Dr Eby), Saint Louis University Hospital. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, San Antonio, TX, September 13-16, 1998, as a poster presentation. Reprint requests: James H. Boyd, MD, FACS, Department of Otolaryngology–Head and Neck Surgery, St Louis University Hospital, 3635 Vista at Grand Blvd. St Louis, MO. 63110. Otolaryngol Head Neck Surg 2001;125:270-1. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/4/116791 doi:10.1067/mhn.2001.116791 270
declined becoming undetectable at 27 months. Palatal mucosal biopsy results were obtained at 30 months and direct immunoflourescence staining was positive for IgG and complement along the basal lamina indicating that the patient is not in histologic remission. Current plans are to continue oral Cytoxan and periodically obtain mucosal biopsy specimens for immunofluorescent staining. When a histologic remission is obtained, operative release of laryngeal scarring (Fig 1) with subsequent decannulation is planned. DISCUSSION
EBA is a noninherited autoimmune disorder that is distinguished from the other varieties of epidermolysis bullosa by its lack of inheritability and its spontaneous onset later in life. The diagnosis of EBA was based on history and examination until the development of immunofluorescence methods that detect IgG were able to show antibodies and complement binding to the dermal side of split skin beneath the basal lamina. These patients may also have circulating autoantibodies against the EBA antigens: 290 and 145 kd glycoproteins that are identical to the globular regions of type VII procollagen.1 Symptoms of EBA typically include extreme skin fragility over joints and extensor surfaces. Oral mucosal involvement is present in 50% of patients. Head and neck manifestations include oral ulcers, esophageal stricture, and laryngeal involvement.1,2 This case shows severe involvement of the oral cavity and larynx with less severe involvement of the skin. In our experience, the laryngeal involvement does not extend below the cricoid despite mucosal irritation caused by the tracheostomy. The time course of EBA is unclear, however, symptoms can persist for years. Acquired coagulopathy secondary to autoantibodies against factor VIII is also a rare disorder with an incidence of 0.2 to 1 per million.3 Acquired factor VIII inhibitors often present with severe spontaneous bleed-
Otolaryngology– Head and Neck Surgery Volume 125 Number 3
HURLEY et al
271
ing that can be life threatening. The treatment with immunosuppression is frequently effective; however, remission can take months and the mortality rate approaches 30%.3 Because both of these diseases are autoimmune phenomena, it is possible that they share a common cause that is not yet defined. Although this combination has never been reported, there have been previous reports of acquired factor VIII inhibitors in association with other autoimmune dermatologic disorders such as bullous dermatitis4 and pemphigus vulgaris.5 REFERENCES 1. Clement M, Ratnesar P, Thirumoorthy T, et al. Epidermolysis bullosa acquisita: a case with upper airway obstruction requiring tracheostomy and responding to cyclosporine. Clin Exp Dermatol 1993;18:548-51. 2. Ramadass J, Thenhauelu T. Epidermolysis bullosa and its ENT manifestations. J Laryngol Otol 1978;92:441-6. 3. Kessler C, Garvey M, et al. Acquired hemophilia, 2nd ed. Excerpta Medica 1995;1-8:91-112. 4. Cooke J, Anderson J, Gamble W. Circulating factor VIII anticoagulant in bullous dermatitis. Arch Intern Med 1962;110: 511-5. 5. Ishikawa O, Tamura A, et al. Pemphigus vulgaris associated with acquired hemophilia A due to factor VIII inhibitor. Acta Derm Venereol 1993;73:229-30.
Fig 1. Photo shows the restriction of airway by laryngeal scarring as well as fixation of arytenoids to each other.