CASE REPORT Clinical and serological responses following plasmapheresis in bullous pemphigoid: two case reports and a review of the literature Brian Chang, Ashok Tholpady, Richard S.P. Huang, Elena Nedelcu, Yu Bai Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America
Case reports
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Plasmapheresis has been proven to be an effective treatment for a variety of conditions, especially those in which circulating antibodies are known or thought to be involved in pathogenesis. The current American Society For Apheresis (ASFA) guidelines1 make recommendations on 120 specific indications encompassing a total of 68 distinct disease processes. Among the autoimmune blistering disorders of the skin, pemphigus vulgaris is the sole entity included and plasmapheresis is considered a category IV indication (disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful). In pemphigus vulgaris auto-antibodies are directed against the adhesion molecule desmoglein2, whereas in a related entity known as bullous pemphigoid (BP) auto-antibodies are targeted against the hemidesmosome components BP1803 and BP2304. Although no formal recommendation exists for BP, plasmapheresis has been deployed successfully as adjunctive therapy5-8. In describing our own institution's recent experience in treating BP we add to the growing evidence supporting the use of plasmapheresis under appropriate conditions. We also include an examination of serial BP180 and BP230 titres measured by enzyme-linked immunosorbent assay (ELISA) during plasmapheresis therapy.
The younger patient, herein referred to as Patient Two, was a 23-year old Asian-American male with no significant medical history. He was definitively diagnosed with BP only after admission and inpatient evaluation by a consultant dermatologist. A skin biopsy and direct immunofluorescence testing were also performed. Three weeks previously he had presented to a primary care clinic with a localised erythematous rash and was treated with just oral antihistamines and a topical steroid cream. After rapid and continued spread of the rash along with the eruption of numerous blisters and bullae, Patient Two also presented to our institution for urgent management. Each patient underwent a series of five plasmapheresis procedures each exchanging approximately one plasma volume using a COBE Spectra Apheresis System (centrifuge-based technology) with 5% albumin replacement fluid. For each litre of plasma processed, one gram of 10% calcium gluconate was administered as prophylaxis against hypocalcaemia. Haemoglobin concentrations, platelet counts, and coagulation levels were checked on the day of each procedure and most procedures followed an every other day schedule. Serum samples collected 30 minutes after plasmapheresis were sent for commercial BP180 and BP230 ELISA testing (Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA). Overall, there were six samples from Patient One: a pre-treatment sample and five post-procedure samples. For Patient Two there was only a pre-treatment sample and one post-treatment sample collected at the end of the fifth plasmapheresis. The titres are reported as units per millilitre (U/mL).
rv
Introduction
In March of 2012, two consecutive patients with BP were admitted to, treated in, and discharged from our institution. The older patient, herein referred to as Patient One, was a 36-year old AfricanAmerican male with a medical history of human immunodeficiency virus (HIV) infection treated with highly active anti-retroviral therapy (HAART). He was diagnosed with BP by a dermatologist about 2 months prior to hospitalisation. His workup at the time included a skin biopsy and direct immunofluorescence testing. He then immediately began treatment with 60 mg/day of oral prednisone but due to progressively worsening symptoms over the following 2 months he was eventually admitted for higher level of care.
Results Clinical response In terms of symptomatology, Patient One had more severe disease with diffuse, tense bullae, erosions, crusts, and erythema involving approximately 75% of the total body surface area at admission. The mucous membranes were also involved. Patient One's positive HIV status placed him at greater risk of opportunistic infections. His maximum dose of prednisone was, therefore, limited to approximately 1 mg/kg/day, which was an increase
Blood Transfus 2014; 12: 269-75 DOI 10.2450/2014.0222-13 © SIMTI Servizi Srl
269 All rights reserved - For personal use only No other uses without permission
Chang B et al
formation was ever reported by the patient or documented by the clinicians. As in Patient One, the overall clinical improvement after plasmapheresis was an approximately 50% reduction in blisters and erythema distribution. All procedures were tolerated well and without complications in either patient.
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Serological response Just prior to his first plasmapheresis Patient One had an elevated BP180 titre of 218 U/mL (reference range ≤14 U/ mL). Conversely, his BP230 titre was not increased (reference range
Case reports
©
SI M
Sr l
iz i
TI
Se
Plasmapheresis has been proven to be an effective treatment for a variety of conditions, especially those in which circulating antibodies are known or thought to be involved in pathogenesis. The current American Society For Apheresis (ASFA) guidelines1 make recommendations on 120 specific indications encompassing a total of 68 distinct disease processes. Among the autoimmune blistering disorders of the skin, pemphigus vulgaris is the sole entity included and plasmapheresis is considered a category IV indication (disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful). In pemphigus vulgaris auto-antibodies are directed against the adhesion molecule desmoglein2, whereas in a related entity known as bullous pemphigoid (BP) auto-antibodies are targeted against the hemidesmosome components BP1803 and BP2304. Although no formal recommendation exists for BP, plasmapheresis has been deployed successfully as adjunctive therapy5-8. In describing our own institution's recent experience in treating BP we add to the growing evidence supporting the use of plasmapheresis under appropriate conditions. We also include an examination of serial BP180 and BP230 titres measured by enzyme-linked immunosorbent assay (ELISA) during plasmapheresis therapy.
The younger patient, herein referred to as Patient Two, was a 23-year old Asian-American male with no significant medical history. He was definitively diagnosed with BP only after admission and inpatient evaluation by a consultant dermatologist. A skin biopsy and direct immunofluorescence testing were also performed. Three weeks previously he had presented to a primary care clinic with a localised erythematous rash and was treated with just oral antihistamines and a topical steroid cream. After rapid and continued spread of the rash along with the eruption of numerous blisters and bullae, Patient Two also presented to our institution for urgent management. Each patient underwent a series of five plasmapheresis procedures each exchanging approximately one plasma volume using a COBE Spectra Apheresis System (centrifuge-based technology) with 5% albumin replacement fluid. For each litre of plasma processed, one gram of 10% calcium gluconate was administered as prophylaxis against hypocalcaemia. Haemoglobin concentrations, platelet counts, and coagulation levels were checked on the day of each procedure and most procedures followed an every other day schedule. Serum samples collected 30 minutes after plasmapheresis were sent for commercial BP180 and BP230 ELISA testing (Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA). Overall, there were six samples from Patient One: a pre-treatment sample and five post-procedure samples. For Patient Two there was only a pre-treatment sample and one post-treatment sample collected at the end of the fifth plasmapheresis. The titres are reported as units per millilitre (U/mL).
rv
Introduction
In March of 2012, two consecutive patients with BP were admitted to, treated in, and discharged from our institution. The older patient, herein referred to as Patient One, was a 36-year old AfricanAmerican male with a medical history of human immunodeficiency virus (HIV) infection treated with highly active anti-retroviral therapy (HAART). He was diagnosed with BP by a dermatologist about 2 months prior to hospitalisation. His workup at the time included a skin biopsy and direct immunofluorescence testing. He then immediately began treatment with 60 mg/day of oral prednisone but due to progressively worsening symptoms over the following 2 months he was eventually admitted for higher level of care.
Results Clinical response In terms of symptomatology, Patient One had more severe disease with diffuse, tense bullae, erosions, crusts, and erythema involving approximately 75% of the total body surface area at admission. The mucous membranes were also involved. Patient One's positive HIV status placed him at greater risk of opportunistic infections. His maximum dose of prednisone was, therefore, limited to approximately 1 mg/kg/day, which was an increase
Blood Transfus 2014; 12: 269-75 DOI 10.2450/2014.0222-13 © SIMTI Servizi Srl
269 All rights reserved - For personal use only No other uses without permission
Chang B et al
formation was ever reported by the patient or documented by the clinicians. As in Patient One, the overall clinical improvement after plasmapheresis was an approximately 50% reduction in blisters and erythema distribution. All procedures were tolerated well and without complications in either patient.
iz i
Sr l
Serological response Just prior to his first plasmapheresis Patient One had an elevated BP180 titre of 218 U/mL (reference range ≤14 U/ mL). Conversely, his BP230 titre was not increased (reference range
