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Trauma-induced blistering in a patient with lupus erythematosus: Epidermolysis bullosa acquisita or bullous lupus erythematosus?
CONNECTIVE TISSUE DISEASE P1200 Dermatologic symptoms of dermatoyositis do not lead to early detection of ovarian cancer Rodrigo Valdes, MD, New York Downtown Hospital, New York, NY, United States; Giuseppe Del Priore, MD, MPH, New York Downtown Hospital, New York, NY, United States; Jose R Martinez, MD, New York Downtown Hospital, New York, NY, United States Background: Dermatomyositis and polymyositis (DP) are associated with an underlying malignancy. Early cancer diagnosis may be possible. Objective: To determine if dermatologic symptoms can lead to early detection of ovarian cancer (OC), and describe and characterized OC among patient with DP.
P1202 Trauma-induced blistering in a patient with lupus erythematosus: Epidermolysis bullosa acquisita or bullous lupus erythematosus? Alia Sampson Brown, PhD, University of Louisville, Louisville, KY, United States; Carol Kulp-Shorten, MD, University of Louisville, Louisville, KY, United States; Jeffrey Callen, MD, University of Louisville, Louisville, KY, United States Background: Bullous lupus erythematosus (BLE) is a rare manifestation of systemic lupus that is characterized by tense vesicles and bullae which remit without scarring. BLE is a subepidermal blistering disorder caused by antibodies against type VII collagen, making it histologicly and immunologically indistinguishable from epidermolysis bullosa acquisita (EBA). We present a case of a woman with a known history of systemic lupus erythematosus (SLE) who presented with extensive bullous lesions that occurred over areas of minor trauma and resulted in scarring and milia formation.
Conclusions: Despite a high risk for OC, woman with DP were not diagnosed at an earlier stage or lower Ca-125 level. The small sample size limits our power. Additional cases will be ascertained and presented. Current methods for early detection of ovarian carcinoma in DP patients are ineffective. Early OC may ‘‘whisper,’’ but it doesn’t itch.
Observation: A 47-year-old female with longstanding SLE developed widespread, tense bullae. The bullae were concentrated over bony prominences; the grouping was not noted. In addition, healing occurred with scarring, milia, loss of fingernails, and decreased mobility. Initial biopsies from 1998 revealed a subepidermal split with neutrophils, and immunoflourescent studies were negative. A diagnosis of BLE was made, and she was treated with oral dapsone 50 mg daily which resulted in a decrease in the appearance of new bullous lesions. Dapsone was discontinued because of the development of a hypersensitivity syndrome. She was then placed on oral azathioprine 75 mg daily and oral hydroxychloroquine 200 mg twice daily, with varying doses of systemic corticosteroids. She continued to have blisters, and 1 year ago her nephrologist replaced azathioprine with mycophenolate mofetil; the patient correlates her worsening disease with the initiation of this medicine. With no improvement of her bullous lesions, she was recently admitted to the hospital with widespread blistering, lupus nephritis, pneumonitis, and pneumonia. Two punch biopsies were obtained for hemtoxylineeosin staining and direct and indirect immunoflourescent studies were also undertaken, which showed linear deposits of immunoglobulin G along the dermal basement membrane compatible with BLE or EBA. Azathioprine was increased to 150 mg daily based upon an elevated thiopurine methyl transferase level; in addition, hydroxychloroquine 200 mg daily and prednisone 15 mg daily were continued. Conclusions: BLE and EBA are histopathologically and immunologically indistinguishable; both having a subepidermal blister and antibodies to type VII collagen. We present a patient with bullous lesions initially thought to be BLE; however, because of the distribution of the lesions over the ‘‘areas of trauma,’’ the lack of grouping of the lesions, and the resolution with scarring and milia, the diagnosis of EBA is favored.
Commercial support: None identified.
Commercial support: None identified.
Methods: We conducted a case control analysis using all cases identified from PubMed and Google Scholar searches using the following key words: ‘‘dermatomyositis,’’ ‘‘polymyositis,’’ ‘‘ovarian cancer,’’ ‘‘case report,’’ and combinations of those terms; in addition, a manual search of included references was conducted. We only considered cases of DP with ovarian or breast and ovary cancer. Cases identified were abstracted for age, stage, grade, histology, and level of Ca-125. ‘‘Cases’’ were OC diagnosed after DP and were compared to ‘‘controls’’ (OC diagnosed before DP). Results: Forty-two articles were found; 25 were excluded because of concurrent other malignancies or the fact that the articles not readily available. From the remaining 18 articles, 46 patients were identified, including 35 cases and 11 controls. Mean age in the cases was 57.5 years, and for controls was 58 years (P ¼ NS). Only one case was stage I (3.70%). Most cases and controls were in advanced stages (III-IV; 96.3% and 100%, respectively [P ¼ NS]). Time from DP to OC diagnosis was 13.4 months (range, 1-68 mos) versus 15.4 months (range, 1-72 mos) from OC to DP (P ¼ NS). The median time from initial presentation of DP to cancer was 10.5 versus 6 months for controls (P ¼ NS). Ca-125 was 1304 (range, 44-7710) in cases versus 1157 (range, 145-3200) in controls (P ¼ NS). OC was otherwise asymptomatic except for DP and diagnosis by screening test in 54.8% of cases. In control patients, where the initial diagnosis was OC followed by DP, only 30% where asymptomatic for OC (P ¼ NS).
P1201 A phase I clinical trial of topical peptide p144 TGF-beta1 inhibitor in healthy volunteers Belen Sabada, Clinica Universitaria de Navarra, Pamplona, Spain; Belen Ruiz, MD, Hospital Universitario Puerta de Hierro, Madrid, Spain; Juan Ruiz, MD, Digna Biotech, Madrid, Spain; Rau ´ l Insa, MD, PhD, ISDIN, Barcelona, Spain Introduction: P144 is a transforming growth factor-beta 1 (TGFb1) inhibitor peptide. TGFb1 contributes to the excessive production of collagen and other extracellular matrix components. TGFb1 inhibition could be an effective target in different serious diseases with fibrosis development. P144 has shown promising results, through topical application, in an established mice scleroderma model in which skin fibrosis is induced by repeated bleomicyn subcutaneous injections. Methods: The objective of this study is to assess the tolerability, safety, and bioavailability of the peptide 144 TGFb1 inhibitor after topical administration to healthy volunteers through a phase I multicenter, multiple dose, double-blind, placebo-controlled, randomized clinical trial which was conducted in 36 healthy volunteers. The volunteers were randomized to receive active or placebo cream, and distributed into three treatment groups according to the different doses tested for P144: 100, 200, and 300 g/mL of P144 cream. A daily application during 3 weeks was of 1 mL of active or placebo cream onto a controlled surface at the back was used. The tolerability was evaluated by dermatologists (blinded evaluation) based on the Frosch and Kligman visual scale. To evaluate bioavailability, plasma measurements were taken before cream administration and up to 24 hours after.
P1203 A study of systemic scleroderma in the southern region of Brazil: Cutaneous manifestations and clinical and laboratory marker association Hermenio C. Lima, Universidade Federal do Parana, Curitiba, PR, Brazil; Carolina Muller, MD, Universidade Federal do Parana, Curitiba, PR, Brazil; Eduardo Paiva, MD, Universidade Federal do Parana, Curitiba, PR, Brazil Background: Scleroderma is a cutaneous and systemic autoimmune disorder seen in a wide range of clinical specialties including dermatology. Systemic sclerosis and its subtypes differ significantly from other diseases, because the aberrant activation of the immune system does not result in an inflammation-driven destruction but in a progressive matrix synthesis, especially of the skin. Objectives: To determine the relative frequency and characteristics of the three principal subsets (limited, diffuse, and overlap) and their association with clinical and laboratory data.
Conclusions: Topical application of P144 up to a concentration of 300 g/mL has good local and systemic safety profile. No systemic exposure was found. The good local and systemic tolerability recommends going forward in the development through a phase II clinical trial to evaluate the efficacy and safety of topical administration of P144 in outpatients with skin manifestations of sclerosis.
Methods: Outpatients from dermatology and rheumatology clinics in a large university hospital in the southern region of Brazil with the diagnosis of scleroderma were reviewed between January 2007 and May 2008. Seventy-five patients were identified and their scleroderma diagnoses validated. Other characteristics, such as sex, mean age at diagnosis, extent of skin involvement, internal organ involvement, and serology and other laboratory markers were analyzed. Results: The female to male ratio was 11.5:1. The majority of patients had limited disease, with a ratio of 6.57:2.85:1 of limited to diffuse to overlap. None of the systemic involvement (excluding atrophic skin, which is present more often in the diffuse form [x 2; P ¼ .03]), was found to predominate in any group. The Rodnan score, diffusion capacity of carbon monoxide (DLCO), and urine protein were statistically associated with diffuse form. Autoimmune serology was positive in 88.4% of patients, with antinuclear antibodies and anticentromere antibodies being more common in the limited form and antiRNA polymerase III being more common in diffuse scleroderma. Conclusions: This study demonstrated that limited disease is more common than diffuse or overlap disease. However, distinct clinical features and laboratory parameters can be independent predictive markers for the outcome of a given patient. A detailed profile of the affected patients should be determined for the area where the patient lives to indentify the factors associated with the disease prognosis. Monitoring should be performed on a regular basis as early as possible to reduce morbidity and mortality of the affected patients.
Commercial support: 50% sponsored by ISDIN and 50% by Digna-Biotech.
Commercial support: None identified.
Results: No clinical local or systemic reactions were seen in any of the volunteers. The next active dose was tested after the safety of the previous formulation was assessed for at least one week of treatment. In total, the dermatologist reported skin toxicity in two volunteers; one receiving placebo cream who had grade I erythema and other one had flaking and thin cracks after receiving P144 cream 300 g/mL. Other adverse events reported were rated as being of mild severity. No additional measures should be adopted after administration of active or placebo cream, such as discontinuation or treatment for local toxicity. No P144 levels above 0.5 ng/m: were quantified in the plasma samples.
MARCH 2009
J AM ACAD DERMATOL
AB63
P1202 Trauma-induced blistering in a patient with lupus erythematosus: Epidermolysis bullosa acquisita or bullous lupus erythematosus? Alia Sampson Brown, PhD, University of Louisville, Louisville, KY, United States; Carol Kulp-Shorten, MD, University of Louisville, Louisville, KY, United States; Jeffrey Callen, MD, University of Louisville, Louisville, KY, United States Background: Bullous lupus erythematosus (BLE) is a rare manifestation of systemic lupus that is characterized by tense vesicles and bullae which remit without scarring. BLE is a subepidermal blistering disorder caused by antibodies against type VII collagen, making it histologicly and immunologically indistinguishable from epidermolysis bullosa acquisita (EBA). We present a case of a woman with a known history of systemic lupus erythematosus (SLE) who presented with extensive bullous lesions that occurred over areas of minor trauma and resulted in scarring and milia formation.
Conclusions: Despite a high risk for OC, woman with DP were not diagnosed at an earlier stage or lower Ca-125 level. The small sample size limits our power. Additional cases will be ascertained and presented. Current methods for early detection of ovarian carcinoma in DP patients are ineffective. Early OC may ‘‘whisper,’’ but it doesn’t itch.
Observation: A 47-year-old female with longstanding SLE developed widespread, tense bullae. The bullae were concentrated over bony prominences; the grouping was not noted. In addition, healing occurred with scarring, milia, loss of fingernails, and decreased mobility. Initial biopsies from 1998 revealed a subepidermal split with neutrophils, and immunoflourescent studies were negative. A diagnosis of BLE was made, and she was treated with oral dapsone 50 mg daily which resulted in a decrease in the appearance of new bullous lesions. Dapsone was discontinued because of the development of a hypersensitivity syndrome. She was then placed on oral azathioprine 75 mg daily and oral hydroxychloroquine 200 mg twice daily, with varying doses of systemic corticosteroids. She continued to have blisters, and 1 year ago her nephrologist replaced azathioprine with mycophenolate mofetil; the patient correlates her worsening disease with the initiation of this medicine. With no improvement of her bullous lesions, she was recently admitted to the hospital with widespread blistering, lupus nephritis, pneumonitis, and pneumonia. Two punch biopsies were obtained for hemtoxylineeosin staining and direct and indirect immunoflourescent studies were also undertaken, which showed linear deposits of immunoglobulin G along the dermal basement membrane compatible with BLE or EBA. Azathioprine was increased to 150 mg daily based upon an elevated thiopurine methyl transferase level; in addition, hydroxychloroquine 200 mg daily and prednisone 15 mg daily were continued. Conclusions: BLE and EBA are histopathologically and immunologically indistinguishable; both having a subepidermal blister and antibodies to type VII collagen. We present a patient with bullous lesions initially thought to be BLE; however, because of the distribution of the lesions over the ‘‘areas of trauma,’’ the lack of grouping of the lesions, and the resolution with scarring and milia, the diagnosis of EBA is favored.
Commercial support: None identified.
Commercial support: None identified.
Methods: We conducted a case control analysis using all cases identified from PubMed and Google Scholar searches using the following key words: ‘‘dermatomyositis,’’ ‘‘polymyositis,’’ ‘‘ovarian cancer,’’ ‘‘case report,’’ and combinations of those terms; in addition, a manual search of included references was conducted. We only considered cases of DP with ovarian or breast and ovary cancer. Cases identified were abstracted for age, stage, grade, histology, and level of Ca-125. ‘‘Cases’’ were OC diagnosed after DP and were compared to ‘‘controls’’ (OC diagnosed before DP). Results: Forty-two articles were found; 25 were excluded because of concurrent other malignancies or the fact that the articles not readily available. From the remaining 18 articles, 46 patients were identified, including 35 cases and 11 controls. Mean age in the cases was 57.5 years, and for controls was 58 years (P ¼ NS). Only one case was stage I (3.70%). Most cases and controls were in advanced stages (III-IV; 96.3% and 100%, respectively [P ¼ NS]). Time from DP to OC diagnosis was 13.4 months (range, 1-68 mos) versus 15.4 months (range, 1-72 mos) from OC to DP (P ¼ NS). The median time from initial presentation of DP to cancer was 10.5 versus 6 months for controls (P ¼ NS). Ca-125 was 1304 (range, 44-7710) in cases versus 1157 (range, 145-3200) in controls (P ¼ NS). OC was otherwise asymptomatic except for DP and diagnosis by screening test in 54.8% of cases. In control patients, where the initial diagnosis was OC followed by DP, only 30% where asymptomatic for OC (P ¼ NS).
P1201 A phase I clinical trial of topical peptide p144 TGF-beta1 inhibitor in healthy volunteers Belen Sabada, Clinica Universitaria de Navarra, Pamplona, Spain; Belen Ruiz, MD, Hospital Universitario Puerta de Hierro, Madrid, Spain; Juan Ruiz, MD, Digna Biotech, Madrid, Spain; Rau ´ l Insa, MD, PhD, ISDIN, Barcelona, Spain Introduction: P144 is a transforming growth factor-beta 1 (TGFb1) inhibitor peptide. TGFb1 contributes to the excessive production of collagen and other extracellular matrix components. TGFb1 inhibition could be an effective target in different serious diseases with fibrosis development. P144 has shown promising results, through topical application, in an established mice scleroderma model in which skin fibrosis is induced by repeated bleomicyn subcutaneous injections. Methods: The objective of this study is to assess the tolerability, safety, and bioavailability of the peptide 144 TGFb1 inhibitor after topical administration to healthy volunteers through a phase I multicenter, multiple dose, double-blind, placebo-controlled, randomized clinical trial which was conducted in 36 healthy volunteers. The volunteers were randomized to receive active or placebo cream, and distributed into three treatment groups according to the different doses tested for P144: 100, 200, and 300 g/mL of P144 cream. A daily application during 3 weeks was of 1 mL of active or placebo cream onto a controlled surface at the back was used. The tolerability was evaluated by dermatologists (blinded evaluation) based on the Frosch and Kligman visual scale. To evaluate bioavailability, plasma measurements were taken before cream administration and up to 24 hours after.
P1203 A study of systemic scleroderma in the southern region of Brazil: Cutaneous manifestations and clinical and laboratory marker association Hermenio C. Lima, Universidade Federal do Parana, Curitiba, PR, Brazil; Carolina Muller, MD, Universidade Federal do Parana, Curitiba, PR, Brazil; Eduardo Paiva, MD, Universidade Federal do Parana, Curitiba, PR, Brazil Background: Scleroderma is a cutaneous and systemic autoimmune disorder seen in a wide range of clinical specialties including dermatology. Systemic sclerosis and its subtypes differ significantly from other diseases, because the aberrant activation of the immune system does not result in an inflammation-driven destruction but in a progressive matrix synthesis, especially of the skin. Objectives: To determine the relative frequency and characteristics of the three principal subsets (limited, diffuse, and overlap) and their association with clinical and laboratory data.
Conclusions: Topical application of P144 up to a concentration of 300 g/mL has good local and systemic safety profile. No systemic exposure was found. The good local and systemic tolerability recommends going forward in the development through a phase II clinical trial to evaluate the efficacy and safety of topical administration of P144 in outpatients with skin manifestations of sclerosis.
Methods: Outpatients from dermatology and rheumatology clinics in a large university hospital in the southern region of Brazil with the diagnosis of scleroderma were reviewed between January 2007 and May 2008. Seventy-five patients were identified and their scleroderma diagnoses validated. Other characteristics, such as sex, mean age at diagnosis, extent of skin involvement, internal organ involvement, and serology and other laboratory markers were analyzed. Results: The female to male ratio was 11.5:1. The majority of patients had limited disease, with a ratio of 6.57:2.85:1 of limited to diffuse to overlap. None of the systemic involvement (excluding atrophic skin, which is present more often in the diffuse form [x 2; P ¼ .03]), was found to predominate in any group. The Rodnan score, diffusion capacity of carbon monoxide (DLCO), and urine protein were statistically associated with diffuse form. Autoimmune serology was positive in 88.4% of patients, with antinuclear antibodies and anticentromere antibodies being more common in the limited form and antiRNA polymerase III being more common in diffuse scleroderma. Conclusions: This study demonstrated that limited disease is more common than diffuse or overlap disease. However, distinct clinical features and laboratory parameters can be independent predictive markers for the outcome of a given patient. A detailed profile of the affected patients should be determined for the area where the patient lives to indentify the factors associated with the disease prognosis. Monitoring should be performed on a regular basis as early as possible to reduce morbidity and mortality of the affected patients.
Commercial support: 50% sponsored by ISDIN and 50% by Digna-Biotech.
Commercial support: None identified.
Results: No clinical local or systemic reactions were seen in any of the volunteers. The next active dose was tested after the safety of the previous formulation was assessed for at least one week of treatment. In total, the dermatologist reported skin toxicity in two volunteers; one receiving placebo cream who had grade I erythema and other one had flaking and thin cracks after receiving P144 cream 300 g/mL. Other adverse events reported were rated as being of mild severity. No additional measures should be adopted after administration of active or placebo cream, such as discontinuation or treatment for local toxicity. No P144 levels above 0.5 ng/m: were quantified in the plasma samples.
MARCH 2009
J AM ACAD DERMATOL
AB63