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Toxic epidermal necrolysis associated to Mycoplasma pneumoniae and drugs: Three cases and review of the literature
Mycophenolate mofetil as an adjuvant drug for the treatment of pemphigus vulgaris and pemphigus foliaceus
Rituximab monotherapy in patients with pemphigus foliaceus as first line therapy: Clinical, immunologic, and confocal microscopy evaluation
Vivian Barzi Loureiro, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Celina Maruta, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Claudia Giuli Santi, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Valeria Aoki, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil
Methods: The study analyzed 23 patients diagnosed as pemphigus vulgaris (N ¼ 17) or pemphigus foliaceus (N ¼ 6), who had failed to previous treatments or experienced significant adverse effects with azathioprine, and were treated with mycophenolate mofetil. We also performed indirect immunofluorescence before and after introduction of Mycophenolate Mofetil. Results: Remission was achieved in 20 out of 23 patients (87%), and was characterized as follows: complete remission off therapy (N ¼ 2), complete remission on minimal therapy (N ¼ 6), partial remission on therapy (N ¼ 6) and partial remission on minimal therapy (N ¼ 6). Failure occurred in three out of 23 patients. Mycophenolate mofetil was well tolerated, once 20 out of 23 patients had no adverse effects. Conclusion: Mycophenolate mofetil has been demonstrated to be an effective and safe adjuvant drug in the treatment of pemphigus vulgaris and foliaceus, who had failed to previous treatments or experienced significant adverse effects with azathioprine.
Lidia Rudnicka, Faculty of Medical Sciences, Warszawa, Poland; Agnieszka Kardynal, MD, Department of Dermatology, CSK MSWiA, Warsaw, Poland; Justyna Sicinska, MD, PhD, Department of Dermatology, CSK MSWiA, Warsaw, Poland; Malgorzata Olszewska, MD, PhD, Department of Dermatology, Warsaw Medical University, Warsaw, Poland Rituximab is a chimeric human-mouse monoclonal antibody, which binds to the CD20 antigen on B and pre-B lymphocytes and causes depletion of CD 20+ cells in the mechanism of complement-dependent and independent cytolysis, antibodydependent cell cytotoxicity and mechanism of apoptosis. Rituximab is currently registered for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis. Rituximab also demonstrated efficacy in a number of other autoimmune diseases, including systemic lupus erythematosus and Sj€ ogren syndrome. In severe or recalcitrant cases of pemphigus vulgaris and pemphigus foliaceus, rituximab was applied as an adjuvant drug. We present 2 patients with pemphigus foliaceus, a 66-year-old man and a 61-year-old woman, who were treated with rituximab in monotherapy as a first-line treatment. In the first patient serologic investigation and improvement were observed 4 months after therapy initiation. After 8 months further, significant clinical improvement, with sparse residual lesions, was observed. Reflectance confocal microscopy of selected lesions showed intraepidermal blisters before treatment with numerous acantholytic cells and lymphocytic infiltration. After 4 weeks only an intraepidermal cleft is visible with few acantholytic cells, but no inflammatory infiltrate was observed. In the healing phase the epidermis did not retain the characteristic honeycomb structure. Normalization of the epidermal structure was observed 4 months after therapy. In patients with pemphigus foliaceus significant improvement was observed after rituximab monotherapy. Serological negativisation was achieved prior to clinical remission. This unusual phenomenon may be explained by rapid depletion of CD20+ cells and inhibition of antibody production, while in vivo bound pathogenic pemphigus antibodies remained active.
Commercial support: None identified.
Commercial support: None identified.
(Poster reference number 5693)
Background: Pemphigus is a rare autoimunne bullous disease, characterized by blisters and erosions of the skin and/or mucous membranes. Its potentially lifethreatening condition has been modified after the introduction of systemic corticosteroids. However, the long-term use of corticosteroids may lead to serious adverse effects. Mycophenolate mofetil has been used as a corticosteroid-sparing agent in the treatment of pemphigus. Objectives: To evaluate the effectiveness and safety of mycophenolate mofetil as adjuvant therapy in patients with pemphigus vulgaris and foliaceus.
Paraneoplastic pemphigus: A retrospective study of 9 cases at a large university-based hospital
(Poster reference number 5108)
Jungting Kao, MD, National Taiwan University Hospital, Taipei, Taiwan; Chiayu Chu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan Background: Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune bullous disease associated with neoplasia. Clinically, it is characterized by extensive mucosal erosions and polymorphous cutaneous lesions. Little is known about the clinical features of this disease in Taiwan. Objective: The aim of this study was to investigate the clinical features of PNP in the Taiwanese population. Methods: Clinical records from National Taiwan University Hospital over the last 11 years (1998-2008) were reviewed. Cases of biopsy, direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and immunoblotting-proven PNP were identified. Relevant clinical variables and follow-up data were extracted from the medical records. Results: A total of 9 PNP cases were identified. There seemed to be no gender difference in our case series (M:F ¼ 5:4). The mean age at onset was 61.7 years. All patients (100%) had extensive oral mucosal erosions. 3 patients (33.3%) had genital ulcers and 2 patients (22.2%) had ocular involvements. 7 patients (77.8%) had polymorphous cutaneous lesions, including eruptions resembling pemphigus vulgaris, pemphigus foliaceus, lichen planus, and erythema multiforme, while 2 patients (22.2%) had predominantly lichenoid papules. The histopathology in all patients showed variable suprabasal acantholysis, scattered necrotic keratinocytes, basal vacuolization, and lichenoid inflammation. The immunologic feature is the presence of serum autoantibodies against proteins in stratified squamous epithelia and transitional columnar epithelia, which is proven by IIF (rat bladder) or immunoblotting. The associated disorders included Castleman tumor (3/9), follicular dendritic cell sarcoma (2/9), thymoma (2/9), non-Hodgkin lymphoma (1/9), and squamous cell carcinoma of the lung (1/9). Five patients had progressive dyspnea while 2 of them had fatal bronchiolitis obliterans. 6 patients (66.7%) died of this disease.
(Poster reference number 4629)
Toxic epidermal necrolysis associated to Mycoplasma pneumoniae and drugs: Three cases and review of the literature
(Poster reference number 5601)
Montserrat Molg o, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Constanza del Puerto, MS, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Consuelo Cardenas, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Sergio Gonzalez, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile Background: StevenseJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the extremes of the same disease. Drugs are the main cause of SJS/TEN, and respiratory tract infections by Mycoplasma pneumoniae are the most frequent infections associated with SSJ. Case 1: A 20-year-old healthy man presented with 3 weeks of respiratory symptoms. He received treatment with Tamiflu, ibuprofen, and chlormezanone. Three hours later was hospitalized at the intensive care unit because of a rapidly progressive bullous skin rash and mucous compromise. TEN was diagnosed and IgG IV was started. M pneumoniae infection was suspected and serology tests were positive. Antibiotics were started, with excellent response. The patient was discharged after 30 days of treatment with complete skin recovery.
Conclusion: The clinical, pathologic, and immunologic features of these patients were similar to those of the literature except the ocular involvement and associated tumors. More investigations are needed for further exploring the pathogenesis of ocular involvement.
Case 2: A 6-year-old healthy boy without any drug use since the last 6 weeks, presented with an upper respiratory tract infection. The patient did not receive any treatment. He started with an extensive maculopapular, pruritic exanthema and rapidly progressed with skin pain, and mucous involvement. TEN was diagnosed. M pneumonia serology was positive and antibiotic were started, with excellent response. Case 3: A 19-year-old healthy puerperal woman with a story of 7 days of upper respiratory tract infection treated with amoxicillin started with skin rash that rapidly compromised 90% of skin surface and mucosal compromise. TEN was diagnosed, serology for mycoplasma pneumonia was positive. Antibiotics were started. Unfortunately, patient had a systole and died after 20 hours at our center. Discussion: Drugs are the most frequent etiology of TEN, but M pneumoniae infection has an important pathogenic role. There are many case reports that suggest that SJS or TEN secondary to M pneumoniae have better outcomes, and no mortality cases reported. Here we describe three patients with TEN associated to M pneumoniae infection with severe manifestations and poor outcomes, including death. We and others suggest to perform M pneumoniae serology or PCR in every case of SJS-TEN.
Commercial support: None identified.
Commercial support: None identified.
APRIL 2012
J AM ACAD DERMATOL
AB105
Rituximab monotherapy in patients with pemphigus foliaceus as first line therapy: Clinical, immunologic, and confocal microscopy evaluation
Vivian Barzi Loureiro, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Celina Maruta, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Claudia Giuli Santi, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Valeria Aoki, Department of Dermatology, University of S~ao Paulo Medical School, S~ao Paulo, Brazil
Methods: The study analyzed 23 patients diagnosed as pemphigus vulgaris (N ¼ 17) or pemphigus foliaceus (N ¼ 6), who had failed to previous treatments or experienced significant adverse effects with azathioprine, and were treated with mycophenolate mofetil. We also performed indirect immunofluorescence before and after introduction of Mycophenolate Mofetil. Results: Remission was achieved in 20 out of 23 patients (87%), and was characterized as follows: complete remission off therapy (N ¼ 2), complete remission on minimal therapy (N ¼ 6), partial remission on therapy (N ¼ 6) and partial remission on minimal therapy (N ¼ 6). Failure occurred in three out of 23 patients. Mycophenolate mofetil was well tolerated, once 20 out of 23 patients had no adverse effects. Conclusion: Mycophenolate mofetil has been demonstrated to be an effective and safe adjuvant drug in the treatment of pemphigus vulgaris and foliaceus, who had failed to previous treatments or experienced significant adverse effects with azathioprine.
Lidia Rudnicka, Faculty of Medical Sciences, Warszawa, Poland; Agnieszka Kardynal, MD, Department of Dermatology, CSK MSWiA, Warsaw, Poland; Justyna Sicinska, MD, PhD, Department of Dermatology, CSK MSWiA, Warsaw, Poland; Malgorzata Olszewska, MD, PhD, Department of Dermatology, Warsaw Medical University, Warsaw, Poland Rituximab is a chimeric human-mouse monoclonal antibody, which binds to the CD20 antigen on B and pre-B lymphocytes and causes depletion of CD 20+ cells in the mechanism of complement-dependent and independent cytolysis, antibodydependent cell cytotoxicity and mechanism of apoptosis. Rituximab is currently registered for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis. Rituximab also demonstrated efficacy in a number of other autoimmune diseases, including systemic lupus erythematosus and Sj€ ogren syndrome. In severe or recalcitrant cases of pemphigus vulgaris and pemphigus foliaceus, rituximab was applied as an adjuvant drug. We present 2 patients with pemphigus foliaceus, a 66-year-old man and a 61-year-old woman, who were treated with rituximab in monotherapy as a first-line treatment. In the first patient serologic investigation and improvement were observed 4 months after therapy initiation. After 8 months further, significant clinical improvement, with sparse residual lesions, was observed. Reflectance confocal microscopy of selected lesions showed intraepidermal blisters before treatment with numerous acantholytic cells and lymphocytic infiltration. After 4 weeks only an intraepidermal cleft is visible with few acantholytic cells, but no inflammatory infiltrate was observed. In the healing phase the epidermis did not retain the characteristic honeycomb structure. Normalization of the epidermal structure was observed 4 months after therapy. In patients with pemphigus foliaceus significant improvement was observed after rituximab monotherapy. Serological negativisation was achieved prior to clinical remission. This unusual phenomenon may be explained by rapid depletion of CD20+ cells and inhibition of antibody production, while in vivo bound pathogenic pemphigus antibodies remained active.
Commercial support: None identified.
Commercial support: None identified.
(Poster reference number 5693)
Background: Pemphigus is a rare autoimunne bullous disease, characterized by blisters and erosions of the skin and/or mucous membranes. Its potentially lifethreatening condition has been modified after the introduction of systemic corticosteroids. However, the long-term use of corticosteroids may lead to serious adverse effects. Mycophenolate mofetil has been used as a corticosteroid-sparing agent in the treatment of pemphigus. Objectives: To evaluate the effectiveness and safety of mycophenolate mofetil as adjuvant therapy in patients with pemphigus vulgaris and foliaceus.
Paraneoplastic pemphigus: A retrospective study of 9 cases at a large university-based hospital
(Poster reference number 5108)
Jungting Kao, MD, National Taiwan University Hospital, Taipei, Taiwan; Chiayu Chu, MD, PhD, National Taiwan University Hospital, Taipei, Taiwan Background: Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune bullous disease associated with neoplasia. Clinically, it is characterized by extensive mucosal erosions and polymorphous cutaneous lesions. Little is known about the clinical features of this disease in Taiwan. Objective: The aim of this study was to investigate the clinical features of PNP in the Taiwanese population. Methods: Clinical records from National Taiwan University Hospital over the last 11 years (1998-2008) were reviewed. Cases of biopsy, direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and immunoblotting-proven PNP were identified. Relevant clinical variables and follow-up data were extracted from the medical records. Results: A total of 9 PNP cases were identified. There seemed to be no gender difference in our case series (M:F ¼ 5:4). The mean age at onset was 61.7 years. All patients (100%) had extensive oral mucosal erosions. 3 patients (33.3%) had genital ulcers and 2 patients (22.2%) had ocular involvements. 7 patients (77.8%) had polymorphous cutaneous lesions, including eruptions resembling pemphigus vulgaris, pemphigus foliaceus, lichen planus, and erythema multiforme, while 2 patients (22.2%) had predominantly lichenoid papules. The histopathology in all patients showed variable suprabasal acantholysis, scattered necrotic keratinocytes, basal vacuolization, and lichenoid inflammation. The immunologic feature is the presence of serum autoantibodies against proteins in stratified squamous epithelia and transitional columnar epithelia, which is proven by IIF (rat bladder) or immunoblotting. The associated disorders included Castleman tumor (3/9), follicular dendritic cell sarcoma (2/9), thymoma (2/9), non-Hodgkin lymphoma (1/9), and squamous cell carcinoma of the lung (1/9). Five patients had progressive dyspnea while 2 of them had fatal bronchiolitis obliterans. 6 patients (66.7%) died of this disease.
(Poster reference number 4629)
Toxic epidermal necrolysis associated to Mycoplasma pneumoniae and drugs: Three cases and review of the literature
(Poster reference number 5601)
Montserrat Molg o, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Constanza del Puerto, MS, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Consuelo Cardenas, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile; Sergio Gonzalez, MD, Pontificia Universidad Cat olica de Chile, Santiago, Chile Background: StevenseJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the extremes of the same disease. Drugs are the main cause of SJS/TEN, and respiratory tract infections by Mycoplasma pneumoniae are the most frequent infections associated with SSJ. Case 1: A 20-year-old healthy man presented with 3 weeks of respiratory symptoms. He received treatment with Tamiflu, ibuprofen, and chlormezanone. Three hours later was hospitalized at the intensive care unit because of a rapidly progressive bullous skin rash and mucous compromise. TEN was diagnosed and IgG IV was started. M pneumoniae infection was suspected and serology tests were positive. Antibiotics were started, with excellent response. The patient was discharged after 30 days of treatment with complete skin recovery.
Conclusion: The clinical, pathologic, and immunologic features of these patients were similar to those of the literature except the ocular involvement and associated tumors. More investigations are needed for further exploring the pathogenesis of ocular involvement.
Case 2: A 6-year-old healthy boy without any drug use since the last 6 weeks, presented with an upper respiratory tract infection. The patient did not receive any treatment. He started with an extensive maculopapular, pruritic exanthema and rapidly progressed with skin pain, and mucous involvement. TEN was diagnosed. M pneumonia serology was positive and antibiotic were started, with excellent response. Case 3: A 19-year-old healthy puerperal woman with a story of 7 days of upper respiratory tract infection treated with amoxicillin started with skin rash that rapidly compromised 90% of skin surface and mucosal compromise. TEN was diagnosed, serology for mycoplasma pneumonia was positive. Antibiotics were started. Unfortunately, patient had a systole and died after 20 hours at our center. Discussion: Drugs are the most frequent etiology of TEN, but M pneumoniae infection has an important pathogenic role. There are many case reports that suggest that SJS or TEN secondary to M pneumoniae have better outcomes, and no mortality cases reported. Here we describe three patients with TEN associated to M pneumoniae infection with severe manifestations and poor outcomes, including death. We and others suggest to perform M pneumoniae serology or PCR in every case of SJS-TEN.
Commercial support: None identified.
Commercial support: None identified.
APRIL 2012
J AM ACAD DERMATOL
AB105