- Email: [email protected]
IgA pemphigus: Case series with emphasis on therapeutic response
J AM ACAD DERMATOL
200 Letters
The referent group (RR of 1.00) refers to high ( greater than or equal to the mean or median) unless otherwise specified. Cases with missing data were excluded from relevant analyses. Analyses were conducted in Stata 12.1 (Stata Corp, College Station, TX). We identified 10,841 invasive melanomas among young women and 6549 among young men. Among young women, 19.2% of melanomas with known depth (1931/10,063) were thicker, and 2.2% with known prognosis (242/10,828) were lethal; among young men, 28.1% of melanomas with known depth (1,690/6008) were thicker, and 6.5% with known prognosis (422/6524) were lethal. Low county bachelor’s degree completion was associated with increased risk of thicker and lethal melanoma in young women and young men (Tables I and II). Low county Pap test rate and low and moderate dermatologist density were associated with increased risk of thicker melanoma, and low proportion uninsured was associated with decreased risk of lethal melanoma in young women. Low county median income was not associated with increased risk of thicker or lethal melanoma in young women or young men, but it was in the general adult population. Our results suggest that community-level factors are associated with melanoma outcomes and that greater utilization of health care resources (dermatologists, cancer screenings [Pap tests]) may help explain the lower proportion of thicker melanomas in young women than in young men. Strikingly, however, education level in one’s community was the only factor associated with mortality in young men and was the strongest factor associated with mortality in young women. Furthermore, and in contrast to the general adult population, median county income did not impact risk of thicker or lethal melanoma in young adults. Primary limitations include lack of data on other known risk factors for melanoma, inability to identify melanoma-related deaths that occurred after 2009, and potential for ecological fallacy, where effects relevant to a group are not or less relevant to individuals within that group. Knowledge about melanoma is lacking among less educated individuals, which may result in delayed presentation for assessment or recognition of a melanoma. Only 16% of Americans without a high school degree know that melanoma is a skin cancer,3 and non-college graduates tan indoors at higher rates than college graduates.4 While melanoma mortality is declining overall, mortality due to thick melanoma is stable.1 Given our results and the lower burden of disease in younger than in older adults, educational programs and counseling focusing on risk reduction and melanoma self-detection may be
JANUARY 2014
more appropriate than screening programs for young adults5 and have the highest yield in counties with low educational attainment. We are grateful to Elan Cohen, MS and Amber Barnato, MD, MS, MPH at the University of Pittsburgh for statistics consultation.
Jacqueline F. Moreau, MS,c Daniel G. Winger, MS,a Molly B. Conroy, MD, MPH,d Laura K. Ferris, MD, PhDb Clinical and Translational Science Institutea and Department of Dermatology,b University of Pittsburgh School of Medicinec; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health,d Pittsburgh, PA Funding sources: This study was supported in part by Clinical Research Fellowship funding from the Doris Duke Charitable Foundation (JFM) and by UL1 RR024153-04 (LKF). Statistics consultation funding from the National Institutes of Health (Grant Numbers UL1 RR024153 and UL1TR000005). Conflicts of interest: None of the authors has a conflict of interest relevant to this manuscript. Correspondence to: Laura K. Ferris, MD, PhD, Department of Dermatology, University of Pittsburgh School of Medicine, 3601 Fifth Ave, Fifth Floor, Pittsburgh, PA 15213. E-mail: [email protected] REFERENCES 1. Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol 2011;65: S17-25.e1-3. 2. Eide MJ, Weinstock MA, Clark MA. Demographic and socioeconomic predictors of melanoma prognosis in the United States. J Health Care Poor Underserved 2009;20:227-45. 3. Miller DR, Geller AC, Wyatt SW, Halpern A, Howell JB, Cockerell C, et al. Melanoma awareness and self-examination practices: results of a United States survey. J Am Acad Dermatol 1996;34: 962-70. 4. Use of indoor tanning devices by adultseUnited States, 2010. MMWR Morb Mortal Wkly Rep 2012;61:323-6. 5. Moyer VA. Behavioral counseling to prevent skin cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:59-65. http://dx.doi.org/10.1016/j.jaad.2013.08.048
IgA pemphigus: Case series with emphasis on therapeutic response To the Editor: We herein report 9 IgA pemphigus patients, characterized by their clinical, histopathologic, and immunopathologic findings. One patient had the
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intraepidermal neutrophilic dermatosis-type IgA pemphigus (IEN-type) and the remaining 8 had the subcorneal pustular dermatosis-type IgA pemphigus (SPD-type). The aim of this study focused the IgA pemphigus therapeutic approach, with a follow-up length from 1 to 12 years (mean 3.8 years). The following treatments were used: dapsone, colchicine, prednisone, acitretin, isotretinoin, tetracycline, sulfamethoxazole/trimethoprim, methotrexate, cyclosporine, adalimumab, sulfamethoxypyridazine, azathioprine, and PUVA. Dapsone was used as a first line therapy (25 to 125 mg/day) in 6 patients. One patient with IEN-type disease was in complete remission off therapy. Two patients with SPD-type disease had a partial response. Three of 9 patients had side effects (methemoglobinemia and hemolysis) of dapsone therapy, and withdrawal of medication was necessary. Another 2 of 9 patients showed no response to any of the proposed therapies. Five of 9 patients were treated with colchicine (0.5 to 2 g/day)1,2: 4 had no response and 1 was lost to follow-up. Four of 9 patients received prednisone (0.5 to 1.5 mg/kg/day): 3 had no response with medication withdrawal, and 1 patient stayed in partial remission on therapy. Two of 9 patients were treated with tetracycline (1 to 2 g/day): acute urticaria developed in 1 patient, and 1 showed no response to treatment. Two of 9 patients were unresponsive to treatment and so were treated with multiple drugs. The condition of 1 of these patients stabilized in partial remission with adalimumab 40 mg biweekly,3 and she is currently receiving 40 mg bimonthly, 1 year after treatment was initiated, without any side effect so far. This was the most recalcitrant IgA pemphigus case of our series, with the patient showing no response to 10 therapeutic options over 6 years. The other patient had a severe form of the disease and received acitretin 30 mg/day4 after undergoing a hysterectomy for postpartum hemorrhage. This patient had a very good response and no longer required frequent hospitalization. Although her case is classified as a partial remission on therapy, acitretin exerted a great impact on her quality of life. Five patients were in partial remission on therapy, 1 patient was lost to follow-up, and 2 patients died of unrelated causes. The only patient who had complete remission off therapy was the patient with IEN-type disease. A review of 49 patients of both subtypes of IgA pemphigus suggests that those with IEN-type showed a better response to treatment, in comparison to SPD-type.5 Our experience was limited to one IEN-type patient, and therefore we
could not conclude that IEN- or SPD-type showed different responses to treatment. So far, there is no consensus on IgA pemphigus treatment.1-5 Our results confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this group of IgA diseases is needed. Ana Carulina L. Moreno, MD,a Claudia G. Santi, MD,a Tatiana V. B. Gabbi, MD,a Valeria Aoki, MD,a Takashi Hashimoto, MD,b and Celina W. Maruta, MDa Department of Dermatology,a University of Sao Paulo Medical School, Brazil; University of Kurume,b Japan Funding sources: None. Conflicts of interest: None declared. Correspondence to: Ana Carulina L. Moreno, MD, Av Dr Eneas de Carvalho Aguiar, 255 - Cerqueira Ce sar e CEP 05403-002, S~ ao Paulo, Brazil E-mail: [email protected] REFERENCES 1. Oliveira JP, Gabbi TV, Hashimoto T, Aoki V, Santi CG, Maruta CW, et al. Desmocollin 1 is the autoantigen in two Brazilian cases of IgA pemphigus. J Dermatol 2003;30(12):886-91. 2. Hodak E, Lapidoth M, David M. Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus. J Am Acad Dermatol 1999;40(1):91-4. 3. Howell S, Bessinger G, Altman C, Belnap C. Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to treatment with adalimumab and mycophenolate mofetil. J Am Acad Dermatol 2005;53(3):541-3. 4. Gruss C, Zillikens D, Hashimoto T, Amagai M, Kroiß M, Vogt T, et al. Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin. J Am Acad Dermatol 2000;43(5 Pt 2):923-6. 5. Yasuda H, Kobayashi H, Hashimoto T, Itoh K, Yamane M, Nakamura J. Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of autoantibodies to desmocollin-1 and clinical review. Br J Dermatol 2000;143(1):144-8. http://dx.doi.org/10.1016/j.jaad.2013.09.037
Primary nonadherence (failure to obtain prescribed medicines) among dermatology patients To the Editor: Primary nonadherence, defined as when a patient fails to obtain a prescribed medication, has been largely unstudied in dermatology. However, medication nonadherence in general has been shown to be a major public health issue that is associated with increased morbidity and mortality in patients across multiple fields of medicine,1-3 placing a substantial economic burden on the
200 Letters
The referent group (RR of 1.00) refers to high ( greater than or equal to the mean or median) unless otherwise specified. Cases with missing data were excluded from relevant analyses. Analyses were conducted in Stata 12.1 (Stata Corp, College Station, TX). We identified 10,841 invasive melanomas among young women and 6549 among young men. Among young women, 19.2% of melanomas with known depth (1931/10,063) were thicker, and 2.2% with known prognosis (242/10,828) were lethal; among young men, 28.1% of melanomas with known depth (1,690/6008) were thicker, and 6.5% with known prognosis (422/6524) were lethal. Low county bachelor’s degree completion was associated with increased risk of thicker and lethal melanoma in young women and young men (Tables I and II). Low county Pap test rate and low and moderate dermatologist density were associated with increased risk of thicker melanoma, and low proportion uninsured was associated with decreased risk of lethal melanoma in young women. Low county median income was not associated with increased risk of thicker or lethal melanoma in young women or young men, but it was in the general adult population. Our results suggest that community-level factors are associated with melanoma outcomes and that greater utilization of health care resources (dermatologists, cancer screenings [Pap tests]) may help explain the lower proportion of thicker melanomas in young women than in young men. Strikingly, however, education level in one’s community was the only factor associated with mortality in young men and was the strongest factor associated with mortality in young women. Furthermore, and in contrast to the general adult population, median county income did not impact risk of thicker or lethal melanoma in young adults. Primary limitations include lack of data on other known risk factors for melanoma, inability to identify melanoma-related deaths that occurred after 2009, and potential for ecological fallacy, where effects relevant to a group are not or less relevant to individuals within that group. Knowledge about melanoma is lacking among less educated individuals, which may result in delayed presentation for assessment or recognition of a melanoma. Only 16% of Americans without a high school degree know that melanoma is a skin cancer,3 and non-college graduates tan indoors at higher rates than college graduates.4 While melanoma mortality is declining overall, mortality due to thick melanoma is stable.1 Given our results and the lower burden of disease in younger than in older adults, educational programs and counseling focusing on risk reduction and melanoma self-detection may be
JANUARY 2014
more appropriate than screening programs for young adults5 and have the highest yield in counties with low educational attainment. We are grateful to Elan Cohen, MS and Amber Barnato, MD, MS, MPH at the University of Pittsburgh for statistics consultation.
Jacqueline F. Moreau, MS,c Daniel G. Winger, MS,a Molly B. Conroy, MD, MPH,d Laura K. Ferris, MD, PhDb Clinical and Translational Science Institutea and Department of Dermatology,b University of Pittsburgh School of Medicinec; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health,d Pittsburgh, PA Funding sources: This study was supported in part by Clinical Research Fellowship funding from the Doris Duke Charitable Foundation (JFM) and by UL1 RR024153-04 (LKF). Statistics consultation funding from the National Institutes of Health (Grant Numbers UL1 RR024153 and UL1TR000005). Conflicts of interest: None of the authors has a conflict of interest relevant to this manuscript. Correspondence to: Laura K. Ferris, MD, PhD, Department of Dermatology, University of Pittsburgh School of Medicine, 3601 Fifth Ave, Fifth Floor, Pittsburgh, PA 15213. E-mail: [email protected] REFERENCES 1. Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol 2011;65: S17-25.e1-3. 2. Eide MJ, Weinstock MA, Clark MA. Demographic and socioeconomic predictors of melanoma prognosis in the United States. J Health Care Poor Underserved 2009;20:227-45. 3. Miller DR, Geller AC, Wyatt SW, Halpern A, Howell JB, Cockerell C, et al. Melanoma awareness and self-examination practices: results of a United States survey. J Am Acad Dermatol 1996;34: 962-70. 4. Use of indoor tanning devices by adultseUnited States, 2010. MMWR Morb Mortal Wkly Rep 2012;61:323-6. 5. Moyer VA. Behavioral counseling to prevent skin cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:59-65. http://dx.doi.org/10.1016/j.jaad.2013.08.048
IgA pemphigus: Case series with emphasis on therapeutic response To the Editor: We herein report 9 IgA pemphigus patients, characterized by their clinical, histopathologic, and immunopathologic findings. One patient had the
J AM ACAD DERMATOL
Letters 201
VOLUME 70, NUMBER 1
intraepidermal neutrophilic dermatosis-type IgA pemphigus (IEN-type) and the remaining 8 had the subcorneal pustular dermatosis-type IgA pemphigus (SPD-type). The aim of this study focused the IgA pemphigus therapeutic approach, with a follow-up length from 1 to 12 years (mean 3.8 years). The following treatments were used: dapsone, colchicine, prednisone, acitretin, isotretinoin, tetracycline, sulfamethoxazole/trimethoprim, methotrexate, cyclosporine, adalimumab, sulfamethoxypyridazine, azathioprine, and PUVA. Dapsone was used as a first line therapy (25 to 125 mg/day) in 6 patients. One patient with IEN-type disease was in complete remission off therapy. Two patients with SPD-type disease had a partial response. Three of 9 patients had side effects (methemoglobinemia and hemolysis) of dapsone therapy, and withdrawal of medication was necessary. Another 2 of 9 patients showed no response to any of the proposed therapies. Five of 9 patients were treated with colchicine (0.5 to 2 g/day)1,2: 4 had no response and 1 was lost to follow-up. Four of 9 patients received prednisone (0.5 to 1.5 mg/kg/day): 3 had no response with medication withdrawal, and 1 patient stayed in partial remission on therapy. Two of 9 patients were treated with tetracycline (1 to 2 g/day): acute urticaria developed in 1 patient, and 1 showed no response to treatment. Two of 9 patients were unresponsive to treatment and so were treated with multiple drugs. The condition of 1 of these patients stabilized in partial remission with adalimumab 40 mg biweekly,3 and she is currently receiving 40 mg bimonthly, 1 year after treatment was initiated, without any side effect so far. This was the most recalcitrant IgA pemphigus case of our series, with the patient showing no response to 10 therapeutic options over 6 years. The other patient had a severe form of the disease and received acitretin 30 mg/day4 after undergoing a hysterectomy for postpartum hemorrhage. This patient had a very good response and no longer required frequent hospitalization. Although her case is classified as a partial remission on therapy, acitretin exerted a great impact on her quality of life. Five patients were in partial remission on therapy, 1 patient was lost to follow-up, and 2 patients died of unrelated causes. The only patient who had complete remission off therapy was the patient with IEN-type disease. A review of 49 patients of both subtypes of IgA pemphigus suggests that those with IEN-type showed a better response to treatment, in comparison to SPD-type.5 Our experience was limited to one IEN-type patient, and therefore we
could not conclude that IEN- or SPD-type showed different responses to treatment. So far, there is no consensus on IgA pemphigus treatment.1-5 Our results confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this group of IgA diseases is needed. Ana Carulina L. Moreno, MD,a Claudia G. Santi, MD,a Tatiana V. B. Gabbi, MD,a Valeria Aoki, MD,a Takashi Hashimoto, MD,b and Celina W. Maruta, MDa Department of Dermatology,a University of Sao Paulo Medical School, Brazil; University of Kurume,b Japan Funding sources: None. Conflicts of interest: None declared. Correspondence to: Ana Carulina L. Moreno, MD, Av Dr Eneas de Carvalho Aguiar, 255 - Cerqueira Ce sar e CEP 05403-002, S~ ao Paulo, Brazil E-mail: [email protected] REFERENCES 1. Oliveira JP, Gabbi TV, Hashimoto T, Aoki V, Santi CG, Maruta CW, et al. Desmocollin 1 is the autoantigen in two Brazilian cases of IgA pemphigus. J Dermatol 2003;30(12):886-91. 2. Hodak E, Lapidoth M, David M. Effect of colchicine in the subcorneal pustular dermatosis type of IgA pemphigus. J Am Acad Dermatol 1999;40(1):91-4. 3. Howell S, Bessinger G, Altman C, Belnap C. Rapid response of IgA pemphigus of the subcorneal pustular dermatosis subtype to treatment with adalimumab and mycophenolate mofetil. J Am Acad Dermatol 2005;53(3):541-3. 4. Gruss C, Zillikens D, Hashimoto T, Amagai M, Kroiß M, Vogt T, et al. Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin. J Am Acad Dermatol 2000;43(5 Pt 2):923-6. 5. Yasuda H, Kobayashi H, Hashimoto T, Itoh K, Yamane M, Nakamura J. Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of autoantibodies to desmocollin-1 and clinical review. Br J Dermatol 2000;143(1):144-8. http://dx.doi.org/10.1016/j.jaad.2013.09.037
Primary nonadherence (failure to obtain prescribed medicines) among dermatology patients To the Editor: Primary nonadherence, defined as when a patient fails to obtain a prescribed medication, has been largely unstudied in dermatology. However, medication nonadherence in general has been shown to be a major public health issue that is associated with increased morbidity and mortality in patients across multiple fields of medicine,1-3 placing a substantial economic burden on the