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Correspondence
2 Li J, Zheng HY. Erythroderma: a clinical and prognostic study. Dermatology 2012; 225: 154–162. 3 Tappeiner G, Konrad K, Holubar K. Erythrodermic bullous pemphigoid. Report of a case. J Am Acad Dermatol 1982; 6: 489–492. 4 Alonso-Llamazares J, Dietrich SM, Gibson LE. Bullous pemphigoid presenting as exfoliative erythroderma. J Am Acad Dermatol 1998; 39: 827–830. 5 Amato L, Gallerani I, Mei S, et al. Erythrodermic bullous pemphigoid. Int J Dermatol 2001; 40: 343–346.
Heavy metals and hand dermatitis: analysis of data in the US National Health and Nutrition Examination Survey
Editor, Hand dermatitis is a common, chronic, relapsing skin disease1 that results from a variety of causes including environmental exposures to irritants and allergens.2–4 It is also a common occupational skin disease.1 Quality of life and eczema severity have previously been reported to be associated with environmental or occupational exposure to heavy metals.5 We investigated whether the diagnosis of active hand dermatitis was associated with whole blood levels of three heavy metals (lead, inorganic mercury, and cadmium) among participants in the 2003–2004 US National Health and Nutrition Examination Survey (NHANES). In our analysis of interest, randomly selected individuals aged 20–59 years were interviewed and subsequently completed health and laboratory examinations. Standardized photographs of the dorsal and palmar views of the hands were available for all study participants. These photographs were read by two dermatologists for the presence of hand dermatitis. Whole blood concentrations of lead, inorganic mercury, and cadmium were determined using inductively coupled plasma mass spectrome-
try. Variables such as age, gender, work status, atopic diathesis, and body mass index (BMI) were included for analysis as possible confounding factors. Using the Mann–Whitney U-test, heavy metal blood levels were compared between those with and without hand dermatitis. Multivariate logistic regression analysis was performed to adjust for possible confounding factors. A total of 2688 study participants were included in the analysis. Among them, 42 (1.6%) cases of active hand dermatitis were diagnosed. Whole blood lead and cadmium levels were found to be significantly higher in those with active hand dermatitis compared to those without (P < 0.001 and P = 0.008, respectively). Blood inorganic mercury levels did not differ significantly between those with and without active hand dermatitis. The results are summarized in Table 1. In multivariate logistic regression, blood lead levels remained significantly associated with active hand dermatitis after adjusting for age, gender, work status, atopic diathesis, and BMI (P = 0.026). The odds of having active hand dermatitis increased by 1.11 for each unit increase in blood lead levels. However, the associations between active hand dermatitis and blood levels of inorganic mercury and cadmium were not significant (P = 0.871 and P = 0.132, respectively). In this study, although the diagnosis of active hand dermatitis was significantly associated with raised blood lead levels, all participants demonstrated blood lead levels within normal limits. Our results are consistent with findings reported in the current literature. Hon et al.5 reported that despite being within normal limits, raised serum lead levels were positively correlated with eczema severity, poor quality of life, eosinophil count, and logtransformed immunoglobulin E (IgE) in children, whereas serum levels of cadmium and mercury showed no such
Table 1 Characteristics of 2688 study participants with (n = 42) and without (n = 2646) hand dermatitis Characteristic
Hand dermatitis
Age, years, mean Gender, n (%) Male (n = 1301) Female (n = 1387) Work status, n (%) Working (n = 1850) Not working (n = 837) Atopic diathesis, n (%) Yes (n = 859) No (n = 1829) Body mass index, kg/m2, mean Blood lead level, lg/l, median Blood inorganic mercury level, lg/l, median Blood cadmium level, lg/l, median
40.4
No hand dermatitis
OR (95% CI)
37.7
P-value 0.129
10.4 (3.70–29.2) 1.00
< 0.0001
38 (2.9%) 4 (0.3%)
1263 (97.1%) 1383 (99.7%)
33 (1.8%) 9 (1.1%)
1817 (98.2%) 828 (98.9%)
1.67 (0.80–3.51) 1.00
0.170
7 (0.8%) 35 (1.9%) 29.5 2.20 0.30 0.60
852 (99.2%) 1794 (98.1%) 28.5 1.40 0.30 0.30
0.42 (0.19–0.95) 1.00
0.0322 0.328 < 0.001 0.494 0.008
95% CI, 95% confidence interval; OR, odds ratio. International Journal of Dermatology 2016, 55, e105–e120
ª 2015 The International Society of Dermatology
Correspondence
correlations. By contrast, a study conducted in Germany reported an association between the body burden of mercury and acute atopic eczema.6 The effects of heavy metals on the immune system partly explain their roles in the pathogenesis of eczema. Heavy metals such as lead can tip the Th1/Th2 balance to favor Th2 predominance.7 They are also capable of switching B lymphocytes to IgE antibody production, thus promoting hypersensitivity reactions.7,8 Not only is lead cytotoxic to epithelial cells, it also increases the generation of reactive oxygen species and production of proinflammatory cytokines.9 It is likely that physician assessments of standardized photographs are more specific in detecting cases of hand dermatitis that are more severe and persistent at the time of examination. Higher blood levels of lead in those with active hand dermatitis may signify an increased environmental exposure to lead, which is, in turn, associated with the more persistent and severe type of hand dermatitis observed in our study. The penetration of lead through damaged skin can be many times higher than that through intact skin, especially with the use of skin cleansers.10 Therefore, it is prudent for dermatologists to recommend that patients with hand dermatitis should practice hand protection and minimize the vicious cycle of further occupational exposure to environmental toxins, including heavy metals.
Yi C. Lai, BA Yik Weng Yew, MD Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA, USA Yik Weng Yew, MD Department of Dermatology National Skin Centre Singapore E-mail: [email protected] References 1 Meding B, Swanbeck G. Prevalence of hand eczema in an industrial city. Br J Dermatol 1987; 116: 627–634. 2 Meding B, Swanbeck G. Predictive factors for hand eczema. Contact Dermatitis 1990; 23: 154–161. 3 Meding B, Liden C, Berglind N. Self-diagnosed dermatitis in adults. Results from a population survey in Stockholm. Contact Dermatitis 2001; 45: 341–345. 4 Meding B, J€arvholm B. Hand eczema in Swedish adults – changes in prevalence between 1983 and 1996. J Invest Dermatol 2002; 118: 719–723. ª 2015 The International Society of Dermatology
5 Hon KL, Wang SS, Hung EC, et al. Serum levels of heavy metals in childhood eczema and skin diseases: friends or foes. Pediatr Allergy Immunol 2010; 21: 831–836. 6 Weidinger S, Kramer U, Dunemann L, et al. Body burden of mercury is associated with acute atopic eczema and total IgE in children from southern Germany. J Allergy Clin Immunol 2004; 114: 457–459. 7 Mishra KP. Lead exposure and its impact on immune system: a review. Toxicol In Vitro 2009; 23: 969–972. 8 Min JY, Min KB, Kim R, et al. Blood lead levels and increased bronchial responsiveness. Biol Trace Elem Res 2008; 123: 41–46. 9 Theron AJ, Tintinger GR, Anderson R. Harmful interactions of non-essential heavy metals with cells of the innate immune system. J Clinic Toxicol 2012; S3: 005. 10 Filon FL, Boeniger M, Maina G, et al. Skin absorption of inorganic lead (PbO) and the effect of skin cleansers. J Occup Environ Med 2006; 48: 692–699.
Cerebral tuberculoma with pulmonary tuberculosis in a patient with psoriasis treated with adalimumab, an antitumor necrosis factor-a agent
Editor, Anti-tumor necrosis factor-a (TNF-a) agents are highly effective in the treatment of psoriasis.1 However, their use is associated with an increased risk for tuberculosis (TB) because TNF-a plays an important role in host defense against Mycobacterium tuberculosis.2–5 Screening for and subsequent chemoprophylaxis of diagnosed latent TB infections (LTBIs) have been found to dramatically reduce the risk for active disease in patients on anti-TNFa therapy.6 More than 50% of cases of active TB reported in patients on anti-TNF-a agents are extrapulmonary, but cerebral TB is rare.2–5 We describe a patient with severe psoriasis and psoriatic arthritis who developed cerebral tuberculoma with pulmonary TB while on adalimumab treatment despite an initial negative screening for LTBI. A 60-year-old man with a 25-year history of psoriasis and a 7-year history of severe disabling spondyloarthritis was hospitalized in August 2012. His comorbidities included hypertension, diabetes mellitus, stable ischemic heart disease, and previous cerebrovascular accident. He was started on subcutaneous adalimumab 40 mg administered every fortnight. The patient had no history of prior treatment with systemic immunosuppressants. His plain chest radiograph (CXR) was normal, and Mantoux test was zero prior to commencement of adalimumab. He showed marked improvement and was able to ambulate independently after 3 months of adalimumab, which was continued at 40 mg per fortnight. However, at 8 months post-therapy, the patient developed gradual weakness of International Journal of Dermatology 2016, 55, e105–e120
e115
Correspondence
2 Li J, Zheng HY. Erythroderma: a clinical and prognostic study. Dermatology 2012; 225: 154–162. 3 Tappeiner G, Konrad K, Holubar K. Erythrodermic bullous pemphigoid. Report of a case. J Am Acad Dermatol 1982; 6: 489–492. 4 Alonso-Llamazares J, Dietrich SM, Gibson LE. Bullous pemphigoid presenting as exfoliative erythroderma. J Am Acad Dermatol 1998; 39: 827–830. 5 Amato L, Gallerani I, Mei S, et al. Erythrodermic bullous pemphigoid. Int J Dermatol 2001; 40: 343–346.
Heavy metals and hand dermatitis: analysis of data in the US National Health and Nutrition Examination Survey
Editor, Hand dermatitis is a common, chronic, relapsing skin disease1 that results from a variety of causes including environmental exposures to irritants and allergens.2–4 It is also a common occupational skin disease.1 Quality of life and eczema severity have previously been reported to be associated with environmental or occupational exposure to heavy metals.5 We investigated whether the diagnosis of active hand dermatitis was associated with whole blood levels of three heavy metals (lead, inorganic mercury, and cadmium) among participants in the 2003–2004 US National Health and Nutrition Examination Survey (NHANES). In our analysis of interest, randomly selected individuals aged 20–59 years were interviewed and subsequently completed health and laboratory examinations. Standardized photographs of the dorsal and palmar views of the hands were available for all study participants. These photographs were read by two dermatologists for the presence of hand dermatitis. Whole blood concentrations of lead, inorganic mercury, and cadmium were determined using inductively coupled plasma mass spectrome-
try. Variables such as age, gender, work status, atopic diathesis, and body mass index (BMI) were included for analysis as possible confounding factors. Using the Mann–Whitney U-test, heavy metal blood levels were compared between those with and without hand dermatitis. Multivariate logistic regression analysis was performed to adjust for possible confounding factors. A total of 2688 study participants were included in the analysis. Among them, 42 (1.6%) cases of active hand dermatitis were diagnosed. Whole blood lead and cadmium levels were found to be significantly higher in those with active hand dermatitis compared to those without (P < 0.001 and P = 0.008, respectively). Blood inorganic mercury levels did not differ significantly between those with and without active hand dermatitis. The results are summarized in Table 1. In multivariate logistic regression, blood lead levels remained significantly associated with active hand dermatitis after adjusting for age, gender, work status, atopic diathesis, and BMI (P = 0.026). The odds of having active hand dermatitis increased by 1.11 for each unit increase in blood lead levels. However, the associations between active hand dermatitis and blood levels of inorganic mercury and cadmium were not significant (P = 0.871 and P = 0.132, respectively). In this study, although the diagnosis of active hand dermatitis was significantly associated with raised blood lead levels, all participants demonstrated blood lead levels within normal limits. Our results are consistent with findings reported in the current literature. Hon et al.5 reported that despite being within normal limits, raised serum lead levels were positively correlated with eczema severity, poor quality of life, eosinophil count, and logtransformed immunoglobulin E (IgE) in children, whereas serum levels of cadmium and mercury showed no such
Table 1 Characteristics of 2688 study participants with (n = 42) and without (n = 2646) hand dermatitis Characteristic
Hand dermatitis
Age, years, mean Gender, n (%) Male (n = 1301) Female (n = 1387) Work status, n (%) Working (n = 1850) Not working (n = 837) Atopic diathesis, n (%) Yes (n = 859) No (n = 1829) Body mass index, kg/m2, mean Blood lead level, lg/l, median Blood inorganic mercury level, lg/l, median Blood cadmium level, lg/l, median
40.4
No hand dermatitis
OR (95% CI)
37.7
P-value 0.129
10.4 (3.70–29.2) 1.00
< 0.0001
38 (2.9%) 4 (0.3%)
1263 (97.1%) 1383 (99.7%)
33 (1.8%) 9 (1.1%)
1817 (98.2%) 828 (98.9%)
1.67 (0.80–3.51) 1.00
0.170
7 (0.8%) 35 (1.9%) 29.5 2.20 0.30 0.60
852 (99.2%) 1794 (98.1%) 28.5 1.40 0.30 0.30
0.42 (0.19–0.95) 1.00
0.0322 0.328 < 0.001 0.494 0.008
95% CI, 95% confidence interval; OR, odds ratio. International Journal of Dermatology 2016, 55, e105–e120
ª 2015 The International Society of Dermatology
Correspondence
correlations. By contrast, a study conducted in Germany reported an association between the body burden of mercury and acute atopic eczema.6 The effects of heavy metals on the immune system partly explain their roles in the pathogenesis of eczema. Heavy metals such as lead can tip the Th1/Th2 balance to favor Th2 predominance.7 They are also capable of switching B lymphocytes to IgE antibody production, thus promoting hypersensitivity reactions.7,8 Not only is lead cytotoxic to epithelial cells, it also increases the generation of reactive oxygen species and production of proinflammatory cytokines.9 It is likely that physician assessments of standardized photographs are more specific in detecting cases of hand dermatitis that are more severe and persistent at the time of examination. Higher blood levels of lead in those with active hand dermatitis may signify an increased environmental exposure to lead, which is, in turn, associated with the more persistent and severe type of hand dermatitis observed in our study. The penetration of lead through damaged skin can be many times higher than that through intact skin, especially with the use of skin cleansers.10 Therefore, it is prudent for dermatologists to recommend that patients with hand dermatitis should practice hand protection and minimize the vicious cycle of further occupational exposure to environmental toxins, including heavy metals.
Yi C. Lai, BA Yik Weng Yew, MD Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA, USA Yik Weng Yew, MD Department of Dermatology National Skin Centre Singapore E-mail: [email protected] References 1 Meding B, Swanbeck G. Prevalence of hand eczema in an industrial city. Br J Dermatol 1987; 116: 627–634. 2 Meding B, Swanbeck G. Predictive factors for hand eczema. Contact Dermatitis 1990; 23: 154–161. 3 Meding B, Liden C, Berglind N. Self-diagnosed dermatitis in adults. Results from a population survey in Stockholm. Contact Dermatitis 2001; 45: 341–345. 4 Meding B, J€arvholm B. Hand eczema in Swedish adults – changes in prevalence between 1983 and 1996. J Invest Dermatol 2002; 118: 719–723. ª 2015 The International Society of Dermatology
5 Hon KL, Wang SS, Hung EC, et al. Serum levels of heavy metals in childhood eczema and skin diseases: friends or foes. Pediatr Allergy Immunol 2010; 21: 831–836. 6 Weidinger S, Kramer U, Dunemann L, et al. Body burden of mercury is associated with acute atopic eczema and total IgE in children from southern Germany. J Allergy Clin Immunol 2004; 114: 457–459. 7 Mishra KP. Lead exposure and its impact on immune system: a review. Toxicol In Vitro 2009; 23: 969–972. 8 Min JY, Min KB, Kim R, et al. Blood lead levels and increased bronchial responsiveness. Biol Trace Elem Res 2008; 123: 41–46. 9 Theron AJ, Tintinger GR, Anderson R. Harmful interactions of non-essential heavy metals with cells of the innate immune system. J Clinic Toxicol 2012; S3: 005. 10 Filon FL, Boeniger M, Maina G, et al. Skin absorption of inorganic lead (PbO) and the effect of skin cleansers. J Occup Environ Med 2006; 48: 692–699.
Cerebral tuberculoma with pulmonary tuberculosis in a patient with psoriasis treated with adalimumab, an antitumor necrosis factor-a agent
Editor, Anti-tumor necrosis factor-a (TNF-a) agents are highly effective in the treatment of psoriasis.1 However, their use is associated with an increased risk for tuberculosis (TB) because TNF-a plays an important role in host defense against Mycobacterium tuberculosis.2–5 Screening for and subsequent chemoprophylaxis of diagnosed latent TB infections (LTBIs) have been found to dramatically reduce the risk for active disease in patients on anti-TNFa therapy.6 More than 50% of cases of active TB reported in patients on anti-TNF-a agents are extrapulmonary, but cerebral TB is rare.2–5 We describe a patient with severe psoriasis and psoriatic arthritis who developed cerebral tuberculoma with pulmonary TB while on adalimumab treatment despite an initial negative screening for LTBI. A 60-year-old man with a 25-year history of psoriasis and a 7-year history of severe disabling spondyloarthritis was hospitalized in August 2012. His comorbidities included hypertension, diabetes mellitus, stable ischemic heart disease, and previous cerebrovascular accident. He was started on subcutaneous adalimumab 40 mg administered every fortnight. The patient had no history of prior treatment with systemic immunosuppressants. His plain chest radiograph (CXR) was normal, and Mantoux test was zero prior to commencement of adalimumab. He showed marked improvement and was able to ambulate independently after 3 months of adalimumab, which was continued at 40 mg per fortnight. However, at 8 months post-therapy, the patient developed gradual weakness of International Journal of Dermatology 2016, 55, e105–e120
e115
