e64
Correspondence
Aysßen Karaduman, MD Department of Dermatology Faculty of Medicine Hacettepe University Ankara Turkey Conflicts of interest: None. References 1 Maeda E, Akahane M, Kiryu S, et al. Spectrum of Epstein-Barr virus-related disease: a pictorial review. Jpn J Radiol 2009; 27: 4–19. 2 Baldari U, Cancellieri C, Celli B, et al. Skin disorders and Epstein Barr virus primary infection: results of a 31 month survey. J Eur Acad Dermatol Venereol 1995; 4: 239. 3 Ikediobi NI, Tyring SK. Cutaneous manifestations of EpsteinBarr virus infection. Dermatol Clin 2002; 20: 283–289. 4 Mendoza N, Diamantis M, Arora A, et al. Mucocutaneous manifestations of Epstein-Barr virus infection. Am J Clin Dermatol 2008; 9: 295–305. 5 Cho KH, Lee SH, Kim CW, et al. Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol 2004; 151: 372–380.
Tick bite-related meat allergy as a cause of chronic urticaria, angioedema, and anaphylaxis in endemic areas
Chronic Urticaria Here we describe a patient from the Eastern United States who developed a novel, more recently described cause of chronic urticaria. He was found to produce IgE antibodies to galactose-a-1,3-galactose (alpha-gal); a mammalian oligosaccharide present in many of the red meats consumed in the world. Upon discontinuing the consumption of trigger meats, the patient’s symptoms resolved. A 52-year-old Caucasian man from West Virginia presented to our clinic with a 2-year history of hives. The patient described his skin lesions as sporadic welts, which resolved within 24 hours. He had three severe breakouts requiring emergency room visits. On one occasion, he developed hives, tongue swelling, chest tightness, and diarrhea requiring admission to the hospital. On two other occasions, his symptoms were less severe, only requiring treatment with diphenhydramine and prednisone. He did relate his breakouts to meat consumption. He is a taxidermist by trade and enjoys hunting, hiking, and being outdoors. Notably, he had a history of frequent tick bites. Laboratory testing was within normal limits, including complete blood count, complete metabolic panel, thyroid stimulating hormone, antithyroglobin and antithyroid perInternational Journal of Dermatology 2015, 54, e56–e69
oxidase antibodies, complement levels, and serum tryptase. Upon a more thorough investigation, it was discovered that the patient produced IgE antibodies to alpha-gal. He was told to avoid all forms of meat, including beef, pork, chicken, and game meats. The patient discovered through his own experimentation that he could tolerate only venison; other forms of meat caused delayed-onset urticaria. Since our discovery of this patient’s alpha-gal-specific IgE and avoidance of triggers, he experienced only one episode of urticaria in the last year. This occurred when his venison steak was cooked on a grill that was just used for preparing beef. IgE antibodies against the mammalian oligosaccharide alpha-gal were first described in 2008 in patients experiencing severe hypersensitivity reactions to the monoclonal antibody, cetuximab, which is approved for use in colorectal cancer and squamous cell carcinoma of the head and neck.1 A relationship between IgE antibodies to alpha-gal and recurrent episodes of anaphylaxis, angioedema, or urticaria after meat ingestion was later described in 2009.2,3 The alpha-gal moiety is present in a variety of proteins consumed by humans, including poultry, pork, and beef. The production of these IgE antibodies has been linked to bites from Ixodes holocyclus in Australia2 and Amblyomma americanum (lone star tick) in the United States.4 Screening studies have shown that seropositive individuals are predominately in the Southeastern United States, Northern Australia, Kenya, and Ecuador, but not in regions with low tick density.2–4 A previous study described three individuals who developed urticaria, angioedema, respiratory distress, or syncope and seroconversion after tick bites and meat ingestion in Virginia.4 This prospective series demonstrated previously normal IgE alpha-gal antibody level rose to 20 times after their exposure to tick bites.4 There seems to be a correlation between severity of tick bite-mediated local cutaneous reaction and the development of alpha-gal antibodies as well.4 More recently, Hamsten et al. reported alpha-gal in the gastrointestinal tract of the tick Ixodes ricinus in a Swedish population. Immunohistochemical staining of sera showed binding to these epitopes in tick gastrointestinal tract.5 In conclusion, we believe that patients that suffer from chronic urticaria should be questioned about tick bites and their symptoms in relationship to meat ingestion, particularly in tick endemic areas. IgE antibodies to alpha-gal titers can help confirm the diagnosis in appropriate clinical settings. We also report that venison may be tolerable for patients with alpha-gal allergy under controlled challenges as seen in our patient. Advice to avoid trigger meats in these individuals may decrease exacerbations significantly and dramatically improve their quality of life. ª 2014 The International Society of Dermatology
Correspondence
Grant K. Ghahramani, MD Department of Dermatology University of Iowa Hospitals and Clinics Iowa City IA, USA E-mail: [email protected] James Temprano, MD Division of Infectious Diseases, Allergy and Immunology Department of Internal Medicine School of Medicine Saint Louis University St. Louis MO, USA Grant K. Ghahramani and James Temprano contributed equally to this article. Conflicts of interest: None. References 1 Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-a-1,3-galactose. N Engl J Med 2008; 358: 1109–1117. 2 Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009; 123: 426–433. 3 Van Nunen SA, OConnor KS, Clarke LR, et al. An association between tick bite reactions and red meat allergy in humans. Med J Aust 2009; 190: 510–511. 4 Commins SP, James HR, Kelly LA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-a-1,3-galactose. J Allergy Clin Immunol 2011; 127: 1286–1293. 5 Hamsten C, Starkhammar M, Tran TA, et al. Identification of galactose-a-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy 2013; 68: 549–552.
Severe contact dermatitis due to a metal scratcher
New causes of nickel contact dermatitis are constantly discovered, and the source of nickel exposure in a single patient can be unexpected and very difficult to anticipate. We report a new but possibly common cause of nickel contact dermatitis. A 63-year-old Caucasian female was referred for patch testing in December 2012 with a severe, diffuse dermatitis involving all of her body surfaces except her face, palms, and soles. She complained of terrible pruritus and showed ª 2014 The International Society of Dermatology
evident signs of linear scratching (Fig. 1a). Her history revealed that the rash first developed in June 2010 around her wrists and gradually spread to the rest of her body. Multiple skin biopsies showed spongiotic dermatitis. Laboratory tests were within normal range except for circulating eosinophils at 655 cells/ml. She had no significant personal or familiar history of atopy. She had negative prick tests to aeroallergens. Topical high potency steroids, systemic steroids, and antihistamines were of limited benefit. The patient also tried cyclosporine 3 mg/kg per day for three weeks, which did not improve the condition and had to be stopped due to secondary gastrointestinal upset. The dermatitis did not improve when she was out of her house on vacation. Although most of her skin was compromised by the eczema, we decided to patch test. Patch-test preparations were obtained from Chemotechnique Diagnostics AB (Vellinge, Sweden) with IQ-Ultra chambers (Chemotechnique Diagnostics AB) and Hypafix tape (BSN medical, Hamburg, Germany). We applied the North American Standard Series to areas of the back that were less compromised. Readings were performed at D2 and D4 according to the International Contact Dermatitis Research Group guidelines. The patient had a 3+ reaction to nickel (Fig. 1b). The patient was given a short course of prednisone (40 mg/day for 3 days) and instructions to avoid possible nickel containing objects. She was wearing a metal watch at that time. At follow-up after 10 days, the skin lesions were almost completely cleared and the pruritus was gone. The patient realized she was constantly using two metal scratchers to reach all her itching body areas (Fig. 1c). These scratchers tested positive to the dimethylglyoxime test. They had a telescopic handle that could reach up to 20 inches and a curved end with five fingers. They are marketed as stainless steel with a nickel-plated pewter finish. She also could retrospectively identify the initial sites of itching in the areas where she had contact with her jewelry on the neck and wrists. After one month of follow-up, the patient remained clear with minimal topical steroid application and no systemic medications. New sources for nickel sensitization are constantly described; these include cellphones,1,2 musical instruments,3 guitar strings,4 and laptop computers.5 To our knowledge, this is the first report of diffuse nickel dermatitis due to metal scratchers. This patient had a 2-year history of poor quality of life because of the itching. This is why we decided to perform the patch tests even with a widespread dermatitis. Although metals can cause irritant reactions, in this situation, we believe that the complete resolution of the dermatitis after avoiding the offending scratchers as well as the persistence of the patch-test reaction 14 days after application confirm the diagnosis. This case is presented to draw physicians’ International Journal of Dermatology 2015, 54, e56–e69
e65
Correspondence
Aysßen Karaduman, MD Department of Dermatology Faculty of Medicine Hacettepe University Ankara Turkey Conflicts of interest: None. References 1 Maeda E, Akahane M, Kiryu S, et al. Spectrum of Epstein-Barr virus-related disease: a pictorial review. Jpn J Radiol 2009; 27: 4–19. 2 Baldari U, Cancellieri C, Celli B, et al. Skin disorders and Epstein Barr virus primary infection: results of a 31 month survey. J Eur Acad Dermatol Venereol 1995; 4: 239. 3 Ikediobi NI, Tyring SK. Cutaneous manifestations of EpsteinBarr virus infection. Dermatol Clin 2002; 20: 283–289. 4 Mendoza N, Diamantis M, Arora A, et al. Mucocutaneous manifestations of Epstein-Barr virus infection. Am J Clin Dermatol 2008; 9: 295–305. 5 Cho KH, Lee SH, Kim CW, et al. Epstein-Barr virus-associated lymphoproliferative lesions presenting as a hydroa vacciniforme-like eruption: an analysis of six cases. Br J Dermatol 2004; 151: 372–380.
Tick bite-related meat allergy as a cause of chronic urticaria, angioedema, and anaphylaxis in endemic areas
Chronic Urticaria Here we describe a patient from the Eastern United States who developed a novel, more recently described cause of chronic urticaria. He was found to produce IgE antibodies to galactose-a-1,3-galactose (alpha-gal); a mammalian oligosaccharide present in many of the red meats consumed in the world. Upon discontinuing the consumption of trigger meats, the patient’s symptoms resolved. A 52-year-old Caucasian man from West Virginia presented to our clinic with a 2-year history of hives. The patient described his skin lesions as sporadic welts, which resolved within 24 hours. He had three severe breakouts requiring emergency room visits. On one occasion, he developed hives, tongue swelling, chest tightness, and diarrhea requiring admission to the hospital. On two other occasions, his symptoms were less severe, only requiring treatment with diphenhydramine and prednisone. He did relate his breakouts to meat consumption. He is a taxidermist by trade and enjoys hunting, hiking, and being outdoors. Notably, he had a history of frequent tick bites. Laboratory testing was within normal limits, including complete blood count, complete metabolic panel, thyroid stimulating hormone, antithyroglobin and antithyroid perInternational Journal of Dermatology 2015, 54, e56–e69
oxidase antibodies, complement levels, and serum tryptase. Upon a more thorough investigation, it was discovered that the patient produced IgE antibodies to alpha-gal. He was told to avoid all forms of meat, including beef, pork, chicken, and game meats. The patient discovered through his own experimentation that he could tolerate only venison; other forms of meat caused delayed-onset urticaria. Since our discovery of this patient’s alpha-gal-specific IgE and avoidance of triggers, he experienced only one episode of urticaria in the last year. This occurred when his venison steak was cooked on a grill that was just used for preparing beef. IgE antibodies against the mammalian oligosaccharide alpha-gal were first described in 2008 in patients experiencing severe hypersensitivity reactions to the monoclonal antibody, cetuximab, which is approved for use in colorectal cancer and squamous cell carcinoma of the head and neck.1 A relationship between IgE antibodies to alpha-gal and recurrent episodes of anaphylaxis, angioedema, or urticaria after meat ingestion was later described in 2009.2,3 The alpha-gal moiety is present in a variety of proteins consumed by humans, including poultry, pork, and beef. The production of these IgE antibodies has been linked to bites from Ixodes holocyclus in Australia2 and Amblyomma americanum (lone star tick) in the United States.4 Screening studies have shown that seropositive individuals are predominately in the Southeastern United States, Northern Australia, Kenya, and Ecuador, but not in regions with low tick density.2–4 A previous study described three individuals who developed urticaria, angioedema, respiratory distress, or syncope and seroconversion after tick bites and meat ingestion in Virginia.4 This prospective series demonstrated previously normal IgE alpha-gal antibody level rose to 20 times after their exposure to tick bites.4 There seems to be a correlation between severity of tick bite-mediated local cutaneous reaction and the development of alpha-gal antibodies as well.4 More recently, Hamsten et al. reported alpha-gal in the gastrointestinal tract of the tick Ixodes ricinus in a Swedish population. Immunohistochemical staining of sera showed binding to these epitopes in tick gastrointestinal tract.5 In conclusion, we believe that patients that suffer from chronic urticaria should be questioned about tick bites and their symptoms in relationship to meat ingestion, particularly in tick endemic areas. IgE antibodies to alpha-gal titers can help confirm the diagnosis in appropriate clinical settings. We also report that venison may be tolerable for patients with alpha-gal allergy under controlled challenges as seen in our patient. Advice to avoid trigger meats in these individuals may decrease exacerbations significantly and dramatically improve their quality of life. ª 2014 The International Society of Dermatology
Correspondence
Grant K. Ghahramani, MD Department of Dermatology University of Iowa Hospitals and Clinics Iowa City IA, USA E-mail: [email protected] James Temprano, MD Division of Infectious Diseases, Allergy and Immunology Department of Internal Medicine School of Medicine Saint Louis University St. Louis MO, USA Grant K. Ghahramani and James Temprano contributed equally to this article. Conflicts of interest: None. References 1 Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-a-1,3-galactose. N Engl J Med 2008; 358: 1109–1117. 2 Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009; 123: 426–433. 3 Van Nunen SA, OConnor KS, Clarke LR, et al. An association between tick bite reactions and red meat allergy in humans. Med J Aust 2009; 190: 510–511. 4 Commins SP, James HR, Kelly LA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-a-1,3-galactose. J Allergy Clin Immunol 2011; 127: 1286–1293. 5 Hamsten C, Starkhammar M, Tran TA, et al. Identification of galactose-a-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy 2013; 68: 549–552.
Severe contact dermatitis due to a metal scratcher
New causes of nickel contact dermatitis are constantly discovered, and the source of nickel exposure in a single patient can be unexpected and very difficult to anticipate. We report a new but possibly common cause of nickel contact dermatitis. A 63-year-old Caucasian female was referred for patch testing in December 2012 with a severe, diffuse dermatitis involving all of her body surfaces except her face, palms, and soles. She complained of terrible pruritus and showed ª 2014 The International Society of Dermatology
evident signs of linear scratching (Fig. 1a). Her history revealed that the rash first developed in June 2010 around her wrists and gradually spread to the rest of her body. Multiple skin biopsies showed spongiotic dermatitis. Laboratory tests were within normal range except for circulating eosinophils at 655 cells/ml. She had no significant personal or familiar history of atopy. She had negative prick tests to aeroallergens. Topical high potency steroids, systemic steroids, and antihistamines were of limited benefit. The patient also tried cyclosporine 3 mg/kg per day for three weeks, which did not improve the condition and had to be stopped due to secondary gastrointestinal upset. The dermatitis did not improve when she was out of her house on vacation. Although most of her skin was compromised by the eczema, we decided to patch test. Patch-test preparations were obtained from Chemotechnique Diagnostics AB (Vellinge, Sweden) with IQ-Ultra chambers (Chemotechnique Diagnostics AB) and Hypafix tape (BSN medical, Hamburg, Germany). We applied the North American Standard Series to areas of the back that were less compromised. Readings were performed at D2 and D4 according to the International Contact Dermatitis Research Group guidelines. The patient had a 3+ reaction to nickel (Fig. 1b). The patient was given a short course of prednisone (40 mg/day for 3 days) and instructions to avoid possible nickel containing objects. She was wearing a metal watch at that time. At follow-up after 10 days, the skin lesions were almost completely cleared and the pruritus was gone. The patient realized she was constantly using two metal scratchers to reach all her itching body areas (Fig. 1c). These scratchers tested positive to the dimethylglyoxime test. They had a telescopic handle that could reach up to 20 inches and a curved end with five fingers. They are marketed as stainless steel with a nickel-plated pewter finish. She also could retrospectively identify the initial sites of itching in the areas where she had contact with her jewelry on the neck and wrists. After one month of follow-up, the patient remained clear with minimal topical steroid application and no systemic medications. New sources for nickel sensitization are constantly described; these include cellphones,1,2 musical instruments,3 guitar strings,4 and laptop computers.5 To our knowledge, this is the first report of diffuse nickel dermatitis due to metal scratchers. This patient had a 2-year history of poor quality of life because of the itching. This is why we decided to perform the patch tests even with a widespread dermatitis. Although metals can cause irritant reactions, in this situation, we believe that the complete resolution of the dermatitis after avoiding the offending scratchers as well as the persistence of the patch-test reaction 14 days after application confirm the diagnosis. This case is presented to draw physicians’ International Journal of Dermatology 2015, 54, e56–e69
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