- Email: [email protected]
Protein contact dermatitis and food allergy to mare milk
390
Letters / Ann Allergy Asthma Immunol 110 (2013) 386e393 #
Terada Kid’s Allergy & Asthma Clinic Nagoya, Japan **Department of Hygiene School of Medicine Fujita Health University Toyoake, Japan [email protected]
References [1] Palmer CNA, Irvine AD, Terron-Kwiatkowski A, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38:441e446. [2] Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WHI, Shimizu H. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema. Br J Dermatol. 2009;161: 1387e1390.
[3] van den Oord RAHM, Sheikh A. Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and metaanalysis. BMJ. 2009;339. b2433. [4] Paternoster L, Standl M, Chen C-M, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet. 2012;44:187e192. [5] Fallon PG, Sasaki T, Sandilands A, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009;41:602e608. [6] Brown SJ, Asai Y, Cordell HJ, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011;127: 661e667. [7] Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh). 1980;92(suppl):44e47. [8] Tan H-TT, Ellis JA, Koplin JJ, et al. Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants. J Allergy Clin Immunol. 2012;130:1211e1213. [9] Gao P-S, Rafaels NM, Hand T, et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol. 2009;124:507e513.
Protein contact dermatitis and food allergy to mare milk Introduction A 44-year-old atopic woman developed chronic itchy, vesiculosus, and erythematous cupboards lesions on the extensor surfaces of both forearms for several weeks. She had a medical history of seasonal rhinitis. She had used mare milk (MM)ebased organic cosmetics (soap and shampoo) for 3 months and took dietary supplements (pills, MM-based) (Chevaline Cosmetics, Lohne, Germany). Cutaneous symptoms were exacerbated immediately after the use of those cosmetics, and she vomited repeatedly immediately after the first intake of MM pills. The skin symptoms (and vomiting) disappeared during a travel but resumed once at home. Cow milk was tolerated. Skin prick tests (SPT) (ALK-Abello, Courbevoie, France) were positive for Betula verrucosa 4 mm and Dactylis glomerata 5 mm (Hist 5mm). SPT for crude MM (8 mm), boiled MM (15 mm), pill powder (10 mm), and shampoo (7 mm) were positive in immediate and delayed (72 h) read. SPT were positive for goat (4 mm) and sheep (6 mm) milk, whereas they were negative for cow milk and horse dander. Specific IgEs (ImmunoCAP, Phadia, Sweden) were positive for rBetv1 (185 kU/L), rPhlp1-p5 (58 kU/L), goat milk (15.4 kU/L), sheep milk (15 kU/L), MM (500 kU/L), and cow milk (8.46 kU/L). IgE a-lactalbumin (1.65 kU/L), b-lactoglobulin (1.50 kU/L), and caseins (14.1 kU/L) from cow milk were also positive. Horse dander IgE was less than 0.10 kU/L. Food challenges with sheep and goat milk were negative. IgEs against the patient’s shampoo, pill powder, and MM extracts were positive (measured by enzyme-linked immunosorbent assay. Shampoo, MM, and pill powder extracts were also analyzed by Western blot. This showed that the shampoo and pills contained the same proteins with MM and that the patient’s serum recognized many allergens, mainly at 150 kDa, 30 to 35 kDa, 18 kDa, and 66 kDa (Fig 1). A lymphoblastic transformation test (measured by CD69 and CD25 expression) was positive for the pill powder (50, 100, 200, and 400 mg/mL). Those tests confirmed immediate and delayed sensitivity to MM and its derivatives (pills and shampoo). Symptom resolution was achieved after exclusion of all MM-based products. Milk from mare (Equus caballus) can be consumed fresh or as food supplement pills and is used for cosmetics manufacturing. Allergy to MM is rare, but the literature report some food anaphylaxis cases.1e3
Disclosures: Authors have nothing to disclose.
Several allergens from MM have been described: albumin (Equ c 3), alpha-lactoglobulin, beta-lactoglobulin, and casein (www. allergome.org). Our patient was sensitized to different allergens corresponding to immunoglobulins (150 kDa), caseins (30e35 kDa), beta-lactoglobulin (18 kDa), and horse albumin (66 kDa). Some of them are common to other mammalian milk or horse
Figure 1. Mare milk (MM), pills (P), and shampoo (S) extracts were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis Western blot. IgE reactivity from the patient (1) was revealed by an anti-IgE alkaline phosphatase label. Patient serum was diluted 1/10, and blocking buffer was used as a negative control (C).
Letters / Ann Allergy Asthma Immunol 110 (2013) 386e393
dander, but clinical cross-reactions are rare.1e4 Businco et al4 showed that only 2 of 25 cow’s milkeallergic children had positive SPT for MM, and 1 had a positive MM food challenge.5 Low-level sequences’ identity between allergens could be an explanation. For casein, Jenkins et al5 demonstrated that the homologies between aS1-casein and b-casein from MM and cow milk were 39% and 56%, respectively, too low of a level to induce clinical cross-reactivity. The authors proposed that the evolutionary distance between humans and animals could explain differences among allergenicity (ie, bovines are more distant from human than from horse).5 Other authors have studied cross-reactivity between cow milk and other mammalian milk. They showed that cross-reactivities between cow milk and goat or sheep milk were high, unlike mare, camel, or donkey milk.6e9 Protein contact dermatitis was first described in 1976 in Danish food handlers. The most frequent symptom is a chronic eczema with occasional urticarial or vesicular exacerbation a few minutes after contact with the sensitizing protein, which could be of either animal or vegetal origin. It involves a type I hypersensitivity reaction, but the precise pathophysiological mechanism remains unclear. Some authors have reported a combination of type I and IV hypersensitivity. Allergic contact dermatitis is the main differential diagnosis and is induced by low-molecular-weight allergens and involves type IV hypersensitivity.10 In our patient, we demonstrated the type I hypersensitivity mechanism and the positive lymphoblastic transformation test associated with the delayed positive skin prick tests suggested an associated cellular mechanism. In conclusion, we have shown, for the first time, that topical cutaneous use of MM-based cosmetics can lead to protein contact dermatitis and secondarily to food allergy. Because MM is proposed as an “alternative medicine” for treatment of skin disorders and because topical usage can secondarily lead to potentially severe food allergy, we want to report this case. Virginie Doyen, MD* Virginie Leduc, PhDy Francis Corazza, PhDz Michel Mairesse, MD*
391
Claire Ledent, MD* Olivier Michel, PhD* *Clinic of Immuno-Allergology CHU Brugmann Université Libre de Bruxelles (ULB) Brussels, Belgium y Research Department ALK-Abello Courbevoie, France z Laboratory of Immunology CHU Brugmann Université Libre de Bruxelles (ULB) Brussels, Belgium [email protected]
References [1] Robles S, Torres MJ, Mayorga C, Rodríguez-Bada JL, Fernández TD, Blanca M, Bartolomé B. Anaphylaxis to Mare’s milk. Ann Allergy Asthma Immunol. 2007; 98:600e602. [2] Fanta C, Ebner C. Allergy to mare’s milk. Allergy. 1998;53:539e540. [3] Gall H, Kalveram CM, Sick H, Sterry W. Allergy to the heat-labile proteins alpha-lactalbumin and beta-lactoglobulin in mare’s milk. J Allergy Clin Immunol. 1996;97:1304e1307. [4] Businco L, Giampietro PG, Lucenti P, et al. Allergenicity of mare’s milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2000;105: 1031e1034. [5] Jenkins JA, Breiteneder H, Mills EN. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol. 2007;120:1399e1405. [6] Monti G, Bertino E, Muratore MC, et al. Efficacy of donkey’s milk in treating highly problematic cow’s milk allergic children: an in vivo and in vitro study. Pediatr Allergy Immunol. 2007;18:258e264. [7] Muraro MA, Giampietro PG, Galli E. Soy formulas and nonbovine milk. Ann Allergy Asthma Immunol. 2002;89:97e101. [8] Restani P, Gaiaschi A, Plebani A, et al. Cross-reactivity between milk proteins from different animal species. Clin Exp Allergy. 1999;29:997e1004. [9] Hinz K, O’Connor PM, Huppertz T, Ross RP, Kelly AL. Comparison of the principal proteins in bovine, caprine, buffalo, equine and camel milk. J Dairy Res. 2012;79:185e191. [10] Amaro C, Goossens A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review. Contact Dermatitis. 2008;58: 67e75.
Hyper immunoglobulin M syndrome in a 15-year-old boy caused by a Gly219Arg missense mutation Introduction Hyperimmunoglobulin M syndrome is a primary immunodeficiency disorder characterized by low or absent immunoglobulin (Ig) G, IgA, and IgE, with normal or elevated IgM levels.1 X-linked hyper-IgM syndrome (X-HIGM or HIGM1) is the most frequent subtype of HIGM, which is caused by mutations in CD40 ligand (CD40L or CD154) gene encoding for the CD40L expressed on activated T cells.1 CD40L plays an important role in class switching and maturation of B-lymphocytes by interacting with its receptor CD40 on B-cells. CD40L is also important for activation of T-cells. Mutations of CD40L result in a combined T- and B-cell immunodeficiency. Thus, patients with X-HIGM are susceptible to bacterial, fungal, and opportunistic microorganisms.1e3 We report a case of X-HIGM caused by a c.655G>A missense mutation, resulting in decreased but not absent CD40L expression and function on activated T-cells.
Disclosures: Authors have nothing to disclose.
A 15-year-old boy was evaluated for a chronic purulent productive cough present for more than 2 years. He also reported fatigue, nasal congestion with purulent rhinorrhea, chronic gingivitis, and weight loss. His medical history included 5 hospitalizations for pneumonia requiring parenteral antibiotics. He also had a history of recurrent sinusitis, otitis media, severe varicella as an infant, and herpes zoster at age 10 years. He had myringotomy and tympanostomy tubes placed. There was no history of fungal infections. He had aplastic anemia at age 5 years and Crohn’s disease diagnosed at age 8 years. No family history of primary immune deficiency or cystic fibrosis was present. Physical examination was notable for scarring of the tympanic membranes, purulent postnasal drainage, small tonsils, bibasilar rales, splenomegaly, and clubbing. Chest computed tomography scan showed extensive bronchiectasis of the lungs bilaterally. As seen in Table 1, the immunologic evaluation showed decreased IgG, but normal IgM with decreased antibody titers to diphtheria, Haemophilus influenza type B antibody, Streptococcus pneumoniae antibody. Peripheral blood flow cytometry revealed decreased CD3þ T cells, CD4þ T cells, CD8þ T cells, and memory
Letters / Ann Allergy Asthma Immunol 110 (2013) 386e393 #
Terada Kid’s Allergy & Asthma Clinic Nagoya, Japan **Department of Hygiene School of Medicine Fujita Health University Toyoake, Japan [email protected]
References [1] Palmer CNA, Irvine AD, Terron-Kwiatkowski A, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38:441e446. [2] Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WHI, Shimizu H. FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema. Br J Dermatol. 2009;161: 1387e1390.
[3] van den Oord RAHM, Sheikh A. Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and metaanalysis. BMJ. 2009;339. b2433. [4] Paternoster L, Standl M, Chen C-M, et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet. 2012;44:187e192. [5] Fallon PG, Sasaki T, Sandilands A, et al. A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming. Nat Genet. 2009;41:602e608. [6] Brown SJ, Asai Y, Cordell HJ, et al. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol. 2011;127: 661e667. [7] Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh). 1980;92(suppl):44e47. [8] Tan H-TT, Ellis JA, Koplin JJ, et al. Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants. J Allergy Clin Immunol. 2012;130:1211e1213. [9] Gao P-S, Rafaels NM, Hand T, et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol. 2009;124:507e513.
Protein contact dermatitis and food allergy to mare milk Introduction A 44-year-old atopic woman developed chronic itchy, vesiculosus, and erythematous cupboards lesions on the extensor surfaces of both forearms for several weeks. She had a medical history of seasonal rhinitis. She had used mare milk (MM)ebased organic cosmetics (soap and shampoo) for 3 months and took dietary supplements (pills, MM-based) (Chevaline Cosmetics, Lohne, Germany). Cutaneous symptoms were exacerbated immediately after the use of those cosmetics, and she vomited repeatedly immediately after the first intake of MM pills. The skin symptoms (and vomiting) disappeared during a travel but resumed once at home. Cow milk was tolerated. Skin prick tests (SPT) (ALK-Abello, Courbevoie, France) were positive for Betula verrucosa 4 mm and Dactylis glomerata 5 mm (Hist 5mm). SPT for crude MM (8 mm), boiled MM (15 mm), pill powder (10 mm), and shampoo (7 mm) were positive in immediate and delayed (72 h) read. SPT were positive for goat (4 mm) and sheep (6 mm) milk, whereas they were negative for cow milk and horse dander. Specific IgEs (ImmunoCAP, Phadia, Sweden) were positive for rBetv1 (185 kU/L), rPhlp1-p5 (58 kU/L), goat milk (15.4 kU/L), sheep milk (15 kU/L), MM (500 kU/L), and cow milk (8.46 kU/L). IgE a-lactalbumin (1.65 kU/L), b-lactoglobulin (1.50 kU/L), and caseins (14.1 kU/L) from cow milk were also positive. Horse dander IgE was less than 0.10 kU/L. Food challenges with sheep and goat milk were negative. IgEs against the patient’s shampoo, pill powder, and MM extracts were positive (measured by enzyme-linked immunosorbent assay. Shampoo, MM, and pill powder extracts were also analyzed by Western blot. This showed that the shampoo and pills contained the same proteins with MM and that the patient’s serum recognized many allergens, mainly at 150 kDa, 30 to 35 kDa, 18 kDa, and 66 kDa (Fig 1). A lymphoblastic transformation test (measured by CD69 and CD25 expression) was positive for the pill powder (50, 100, 200, and 400 mg/mL). Those tests confirmed immediate and delayed sensitivity to MM and its derivatives (pills and shampoo). Symptom resolution was achieved after exclusion of all MM-based products. Milk from mare (Equus caballus) can be consumed fresh or as food supplement pills and is used for cosmetics manufacturing. Allergy to MM is rare, but the literature report some food anaphylaxis cases.1e3
Disclosures: Authors have nothing to disclose.
Several allergens from MM have been described: albumin (Equ c 3), alpha-lactoglobulin, beta-lactoglobulin, and casein (www. allergome.org). Our patient was sensitized to different allergens corresponding to immunoglobulins (150 kDa), caseins (30e35 kDa), beta-lactoglobulin (18 kDa), and horse albumin (66 kDa). Some of them are common to other mammalian milk or horse
Figure 1. Mare milk (MM), pills (P), and shampoo (S) extracts were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis Western blot. IgE reactivity from the patient (1) was revealed by an anti-IgE alkaline phosphatase label. Patient serum was diluted 1/10, and blocking buffer was used as a negative control (C).
Letters / Ann Allergy Asthma Immunol 110 (2013) 386e393
dander, but clinical cross-reactions are rare.1e4 Businco et al4 showed that only 2 of 25 cow’s milkeallergic children had positive SPT for MM, and 1 had a positive MM food challenge.5 Low-level sequences’ identity between allergens could be an explanation. For casein, Jenkins et al5 demonstrated that the homologies between aS1-casein and b-casein from MM and cow milk were 39% and 56%, respectively, too low of a level to induce clinical cross-reactivity. The authors proposed that the evolutionary distance between humans and animals could explain differences among allergenicity (ie, bovines are more distant from human than from horse).5 Other authors have studied cross-reactivity between cow milk and other mammalian milk. They showed that cross-reactivities between cow milk and goat or sheep milk were high, unlike mare, camel, or donkey milk.6e9 Protein contact dermatitis was first described in 1976 in Danish food handlers. The most frequent symptom is a chronic eczema with occasional urticarial or vesicular exacerbation a few minutes after contact with the sensitizing protein, which could be of either animal or vegetal origin. It involves a type I hypersensitivity reaction, but the precise pathophysiological mechanism remains unclear. Some authors have reported a combination of type I and IV hypersensitivity. Allergic contact dermatitis is the main differential diagnosis and is induced by low-molecular-weight allergens and involves type IV hypersensitivity.10 In our patient, we demonstrated the type I hypersensitivity mechanism and the positive lymphoblastic transformation test associated with the delayed positive skin prick tests suggested an associated cellular mechanism. In conclusion, we have shown, for the first time, that topical cutaneous use of MM-based cosmetics can lead to protein contact dermatitis and secondarily to food allergy. Because MM is proposed as an “alternative medicine” for treatment of skin disorders and because topical usage can secondarily lead to potentially severe food allergy, we want to report this case. Virginie Doyen, MD* Virginie Leduc, PhDy Francis Corazza, PhDz Michel Mairesse, MD*
391
Claire Ledent, MD* Olivier Michel, PhD* *Clinic of Immuno-Allergology CHU Brugmann Université Libre de Bruxelles (ULB) Brussels, Belgium y Research Department ALK-Abello Courbevoie, France z Laboratory of Immunology CHU Brugmann Université Libre de Bruxelles (ULB) Brussels, Belgium [email protected]
References [1] Robles S, Torres MJ, Mayorga C, Rodríguez-Bada JL, Fernández TD, Blanca M, Bartolomé B. Anaphylaxis to Mare’s milk. Ann Allergy Asthma Immunol. 2007; 98:600e602. [2] Fanta C, Ebner C. Allergy to mare’s milk. Allergy. 1998;53:539e540. [3] Gall H, Kalveram CM, Sick H, Sterry W. Allergy to the heat-labile proteins alpha-lactalbumin and beta-lactoglobulin in mare’s milk. J Allergy Clin Immunol. 1996;97:1304e1307. [4] Businco L, Giampietro PG, Lucenti P, et al. Allergenicity of mare’s milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2000;105: 1031e1034. [5] Jenkins JA, Breiteneder H, Mills EN. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol. 2007;120:1399e1405. [6] Monti G, Bertino E, Muratore MC, et al. Efficacy of donkey’s milk in treating highly problematic cow’s milk allergic children: an in vivo and in vitro study. Pediatr Allergy Immunol. 2007;18:258e264. [7] Muraro MA, Giampietro PG, Galli E. Soy formulas and nonbovine milk. Ann Allergy Asthma Immunol. 2002;89:97e101. [8] Restani P, Gaiaschi A, Plebani A, et al. Cross-reactivity between milk proteins from different animal species. Clin Exp Allergy. 1999;29:997e1004. [9] Hinz K, O’Connor PM, Huppertz T, Ross RP, Kelly AL. Comparison of the principal proteins in bovine, caprine, buffalo, equine and camel milk. J Dairy Res. 2012;79:185e191. [10] Amaro C, Goossens A. Immunological occupational contact urticaria and contact dermatitis from proteins: a review. Contact Dermatitis. 2008;58: 67e75.
Hyper immunoglobulin M syndrome in a 15-year-old boy caused by a Gly219Arg missense mutation Introduction Hyperimmunoglobulin M syndrome is a primary immunodeficiency disorder characterized by low or absent immunoglobulin (Ig) G, IgA, and IgE, with normal or elevated IgM levels.1 X-linked hyper-IgM syndrome (X-HIGM or HIGM1) is the most frequent subtype of HIGM, which is caused by mutations in CD40 ligand (CD40L or CD154) gene encoding for the CD40L expressed on activated T cells.1 CD40L plays an important role in class switching and maturation of B-lymphocytes by interacting with its receptor CD40 on B-cells. CD40L is also important for activation of T-cells. Mutations of CD40L result in a combined T- and B-cell immunodeficiency. Thus, patients with X-HIGM are susceptible to bacterial, fungal, and opportunistic microorganisms.1e3 We report a case of X-HIGM caused by a c.655G>A missense mutation, resulting in decreased but not absent CD40L expression and function on activated T-cells.
Disclosures: Authors have nothing to disclose.
A 15-year-old boy was evaluated for a chronic purulent productive cough present for more than 2 years. He also reported fatigue, nasal congestion with purulent rhinorrhea, chronic gingivitis, and weight loss. His medical history included 5 hospitalizations for pneumonia requiring parenteral antibiotics. He also had a history of recurrent sinusitis, otitis media, severe varicella as an infant, and herpes zoster at age 10 years. He had myringotomy and tympanostomy tubes placed. There was no history of fungal infections. He had aplastic anemia at age 5 years and Crohn’s disease diagnosed at age 8 years. No family history of primary immune deficiency or cystic fibrosis was present. Physical examination was notable for scarring of the tympanic membranes, purulent postnasal drainage, small tonsils, bibasilar rales, splenomegaly, and clubbing. Chest computed tomography scan showed extensive bronchiectasis of the lungs bilaterally. As seen in Table 1, the immunologic evaluation showed decreased IgG, but normal IgM with decreased antibody titers to diphtheria, Haemophilus influenza type B antibody, Streptococcus pneumoniae antibody. Peripheral blood flow cytometry revealed decreased CD3þ T cells, CD4þ T cells, CD8þ T cells, and memory