556
Inhibition of contact
allergy reactions by
topical FK506 SiR,—The immunosuppressant cyclosporin has been used to treat inflammatory skin disorders such as psoriasis.’ Because of adverse effects with systemic cyclosporin, topical preparations have been studied with conflicting results.2,3 The immunosuppressant FK506 has a similar action in psoriasis, and similar side-effects, such as nephrotoxicity.4 Because topical FK506 inhibits allergic contact dermatitis in skin of domestic pigs,5 we investigated whether it also had a therapeutic effect in man. Five male volunteers with contact hypersensitivity to 1-chloro2,4-dinitrobenzene (DNCB) participated. FK506 was obtained from Sandoz. Polypropylene chambers were used to pretreat adjacent, healthy forearm skin with 100 lil 1%, 0-1%, and 0-01% FK506 in ethanol and with ethanol control for 48 h. Subsequently, 17 ul 0 1 % DNCB in ethanol in aluminium chambers was used on four pretreated sites and an additional non-treated site for 24 h. Reactions were graded openly. For histopathological examination, biopsy specimens were taken from ethanol and 1 % FK506 pretreated areas from one volunteer 5 days after DNCB challenge. Throughout a 5 day follow-up there was an overall suppression of allergic reactions to DNCB in all subjects on sites pretreated with FK506. Results on the second day after challenge showed that even 0-01% FK506 suppressed the reactions: Subject __._...,._..._. "1
no: A
L
of the FK506-pretreated area, which macroscopically looked normal, revealed no inflammatory changes; in the ethanoltreated area intense dermatitis was seen. No systemic side-effects were seen in any volunteers.
Biopsy
Thus, FK506 has anti-inflammatory activity as a topical preparation. Therefore it may be possible to minimise unwanted systemic adverse effects while attaining a therapeutic local effect. Topical FK506 may offer promise for skin disorders that respond to systemic cyclosporin and may become a treatment for inflammatory skin disorders. Department of Dermatology, University of California, San Francisco, California 94143-0989, USA
ANTTI I. LAUERMA HOWARD I. MAIBACH
Department of Dermatology and Allergic Diseases, Helsinki University Central Hospital, Helsinki, Finland
HAKAN GRANLUND PEKKA ERKKO MATTI KARTAMAA SAKARI STUBB
6 months, and for 9 months in at least 20%), and because infants receiving the adapted formula were significantly more often sick (40% vs 13%). One would therefore expect a less favourable weight gain in the adapted formula group. In my opinion, an evaluation of the nutritional properties of a feed requires symptom-free infants to receive that feed exclusively. Arshad et al state that "similar hydrolysed milk was used for the treatment of cow’s milk allergy" (referring to a study by Zeiger and colleagues1). As I understand that paper, Nutramygen (whey hydrolysate) was used to prevent allergy, not to treat cow’s milk protein allergy. Aptamil HA is a soy and collagen hydrolysate with addition of free aminoacids, which is very different from a whey hydrolysate. Chandra et al2 was also a preventive study with Nutramygen, and not a therapeutic trial, as indicated by Arshad. Arshad’s trial seems to confirm previous data on the preventive effect of food-allergen only avoidance with whey hydrolysate. Published studies not referenced by Arshad show a reduction in the incidence of allergic disorders in infants:
Group
5.
severe recalcitrant psoriasis. Transplant Proc 1991; 23: 3322-24. Meingassner JG, Stutz A. Immunosuppressive macrolides of the type FK506: a novel class of topical agents for treatment of skin diseases? J Invest Dermatol 1992; 98:
Arshad
The risk of allergic manifestations developing in the infants in these trials was comparable because "dual heredity" was the main inclusion criterion in all of them (confirmed by the very similar incidence of allergic disorders at 12 months in the controls). However, in Chandra and Hamed’s study3 and ours4,5 the infants in the prophylactic group were exclusively formula fed (and for 6 months only, compared with 9 months in the study by Arshad). Although the control data can be compared between studies, the "prophylactic groups" cannot be compared because of the different
designs (eg, prolonged breastfeeding by mothers on a hypoallergenic diet). However, the decreased incidence at 12 months (13% in Arshad compared with about 20%3-5) could as well be related to breastfeeding (providing also protection against infection) up to 9 months in 20% of all infants as to the longer period of hypo-allergenic formula, a better prophylactic effect of the formula used, or the additional effect of avoidance of inhaled allergens. The difference between 13 % in the Arshad study (with "total" allergen avoidance up to the age of 9 months) and about 20 % in the Chandra and Vandenplas studies (with food-allergen only avoidance up to the age of 6 months without additional beneficial effects of breastfeeding) is smaller than one would expect. Academic Children’s Hospital, Free University of Brussels, 1090 Brussels, Belgium
1.
2. 1. Mueller W, Hermann B. Cyclosporin A for psoriasis. N Engl J Med 1979; 301: 555. 2. Gnffiths CEM, Powles AV, Baker BS, Fry L, Valdimarsson H. Topical cyclosporin and psoriasis. Lancet 1987; i: 806. 3. Mizoguchi M, Kawaguchi K, Ohsuga Y, Ikara Y, Yanagawa A, Mizushima Y. Cyclosporin ointment for psoriasis and atopic dermatitis. Lancet 1992; 339: 1120. 4. Abu-Elmagd K, Van Thiel D, Jegasothy BV, et al. FK506: a new therapeutic agent for
Allergic disorders (%) Vandenplas4,5
Chandra’
YVAN VANDENPLAS
Zeiger RS, Heller S, Mellon MH, et al. Effect of combined maternal and infant food allergen avoidance on development of atopy in early infancy: a randomised study. J Allergy Clin Immunol 1989; 84: 72-89 Chandra RK, Pun S, Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants. BMJ 1989,
299: 228—30. 3. Chandra RK, Hamed A. Cumulative incidence of atopic disorders in high nsk infants fed whey hydrolysate, soy, and conventional cow milk formulas Ann Allergy 1991, 67: 129-32. 4. Vandenplas Y, Hauser B, Van den Borre C, et al. Effect of a whey hydrolysate prophylaxis of atopic disease. Ann Allergy 1992; 68: 419-24. 5. Vandenplas Y. Atopy at 3 years in high-risk infants fed whey hydrolysate or conventional formula. Lancet 1992; 339: 1118.
851-55.
Prevention of
atopic disease in children
SIR,-Dr Arshad and co-workers’ well-conducted study (June 20, p 1493), shows that combined "allergen" (food and inhaled
allergens) avoidance decreases the incidence of allergic disorder in infancy. Arshad et al conclude that incidence of allergy during the first years of life was decreased, but the follow-up was limited to 12 months. It is difficult to draw conclusions about the nutritional aspects of both tested formulae (adapted and "hypo-allergenic") because many of the infants were breastfed (over half for 3 months, 30 % for
Traveller’s diarrhoea associated with cyanobacterium-like bodies SIR,-Cyanobacterium-like bodies (CLB) have been associated with diarrhoeal illness in several countries. We have detected CLB in faeces from ten UK patients. All were either seen at this hospital or had specimens sent to the parasitology department for confirmation. Stool samples were treated with 10% formalin and concentrated by ether sedimentation. The unstained wet concentrate was examined by light microscopy. CLB were recognisible as spherical bodies 8-10 µm in diameter with a central morula of several
Inhibition of contact
allergy reactions by
topical FK506 SiR,—The immunosuppressant cyclosporin has been used to treat inflammatory skin disorders such as psoriasis.’ Because of adverse effects with systemic cyclosporin, topical preparations have been studied with conflicting results.2,3 The immunosuppressant FK506 has a similar action in psoriasis, and similar side-effects, such as nephrotoxicity.4 Because topical FK506 inhibits allergic contact dermatitis in skin of domestic pigs,5 we investigated whether it also had a therapeutic effect in man. Five male volunteers with contact hypersensitivity to 1-chloro2,4-dinitrobenzene (DNCB) participated. FK506 was obtained from Sandoz. Polypropylene chambers were used to pretreat adjacent, healthy forearm skin with 100 lil 1%, 0-1%, and 0-01% FK506 in ethanol and with ethanol control for 48 h. Subsequently, 17 ul 0 1 % DNCB in ethanol in aluminium chambers was used on four pretreated sites and an additional non-treated site for 24 h. Reactions were graded openly. For histopathological examination, biopsy specimens were taken from ethanol and 1 % FK506 pretreated areas from one volunteer 5 days after DNCB challenge. Throughout a 5 day follow-up there was an overall suppression of allergic reactions to DNCB in all subjects on sites pretreated with FK506. Results on the second day after challenge showed that even 0-01% FK506 suppressed the reactions: Subject __._...,._..._. "1
no: A
L
of the FK506-pretreated area, which macroscopically looked normal, revealed no inflammatory changes; in the ethanoltreated area intense dermatitis was seen. No systemic side-effects were seen in any volunteers.
Biopsy
Thus, FK506 has anti-inflammatory activity as a topical preparation. Therefore it may be possible to minimise unwanted systemic adverse effects while attaining a therapeutic local effect. Topical FK506 may offer promise for skin disorders that respond to systemic cyclosporin and may become a treatment for inflammatory skin disorders. Department of Dermatology, University of California, San Francisco, California 94143-0989, USA
ANTTI I. LAUERMA HOWARD I. MAIBACH
Department of Dermatology and Allergic Diseases, Helsinki University Central Hospital, Helsinki, Finland
HAKAN GRANLUND PEKKA ERKKO MATTI KARTAMAA SAKARI STUBB
6 months, and for 9 months in at least 20%), and because infants receiving the adapted formula were significantly more often sick (40% vs 13%). One would therefore expect a less favourable weight gain in the adapted formula group. In my opinion, an evaluation of the nutritional properties of a feed requires symptom-free infants to receive that feed exclusively. Arshad et al state that "similar hydrolysed milk was used for the treatment of cow’s milk allergy" (referring to a study by Zeiger and colleagues1). As I understand that paper, Nutramygen (whey hydrolysate) was used to prevent allergy, not to treat cow’s milk protein allergy. Aptamil HA is a soy and collagen hydrolysate with addition of free aminoacids, which is very different from a whey hydrolysate. Chandra et al2 was also a preventive study with Nutramygen, and not a therapeutic trial, as indicated by Arshad. Arshad’s trial seems to confirm previous data on the preventive effect of food-allergen only avoidance with whey hydrolysate. Published studies not referenced by Arshad show a reduction in the incidence of allergic disorders in infants:
Group
5.
severe recalcitrant psoriasis. Transplant Proc 1991; 23: 3322-24. Meingassner JG, Stutz A. Immunosuppressive macrolides of the type FK506: a novel class of topical agents for treatment of skin diseases? J Invest Dermatol 1992; 98:
Arshad
The risk of allergic manifestations developing in the infants in these trials was comparable because "dual heredity" was the main inclusion criterion in all of them (confirmed by the very similar incidence of allergic disorders at 12 months in the controls). However, in Chandra and Hamed’s study3 and ours4,5 the infants in the prophylactic group were exclusively formula fed (and for 6 months only, compared with 9 months in the study by Arshad). Although the control data can be compared between studies, the "prophylactic groups" cannot be compared because of the different
designs (eg, prolonged breastfeeding by mothers on a hypoallergenic diet). However, the decreased incidence at 12 months (13% in Arshad compared with about 20%3-5) could as well be related to breastfeeding (providing also protection against infection) up to 9 months in 20% of all infants as to the longer period of hypo-allergenic formula, a better prophylactic effect of the formula used, or the additional effect of avoidance of inhaled allergens. The difference between 13 % in the Arshad study (with "total" allergen avoidance up to the age of 9 months) and about 20 % in the Chandra and Vandenplas studies (with food-allergen only avoidance up to the age of 6 months without additional beneficial effects of breastfeeding) is smaller than one would expect. Academic Children’s Hospital, Free University of Brussels, 1090 Brussels, Belgium
1.
2. 1. Mueller W, Hermann B. Cyclosporin A for psoriasis. N Engl J Med 1979; 301: 555. 2. Gnffiths CEM, Powles AV, Baker BS, Fry L, Valdimarsson H. Topical cyclosporin and psoriasis. Lancet 1987; i: 806. 3. Mizoguchi M, Kawaguchi K, Ohsuga Y, Ikara Y, Yanagawa A, Mizushima Y. Cyclosporin ointment for psoriasis and atopic dermatitis. Lancet 1992; 339: 1120. 4. Abu-Elmagd K, Van Thiel D, Jegasothy BV, et al. FK506: a new therapeutic agent for
Allergic disorders (%) Vandenplas4,5
Chandra’
YVAN VANDENPLAS
Zeiger RS, Heller S, Mellon MH, et al. Effect of combined maternal and infant food allergen avoidance on development of atopy in early infancy: a randomised study. J Allergy Clin Immunol 1989; 84: 72-89 Chandra RK, Pun S, Hamed A. Influence of maternal diet during lactation and use of formula feeds on development of atopic eczema in high risk infants. BMJ 1989,
299: 228—30. 3. Chandra RK, Hamed A. Cumulative incidence of atopic disorders in high nsk infants fed whey hydrolysate, soy, and conventional cow milk formulas Ann Allergy 1991, 67: 129-32. 4. Vandenplas Y, Hauser B, Van den Borre C, et al. Effect of a whey hydrolysate prophylaxis of atopic disease. Ann Allergy 1992; 68: 419-24. 5. Vandenplas Y. Atopy at 3 years in high-risk infants fed whey hydrolysate or conventional formula. Lancet 1992; 339: 1118.
851-55.
Prevention of
atopic disease in children
SIR,-Dr Arshad and co-workers’ well-conducted study (June 20, p 1493), shows that combined "allergen" (food and inhaled
allergens) avoidance decreases the incidence of allergic disorder in infancy. Arshad et al conclude that incidence of allergy during the first years of life was decreased, but the follow-up was limited to 12 months. It is difficult to draw conclusions about the nutritional aspects of both tested formulae (adapted and "hypo-allergenic") because many of the infants were breastfed (over half for 3 months, 30 % for
Traveller’s diarrhoea associated with cyanobacterium-like bodies SIR,-Cyanobacterium-like bodies (CLB) have been associated with diarrhoeal illness in several countries. We have detected CLB in faeces from ten UK patients. All were either seen at this hospital or had specimens sent to the parasitology department for confirmation. Stool samples were treated with 10% formalin and concentrated by ether sedimentation. The unstained wet concentrate was examined by light microscopy. CLB were recognisible as spherical bodies 8-10 µm in diameter with a central morula of several
