CORRESPONDENCE
patients who do not respond to, or have
toxic side-effects from, a single chelating
drug.
George J Kontoghiorghes
Postgraduate Resaerch Institute of Science,
Technology, Environment, and Medicine,
Limassol 3021, Cyprus
(e-mail: pri_gjk@cylink.com.cy)
1 Nisbet-Brown E, Olivieri N F, Giardina PJ,
et al. Effectiveness and safety of ICL670 in
iron-loaded patients with thalassaemia: a
randomised, double-blind, placebo-
controlled, dose-escalation trial. Lancet 2003;
361: 1597–1602.
2 Olivieri NF, Koren G, Hermann C, et al.
Comparison of iron chelator L1 and
desferrioxamine in iron loaded patients.
Lancet 1990; 336: 1275–79.
3 Agarwal MB, Gupte SS, Viswanathan C,
et al. Long term assessment and safety of L1,
an oral iron chelator, in transfusion
dependent thalassaemia: Indian trial.
Br J Haematol 1992; 82: 460–66.
4 Kontoghiorghes GJ, Neocleous K,
Kolnagou A. Benefits and risks of
deferiprone in iron overload in thalassaemia
and other conditions. Comparison of
epidemiological and therapeutic aspects
with deferoxamine. Drug Safety 2003; 26:
553–84.
5 Yamamoto RS, Williams GM, Frankel HH,
Weisburger JH. 8-Hydroxyquinoline: chronic
toxicity and inhibitory effect on the
carcinogenicity of N-2-fluorenylacetamide.
Toxic Appl Pharmacol 1971; 19: 687–98.
Probiotics for prevention of
atopic disease?
Sir—Marko Kalliomäki and colleagues
(May 31, p 1869)1,2 conclude that the
results of their study suggest that the
preventive effect of Lactobacillus
rhamnosus strain GG on atopic eczema
extends beyond infancy. Although their
study is well designed, we have several
comments.
First, are there any data on the
severity of eczema in participants?
Was, for instance, a SCORAD score3
obtained? Such information would
contribute to the discussion on the
indication of probiotics in this specific
group of infants.
Second, we disagree with Kalliomäki
and colleagues’ conclusion that
treatment with lactobacillus results in
prevention of atopic disease; such a firm
conclusion cannot be drawn on the basis
of the data generated by their study.
Almost 25% of participants were lost to
follow-up by age 4 years. Selection bias
cannot, therefore, be excluded.
Furthermore, among the participants,
there was a non-significant trend
towards an increased rate of atopic
disorders in the group treated with
lactobacillus compared with those given
placebo (ten of 53 and five of 54
developed allergic rhinitis, and three of
53 and one of 54 developed asthma,
496
For personal use. Only reproduce with permission from The Lancet.
respectively). Finally, no significant
difference in the number of children
with positive skin-prick tests was noted
in either group (ten in the probiotic
group versus nine in the placebo group).
Would, therefore, a diagnosis of eczema
rather than atopic eczema, be more
appropriate in this instance? If so, the
findings would suggest that treatment
with lactobacillus results in a reduction
in the rate of non-atopic eczema, a
conclusion that would lend support to
the notion that not all eczema is
characterised by atopy.
Further studies should be done before
firm conclusions are drawn on the
preventive effect of lactobacillus in high-
risk infants with respect to development
of atopic disease.
L E M Niers, G Rijkers, E F Knol, Y Meijer,
*M O Hoekstra
Centre for Paediatric Allergology, Wilhelmina
Childrens Hospital, University Medical Centre
Utrecht, Utrecht, PO Box 85090, 3508 AB,
Netherlands
(e-mail: m.o.hoekstra@wkz.azu.nl)
1 Kalliomäki M, Salminen S, Poussa T,
Arvilommi H, Isolauri E. Probiotics and
prevention of atopic disease: 4-year follow-up
of a randomised placebo-controlled trial.
Lancet 2003; 361: 1869–71.
2 Kalliomäki M, Salminen S, Arvilommi H,
Kero P, Koskinen P, Isolauri E. Probiotics in
primary prevention of atopic disease: a
randomised placebo-controlled trial. Lancet
2001; 357: 1076–79.
3 Anon. Severity scoring of atopic dermatitis :
the SCORAD index—consensus report of the
European Task Force on Atopic Dermatitis.
Dermatology 1993; 186: 23–31.
Authors’ reply
Sir—L Niers and colleagues have raised
some points about our study; due to
limited space available, many details
had to be left out of our report.
We did assess the severity of atopic
eczema at age 4 years with the
SCORAD score (mean 17, range
11–26). The score did not differ
between groups, and was comparable to
the findings presented in our original
report of the study in 2001.
The diagnosis of atopic eczema was
based on the criteria prepared by
Hanifin1 especially for infants and
children. These criteria were the only
criteria available at the beginning of the
study. Alternative definitions of atopic
eczema—eg, atopiform dermatitis and
atopic eczema/dermatitis syndrome
(AEDS)2—have been proposed, since a
proportion of patients with atopic
eczema do not manifest with skin-prick
test reactivity but do display positive
patch testing, indicating delayed
reactions to antigens.3 So far, however, a
universal consensus about these
proposed definitions has not been
reached.
THE LANCET • Vol 362 • August 9, 2003 • www.thelancet.com
Treatment with lactobacillus resulted
in prevention of atopic eczema. The
frequencies of skin-prick test reactivity,
however, were comparable between the
groups. The same distinction between
early antigen-specific IgE response and
atopic disease has been noted in
childhood asthma.4 Lau and colleagues
postulated that “the induction of
specific IgE responses and the
development of childhood asthma are
determined by independent factors”.4
Our observations on atopic eczema,
another form of atopic disease, lend
support to this suggestion. Moreover,
there is a considerable overlap in
antigen-specific IgE concentrations
between healthy children and those with
atopic disease during the first 5 years of
life.5
Taken together, these clinical findings
and the unestablished status of the
definitions of atopic eczema, suggest the
effects of lactobacillus on antigen-
specific IgE and clinical status of
individuals should be reported
separately. We agree that additional
studies to address the role of probiotics
in the prevention of atopic disease are
warranted.
*M Kalliomäki, S Salminen, H Arvilommi,
E Isolauri
*Turku University Hospital, Department of
Pediatrics, PO Box 52, FI-20521 Turku, Finland
(MK); Departments of Paediatrics (MK, EI), and
Biochemistry and Food Chemistry (SS), University
of Turku, Turku; National Public Health Institute,
Turku (AH)
(e-mail: markal@utu.fi)
1 Hanifin JM. Atopic dermatitis in infants and
children. Pediatr Clin North Am 1991; 38:
763–89.
2 Johansson SG, Hourihane JO, Bousquet J,
et al. A revised nomenclature for allergy: an
EAACI position statement from the EAACI
nomenclature task force. Allergy 2001; 56:
813–24.
3 Isolauri E, Turjanmaa K. Combined skin
prick and patch testing enhances
identification of food allergy in infants with
atopic dermatitis. J Allergy Clin Immunol
1996; 97: 9–15.
4 Lau S, Illi S, Sommerfeld C, et al. Early
exposure to house-dust mite and cat allergens
and development of childhood asthma: a
cohort study. Lancet 2000; 356: 1392–97.
5 Kulig M, Bergmann R, Klettke U, Wahn V,
Tacke U, Wahn U. Natural course of
sensitization to food and inhalant allergens
during the first 6 years of life.
J Allergy Clin Immunol 1999; 103:
1173–79.
DEPARTMENT OF ERROR
Thorpe A, Neal D. Benign prostatic hyperplasia.
Lancet 2003: 361: 1359–67—In this Seminar
(April 19), the first two sentences of the
Summary should have read: “In both ageing
men and women, there is an increasing
incidence of lower urinary tract symptoms
(LUTS), which have many possible causes—
including smooth muscle dysfunction,
neurological factors, and benign prostatic
hyperplasia”.