Wed, 30 May 2001 

Nickel Allergy Is Found in a Majority of Women with Chronic Fatigue
Syndrome and Muscle Pain - And May Be Triggered by Cigarette Smoke and
Dietary Nickel Intake

Journal of Chronic Fatigue Syndrome, Vol.8(1) 2001, pp. 57-65

Björn Regland, MD; Olof Zachrisson, MD; Vera Stejskal, PhD;
Cari-Gerhard Gottfries, MD

Björn Regland is Assistant Professor, Olof Zachrisson is
Assistant Professor, and Cari-Gerhard Gottfries is Professor, all
affiliated with the Department of Psychiatry, Sahlgrenska University
Hospital/Mölndal and Institute of Clinical Neuroscience, Göteborg,
Sweden.
Vera Stejskal is Assistant Professor, Department of Clinical Chemistry,
Danderyd Hospital and Karolinska Institute, Stockholm.
Address correspondence to: Björn Regland, Institute of Clinical
Neuroscience, Sahlgrenska University Hospital, SE-431 80 Mölndal, Sweden
(E-mail: mailto:bjorn.regland@ms.se).

The authors express their thanks to Swiss Serum & Vaccine Institute Berne
for providing them with the Staphylococcus vaccine, and to Veronica
Nordman for the performance of in vitro testing.

ABSTRACT.
Two hundred and four women with chronic fatigue and muscle pain, with no
signs of autoimmune disorder, received immune stimulation injections with
a Staphylococcus vaccine at monthly inter­vals over 6 months. Good
response was defined as a decrease by at least 50% of the total score on
an observer's rating scale. Nickel allergy was evaluated as probable if
the patient had a positive history of skin hyper­sensitivity from
cutaneous exposure to metal objects. The patient's smoking habits were
recorded. Fifty-two percent of the patients had a positive history of
nickel contact dermatitis. There were significantly more good responders
among the non-allergic non-smokers (39%) than among the allergic smokers
(6%). We also present case reports on nickel-allergic patients who
apparently improved after cessation of cig­arette smoking and reducing
their dietary nickel intake. Our observa­tions indicate that exposure to
nickel, by dietary intake or inhalation of cigarette smoke, may trigger
systemic nickel allergy and contribute to syndromes of chronic fatigue
and muscle pain.

KEYWORDS. Nickel allergy, cigarette smoking, dietary nickel, fa­tigue,
muscle pain


INTRODUCTION

Nickel is a common sensitizing agent responsible for the high prev­alence
of allergic contact dermatitis. However, the health hazards of nickel
allergy with regard to diffuse and general symptomatology, such as
chronic fatigue and muscle pain, appear not to be fully under­stood and
are probably underestimated.

The prevalence of nickel contact dermatitis among women has in­creased
remarkably and there is a clear relationship between ear pierc­ing and
induction of nickel allergy (1). In two Norwegian unselected populations,
the prevalence figures for women were reported to be 27.5 and 31.1%,
respectively (2). Although in the same study the prevalence for men was
5%, the modern fashion of piercing also anticipates an increasing
prevalence among men (3). Nickel allergy is associated with fatigue
syndromes with or without autoimmunity (4). In women with chronic fatigue
syndrome the prevalence of nickel contact dermatitis has been reported to
be as high as 52% (5).

Recently we chanced upon findings regarding nickel allergy in a study set
up with quite another purpose. Immune stimulation with a Staphylococcus
vaccine was tested in clinical trials of female patients with chronic
fatigue and muscle pain (see 6 for a preliminary report). The patients
received subcutaneous injections at monthly intervals. The results are
interesting, showing clinical improvement in a substan­tial number of
patients. Moreover, we unexpectedly found that nickel allergy influenced
the efficiency of the treatment and that nickel aller­gy was interrelated
with cigarette smoking.

The primary incidental finding of nickel sensitization came out of a
Memory Lymphocyte Immuno Stimulation Assay (MELISA®) in 16 patients who
did not improve or had reacted adversely to the vaccine treatment (7).
MELISA® is an optimized lymphocyte proliferation test (8). The purpose of
using MELISA® in the study was to check wheth­er the unresponsiveness to
the vaccine could be due to hypersensitivity to the preservative
thiomersal (syn. merthiolate, thimerosal). In addi­tion, reactivity was
tested to various metals such as nickel, although the vaccine compound
does not contain nickel. The main finding was that 13 of the 16 tested
patients (81%) reacted strongly against nickel in vitro (7). Moreover, we
found a substantial number of cigarette smokers among the non-responding
and MELISA®-positive nickel-al­lergic patients, whereas the combination
of smoking and contact aller­gy was hardly seen at all in the group of
patients rated as good re­sponders. Thus, we were made attentive to the
intriguing possibility that a connection might exist between nickel
allergy and cigarette smoking. As nickel and a variety of other metals
occur in trace amounts in mainstream cigarette smoke (9), it would be a
plausible suggestion that exposure to cigarette smoke may be
nickel-sensitizing or, at least, a potential trigger of hyperreactivity
in a person already sensitized to nickel.

The aim of this study was to further explore the impact of nickel allergy
and its interrelation with cigarette smoking in a large number of women
with chronic fatigue and muscle pain included in clinical trials of
immune stimulation therapy.

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