Stress Vulnerability in Patients with Drug Allergy –
Psychological Aspects Revealed from some Personal Studies
I.B. IAMANDESCU, LILIANA DIACONESCU
“Carol Davila” University of Medicine and Pharmacy, Department of Medical Psychology, Bucharest, Romania
Previous studies revealed the fact that patients with allergic-type reactions to drugs display
very frequently psychical disturbances, possibly in relation to the large amount of stress perceived by
them. Some of these patients with psychiatric comorbidity show a disproportionate reaction,
manifested as extensive psychosomatic disturbances, mimicking the psychic and somatic symptoms
of a previous anaphylactic or anaphylactoid reaction, when a new drug or even when placebo
preparations are given. The neurotic symptoms, very frequently encountered in patients with allergictype reactions to drugs (including asthma patients) appear to be secondarily-induced by the anxious
experience of the drug-provoked accident.
The vulnerability to psychic stress, together with many life stressors events may represent a
potential risk for developing drug allergy. Their main problem is the risk of repeating the allergic
accidents, especially in patients with various comorbidity which need medication.
Key words: drug allergy, psychotomatic disease.
Belonging to allergic diseases, drug allergy is
considered a psychosomatic disease with multifactorial
etiology with a psychogenic component binding [1].
In iatrogenic pathology, patients with allergic
reactions to drugs are a specific subpopulation both
in terms of allergic mechanisms of allergic reactions
to medicines and of the site of these reactions –
skin and mucous membranes (especially respiratory
and digestive) as tissues with a barrier role.
Together with allergic reactions to drugs can
be considered a fairly large group of “pseudoallergic” reactions included under the term “nonallergic hypersensitivity” [2] whose mechanism
does not “appeal” to allergic antibodies or to the
sensitized cells, but other “non-allergic” mechanisms
(e.g., cyclooxygenase inhibition by NSAIDs, direct
action on mast cell as polymixine). These nonallergic mechanisms “use” the effector link of allergic
reaction represented by mast cell degranulation and
other blood cells, as eosinophils, resulting in the
release of allergic mediators (histamine, leukotriene,
PAF, etc.).
Therefore, since both allergic reactions and
non-allergic reactions to drugs have same causes,
one of us (Iamandescu) grouped both types of
reactions as “allergic-type reactions to drugs
(medicines)” (AtRD). Since the psychological effects
of these reactions are the same, the references to
drug allergy presented in this article will actually
refer AtRD term, which is less used in the
literature.
ROM. J. INTERN. MED., 2010, 48, 4, 371–375
Psychological vulnerability to stress may be
regarded as a particular feature of individuals
which respond in an easy manner to psychological
stress in a wide range of stress agents [3] and
appears as an element favoring psychosomatic
disease in which an organ vulnerability is associated
[4]. Meanwhile, any psychosomatic disease generates
somato-psychic disorders, which are enhanced by
this type of personality with an increased vulnerability (especially in the field of affective-emotional)
[5]. We can speak about a double vulnerability:
psychological and physical.
In selected cases, may consider the presence
of a constitutional vulnerability to stress (generated
by inducing genes of such vulnerabilities, which
coexist with genes bearing immunological characteristics of future allergic). But no matter whether
we speak about an acquired or constitutional
vulnerability, patients who experienced an allergic
reaction to medication, especially if it was severe
(anaphylactic shock, glottis edema), may submit a
series of psychological symptoms, arising from the
allergic reaction recurrence [6] [7]:
– a high degree of anxiety in the event of an
illness requiring medical treatment;
– fear of a new allergic accident, resulting in
anxious expectation of possible allergic reactions;
– disease phobia and drug phobia especially
to drugs;
– (in surgery) assumption of increased suffering
due to fear of developing allergy after anesthesia;
372
I.B. Iamandescu and Liliana Diaconescu
– extrapolation of allergic reactions from
certain drugs to all drugs;
– excessive neuro-vegetative reactions (headache, dizziness, palpitations, tachycardia) at the
administration of medicines, and some-times even
in placebo-prepared (in which case we speak about
nocebo effect).
These symptoms may be a clinical expression
of a state of extreme anxiety.
Personality type and psychic symptoms of
patients with allergic reactions to drugs
Two sub-populations can be distinguished,
from the viewpoint of personality features, corresponding to the two clinical-pathogenic groups
defined above [8]:
1) Patients with pure allergy or with pseudoallergy to drugs (group A)
From the 79 patients that we investigated,
55.7% had T values over 70 percentile on the Hs
(Hipocondria), D (Depression) and Hy (Hysteria)
scales, constituting together the so-called “neurotic
triad”. Also, a record of events on the Holmes and
Rahe scale showed that 82.3% of these patients had
a total score over 300 points, with regard to the
summation of psycho-traumatizing events occurred
in the last 6 months preceding the allergic-type
reactions to drugs.
2) Patients with psychosomatic disturbances –
mimicking drug allergy – on repeated administration of drugs (other than the initial ones, that
had triggered allergic-type reactions) (group B).
This subgroup included 40 patients with
characteristics indicating coexistence of a true
neurosis, both by the large number of neurotic
symptoms (> 5) found in almost each patient (90%
of all cases), and by the high values of T levels on
the neurotic triad scales as evaluated with the
MMPI Questionnaire (96% of all cases).
All the patients had been submitted to psychical
stress, and had scores above 300 points on the
Holmes and Rahe Scale over the last 6 months that
had preceded the first episode of allergic-type
intolerance to certain drugs.
Concluding on these relationships mentioned
above the following can be inferred:
• The permeability factor for the onset of
allergic-type reactions to drugs, as well as
of neurotic disturbances secondary to these
reactions was the overall vulnerability to
stress of most of the patients, as demonstrated with the psychological MMPI test,
which showed values characteristic for
2
neurotic patients(the neurotic triad: Hs +
Hy + D) in 55.7% of the cases in the first
group (A) (with lower neurotic disturbances), and in 90% of the patients in the
second group (B) (with chronic neurotic
disturbances and “noisy” psychosomatic
reactions to placebo testing).
• In the vast majority of patients with
allergic-type reactions to drug – 82.3% of
the 79 patients with exclusive allergic or
pseudo-allergic reactions to drugs group and
in 100% of the 40 patients with initial allergic
reactions followed by psychosomatic disturbances to placebo administration – the
presence of major stresses was noted,
before the onset of first allergic-type
manifesttations, and these stresses were
later exacerbated by the psychologicallytraumatizing experience of drug-induced
accidents, including the fear for their
possible recurrence.
• Neurotic symptoms evidenced by us in
patients with allergic-type reactions to drugs
(considered at present to be “neurotic
disturbances of personality”) were present
in these patients, either in an isolated form
of 1–2 symptoms (for instance: anxiety and
depression), with a transient evolution, or
as “true neurotic syndromes” with a chronic
evolution.
To conclude (Table I):
• Patients with allergic-type reactions to
drugs display very frequently psychical
disturbances, possibly in relation to the
large amount of stress perceived by them;
• Many of these patients are neurotic and a
large part of them show a disproportionate
reaction, manifested as extensive psychosomatic disturbances, mimicking the psychic
and somatic symptoms of a previous
anaphylactic or anaphylactoid reaction, when
a new drug or even when placebo preparations are given;
• The neurotic symptoms, very frequently
encountered in patients with allergic-type
reactions to drugs (including asthma patients),
appear to be secondarily-induced by the
anxious experience of the drug-provoked
accident. This authentic somato-psychic
reaction to drug allergy can be conditioned
in some patients (see group B), but it
achieves this secondary “neurotic state”
only when certain personality features already
exist (that can even reflect personality
3
Stress vulnerability and drug allergy
disturbances!), making these patients highly
vulnerable to psychical stress;
• The vulnerability to psychic stress, together
with many life stressors events may repre-
373
sent a potential risk for developing drug
allergy in a predisposed patient, but this
hypothesis – emerged from our studies –
has still to be demonstrated.
Table I
Psychotic parameters
1. Stresors of life events
Subpopulations of patients with drug
induced symptoms
Allergy or pseudo-allergy
Mimicking allergy
(Group A)
(Group B)
↑ ↑ ↑
↑ ↑ ↑ ↑
2. High vulnerability to stress (MMPI)
3. Neurotic symptoms
- absent
- few (< 5)
- many (> 5)
(real neurotic patients)
Depression and anxiety
Allergic patients have a high rate of anxiety
disorders and/or depression [9] [10]. Furthermore,
studies on patients with affective and anxiety
disorders [11] showed a high prevalence of allergic
reactions. In these patients a higher percentage of
affective disorders, anxiety, depression and panic
have been present. Anxiety is characterized by
excessive anxiety and vegetative hyperexcitation
associated with distorted perceptions of symptoms,
leading to an increased number and severity of
complaints/symptoms [12] [13] and avoidant behaviour [14].
Somato-psychic recoil
In addition to somatic or psychological terrain
favorable to allergic reactions, a definite contribution to the perpetuation of an allergy is somatopsychic recoil [9]. In this regard, the doctor should
discover the individual representations of allergic
reaction to medication which are related to issues
such as [15]:
– a correct identification of allergy;
– identifying the consequences (physical,
emotional, social, economic);
– the patient knowledge about the real causes
of allergy;
– the control of drug allergy (the extent to
which the patient identifies the allergic reaction as
a problem that can be controlled).
If drug allergy has or has not vital risk, patients
with allergic-type reactions will use adaptive
strategies, such as [15]:
↑ ↑
↑ ↑ ↑ ↑
↑ ↑ ↑
↑ ↑
↑
0
↑
↑ ↑ ↑ ↑
– reorganization of the relationship with others;
– reorganization of the self image;
– affective and behavioral regression;
– emotional reactions (anxiety, depression);
– problem-centered coping (e.g., analyzing,
resolving/minimizing the situation) or emotioncentered coping (e.g. denying, resignation, fatalism).
We conducted a recent study (2009) in order
to highlight some psychodiagnostic and experimental aspects in drug allergy.
MATERIAL AND METHOD
In the study 30 subjects with drug allergy and
30 healthy subjects were included. In both groups
of subjects psychological tests were applied:
• Anxiety and Depression Scale – HADS [16].
It is a brief self-report questionnaire (14
items) which assesses anxiety (HADS-A)
and depression (HADS-D) as two distinct
dimensions in non-psychiatric populations.
It has been used widely in clinical settings
where anxiety and depression can co-occur
with physical pathology.
• Perceived Stress Scale [17]. It is a psychological instrument (10 items) which measures
a global perception of stress. The questions
ask about feelings and thoughts during the
last month. Items were designed to tap how
unpredictable, uncontrollable and overloaded
respondents find their lives.
• Stress Vulnerability Scale [18]. It is a self
report questionnaire (20 items) which
374
I.B. Iamandescu and Liliana Diaconescu
measures how vulnerable is someone to
stress. It refers to a number of factors that
affect one’s vulnerability to stress – among
them are eating and sleeping habits, caffeine
and alcohol intake, and how people express
their emotions.
Considering the finding that emotional stimuli
modify the sudor secretion [19], the subjects were
submitted to a musical-test diagnostic (MTD,
Iamandescu) including 3 sets of music as a psychosomatic stimulus that induces changes in the
moisture of skin which was measured with the
Multi Skin Test Center MC 750.
4
RESULTS (shown in Table II)
Levels of anxiety, depression and perceived
stress were significantly elevated in patients with
drug allergy compared with the control group.
Increased scores at the stress vulnerability (with
values between 32 and 65 points) correlated with
high scores on perceived stress scale (.408, p <
0.01).
Sudor secretion was increased in patients with
drug allergy after hearing each music fragment, but
especially after the sad music pieces (perceived as
a distressing stimulus).
Table II
Anxiety
Depression
Perceived stress
Stress vulnerability
Patients with drug allergy
9.25
5.72
41.55
38.97
Healthy subjects
6.73
3.80
28.80
31.46
Considering those issues is useful and necessary
a psychosomatic approach of patients with drug
allergy, an approach that focuses on items like:
1. High levels of anxiety and depression that
– the evolution of allergy, although disconpatients have presented underline the somatic-psychic
tinuous
and sometimes with the possibility of
recoil and psychological impact of allergic reactions.
avoiding allergic episodes remains often unpre2. High scores on scales of perceived stress
dictable;
and vulnerability to stress indicate that these
– the risk of occurrence of episodes which
patients are characterized by a particular psychocan endanger life (shock, glottis edema);
logical profile, with personality traits that imply the
– personality traits dominated by the presence
existence of a psychological vulnerability to stress.
of anxiety, depression;
3. Higher value of perceived stress and
– psychological stress vulnerability that entails
vulnerability to stress in patients with drug allergy
which can maximize the role of stressful life
(comparing with healthy subjects) may indicate
context and enhance the appearance of somatothat these patients would have limited capacity to
psychic recoil with anticipatory anxiety and phobia
cope with stressful events), generated either by
towards drugs and any condition that requires
acquired or constitutional vulnerability.
treatment, the feeling of helplessness and hope4. The increasing of sweat secretion level
lessness or neuro-vegetative reactions that mimic
especially after the sad music passage (as a psychoan allergic reaction;
– the utility of psychotherapeutic interventions,
somatic stimulus) is an objective proof of the
at least supportive or relaxant therapies.
influence of psychic stress.
___________________________________________________________________
DISCUSSION
Studiile precedente au relevat faptul că pacienţii cu reacţii de tip alergic la
medicamente prezintă tulburări psihice foarte frecvent, eventual în relaţie cu
încărcătura de stres perceput. Unii dintre aceşti pacienţi cu comorbiditate
psihiatrică au o reacţie disproporţionată, manifestată prin tulburări psihosomatice
extinse, ce pot mima simptome psihice şi somatice ale unei reacţii anafilactice sau
anafilactoide anterioare, atunci când este administrat un nou medicament sau
chiar un preparat placebo. Simptomele nevrotice, foarte frecvent întâlnite la
pacienţii cu reacţii de tip alergic la medicamente (inclusiv la pacienţii cu astm),
par a fi induse în mod secundar şi de experienţa anxioasă a unui accident provocat
de medicamente.
5
Stress vulnerability and drug allergy
375
Vulnerabilitatea la stres psihic, împreună cu evenimentele stresante de viaţă,
poate reprezenta un risc potenţial pentru apariţia reacţiilor alergice la medicamente.
Problema principală este reprezentată de riscul repetării accidentelor alergice, în
special la pacienţii cu diferite comorbidităţi şi care necesită medicaţie.
___________________________________________________________________
Corresponding author: Liliana Diaconescu
Email: idiac2002@yahoo.com
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Received September 25, 2010