Chapter 7
Stigmata of the Atopic Constitution
B. Przybilla, C. Bauer
Atopy is a constitutional state that can be defined as a
genetically determined disposition to develop atopic
eczema, allergic rhinoconjunctivitis, and/or allergic
asthma. Up to now, no definite marker has been available that would enable one to decide with certainty
whether atopy is present or absent in a given individual. This hampers not only the recognition of atopy in
persons without manifest symptoms, but even the
diagnostic classification of overt disease: it may not be
possible to diagnose a condition as atopic when considering only its immediate symptoms. This holds true
particularly for the diagnosis of atopic eczema. Thus,
in order to establish the presence of an atopic disposition or of an atopic disease, it is necessary to look for
features known to be characteristically related to atopy.
7.1
Features of Atopy
There are numerous features that are characteristic, yet
mostly nonspecific indicators of atopy. With regard to
the diagnosis of atopic eczema, the criteria established
by Hanifin and Rajka [12], based on previous suggestions of these authors [11, 36], are those most often
referred to. These and additional clues to atopy status
can be obtained from the patient history, physical findings, or skin or laboratory tests (Table 7.1).
7.1.1
History
Anamnestic data on previous clinical findings may be
reported by the patient, or information may be
obtained from medical records. This makes a difference with regard to reliability. In particular, a history
negative for atopic symptoms cannot be considered as
Table 7.1. Features of atopy
Anamnestic Data
Atopic diseases (atopic eczema, allergic rhinoconjunctivitis,
allergic asthma):
Personal history
Family history
Eczema with the following characteristics:
Pruritus
Early age of onset
Chronically relapsing course
Seasonal variation
Influenced by environmental or emotional factors, or
infections
Nonspecific hand dermatitis
Food intolerance
Allergic (contact) urticaria
Cutaneous infections
Itch when sweating
Light sensitivity
Irritation from textiles
Wool intolerance
Intolerance of occlusive clothing
Solvent intolerance
Physical Findings
Atopic eczema: manifestations and sequelae
Full-blown typical atopic eczema (age-dependent)
(Infantile) seborrheic atopic eczema
Patchy pityriasiform lichenoid eczema
Nummular atopic eczema
Pityriasis alba
Widespread skin infection
Atopic hand eczema
Dyshidrotic eczema (pompholyx)
Pulpitis sicca
Nipple eczema
Cheilitis
Perlèche (angular cheilitis)
Median fissuring of the lower lip
Retroauricular intertrigo
Infra-auricular fissuring
Anterior neck folds
Linear grooves
Polished nails
7
62
7 Stigmata of the Atopic Constitution
Table 7.1. (cont.)
Pigmentary changes
Depigmentation
Hyperpigmentation
Atopic respiratory disease: manifestations and sequelae
Manifest allergic rhinitis, conjunctivitis or asthma (due to
common aeroallergens)
Facial mannerisms (“allergic salute”, nose or mouth wrinkling)
Transverse nasal crease
Mouth breathing
Gingival hyperplasia
Furrowed mouth syndrome
Hypertrophy of the tonsils
Granular pharyngitis
Facial deformities (e.g., longer face, flattened malar eminences, pinched nostrils, raised upper lip, overbite)
Thoracic deformities (pectus carinatum/excavatum)
Pulmonary emphysema
Associated conditions
Ichthyosis vulgaris
Keratosis pilaris
Lingua geographica
Juvenile plantar dermatosis
Keratosis punctata
Lichen striatus
Cataract
Keratoconus
Constitutional stigmata of atopy
Dry skin
Hyperlinearity of the palms/soles
Infraorbital fold
White dermographism
Facial pallor
Orbital darkening
Hertoghe’s sign
Low hairline
Skin and Laboratory Test Findings
Immediate type (type I) skin test reactions to common
allergens
Specific serum IgE antibodies to common allergens
Elevated serum level of total IgE
Abnormal vascular reactions (e.g., delayed blanch to cholinergic stimulation, white reaction to nicotinic acid esters)
Depressed cellular immunity
Shift toward a Th2 immune response
definitely diagnostic, whereas a positive history of
clear-cut atopic disease, especially when obtained from
medical records, provides valuable clues.
7.1.2
Physical Findings
Physical findings related to atopy fall into three categories.
Clinical Manifestations of Atopic Diseases. By definition, the presence of characteristic atopic eczema or
allergic respiratory disease due to common inhalant
allergens constitutes a definite diagnosis of atopy.
Besides full-blown atopic eczema, there are minor
skin manifestations, such as nonspecific hand dermatitis, nipple eczema, cheilitis, or infra-auricular fissuring
(Table 7.1). They have been referred to as indicators of
atopic eczema. However, as they are manifestations of
atopic eczema, they do not provide additional independent clues to the presence of atopy in a given individual.
Secondary to atopic disease, characteristic sequelae
may occur (Table 7.1). These include, for example,
reticulate pigmentation of the neck, pityriasis alba, and
polished nails due to atopic eczema, or transverse nasal
crease, facial deformity, and facial mannerism due to
respiratory atopic disease.
Associated Conditions. Although not direct manifestations or sequelae of atopic diseases, a heterogeneous
group of conditions has been found to be related to
atopy (Table 7.1).
Stigmata of the Atopic Constitution. Only features
that are not associated with morbidity, i.e., that are neither manifestations nor consequences of disease,
should be regarded as true constitutional stigmata.
Furthermore, they should be observable without technical devices. These features are listed in Table 7.1.
7.1.3
Skin and Laboratory Testing
Demonstration of positive immediate type skin test
reactions or specific serum IgE antibodies to a common environmental allergen or of an elevated serum
level of total IgE is frequently used to state atopy in a
clinical setting. The diagnostic relevance of these
parameters is discussed elsewhere in this volume.
7.2 Constitutional Stigmata of Atopy
7.2
Constitutional Stigmata of Atopy
7.2.1
Dry Skin
Dry skin (xerosis, sebostasis) (Fig. 7.1) is a hallmark of
the patient with atopic eczema. Clinically, it is characterized by a skin surface that is rough to the touch,
noninflamed, and sometimes slightly scaly.
“Dry skin” has been regarded a misnomer, as the
actual perception is “rough skin,” which would be a
more appropriate designation [32]. Indeed, an increased roughness of dry skin in atopic eczema could
be measured [55]. However, there is a long tradition of
using the term “dry skin.” Also, “rough skin” may be
mistaken for keratosis follicularis.
The occurrence of dry skin must be considered as
influenced by exogenous factors, e.g., season of the
year or skin care measures. Already short exposure to
low air humidity increases skin roughness [7]. Also,
“localized” and “generalized” dry skin have been distinguished [51].
Biopsies taken from dry, clinically noninflamed skin
of patients with atopic eczema have been reported to
exhibit the histological picture of mild eczema, suggesting that dry skin is a minor manifestation of the
disease [10, 49, 51]. However, these results were not
confirmed by others, who found histologically eczematous changes in less than 10 % of biopsies taken from
the dry skin of atopic eczema patients [8, 9]. Thus, dry
skin cannot be regarded simply as a subclinical variant
of eczema, but minor disease manifestations may present as dry skin.
Another concept is that dry skin, if it is not eczema,
may actually be autosomal dominant ichthyosis vulgaris, which was reported in up to 30 % of atopic eczema
patients [49, 51]. The diagnosis of ichthyosis vulgaris
was based in these studies merely on clinical findings
(ichthyotic scaling, hyperlinearity of the palms) and
light microscopical features, such as an absent or
reduced granular layer [49, 51]. However, ultrastructural studies of dry skin in atopic eczema have disclosed that concomitant ichthyosis vulgaris, proven by
the presence of abnormal keratohyaline granules,
occurs in only 4 % of patients [8, 9]. Thus dry skin is
related to both atopic eczema and ichthyosis vulgaris
[9]. “Ichthyosis vulgaris” should not be used to
describe ichthyosiform scaling in atopic eczema
patients.
The prevalence of dry skin has been assessed in
numerous studies (Table 7.2). In patients with atopic
eczema, dry skin was present in 48 %–100 %, whereas it
was seen in only 8 %–40 % of controls. Dry skin is significantly linked to atopic eczema.
7.2.2
Hyperlinearity of the Palms or Soles
Fig. 7.1. Dry skin
Hyperlinearity of the palms (Fig. 7.2) is a well-known
feature of atopic eczema; hyperlinearity of the soles has
attracted less attention. Palmar creases can be divided
into three groups: major, minor, and secondary [42]:
63
64
7 Stigmata of the Atopic Constitution
Study
Svensson et al. 1985 [46]
Kang and Tian 1987 [15]
Diepgen et al. 1989 [4]
Werner Linde 1989 [54]
Kanwar et al. 1991 [16]
Przybilla et al. 1991 [34]
Diepgen and Fartasch 1992 [5]
Rudzki et al. 1994 [41]
Nagaraja et al. 1996 [31]
Böhme et al. 2000 [2]
Lee et al. 2000 [20]
Patients with atopic
Controlsa
eczema
Total (n) Dry skin ( %) Total (n) Dry skin ( %)
47
372
110
50
50
34
428
481
100
157
130
98
65
96
48
80
74
91
85
76
100
68
47
213
527
50
50
23
628
150
100
99
198
the major and minor (primary) creases represent
defined skin markings, the term “secondary crease”
describes any visible palmar line other than the primary ones. Systems for quantitative evaluation of palmar
creases have been devised using either five or three
grades of intensity [42, 47]. These refer particularly to
the area of the palms that is traversed by secondary
creases. Furthermore, the density and depth of creases
can be evaluated. Imprints are the best method to visualize crease patterns. For clinical purposes, such a procedure is too sophisticated, and usually the overall
impression of “hyperlinearity” is considered.
The expression of palmar markings can be influenced by environmental factors (e.g., manual work as
well as chemical and thermal factors) or age, and there
may be differences between the right and left sides [13].
The relation of palmar hyperlinearity to autosomal
dominant ichthyosis vulgaris has been a matter of discussion. It has been suggested that hyperlinearity in
patients with atopic eczema is indicative of concomitant ichthyosis vulgaris [28, 49 – 51]. This has been
doubted for clinical reasons [14, 45]. By ultrastructural
analysis, it could be shown that abnormal keratohyaline granules, proving autosomal dominant ichthyosis
vulgaris, are demonstrable only in a minority (2/17) of
atopic eczema patients with hyperlinearity of the
palms [9]. Hyperlinearity thus is associated with both
ichthyosis vulgaris and atopic eczema.
Studies on the prevalence of palmar and plantar
hyperlinearity are summarized in Table 7.3. For the
most part, this feature was significantly more frequent
in patients than in controls.
34
18
25
14
8
31
26
11
14
40
18
P
< 0.001
< 0.01
< 0.01
< 0.01
< 0.01
< 0.01
23.2 – 33.8b
< 0.001
< 0.01
< 0.05
< 0.001
Fig. 7.2. Palmar hyperlinearity
Table 7.2. Prevalence of dry
skin
a
b
See Table 7.9
Odds ratio, 95 % confidence interval
7.2 Constitutional Stigmata of Atopy
Table 7.3. Prevalence of hyperlinearity of the palms or soles
Study
Hirth et al. 1971 [13]
Mevorah et al. 1985 [28]
Kang and Tian 1987 [15]
Diepgen et al. 1989 [4]
Kanwar et al. 1991 [16]
Przybilla et al. 1991 [34]
Diepgen and Fartasch 1992 [5]
Nagaraja et al. 1996 [31]
Böhme et al. 2000 [2]
Lee et al. 2000 [20]
Patients with atopic eczema
Total (n) Hyperlinearity ( %)
Palm
Sole
Palm
Sole
17
17
61c
372
110
50
34
34
428
100
157
130
65b
65b
33
49
49
54
88
74
50
23
4
32
P
Controlsa
Total (n)
Hyperlinearity ( %)
300
300
247
213
527
50
23
23
628
100
99
198
31b
29b
22
9
6
20
48
30
8
4
0
12
NG
NG
NS
< 0.01
< 0.01
< 0.05
< 0.01
< 0.01
9.8 – 13.9d
< 0.01
NS
< 0.001
NG, not given; NS, not significant
a
See Table 7.9, b Intensity grade III or IV, c Patients with both atopic eczema and “frank ichthyosis” were excluded,
d Odds ratio, 95 % confidence interval
7.2.3
Infraorbital Fold
Infraorbital fold (Fig. 7.3) is included in most descriptions of atopic eczema. Morgan [30] was the first to
report this sign. He referred to Dennie, who had considered a “definite wrinkle just beneath the margin of
the lower lid of both eyes” to be pathognomonic for
allergy, especially eczema, hay fever, and asthma.
Accordingly, this feature is known also as Dennie-Morgan infraorbital fold, Morgan’s fold, or Dennie’s fold.
There may be single or double folds. Usually, the
wrinkle is present on both eyelids, but occasionally a
unilateral manifestation is seen [29, 48]. The original
definition [30] has been modified by some who read
the sign as being present only if there is a definite dou-
Fig. 7.3. Infraorbital fold
ble fold [26] or if one or more creases, outlining skin
folds and starting at the inner canthus, extend laterally
at least beyond an imaginary perpendicular line
through the pupil [29]. When creases are considered,
the physiologic sulcus palpebralis inferior must not be
mistaken for the stigma.
It has been claimed that infraorbital folds are related
to eyelid eczema: Uehara found this feature in 83 % of
atopic eczema patients with, but in only 7 % of patients
without lower eyelid dermatitis [48]. Furthermore, he
saw infraorbital folds in 8 of 11 nonatopic patients with
allergic contact dermatitis of the lower eyelids [48]. On
the other hand, infraorbital folds are not infrequent in
subjects without eczema [44, 46, 57], indicating that
not all folds are due to inflammation. We found infraorbital folds in patients with atopic eczema as frequently as in subjects with respiratory atopic diseases
without a history of eczema [34].
Infraorbital folds were significantly more frequent
among atopic eczema patients than controls in the
majority of studies; however, in a substantial number of
studies this was not the case (Table 7.4). These differences may be related not only to the definition of “infraorbital fold,” but also to ethnic variations or to inclusion
criteria for patients and controls. Infraorbital folds were
less prevalent in Japanese patients [48]; Kang and Tian
[15] did not find “meaningful infraorbital folds” in Chinese individuals. On the other hand, a prominent infraorbital crease was found in 49 % of normal black children, compared with 25 % of white children [57], but a
rather high prevalence of infraorbital folds (31 % or
65
66
7 Stigmata of the Atopic Constitution
Study
Meenan 1980 [26]
Meenan 1981 [27]
Uehara 1981 [48]
Svensson et al. 1985 [46]
Mevorah et al. 1988 [29]
Diepgen et al. 1989 [4]
Kanwar et al. 1991 [16]
Przybilla et al. 1991 [34]
Diepgen and Fartasch 1992 [5]
Rudzki et al. 1994 [41]
Nagaraja et al. 1996 [31]
Williams and Pembroke 1996 [57]
Singh and Kanwar 1997 [44]
Böhme et al. 2000 [2]
Lee et al. 2000 [20]
Patients with atopic
Controlsa
eczema
Total (n) Infraorbital Total (n) Infraorbital
fold ( %)
fold ( %)
100
148
300
47
105
110
50
34
428
481
100
15
20
157
130
9
12
25
60
51
57
82
82
68
78
63
27
20
3
52
100
168
300
47
113
527
50
23
628
150
100
145
480
99
198
2
1
2
38
51
17
54
13
16
49
27
34
36
2
14
P
NG
NG
NG
< 0.05
NS
< 0.01
< 0.01
< 0.01
9.4 – 12.7b
< 0.001
< 0.01
NS
NS
NS
< 0.001
Table 7.4. Prevalence of infraorbital fold
NG, not given;
NS, not significant
a
See Table 7.9
b
Odds ratio, 95 % confidence interval
51 %) in control subjects was also found in two studies
evidently conducted with Caucasian subjects [29, 46].
The wide variation of prevalence of infraorbital folds
among patients and controls in different studies might
also be explained by their association with “pure”
respiratory atopic disease, i.e., their presence in atopic
patients without eczema [34]. The presence or absence
of respiratory atopic disease among patients or controls (Table 7.9) was not always considered.
7.2.4
White Dermographism
White dermographism (Fig. 7.4) is a “classic” finding
in patients with atopic eczema. According to Korting
[18], it was first described by Marey in 1858. Whereas
firm stroking of normal skin with a blunt instrument
leads to a partially or fully developed triple response of
Lewis (red, more or less urticarial “line” with reflex
erythema) in the majority of the population [58], white
dermographism (white line) develops instead in some
individuals. This white reaction replaces the initially
mechanically provoked red line about 15 – 60 s after
stroking [3, 58]. White dermographism in atopic eczema patients has a longer time to start and a shorter
duration than red dermographism in controls [59].
Usually dermographism is elicited with an instrument
that is readily available, such as a paper clip or a tongue
depressor. For quantitative studies, various instruments have been devised [6, 38, 43, 59].
Fig. 7.4. White dermographism
The elicitation of white dermographism depends on a
number of factors. It has been said to occur more easily
on the lower than on the upper half of the body [3], and
on the arms, legs, and neck rather than on the abdomen and trunk [33, 38]. Its occurrence may also be
restricted to some localized skin sites [18]. Even slight
stroking can elicit white dermographism [56]. The
reaction to a stimulus that is too strong may be a red
line with a white halo instead [38]. White dermographism has been found to occur with greater ease in
individuals up to 30 years of age than in older ones [6].
However, during infancy the ability to develop white
dermographism is reduced and was found to increase
with age [1]. In patients with atopic eczema, the occurrence of white dermographism on skin appearing clinically normal was related to disease severity [40, 60].
7.2 Constitutional Stigmata of Atopy
The pathophysiologic aspects of abnormal vascular
reactivity of patients with atopic eczema are reviewed
elsewhere in this volume. Here, only the relation of
white dermographism to eczema itself will be briefly
considered. For more than 70 years, it has been known
that white dermographism can be elicited almost regularly in the diseased skin of patients with atopic eczema
[40]. However, it can also be elicited in lesions of other
chronic inflammatory dermatoses [38, 56]. In atopic
eczema patients, white dermographism was found on
lichenified skin in 86 %, on dry and rough skin in 76 %,
and on normal appearing skin in only 1 % [52]. As histologic examination of biopsies taken from dry and rough
skin revealed eczematous changes, it was concluded that
white dermographism is a secondary phenomenon
related to inflammation. Nonetheless, since white dermographism is more frequent in atopic eczema than in
other types of eczema [15, 52], the atopic state may predispose one to this form of reaction. Furthermore, the
observation of white dermographism on the normal
skin of individuals without atopic eczema (Table 7.5)
argues against the concept that white dermographism is
only secondary to inflammatory skin changes. It is
assumed that white dermographism can have different
causes, inflammation and the atopic state concurring in
the lesional skin of patients with atopic eczema.
The reported prevalence of white dermographism
in both atopic eczema patients or controls was 0 %–
100 % (Table 7.5). These large differences are probably
due to varying test modalities. Nevertheless, in the
majority of studies a significant association between
atopic eczema and white dermographism was found.
7.2.5
Facial Pallor
Facial pallor is generally regarded as a characteristic
feature of atopic eczema. Just like white dermographism, this diffuse paleness is attributable to an abnormal vascular reactivity with a tendency toward vasoconstriction of small blood vessels. Beyond the clinical
impression, facial pallor can be recognized more distinctly by comparing a skin area rendered anemic by
pressure of a glass spatula to the natural skin color.
Maximum pallor is characterized by the finding of no
difference in response to this maneuver. Patchy pale
areas on the face may also occur due to rubbing in
patients with white dermographism, and flushing or
erythema can alternate with pallor [11, 36]. Facial pallor (erythema) was found to be more frequent in younger than in older patients [15, 46], but in children only
2 years old it was virtually absent [2].
Table 7.5. Prevalence of white dermographisma
Study
Patients with atopic
eczema
Total
White dermo(n)
graphism (%)
Controlsb
Total
(n)
White dermographism (%)
Rajka 1960 [35]
100
81
40
10
Uehara and Ofuji 1977 [52]
100
20
18
Svensson et al. 1985 [46]
Kang and Tian 1987 [15]
Mevorah et al. 1988 [29]
47
230
103
86
76
1
100
60
42
47
32
111
0
100
34
14
Kanwar et al. 1991 [16]
50
12
50
2
Przybilla et al. 1991 [34]
34
38
23
4
116
141
3
0
0
99
1
Böhme et al. 2000 [2]
P
NG
Test site
Diseased skin (atopic eczema
patients)
NG
Lichenified skin
Dry and rough skin
Normal skin
Normal skin of the foreleg
< 0.05 Lesioned skin
< 0.005 Uninvolved skin (usually on
the forehead)
NS
Eczematous as well as uninvolved skin of the back
< 0.01 Clinically normal skin
(usually on the upper back)
Lesional
NS
Nonlesional
NG, not given; NS, not significant
a Studies indicating the condition of the test site and not using a test apparatus, b See Table 7.9
67
68
7 Stigmata of the Atopic Constitution
Study
Svensson et al. 1985 [46]b
Kang and Tian 1987 [15]
Kanwar et al. 1991 [16]b
Przybilla et al. 1991 [34]
Diepgen and Fartasch 1992 [5]b
Nagaraja et al. 1996 [31]
Böhme et al. 2000 [2]
Lee et al. 2000 [20]b
Patients with atopic
eczema
Total Facial pallor
(n)
( %)
47
372
50
34
428
100
157
130
64
22
14
85
39
26
1
41
Controlsa
Total
(n)
Facial pallor
( %)
47
213
50
23
628
100
99
198
32
4
0
13
11
6
0
5
Nearly all studies assessing the prevalence of facial pallor found it to be significantly more frequent in patients
with atopic eczema than in controls (Table 7.6).
7.2.6
Orbital Darkening
Orbital darkening (Fig. 7.5) is regarded as a feature of
both atopic eczema [11, 12, 37, 39] and allergic nasal
disease [22 – 25]. Also known as allergic shiners, this
sign is characterized by a brownish to grayish or bluish
discoloration of the orbital region, particularly in its
lower half. Sometimes there is also slight edema. Altogether, this gives the patient a tired look [21]. Orbital
darkening was reported to be correlated with young
age [46].
Orbital darkening in patients with atopic eczema
may be interpreted as secondary hyperpigmentation
following chronic inflammation. Thus, it could be
caused by eyelid eczema. Another mechanism has been
Fig. 7.5. Orbital darkening
P
< 0.001
< 0.01
< 0.05
< 0.01
4.5 – 6.3c
< 0.01
NS
< 0.001
Table 7.6. Prevalence of facial
pallor
NS, not significant
a See Table 7.9
b
Facial pallor/erythema
considered
c Odds ratio, 95 % confidence interval
suggested for orbital darkening associated with perennial rhinitis. Persistent edema of the mucous membranes of the nasal cavities and perhaps also spasm of
the musculus tarsalis would impede venous blood flow
from the orbital region, thus causing edema and discoloration [22, 23]. Both mechanisms can explain the
occurrence of orbital darkening, and in either case it
would be a sequela of disease. However, it is a common
clinical observation that orbital darkening may also be
seen in atopic patients who have never had eczema of
the eyelids or manifest respiratory disease. In the
majority of studies, orbital darkening was found to be
significantly more prevalent in atopic eczema patients
than in controls (Table 7.7).
7.2.7
Hertoghe’s Sign
Thinning or complete absence of the eyebrows in their
lateral aspects (Fig. 7.6) was first described by Hertog-
Fig. 7.6. Hertoghe’s sign
7.2 Constitutional Stigmata of Atopy
Table 7.7. Prevalence of
orbital darkening
NS, not significant
a See Table 7.9
Table 7.8. Prevalence of
Hertoghe’s sign
NS, not significant
a
See Table 7.9
b
Odds ratio, 95 %
confidence interval
Study
Patients with atopic
eczema
Total
Orbital
(n)
darkening (%)
Svensson et al. 1985 [46]
Kang and Tian 1987 [15]
Kanwar et al. 1991 [16]
Przybilla et al. 1991 [34]
Rudzki et al. 1994 [41]
Nagaraja et al. 1996 [31]
Böhme et al. 2000 [2]
Lee et al. 2000 [20]
Study
Diepgen et al. 1989 [4]
Przybilla et al. 1991 [34]
Diepgen and Fartasch 1992 [5]
Nagaraja et al. 1996 [31]
Lee et al. 2000 [20]
he at the turn of the nineteenth to the twentieth century
as a feature related to hypothyroidism [18]. Its occurrence in patients with atopic eczema was attributed to
different causes: It has been interpreted as secondary to
rubbing of the skin [53], but others have suggested that
it is related to disturbances of the autonomic nervous
system [18]. Indeed, rubbing or scratching of the eyebrow region may mechanically cause loss of the brows,
but there are individuals who exhibit typical Hertoghe’s sign without any manifest or previous eczema or
other inflammatory skin disease of the face. It has been
proposed to term rarefied eyebrows secondary to
mechanical injury “pseudo“ Hertoghe’s sign in order
to delineate them from “true” Hertoghe’s sign [18].
However, in the individual patient with atopic eczema,
it will be difficult or impossible to differentiate in this
way. Assessed only in a few studies, Hertoghe’s sign was
found mostly to be significantly associated with atopic
eczema (Table 7.8).
47
372
50
34
481
100
157
130
47
55
32
85
53
12
0
39
Total
(n)
Orbital
darkening (%)
47
213
50
23
150
100
99
130
32
7
8
26
7
2
9
9
Patients with atopic
Controlsa
eczema
Total Hertoghe’s sign Total Hertoghe’s sign
(n)
( %)
(n)
( %)
110
34
428
100
130
39
68
42
0
20
527
23
628
100
198
1
44
2
0
0
P
NS
< 0.01
< 0.01
< 0.01
< 0.001
< 0.05
NS
< 0.001
P
< 0.01
< 0.01
32.1 – 62.6b
NS
< 0.001
hat-like hairline” describes this feature in plain words
[19]. Often, the low hairline is most prominent in the
temporal region, where there may be, between the
scalp and the margin of the eyebrows, not only a
reduced distance, but even a direct connection by some
terminal hairs. Rarefied lateral eyebrows, that is Hertoghe’s sign, do not preclude this feature. We found a
low hairline, defined as a distance of e 3 cm between
scalp and margin of the eyebrows, in 88 % of 34 atopic
eczema patients and in 52 % of 23 controls (p < 0.01,
definition of controls in Table 7.9) [34].
7.2.8
Low Hairline
A low hairline (Fig. 7.7) in the frontal and temporal
region has been mentioned only rarely as a stigma of
patients with atopic eczema [17, 18, 39]. The term “fur
Controlsa
Fig. 7.7. Low hairline
69
70
7 Stigmata of the Atopic Constitution
Table 7.9. Studiesa on the prevalence of constitutional atopy stigmata in atopic eczema patients: selection criteria for controls
Study
Selection criteria for controls
Rajka 1960 [35]
Hirth et al. 1971 [13]
Uehara and Ofuji 1977 [52]
Meenan 1980, 1981 [26, 27]
Uehara 1981 [48]
Mevorah et al. 1985 [28]
Patients with asthma bronchiale and/or atopic rhinitis
Persons without skin disease
Patients with contact dermatitis
Children suffering from warts and with no history of atopy
Persons with no personal or family history of atopy
Patients with dermatoses other than ichthyosis or atopic eczema and without a past history
of atopic eczema or a known family history of ichthyosis or scaling
Svensson et al. 1985 [46]
Patients without a present eczematous dermatitis or previous medical care for such a disease
Kang and Tian 1987 [15]
Assessment of white dermographism: Patients with chronic eczema without atopy
Assessment of other stigmata: Dermatological patients without atopy
Mevorah et al. 1988 [29]
Individuals without a personal or family (close relatives) history of eczema, asthma, or allergic rhinitis
Diepgen et al. 1989 [4]
Persons without present or previous flexural eczema
Werner Linde 1989 [54]
Persons from the venereal disease outpatient clinics without atopy
Kanwar et al. 1991 [16]
Patients with neither personal nor family history of any atopic disorder
Przybilla et al. 1991 [34]
Individuals without a personal or family history of atopic eczema, allergic rhinitis, or asthma
and with no prick test reaction to common aeroallergens (grass pollen, cat epithelia, house
dust mite).
Diepgen and Fartasch 1992 [5] Individuals without eczema or respiratory allergy (n = 510)
Patients with respiratory allergy without eczema (n = 118)
Rudzki et al. 1994 [41]
Individuals without any skin changes or atopic diseases
Nagaraja et al. 1996 [31]
Patients with dermatoses other than eczema, exclusion of those with either a personal or a
family history of atopy
Williams et al. 1996 [57]
Absence of active atopic eczema
Singh et al. 1997 [44]
Absence of active atopic eczema
Böhme et al. 2000 [2]
No history of eczema
Lee et al. 2000 [20]
Volunteers with no personal or family history of atopic disease
a
For results, see Tables 7.2 – 7.8
7.3
Constitutional Stigmata as Markers of Atopy
The stigmata reviewed here are nonspecific with
regard to atopic eczema, as they can be found also in
other conditions (e.g., hyperlinearity of the palms or
dry skin in autosomal dominant ichthyosis vulgaris) or
in controls. However, although in different studies the
prevalence rates found for certain stigmata varied considerably, there was overall a significant association
between these features and atopic eczema.
Some features (dry skin, infraorbital fold, white dermographism, orbital darkening, Hertoghe’s sign) have
been said to be direct manifestations or sequelae of
atopic eczema itself. These then would not fulfill the
criteria proposed for “true” constitutional stigmata.
An interpretation of some features as secondary to disease is correct apparently in certain, but evidently not
in all cases, as stigmata are present also in controls
without eczema. Further, secondary changes are not
necessarily just phenocopies; they may represent provoked manifestations under conditions of a given lia-
bility. This is exemplified by white dermographism,
which is more frequent in the lichenified skin of atopic
than of nonatopic eczema [52].
Constitutional stigmata have been discussed mainly
in relation to atopic eczema. The question arises as to
their prevalence in respiratory atopic disease. White
dermographism was reported to occur in 10 % of
patients with asthma and/or atopic rhinitis compared
to 81 % with the lesioned skin of atopic eczema [35]. A
significant correlation between the absence of orbital
darkening and allergic rhinitis or asthma has been
reported [46], which contrasts with other opinions
[22 – 25, 39]. Furthermore, the same authors [46] found
an association between asthma and the absence of an
intraorbital fold.
We evaluated the prevalence of constitutional stigmata discussed here in patients with allergic rhinoconjunctivitis and/or asthma without any present or previous atopic eczema [34]: with the exception of Hertoghe’s sign, dry skin, and white dermographism, all other
features were significantly more frequent in patients
with respiratory atopic disease than in controls; except
7.3 Constitutional Stigmata as Markers of Atopy
for dry skin, individuals with atopic eczema or respiratory atopic disease did not differ significantly with
regard to any of the other stigmata investigated [34].
This suggests that most of these stigmata are related to
the atopic state and not only to atopic eczema. Therefore, patients with atopic respiratory disease should be
omitted from control groups in studies on the prevalence of stigmata in atopic eczema, which was not
always done (Table 7.9).
There are as yet no definite test methods to establish the presence of an atopic state in the absence of
manifest atopic disease. In this respect, the assessment
of constitutional stigmata of atopy may be helpful.
Identification of presumably atopic, but not yet diseased, individuals (“silent atopy”) will, for example,
allow their counseling at the start of an occupational
career or their exclusion from control groups in studies on atopic conditions. Markers of atopy also can
corroborate the clinical diagnosis of manifest atopic
disease. The use of atopic stigmata for such purposes is
hampered by their nonspecificity. Practically, only in
the presence of several clear-cut features should atopy
be presumed.
Further studies are needed to determine the value of
assessing constitutional atopy stigmata more precisely.
Their expression should be evaluated with regard to
possibly modifying parameters (e.g., disease activity,
environment, age, ethnic background) and the developmental mechanisms leading to their expression. It
would be important to define stigmata clearly with
reproducible criteria also considering their grades of
expression. A proposal for a classification is given in
Table 7.10.
Acknowledgements. The authors wish to thank Mr. P.
Bilek, photographer, for skillful photography.
Table 7.10. Assessment of constitutional stigmata of atopy
a
Gradinga
Stigma
Parameter
Dry skin
Clinical impression ob- Absent
tained by evaluation of
the entire skin surface
Mild
Moderate
Prominent
Hyperlinearity of
palms or soles
Clinical impression
Absent
Mild
Moderate
Prominent
Infraorbital fold
Fold starting at the
inner corner of the eye
and running laterally
Absent
Mild: underlining
at most half of the
medial palpebral
fissure
Prominent: running
Moderate: underbeyond the palpebral
lining at most
whole palpebral fis- fissure
sure
White dermographism
Testing on clinically
normal skin (preferably on the upper back)
with a blunt instrument
Red dermographism
Red dermographism with a
white halo
White dermographism
Facial pallor
Clinical impression
Absent
Mild
Moderate
Prominent
Orbital darkening Clinical impression
Absent
Mild
Moderate
Prominent
Hertoghe’s sign
Lateral thinning/absence of the eyebrows
extending medially
Absent
Mild: thinning/
absence extending
not beyond the
lateral corner of
the palpebral fissure
Moderate:
thinning/absence
involving the eyebrow above the lateral quarter of the
palpebral fissure
Prominent: thinning/
absence extending to
the eyebrow above the
medial three quarters
of the palpebral fissure
Low hairline
Lowest distance
between scalp hairs
and the margin of the
eyebrows
Absent:
> 3.0 cm
Mild: 1.6 cm –
3.0 cm
Moderate: up to
1.5 cm
Prominent: direct
transition from scalp
hair to eyebrows
External influences (e.g., the use of emollients on dry skin, the effect of eyebrow plucking on Hertoghe’s sign) have to be
considered
71
72
7 Stigmata of the Atopic Constitution
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