Normally dermatologists in the description of a skin disease start with the “primary lesion.” There is no consensus with regard to the primary lesion of atopic eczema; it is described as erythema, papule, and seropapule. Some authors, starting with Jacquet (1904) and the French School, stress the symptom “pruritus.” According to good tradition the author says, together with Saint John the Evangelist or Johann Wolfgang von Goethe (Faust): “In the beginning there was the itch!” (Rajka 1980, 1989; Ring 1982a).

Rarely it is possible to observe the acute development of an eczematous skin lesion in atopic dermatitis directly; however, sometimes—e.g., with your own children or under provocation tests in the hospital—it is possible. From this experience it can be concluded that human beings, who never before have shown any signs of eczematous skin changes, triggered by some environmental or psychologic factors suddenly develop itch and start scratching on apparently normal skin. Only hours later the typical clinical manifestations of atopic dermatitis develop. These phenomena are especially common in the areas mostly affected such as the elbow, knee flexures, or eyelids. It is a pity that there is little scientific documentation with regard to these early manifestations in the individual initial phase. Many colleagues, parents, and patients have made this experience.

Itch as “dermatose invisible” is the primary lesion of atopic dermatitis which, via the scratch reaction, then gives rise to the characteristic morphologic skin changes (Fig. 2.1). Besides, it is possible that primarily skin changes occur which go along with increased itch. The borders are fluent. A typical atopic eczema without itch is extremely rare, if not inexistent. Since the French School at the beginning of the twentieth century, the central importance of itch for atopic dermatitis has been stressed by many authors (Borelli and Schnyder 1962; Braun-Falco and Ring 1984; Breit 1997; Engman et al. 1936; Haxthausen 1957; Kimura and Miyazawa 1989; Koblenzer 1999; Rajka 1989; Ring et al. 2006; Talbot 1918).

Itch is the most agonizing symptom of manifest disease and often is perceived as “incurable.” It leads to sleep loss, nightly scratch attacks with bloody bedding, a feeling of “powerlessness,” because it cannot be stopped voluntarily. Unfortunately this symptom is not yet taken seriously by many physicians and the society, contrary to the other main subjective symptom “pain.” Regarding the latter, everybody is full of compassion (Ständer et al. 2010). I personally know patients who wanted to commit suicide because of severe itch, a fact also observed by other authors (Dieris-Hirche et al. 2009).

The old sentence “It is not the rash which itches, but the itch that rashes” (Engman et al. 1936) illustrates the situation. Early attempts of treatment 80 years ago quite brutally used procedures like fixation of children in bed or applying plaster to their extremities, so that scratching became impossible. Lesions in unreachable skin areas were indeed healing faster. Pathophysiologically this indicates that by scratching proinflammatory substances may be released (see Chap. 3).

Today the treatment of itch is the focus in the management of atopic dermatitis, and the prevention of direct scratch effects by mechanical procedures such as wet wraps with tube bandages plays a central role (see Chap. 5).

Mild cases or the beginning of an exacerbation become manifest in flat, mildly infiltrated, erythematous patches with only little epidermal involvement which in the course can be excoriated and change to oozing crusting areas (Fig. 2.2).

In the severity scoring of the SCORAD (see Sect. 2.8.2, page 64), these criteria “erythema,” “edema and papule,” but also “lichenification” are enlisted.

It is important to stress that there are these manifestations since they are not clearly mentioned in many textbooks.

Especially in childhood, often patchy or punctate erosive or excoriated erythematous skin changes with mild scaling are observed, going along with intense itch (Fig. 2.3).

Histologically these lesions are characterized by spongiotic changes in the epidermis. This form often has been called “eczematoid type” in the restricted sense. This may have contributed to dissatisfaction with the name “eczema” for the whole disease and may be a reason for the terminology and preference of the unprecise term “dermatitis.”

In the broader definition of eczema (see Sect. 2.8.2), it becomes clear that in the local and timely course, the polymorphy of symptoms in eczema also includes other morphologies like lichenification, prurigo-type excoriated papules, etc.

Maybe strongly oozing and crusty skin changes in childhood represent signs of superinfection with, e.g., Staphylococcus aureus (see Sect. 2.6).

This morphology also can be observed in circumscribed skin lesions with nummular variants (see Page 37). Whether nummular eczema in childhood represents an own identity is still to be discussed. In the opinion of the author, this nummular variant is a subtype of atopic eczema in childhood.

The more chronic the skin changes, the more it shows a tendency to lichenification. This means a coarsening of the skin signs with thickening of the skin and livid red color “purple.” These skin changes occur predominantly in the flexures of the big joints (elbow, knee flexure), but also as large plaques on the dorsum of the hands and feet. They also represent most likely the consequence of long-lasting scratch effects (Fig. 2.4).

The entity of lichen simplex chronicus (Vidal) or “circumscribed neurodermatitis” can be regarded as a subgroup of localized variants of atopic eczema; however, this is a matter of discussion.

Lichenification can be provoked by scratching as could be shown in classic experiments with the use of a scratch machine with a pressure of 75 g on the skin. After 60–90 h lichenification could be provoked (Goldblum and Piper 1954).

When the follicular affection in chronic courses is prominent especially in adults, a variant can be observed which shows the clinical symptoms of prurigo; it is relatively marked by strongly itching papules or nodules with a diameter of 0.5–3 mm and central excoriation and crusting. This variant most likely gave rise to the term “prurigo Besnier” and can be found commonly in the severe manifestations in adults (Fig. 2.5).

Contrary to other dermatoses, atopic dermatitis does not show a clear-cut morphology. The primary lesion can best be described as itch which then via scratching leads to the formation of skin changes. Several variants with “infiltrated erosive erythema,” “chronic lichenification,” or “prurigo type” of atopic dermatitis can be observed. Exudative eczematous skin changes can be found predominantly during childhood or when superinfection occurs. Minimal manifestations comprise infra-auricular fissures, cheilitis sicca, infranasal erosion, eyelid eczema, finger or toe eczema, and pityriasis alba.

Dry skin is a major characteristic of atopic dermatitis, also called sebostasis or xerosis; it is visible as rough skin, sometimes slightly scaling (Fig. 2.25). The term “dry” skin can be questioned pathophysiologically since, in investigations with regard to the percentage of water in the skin, no real decrease has been found, but an increased transepidermal water loss (TEWL) due to disturbed skin barrier function. Furthermore, mild signs of inflammation have been found in “dry skin of atopic dermatitis” in uninvolved areas (Uehara 1985).

The term sebostasis indicates a diminished sebum secretion which is controversial. The lipid content of the epidermis has been investigated by several groups and found to be altered especially with regard to different patterns of ceramides (see Chap. 3).

Finally a major characteristic is roughness which can be recognized by the patient and physician and feels like “dryness.” It is not clear whether this “dry” aspect actually corresponds to the deficiency of the epidermal protein filaggrin (see Chap. 3) found in many patients with atopic eczema.

This stigma is well known in patients with the autosomal dominant disease ichthyosis vulgaris. Marked linear furs or lines can be seen, partly in a bizarre or linear configuration mostly on the palms, but in infants commonly also on the soles (Fig. 2.26).

This sign, first described by Leutgeb et al. (Leutgeb et al. 1972), was regarded for a long time as proof for concomitantly occurring ichthyosis vulgaris and can now better be explained by the filaggrin deficiency in heterozygous states in many atopic dermatitis patients. Only in a small part of eczema patients the typical signs of ichthyosis vulgaris can be seen in histopathology or by electron microscopy, namely, abnormal keratohyalin granules (Fartasch et al. 1989).

A subgroup of ichthyosis hands or feet can be seen in linear grooves often horizontal to the papillary lines on the fingertips (Fig. 2.27).

This sign has first been described in a letter by Dr. Morgan as “definite wrinkle just beneath the margin of the lower lid of both eyes,” who mentioned it to Dr. Dennie (Morgan 1948) as a sign of atopy. The fold can be single or double. Mostly it is present on both lower eyelids, sometimes, however, only unilaterally. The exact definition implies a clear-cut double fold beginning mostly at the inner (medial) canthus and reaching laterally at least beyond the center of the pupil. The atopy fold must not be confounded with the physiological sulcus palpebralis inferior (Przybilla et al. 1991; Uehara 1981) (Fig. 2.28). Many authors regard the Dennie-Morgan fold as a sequel of lid eczema due to increased rubbing and scratching. However, clear-cut clinical observations have shown that this stigma can be present many years before the first occurrence of atopic dermatitis, mostly starting in other body areas like the elbows or knee joints and without lid eczema.

The atopy fold is also present in respiratory atopic diseases. In Asian patients, the infraorbital fold seems to be a less suitable marker.

This sign, also called halo eyes (Fig. 2.29), can be observed in atopic eczema, but also in respiratory atopy as allergic rhinoconjunctivitis and has been called “allergic shiners”; the manifestation is a dark gray, brownish discoloration of the periorbital areas, sometimes associated with mild edema. The patients give an impression of sleeplessness (“bleary eyed”). Some of my coworkers call them “disco shadows.” Once an actress came to me as a patient just because of this skin change, for the director would not give her a role in a play anymore, since she looked “worn out” (“kaputt”).

Pathophysiologically swellings and congestion of postcapillary venules in the area of the nasal sinuses have been incriminated. Occasionally a secondary hyperpigmentation on the basis of existing chronic eczema has been observed; this, however, does not correspond to a stigma. Together with the common pallor of the face, this stigma can be regarded as imbalance of the autonomic nervous system with increased alpha-adrenergic and cholinergic impulses and decreased beta-adrenergic reactions (Korting 1954).

This sign has been first described at the beginning of the twentieth century by Hertoghe in a patient with hypothyreosis. In patients with atopic eczema, some authors see an association to increased rubbing of eyebrows, when eyebrow eczema can be diagnosed at the same time (Fig. 2.30). For a long time it was regarded as a classic stigma of altered skin independent of immune reactivity. Saurat observed a regrowth of lateral eyebrow hair after successful bone marrow transplantation in patients with Wiskott-Aldrich syndrome with massive atopic eczema and atopy stigmata (Saurat 1985). It is obvious that artificial manipulations (plucking of eyebrows) (pseudo-Hertoghe) have to be differentiated from the true stigma.

This stigma describes a decreased distance between the temporal hairline and the end of the lateral eyebrows; sometimes there is no distance in between (Fig. 2.31). Quantitatively the distance between the temporal hairline and eyebrow should be more than 3 cm. The stigma can be observed in almost 90 % of patients with atopic dermatitis (Przybilla et al. 1991).

A positive Hertoghe phenomenon does not exclude a low temporal hairline sign.

The white dermographism is one of the best-known stigmata of atopy. While in healthy individuals tangential pressure (e.g., with a spatula) leads to a redness of the skin within 30–60 s (red dermographism), in atopic individuals sometimes the skin turns white (Fig. 2.32); sometimes there is a contrasting whitening next to a central red part (red dermographism with a white edge). Pathophysiologically most likely an increased local vasoconstriction is the basis of white dermographism (Wong et al. 1984).

After injection of acetylcholine (intradermal), some patients with atopic eczema develop a long-lasting white discoloration in the injection area called delayed blanch reaction or delayed white reaction (Hanifin and Lobitz 1977; Lobitz and Campbell 1953; Whitfield 1938).

White dermographism and delayed blanch can be regarded as signs of autonomic dysregulation in atopics. They are not specific for atopic dermatitis but also can be seen in respiratory atopy.

It is important not to elicit white dermographism in an involved or inflamed skin area. On inflamed skin, white dermographism can be elicited also in other skin conditions.

Many studies have investigated the prevalence of atopy stigmata in patients with atopic eczema and other atopic diseases as well as in healthy control persons. In an intense and quantitative measurement in patients with various atopic diseases and healthy controls, we found that all of the abovementioned stigmata were significantly more prevalent in atopics compared to non-atopic controls (Przybilla et al. 1991). The strongest association with atopic eczema (and significantly higher than in respiratory atopy) were:

Similar to the increased tendency to IgE production (see Sect. 1.​3.​1), there also may be overlaps in the manifestation of atopy on the skin with “minimal” or “latent” atopy which only become manifest in stigma or presence of stigmata without ever turning into actual clinical eczema.

Stigmata have to be distinguished from actual symptoms of disease. They are signs of the skin organ not necessarily connected with feeling ill which give hints to the existence of an “atopic” diathesis. They comprise dry skin (xerosis, sebostasis), hyperlinearity of the palms and soles (ichthyosis “hands” or “feet”), increased infraorbital fold (atopy fold Dennie-Morgan), facial pallor with periorbital halo, rarefaction of lateral eyebrows (Hertoghe), fur cap hair growth with low temporal hairline, as well as white dermographism and delayed blanch.

In the first months of life, it is mainly seborrheic dermatitis or diaper dermatitis which has to be considered (Fig. 2.33). Often there is no clear-cut diagnosis in the first months of life, and then the term “eczema infantum” (infantile eczema) is helpful (Edgren 1943).

There is a valuable rule: bipolar occurrence (especially head and scalp and genital area involved) allures seborrheic dermatitis (Fig. 2.34). Skin changes in the head and trunk with the uninvolved diaper area are typical for atopic eczema. This commonly observed “diaper phenomenon” is poorly investigated scientifically. One can speculate whether the diaper offers protection against scratching or the contents act like a wet wrap. It is surprising that in severely affected infants with atopic eczema, often only the diaper area is totally uninvolved (Fig. 2.35).

Another sign visible to everybody but not often recognized is the absence of eczema on the tip of the nose (Yamamoto sign, personal communication via Kristian Thestrup-Pedersen 2005).

In infants, but also in small children, psoriasis can be a difficult differential diagnosis, especially in cases of so-called figurated eczema or when there is a coincidence of both diseases. Thirty years ago this was no problem; eczema and psoriasis seemed to exclude each other. Only by the epidemiological studies by Henseler and Christophers (1995), it became clear that psoriasis and atopic eczema can occur in one and the same individual, although rarely. Due to the increase in eczema prevalence, this subgroup of patients may be seen more often.

Furthermore existing eczema may trigger latent psoriasis via scratching and mechanical traumatization in the sense of a Koebner phenomenon.

A difficult differential diagnosis can be the localized involvement of palms and soles together with dyshidrosis (pompholyx). This type of hand eczema can occur in atopic eczema, but also in allergic contact dermatitis, and also in patients with tinea. According to some authors, dyshidrotic hand or foot eczema always corresponds to atopic dermatitis and should be called atopic palmoplantar eczema (Schwanitz 1992).

The co-occurrence or absence of other inflammatory diseases in atopic dermatitis is an interesting phenomenon and gives rise to new pathophysiological concepts (see Chap. 3).