8 Minimal Forms of Atopic Eczema

schwarz, S. 74

cyan, S. 74

gelb, S. 74

magenta, S. 74

Chapter 8

8 Minimal Forms of Atopic Eczema Brunello Wüthrich

In the diagnosis of atopic eczema (atopic dermatitis), the criteria established by Hanifin and Rajka [1] are those most often referred to. However, besides fullblown cases of atopic eczema, there are minor or atypical disease manifestations. The description of these forms can be attributed primarily to French authors in the mid-1960s and early 1970s [2 – 6] and to Herzberg [7 – 9] in the German-speaking sphere. Special credit is due to this author for having alluded to atopic eczema found usually in two but occasionally even in three and four generations of patients, based on his clinical observations and skin reaction studies. These special forms and minimal variants may occur alone, together, or alternate with the more typical eczematous, lichenoid, pruriginous, and seborrheic forms whose occurrence is related to age, individual predisposition, and disease duration, and is indicative of their status as atopic skin manifestations [1]. When occurring alone, without the major features of atopic eczema, and without other atopic manifestations, such as allergic rhinitis, allergic asthma, or food allergy, their classification as a minimal form of atopic eczema may be disputable, especially in the intrinsic type or in non-IgE-associated atopic eczema/dermatitis syndrome in which no demonstrable sensitization to atopic allergens exists [10 – 15]. Thus, the diagnosis can only be finally accepted on the basis of a family and personal history, progress monitoring, further clinical features related to other stigmata of the atopic constitution, positive skin reactions (e.g., white dermographism), exclusion of a contact allergy to haptens, and histology, which demonstrate eczematous, inflammatory changes. The special forms of presentation attract attention because they are clinical and morphological variants, and because of their particular sites of location, such as the eyelids, lips, nipples, vulva, finger pads and toes.

8.1 Localized Minimal Variants of Atopic Eczema Such localized variants include: ) Lower lid eczema, frequently occurring in the spring as a pollinosis equivalent [11] (Figs. 8.1, 8.2)

Fig. 8.1. Atopic lower lid eczema (31-year-old female with grass pollen allergy)

Fig. 8.2. Atopic eyelid eczema (35-year-old man with pollinosis)

schwarz, S. 75

cyan, S. 75

gelb, S. 75

magenta, S. 75

8.1 Localized Minimal Variants of Atopic Eczema

) Exfoliating cheilitis with perlèche (Figs. 8.3, 8.4) ) Earlobe rhagades or retroauricular intertrigo (Figs. 8.5, 8.6)

) Rhagades of the nasal orifices, often with chronic nasal obstruction as the expression of a perennial allergic rhinitis

Fig. 8.3. Exfoliating cheilitis with perlèche (6-year-old boy)

Fig. 8.5. Earlobe rhagades (6-year-old boy)

Fig. 8.4. Cheilitis with perioral eczema (8-year-old girl)

Fig. 8.6. Retroauricular intertrigo (20-year-old man)

75

schwarz, S. 76

76

cyan, S. 76

gelb, S. 76

magenta, S. 76

8 Minimal Forms of Atopic Eczema

) Nipple eczema (Fig. 8.7) ) Genital eczema (vulva, penis [Fig. 8.8], or scrotum)

) Tylotic, rhagadiform, finger pad eczema (pulpite sèche or pulpite digitale keratosique craquelée récidivante; “atopic hands”) (Figs. 8.9, 8.10) ) Similar manifestations on the toes (“atopic feet” or” atopic winter feet”), often misdiagnosed as foot mycosis (Figs. 8.11, 8.12),

Fig. 8.7. Nipple eczema (17-year-old female)

Fig. 8.10. Atopic fingerpad eczema (6-year-old boy)

Fig. 8.8. Isolated eczema of the dorsum penis with painful rhagades (17-year-old man)

Fig. 8.11. “Atopic feet” or “atopic winter feet,” dorsal aspect (5-year-old boy)

Fig. 8.9. “Atopic hands”: tylotic, rhagadiform, fingerpad eczema (pulpite sèche or pulpite digitale keratosique craquelée récidivante (23-year-old female)

Fig. 8.12. “Atopic feet” or “atopic winter feet,” plantar aspect (same 5-year-old boy as in Fig. 8.11)

schwarz, S. 77

cyan, S. 77

gelb, S. 77

magenta, S. 77

8.2 Juvenile Plantar Dermatosis

Fig. 8.13. “Juvenile plantar dermatosis,” lateral aspect (10-yearold boy)

sonal examination at the mean age of 23 years, it was found that 72.3 % of them were still suffering from atopic skin problems [16]. In 66 % of the 47 patients, minor manifestations were present, most frequently perlèches (40.4 %), retroauricular intertrigo (34 %), eyelid eczema (21 %), and fingerpad eczema (21.3 %). The allocation of these localized variants to atopic eczema obviously postulates negative epicutaneous testing to possible contact allergens (standard series, perioral group, shoe eczema group, etc.). In a prospective study of 195 patients with typical atopic eczema (average age, 8.5 years) and 113 controls without eczema, a study [17] came to the conclusion that retroauricular rhagades, cheilitis, nipple eczema, and pityriasis alba are undoubtedly statistically highly significant (p< 0.005) for diagnosing atopic eczema, but that Dennie-Morgan infraorbital fold and anterior neck creases are not. Also controversial is the allocation to atopic eczema of the “dirty neck” sign, a reticular pigmentation of the neck, that makes it appear unwashed [18], and the correlation between “geographic tongue” and atopy [19].

8.2 Juvenile Plantar Dermatosis Fig. 8.14. “Juvenile plantar dermatosis,” plantar aspect (same 10-year-old boy as in Fig. 13)

) The “juvenile plantar dermatosis” (see below) (Figs. 8.13, 8.14). According to Herzberg [7 – 9], over 70 % of patients with fingerpad eczema are women, in whom the role of skin traumatization in influencing localization is emphasized by the fact that the pads of the first to third fingers are initially affected and those of the fourth and fifth fingers only later. Furthermore in the right-handed person, the right hand is more affected than in the left. Apart from the clinical signs of a pale erythema, keratosis, scaling, and fissuring, concomitant pain leads subjectively to impairment of function in the involved hand. As a practical sign, delicate materials such as nylon stockings are torn by the sharp edges of the fissures when being put on or taken off. Atopic hands and atopic feet occur more often in children, and often improve during summer holidays at the seaside, and after puberty. In our follow-up study of 47 patients who had suffered from atopic eczema in infancy (< 2 years of age), which was conducted using a questionnaire and per-

Juvenile plantar dermatosis is a painful variant of atopic eczema, frequently occurring in children. It is chiefly observed on the anterior part of the sole and is characterized by erythema, hyperkeratosis, and rhagades (Figs. 8.13, 8.14). Histologically, there is an eczematous dermatitis with spongiosis and lymphohistiocytic, subepidermal, and perivascular infiltration. As early as 1966, Racouchot [4] had explicitly alluded to its relationship with the group of atopic forms: “La kératose plantaire et les fissures hivernales des bords des talons sont a` retenir” (Plantar hyperkeratosis and rhagades occurring in winter at the edges of the heels must be observed). In 1968 Silvers and Glickman [20] gave a thorough description of the special features of atopic eczema of the feet in children. On 1972, this disorder became well known due to a publication by Moller [21], who proposed the name of “atopic winter feet.” However, it also occurs in the summer months, so that in practice it is often misdiagnosed as a foot mycosis and thus erroneously treated with antimycotics. Verbov [22] as well as Hambly and Wilkinson [23] described “forefoot eczema” in the context of atopic eczema, Mackie and Husain [24] considered “juvenile

77

schwarz, S. 78

78

cyan, S. 78

gelb, S. 78

magenta, S. 78


plantar dermatosis” to be a new entity since only nine of the 102 children they studied had manifest atopy. They attributed the cause to nylon socks. Subsequently, other terms were proposed such as “dermatitis plantaris sicca” [25, 26], “peridigital dermatitis” [27], or “wet and dry foot syndrome” [28], but the term most commonly used today is the simple descriptive “juvenile plantar dermatosis” (JPD). Association with atopy has been found by various authors, ranging from 50.3 % of patients [29] to 61 % [23], and 74 % [30]. Other authors found no preponderance of atopy [24, 31]. Rajka [32] suggested distinguishing between an “atopy-associated” and a “nonatopic” variant. In both types, along with a possible constitutional weakness of the skin, various other endogenous and exogenous factors have been discussed as pathogenetic, such as frequently repeated microtraumata (“frictional contact dermatitis”), a clammy microclimate due to the wearing of synthetic socks and high shoes, or contact allergy to parts of shoes. Pirkl et al. [33] suggested broad-spectrum epicutaneous testing in JPD in the following circumstances:

dren” [39], “summer lichenoid dermatitis of the elbows in children” [40], “dermatite du toboggan” [41], “Sutton’s summer prurigo of the elbows” [42], “dermatitis papulosa juvenilis” [43], “papular neurodermatitis” [44], and “recurrent papular eruption of childhood” [45]. Changes observed in biopsy specimens show hyperkeratosis, a moderate degree of acanthosis and a lymphocytic perivascular infiltrate in the upper dermis [37, 44]. The pathogenetic influence of such rough materials as sand and wool and of a photosensitivity in patients with atopic predisposition is suggested by many authors [44 – 46]. Already in 1983, we assigned these acro-located, small papular lesions to atopic eczema based on family and personal history, demonstration of specific IgE to inhaled or food allergens, and an eczematous histologic picture [44] (Figs. 8.15 – 8.18).

) The appearance of JPD after wearing new shoes ) Characteristic JPD which spreads secondarily over the heels, or dorsum of the foot or toes, or the outer border of the foot ) Severe JPD with primary involvement of the heels. If the rare cases of allergic contact eczema are excluded, follow-up studies have shown that complete recovery may be expected with puberty in the majority of patients after a course of 7 – 8 years on average [28, 34, 35].

8.3 Juvenile Papular Dermatosis: The Papular Form of Atopic Eczema Juvenile papular dermatosis (Dermatitis papulosa juvenilis [DPJ]) is characterized by lichenoid flat papules, is often hypopigmented, with a predilection for the dorsa of the hands, the elbows, and the knees [36]. Fölster-Holst et al. [37] reported a 9-year-old boy who developed particularly severe lesions of juvenile papular dermatitis on the face and the back of the knee and extreme pruritus during the summer. In fact, the disease affects children in the summer months. Sutton first described this skin disease in 1956 under the name of “summertime pityriasis of the elbow and knee” [38]. Others terms are “frictional lichenoid eruption in chil-

Fig. 8.15. Papular form of atopic eczema: disseminated flat papules on elbows (7-year-old boy)

schwarz, S. 79

cyan, S. 79

gelb, S. 79

magenta, S. 79

8.4 Patchy Pityriasiform Lichenoid Eczema: The Follicular Form of Atopic Eczema

Fig. 8.16. Papular form of atopic eczema: several itchy flat papules on the hollow of the knee (same patient as in Fig. 8.15)

Fig. 8.17. Papular form of atopic eczema: flat papules on extensor aspect of knees (5-year-old girl)

The occurrence mainly in the spring and summer, often in association with pollinosis, is pathogenetically suggestive of an inhaled precipitant such as a hay fever equivalent [11, 47], in addition to a mechanical component (friction, chafing) and photosensitivity.

that together with Takahashi and Sasagawa he had described a plaque-shaped, lichenoid, scaly eczema as an independent dry type of childhood eczema. This type, evidently common in Japan, was allocated by Sasagawa in 1967 to the group of atopic eczema [50]. In 1981, we described this at that time scarcely known manifestation of atopic eczema in childhood [51]. Thus, clinically there are partly confluent areas with densely juxtaposed, mildly bran-like, scaly, nonhyperkeratotic, skin-colored papules (Figs. 8.19 – 8.21). They are found, with a generally dry integument, especially on the trunk but also on the nape of the neck and the knees. Histologically, these itchy “goose-flesh spots” exhibit a spongiosis of the follicular epithelium and an intra- and perifollicular lymphohistiocytic infiltration, which indicated the eczematous nature of this condi-

8.4 Patchy Pityriasiform Lichenoid Eczema: The Follicular Form of Atopic Eczema Patchy pityriasiform lichenoid eczema is a dry, only slightly itching, follicular form of atopic eczema occurring in childhood. Its first description is attributable to Japanese authors as far back as 1950 [48]. In a 1966 paper published in German, Kitamura [49] mentioned-

79

schwarz, S. 80

80

cyan, S. 80

gelb, S. 80

magenta, S. 80


Fig. 8.18. Histologic findings in papule of right knee: spongiosis in the epidermis lymphohistiocytic infiltrate in the dermis, perivascular (same patient as in Fig. 8.17)

Fig. 8.19. Follicular form of atopic eczema (patchy pityriasiform lichenoid eczema, Kitamura-Takahashi-Sasagawa): plaqueshaped “goose-flesh spots” on infrascapular region of back (1-year-old boy, dark skinned)

Fig. 8.20. Follicular form of atopic eczema: closely packed, skin-colored follicular papules on the trunk (3-year-old boy)

tion [48 – 51] (Fig. 8.22). Pruritus is usually present, though not always severe. Mildly scaly depigmented areas, rather like pityriasis alba [52, 53] and isolated, frequently asymmetric, typical lichenified foci on the backs of the hands or elbows are occasionally present. In our series, a discrete perennial or seasonal allergic rhinitis was frequently associated. Progression of the disease is observed particularly in winter, whereas summer visits to the seaside usually lead to improvement or healing of the rash. Ofuji and Uehara [54] also found similar itchy follicular papules in 96 % of their patients with atopic eczema, particularly on the lateral parts of the trunk. They suggested that these lesions probably constitute the primary efflorescence of atopic eczema.

schwarz, S. 81

cyan, S. 81

gelb, S. 81

magenta, S. 81

8.5 Comments

Fig. 8.21. Histologic findings showed the follicular form of atopic eczema in a 10-year-old girl. Follicular papule with spongiosis of the epidermis and lymphohistiocytic intra- and perifollicular infiltration

Fig. 8.22. Histologic findings: spongiosis of follicular epithelium with lymphohistiocytic infiltration (same patients as in Fig. 8.21)

Differential diagnosis requires distinction from suprafollicular keratosis, follicular hyperkeratosis in the context of an autosomal dominant ichthyosis vulgaris, lichen planopilaris, lichen nitidus, and the various lichenoid-id reactions, e.g., mykid or Gianotti-Crosti syndrome [55].

appropriate therapy. An atopic background should be carefully assessed by allergy investigations (skin prick tests and IgE determination to environmental allergens and fungi, e.g., Malassezia sympodialis [56]). Moreover, it would be of interest to perform atopy patch tests to standard aeroallergens, food, and fungi in these conditions, which are often non-IgE-associated, to evaluate cell-mediated immunity. There is also a need for setting up cohort studies relating to the natural history of such atypical or minimal forms of atopic eczema, especially of the so-called intrinsic or non-IgE-associated type [57, 58].

8.5 Comments The knowledge of the minimal forms of atopic eczema, together with the evaluation of constitutional atopy stigmata, is a prerequisite for the right diagnosis and

81

schwarz, S. 82

82

cyan, S. 82

gelb, S. 82

magenta, S. 82


References 1. Hanifin JM, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol [Suppl] (Stockh) 92:44 – 47 2. Basex A, Salvador R, Dupré A, Christol B (1965) Eczéma nummulaire : ses rapports avec l’eczema atopique. Bull Soc Fr Dermatol Syphiligr 72:432 – 434 3. Basex A, Dupré A, Christol B (1966) Aspects morphologiques atypiques de l’ eczéma atopique. Rev Med 1:62 – 65 4. Racouchot MJ (1966) Les petits signes cliniques du terrain eczémateux. Bull Soc Fr Dermatol Syphiligr 73:531 – 535 5. Temime P, Oddoze L (1970) La chéilite exfoliatrice et la pulpite digitale keratosique craquelée récidivante peuvent eˆtre des manifestations atopiques. Bull Soc Fr Dermatol Syphiligr 77:150 – 156 6. Temime P, Basex A, de Graciansky P (1972) The atypical cutaneous manifestations of atopy. Excerpta Med Int Congr Ser 251:147 – 148 7. Herzberg J (1972) Wenig bekannte Ausdrucksformen der Neurodermitis. Arch Dermatol Forsch 244:350 – 352 8. Herzberg J (1973) Wenig bekannte Formen der Neurodermitis. Hautarzt 24:47 – 51 9. Herzberg J (1976) Besondere Manifestationsformen der Neurodermitis diffusa (atopische Dermatitis). In: BraunFalco O, Marghescu S (eds) Fortschritte der praktischen Dermatologie und Venereologie. Springer, Berlin Heidelberg New York, pp 19 – 24 10. Wüthrich B (1983) Neurodermitis atopica sive constitutionalis. Ein pathogenetisches Modell aus der Sicht des Allergologen. Aktuel Dermatol 9:1 – 7 11. Wüthrich B (1987) Atopic dermatitis flare provoked by inhalant allergens. Dermatologica 178:51 – 53 12. Wüthrich B (1999) What is atopy? Condition, disease or a syndrome? In: Wüthrich B (ed) The atopy syndrome in the third millenium. S. Karger, Basel, pp 1 – 8 13. Schmid-Grendelmeier P, Simon D, Simon HU, Akdis CA, Wüthrich B (2001) Epidemiology, clinical features, and immunology of the “intrinsic” (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis) Allergy 56: 841 – 849 14. Wüthrich B, Schmid-Grendelmeier P (2002) Definition and diagnosis of intrinsic versus extrinsic atopic dermatitis. In: Bieber T, Leung DYM (eds) Atopic dermatitis. Marcel Dekker, New York, pp 1 – 20 15. Wüthrich B, Schmid-Grendelmeier P (2003) The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE-associated (“extrinsic”) and the nonallergic (“intrinsic”) AEDS. J Invest Allergol Clin Immunol 13:1 – 5 16. Kissling S, Wüthrich B (1994) Lokalisationen, Manifestationstypen sowie Mikromanifestationen der atopischen Dermatitis bei jungen Erwachsenen. Hautarzt 45:368 – 371 17. Mevorah B, Frenk E, Wietlisbach V, Carrel CF (1988) Minor clinical features of atopic dermatitis. Evaluation of their diagnostic significance. Dermatologica 177:360 – 364 18. Colver GB, Mortimer PS, Millard PR (1987) The “dirty neck” – a reticulate pigmentations in atopics. Clin Exp Dermatol 12:1 – 4 19. Marks S, Simons MJ (1979) Geographic tongue – a manifestation of atopy. Br J Dermatol 101:159 – 162

20. Silvers SH, Glickman FS (1968) Atopy and eczema of the feet in children. Am J Dis Child 116:400 – 401 21. Moller H (1972) Atopic winter feet in children. Acta Derm Venereol (Stockh) 52:401 – 405 22. Verbov J (1978) Atopic eczema localized to the forefoot. An unrecognized entity. Practioner 220 (1313):456 – 466 23. Hambly EM, Wilkinson DS (1978) Sur quelques formes atypiques d’ eczéma chez l’enfant. Ann Dermatol Venereol 105:369 – 371 24. Mackie RM, Husain SL (1976) Juvenile plantar dermatosis: a new entity? Clin Exp Dermatol 1:253 – 260 25. Friis B (1974) Dermatitis plantaris sicca bei Kindern. Dermatol Monatsschr 160:614 – 620 26. Kint A, van Hecke E, Leys G (1982) Dermatitis plantaris sicca. Dermatologica 165:500 – 509 27. Enta T (1980) Peridigital dermatitis in children. Int J Dermatol 19:390 – 391 28. Steck WD (1983) Juvenile plantar dermatosis: The “wet and dry foot syndrome”. Cleve Clin Q 50:145 – 149 29. Verbov J (1989) Juvenile plantar dermatosis (JPD) Acta Derm Venereol [Suppl] (Stockh) 144:153 – 154 30. Voss Jepsen l (1978) Dermatitis plantaris sicca: a retrospective study of children with recurrent dermatitis of the feet. Acta Derm Venereol (Stockh) 59:4257 – 259 31. Young E (1986) Forefoot eczema – further studies and a review. Clin Exp Dermatol 11:523 – 528 32. Rajka G (1989) On definition and framework of atopic dermatitis Acta Derm Venereol [Suppl] (Stockh) 144:10 – 12 33. Pirkl S, Tennstedt D, Egger S, Lachapelle JM (1990) Juvenile plantar dermatosis: wann sind Epikutantestungen indiziert? Hautarzt 41:22 – 26 34. Jones SK, English JSC, Forsyth A, Mackie RM (1987) Juvenile plantar dermatosis – an 8-year follow-up of 102 patients. Clin Exp Dermatol 12:5 – 7 35. Malleville J, Marsan PH, Coindre MCL (1984) Une dermatose infantile peu connue : la pulpite sèche de l’ avant-pied ou dermatose plantaire juvénile. A propos de 68 cas. Sem Hop Paris 60:2401 – 2404 36. Rook A (1978) Juvenile papular dermatitis. In: Rook A, Wilkinson DS, Ebling FJG (eds) Textbook of dermatology, vol 1, 3rd edn, Blackwell, Oxford, p 676 37. Fölster-Holst R, Kiene P, Brodersen JP, Christophers E (1996) Dermatitis papulosa juvenilis. Hautarzt 47:129 – 131 38. Sutton RL (1956) Summertime pityriasis of the elbow and knee. In: Sutton RL Jr (ed) Disease of the skin, 2edn. CV Mosby, St. Louis, p 898 39. Waisman M, Gables C, Sutton RL (1966) Frictional lichenoid eruption in children. Arch Dermatol 94:592 – 593 40. Goldman L, Kitzmiller KW, Richfield DF (1974) Summer lichenoid dermatitis of the elbows in children. Cutis 13:836 – 838 41. Dupré MMA, Christol B, Bonafe JL (1974) La dermatite du toboggan (variant de “frictional lichenoid eruption in children”). Bull Soc Fr Dermatol Syphiligr 81:203 – 205 42. Rasmussen JE (1978) Sutton’s summer prurigo of the elbows. Acta Derm Venereol (Stockh) 58:547 – 549 43. Bork K, Hoede N (1978) Juvenile papulöse Dermatitis. Hautarzt 290:216 – 219 44. Wüthrich B (1983) Papulöse Neurodermitis atopica: eine

schwarz, S. 83

cyan, S. 83

gelb, S. 83

magenta, S. 83

References

45. 46. 47. 48. 49. 50. 51.

besondere Form der juvenilen papulöse Dermatitis? Dermatologica 167:196 Patrizi A, Di Lernia V, Ricci G, Masi M (1990) Atopic background of a recurrent papular eruption of childhood (frictional lichenoid eruption) Pediatr dermatol 7:111 – 115 Menni S, Piccinno R, Baietta S, Pigatto P (1987) Sutton’s summer prurigo: a morphologic variant of atopic dermatitis. Pediatr Dermatol 4:205 – 208 Storck H (1960) Neurodermitis disseminata mit Verschlechterung im Sommer, Aufflammen nach Inhalation von Pollenallergenen. Dermatologica 121:150 – 151 Kitamura K, Takahashi Y, Sasagawa S (1950) (in Japanese). Jpn J Dermatol 60:59 Kitamura K (1966) Zur Frage des Kinderekzems. Hautarzt 17:53 – 55 Sasagawa S (1967) Studies on the dry form of eczema in childhood patchy pityriasiform lichenoid eczema (Kitamura-Takahashi-Sasagawa) Jpn J Dermatol 77:62 – 87 Wüthrich B, Schnyder UW (1983) Eine wenig bekannte Ausdrucksform der Neurodermitis atopica im Kindesal-

52. 53. 54. 55. 56.

57. 58.

ter: Das Patchy Pityriasiform Lichenoid Eczema (“Kitamura-Takahashi-Sasagawa”) Aktuel Dermatol 7:85 – 87 Watkins CDB (1961) Pityriasis alba: a form of atopic dermatitis. Arch Dermatol 83:915 – 919 Wolf R, Sandbank M, Krakowski A (1983) Extensive pityriasis alba and atopic dermatitis. Br J Dermatol 84:247 Ofuji S, Uehara M (1973) Follicular eruption of atopic dermatitis. Arch Dermatol 107:54 – 55 Gianotti F (1976) Papular acrodermatitis of childhood and other papulovesicular acro-located syndromes. Br J Dermatol 100:49 – 58 Schmid-Grendelmeier P, Fischer B, Wüthrich B (2002) IgE to Malassezia furfur / M. sympodialis. A serologic marker for the atopic eczema/dermatitis syndrome? Allergy Clin Immunol Int 14:140 – 142 Novembre E, Cianferoni A, Lombardi E, Bernardini R, Pucci N, Vierucci A (2001) Natural history of “intrinsic” atopic dermatitis. Allergy 56:453 – 454 Wüthrich B, Schmid-Grendelmeier P (2002) Natural course of AEDS. Allergy 57:267 – 268

83