In the beginning of the twentieth century, knowledge has been accumulated in the field of immunology and allergology. The concept of atopic hypersensitiveness was introduced by Coca and Cook [7]. Those authors classified hypersensitiveness into two groups, physiological and abnormal hypersensitiveness. Dermatitis venenata and serum sickness were included in the former group and anaphylaxis, hypersensitivity of infection, and atopy in the latter group. They explained that atopic hypersensitiveness was a reaction induced against nonprecipitable substance as well as against precipitable substances. The hypersensitive state has not been shown to be passively transferable to normal individuals with serum except one observation. It could be greatly lessened but not completely removed by suitable injection of active substance. The reaction was characteristic to human and different from anaphylaxis of animals. It was inherited and accompanied with hay fever and asthma [7]. Although minor differences of understanding are present when compared with our recent understandings, Sulzburger applied the concept of atopy to this intractable eczematous disease. He recognized that all the features of atopy could be found in each and every case of atopic dermatitis. He explained that neurodermatitis disseminatus of Brocq and Jacquet was the most classical type of atopic dermatitis and that those of Besnier were its evoluted type. The name “neurodermatitis” was not a proper one because skin disease of nervous origin was misunderstood as the disease of psychiatric origin [8]. An article of New York Times in 1954 reported that an aviation engineer was dismissed for 5 months from his job by being diagnosed his skin disease as neurodermatitis that was confused with psychoneurosis [5]. He named “atopic dermatitis” to this skin disease according to the concept of atopic hypersensitiveness and classified into three stages: (1) infantile eczema of atopic type, i.e., atopic eczema, (2) atopic dermatitis of childhood, and (3) atopic dermatitis in the adolescent and young adult. He used the terms atopic eczema for the infantile cases and atopic dermatitis for the lichenified cases [9, 10]. Skin symptoms of atopic eczema are non-characteristic and polymorphous ones, consisting of papulovesicular rash, exudative erythema, or sometimes wheal. They spread from cheeks to trunk and extremities. Patients in childhood stage show papulation rather than exudation. Lichenified lesions appear on cubital and popliteal fossae, the neck, and wrists accompanying with intense pruritus. Atopic dermatitis in adolescence and young adult shows gray to dark pigmented lichenified lesions on the face, neck, and cubital fossae with occasional oozing, weeping, and crusting. The patients show dry skin with intense itching. The cases in adolescent and young adult correspond to neurodermite disseminatus of Blocq and Jacquet and prurigo diathetique of Besnier. And infantile eczema is the forerunner of atopic dermatitis. Patients have high rate of family history of atopic manifestation and personal history of atopic diseases and infantile eczema [9].

Hill and Sulzburger demonstrated relationship between atopens, allergens, and regains, IgE antibodies [8]. Positive skin test by food materials was more common in infantile cases, and rate of the positive skin test with environmental materials was increasing with their age. Significance of food allergens in atopic dermatitis has already been discussed among researchers in those days. Oral challenge of food materials responsible for the positive skin test did not induce exacerbation of atopic dermatitis [11]. Role of food allergens has been insisted by pediatric researchers even until recently; however, its significance has already been discussed at the beginning of history of atopic dermatitis.

The term “atopic dermatitis” was accepted worldwide after the World War II. We have had only limited cases of adolescent and young adult cases at that time. Almost all of the cases with atopic dermatitis were limited in children, and the severity of the disease was also limited. Especially almost all cases were easily treated with mild topical corticosteroid.

The situation around atopic dermatitis has changed in the 1980s in Japan. Numbers of adult cases with atopic dermatitis were increased [12, 13]. Age distribution pattern of atopic dermatitis has changed much between 1975 and 1985. The age distribution pattern of patients with atopic dermatitis in outpatient clinic of Kitasato University Hospital showed a sharp peak at age 1–2 and a gentle slope to the increasing age in 1975. In contrast two peaks were observed in 1985, a sharp peak at age 1–2 and second sharp high peak at age 15–25. Atopic dermatitis in 1975 was the disease of childhood. It became the disease of adolescence and young adult in addition to those of childhood in 1985. Such adult patients showed peculiar skin symptoms in addition to the classical symptoms of atopic dermatitis: (1) red face with frequent swelling and oozing (Fig. 1.1), (2) rippled pattern pigmentation on the neck [14], and (3) erythrodermic skin on trunk and extremities with (4) occasional swelling of lower extremities. Their skin manifestation was different from that described by Besnier and that by Sulzburger for atopic dermatitis in adolescent and young adult. Therefore, we called this condition as “adult type atopic dermatitis” to study its pathogenesis [12, 15]. Thirty-nine percent of our 64 patients started their skin symptoms within 6 months after birth and 28% at 1–4 years of age. Seventy-five percent of them had the onset before 10 years of age. The course of their skin symptom was classified into three groups; 75% of our cases started their skin symptom at their early infancy. (1) Skin symptoms persisted and progressed gradually to other parts of the body in 56% of cases, (2) 19% of them cleared skin symptom for years and then redeveloped after their adolescence, and (3) the rest (25%) had no skin troubles before their adolescence and their skin symptoms started after adolescent and adult age. Their skin symptoms were highly resistant to the conventional topical corticosteroid therapy. In these patients, we recognized the significance of irritant and allergic substances in their daily life. Those substances stimulated their skin to induce inflammatory reaction as well as to enhance and modulate their immune response. We have analyzed the exacerbating factors of those cases [16]. We found shampoo and soap, topical agents including skin care products and cosmetics, and focal and latent infections such as tonsillitis, odontoradiculitis, etc., as important exacerbating factors of these severe cases of adult-type atopic dermatitis (Fig. 1.2). The focal and latent infections modulated their immune conditions to enhance the inflammatory reaction. Those factors intermingled with each other to induce the skin condition. It was not unusual that multiple exacerbating factors were detected in a single case. Their skin symptoms were not improved by removing a single exacerbating factor. Careful effort to remove such factors from their daily life resulted in improvement of their symptoms dramatically [17].