Atopic Dermatitis—Part I: Early Research and Causes

Atopic dermatitis (AD) is a common, chronic, pruritic, inflammatory skin disease that is on the rise and seen in people of all ages, often those with a family history of allergic rhinitis, conjunctivitis and asthma.1 The etiology and pathogenesis are not resolved and highly debated. It has been suggested that AD sufferers may have a predisposed intolerance to many skin care/cosmetic products; therefore, the disease must be better understood.

This is the first column in a two-part series on AD. Here, the authors explore early investigations of AD by 20th century pioneers to review the different hypothetical causes of this disease. The second column will discuss the criteria of AD over time to understand its origins and propose important methods to investigate it further. (See Part II).

History of AD and Atopy

While Hippocrates described chronic itchy conditions consistent with AD, the first reference to atopic diseases may have been reported by the Roman historian Suetonus who described the emperor Augustus2 as suffering from hereditary conditions of itchy, dry skin and seasonal respiratory disorders. Besnier, along with Broncq, Jacquet and Rost, was also one of the first pioneers to describe the condition.3 He referred to “prurigo diathésique,” with itch as the major symptom, and found the accompanying skin lesions non-specific. Besnier noted that internal manifestations such as emphysema, bronchial asthma, hay fever and gastrointestinal issues could occur with AD as well, adding there was a hereditary predisposition for it and that the disease was not restricted to lower social classes.

The term atopy was first used by Coca and Cooke, early 20th century immunology pioneers, in collaboration with Perry, a professor in Greek language, to denote the sense of a strange disease. It came about as part of a definition for hypersensitivity.4 Coca and Cooke described hypersensitivity as a purely immunological reaction having both normal and abnormal patterns due to a “susceptibility in [men or animals] mediated by a special mechanism.” Atopy was categorized, along with anaphylaxis and hypersensitivity to infections, as an abnormal immunology pattern. The “atopic theory” used five criteria to determine it was an inherited disease that produced allergic rhinitis, asthma, AD and other allergic phenomena when provoked by proteins in the environment; it was not contagious or transferable via blood from other sensitive individuals. Two years later, Coca and Grove proposed calling the substances responsible for the transfer of allergies “atopic reagins.”5

Atopic Dermatitis

Ten years after the introduction of the term atopy, Sulzberger and Wise coined the term atopic dermatitis in the 1933 Year Book of Dermatology and Syphilology.6 They described a disease distinct from other skin conditions, such as contact and seborrheic eczema, and pruritic and lichenified conditions, and later defined the nine cardinal qualities of AD (see Nine Cardinal Qualities of AD). Sulzberger and Wise stated that the logical therapy was eliminating all foods and inhalants giving the patients positive wheal reactions, such as those seen in allergen tests immediately after injection, as well as desensitization treatments with the most suspected substances, similar to practices for treating asthma and hay fever.

Two years later, Sulzberger and Hill postulated7 that the fundamental basis of AD is the same at all ages, even though the clinical appearance looks different. They noted, “The infant is not merely a small man: He is a different sort of small man (…) it is not strange, then, that atopic dermatitis is not similar in clinical appearance at different age periods. It would be strange if it were similar.” They described clinical highlights of sensitivity in different ages to delineate three stages of AD: infantile eczema of the atopic type (0-2 years), AD of childhood (2-12 years) and adult AD.

AD Treatments and Causes

In the first half of the 20th century, allergy was thought to be the primary etiology of AD. Attempts in diet management and the desensitization of patients, as dictated from Wise and Sulzberger, were made with little success. On the other hand, topical corticosteroids popularized in 1951 by Sulzberger had an extensive impact.8

In the 1960s, new etiological theories on atopy were explored. The beta blockade approach to atopy proposed by Szentivanyi,9 which indicated a defective catecholamine/beta-adrenerg homeostasis in atopic skin, was investigated until the 1980s. With Ishizaka’s discovery of the immunoglobulin E (IgE) molecule as the allergy reagin10 in 1966, and high IgE levels in patients with AD,11 the exploration of IgE’s role in activating mast, eosinophil and dendritic cells in atopic patients was further explored in the last part of the 20th century.

The focus of immunological and inflammatory processes as the etiology of AD was challenged in the late 2000s by Palmer’s finding of filaggrin null-mutations as a strong predictor of AD and asthma.12 Today, many recognize both immunological and barrier problems as contributing factors in the etiology of atopic diseases.

Conclusion: Part I

The follow-up to this column will explore the evolution of AD criteria over time and discuss methods of investigating these features to approach this multifaceted disease. Hopefully, by utilizing current knowledge to quantify the atopic diathesis including AD, the relationship between atopy and cosmetic tolerance/intolerance will be clearer.

(continue to Part II)


    1. IAG Deckers, S McLean, S Linssen, M Mommers, CP van Schayck and A Sheikh, Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: A systematic review of epidemiological studies, PLoS One 7(7) (Jul 11, 2012)
    2. P Mier, Earliest description of the atopic syndrome? Br J Dermatol 92(1) 359 (Jul 1974)
    3. E Besnier, Première note et observations préliminaires pour servir d’introduction à l’étude des prurigos diathésiques (dermatitis multiformes prurigineuses chroniques exacerbantes et paroxystiques, du type du prurigo de Hebra), Ann Dermatol Syph 3 634–648 (Feb 1892)
    4. AAF Coca and RAR Cooke, On the classification of the phenomena of hypersensitiveness, J Immunol 8(3) 163–182 (May 1923)
    5. A Coca and E Grove, Studies in Hypersensitiveness XIII. A Study of the Atopic Reagins, J Immunol 10(2) 445-464 (1925)
    6. F Wise and M Sulzberger, The 1933 Year Book of Dermatology and Syphilology. The Year Book Publishers: Chicago, USA (1933)
    7. LW Hill and MB Sulzberger, Evolution of atopic dermatitis, Arch Dermatol 32(3) 451-463 (1935)
    8. MB Sulzberger, G Sauer and F Herrmann, Effects of ACTH and cortisone on certain sideases and physiologic functions of the skin: I. Effects of ACTH, J Invest Dermat 16 323–337 (1951)
    9. A Szentivanyi, The beta adrenergic theory of the atopic abnormality in bronchial asthma, J Allergy 42(4) 203–232 (Oct 1968)
    10. K Ishizaka, T Ishizaka and MM Hornbrook, Physicochemical properties of reaginic antibody: V . correlation of reaginic activity with gamma-g-globulin antibody, J Immunol 97 840–853 (1966)
    11. L Juhlin, Immunoglobulin E in dermatoses: Levels in atopic dermatitis and urticaria, Arch Dermatol 100 12–16 (1969)
    12. CN Palmer et al, Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis, Nat Genet 38(4) 441–6 (Apr 2006)
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