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To determine whether serum IgE levels in patients with atopic dermatitis bear a relationship to the severity and course of the dermatitis, serum levels were measured over several months in 24 patients. Excluded were patients with concurrent rhinitis or asthma, or those receiving therapy (hyposensitization, systemic corticosteroids) which might have affected serum levels. A clinical profile was developed to gauge the severity and extent of the dermatitis during the course of the study. The results show that many patients with atopic dermatitis have normal serum IgE levels. No significant fluctuation of serum IgE levels in individual patients was noted during the course of the study even though the dermatitis varied in severity. However, there was a positive relationship of significance (p < .05) between overall severity of the dermatitis and elevated serum levels of this immunoglobulin.

Serum IgE levels and white dermographism were evaluated in atopic dermatitis, atopic skin, and infantile eczema. Elevated serum IgE levels were found in some atopics. In atopic dermatitis there was an increase in serum IgE levels and a more constant presence of white dermagraphism in association with increased severity of dermatitis. Likewise, in atopic skin there was an association of increased serum IgE levels with white dermographism. In infantile eczema, IgE was not increased above normal adult levels nor was there white dermographism.

A survey was conducted to evaluate the serum IgE concentrations of 58 patients with atopic dermatitis of varying severity and activity. The determination of serum IgE concentrations does not provide a diagnostic criterion for atopic dermatitis because 57% of the patients had levels of IgE considered to be within a normal range. When serum IgE concentrations are elevated in atopic dermatitis, this is associated with an increased severity of the disease, with coexistent atopic respiratory disease or with both. This association may have relevance to the pathogenesis of the respiratory disease, which is IgE-mediated, the severity of the dermatitis, or both. The manner in which this may occur, if there is more than a coincidental relationship, is uncertain.

Summary.— Tests of immune function over a 12-month period in a young woman and a young man with life-long atopic dermatitis showed depressed cell-mediated immunity (CMI) (delayed-type skin test unresponsiveness, inability to be sensitized to DNCB, diminished responsiveness of cultured lymphocytes to phytohaemagglutinin, enlarged subcutaneous lymph nodes without any cell-mediated immunopathology, but with the structure of a node involved in humoral antibody production). Direct immunofluorescence localized IgE in the germinal centres of these subcutaneous lymph nodes. No anti-immunoglobulin or anti-C3 complement fluorescent conjugates were localized in their involved or uninvolved skin. Cells corresponding to small-and medium-sized lymphocytes in concentrated peripheral leucocyte smears stained with FITC antiserum to human IgE. The woman's lymphocyte transformation suppression improved during a remission and relapsed during an exacerbation of the dermatitis.

The serum level of immunoglobulin E (IgE) was found to be significantly greater than normal in a group of 23 out of 28 patients with atopic dermatitis. Each member of this group also showed several positive reactions to intradermal tests with 36 common antigens. The three atopic patients with the lowest IgE levels gave negative or, in one case, a single weak intradermal test. There was no correlation between the IgE level and the severity of clinical symptoms or a history of asthma or hay fever. IgE values were generally normal in a group of 34 patients with acute or chronic urticaria and in a larger group of patients with nonatopic dermatitis and various dermatological conditions.

The clinical and immunologic features of two adolescent boys who had recurrent pyogenic infections are judged to constitute a new syndrome. Its characteristics include: recurrent cutaneous, pulmonary, and joint abscesses; growth retardation; coarse facies; chronic dermatitis; exquisite immediate hypersensitivity associated with exceptionally high serum concentrations of IgE and eosinophilia; and depressed in vivo cellular immunity and antibody formation. These patients lacked evidence of respiratory allergy or parasitism. Atopic dermatitis was not present in one boy and the physical characteristics of the other boy's dermatitis were not typical for that entity. Concentrations of immumnoglobulins G, A, M, D and the various IgG subtypes were normal, as were natural antibody titers to red cell antigens. Nevertheless, depressed anamnestic antibody responses were noted to diphtheria and tetanus antigens and neither patient demonstrated responses to primary immunization with KLH, typhoid, and DNCB antigens. Complement and polymorphonuclear functions were normal. In vitro lymphocyte studies done demonstrated normal DNA synthesis in phytohemagglutinin and staphylococcal antigen-stimulated cultures and MIF production by some antigen-stimulated cultures from each. The explanation for the undue susceptibility to infection, increased IgE production, subnormal antibody formation, and impaired in vivo cell-mediated immunity in these patients remains conjectural.

The term " atopic dermatitis " was given by Wise and Sulzberger (1933) to those inflammatory dermatoses which are intimately associated with other allergic manifestations with a strong hereditary influence, such as hay-fever and asthma, described by Coca and Cooke (1923) as atopic. Patients suffering" from atopic conditions have a high incidence of circulating antibodies of a particular type. These antibodies, known as reagins, are responsible for positive immediate-type hypersensitivity reactions when the patient is skin-tested with a wide range of naturally occurring antigens. These antibodies cannot be demonstrated by in vitro techniques. However, their presence can be shown by the passive transfer technique of Prausnitz and K?stner (1921). They also differ from other circulating antibodies by having a high affinity for skin and being heat-labile. In June 1964 a committee of the World Health Organization defined proteins of animal origin with known antibody activity as immunoglobulins. The human immunoglobulins have been divided into three major groups. Two groups of molecular weight -^150,000 were called IgG (previously y, 7Sy, yss, or y2) and IgA (previously ?2A or YiO The third group consists of the macroglobulins of molecular weight r?900,000 and is called IgM (previously Yi*_ P^m, or 19Sy). Most circulating antibodies occur in the IgG fraction, though the IgM fraction contains red-cell iso-antibodies, saline anti-D (rhesus) antibodies, and immune antibodies directed against the somatic antigens of Salmonella spp. Until recently many workers considered reagin-type anti bodies to be immunoglobulins of the type IgA. However, more recently there has been evidence to suggest that the concept has been somewhat oversimplified, and in fact molecules of the class of IgG might be involved. As there is no doubt that reagin type antibodies are readily demonstrated in patients with atopic eczema, the present study was undertaken to determine the levels of immunoglobulins in patients with atopic eczema as compared with those with other skin conditions, including other patterns of eczema. Until recently this has not been possible because of the lack of a simple quantitative technique for deter mining accurately the levels of these different forms of immunoglobulins (Fahey and McKelvey, 1965). Previous work has been of a semi-quan?i?ative type either by the use of scanning of electrophoresis strips (Tickner, McCabe, and Mier, 1959), or, more recently, by the arbitrary assessment of the degree of precipitation in immunoelectrophoresis (K?lder, 1965).

SUMMARY The distribution pattern of immunoglobulin- or complement-bearing lymphocytes in healthy controls and in patients with contact dermatitis and with atopic dermatitis has been investigated. A significant predominance of IgD- and C3-bearing lymphocytes was found in ten patients with contact dermatitis. In atopic dermatitis patients the number of IgE- and to a lesser extent of C3-bearing lymphocytes was increased. The results indicate induction of stimulation of two distinct classes of immuno-logically competent lymphoid cell lines, one in contact and the other in atopic dermatitis. The increased number of B-cells in dermatitis indicates a decreased T-cell population and suggests a deficiency or disturbance of the recirculation of this population.

A case of anaphylactic shock following topical administration of an ointment containing bacitracin and neomycin is described. Antibacitracin reagins were demonstrated in sera from a patient with atopic dermatitis and there is strong evidence that the anaphylactic reaction was due to hypersensitivity to this drug.

Among 26 children with asthma whose serum levels of immunoglobulin E were measured monthly for a year, significant fluctuations were found, especially when initial values were high. These changes related directly to changing severity of atopic dermatitis and exposure to allergens but failed to relate to variations in severity of asthma or rhinitis. Evidence was also gathered supporting the possibility that systemic corticosteroid therapy may suppress formation of newly stimulated IgE.

SUMMARY.— In patients with atopic dermatitis, eczema and urticaria, systemic treatment with prednisone had no effect on the serum immunoglobulin E level (IgE) but improved their clinical condition. Neither was there any effect on the IgE level after the immunosuppressive, azathioprine. The increased level of IgE found in patients with atopic dermatitis was not seen in those who had been free from symptoms for more than a year even if they had a persistent or recurring eczema of the hands or nummular eczema.

Publisher Summary This chapter reviews some pharmacologic approaches to management of the clinical immediate hypersensitivity states. By definition, the diseases of immediate hypersensitivity are reagin-mediated, that is, the pathophysiological changes, characteristic of the condition, are initiated by the interaction of a specific antigen with homologous immunoglobulin E (IgE) antibody bound to tissue mast cells or circulating basophils. The classical diseases of immediate hypersensitivity are seasonal and perennial allergic rhinitis and asthma, anaphylaxis, certain cases of urticaria and angioedema, occasional cases of atopic dermatitis (eczema), certain instances of food and drug reactions, and bee sting hypersensitivity. Patients with regain-mediated disorders usually (1) show positive skin or mucosal tests to appropriate antigens, (2) often have elevated levels of serum IgE, and (3) incubation of their peripheral leukocytes results in the release of histamine from basophils. Several reports suggest that alpha adrenergic blockers such as phentolamine, thymoxamine, and dibenamine may be useful in the management of asthma. Disodium Cromoqlycate (DSC) enjoys an established reputation as an effective adjunct in the management of asthma as well as possibly reducing Type III immunologic lung injury. It is administered as an aerosol and is nontoxic. Chlorphenesin, a muscle relaxant carbamic acid derivative, inhibits immunologic histamine release in human leukocytes and both histamine and anaphylaxis (SRS-A) release from monkey lung.

Fifty-eight patients with a clinical diagnosis of atopic dermatitis were evaluated. Serum IgE levels, measured by a double antibody radioimmunossay, varied from 2 to 46,560 ng/ml in 55 patients (mean, 6,793 ng/ml median, 2,639 ng/ml). The three other patients had extremely high IgE values (77,704, 101,663, and 156,444 ng/ml). Three patients with atopic dermatitis had subnormal serum IgE levels and may represent a distinctive subgroup that should be studied further. Statistical analysis by nonparametric methods showed significant correlation of the serum IgE level with the extent of skin involvement. The ``atopic index," defined as the ratio of the number of positive intradermal skin tests to the number administered, and the intensity of the delayed blanch phenomenon also correlated significantly with IgE level. There was no correlation between IgE level and the subjective assessment of severity of dermatitis.

An unusual case of Wiskott-Aldrich syndrome is reported. The patient has now reached an age of 15 years. To my knowledge, he is the oldest living patient suffering from this syndrome. He still has diminished resistance to infections, thrombocytopenia, and atopic dermatitis. The patient has blood type O, his titer of isoagglutinin A is significantly reduced, and isoagglutinin B was not demonstrable. Furthermore, an increased value of IgE was registered. The displacements in IgM and IgA were the same as reported by other authors. Serum-type and tissue-type were also examined. Reaction to prostaglandin E 1 injected intracutaneously was normal, but the same administration of histamine resulted in a blanching that is usually seen in patients suffering from atopic dermatitis.

Intradermal tests with anti-IgE and measurements of serum IgE levels were done in patients with atopic dermatitis who did not have concurrent hay fever or asthma, patients with psoriasis, and nonatopic volunteers. The minimal amount of anti-IgE required to elicit a standard wheal and flare reaction 15 minutes after injection in patients with atopic dermatitis did not differ significantly from the two control groups. Also, there was no correlation between the results of the intradermal testing and severity of the dermatitis. The mean serum of IgE levels in patients with atopic dermatitis were higher than those of the two control groups. In addition, in patients with atopic dermatitis there was a strong correlation between the level of serum IgE and the severity of dermatitis, whether or not a positive history for asthma or hay fever was elicited.

Nummular eczema is reported to be a manifestation of atopic dermatitis. Because IgE levels are elevated in approximately 80% of people with active atopic dermatitis, we measured IgE levels in 26 patients with nummular eczema. Patients selected had moderate to severe chronic involvement, and no past or present evidence of parasitosis, atopic dermatitis, asthma, or hay fever. IgE levels as measured by radioimmunoassay demonstrated only two patients with values above 1,000 ng/ml. Comparing our group to that with atopic eczema shows our group to have significantly lower IgE levels P >.01. Therefore, atopic eczema and nummular eczema are unrelated on the basis of IgE levels.

Serum IgE levels were determined on 147 patients with atopic dermatitis and other skin disorders, and on pooled serum from 20 nonatopic control subjects. Mean IgE levels of patients with atopic dermatitis were compared with the mean level of pooled normal serum plus subjects with nonatopic dermatoses and found to be significantly higher. Severity of the atopic dermatitis was highly correlated to the levels of serum IgE. Other findings suggested the use of serum IgE determinations in the recognition of atopy in some patients with limited cutaneous involvement or with adult onset of a nonspecific eczematous dermatosis.