Atopic dermatitis (AD) is a complex disease traditionally involving interaction of genetic, environmental, and immunologic factors. Recent studies suggest psycho-neuro-immunologic factors and emotional stress are important in its evolution. The observations that internal (bacterial infections) or external (psycho-logic) stressors may induce AD flares is explained by studies showing that stress impairs the skin barrier function and favors a shift in immunity toward a T helper type 2 cell/allergic response. Furthermore, those with AD appear to have an inherited hypothalamic deficiency that impairs normal hypothalamic-pituitary-adrenal axis function. Neuropeptides released in the skin may also mediate neurogenic inflammation, including mast cell degranulation. AD causes significant stress and impaired quality of life in patients and their family members. Psychologic and stress-reduction interventions were recently shown to improve patient well-being, and to significantly improve cutaneous manifestations.

Psoriasis is a common dermatologic disorder with psychiatric comorbidity that often goes undetected and untreated. Psoriasis has higher associations with psychiatric illness than do other dermatologic conditions. We conducted a comprehensive qualitative review of all published medical literature on psoriasis and psychiatric comorbidities since 2005. We found that psoriasis patients suffer psychiatric and psychosocial morbidity that is not commensurate with the extent of cutaneous lesions. Biologic therapies and nonpharmacologic psychosocial interventions show promise in treating comorbid psychiatric illness. The main limitations of this review are the low quality of published studies and the infrequent use of basic science endpoints in reporting treatment outcomes. The literature examining the psychiatric comorbidity of psoriasis is expanding but remains of variable quality. Stronger studies will be necessary to more accurately estimate comorbidities and help identify and comprehensively treat suffering patients.

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Psychoneuroimmunology (PNI) is a discipline that has evolved in the last 40 years to study the relationship between immunity, the endocrine system, and the central and peripheral nervous systems. In this manner, neurotransmitters, hormones, and neuropeptides have been found to regulate immune cells, and these in turn are capable of communicating with nervous tissue through the secretion of a wide variety of cytokines. Of critical importance is the effect of products of the CNS and nerves on the maintenance of the delicate balance between cell-mediated (Th1) and humoral (Th2) immune responses. A good example of how this concept operates in vivo becomes evident when analyzing the effects of stressors. Chronic stress affects significantly the function of the immune system as well as modifies the evolution of a variety of skin diseases, as psychosocial interventions have proved to be effective in their therapy.

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Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme responsible for the alpha-amidation of peptides in secretory granules of neuroendocrine cells. The single gene encoding PAM undergoes tissue-specific alternative splicing and endoproteolytic processing to generate bifunctional membrane proteins with a single transmembrane domain as well as soluble proteins that are mono- or bifunctional. In order to examine the endoproteolytic processing and subcellular localization of the various forms of PAM in cells lacking regulated secretory granules, we established stably transfected hEK-293 cell lines expressing naturally occurring and mutant forms of PAM. As expected, newly synthesized soluble PAM proteins were rapidly secreted into the medium. Integral membrane protein forms of PAM were largely localized in the perinuclear region with punctate staining visible throughout the cell and 2-5% of the enzyme activity detectable on the cell surface. Bifunctional PAM proteins were slowly released into the medium after expression of integral membrane protein forms of PAM. Deletion of 77 amino acids from the COOH-terminus of the integral membrane forms of PAM resulted in a membrane-bound protein which retained both enzymatic activities but accumulated on the cell surface. Rapid internalization of full-length PAM proteins was observed by incubating live cells with antiserum to PAM; deletion of the COOH-terminal domain eliminated the ability of cells to internalize PAM. Thus the cytoplasmic domain of integral membrane PAM contains a routing determinant recognized by cells lacking the regulated secretory pathway.

Background: The use of psychological therapies for patients with psoriasis has been proposed based on observations that the severity of their disease may correlate with emotional stress. The aim of this pilot study was to evaluate the effect of hypnosis as a treatment modality for patients with psoriasis. Methods: We performed a 3-month randomized, single-blind, controlled trial of the use of hypnosis in adults with stable, chronic, plaque-type psoriasis. Highly or moderately hypnotizable subjects were randomized to receive either hypnosis with active suggestions of improvement (5 patients) or neutral hypnosis with no mention of their disease process (6 patients). After this period, the study was unblinded, and all the patients were treated for an additional 3 months with hypnosis with active suggestions of improvement. Results: Highly hypnotizable subjects showed significantly greater improvement than did moderately hypnotizable subjects, independent of treatment group assignment (active suggestion or neutral hypnosis). Conclusion: Although this study included a very limited number of patients, the results suggest that hypnosis may be a useful therapeutic modality for highly hypnotizable subjects with psoriasis, and merits further testing in a larger patient population.

We studied levels of erythrocyte C3b receptors (E-CR1) and correlated them to the level of circulating immune complexes (CIC) and complement activation in patients with or at risk for acquired immunodeficiency syndrome (AIDS). A significant reduction was found in patients with AIDS (185±93 CR1/cell), AIDS-related complex, and generalized lymphadenopathy, whereas healthy male homosexuals or normal controls had 434±193 and 509±140 CR1/cell, respectively (P < 0.001).Family studies indicate that this defect is acquired. Reduction in E-CR1 was associated with increased levels of CIC when assayed by binding to Raji cells, but not when tested by Clq binding. Complement activation was assessed by levels of C3bi/ C3d-g in plasma, measured with a monoclonal antibody specific for a neoantigen in C3d. AIDS patients had increased C3 activation (2.68±1.67%) when compared with normal controls (0.9±0.22%) (P < 0.01). The decreased E-CR1, the presence of CIC, and C3 activation suggest that complement activation by immune complexes may play a role in the clinical expression of the disease.