PubMed Health⌕ Search

Biomedical subjects

E A Abel

Publications and source records attributed to E A Abel.

At least 19 recordsLinked to original sources

Phototherapy: UVB and PUVA.

The following paper is a review of the benefits of natural and artificial ultraviolet light in psoriasis. Phototherapy has been administered alone or in combination with topical corticosteroids, tars, anthralin, calcipotriene, and tazarotene, and with systemic therapies, such as methotrexate, acitretin, and cyclosporine. The choice of treatment with ultraviolet light B or psoralen plus ultraviolet light A is based on a history of previous response to treatment, skin type, severity of psoriasis, and patient considerations, including compliance and responsibility for observing the precautions to avoid potential side effects.

Humans↗

Phototherapy.

This review illustrates that UVB phototherapy is not only a time-honored treatment, but also highly effective for widespread psoriasis. Treatment parameters include the frequency of irradiation, initial dose based on skin type or MED, increments of UV exposure, and maintenance schedule, according to defined protocols. UVB can be combined with adjunctive topical or systemic therapies either concomitantly or sequentially for additive effect. The use of various therapeutic modalities, including UVB phototherapy on a rotational basis, has been advocated for long-term control with reduced toxicity. UVB with emollients in an erythemogenic dosage schedule is as effective as PUVA for clearing of psoriasis in selected fair-skinned patients. Unlike PUVA, it does not involve a systemic photosensitizing drug and is relatively convenient and simple to use. UVB is the most commonly used therapy by dermatologists for widespread psoriasis that does not respond to topical therapies; it has been shown to be one of the most cost-effective therapies for widespread psoriasis.

Humans↗

Diagnosis of drug-induced psoriasis.

Certain drugs have been reported to precipitate or to exacerbate psoriasis. These cases occur mostly in patients with a history of psoriasis, although occasionally the new onset of psoriasis has followed treatment with certain drugs. The suspect drugs include lithium, beta adrenergic antagonists, antimalarials, and non-steroidal anti-inflammatory drugs (NSAID), in addition to various miscellaneous agents, including tetracycline. Evidence for these reports must be critically examined based on clinical and histological data, time course between drug intake and psoriasis exacerbation or resistance to psoriasis therapy, and response to drug rechallenge when available. The clinical context must be taken into consideration, including effects of concomitant antipsoriatic therapy, and the possible role of other triggering factors, such as infection. Controlled, prospective studies of the use of NSAID in patients with psoriasis may help to clarify their varied cutaneous effects. Further knowledge of the mechanisms involved in drug exacerbation of psoriasis may help to elucidate the etiopathogenesis of this chronic skin disorder.

Adrenergic beta-Antagonists↗

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult↗

Most CD8+ cells in skin lesions of CD3+ CD4+ mycosis fungoides are CD3+ T cells that lack CD11b, CD16, CD56, CD57, and human Hanukah factor mRNA.

To define further the characteristics of CD8+ cells in skin lesions of CD3+ CD4+ mycosis fungoides (MF), the authors used single- and double-label immunohistologic techniques and in situ hybridization to detect antigens and transcripts associated with certain types of cytotoxic or suppressor function. The cytotoxic markers included CD16, CD56, CD57, and an anti-sense probe for human Hanukah factor (HuHf) mRNA. Analysis of 23 cases demonstrated that lesional CD8+ cells were CD3+ T cells that generally lacked expression of any of the cytotoxic markers studied. Analysis of another 10 cases confirmed the CD3+ T-cell lineage of lesional CD8+ cells and demonstrated that these cells also lacked expression of the suppressor-associated marker, CD11b. In aggregate, these results indicate that most CD8+ cells in CD3+ CD4+ MF skin lesions are of T-cell rather than NK-cell differentiation. Their overall phenotype suggests that they may be major histocompatibility complex (MHC)-restricted cytotoxic T cells lacking appreciable levels of HuHF serine protease. Because the induction of CD8+ suppressor T cells is mediated by CD4+ T cells expressing the CD45RA+ RO- phenotype, CD45 epitope expression was studied in 15 MF cases. The vast majority (13/15) contained CD3+ CD4+ tumor cells that were CD45+ RA- RB+ RO+ 2B11+. This phenotype is consistent with memory T cells rather than suppressor-inducer T cells, and correlates with the paucity of phenotypically defined suppressor T cells in CD3+ CD4+ MF skin lesions.

Antigens, CD↗

Leu-8/CD7 antigen expression by CD3+ T cells: comparative analysis of skin and blood in mycosis fungoides/Sézary syndrome relative to normal blood values.

Deficiencies of Leu-8 and CD7 antigens are exhibited by CD3+ T cells in the skin lesions of most patients with mycosis fungoides/Sézary syndrome. To determine whether these antigenic abnormalities are limited to involved skin, we studied Leu-8/CD7 expression in 21 skin lesions of mycosis fungoides/Sézary syndrome obtained from 16 patients and compared them with their peripheral blood leukocytes obtained concurrently. There was no correlation between Leu-8/CD7 values in skin lesions versus blood. Blood values were relatively uniform; most patients had 50% or greater of CD3+, Leu-8+ T cells and CD3+, CD7+ T cells. In contrast, skin values were highly heterogeneous; most patients lacked expression of Leu-8 or CD7 by the majority of lesional CD3+ T cells. Furthermore, Leu-8/CD7 antigen deficiency was present in lesional skin in one patient with mycosis fungoides but not in her concurrently sampled pityriasis lichenoides chronica or blood. These findings suggest that Leu-8/CD7 antigen deficiencies in skin lesions of mycosis fungoides/Sézary syndrome do not represent generalized antigenic abnormalities of CD3+ T cells in other body compartments and that within the skin, these deficiencies are disease specific within individual patients with more than one dermatosis. Comparative peripheral blood immunophenotyping of the patients with mycosis fungoides/Sézary syndrome and of the control subjects indicated that the control ranges of CD3+/Leu-8+ and CD3+/CD7+ T cells (33% or greater) extend lower than reported previously (60% or greater) and suggested that leukemic involvement in patients with mycosis fungoides/Sézary syndrome may correlate with percentages of CD3+, Leu8+ and/or CD3+, CD7+ T cells that fall below the revised control range.

Antigens, CD↗

Psoriasis patient support group and self-care efficacy as an adjunct to day care center treatment.

Patients treated with chronic disabling psoriasis often have psychosocial concerns that need to be addressed. The weekly patient support group at Stanford, led by a psychiatrist, is an integral part of the Psoriasis Day Care program. Although not considered group therapy in the traditional sense due to its self-selective nature, the support group aims to reduce feelings of isolation and to enhance coping skills and self-efficacy. In this setting, patients explore their feelings about psoriasis enabling them to better adapt to a visible disease. Common topics for discussion include lifestyle changes, stressful relationships, associated emotional reactions, occupational limitations, and treatment concerns. Components of the Psoriasis Day Care Center that enhance treatment response and responsibility for self-care include: health education, psychosocial support systems, stress reduction, and enhanced coping skills acquired through shared experiences with other patients and medical personnel.

Adaptation, Psychological↗

Discordant expression of antigens between intraepidermal and intradermal T cells in mycosis fungoides.

Using immunohistochemical methods, the authors studied the expression of pan-T- and majority-T-cell antigens (CD5, CD2, CD3, TCR-beta, CD7) and T-cell subset antigens (CD4, CD8) in cutaneous T cells in mycosis fungoides (MF) (177 biopsies from 124 patients) and a variety of inflammatory lesions (45 biopsies from 45 patients). The authors detected the absence of pan-T- or majority-T-cell antigens, or of both T-cell subset antigens, from T cells in the epidermis but not the dermis in 15 MF biopsies (8%) from 11 MF patients (9%), but in none of the inflammatory skin lesions. The opposite picture, characterized by lack of antigen expression by the dermal T cells only, was not seen in any of the MF or inflammatory lesions. The absence of antigen expression by epidermal but not dermal T cells, which the authors have termed antigen discordance, was most prevalent for CD5, CD7, and TCR-beta, each being discordant in 6% to 7% of MF cases or patients tested. Among the MF biopsies showing antigen discordance, 14 of 15 biospies (93%) from 10 of 11 patients (91%) were discordant for two or more antigens. Antigen discordance was not an artifact of treatment, because none of the patients showing discordance was receiving treatment at the time of their initial discordant biopsy. The discordance was the only immunophenotypic abnormality detected in 8 of 15 (53%) of the discordant MF biopsies. Thus, this antigen discordance was an important diagnostic feature that allowed the immunophenotypic distinction of MF from a variety of inflammatory skin lesions.

Antigens, Differentiation, T-Lymphocyte↗

Mycosis fungoides and occupational exposures. Is there an association?

In a case-control study, the author and coinvestigators found no positive association between occupational or chemical exposures and the risk of mycosis fungoides. Thus, there was no support for the hypothesis that chronic antigenic stimulation is an etiologic factor in this disease.

Environmental Exposure↗

Mycosis fungoides in relation to environmental exposures and immune response: a case-control study.

Mycosis fungoides is a cutaneous T-cell lymphoma of unknown etiology, thought to be a rare sequela of chronic antigenic stimulation that may occur, for example, with exposure to contact allergens. To explore this possibility, we interviewed 174 patients with mycosis fungoides and 294 randomly selected control subjects in the San Francisco, Los Angeles, and Seattle areas concerning their lifetime histories of employment, chemical exposures, allergy, atopy, and certain medical conditions. Patients reported higher prevalence of cancers other than the non-Hodgkin's lymphomas and skin cancers (relative risk = 3.3, P less than .001) and were more likely than controls to burn when exposed to the sun (for nonblacks, relative risk = 1.7, P = .01). The latter difference may reflect a manifestation rather than a precursor of the disease. We found no consistent or biologically plausible differences between patients and controls with respect to types of jobs held, or to occupational or vocational exposures to chemicals. These findings do not support the hypothesis that persistent antigenic stimulation by contact allergens is etiologically important in the pathogenesis of mycosis fungoides.

Case-Control Studies↗

Cutaneous manifestations of immunosuppression in organ transplant recipients.

Skin disease is a significant cause of morbidity in chronically immunosuppressed patients, including organ transplant recipients. Cutaneous drug reactions may be caused by immunosuppressive therapy that commonly includes corticosteroids, cyclosporine, azathioprine, and antithymocyte and antilymphocyte globulins. Immunosuppressive drugs can also potentiate the effects of other carcinogens, such as ultraviolet radiation, that cause premalignant lesions and squamous cell carcinoma. The risk of Kaposi's sarcoma is increased in these immunosuppressed patients, particularly in renal transplant recipients. Oncogenic viruses such as the Epstein-Barr virus have been associated with the development of non-Hodgkin's lymphoma in transplant recipients. In transplant patients human papillomavirus infections may be predisposed to malignant transformation, particularly at genital sites. Opportunistic infections caused by bacteria, fungi, viruses, or protozoa are the most common cause of death in transplant recipients. Skin manifestations of infection in immunosuppressed patients may be an important clue to their presence.

Graft Enhancement, Immunologic↗

Expression of T-cell receptor antigens in mycosis fungoides and inflammatory skin lesions.

Using immunohistologic methods, we studied the expression of the T-cell receptor (TCR)-associated antigens CD3, TCR-beta, and TCR-delta by cutaneous T cells in mycosis fungoides (MF) (36 patients) and a variety of inflammatory diseases (16 patients). Most T cells in the inflammatory diseases and patch/plaque mycosis fungoides expressed the immunophenotype characteristic of the vast majority of mature peripheral T cells: CD3+ TCR-beta+ TCR-delta-. In contrast, abnormal CD3/TCR-beta antigen expression was seen in 3 of 6 cases (50%) of tumor stage mycosis fungoides. Furthermore, we were able to document its evolution from the normal pattern present in earlier patch/plaque lesions of the two cases in which serial biopsies were available for study. Divergence of epidermal versus dermal CD3/TCR-beta antigen expression was seen in 2 of 34 (6%) of biopsies of patch/plaque mycosis fungoides but not in inflammatory controls. The TCR-delta+ cells were generally rare regardless of diagnosis. We conclude that inflammatory skin diseases and most patch/plaque mycosis fungoides are typically composed of T lymphocytes that resemble mature peripheral T cells in regard to their expression of TCR-associated antigens. In contrast, aberrant patterns of TCR-associated antigen expression can be seen in tumor stage MF, and, more rarely in patch/plaque MF.

Antigens, Differentiation, T-Lymphocyte↗

Detection of clonal T-cell receptor gene rearrangements in the peripheral blood of patients with mycosis fungoides/Sezary syndrome.

Involvement of the peripheral blood in mycosis fungoides/Sezary syndrome (MF/SS) has a significant impact upon prognosis, but it is often difficult to distinguish circulating cells of MF/SS from atypical reactive lymphocytes. We compared the standard morphologic method of identifying leukemic cells, the Sezary preparation, to a genotypic method using Southern blot analysis of T-cell receptor gene rearrangements in concurrent blood samples. We studied 26 MF/SS patients, five of them in remission, together with five controls from cases of various non-MF/SS skin diseases. Six of 26 MF/SS patients had morphologically atypical circulating leukocytes (3%, 4%, 5%, 14%, 16%, 19%). Seven of 26 MF/SS patients had clonal T-cell receptor gene rearrangements, including the four patients with the greatest percentages of atypical cells and three patients lacking atypical cells. Six of seven patients had skin disease at the time of sampling, including three with erythroderma, two with generalized thick plaques, and one with generalized patches, while one patient was in clinical remission. All five controls lacked morphologic and genotypic evidence of atypical or clonal T-cells. Relative to genotyping, in our series the Sezary preparation was less sensitive and less specific. There were three apparent false negative results in the Sezary preparations, and two potential false positive (patients with 3% and 4% atypical leukocytes); however, there was agreement between the two techniques in most cases. We conclude that gene rearrangement studies may provide an effective test with which to assess the peripheral blood of MF/SS patients.

Blotting, Southern↗