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Biomedical subjects

D G Deneau

Publications and source records attributed to D G Deneau.

13 recordsLinked to original sources

Immunohistology of pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica. Evidence for their interrelationship with lymphomatoid papulosis.

Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica are idiopathic, papular eruptions that exhibit certain clinicopathologic similarities to each other and to lymphomatoid papulosis. In order to determine if these disorders are also similar immunologically, we studied the immunopathology of five biopsy specimens from three cases of pityriasis lichenoides et varioliformis acuta and three biopsy specimens from three cases of pityriasis lichenoides chronica. We then compared them to our prior immunohistologic study of nine cases of lymphomatoid papulosis. Pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica both exhibited a dermal and epidermal infiltrate of CD4+ and CD8+ T cells expressing activation antigens. These were admixed with numerous macrophages. The lesional epidermis was diffusely human lymphocyte antigen (HLA)-DR+ and contained decreased CD1+ dendritic cells. Endothelial cells were also HLA-DR+. Cells bearing the phenotypes of B cells, follicular dendritic cells, or natural killer/killer cells were essentially absent. Except for the lack of large atypical cells, the results resembled those described previously for lymphomatoid papulosis. These findings indicate that pityriasis lichenoides chronica, pityriasis lichenoides et varioliformis acuta, and lymphomatoid papulosis share several immunohistologic features. Together with certain clinicopathologic similarities, they are consistent with the hypothesis that these three disorders are interrelated.

Acute Disease↗

Mycosis fungoides: management with topical nitrogen mustard.

The technique of treatment, response rate, freedom from relapse, survival, and complications of therapy in 123 patients treated with topical nitrogen mustard (HN2) for cutaneous mycosis fungoides (MF) at Stanford University Medical Center are reviewed. Patients were treated with HN2 in an aqueous or ointment base with equal efficacy. Response rates depended on the extent of skin involvement. In limited plaque (T1) disease, complete and overall response rates were 51% and 88%, respectively, while in generalized plaque (T2) disease they were 26% and 69%. No patients with tumorous involvement (T3) achieved complete skin clearance and all 13 of these patients developed progression of disease. Only two of nine patients with erythrodema (T4) achieved a complete response (CR), and both later relapsed. After achieving a CR, 40% of patients with T1 disease and 60% with T2 disease later relapsed; however, subsequent therapies, including repeat courses of topical HN2, often were successful in achieving later skin clearance. Overall, 42% of T1 patients and 31% of T2 patients were without evidence of MF at last follow-up. When death occurred, it was usually unrelated to MF in the T1 group. However, half of the deaths of patients with T2 disease were attributable to MF. Among the 22 patients with T3 or T4 disease, 80% of deaths were attributable to MF. The most common complication observed was a cutaneous hypersensitivity reaction, which occurred much more commonly with the aqueous than the ointment preparation. Fourteen patients (11%) developed subsequent cutaneous malignancies.

Adult↗

Lymphomatoid papulosis expresses immunophenotypes associated with T cell lymphoma but not inflammation.

Twelve skin biopsy specimens of lymphomatoid papulosis from nine patients were studied immunohistologically. The large atypical cells morphologically resembled Reed-Sternberg cells in six cases and large cerebriform mononuclear cells in three cases. These cells expressed pan-T cell antigens (Leu-4 and/or Leu-5) and helper T cell antigen (Leu-3) in each case. They also expressed activation antigens: HLA (human lymphocyte antigen)-DR, HLA-DQ, Tac, and T9. Reactivity of many nuclei with Ki-67 indicated a high proliferative index. Phenotypic abnormality of the large atypical cells was evident by their deficiency of T cell antigens Leu-1 and/or Leu-9 in eight of nine cases. Neither Ki-1 nor Leu-M1 were reliable markers for lymphomatoid papulosis in this series, since large atypical cells were Ki-1-positive in only three of eight cases and were Leu-M1-negative in all eight cases tested. The remainder of the cutaneous infiltrate consisted of small T cells, macrophages, Langerhans cells, and granulocytes. The small T cells expressed a normal phenotype except in some cases associated with mycosis fungoides in which they were deficient in various T cell antigens. Comparison of concurrent lymphomatoid papulosis and mycosis fungoides skin biopsy specimens in two patients revealed that they were composed of phenotypically distinct T cell subpopulations. These results indicate that the large atypical cells of lymphomatoid papulosis are a proliferating population of activated helper T cells that are deficient in certain T cell antigens. Such abnormal T cell phenotypes are common in T cell lymphoma but are rarely, if ever, observed in cutaneous inflammation. In conjunction with the cytologic atypia, aneuploidy, and association with other lymphomas documented in this or previous reports, these data suggest that lymphomatoid papulosis represents a T cell lymphoproliferative disorder rather than an inflammatory disorder.

Adult↗

Malignant histiocytosis X. Report of a rapidly fatal case in an elderly man.

A 71-year-old white man developed an increasing number of 1-to-10 mm, erythematous nodules, many with central ulceration, most prominent on the head and trunk. Biopsy of a nodule showed infiltration of the dermis and epidermis by large cells with multilobulated nuclei and numerous mitoses. Electron microscopy showed that most tumor cells contained Langerhans' cell granules. Immunohistochemical studies demonstrated a pattern of antigen expression similar to that of Langerhans' cells including Ia and Leu-6 (T6) antigens. Chest x-ray showed diffuse pulmonary infiltration and similar tumor cells were present in the sputum and urine. He developed increasing dyspnea and jaundice despite chemotherapy, and died 6 months after the onset of the disease. Autopsy showed massive tumor infiltration of the lungs, liver, spleen, and lymph nodes, and focal involvement of the myocardium, skin and bladder. Clinical and cytologic features indicated this case to be a rare example of highly malignant histiocytosis X in an elderly man.

Aged↗

Woringer-Kolopp disease (pagetoid reticulosis). Four cases with histopathologic, ultrastructural, and immunohistologic observations.

Four patients had localized lesions of Woringer-Kolopp disease (pagetoid reticulosis). The clinical appearances and histopathologic features with light microscopy of the four cases were similar. However, electron microscopy in all four cases and enzyme histochemistry studies and immunophenotyping with monoclonal antibodies in three cases disclosed two subgroups of patients. The features of the predominant cells in the intraepidermal infiltrate of three cases were most consistent with those of helper T lymphocytes with cerebriform nuclei, as found in many cases of mycosis fungoides. In one case, however, the epidermis contained a predominant population of small, medium, and large lymphoid cells of cytotoxic/suppressor T-lymphocyte cell phenotype. It remains to be determined whether Woringer-Kolopp disease is a variant of mycosis fungoides (ie, within the spectrum of the cutaneous T-cell lymphomas), a benign reactive process, or a syndrome with various causes.

Adult↗

Ointment-based mechlorethamine treatment for mycosis fungoides.

The treatment of skin disease with topical mechlorethamine has been restricted because of the frequent development of contact dermatitis. A series of 43 patients with mycosis fungoides in Stages 1A (17), IB (22), II (2), and III (2) were treated with an ointment-based mechlorethamine, prepared by an anhydrous method. Complete clearing occurred in 26 patients over a 42-month evaluation period. The incidence of contact dermatitis was very low. Only 1 of 31 patients exposed to mechlorethamine for the first time, and only 3 of 12 patients with a history of previous hypersensitivity to mechlorethamine, developed contact dermatitis to the ointment-based mechlorethamine.

Administration, Topical↗

Classification of chronic blepharitis.

Since last thoroughly evaluated over three decades ago, the clinical spectrum of chronic blepharitis has changed. The relative prevalence of Staphylococcus aureus alone or in combination with seborrheic blepharitis has decreased. The relative prevalence has increased of seborrheic blepharitis with or without associated excess meibomian secretions (meibomian seborrhea) or inflammation (meibomitis). Primary meibomitis appears not to be a primarily infectious entity but to represent a facet of generalized sebaceous gland dysfunction and to be found in association with seborrheic dermatitis or acne rosacea. The keratoconjunctivitis found in association with primary meibomitis may be contributed to by the production of bacterial lypolytic exoenzymes that split neutral lipids, resulting in an increased level of free fatty acids in the tears. A frequent finding of keratoconjunctivitis sicca in this patient population, especially the S. aureus group (50%), is of note. Of particular importance is that these entities be recognized as chronic diseases requiring control and ones for which there is no "cure."

Adolescent↗

Subtypes of cutaneous T-cell lymphoma defined by expression of leu-1 and Ia.

Monoclonal antibodies were used to characterize immunohistologically the expression of cellular antigens in 25 patients with cutaneous T-cell lymphoma (CTCL). Although all cases expressed the Leu-2a-/Leu-3a+ immunophenotype characteristic of helper T cells, four subtypes were defined based on variable expression of Leu-1 and Ia. In individual patients, the immunophenotype was constant irrespective of body compartment sampled or interim therapy. Ia+ non T-cells typically constituted one-third of the cellular infiltrate. Along with neoplastic cells, Ia+/T6+ dendritic cells were observed within Pautrier microabscesses, dermis, and individually throughout the epidermis. It will be important to determine if different CTCL immunophenotypes represent different biologic subsets of disease or have prognostic relevance. Prospective studies will be facilitated by single- and double-label immunohistologic techniques that allow the simultaneous evaluation of cellular antigen expression and architectural detail.

Adult↗

The treatment of mycosis fungoides with ointment-based mechlorethamine.

The use of topical mechlorethamine hydrochloride in the treatment of skin disease has been restricted because of the frequent development of contact dermatitis. A series of 24 patients with mycosis fungoides in stages 1A (eight patients), 1B (15 patients), and 2 (one patient) were treated with ointment-based mechlorethamine, prepared by an anhydrous method. This preparation was therapeutically effective. Complete clearing occurred in 15 of 18 patients with active disease over evaluation periods of up to 27 months, and one patient had partial clearing. Two patients showed a partial relapse during their evaluation periods. The incidence of contact dermatitis was very low: 8% in individuals with a history of hypersensitivity to mechlorethamine and 0% in patients being exposed to the medication for the first time. This new preparation has been shown to be effective therapy for mycosis fungoides. Patient use is associated with minimal side effects.

Administration, Topical↗

PUVA treatment of erythrodermic and plaque type mycosis fungoides.

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.

Adult↗

Response of chronic psoriatic plaques to localized heating induced by ultrasound.

Since tumor regression occurs after hyperthermia, this modality was applied to lesions of psoriasis. A relatively uniform temperature and heat distribution within a lesion was induced using an ultrasound transducer operating at 5.265 MHz. Twenty-two chronic psoriatic plaques in nine patients were heated to temperatures ranging from 42 to 45 degrees C for 30-minute periods three time weekly for a total of four to ten treatments. Fifteen lesions (68%) cleared completely within the heated zone, five lesions (23%) responded partially, and two lesions (9%) remained unchanged. Biopsy specimens taken before and during treatment showed reformation of the granular layer as the earliest and most consistent change in responsive lesions. Remissions were temporary, and the lesions usually relapsed within three months. Hyperthermia may be a useful therapeutic and investigative tool for the problem of psoriasis.

Hot Temperature↗

Epidermal synthesis of prostaglandins and their effect on levels of cyclic adenosine 3', 5'monophosphate.

Extracts of guinea-pig and human skin epidermis were analyzed for prostaglandins PGE1, E2, and F2alpha by radioimmunoassy, and found to contain a total of 62.0 (guinea pig) and 144.7 (human) ng/gm wet weight. the three prostaglandins occurred in approximately equal amounts. Guinea=pig epidermal homogenates converted labeled arachidonic acid to PGE2 and PGF2alpha, the rate of formaiton being 10 and 2.5 pmoles per mg protein in O.K hr, respectively. Conversion in the dermis occurred to a much smaller extent. Homogenates of univolved and involved epidermis from 10 subjects with psoriasis produced PGE2 from arachidonic acid at rates of 6.48 and 2...

Animals↗

The treatment of psoriasis with azaribine.

An open study was made of 25 patients with severe, recalcitrant psoriasis treated with azaribine (6-azauridine triacetate). Most patients received 125 mg/kg/day for a period of 8 weeks. A good to excellent response with 60-100% clearing of lesions was observed in 14 patients and a fair response with 40-60% improvement in another 6 patients. Thus 20 patients (80% of the series) exhibited a favorable clinical response. 16 of these 20 patients relapsed to approximately pretreatment status within 1 month after stopping therapy. The most frequently observed side-effects were mild reversible anemia, fatigue and mild transient gastrointestinal symptons. 8 patients (32% of the series) exhibited sufficient toxicity to necessitate the discontinuance of therapy. 1 patient experienced an unexplained femoral arterial thrombotic episode while on the drug. Azaribine may find a place in the therapy of severe psoriasis particularly in patients with hepatic disease. However, further studies of its potential for toxicity are indicated.

Adolescent↗