Combined modality therapy for tumor stage mycosis fungoides: results of a 10-year follow-up.

Twenty-one patients with tumor stage mycosis fungoides (MF) with or without lymph node (LN) involvement, were treated with total skin electron beam irradiation (TSEB) followed by six monthly cycles of systemic chemotherapy (CT) of either mechlorethamine (HN2) or cyclophosphamide (CTX) with vincristine (VCR), procarbazine, and prednisone (PRD) (COPP or MOPP). All patients had complete clearing of the skin after TSEB. However, while receiving chemotherapy, two patients developed visceral involvement and eight patients relapsed with limited cutaneous plaques (LCP). The median duration of remission was 12 months from the completion of TSEB, and all patients relapsed with cutaneous plaques within 25 months. Complete remission was again achieved using additional electron irradiation and maintenance therapy in all but one patient. Multiple cutaneous recurrences occurred in all patients. Median survival from the initiation of TSEB is 6 years. Five patients are living beyond 8 years (four off treatment without disease for 1 to 7 years). LN involvement did not influence initial response or survival. Combined modality therapy for tumor stage MF using TSEB followed by systemic CT and subsequent maintenance therapy may lead eventually to prolonged disease-free survival (DFS) in selected patients.

Immunofluorescence localization of peripheral proteins in cultured human keratinocytes.

To gain preliminary data on the location of a 195 kD cell peripheral protein of epidermal keratinocytes recognized by monoclonal antibody AE11, immunofluorescence staining was carried out on cultured human epidermal cells. B11 antidesmosomal polyclonal antibody and AE3 antikeratin monoclonal antibody staining were used as comparative reference controls. Desmosomal antigens span the cell membrane and keratins constitute a family of cytoplasmic proteins. The cultured cells were systematically used either unfixed, fixed with 4% paraformaldehyde, or fixed with methanol at 4 degrees C. The former two preparations were designed to expose only the surface antigens, whereas the latter method permeated the membrane to allow cytoplasmic staining. Differences in staining patterns were observed in the basal layer as compared with the upper layers with all three antibodies. B11 antidesmosomal antibody staining was consistent in pattern after either paraformaldehyde or methanol fixation. In addition to the punctate staining along adjacent cell surfaces as shown in the basal layer, the surface planes of the upper cells exhibited parallel arrays of linear streaks, demonstrating the distribution of desmosomal proteins. Antikeratin staining by AE3 showed the typical filamentous staining in basal cells. However, a homogeneous patchy staining of suprabasal cells was observed. The presence of punctate surface staining using antikeratin antibody on paraformaldehyde fixed cells suggests leakage of keratin to the cell surface. AE11 showed stronger staining in the top cells on methanol treated cultures and a punctate surface staining of the cells fixed with paraformaldehyde. These observations provide useful preliminary information in localizing peripheral proteins in epidermal keratinocytes.

Demonstration by labeled treponemal antigen of specific antibodies in the tissue infiltrates of secondary syphilis.

Specific antitreponemal antibodies have been demonstrated by immunofluorescence techniques in the lymphoplasmocytic infiltrates which characterize early symphilitic lesions. A purified suspension of Nichols strain Treponema pallidum was sonified and labeled with fluorescein isothiocyanate and applied to cryostat sections of 12 biopsy specimens from the cutaneous lesions of 11 patients with proven secondary syphilis, using a modified direct immunofluorescence procedure. Specimens from various inflammatory dermatoses processed similarly served as controls. Granular fluorescence was noted in the dermis in 9 of the 12 specimens corresponding to areas of heavy plasma cell infiltration and some fluorescence was found directly on plasma cells which were identified by subsequent hematoxylin and eosin staining. This fluorescence could be blocked by prior incubation of the sections with unlabeled sonified treponemal suspension. Control slides did not reveal any fluorescence. The use of labeled treponemal antigen may aid the tissue diagnosis of early syphilitic lesions which can mimic a variety of dermatological disorders.

The inefficacy of riboflavin against ultraviolet-induced carcinogenesis.

Flavins are reported to protect cellular DNA against UV irradiation injury in vitro. The possible photoprotective effects of riboflavin in vivo on UV-induced carcinogenesis were studied in three groups of HR-hairless mice. Group I served as control. Group II was painted daily with a 15 mg per ml solution of riboflavin. In Group III, drinking water was replaced with a 15 mg per ml solution of riboflavin in water. All three groups were simultaneously irradiated in a light box with two Westinghouse FS20 sunlamps from a distance of 30 cm for 5 min daily 6 days a week throughout the experiment. By the 11th month all surviving mice developed several histologically proven squamous cell carcinomas. The total numbers and times of onset of tumors did not vary in the three groups. Thus, no protective effect of massive amounts of riboflavin on ultraviolet-induced carcinogenesis in the hairless mouse could be demonstrated when such high dose rates of UV were used.

Antipruritic effect of an opiate antagonist, naloxone hydrochloride.

Central elicitation of itch by morphine may result from binding to opiate receptors, mimicking the physiological binding of endorphins and enkephalins to these receptors. Pretreatment of normal subjects with naloxone hydrochloride resulted in diminution or abolition of histamine-provoked itch. These results suggest an important role for central opioid peptides as mediators of the itch sensation.

Inhibition of axon reflex vasodilatation by topically applied capsaicin.

Topical application of capsaicin to human skin produced an initial burning erythematous reaction which diminished over 24 hr leaving the skin unresponsive to histamine-induced axon reflex vasodilatation without altering sensitivity to pain, touch and temperature. Depletion of substance P from local sensory nerve terminals is suggested as a possible explanation for this capsaicin effect.

Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor.

Androgen receptors were localized in cryostat sections of human skin using monoclonal antibodies to the human androgen receptor. Bound antibodies were detected using biotinylated rabbit anti-rat IgG, peroxidase-conjugated streptavidin, and diaminobenzidine as chromogen. In the neonatal foreskin, antibody to androgen receptor bound to keratinocytes in the epidermis and to fibroblasts and vascular endothelial cells in the dermis. Immunohistochemical staining was stronger in nuclei than in cytoplasm. This staining was specific, because there was no significant staining when antibody to the androgen receptor was replaced with IgG from nonimmunized rats or with buffer, or when antibody to androgen receptor was incubated, prior to immunostaining, with a trp E-human androgen-receptor fusion protein used as immunogen. Incubation of androgen receptor antibody with trp E alone did not affect staining. Androgen-receptor antibody also bound to keratinocytes, fibroblasts, and endothelial cells in skin from adult men and women. Skin from the scalp, nose, lip, back, and chest gave positive staining for androgen receptor. Antibody to androgen receptor also bound to the coil and ductal cells of eccrine glands, external root sheath of hair follicles, epithelium in the hair bulb, dermal papilla cells, and sebocytes. There was no significant binding to adipocytes, collagen, or stratum corneum. These results show that androgen receptor is present in cells that are known to be targets for androgens and also in cells in which the biologic effects of androgens are yet to be characterized.

Erythema elevatum diutinum treated with niacinamide and tetracycline.

A 60-year-old woman with recurrent papular and vesiculobullous lesions of erythema elevatum diutinum responded to treatment with 100 mg of oral niacinamide three times a day and 250 mg of tetracycline hydrochloride four times a day. Prior therapy with 2.5 mg of dexamethasone daily and 1.0 g of erythromycin daily had been unsuccessful. After four weeks, tetracycline therapy was discontinued, and niacinamide alone sufficed to suppress the disorder. Recurrent lesions developed whenever niacinamide therapy was stopped.

The treatment of bullous pemphigoid with tetracycline and niacinamide. A preliminary report.

Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.

Incidence of acute renal transplant rejection in atopic individuals.

BACKGROUND AND DESIGN: It is been shown that atopic individuals can exhibit a T-cellular response (ie, "late-phase reaction") when exposed to relevant allergens and that they have more lymphocytes in an activated state. The purpose of this study was to demonstrate whether atopic individuals could mount more frequent and more severe episodes of acute renal transplant rejection, a phenomenon that is also mediated by T cells. A 6-month retrospective study was conducted comparing episodes of acute renal transplant rejection in nine atopic patients and nine nonatopic patients. The atopic patients used in this study all had allergic rhinitis. The hypothesis was that atopic individuals, who already have a proposed form of cell-mediated hypersensitivity to allergens, should also be able to experience more frequent and more severe episodes of acute allograft rejection. RESULTS: The atopic patients in this study were found to have more frequent episodes of acute renal transplant rejection than the nonatopic group. In addition, they were found to have more severe episodes of rejection than the nonatopic group. CONCLUSIONS: In our study, we observed that atopic individuals are more likely to exhibit acute rejection phenomena after renal transplant. Thus, our study presumes that the T-cellular hypersensitivity reactions observed in atopic individuals are analogous to the T-cell-mediated acute transplant rejection episode. The question of whether the same subset of T cells is active in these two reactions still needs to be explored, and the T cells in question need to be further characterized. In addition, the effect of immunosuppressive therapy on T-cell kinetics in atopic individuals needs to be further defined.

Pagetoid reticulosis (Woringer-Kolopp disease). Histopathologic and ultrastructural observations.

Histopathologic and ultrastructural observations in a case of Pagetoid reticulosis (Woringer and Kolopp disease) are reported. The most important clinical feature of this disease is manifestation as a single very slowly enlarging verrucoid, plaque-type skin lesion without internal organ involvement. Histologically, the epidermis is extremely acanthotic and densely infiltrated with numerous atypical appearing cells that are entirely absent from the dermis, which simply contains a banal dense chronic inflammatory infiltrate. Ultrastructural study showed that there are two major types of unusual cells infiltrating the epidermis. One type is a large lymphoid cell similar to the stimulated lymphocyte. The second type differs from the first in having paler staining of the nucleus and cytoplasm and showing cell membrane damage. These cells probably derive by degeneration from the large lymphoid cells. The presence of transitional forms favors this interpretation. Occasionally, degeneration of these cells proceeds to their complete necrosis.

Acral lividosis--a sign of myeloproliferative diseases. Hyperleukocytosis syndrome in chronic myelogenous leukemia.

Acral ischemia with lividity is a well-described dermatologic sign in the myeloproliferative diseases polycythemia vera and essential thrombocythemia. It has not previously been reported as a sign of chronic myelogenous leukemia (CML). We suggest the term acral lividosis to describe this clinical entity in patients with any myeloproliferative disease. We propose that the pathophysiology of acral lividosis in CML involves occlusion of small blood vessels of the skin by large, nondeformable myeloblasts, a process that has been shown histologically to occur in other organs in patients with CML. This process, called leukostasis, occurs in patients with CML who have over 50.0 X 10(9)/L (50,000/mm3) circulating myeloblasts. Patients manifest cardiorespiratory and central nervous system compromise, a clinical constellation known as the hyperleukocytosis syndrome. Acral lividosis occurred in a patient with CML in whom nearly every organ demonstrated leukostasis on autopsy.

Distinctive acral erythema occurring during therapy for severe myelogenous leukemia.

A distinctive acral erythema developed in four patients with myelogenous leukemia, subsequent to blood transfusions and intensive chemotherapy with cytarabine. The clinical and histopathologic features of the eruption were suggestive of a drug-induced toxic eruption. To our knowledge, only one previous similar case has been reported in the literature. For patients in whom this self-limited condition develops, reassurance should serve as the mainstay of therapy.

Lupus erythematosus-like syndrome with a familial deficiency of C2.

Several cases of isolated C2 deficiency in man have been reported in the medical literature. The earliest cases did not seem to be associated with known diseases or syndromes; more recently, reports of C2 deficiency associated with systemic lupus erythematosus; anaphylactoid purpura, recurrent infections, and dermatomyositis have appeared. We report here another case of C2 deficiency. The propositus, a 24-year-old woman, had a lupus erythematosus-like rash and a history of arthralgia, as well as a selective deficiency of C2. Studies of hemolytic C2 of the immediate members of her family indicate an autosomal-recessive mode of inheritance. These findings add to the increasing evidence that a C2 deficiency predisposes some persons to serious vascular diseases.

Levodopa administration and multiple primary cutaneous melanomas.

Malignant melanoma derives from melanocytic cells that possess the special biochemical pathway for the conversion of levodopa to melanin. Levodopa is widely employed in the treatment of Parkinson's disease, and several patients receiving levodopa have been observed to have acquired melanomas, raising concern about a possible relationship between this drug and the tumor. We encountered a 74-year-old woman in whom three distinct primary melanomas developed after she had been receiving long-term therapy with levodopa and a decarboxylase inhibitor. These lesions could be distinguished histologically from epidermotropic metastatic melanoma. Although the association between levodopa and melanoma is tenuous, careful monitoring of pigmentary changes in patients receiving levodopa is advised.

Triad of lichen planus, myasthenia gravis, and thymoma.

Myasthenia gravis in a woman was followed by the development of severe erosive lichen planus and thymoma. Lichen planus is not ordinarily associated with other cutaneous or systemic disorders. The reported immunologic findings in some patients with lichen planus and especially the occasional association of lichen planus with certain disorders linked with immunologic disturbances suggest an autoimmune pathogenesis for this disorder.