Acute febrile neutrophilic dermatosis--a marker of malignancy?

A retrospective survey during a 2-year period disclosed 18 patients with acute febrile neutrophilic dermatosis (Sweet's syndrome). An associated lympho- or myeloproliferative malignancy was found in 6 patients. Attacks of Sweet's syndrome preceded the diagnosis of neoplasia in 4 patients (3 months to 6 years). Some differences in symptoms and signs were found in the group of patients with associated malignancy compared with the group without, that is, male predominance, mucosal symptoms, anemia, and frequent recurrence of skin symptoms. The onset of Sweet's syndrome indicates an acute infectious disease, and the patients are frequently referred to departments of internal medicine and infectious diseases. In addition, the skin lesions may mimic those which often accompany a generalized infection (erythema multiforme, erythema nodosum, vasculitis, pustular eruptions and urticaria). Since Sweet's syndrome may precede the possibly associated malignant disease, the initial diagnosis of the syndrome is important and should be made with confidence with increasing awareness of the characteristic symptoms.

Skin and oral mucosal changes in patients infected with human immunodeficiency virus.

During a 6-month-period, 150 patients infected with Human Immunodeficiency Virus (HIV) were repeatedly examined by dermatologists and dentists for lesions of skin and oral mucosa. The most frequently encountered diseases were: oral hairy leukoplakia (21%), dermatophytosis (including tinea unguium/tinea pedis et inguinalis) (20%), seborrheic dermatitis (19%), viral infections (10%), oral candidiasis (7%), acne vulgaris (6%), and folliculitis (5%). A variety of other manifestations were seen, with frequencies less than 5%. Herpes zoster was seen in 3% of the patients, indicating a rate of 60/1,000 per annum. The presence of seborrheic dermatitis was statistically associated with low T-helper lymphocyte count. Patients with low T-helper lymphocyte count had on average twice as many mucocutaneous lesions as patients with a normal or moderately decreased count. Any one of the manifestations seborrheic dermatitis, oral candidiasis or oral hairy leukoplakia was associated with a greater average number of additional mucocutaneous changes than seen in patients exhibiting none of these three conditions. The high proportion of HIV-infected patients with cutaneous and oral lesions underlines the importance of referring the patients to dermatologists and dentists for examination. Prospective examinations of the study population remain to elucidate the prognostic significance of mucocutaneous manifestations of HIV-infected patients.

Effect of UV irradiation on expression of membrane IL 1 by rat macrophages.

The effect of UV-B irradiation on the expression of membrane-associated IL 1 (mIL 1) by rat pulmonary alveolar macrophages (PAM) was studied. We found that although there was an increase in secreted IL 1 by PAM exposed to UV-B, the expression of mIL 1 was inhibited in a dose-dependent manner. Furthermore, PAM that were allowed to express mIL 1 before UV-B irradiation had a faster decay of mIL 1 activity than unirradiated cells. These data suggested that mIL 1 expression is inhibited by UV-B irradiation, and that under normal circumstances, mIL 1 synthesis and degradation is at a steady state, with the half-life of mIL 1 activity being 24 hr when assayed in an IL 1-dependent cell line proliferation assay. These data indicate that secreted forms of IL 1 and mIL 1 are differentially regulated and that the therapeutic effects of UV irradiation may be due to its inhibition of mIL 1 activity.

Effects of 254 nm UV irradiation of human lymphocytes in vitro studied on chromosomes, cell cycle phase distribution and cell surface antigens.

Isolated human peripheral blood lymphocytes were exposed to 254 nm UV light and stimulated with PHA. Chromosome analysis revealed significant increases in sister chromatid exchanges (SCE's) and micronuclei, and also in gross chromosomal aberrations, but not in breaks and gaps on the chromatid level. By means of flow cytometry it was shown that UV exposure perturbed the cell cycle in that the S and G2/M fraction decreased when UV was given before stimulation with PHA. Labelling the cells with fluorescein-conjugated antibodies did not reveal any changes in the relative frequencies of lymphocyte subsets after exposure, but an overall diminished ability to bind antibody was observed.

A transitional variant of a T-lymphoproliferative malignancy. Two cases of cutaneous T-cell lymphoma co-expressing E and Fc gamma receptors with final leukaemic transformation.

2 cases of malignant T-lymphoproliferative disease are reported. The proliferating cell was a large blast expressing E and Fc gamma receptors but no helper or suppressor phenotypes and no SmIg. Skin infiltrates were the dominant clinical sign with conspicuous perivascular aggregations of T, E, Fc gamma lymphocytes, though both patients initially had disseminated disease with mild lymphadenopathy, splenomegaly and, in case 2, also hepatic infiltrations. Accordingly, DNA measurements on skin biopsies, taken early in the course, showed a dominating hypotetraploid clone (case 1) and a pronounced population in S-phase (case 2). The patients were alive for 6 and 2 yr, respectively, with a final fatal course of about 6 months duration involving a rather sudden progression of the skin infiltrates, increasing lymphadenopathy and splenomegaly, leukaemic transformation of the neoplastic T, E, Fc gamma lymphocyte and practically no response to cytostatic treatment.

Erythema elevatum diutinum and pre-AIDS.

Erythema elevatum diutinum (EED) is a chronic disease with symmetrical persistent erythematous nodules and plaques primarily in an acral distribution. EED is often associated with infections, especially of streptococcals. An immunological reaction has been proposed as pathogenetic mechanism. We describe a patient, who developed EED secondary to a LAV/HTLV III positive lymphadenopathy syndrome. Immunological investigation of a skin lesion and a lymph node biopsy is described.

Penicillin concentrations in serum following weekly injections of benzathine penicillin G.

Twelve patients with syphilis were treated weekly with injections of 1.44 g (2.4 X 10(6) IU) of benzathine penicillin G for up to 3 weeks. Almost daily, serum penicillin concentrations were measured by a sensitive microbiological agar cup method. An individual and interindividual variation was found. Concentrations below the recommended 0.018 micrograms/ml were found 7 days after the first or second injection in 5 samples. Shorter intervals between injections are recommended.

Unique pattern of HTLV-III (AIDS-related) antigen recognition by sera from African children in Uganda (1972).

Of 75 sera collected in the West Nile district of Uganda over a 1-year period between 1972 and 1973, 50 (66%) had antibody reactivity to human T-cell lymphotropic virus subgroup III (HTLV-III) at low titer levels. Sera were initially screened by HTLV-III enzyme linked immunosorbent assay and sera with values less than normal mean + 2 SD were removed from testing. The remaining sera were tested for positivity by an amplified Western blotting procedure which incorporated a three-layer immunoperoxidase procedure. Immunoglobulin reactive with HTLV-III Mr 24,000, 41,000, and 76,000 proteins were present in nearly all positive sera. The antibody status of this group was unlike any normal or acquired immunodeficiency syndrome-risk group previously tested. The high prevalence and relatively low titers suggest the detection as early as 1972 of a relative or predecessor of HTLV-III or of HTLV-III itself but existing in a population acclimated to its presence. It further suggests a likely African origin of HTLV-III.

PIP: Sera from 75 children from an isolated subsistence farming region of the Ugandan Nile valley in 1972-1973 showed a unique pattern of antibody titer to HTLV-III: a high prevalence but low titer for a limited number of viral proteins. The sera were originally collected at random as controls for a study of Burkitt's lymphoma. Mean age was 6.4 years. Sera were tested quantitatively by ELISA and 50 of 55 positives were confirmed by Western blot. The most prominent bands had molecular weights of 76,000, 41,000 and 24,000, coinciding with HTLV-III antigens previously described. The geometric mean titer was 295 with a range of 100-1000. The results suggest high prevalence of a closely related virus in this population.

Evidence for exposure to HTLV-III in Uganda before 1973.

Fifty of 75 serum samples collected in the West Nile district of Uganda between August 1972 and July 1973 contained antibodies reactive with human T-cell leukemia (lymphotropic) virus type 3 (HTLV-III; mean titer, 601), while 12 of 75 samples were positive in a similar test for HTLV type 1 (HTLV-1) antibodies (mean titer, 236). The samples were screened by enzyme-linked immunosorbent assay and positive results were confirmed by a newly developed unlabeled antibody-peroxidase procedure with enhanced sensitivity for detection of antibody binding to immunoblots of HTLV-III antigen, demonstrating antibodies to proteins with molecular weights of 24,000, 41,000, and 76,000 in nearly all positive samples. Analysis of titration data indicated enhanced titers of antibody against HTLV-III and HTLV-I when coinfection occurred. The high prevalence and relatively low titers [compared to serum from patients with acquired immune deficiency syndrome (AIDS)] of antibodies recognizing HTLV-III proteins in sera from this population at a time that may predate or coincide with the appearance or spread of the AIDS agent (HTLV-III) suggest that the virus detected may have been a predecessor of HTLV-III or is HTLV-III itself but existing in a population acclimated to its presence. It further suggests an African origin of HTLV-III.

Retinoid dermatitis mimicking progression in mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Group.

A dermatitis occurring during the treatment of mycosis fungoides with A vitamin analogues (13-cis-retinoic acid and etretinate) and mimicking a progression of the disease is described. It is considered to be a skin reaction due to the treatment. Its benign nature is revealed by histology showing a lymphocytic infiltrate without any atypical sign.

Human T-lymphotropic retrovirus type III (HTLV-III) in Danish homosexuals.

Sera from 119 patients attending a venereal disease clinic in Copenhagen during May 1983 were screened for antibodies to the newly characterized and isolated retrovirus HTLV-III. Ten out of 45 (22%) homosexual patients and two out of 74 (2.7%) heterosexual patients were found to have antibodies against HTLV-III. The homosexual group (except one case that developed AIDS and died during one year observation period) contained otherwise healthy men some of which had no contact with individuals from high-risk areas and only a few sexual partners. These results strongly suggest that Danish homosexuals with only few contacts are also at risk and that sero-epidemiological studies should also include the healthy homosexual group and probably the heterosexual group attending venereal disease clinics.

Activated and cycling lymphocytes in benign dermal lymphocytic infiltrates including psoriatic skin lesions.

Single-cell DNA measurements obtained using flow cytometry have previously been used as a diagnostic tool for various malignant diseases. We used this technique to characterize the dermal infiltrates of 14 patients with psoriatic skin lesions and 22 patients with various benign skin disorders. The DNA histograms of all of the patients exhibited an increased number of cells showing propidium-iodide fluorescence in the hyperdiploid region as compared to those seen in control DNA histograms of normal blood mononuclear cells. The calculated DNA indices revealed one hyperdiploid (G0/G1) peak in 17 cases and two hyperdiploid (G0/G1) peaks in 13 cases. The results suggest that the dermal lymphocytic infiltrate consists of (1) lymphocytes in the cell-division cycle, (2) non-cycling lymphocytes (G0) and (3) activated lymphocytes that may either remain in a non-cycling state or enter the cell cycle.

Raynaud's phenomenon with oral manifestation in systemic lupus erythematosus.

A 24-year-old woman with discoid lupus erythematosus developed systemic lupus erythematosus after 6 years. One of the clinical features was Raynaud's phenomenon in the fingers and toes, and furthermore Raynaud's phenomenon appeared in the tongue when exposed to cold and windy weather.

Characterization of benign cutaneous lymphocytic infiltrates by monoclonal antibodies.

Skin biopsies from nine patients with a histological and/or clinical diagnosis of cutaneous lymphocytoma, lymphoplasia or Jessner's lymphocytic infiltrate were examined by immunoenzymatic labelling with a panel of monoclonal antibodies against lymphocytes and accessory cells. Similar cellular constituents were demonstrated in the biopsies from three patients with lymphocytoma, two with lymphoplasia and two with atypical lymphocytes, but a protracted benign clinical course. The infiltrates from these patients consisted of T cells, Langerhans cells, related HLA-DR positive dendritic dermal cells and clusters of polyclonal B cells. In four patients, the B cell clusters contained B cell accessory follicular dendritic cells, and thereby closely resembled the B cell follicles seen in lymphoid organs. The T cells were predominantly T helper/inducer cells and in all patients the T cells expressed HLA-DR. One patient diagnosed as lymphocytoma cutis differed from the other patients by having no detectable B cells. One patient with Jessner's lymphocytic infiltrate differed from the other patients by having a marked relative predominance of T suppressor/cytotoxic cells. These data suggest that cutaneous lymphocytoma and lymphoplasia are basically similar disorders which may be considered to be exaggerated immune responses, whereas Jessner's lymphocytic infiltrate may be a separate entity. Immunological analysis may assist in establishing a definite diagnosis in cases of lymphocytoma or lymphoplasia with atypical cytological features.

In situ immunological characterization of the infiltrating cells in positive patch tests.

Skin biopsies from positive allergic patch tests were analysed by immunoenzymatic labelling of frozen sections with monoclonal antibodies. In seventeen patients the cellular infiltrate consisted of T cells admixed with Langerhans cells/indeterminate cells, but in two patients there were also many B lymphocytes. The B cells were accompanied by dendritic reticulum cells forming B-cell follicles, indistinguishable from those of normal and hyperplastic lymph nodes. There was no correlation between these two immunohistological staining patterns and the sensitizing antigen, the extent of local reaction or the time from epicutaneous application of allergen to examination (2 to 16 days). The ratio between T-helper and T-suppressor cells varied considerably, and showed no correlation with these variables. In all patients the infiltrating T cells expressed HLA-DR antigen. Transferrin receptors were identified on the infiltrating T cells in biopsies from nine patients. These data indicate activation of T cells in the infiltrate from positive patch tests, and support the functional significance of Langerhans cells in the initiation and maintenance of cutaneous contact allergy. An involvement of B cells and B-cell accessory cells in the pathogenesis of contact allergic reactions is also suggested. The presence of dendritic reticulum cells in skin infiltrates from positive patch tests may reflect a functional implication of the skin in the development of B-cell memory.

Methotrexate in lymphomatoid papulosis.

The effect of weekly methotrexate treatment (5 to 25 mg orally) was studied in three patients with lymphomatoid papulosis. In all three patients a good clinical effect was obtained. Skin biopsies revealed no sign of lymphomatoid papulosis after treatment. Methotrexate appears to be effective in controlling lymphomatoid papulosis and is possibly superior to PUVA in this respect.

Dapsone in the treatment of Kaposi's sarcoma.

Previously we observed clinical and histological regression of Kaposi's sarcoma in the skin in a 38-year-old man with AIDS following treatment with Dapsone. This observation initiated the present study where 6 patients with Kaposi's sarcoma in the skin without clinical signs of systemic spreading were treated with Dapsone 100 mg daily for four months. During this treatment clinical and histological regression of Kaposi's sarcoma was found in three patients. In a further patient only clinical regression was found, while no regression was found in the remaining two patients with Kaposi's sarcoma.