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Twenty patients with severe plaque psoriasis were selected to receive either low-dose cyclosporin A (CyA) or placebo (CyA vehicle) in a double-blind randomized trial at two centres. Within 4 weeks the mean reduction in the Psoriasis Area and Severity Index (PASI) in 10 patients receiving CyA (mean dose 5.5 mg/kg/day) differed significantly from the mean reduction in 10 patients receiving placebo. In eight patients given placebo a switch to CyA therapy resulted within 4 weeks in a mean reduction in PASI of 90%. In a total 15 out of 18 patients given CyA (83%) (mean dose 5.6 mg/kg/day) there was an improvement of greater than or equal to 75% in PASI within 4 weeks. In a 2-month tapering off phase a lower mean CyA dose (3 mg/kg/day) was effective in maintaining the reduced PASI scores in seven of nine patients. Four out of five CyA treated patients who entered a post-treatment observation phase had a relapse (PASI score greater than or equal to 50% of score at baseline) after a mean interval of 6.5 weeks. The most important side-effects were mild reversible hypertension in 5 of 18 patients (28%), and reversible elevated serum creatinine levels in 7 of 18 patients (39%). We consider that further studies are justified in severe chronic psoriasis to establish suitable regimens for maintenance of remission in psoriasis with low-doses of CyA or a combination of CyA with other anti-psoriatic agents.

We evaluated the results of a 5-year period of epicutaneous testing in children and teenagers younger than 16 years of age. In an overall-tested population of 2671 persons, 67 were younger than 16 years. In 16 (23.8%) of these 67 children, a positive epicutaneous test was considered to be clinically relevant for the diagnosis allergic contact dermatitis. From the total of 44 positive tests, the most common allergen was nickel sulfate (18%), followed by balsam of Peru, Carba mix, colophony, and fragrance mix (6% each). As our test population consisted of only a few children, no conclusions were drawn in respect to children younger than 10 years. Despite our careful selection of children with allergic contact dermatitis, the prevalence of positive epicutaneous tests was no different than that reported for unselected populations of children.

8 cases of contact dermatitis from toluenesulfonamide formaldehyde resin in a nail hardener are presented. Most patients had used nail lacquers containing this resin for many years without trouble, but became sensitized to the resin shortly after the introduction of this particular nail hardener. A hypothesis concerning the possible mechanism is given.

A patient with pyoderma gangrenosum without associated disease was studied. Routine investigations showed several abnormalities. High ESR, high alkaline phosphatase and glutamyl transferase (gamma-GT) levels, low iron and iron binding capacity, altered protein spectrum, presence of Staphylococcus aureus and group G hemolytic streptococci in ulcer culture, higher than normal antistreptolysin titers in the serum, and perivascular infiltration in the skin. Biochemical investigations aimed at finding any excessive hydrolytic activity did not reveal the presence of neutral proteases in circulation leaked out from PMN-leukocytes or elsewhere. Lysozyme levels were higher than normal, amylase and lipase levels were normal and 5' nucleotidase levels were below normal range. TCA-soluble polypeptides were present in the serum at levels two times higher than those in normal individuals. Immunochemical investigations showed the absence of immune complexes in the serum but presence of high amounts of C-reactive protein. Total complement activity was higher than normal and so was C3c level. Clq, C4, and C3d levels were within normal range. Biologic studies showed the presence of a factor in patient serum that made guinea pig skin hard, painful, erythematous, and eventually hairless, but not necrotic. A similar factor was either absent in normal serum or present in very low concentration. After salazopyrine treatment, all the above mentioned abnormalities corrected except that 5' nucleotidase activity remained slightly lower than normal, alkaline phosphatase levels remained slightly higher than normal, and C-reactive protein levels remained very high, though lower than those during intense disease activity.

13 patients allergic to the cationic emulsifier oleamidopropyl dimethylamine were tested with a series of related amide-amine type surfactants in order to investigate its cross-reaction pattern. With 1 exception, all patients reacted to at least 4 of the test materials. Most reactions were observed to ricinoleamidopropyl dimethylamine lactate and tallowamidopropyl dimethylamine (11 patients, 85%); 9 patients (of 12 tested, 75%) reacted to lauramidopropyl dimethylamine and 6 (46%) to myristamidopropyl dimethylamine. A certain pattern of cross-reactivity was recognised.

Serological and non-serological tests were performed in matched samples of cerebrospinal fluid and serum from 236 syphilitic patients. An increased IgG or IgM index, or both, was found about 70 times more often in symptomatic neurosyphilis than in latent syphilis without involvement of the central nervous system. An increased Ig index, together with a cell count greater than 5/microL, was only found in symptomatic neurosyphilis. Although the numbers of data are small, we conclude that the IgG and IgM indexes are valuable tests in the diagnosis of syphilitic involvement of the central nervous system.

Synopsis Of 1620 patients routinely patch tested with Kathon CG 100 p.p.m. aqua for suspected allergic contact dermatitis, 81 (5.0%) had a positive reaction. Sixty-two reactions (3.8%) were relevant for the dermatitis for which the patient consulted the dermatologist. Most patients were females who presented with dermatitis of the hands and/or face. Forty-six per cent of the patients had become sensitized by using cosmetic products on healthy skin. The other 54% had pre-existing dermatitis, especially atopic dermatitis and irritant dermatitis. Most reactions were caused by moisturizing creams.

Dendritic cells bearing Langerhans cell (OKT6+) or interdigitating cell (RFD1+) immunophenotype may be regularly detected within the dermis of chronic skin diseases characterized by a lymphohistiocytic (lymphoreticular) infiltrate. These 2 subsets of antigen-presenting cells within the dermis of lesions of exacerbating chronic plaque psoriasis, exacerbating nummular dermatitis (discoid eczema), atopic dermatitis, allergic contact dermatitis, pityriasis rosea, lichen ruber planus, and cutaneous lupus erythematosus were quantified using computer-assisted morphometry. The mean dendrite length per dermal dendritic cell was significantly higher for RFD1 than for OKT6 (74.4 +/- 0.98 microns vs 70.0 +/- 1.26 microns: p = 0.0023). The mean dendrite length per dermal dendritic cell was remarkably constant for each marker in the various diagnostic categories studied. Disease-specific patterns of total dendrite length and number (expressed per 100 infiltrating mononuclear cells) of these 2 dendritic cell types within the subepidermal infiltrates were obtained. Pityriasis rosea was characterized by its unique high percentage of OKT6+ Langerhans cells. Atopic dermatitis and psoriasis had relatively high percentages of both RFD1+ interdigitating cells and OKT6+ Langerhans cells. Nummular dermatitis had an intermediate number and total dendrite length for OKT6, but was relatively low in RFD1+ cells. Allergic contact dermatitis, lichen planus, and lupus erythematosus had low numbers and dendrite lengths for both dendritic cell subsets. It is suggested that pityriasis rosea is characterized by an abnormal migration pattern of Langerhans cells. Psoriasis and atopic dermatitis may be examples of diseases in which skin-localized antigen-presenting and T-cell-inducing events are continuously taking place. The other diseases may reflect inflammatory processes in which local antigen presentation is less relevant to the tissue reaction.

Absolute numbers of CD3+ T lymphocytes and their subpopulations were determined and statistically evaluated in the lesional skin of psoriasis, atopic dermatitis, nummular dermatitis, pityriasis rosea, and lichen planus. Skin sections were divided into horizontal layers and the numbers of CD3+ T cells as well as CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets were counted. In addition, absolute numbers of the two subpopulations of inducer T cells, i.e., "memory" (4B4+ 2H4-) and "naive" (4B4- 2H4+) were evaluated. Unexpectedly, epidermal infiltration by T cells was highest in psoriasis and lowest in atopic dermatitis. In most cases, this exocytosis was dominated by CD8+ suppressor/cytotoxic T lymphocytes, with a minimal epidermal mean CD4/mean CD8 ratio of 0.04 in pityriasis rosea and a maximum of 0.48 in psoriasis. Inducer T cells within the epidermis were almost exclusively of the 4B4+ 2H4- "memory" T-cell subpopulation, whereas 4B4- 2H4+ "naive" T cells were extremely uncommon in lesional epidermis. Similar results were obtained for dermal T cells in all diseases studied, i.e., 4B4- 2H4+ "naive" T cells were relatively rare. Papillary dermis infiltration by T cells was highest in lichen planus where a mean CD4/mean CD8 ratio of 1.10, the minimum in this comparative study, was obtained. The mean CD4/mean CD8 ratio of the papillary infiltrate was highest in atopic dermatitis (4.12). Our results indicate disease-specific and significantly different infiltration patterns of T-lymphocyte subsets in the chronic inflammatory dermatoses investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with syphilitic infections are at risk of development of symptomatic neurosyphilis. Adequate treatment with 2.4-7.2 x 10(6) units benzyl penicillin-G intramuscularly within 1 year after infection will rule out this risk. However, more than 1 year after infection this treatment is not fully reliable. In asymptomatic CNS involvement (asymptomatic neurosyphilis) only intravenous penicillin treatment is considered to be adequate in the prevention of neurosyphilis. In this study we redefined criteria for this condition by comparing serum and cerebrospinal fluid (CSF) samples of symptomatic neurosyphilitic patients with those of latent syphilitic patients without CNS involvement. Diagnostic criteria of the World Health Organization and of Centers of Disease Control for asymptomatic neurosyphilis (positive CSF Venereal Disease Research Laboratory (VDRL) test, combined with raised CSF cell count and/or protein content) were studied and compared with some newer parameters such as signs of intrathecal treponemal antibody production (Treponema pallidum haemagglutination assay and intrathecal Treponema pallidum assay index), immunoglobulin G (IgG) and M (IgM) index. The results of this study in 203 syphilitic patients revealed that either a positive CSF-VDRL or combination of a raised IgG and/or IgM index with an elevated CSF cell count both are useful criteria for "ruling-in" asymptomatic neurosyphilis.

The proliferating skin cells in a case of acute disseminated histiocytosis-X (Abt-Letterer-Siwe disease) confirmed by electron microscopy, were characterized by a panel of monoclonal antibodies using an immunoperoxidase technique. The "histiocytes" were found to stain with OKT-6 (anti-T6) and anti-HLA-DR antibodies. Unexpectedly, slight staining was also observed with Leu 3a (anti-T4) and OKM-1. A proliferative process of T4, T6, HLA-DR, OKM-1 positive Langerhans' cells has not yet been described and may be specific for histiocytosis-X.

An indirect immunofluorescence test (IIF) using guinea pig lip as a substrate was performed with sera from 10 patients with Behçet's disease and the results were compared to IIF with sera of 16 patients with uveitis of Turkish origin, 62 patients with non- Behçet's uveitis, 9 patients with stomatitis aphtosa and 34 healthy controls. Antibodies to guinea pig lip cytoplasmic antigens were present in 70% of the Behçet patients, in 19% of uveitis patients of Turkish origin (P less than 0.05), in 12% of the non Behçet uveitis patients (P less than 0.001), in 11% of the stomatitis aphtosa patients (P less than 0.05) and in 9% of the healthy controls (P less than 0.001). A positive Behçet serum preincubated with the supernatant of guinea pig lip sections incubated in PBS gave an inhibition on the IIF test, indicating that the antigen involved in a soluble cytoplasmic substance. No significant increase in the presence of antibodies against iris, cornea or retina (mouse eye) were detected in the Behçet sera. Of interest was the finding of a positive reaction in 6 out of 10 patients in the episcleral region of the mouse eye. This positive reaction resembles immune complex like material. Our findings suggest that using the external surface of the guinea pig lip as a substrate is useful in selecting out those patients with Behçet's disease from uveitis patients with an unknown etiology and from patients with aphtous stomatitis.

Using a solid-phase radioimmunoassay technique, mean serum IgE concentrations were found to be raised in patients with early syphilis. Antitreponemal specificity of the IgE response was investigated by the fluorescent treponemal antibody absorption test using a fluorescein-isothiocyanate-labelled antiserum against the Fc-fragment of human IgE. Validity of this test procedure was assessed by blocking experiments. The results provide evidence of the antitreponemal specificity of the IgE response in syphilis and indicate a possible role for antitreponemal IgE in the pathogenesis of the Jarisch-Herxheimer reaction and in the immune-complex origin of some of the lesions of secondary syphilis.

In this report we introduce an alternative procedure for enrichment of human epidermal Langerhans cells (LC) from epidermal cell suspensions of normal skin. By means of discontinuous Ficoll-Metrizoate density gradient centrifugation, a fraction containing high numbers of viable, more than 80% pure LC was recovered, as judged by CD1a expression. The purity of the LC-enriched fraction appeared to be dependent on the percentage LC in the crude epidermal cell suspension. LC enriched by this method retained their accessory and antigen-presenting capacities, as determined in the Concanavalin-A induced T-cell response, in the allogeneic mixed leukocyte reaction and in the antigen-specific T-cell proliferation assay in vitro. The great advantage of this method is that it is simple and rapid and that the isolated LC are unlabeled.

The irritation response to anthralin was studied using the chamber-testing technique in 17 patients with vitiligo. Anthralin concentrations of 0.1%, 0.5%, 1%, and 5% in lanette wax were applied to both vitiliginous and adjacent pigmented skin for 24 h. The extent of the erythematous reaction was evaluated on the 2nd day after application. The visual assessment of the paired anthralin patches indicated that the erythema was more intense in pigmented skin than in vitiliginous skin in 15 out of 17 patients. Chromometer readings, however, clearly indicated that the erythematous response was stronger in the vitiliginous skin than in the pigmented skin, confirming the known fact that the human eye is not accurate in the quantitative assessment of complex colors. Immunophenotypification of cellular infiltrates, using the combination of different monoclonal antibodies and the peroxidase technique, showed that inflammatory cell infiltrates caused by the anthralin exposure contained increased numbers of granulocytes and monocytes in vitiliginous skin when compared with normal skin. The percentage of T-cell subsets, Langerhans cells, and mast cells in the same infiltrates of both types of skin were similar. Our results are discussed in accordance with the view that anthralin-induced radical species of the pigmented skin can be neutralized by the scavenging properties of melanin.

We examined the role of antigen-presenting B lymphocytes using panels of antigen-specific CD4+8-T-lymphocyte clones (TLC). All 19 TLC showed a class II major histocompatibility complex-encoded (HLA-II) restricted proliferation to antigen presented by antigen-presenting cells (APC) from the monocyte fraction of peripheral blood. Only six TLC were effectively activated by antigen presented by autologous B lymphocytes activated by EBV transformation. This failure of B lymphocytes was not due to: (i) a high degree of cell surface sialic acid; (ii) a low expression of the cell surface proteins HLA-II, ICAM-1 or LFA-3 that restrict antigen presentation; (iii) lack of secretion of the cytokine IL-1 or other soluble factors that may be required as secondary signals; or (iv) induction of incomplete T-cell activation resulting in the production of growth factor interleukin-2 (IL-2) or the expression of receptors for IL-2 only. These data suggest the involvement of another cell surface interaction in antigen presentation acting besides the interactions known so far.

Normal human oral (check) mucosa was studied to discover whether the oral cavity resembles the Mucosal Immune System (MIS) or the Skin Immune System (SIS). Immunophenotypes of lymphocyte subsets and Langerhans cells (LC) with their exact locations in the epithelium and papillary layer of the normal buccal mucosa were determined and compared with data of normal human skin. In a double staining procedure, the distribution of T-lymphocytes in relation to blood and lymph vessels was determined. Immunophenotyping of LC was done with a CD1a monoclonal antibody. In contrast to the skin, T-lymphocytes in buccal mucosa are not primarily perivascular in location. They are more or less randomly distributed on both sides of the basement membrane. The epithelium of the buccal mucosa contains about 37 times as many T-lymphocytes as the epidermis of normal skin. T-cell numbers in the papillary layer are more or less comparable. The CD4/CD8 ratios of about 1/2 in the epithelium of buccal mucosa and 1/4 in the skin indicates preferential presence of the CD8 subset in both sites, but the helper/inducer T-lymphocytes play a much greater role in the epithelium of the buccal mucosa when compared with skin. B-lymphocytes were not found in the epithelium and papillary layer of the buccal mucosa. Thus, immune response associated cells in buccal mucosa do not show the MIS pattern since B cells are absent. It has more in common with SIS but differences are also apparent. In the epithelium of the buccal mucosa the density of LC does not differ significantly from that of the skin, but the papillary layer of the buccal mucosa contains significantly fewer LC than the skin. As in the skin most of the LC of the buccal mucosa are found in the epithelium.

Seven patients in various stages of syphilis were treated by oral administration of amoxicillin (6 g daily) and probenecid (2 g daily) for 15 days. The treponemicidal level of amoxicillin was studied by a Treponema pallidum immobilization assay and found to be 0.070 micrograms/ml, as compared with 0.003 micrograms of penicillin/ml. Taking into account the WHO-recommended level of 0.018 micrograms/ml of penicillin, the minimal level of amoxicillin was estimated as 0.42 micrograms/ml. This level was obtained in serum and cerebrospinal fluid (CSF) of all patients treated with the above mentioned oral combination. It is concluded that treponemicidal levels of amoxicillin can be obtained in CSF after oral administration. The amoxicillin regimen described may be a valuable alternative to single-dose parenteral penicillin in the treatment of syphilitic patients with suspected CNS involvement, provided that reasonable compliance can be obtained.

Neurological examination and investigation of the cerebrospinal fluid (CSF) was performed on 24 patients with early and 180 patients with late syphilis. In 21 (12%) patients with late syphilis positive CSF treponemal test results and neurological deficits suggestive of symptomatic neurosyphilis were found. Concomitantly all but three patients with neurosyphilis showed one or more of the following abnormal CSF variables: CSF concentration of albumin X 10(3)/serum concentration (albumin ratio) greater than or equal to 7.9; mononuclear cells greater than 5 microliters: ratio of CSF to serum IgG concentrations/ratio of CSF to serum albumin concentrations (IgG index) greater than or equal to 0.7 or of IgM/albumin (IgM index) greater than or equal to 0.1; or oligoclonal CSF immunoglobulins. In 20 (95%) patients with neurosyphilis evidence of the production of treponemal antibodies within the central nervous system (CNS) was shown. Ten (48%) patients with neurosyphilis had been treated previously for late syphilis. These observations emphasise the need to screen for neurosyphilis in patients with late syphilis. Intrathecal production of treponemal antibodies was detected in six (25%) patients with early and 44 (28%) with late syphilis who did not show any neurological deficit. Intrathecal production of treponemal antibodies indicating that the CNS was affected led us to suspect asymptomatic neurosyphilis in these patients. Seventeen (11%) patients with late syphilis but no neurosyphilis and only one (4%) with early syphilis showed additional abnormal CSF variables. Surprisingly, six out of 22 patients with treated early and 20 out of 68 patients with treated late syphilis showed evidence of treponema antibody production within the CNS. We do not know whether these findings indicate that the CNS was affected because of inadequate treatment or merely reflect persistent synthesis of treponemal antibodies associated with cured infection. In one (4%) patient with early and in 21 (13%) with late syphilis but no neurosyphilis abnormal CSF variables in the absence of positive CSF treponemal test results were observed, which excluded syphilitic inflammation of the CNS.

Inflammatory skin T cells were cloned in an antigen-independent way from lesions of patients with experimentally induced nickel-contact dermatitis. In three experiments 7-15% of the CD4+8- T lymphocyte clones (TLC) appeared to be specific for nickel in a proliferation assay. These proliferative response of nickel-specific TLC required the presence of antigen-presenting cells (APC) and were restricted by HLA class II molecules. All TLC recognized nickel presented by APC from epidermal skin. Remarkably, 5 out of 8 nickel-specific TLC exclusively recognized nickel when presented by these skin-specific APC whereas 3 out of these 8 clones could also recognize nickel presented by APC from peripheral blood. The critical APC within the fractions of epidermal cells and peripheral blood appeared to belong to the family of dendritic cells, i.e. Langerhans cells and circulating dendritic cells, respectively.

To determine whether the prevalence of allergic reactions to certain preservatives warrants their inclusion in a routine series for patch testing, a tray of 14 preservatives was tested in 501 consecutive suspected contact dermatitis patients. More than 1% positive reactions were found with DMDM hydantoin, Kathon CG, and alkyl trimethyl ammonium chloride only. The concentration of alkyl trimethyl ammonium chloride (0.1% aqua) was considered too high. Of 6 patients reacting to the formaldehyde releaser DMDM hydantoin, 4 were positive to formaldehyde. Kathon CG may be an important allergen in the Netherlands, and it is worthwhile for dermatologists there to add it to the standard test series. The recent inclusion of quaternium-15 in the ICDRG standard series appears to be of little value to them.

A pocket for tissue expander implantation in the rabbit is described at the level between the skin and the panniculus carnosus. The vascular anatomy of the undermined skin was studied with microangiography which showed a functional (sub)dermal plexus. Expanders were placed in seven rabbits and inflated daily over a period of 10 days. Blood flow in expanded skin, as measured with laser Doppler flowmetry, dropped with increasing inflation pressure. During the course of expansion, the intraluminal pressure returned to a baseline level within 24 hours after each inflation. It is concluded that an expander placed in the described layer in the rabbit causes considerable skin stretch and interferes with cutaneous blood supply and is therefore an improved model for tissue expansion in the human.

In the majority of patients, allergic nickel contact dermatitis is associated with a proliferative response of peripheral blood T lymphocytes to nickel sulfate. Optimal proliferation was found in a concentration range of 1-2 X 10(-4) M nickel sulfate. Nickel-specific response of purified peripheral blood T cells requires the presence of antigen-presenting cells (APC). Both peripheral blood monocytes and skin-derived epidermal cells could function as APC, but epidermal cells were shown to be more potent than monocytes. By testing FcR+ monocytes and FcR- circulating dendritic cells for their antigen-presenting capacities, it was found that the critical APC within the fraction of monocytes is the circulating dendritic cell. Testing highly purified T6+ (CD 1) skin-specific dendritic cells (Langerhans cells, LC) and T6- epidermal cells as APC, the critical APC within the fraction of epidermal cells appeared to be the LC. The crucial role of LC was stressed in experiments using T cells from patients exhibiting a positive patch test to nickel but a low or absent proliferative response to nickel by unpurified peripheral blood cells. Whereas addition of peripheral blood APC was ineffective, addition of LC to purified peripheral T cells was shown to overcome this low responsiveness to nickel. These results indicate the crucial role of dendritic APC subsets in nickel-specific T-cell proliferation.

The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells were not found to be present in normal human skin. Lymphocytes were always of T-cell type, and 90% of these T cells were clustered in 1-3 rows around postcapillary venules of the papillary vascular plexus or adjacent to cutaneous appendages. In such perivascular localizations, they were found to differ from their circulating counterparts in three ways. First, skin perivascular cells were found to be approximately evenly distributed over CD4+ inducer and CD8+ suppressor-cytotoxic T-cell subsets (mean CD4/CD8 ratio: papillary layer 0.96, reticular layer 0.99). Second, within the category of CD4+ inducer T cells, most were phenotyped as CD4+, 4B4+ helper inducer T lymphocytes, whereas CD4+, 2H4+ suppressor inducer T lymphocytes were found to be relatively rare (less than 5%). Third, the majority of skin perivascular T cells were activated as they expressed HLA-DR and interleukin 2 receptors. Intraepidermal, directly subepidermal, and other ("free") lymphocytes were mostly of the CD8+ suppressor-cytotoxic T-cell subset but accounted for less than 10% of the total number of lymphocytes. Intraepidermally localized T cells accounted for less than 2% of the total number of lymphocytes present in normal skin. Our results indicate that preferential perivascular localization of activated T lymphocytes is the characteristic of normal human skin. This might be a reflection of continuous antigen recognition upon endothelial cell presentation and/or continuous T cell-mediated endothelial cell activation thereby inducing enhanced antigen clearing by the skin's endothelium.

The delay in antibody production in response to infection with Treponema pallidum may be caused by a block in the differentiation of antigen-stimulated B (Bursa-dependent) lymphoid cells towards plasma cells. This hypothesis was tested by a study to detect clonal expansion of immunoglobulin-bearing B lymphoid cells by in-vitro immunofluorescence tests in patients with primary syphilis. In addition, antibodies eluted from circulating lymphoid cells were investigated for treponemal binding by the enzyme-linked immunosorbent assay, the T pallidum immobilisation test, and the immunoglobulin class-specific FTA-ABS test. Results indicated that the number of IgG-bearing lymphoid cells were increased in patients with primary syphilis. However, in only a few cases could antitreponemal antibodies be eluted from isolated lymphoid cells. For this reason, the original hypothesis was rejected.

Pityriasis rosea is a skin disease which is obscure in its etiology and pathogenesis. We studied its immunopathology by immunophenotyping the inflammatory cells in situ using monoclonal antibodies that define leukocyte subsets. Findings as to T-cells and their major subsets did not reveal disease-specific data. Monocytes stained only rarely. Neither natural killer cells, B-cells nor plasma cells were ever found. An unexpected finding was the presence within the infiltrates and rarely within the epidermis of cells having the immunophenotype of interdigitating cells (RFD1+). Intense and dendritic staining with anti-T6 and anti-HLA-DR indicated Langerhans cells to be present in the dermal infiltrates, in between these infiltrates in the papillary dermis, and focally within the parakeratotic horny layer. This Langerhans' cell pattern provides evidence for dermal Langerhans cell compartmentalization and transepidermal Langerhans' cell elimination. Such a distribution indicates a change in Langerhans' cell migration processes in pityriasis rosea pathogenesis.

An in vivo comparison was made between the contact allergic stomatitis-inducing capacity of nickel, nickel-containing dental alloys and a non-corrosive precious metal. Fifteen patients with a positive allergic skin reaction to nickel were divided into 3 groups (A, B and C). The patients in Group A (n = 4) were fitted with an intra-oral corrosion-resistant nickel-chromium Alloy A; the patients of Group B (n = 5) received a more corrosion prone nickel-chromium Alloy B and in Group C (n = 6) strongly corroding pure nickel was used. A corrosion-resistant foil of pure palladium was placed on the contralateral side. Reactivity of pure nickel foil was also tested on the skin in Group C. Immunohistological examination of the oral mucosa on the test and reference sides was performed with monoclonal antibodies directed against T-lymphocyte subsets and Langerhans cells (LC). The results showed that at the pure nickel site the LC did increase significantly in the connective tissue (approx. 4X) of the oral mucosa. However, statistical analysis of all 6 patients of Group C together showed no corresponding increase of LC in the epithelium at the site with the pure nickel, although a numerical increase of LC was noted in the epithelium adjacent to the pure nickel foil in 2 patients, which was remarkable. It can be concluded from statistical analysis that both the reference foils and the test foils can influence the number of suppressor/cytotoxic T-lymphocytes in the connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

A 49-year-old patient developed generalized pustular psoriasis after tapering off the methotrexate therapy he had been receiving for severe psoriasis and arthralgia. Treatment with cyclosporin A produced a dramatic reduction of the cutaneous lesions and the joint symptoms.

In the treatment of severe psoriasis, cyclosporin may achieve improvement or remission at low doses, but relapse usually occurs on withdrawal of treatment. An initial dose of 3 mg/kg per day is recommended. Complete remission should not be the objective, and the role of long-term maintenance cyclosporin therapy is uncertain because of potential side-effects--especially nephrotoxicity, hypertension, and a predisposition to malignancy. Guidelines are proposed for the assessment of such treatment.

Dendritic cells from human epidermis, i.e., Langerhans cells (LC), are more potent antigen-presenting cells (APC) than APC from peripheral blood in proliferative in vitro responses of helper T lymphocytes to various soluble antigens. Analysis of antigen recognition by CD4+ T lymphocyte clones indicated that this increased potency of LC as APC results from a preferential requirement for LC of part of the T cell population. These T cells show a long-lasting restoration of antigen responsiveness to peripheral blood APC after antigen-specific restimulation in vitro, indicating that restrictive antigen recognition concerns T cells that are not fully differentiated. A similar restrictive antigen recognition was observed by treatment of the T cells or the APC with neuraminidase. This restoration of responsiveness is associated with the occurrence of nonspecific cell clustering between T cells and APC. These results suggest that the selective requirement for APC is regulated by the function of adhesion molecules that are functionally blocked by sialic acid groups on immature peripheral T cells but that are readily available on peripheral T cells at a later stage of differentiation.

In previous studies to assess the role of cell-mediated immunity in Treponema pallidum infection investigations of delayed type skin hypersensitivity tests, lymphocyte transformation test, leucocyte migration inhibition tests, and histological studies of the reticuloendothelial system have been performed. In this study, the numbers of T (thymus-dependent ) lymphoid cells in 10 patients with primary syphilis (eight untreated) were estimated by the rosette technique. Results indicate a significant decrease in the number of T lymphoid cells in patients with primary syphilis.

The relationship between contact allergy to formaldehyde and positive patch test reactions to DMDM hydantoin was investigated. 35 formaldehyde-allergic patients were patch tested with serial dilutions of formaldehyde (0.1%-0.3%-1.0% aq.) and DM hydantoin (the non-formaldehyde-containing parent compound of DMDM hydantoin). 21 were also patch tested with MDM hydantoin (1 molecule formaldehyde) in serial dilutions: 7 (33%) reacted to 1 or more concentrations. The other 14 were also tested with DMDM hydantoin (2 molecules formaldehyde) in serial dilutions: 8 (57%) reacted to 1 or more concentrations. Patients patch-test-positive to formaldehyde 0.1% and/or 0.3% tended to show more patch test reactivity to (D)MDM hydantoin than those who reacted only to 1%. Aqueous solutions of (D)MDM hydantoin in concentrations as used in cosmetic products therefore contain enough free formaldehyde to cause dermatitis in a patch test system in some formaldehyde-allergic patients: 12 such patients applied a cream containing 1% DMDM hydantoin to the flexor aspect of the lower arm twice daily for 1 week; 4 (33%) developed dermatitis. The use of a cream containing 0.25% DMDM hydantoin in these 4 patients still caused dermatitis in 1 and provoked itching in another. An increase in the use of DMDM hydantoin in cosmetic products will also inevitable increase the risk of cosmetic dermatitis in consumers allergic to formaldehyde.

Immunocompetent cells in exacerbating untreated psoriasis vulgaris skin lesions were immunophenotypically studied by the application of a selection of monoclonal antibodies in a two-stage immunoperoxidase technique. Epidermal changes include: focal accumulation of immunoglobulins in the stratum corneum, as demonstrated by a mixture of monoclonal anti-kappa and anti-lambda antibodies; focal accumulation of OKM-1 positive but Mo-2 negative cells high in the epidermis, reflecting granulocytes in Munro's abscesses; a marked decrease in epidermal Langerhans cells with focal abnormal clumping and smaller dendrites, as demonstrated by monoclonal anti-HLA-DR and anti-T6 (OKT-6) antibodies; and, sporadic exocytosis of mainly T1 (Leu-1), T8 (Leu-2a) positive suppressor/cytotoxic T lymphocytes. The dermal infiltrates were found to consist mainly of partically activated T1 (Leu-1), T4 (Leu-3a) positive T-helper/inducer cells with a smaller compartment of T1 (Leu-1), T8 (Leu-2a) positive suppressor/cytotoxic lymphocytes. These cells were found in close apposition to T6 (OKT-6), HLA-DR positive Langerhans cells and further accompanied by a minor compartment of OKM-1, Mo-2 positive monocytes. No B-cells or plasma cells could be demonstrated in the dermis. Natural killer cells were observed only incidentally. These results fit best with the hypothesis that psoriasis is a chronic inflammatory condition as a result of persistent stimulation of T cells by immunogen(s) of epidermal origin.

Fourteen T lymphocyte clones (TLC) specific for the contact allergen nickel were prepared either from lesional tissue biopsies or from peripheral blood of patients with allergic nickel-contact dermatitis. Two nickel-specific TLC, obtained from lesional tissue, responded to nickel without the participation of antigen-presenting cells (APC). This direct stimulation by nickel was not restricted by major histocompatibility complex-encoded molecules, since antibodies against HLA class I and II molecules did not block nickel-specific proliferation. Proliferation of other nickel-specific TLC was dependent on the presence of APC and was diversely restricted by HLA class II molecules. With one exception, the restriction determinants were present on HLA-DR and HLA-DQ molecules. Four TLC recognized nickel in association with subtypes of these serologically defined molecules. Five TLC seemed to recognize nickel in the context of highly unusual restriction determinants, since their restrictions could not be explained by the function of single polymorphic HLA class II epitopes. The absence of HLA class II restrictions and the occurrence of deviant HLA class II restrictions in part of the nickel-specific TLC are suggested to result from direct interactions of nickel with critical immune response molecules.