Treatment of acute graft-versus-host disease with PUVA (psoralen and ultraviolet irradiation): results of a pilot study.

Acute graft-versus-host disease (aGVHD) is a frequent and major complication after allogeneic stem cell transplantation. For many years psoralen and ultraviolet (UV)-A light have been used in the treatment of chronic cutaneous graft-versus-host disease, but few patients have received PUVA therapy for aGVHD. We assessed 20 patients who received PUVA therapy for acute cutaneous GVHD (grade 2-4). Seven patients showed additional organ manifestations (liver, gut). To better quantify the cutaneous lesions, a new scoring system was introduced: intensity of erythema (0-3) x %body surface + size of bullae (4-5) x %body surface affected. All patients received prednisolone and PUVA for treatment of aGVHD. Fifteen patients (75%), 12 with manifestations restricted to the skin, responded by score classification (average time to a 50% score reduction: 39 days) and reduction of the dosage of prednisolone (average time to a 50% prednisolone reduction: 35 days). PUVA treatment was well tolerated and might play a role in the therapy of acute cutaneous GVHD.

Anaphylactic reaction to bovine serum albumin after embryo transfer.

OBJECTIVE: To increase the awareness of bovine serum albumin (BSA) sensitivity as a potentially lethal complication during ET. DESIGN: Case report. SETTING: Routine ET in university hospital. PATIENT(S): A 26-year-old woman who was undergoing her first ET. INTERVENTION(S): ET with BSA containing standard fluid medium. MAIN OUTCOME MEASURE(S): Specific immunoglobulin (Ig) E antibodies and skin tests. RESULT(S): The patient demonstrated increased levels of specific IgE antibodies to BSA and a clearly positive scratch test for BSA. CONCLUSION(S): Anaphylactic reactions to BSA can occur during ET. The risk can be reduced substantially if a detailed medical history is obtained.

Langerhans' cells in skin tumors.

DESIGN: We studied 58 skin specimens of normal skin (NS), basal cell epithelioma, squamous cell carcinoma, seborrheic keratosis, and malignant melanoma for the presence of Langerhans' cells (LCs) in and above the tumor. Anti-CD1 was used as a marker for LCs. All specimens were also incubated with anti-CD4, which also labels a certain number of LCs. RESULTS: All tumors contained LCs in the tumor and overlying epidermis. The number of LCs over basal cell carcinoma, squamous cell carcinoma, and malignant melanoma was significantly lower than in normal skin and seborrheic keratosis. These results are presented in detail and are compared with former studies discussing the different methodological approaches. CONCLUSIONS: Langerhans' cells were present in the epidermis of all the examined tumors. A certain percentage of LCs express CD4 surface antigen. This percentage varies from tumor to tumor.

Lymphocyte proliferation during PUVA therapy.

The lymphocyte proliferation of 15 psoriatic patients was sutdied after stimulation with tuberculin, trichophytin, varidase, concanavalin A (Con A), and pokeweek mitogen (PMW) during the first and the eighth PUVA treatment, 2 h after oral intake of 8-methoxypsoralen (8-MOP), immediately after UVA-irradiation, and 24 h later. There was a significant decrease of the lymphocyte proliferation, after stimulation with Con A (P less than 0.05), trichophytin (P less than 0.01) and varidase (P less than 0.05), not with PWM and tuberculin, during the first PUVA treatment by 8-MOP alone. This decrease was not significantly changed by the following UVA irradiation and could not be demonstrated after 24 h. No dark effect of 8-MOP on the lymphocyte proliferation could be seen during the eighth treatment. 8-MOP seems to influence lymphocyte proliferation in the dark by interfering with the cell surface, not with the nucleus. The disappearence of this effect during PUVA therapy could be explained by a modification on the surface structure of lymphocytes.

Dark effect of 8-methoxypsoralen (8-MOP) on lymphocytes.

In order to find, whether 8-MOP has an inhibiting effect on the proliferation of lymphocytes in the dark, we studied in vitro the lymphocyte proliferation by a mitogen (HgCl2) and by an antigen (tuberculin) from 16 psoriatic patients during the first oral PUVA treatment immediately before 8-MOP intake (03.--0.5 mg/kg body weight), 2 h later (time of maximal serum concentration) and after 24 h. The percentages of B- and T-lymphocytes were measured from 15 other psoriatic patients at equal times. There was a significant decrease (P less than 0.05) of the lymphocyte proliferation after stimulation with HgCl2 in culture, 2 h after 8-MOP, returning completely to the starting range after 24 h. On the contrary, neither the proliferation capacity of lymphocytes after stimulation with tuberculin nor the percentages of B- and T-lymphocytes were significantly changed. Obviously, 8-MOP, even without UVA irradiation, has a direct inhibiting effect on lymphocyte proliferation in concentrations therapeutically used. However, this effect is seen only with stimulation by a mitogen, not by an antigen. It cannot be explained by a change in the ratio between B- and T-lymphocytes.

[Lymphokine activity in mercury stimulated leucocyte cultures (author's transl)]. / Lymphokin-Aktivität im Uberstand Quecksilber-simulierter Leukozytenkulturen

Blood-lymphocytes from 42 persons reacted, as expected, in the leucocyte-culture with an increased DNA-synthesis, measured by the uptake of tritiated thymidine during the last 16 h of a five days culture, if mercurybichloride was added at the onset of culture. The logarithms of the activity-indices were nearly symmetrically distributed. When the lymphokine-activity in the culture supernatants was studied with the indirect leucocyte-migration-test, using autologues leucocytes, there was a bimodal distribution of the logarithmic migrationindices with a high top in the negative area (migration-inhibition) and a lower one in the positive area (migration-stimulation). These phenomena had no detectable correlations to sex, age, or dermatosis of the patients.

[Mitogenic activity of melanoma extracts in leucocyte cultures (author's transl)]. / Mitogene aktivität von Melanomextrakten in Leukocytenkulturen

From a mixed cell suspension of five primary melanomas an aqueous sterile extract was made and added to homologue leucocyte cultures of eight melanoma patients and seven controls. The extract had a blastogenic and mitogenic effect in all cultures. There was no significant difference between the responses of patients and controls. In experiments with an equally prepared extract of normal skin, added to homologue leucocyte cultures of nine persons, none but one had a positive reaction. This indicates, that the motigenic principle of the melanoma extract is not related to the histocompatibility antigen nor caused by chemical or bacterial contamination of the primary cell suspensions. It seems to be derived from the cytoplasmic fraction of melanoma cells. Other experiments to solve the problem were impossible because of lack of material. There are several reports in the literature which by using different methods indicate, that there might be an immunological reaction to melanoma associated principles in healthy persons, too.

[Cutaneous granulomatous cladosporiosis]. / Kutane granulomatöse Cladosporiose

The case of a 41 year old man with a tumorlike cutaneous cladosporiosis on the fifth right finger is described. Histologically seen there was an unspecific granulomatous inflammatory cellular infiltrate in the upper and middle corium, whereas in the deeper corium there were found big macrophages phagocytizing fungical elements pointing to cladosporiosis. The fungi grew up very slowly at a temperature of 30 degrees C. Since 1971 the patient was suffering from a "symptomatic" epilepsy medicamentally controlled. Though a neurotropic action of some cladosporion species is well known there could not be found any hint for a cerebral abscess.

[Pityrosporum orbiculare in acneiform eruptions]. / Pityrosporum orbiculare bei akneiformen Eruptionen.

Six patients with acneiform eruptions in the predilection sites of pityriasis versicolor are briefly described. Histologically there were abscesses below the acroinfundibulum wherein yeasts could be found with the characteristics of pityrosporum orbiculare. The possible pathogenity of these fungi is discussed.

[Edematous swelling of the eyelids caused by contact allergy]. / Odematöse Schwellung der Augenlider durch Kontaktallergie.

Cosmetics and ophthalmological topical preparations are the main causes of allergic contact eczema about the eye. In most cases, clinical signs are conjunctival injection, blepharitis, periorbital dermatitis and edema of lids, often combined with itching. Pure edematous swelling of the eyelids should not immediately be blamed on a contact allergy, but sufficiently evaluated to exclude a benign or malignant process of the eyelids, orbita, lacrimal duct and paranasal sinus. We present a patient with pure edematous swelling of the eyelids due to a contact allergy by the sympathicomimetic phenylephrine hydrochloride, an uncommon allergen.

[Subcutaneous panniculitic T-cell lymphoma]. / Subkutanes pannikulitisches T-Zell-Lymphom.

Subcutaneous panniculitic T-cell lymphoma is categorized as a subtype of peripheral T-cell lymphoma. Patients typically present with nontender subcutaneous nodules. The characteristic histologic features include the presence of atypical lymphocytes and benign macrophages that infiltrate between the adipocytes of the subcutis mimicking panniculitis. We report a 75-year old patient with a three week history of asymptomatic subcutaneous nodules. The diagnosis of subcutaneous T-cell lymphoma was confirmed by immunohistological and molecular biological studies. Chemotherapy had to be interrupted due to a rapid worsening of the patient's general condition. She died few weeks after confirmation of diagnosis.

[Benzoyl peroxide for the treatment of badly healing leg ulcers. A double-blind study (author's transl)]. / Benzoylpeoxyd zur Therapie schlecht heilender Ulcera cruris. Eine Doppelblindstudie.

According to reports in the literature and the results of our own double-blind trial benzoyl peroxide at a 20% concentration in an oil-in-water emulsion (Benoxyl 20) is a very effective medication especially in problem ulcers. The benefit probably outweighs the considerable dangers of application in the indication mentioned which may consist of a selection of certain gram-negative organisms and an epicutaneous sensitization.

Reduction of minimal erythema dose by sweating.

BACKGROUND/AIMS: Solar ultraviolet (UV) radiation is the most important environmental risk factor for melanoma and non-melanoma skin cancer. It is known that tap water and saltwater baths have a photosensitizing capacity in subsequent UV irradiation of the skin. The aim of the present study was to determine the influence of sweating from heat or from physical activity on the photosensitivity of the skin. METHODS: Minimal erythema dose to ultraviolet B (MED/UVB) was determined on the inner forearms of 22 healthy volunteers with a Saalmann Multi-tester. Sweating had been provoked by heat (sauna for 10 min) and, on another occasion, physical exercise (jogging for 15 min) followed by MED/UVB testing in a similar way. RESULTS: Compared to baseline MED/UVB there was a highly significant decrease in MED/UVB of up to 31.6% (median 15.8%, mean 15.9% +/- 10.0) after 10 min in the sauna and up to 40.9% (median 16.3%, mean 17.2% +/- 12.5) after 15 min jogging (P < 0.0001). CONCLUSION: Sweat influences the hydration of the horny layer of the skin, resulting in a decrease in reflection and dispersion of UV light. Moderate physical activities such as jogging and/or heat may facilitate erythema reaction. By sweating, outdoor workers and people practicing outdoor sports who are exposed to considerable amounts of solar UV radiation further increase their risk of sunburn.

Effects of 8-methoxypsoralen (8-MOP) and UVA on human lymphocytes.

Peripheral lymphocytes of 37 psoriatic patients are tested before and under PUVA treatment using as parameter the non specific stimulation effect of HgCl2 (10 microgram/ml) in culture, measuring the 3H-thymidine incorporation after the last 16 h of a 5-days culture. Oral 8-MOP in therapeutic doses is decreasing the lymphocyte stimulation as well as 8-MOP together with UVA irradiation during the first week of treatment. After 1 week, the stimulation is, on the contrary, significantly enhanced after irradiation. Lymphocytes isolated by centrifugation over Lymphoprep are submitted to PUVA conditions in petri dishes (Hank's solution 8-MOP 1 microgram/ml, irradiation with 350 nm, 93-372 mJ/cm2). The total cell number, the E-rosette formation (as marker for T-lymphocytes) and the EAC-rosette formation (as marker for B-lymphocytes) are determined. PUVA conditions have an energy dependent decreasing effect on the cell number, while the T- and B-cell proportions remain constant. UVA irradiation alone has such an effect only with high energies. 8-MOP without UVA has no significant influence on the cell number.

[Effects of UV-C and of 8-MOP + UV-A on the T- and B-population of human lymphocytes in vitro (author's transl)]. / Wirkung von UV-C und von 8-MOP + UV-A auf die T- und B-Population menschlicher Lymphocyten in vitro.

The transformation of UV-C irradiated leucocytes and lymphocytes by the mitogens Con A, PHA and PWM is measured by the 3H-Tdr. incorporation after 72 h incubation. Furthermore T- and B-cells are determined by the method of rosette formation. A clear inhibition of the cell activity is seen after irradiation of leucocytes with 450 mJ/cm(2) and of a lymphocyte suspension with 5-10 mJ/cm(2). There are no significant differences between the effects of the various mitogens. The number of T-cells decreases proportionality to the various intensity, the number of B-cells remain constant. Irradiation with UV-A + 8-MOP cause, equally for all mitogens, a dosis dependent inhibition of thymidine incorporation.

[Anaphylactic reaction to human insulin. Successful desensitization]. / Anaphylaktische Reaktion auf Humaninsulin. Erfolgreiche Hyposensibilisierung.

A 48-year-old woman with diabetes mellitus (type IIb) had to be treated with insulin because of poor blood-sugar control. Infiltrates at the sight of injection occurred with two different porcine insulin preparations, necessitating a switch to human insulin. After the third injection of the latter an anaphylactic reaction developed within minutes. During a pregnancy in 1968 the patient had briefly received bovine insulin. Tests now revealed an immediate-type allergy against all three available species insulins, which was successfully treated by hyposensitisation.

Hymenoptera-venom-induced upregulation of the basophil activation marker ecto-nucleotide pyrophosphatase/phosphodiesterase 3 in sensitized individuals.

BACKGROUND: Bee and wasp venoms are potent allergens capable of inducing severe clinical reactions. To detect immediate-type hypersensitivity to these allergens, a rapid in vitro test was developed that relies on the upregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 3 (E-NPP3) on activated basophils. METHODS: Blood basophils of 13 healthy donors and 22 patients allergic to bee or wasp venom were analyzed for E-NPP3 (CD203c) expression using monoclonal antibody 97A6. Basophils were analyzed by flow cytometry after activation with anti-IgE antibody or allergen. Venom-induced E-NPP3 upregulation on basophils was compared with diagnostic parameters, including skin tests and assessment of specific IgE. In selected samples, the increase in E-NPP3 expression on activated basophils was compared with histamine release and CD63 upregulation. RESULTS: In 20/22 patients sensitized to wasp or bee venom, E-NPP3 expression on basophils was upregulated in response to activation by allergen or anti-IgE. The maximum increase in E-NPP3 expression (above ten times of baseline) was achieved after 15 min of stimulation with 1 microg/ml of allergen or anti-IgE antibody. Sensitized individuals who failed to upregulate E-NPP3 in response to IgE receptor cross-linking also failed to induce histamine release and CD63 upregulation. CONCLUSIONS: Flow cytometric determination of hymenoptera-venom-induced upregulation of E-NPP3 is a novel in vitro test to identify sensitized individuals.

Granulomatous mycosis fungoides: report of a case with some histopathologic features of granulomatous slack skin.

We describe a case of granulomatous mycosis fungoides, tumor stage, mimicking sarcoidosis in an 82-year-old man with a 2-year history of skin disease. The final diagnosis was established after one of seven biopsy specimens showed a nongranulomatous histologic picture of patch-stage mycosis fungoides. Monoclonality was proven for the lymphocytic population by T-cell-receptor rearrangement studies. The unusually extensive granulomatous inflammation with huge giant cells surrounded by CD1a-positive cells in the other six biopsy specimens was suggestive of the histopathology of granulomatous slack skin, another rare granulomatous cutaneous T-cell lymphoma. Because both a clinical and histologic overlap between granulomatous mycosis fungoides and granulomatous slack skin have been reported in the literature, we conclude that they may belong to the spectrum of a single disease.

Collaborative clinical assay of the biological potency of allergen skin-test extracts.

A multicentre collaborative clinical trial has been made at one centre in each of six countries to decide if the potency of allergen extracts can be determined satisfactorily by skin-prick tests in man. Although there was considerable variation in potency of antigen when determined in different patients, if a sufficiently large group (n = 54) of persons were tested, it was shown to be feasible to compare potencies of sequential batches of the same specificity, and also of antigens of different specificities. It was shown that batches of mite extract were weaker than that of a grass pollen, but it proved to be a simple matter to adjust the concentration to give the same biological potency.