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Summary: Background: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair‐skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. Objectives: To demonstrate noninferiority of BF‐200 ALA (a nanoemulsion gel containing 5‐aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF‐200 ALA was no worse than that for MAL, within a statistical margin of Δ = −15%. Methods: The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5‐year follow‐up. Of 281 randomized patients, 138 were treated with BF‐200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm−2). The results shown include clinical end points and patients’ reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013‐003241‐42). Results: Of the BF‐200 ALA‐treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one‐sided 97·5% confidence interval of −6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%. Conclusions: Treatment of nonaggressive BCC with BF‐200 ALA‐PDT is highly effective and well tolerated with proven noninferiority to MAL‐PDT. It demonstrates low recurrence rates after 1 year of follow‐up. [ABSTRACT FROM AUTHOR]

Prurigo nodularis (PN) is a chronic inflammatory skin disease with nodular itching lesions. UV therapy - both PUVA and NUVB - are known to clear up PN temporarily due to the antipruritic effect of UV light. However, relapse after treatment is common in PN, which means that either long-term therapy is necessary or the treatment protocols have to be optimized to minimize side-effects. The aim of this study was to evaluate the effect that combining bath PUVA and targeted UVB 308 nm excimer radiation has on recalcitrant nodular prurigo. In a prospective trial, 22 patients with PN were treated with either PUVA alone or with a combination of PUVA and excimer UVB. The end point was complete or almost complete remission of PN. Adding a 308-nm excimer UVB to the treatment of the pruritic nodules sped up the healing process; 30% less PUVA radiation was needed. The combination of PUVA and excimer UVB in PN appears to be very efficacious. Reducing psoralen UVA doses by 30% offered long-term benefits in phototherapy of chronic recalcitrant diseases like PN. [ABSTRACT FROM AUTHOR]

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefIned, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocyics arc important for the pat hogenesis of psoriasis. by secretion of pro- inflammatory cytokincs and growth factors in psoriatic skin. IL-I, IL-b. IL-H, [F'N-' and TGF-n are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients Cu = 9) or from healthy controls In - 9). with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. `11W-n and lFN-' levels were elevated in the ethanol-treated psoriatic co-cultures, to 1 50% and 1 75% respectively. hut neither in co-cultures with keratinocytes derived from healthy control individuals nor in rnonocultures. Treatment with ethanol elevated slightly the 114-6 levels in the monocultures from psoriatic and control keratinocytes to 125% hut not in hUT 78 monocultures. In the psoriatic co-cultures. IL-6 levels were elevated in the culture supernatants to almost I 60". but the)' were not influenced by ethanol in co-cultures with control keratinoctes. The cytokine levels of IL-K or EL-I were not significantly influenced in the psoriaticmono- and co-cultures or in HIlT 78 cultures. If ethanol influences the cvtokine secretion of psoriatic keratinocytes and lILT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo. which may explain the aggravation ol this disease in alcohol-c'onsurning psorialic patients. [ABSTRACT FROM AUTHOR]

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Summary: Basal cell carcinoma (BCC), also known as rodent ulcer, is the most common type of non‐melanoma skin cancer worldwide. It affects about 3–10% of people. This study from the U.K. and Germany aimed to find out if BF‐200 ALA gel would work as well as (is non‐inferior to) the already authorised MAL cream in the treatment of non‐aggressive BCC lesions. Both medications are applied topically (on the skin) to the tumour, which is then illuminated with a certified lamp. The illumination causes a chemical reaction that affects the cancer cells so that they eventually die. This kind of procedure is called photodynamic therapy (PDT). Patients in the study were put into the two groups by chance (randomized): 138 in the BF‐200 ALA group and 143 in the MAL group. The treatment scheme for both drugs was the same. Initially, patients had two PDTs one week apart. Four and 12 weeks after the second PDT, patients visited the doctor again, who assessed the treated lesions and patient's health. If all lesions were gone by week 12, the patient entered the 5‐year follow‐up study. In case of remaining lesions, patients received two more PDTs before entering the follow‐up. During the follow‐up, doctors monitor the health of the patients and assess if any of the treated lesions come back. The study found that there was no difference between the two groups, which means that BF‐200 ALA gel worked as well as the already approved MAL cream. In 113 of 121 patients (93.4%) treated with BF‐200 ALA and 101 of 110 patients (91.8%) treated with MAL, lesions disappeared completely. 87% of the BF‐200 ALA‐treated patients rated their satisfaction with the PDT as “very good or good”; 86% of the MAL‐treated patients said the same. Almost all patients experienced mild to moderate local side effects related to the study medications. Common side effects at the application site, which affected more than 1 of 10 patients, were pain, skin reddening (erythema), itching (pruritus), and tissue swelling (oedema). Side effects were similar for both medications. At 12‐month follow‐up, lesions reappeared in 8.4% of the BF‐200 ALA‐treated patients and in 8.5% of the MAL‐treated patients. The follow‐up is still ongoing; further results will be reported after the end of the study. This study showed that BF‐200 ALA gel is as effective and well‐tolerated as MAL cream in the treatment of non‐aggressive BCC. Based on these findings, the European Medicine Agency (EMA) granted approval for BF‐200 ALA for the treatment of non‐aggressive BCC. [ABSTRACT FROM AUTHOR]

Background: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP)., Methods: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012., Results: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments., Conclusions: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

Background: Photoepilation has been an essential field of application of dermatologic laser therapy for many years. The present article evaluates whether the use of a new operation mode of a long-pulsed diode laser can be effective, nearly painless, with few side effects and independent of the skin type. To this aim, its use has been compared to an established method of photoepilation., Material and Methods: In a controlled prospective study with 18 (♀=12, ♂=6) patients aged between 22 and 58 years, the effects of photoepilation with the long-pulsed alexandrite laser and the long-pulsed diode laser, operated in the Super Hair Removal mode (SHR), were compared., Results: The alexandrite laser is slightly more effective with fair skin types; the SHR mode is clearly more effective with dark skin types. Regarding painfulness, the SHR mode is clearly superior. In terms of speed, the two systems are comparable. The alexandrite laser is more user-friendly because of its light and small handpiece., Conclusion: The major advantages of the SHR mode are its effectiveness in dark skin types and its lack of pain. The alexandrite laser is slightly more effective with fair skin types, slightly faster and its handling is considerably more comfortable. None of the two systems has yet brought about a breakthrough with fair hair.

Artificial balneophototherapy is an imitation of the natural balneophototherapy (Dead Sea climatotherapy; DSC) using highly concentrated salt solutions (25%) and UVB radiation. In 2008 the artificial balneophototherapy was included in the German healthcare system as an effective, evidence-based therapy for patients with moderate-severe psoriasis. In contrast, natural DSC is still considered a "non-standard and off-label therapy". Therefore we analyzed all studies published in the past two decades on both artificial and natural balneophototherapy comparing them in effectiveness, length of remission and practicability. Evidence-based studies on DSC showed good clinical results and long remission periods in psoriatic patients; the two methods seem comparable in effectiveness. Patients with chronic, therapy-resistant psoriasis should have access to DSC if they fail routine measures.

UVB 311 nm phototherapy (NUVB) is used successfully in the treatment of psoriasis or atopic dermatitis and is often chosen as "first-line" therapy. In a prospective study we investigated the efficacy of the targeted UVB 308 phototherapy by excimer laser in the treatment of 57 patients with localized, mild therapy-resistant atopic dermatitis. We achieved a complete remission (CR) in nearly 85% and a partial remission (PR) in 15% after 10 treatments during 6-8 weeks in all patients. A mean reduction in patient-reported pruritus was one hallmark after 3-4 treatments. 48 other patients with lichen simplex chronicus Vidal, nodular prurigo, granuloma anulare, alopezia areata (AA) and lichen ruber planus were also treated by targeted NUVB. We found higher rates of CR and PR only in patients with AA and in patients with oral Lichen ruber mucosae. These results and the systematically reviewing of the current medical literature shows that targeted NUVB by excimer laser cannot be successfully transferred for all inflammatory skin diseases. In particular, Excimer UVB treatment expands the therapeutic options in patients with localized and therapy-resistant atopic dermatitis enormously.

Background: Papillomatous intradermal nevi are common acquired melanocytic nevi. Although harmless, they can be - especially on the face - cosmetically disturbing. At selected sites on the trunk, they may be traumatized by clothing, so that patients often wish to have them removed with a low likelihood of recurrence., Material and Methods: In a prospective study with 90 (female symbol=77, male symbol=13) patients aged between 13 and 67 years, 130 intradermal nevi (female symbol=114, male symbol=16) were removed using a combined therapy with CO(2), erbium: YAG and ruby lasers., Results: After therapy, 2.3% of intradermal nevi recurred as a pigmented macule, while 6.9% reappeared as a papule or nodule (volume recurrence). 88% of the patients were very satisfied with the result; 11%, satisfied; and 1%, not satisfied. 99% would undergo the therapy again., Conclusion: The combined laser method (CO(2), erbium: YAG and ruby lasers) for the treatment of intradermal nevi produces excellent cosmetic results, is easily performed, leads to high patient satisfaction and is safe if correctly applied.

Human papilloma viruses (HPV) lead to common warts in 5% of the population and genital warts in 1% of sexually-active individuals. Although about 50% of HPV infections regress spontaneously, the course is uncertain. Expectant waiting often leads to progression and dissemination. Plantar warts may cause pain on walking, while palmar and genital warts may impair social contacts. There are many treatments for warts, including a variety of laser systems. The CO(2) laser is the best ablative approach, producing cure rates of up to 75% for therapy-resistant common warts in cohort and case-control studies. Side effects such as bleeding, pain and reduced function over weeks must be weighed against the likelihood of success. Considering non-ablative approaches, pulsed dye lasers can be used for a selective, non-bloody destruction of extragenital and genital warts and may become the treatment of choice. In prospective randomized studies, they produced cure rates of up to 82% for therapy-resistant warts with few side effects.

Background: Venous lakes of the lip are a cosmetic problem for many patients due to their exposed location, nodularity, fragility and blue color. We sought an effective and well tolerated therapy method., Patients and Methods: Over one year, we treated 20 patients with a combination of diode laser (910 nm) and radiofrequency., Results: In all cases, there was complete regression of the venous lake (average: 1.4 treatment sessions). Side effects were transient pain that was assessed as mild by the patients, and transient swelling. Scarring or hypo-/hyperpigmentation did not occur., Conclusion: This combined approach is a recommended option at least equivalent to other therapy methods (argon laser, CO(2) laser, pulsed-dye-laser, and others), or even superior to them due to the low rates of side effects and low number of treatment sessions.

The development of hand eczema is a relatively commonly seem dermatosis in housewives. In 1986 we presented a first survey of potential contact dermatitis sources for a housewife. Now, we present an update in which we analyse the different contact sources in the household and grade them in comparison to the data of 1986. The results are based on the analysis of a large population of 2633 patients with the occupation "housewife" and the diagnosis "eczema" who have been seen in departments of dermatology belonging to the Information Network of Departments of Dermatology (IVDK).

1. The antiarthritic and anti-inflammatory efficacy of N-acetyl-L-cysteine (NAC) was tested in male DBA/1 hybrid mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index and the phagocytic responses recorded by chemiluminescence in unseparated blood were used for the assessment of disease activity. 2. Mice were immunized by subdermal injection of bovine type II collagen in Freund's complete adjuvant. The treatment with NAC started at day 42 after immunization and was continued over a period of six weeks: in doses ranging up to 50 mg/kg, a dose-dependent suppression of arthritis was noted; between 50 and 200 mg/kg, the inhibition curve had a plateau [ED50 = 50 mg/(kg x day)]. 3. The arthritis index correlated positively with the generation of chemiluminescence by reactive oxygen species (ROS) produced in neutrophils and monocytes activated by 12-O-tetradecanoylphorbol 13-acetate. 4. After treatment with 100 mg/kg of NAC from day 42 after immunization over a period of six weeks, the ROS production was reduced to levels occurring in whole blood of healthy animals. 5. It is concluded that low-molecular-weight antioxidants such as NAC may be adequate for controlling oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.

Background: Periorbital eczema may be an expression of a constitutional disease or an irritant or allergic dermatitis. An allergic contract dermatitis is believed to be the most common cause., Objective: We tried to determine which allergens may cause an allergic contact dermatitis and if there exists a leading allergen., Methods: 609 patients with periorbital eczema were assessed with patch testing in 22 hospitals to evaluate the relevance of an allergic contact dermatitis in the pathogenesis of periorbital eczema. Additionally, 116 patients were tested with their own products., Results: 81% of the cases involving the eyelids were women. A relevant allergic contact dermatitis was found in 52% of the patients with periorbital eczema. Furthermore, a positive patch test was present in every third patient with the clinical diagnosis of an atopic dermatitis. Antibiotics, phenylephrine and thimerosal could be determined to be the leading allergens responsible for allergic periorbital eczema. Positive reactions for potassium dichromate and fragrance mix occurred less frequently in patients with periorbital eczema. 132 positive reactions were found in patients tested with their own products, including 33% with a positive reaction to eye ointments, 15% to face creams, 10% to eye shadows, 10% to makeup, 10% to shampoos and 4% to nail varnish. Only 6% reacted to perfume., Conclusion: The data underline the importance of performing patch tests in the case of periorbital eczema, especially in atopic patients.

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefined, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocytes are important for the pathogenesis of psoriasis, by secretion of pro-inflammatory cytokines and growth factors in psoriatic skin. IL-2, IL-6, IL-8, IFN-gamma and TGF-alpha are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients (n = 9) or from healthy controls (n = 9), with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. TGF-alpha and IFN-gamma levels were elevated in the ethanol-treated psoriatic co-cultures, to 150% and 175% respectively, but neither in co-cultures with keratinocytes derived from healthy control individuals nor in monocultures. Treatment with ethanol elevated slightly the IL-6 levels in the monocultures from psoriatic and control keratinocytes to 125% but not in HUT 78 monocultures. In the psoriatic co-cultures, IL-6 levels were elevated in the culture supernatants to almost 160%, but they were not influenced by ethanol in co-cultures with control keratinocytes. The cytokine levels of IL-8 or IL-2 were not significantly influenced in the psoriatic mono- and co-cultures or in HUT 78 cultures. If ethanol influences the cytokine secretion of psoriatic keratinocytes and HUT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo, which may explain the explain the aggravation of this disease in alcohol-consuming psoriatic patients.

Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P < 0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.

The present study investigates synergistic effects of the TNF-alpha inhibitor thalidomide and the poly(ADP-ribose) polymerase (PARP)-inhibitor nicotinic acid amide (NAA) in male DBA/1 hybird mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index, chemiluminescence and anti-collagen antibody titers were used for the assessment of disease activity: The disease courses demonstrated clearly an inhibitory effect of thalidomide. NAA inhibited established collagen arthritis in a dose-dependent manner. The combined application of thalidomide and NAA caused a powerful synergistic inhibition of arthritis. Furthermore, thalidomide and NAA were tested ex vivo for their inhibition of the NADPH oxidase-dependent generation of reactive oxygen species by activated neutrophils and monocytes in unseparated human blood. Our data show that type II collagen-induced arthritis can be suppressed by the simultaneous inhibition of TNF-alpha, PARP, and NADPH oxidase.

Tumor cell invasion and metastasis are considered to represent a multistep process leading to the degradation of the extracellular matrix by proteolytic enzymes. The functional activity of matrix metalloproteinases (MMPs) is controlled by tissue inhibitor of metalloproteinases-2 (TIMP-2), which has been shown to inhibit tumor cell invasion and metastasis in vitro and in vivo. To assess the role of TIMP-2 in skin-derived epithelial tumors, we have analyzed the expression of TIMP-2 mRNA in primary tissue samples from human cutaneous basal (BCC) and squamous cell carcinoma (SCC) for a correlation with their different invasive and metastatic potential. Comparative quantitative analysis of TIMP-2 mRNA levels by Northern blot hybridization demonstrated significantly higher TIMP-2 tissue levels in BCC than in SCC, indicating an inverse correlation between TIMP-2 expression and the metastatic capacity of these tumors in vivo. By in situ hybridization, tumor stromal cells were identified as the principal source of TIMP-2 mRNA in both BCC and SCC. A comparable distribution has been reported previously for several matrix metalloproteinases in cutaneous BCC and SCC, indicating co-localization of metalloproteinases with their respective inhibitor. These results may suggest that TIMP-2 substantially contributes to the biological behavior of epithelium-derived skin tumors by significantly inhibiting tumor cell metastasis.

FK 506 and cyclosporin A (CyA) are two immunosuppressive drugs which are known to be effective in the treatment of psoriasis by inhibiting the activation of T cells. In contrast, their influence on the proliferation of keratinocytes is discussed controversially. The second messenger cyclic adenosine monophosphate (cAMP) has been regarded as a regulator for cell growth and proliferation for 20 years. Hyperproliferation of many cells and particularly of psoriatic keratinocytes was speculated to be due to a decrease in cAMP levels in the psoriatic epidermis, whereas new findings could not confirm these observations. To clarify this discussion we determined the intracellular cAMP content in isoprenaline-stimulated keratinocytes from psoriatics and controls after treatment with CyA or FK 506. Ethanol and the beta-blocking drug propranolol served as controls. The basal level of cAMP and the response to isoprenaline in psoriatic keratinocytes did not differ from those of controls. CyA dramatically reduced the cAMP level and FK 506 just slightly diminished it in a dose-dependent manner. Both drugs diminished the cAMP level more effectively in the keratinocytes from lesional psoriatic skin than in keratinocytes from controls. These data provide evidence that CyA influences early signal transduction pathways by depressing the intracellular cAMP in keratinocytes. This supports the view of other groups that CyA and perhaps also FK 506 influence not only immuno-competent cells but also keratinocytes in the treatment of psoriasis. Furthermore, it is doubtful that a low cAMP level is a positive regulator for cell growth and the hyperproliferation of psoriatic keratinocytes.

1. The effects of racemic thalidomide (D[+]/L[-] alpha-phthalimido-glutarimide) on acetaminophen (AAP)-induced hepatitis were tested in male NMRI mice (n = 133) and quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). 2. A 2.1-fold increase of GOT and a 1.9-fold increase of GPT activities (P < 0.001) were observed in mice treated perorally with 500 mg/kg of AAP plus 150 mg/kg of thalidomide (Thal). In the absence of AAP, Thal did not display any detectable hepatotoxic effects. 3. The Thal-induced exacerbation of AAP hepatotoxicity was completely inhibited by nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP) (P < 0.0001), suggesting a possible influence of Thal on the hepatic metabolism of NAD-adenoribosylation. 4. We see the main application of nicotinic acid amide as for the combinational use in pharmaceutical preparations of AAP in order to avoid hepatic damage in patients treated with AAP and Thal.

Ras gene mutations have been implicated in the pathogenesis of a variety of human tumors. Mutated ras genes have been isolated from human melanoma cell lines, but subsequent studies indicated that ras gene mutations may be a rare event in melanocytic lesions. Recently, a study reported a high frequency of ras mutations correlated with increasing invasion level. To address this inconsistency in the published data, we analyzed 50 primary melanomas to correlate invasion level, tumor thickness, histologic typing, and body localization with point mutations around codons 12/13/61 of the three ras genes. After micro-dissection of paraffin-embedded tumor tissue, ras gene mutations were analyzed by direct sequencing of tumor DNA amplified by polymerase chain reaction. Only two melanomas exhibited ras gene mutations, one sample containing a transition from A to G at position 2 of N-ras codon 61 and the other exhibiting a transversion from C to A at position 1 and a transition from A to G at position 2 of N-ras codon 61. Both tumors were classified as Clark level IV, with a tumor thickness of 2.5 and 1.2 mm, respectively. Both were typed as superficial spreading melanoma and localized to intermittently sun-exposed body sites. The low frequency of ras mutations in malignant melanoma and the lack of ras mutations in melanoma samples from constantly sun-exposed body sites argue against the hypothesis of ras mutations as a marker of progression in malignant melanoma and the suggestion that ras mutations occur predominantly in melanomas from constantly sun-exposed body sites.

Background: The induction of protein tyrosine kinases (PTKs) is known to be a key element in the activation of lymphocytes., Objective: Because immunologic mechanisms are important in the pathogenesis of psoriasis, we examined the time course of tyrosine-phosphorylated proteins (p-tyr) as a marker for cellular PTK activity in phytohemagglutinin (PHA)-stimulated T cells of psoriatic patients and healthy controls., Methods and Results: PHA-stimulated T cells from both groups expressed peaks of p-tyr after 15 min and 4 h. In T cells from psoriatics, the 15-min peak was smaller but the 4-hour peak reached an enormous maximum, which was 270% higher than the basic p-tyr value. PHA-stimulated T cells were additionally treated with psoriasis-provoking drugs (lithium, chloroquine, propranolol and ethanol) and the two immunosuppressive drugs cyclosporin A and FK 506. Lithium and propranolol were able to increase the p-tyr level after 15 min in PHA-stimulated T cells from psoriatics in contrast to controls. Chloroquine and ethanol did not have a significant effect on T cells of both groups. CsA markedly diminished the phosphorylation of intracellular tyrosines in T cells of psoriatics and controls, whereas FK 506 diminished the p-tyr level in controls only slightly., Conclusion: We have characterized important differences in p-tyr phosphorylation activities of psoriatic T cells compared to controls. This could be a hint to explain the known abnormalities of psoriatic T cells.

Protein tyrosine kinases (PTKs) are closely related to cell growth, proliferation and differentiation. In keratinocytes, various growth factor receptors and cytosolic proteins, including the EGF and IGF receptors, the proteins of the src family and others, exhibit PTK activity. In psoriatic epidermis an increased level of EGF receptors and their ligand TGF-alpha has been found, and this is thought to be one reason for the pathological hyperproliferation of keratinocytes in this disease. Oral treatment with cyclosporin A (CsA) and FK506 or topical treatment with dithranol lead to an improvement in psoriasis. In the present study we examined the effect of these three drugs on the cellular content of phosphorylated tyrosines in highly proliferative HaCaT keratinocytes. HaCaT keratinocytes can be used as a model for highly proliferative epidermis, e.g. psoriatic epidermis. CsA had no effect whereas FK506 and dithranol reduced the phosphorylation of tyrosine residues in HaCaT keratinocytes. The activation of serine/threonine protein kinase C (PKC) is known to downregulate PTKs. Therefore we incubated keratinocytes with the selective PKC inhibitor Ro 31-8220 in addition to the other drugs. Only after the addition of Ro 31-8220 to FK506-treated keratinocytes was the phosphotyrosine (p-tyr) level elevated, but this was only one-third of the increase measured without additional therapeutic drugs. We assume that an induction of PKC alone is not responsible for the reduced p-tyr level after treatment with dithranol and FK506.(ABSTRACT TRUNCATED AT 250 WORDS)