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Background: Despite new treatment options with systemic disease modifiers, topical therapy - especially as combination therapy - plays an important role in psoriasis treatment. Methods: Antipsoriatic efficacy of methylprednisolone aceponate ointment (MPA), tacrolimus 0.1% ointment (FK506) and their combination (MPA+FK506) were investigated in a double-blind randomized pilot study using the psoriasis plaque test. Agents and corresponding placebos were applied once daily under occlusion for 11 days. Test sites were evaluated by sum score (erythema, scaling, infiltration), objective assessment by 20-MHz-sonography and optical coherence tomography (OCT). Results: After 11 days, the sum score significantly improved from baseline value in FK506-treated skin (9.6 vs. 2.9, p < 0.0001). MPA led to a significant improvement of the sum score (9.4 vs. 0.6, p < 0.0001). Combination therapy showed results similar to MPA monotherapy (9.4 vs. 0.4, p < 0.0001). These findings were confirmed by 20-MHz-sonography and OCT data. Conclusion: FK506 is moderately effective in chronic plaque-type psoriasis in our model. Combination therapy with FK506+MPA has no additive effect compared to MPA alone.

Basic research on psoriasis has identified a number of molecular targets which can be of therapeutic interest. While the first two biologics--alefacept and efalizumab--were developed primarily for dermatologists, other agents like cytokine antagonists (TNFα antagonists) were introduced primarily by other medical fields. Knowledge has provided new impulses for research, so that today many therapeutic strategies are being developed, not exclusively limited to biologics. Others branches of dermatology also have benefitted greatly from biologics like ipilimumab or omalizumab.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis vulgaris. Making the diagnosis is not trivial even today. In contrast to older data, relatively high rates of disease progression and joint damage have been found in recent trials. Whether this originates from erroneously included patients with rheumatoid arthritis or true severity of PsA needs to be confirmed. The ClASsification criteria for Psoriatic Arthritis criteria are now widely accepted and used in the setting of clinical studies. Their further validation and development is conducted by Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Correct diagnosis and classification is a prerequisite for valid conclusions from therapeutic and prognostic clinical trials and optimal care for individual patients. This article reviews clinical presentation, diagnostic tools, classification criteria, differential diagnosis and treatment options in PsA.

Psoriasis is a chronic, immune-mediated inflammatory disorder with a genetic background, whose treatment is currently undergoing a paradigm shift. For many patients clinical signs and symptoms of psoriatic skin and joint disease are most important. From the public health perspective, however, recent findings that suggest a high degree of co-morbidity is becoming increasingly relevant. Because it is also highly significant from the patients' perspective, the improvement of health-related quality of life should be considered as the third treatment goal. Modern therapeutic concepts interact with specific pathogenetically relevant molecular targets. The development of such"targeted therapies" reflects our increasing understanding of the pathogenetic principles of psoriasis. Provided that the whole spectrum of approved remedies is employed as indicated, psoriasis has become a condition that is amenable to early intervention and can be treated effectively in the long run.

A 61-year-old patient had a 25-year history of erythematous scaling lesions, diagnosed and treated as psoriasis vulgaris. He presented with a growing nodule within the erythematous plaque. Biopsy shows epithelioid cell granulomas with prominent Langhans giant cells. There was no sign of a squamous cell carcinoma. The tuberculin test was strongly positive and M. tuberculosis complex was detected in the biopsy material by PCR. He was diagnosed with lupus vulgaris, the most frequent form of cutaneous tuberculosis. Other types include tuberculosis verrucosa cutis, tuberculosis cutis orificialis and disseminated military tuberculosis. The patient was treated with rifampicin, isoniazid, pyrazinamide and ethambutol for two months, following a four month treatment with rifampicin and isoniazid. The skin lesions rapidly resolved under antituberculotic treatment.

The scalp is the most common site of disease involvement at the onset and throughout the course of psoriasis. For many patients, psoriasis of the scalp is the most difficult aspect of their disease; yet, despite a wide range of therapy options and an extensive literature base, scalp psoriasis remains difficult to treat, highlighting a long-standing unmet need for the effective treatment of scalp psoriasis. A review of past and current medical literature reveals that a number of interesting therapeutic approaches have been used in the treatment of scalp psoriasis. The diverse and sometimes extreme therapeutic approaches, the marginal benefit of many topical agents, the paucity of controlled studies evaluating the efficacy of topical agents in the treatment of scalp psoriasis and the high level of patient dissatisfaction with currently available treatments for psoriasis all support the need for new, effective and well-tolerated treatment options for scalp psoriasis.

Adalimumab is the first fully human monoclonal antibody against TNFalpha and has been approved for treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Its efficacy for both joint and skin involvement has been confirmed in clinical trials. The recommended dose is 40 mg administered every other week subcutaneously. It may be combined with methotrexate and all topical psoriasis treatment modalities. User-friendly administration devices make self-injection possible. Patients should be evaluated for active/latent tuberculosis and serious infections prior to initiation of therapy. Adalimumab rapidly reduces joint symptoms within a few days. Adalimumab is used for the management of adult psoriatic arthritis patients who have had an inadequate response to disease-modifying antirheumatic drugs. Adalimumab is yet another biological for the treatment of psoriasis. Since the TNFalpha antagonists can be switched if one is ineffective, this agent broadens the therapeutic spectrum.

Morphological and functional properties of the eosinophilic granulocyte (e. G.) feature this haematopoietic stem cell-derived cell type as an important cellular component of defense mechanisms, immunologic reactions and proinflammatory/neoplastic processes. Over the last decade significant advances of the molecular pathophysiology of eosinophilic disorders enable increasingly the distinction between the more common reactive (secondary) and clonal eosinophilia including the hypereosinophilic syndrome. This review features a comprehensive clinical summary of dermatological disorders that are frequently associated with transient or persistent eosinophilia belonging to the reactive eosinophilia. The hypereosinophilic syndrome is a subset of idiopathic eosinophilia frequently associated with major tissue targets as skin, heart and others. Therefore, the hypereosinophilic syndrome has to be considered as important differential diagnosis. Most recently, the identification of selective targets (e. g. IL-5, CD52) has translated into therapeutic approaches with monoclonal antibodies such as mepolizumab, alemtuzumab or SCH55700.

A variety of approaches (in vitro-/ex vivo studies, animal models, human studies and clinical trials) are available to assess compounds with potential antipsoriatic properties. Over the past few years various rodent models that mirror aspects of psoriasis phenotypes and/or pathogenesis have been created (e. g. knockout rodents, xenotransplantation models). Unfortunately these animal models do not reflect the complete pathogenesis of psoriasis. Therefore, screening procedures involving psoriatic lesions in humans are necessary. Even in the era of biologicals, the psoriasis plaque test (PPT) remains an important in vivo tool. In addition to screening potential antipsoriatic substances, the PPT can help answer other questions (frequency of use, dose-response relationship). A prerequisite for correct performance of PPT is knowledge of the toxicological and pharmacological data of the investigational compounds. The PPT is relatively simple, not time-consuming and allows the simultaneous testing of multiple substance. All the results from PPT must be confirmed by controlled clinical trials.

The calcipotriol/betamethasone dipropionate two-compound product Dovobet/Daivobet/Taclonex(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time.To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis.Patients (n = 634) were randomized double-blind to treatment with: (i) 52 weeks of the two-compound product (two-compound group); (ii) 52 weeks of alternating 4-week periods of the two-compound product and calcipotriol (alternating group); or (iii) 4 weeks of the two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). Treatments in all groups were used once daily when required.Adverse drug reactions (ADRs) occurred in 45 (21.7%) patients in the two-compound group, 63 (29.6%) in the alternating group and 78 (37.9%) in the calcipotriol group. The odds ratio for an ADR in the two-compound group relative to the calcipotriol group was 0.46 (95% confidence interval 0.30-0.70; P0.001). ADRs of concern associated with long-term topical corticosteroid use occurred in 10 (4.8%) patients in the two-compound group, six (2.8%) in the alternating group and six (2.9%) in the calcipotriol group; those with the highest incidence were skin atrophy, occurring in four (1.9%), one (0.5%) and two (1.0%) patients, respectively, and folliculitis, in three (1.4%), one (0.5%) and no patients, respectively.Treatment with the two-compound product for up to 52 weeks appears to be safe and well tolerated whether used on its own or alternating every 4 weeks with calcipotriol treatment.

Pancreatic panniculitis is a rare complication occurring in 0.3-3% of patients with pancreatic disease. Clinical features include erythematous painful subcutaneous nodules usually on the lower leg and foot. A 72-year-old man was diagnosed in 2002 with a neuroendocrine carcinoma of the head of the pancreas. In 2003 following surgery and radiation therapy, he developed liver metastases and painful nodules on his legs. Lipase was found to be markedly elevated; amylase and alpha1-antitrypsin were in the normal range. Histopathologic examination of a nodule showed subcutaneous fat necrosis with ghost cells surrounded by an acute inflammatory infiltrate. The pathogenesis of pancreatic panniculitis is unclear. The pancreatic enzyme lipase may induce lipolysis and fat necrosis with secondary tissue inflammation.

Alefacept, a recombinant protein produced by fusion of human LFA(3 )and IgG(1), was the first biologic specially designed and approved for the treatment of psoriasis. Results of clinical trials reveal both an efficacy comparable to established systemic therapies and a high drug safety. A 62-year old male patient with psoriasis and incomplete response to several standard therapies was treated with alefacept (baseline PASI 23.1). After three courses of 15 mg alefacept i.m. weekly for 12 weeks, each followed by a 12 week post-dosing observation period, the PASI regressed to 2.0. Adverse drug reactions were not observed.

Summary Background A two-compound ointment containing calcipotriol 50 µg g−1 and betamethasone dipropionate 0·5 mg g−1 has recently been shown to be an effective treatment for psoriasis. Objectives This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet®/Dovobet®; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 µg g−1 ointment (Daivonex®/Dovonex®; LEO Pharma). Methods In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment. Results The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73·3% for group 1, 68·2% for group 2 and 64·1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55·3% for group 1, 47·7% for group 2 and 40·7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P

In about 60% of cases, atopic eczema can persist in adulthood with distinctive clinical features and disease course. The introduction of the topical calcineurin inhibitors pimecrolimus 1% cream and tacrolimus 0.03 and 0.1% ointment clearly improves the long-term management of atopic eczema in adult patients; this has been shown in several large clinical studies and is confirmed by the growing practical experience with these substances. Topical calcineurin inhibitors are, even when applied for weeks and months, safe, well tolerated and efficient; they have a rapid and positive effect on pruritus and the potential--as shown in clinical studies with pimecrolimus 1% cream--to reduce the number of eczema flares, to significantly prolong the time to a first flare and to reduce or even eliminate the need for topical corticosteroids.

Classical topical treatment regimens in psoriasis including dithranol and corticosteroids are widely used and have been supplemented in recent years by topical vitamin D preparations, by vitamin D analogues and topical retinoids. The combination of these preparations with each other, with UV light or with systemic drugs often lead to improved effectiveness and tolerability when compared with the respective monotherapy. In private offices, the combination of calcipotriol with various corticosteroids is very commonly prescribed for patients with mild to moderate psoriasis. This combination can be sequentially applied twice daily or--in a newly introduced fixed preparation--once daily. In severe psoriasis requiring systemic treatment a concomitant effective topical treatment regimen can greatly improve the overall longtime management in affected patients.

The novel immunomodulatory agent leflunomide exhibits a strong anti-inflammatory action. This isoxazole derivative is chemically unrelated to any hitherto applied immunosuppressants. As a prodrug leflunomide is completely converted to its active metabolite A 77 1726 (M1) which blocks the dihydroorotate dehydrogenase, a key enzyme of the pyrimidine de novo synthesis. Drug-related adverse effects are mild, dose-related and reversible, characterising leflunomide as a safe immunosuppressant. While up to now leflunomide has just been approved for therapy of rheumatoid arthritis, its mechanism of action affects multiple inflammatory pathways, thereby suggesting it to be a potent therapeutic agent in autoimmune diseases, graft rejection, and tumour therapy. First dermatological experience has been gained in psoriasis and bullous pemphigoid. The role of leflunomide in the dermatologist's therapeutic armamentarium will evolve during the next years.

Dapsone (4, 4' diaminodiphenylsulfone) is an efficient antiinflammatory agent. Its therapeutic use may result in a variety of adverse effects. The most frequent unwanted reactions are hemolytic anemia and methemoglobinemia. By oral route dapsone is mainly metabolized to monoacetyldapsone (MADDS) and hydroxylamine dapsone (DDS-NOH). We report a 76-year-old female patient with linear IgA dermatosis who developed a dapsone-induced photosensitivity 8 weeks after initiation of sulfone therapy. She showed a widespread erythematous eruption in UV-exposed skin area. After clearing of skin lesions the photopatch test revealed positive reactions to dapsone, MADDS and DDS-NOH. Dapsone-induced photosensitivity to date has been described only in leprosy patients. We demonstrate for the first time that this adverse reaction is not restricted to leprosy and that dapsone metabolites may also contribute to the mechanism of photosensitivity like the parent sulfone. Dapsone-induced photosensitivity is a rare, not dose-related adverse effect of the sulfone and can also occur in patients with inflammatory skin disorders.

Nail changes often represent diagnostic hallmarks for a variety of systemic diseases. The awareness of drug-induced nail injuries is important in order to avoid unnecessary diagnostic activities. We observed a 21-year-old female patient with Hodgkin's lymphoma, who developed transverse leukonychia of all fingernails associated with polychemotherapy.

Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pre-treated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.

Histamine H1 receptor antagonists are a mainstay in the management of chronic/chronic recurrent urticaria (c./c.r.U.). Since experimental studies have confirmed the presence of cutaneous H2 receptors partially conflicting results have been reported on the use of H2 antagonists in c./c.r.U. 20 patients with c./c.r.U. of idiopathic type were treated with cimetidine plus clemastine or placebo plus clemastine in a double-blind crossover study. Before this treatment traditional H1 antagonists alone failed to show any satisfying therapeutic effect. The results reveal that combined therapy is statistically more effective than corresponding H1 antagonists alone (P = 0.001). The addition of cimetidine is proposed in patients with c./c.r.U. if conventional therapy has been tried and proven ineffective.

Systemic corticosteroids play a predominant role in the treatment of urticarial vasculitis (U.V.). If steroids are contraindicated, there may be applied a variety of pharmacologically different compounds. A female patient suffering from U.V. and metabolic syndrome, who had not shown any positive response to indomethacin, H1 and H2 antagonists, or colchicine, was treated with dapsone. As a result, the clinical symptoms improved within a few days and her hypocomplementemia normalized. We discuss the possible mechanisms of action of sulphones in U.V.

Chloroquine and chloroquine derivatives have proved successful in the therapy of REM syndrome (REMS). Alternative treatment schedules have not been described so far. In a female Patient, chloroquine therapy had to be discontinued because of ophthalmologic contraindication. PUVA therapy induced complete remission, whereas dapsone alone only led to incomplete improvement. Additional UV radiation--mainly UV-A--had a positive effect. Chloroquine contraindication justifies the use of these alternative therapeutic approaches to REMS.

A 25-year-old woman with progressive systemic sclerosis was treated with D-penicillamine. (DPA) 30 days after starting therapy cholestatic jaundice was observed. Moreover, for two years she has taken the pill. Both drugs were discontinued, the jaundice disappeared and the laboratory findings of liver became normal. A rechallenge of D-penicillamine after 9 months induced no reaction. An underlying chronic liver disease before cholestasis could be excluded by liver biopsy. Allergic cutantests and lymphocyte transformation test with D-penicillamine and penicillin gave normal results. The frequency of cholestatic jaundice caused by DPA-therapy is discussed and the possible pathomechanism analyzed.A 25 year old woman with progressive systemic sclerosis was treated with D-penicillamine (DPA). 30 days after the initiation of therapy, cholestatic jaundice was observed. Moreover, for 2 years, the patient has taken the pill. Both drugs were discontinued, the jaundice disappeared, and the laboratory findings of the liver were normal. A rechallenge of DPA after 9 months induced no reaction. An underlying chronic liver disease before cholestasis could be excluded by liver biopsy. Allergic cutantests and lymphocyte transformation test with DPA and penicillin gave normal results. The frequency of cholestatic jaundice caused by DPA therapy is discussed and the possible pathomechanism is analyzed. (author's modified)