Chronic Psoriasis Research Articles

MS010153—The psychosocial adjustment of people with chronic psoriasis

MS010153—The psychosocial adjustment of people with chronic psoriasis

MS010153—The psychosocial adjustment of people with chronic psoriasis

MS010153—The psychosocial adjustment of people with chronic psoriasis

MS01053-The psychoscocial adjustment of people with chronic psoriasis

MS01053-The psychoscocial adjustment of people with chronic psoriasis

Management of palmoplantar pustulosis

Palmoplantar pustulosis or chronic palmoplantar pustular psoriasis (PPP) is an uncommon but disabling and recalcitrant pustular dermatosis affecting the palms and soles. Its onset is strongly linked to cigarette smoking and once it is established it tends to progress gradually over years or decades. Its relationship to psoriasis is disputed. Treatment is unsatisfactory and many different therapeutic manoeuvres have been advocated. We have performed a Cochrane systematic review of PPP in order to assess the evidence for efficacy of treatments for PPP. Randomized controlled trials (RCTs) of interventions for PPP were sought by interrogating the Cochrane Controlled Trials Register, Medline and Embase for the terms (PALM* or PLANT* or SOLE* or BACTERID) and (PUSTUL* or PSORIA*). Additional searches were undertaken by cross-checking with two databases of psoriasis trials collated in our department and by the European Epidermo-Epidemiology Network (EDEN). We found 23 RCTs that met our inclusion criteria. These comprised eight trials of systemic retinoid monotherapy [six vs. placebo, one vs. psoralen photochemotherapy (PUVA), one comparing two retinoids]; four trials of PUVA or retinoid-PUVA (two PUVA vs. placebo, two PUVA vs. PUVA plus systemic retinoid); two trials each in which cyclosporin, hydroxyurea, a tetracycline or colchicine was compared with placebo; one trial of Grenz ray therapy vs. placebo; and two trials of topical corticosteroids under hydrocolloid gel occlusion compared either with steroid alone or with additional PUVA therapy. Many of the studies were of short duration with small numbers of participants. Outcome measures used varied considerably between studies. The following interventions were shown to be significantly better than placebo in reducing disease severity scores in PPP: etretinate, liarazole, PUVA using oral psoralen, low dose cyclosporin, Grenz ray therapy, tetracycline antibiotics. Acitretin was of equal efficacy to etretinate. Overall however, few patients achieved good or excellent results. Potent topical corticosteroids were shown to be more effective if used under occlusion. The addition of PUVA to such therapy was of no extra benefit. No RCT of methotrexate therapy was found but evidence from one open study suggests that it is of limited efficacy. The following interventions were also of no or minimal benefit: PUVA using topical psoralen, hydroxyurea, colchicine. The best results were achieved with systemic retinoid therapy both on its own (40% good or excellent response) and in conjunction with oral PUVA (68% clearance) when it was more effective than topical or oral PUVA alone. The value of systemic retinoids for long-term therapy is, however, diminished by their side-effects. The ideal therapy for PPP remains elusive.

In Brief

Superantigens play a significant role in clinical disorders ranging from acute toxic shock syndrome to chronic psoriasis and eczema. These molecules are pro-inflammatory agents that activate the T-cell transcription factor nuclear factor (NF)-κB. Such activation is normally inhibited to some extent by an inhibitory protein, inhibitor of κB (IκB). Recent studies show that the levels or half-life of IκB can be increased by reducing its degradation by the proteasome system. The effect of proteasome inhibition is to reduce the effects of NF-κB. Inhibiting the proteasome using derivatives of lactacystin, such as PS-519, has been tested in a human SCID murine model of psoriasis, in which it reduces inflammatory responses in vivo and in vitro, improving the psoriasis. For T-cell-mediated disorders, such as those initiated by superantigens, this offers a potential route for treatment that differs from the current immunosuppressives. J. Clin. Invest. (2002) 109, 671–679 CM

Beyond our pages

Beyond our pages

Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis.

Infiltration of the skin by pathogenic T cells is regarded as a key factor in the development of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. To investigate whether T cells containing cytotoxic proteins may contribute to the generation of skin inflammation in these skin diseases. Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD (n = 8) and psoriasis (n = 6), and from non-atopic controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by immunohistochemistry. A significant enhancement of perforin and granzyme B expression was observed in lesional AD skin as compared with normal skin, non-lesional AD skin and psoriasis. Expression of these cytotoxic proteins was also increased in psoriasis as compared with normal skin and non-lesional psoriatic skin. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells located in the perivascular infiltrate. In AD increased numbers of positive cells were also observed focally at sites of spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. Our data suggest that cytotoxic CD4+ and CD8+ T cells containing perforin and granzyme B may play an integral part in eliciting cutaneous inflammation in AD.

Assessment on effect of treatment of chronic plaque type psoriasis by combination therapy of composite Shendi ("Equation missing" ) Decoction and Diyin ("Equation missing" ) Tablet) Tablet

To seek for a better therapy for chronic plaque type psoriasis. The effect of 35 patients in the tested group treated with combination therapy of composite Shendi Decoction (CSDD) and Diyin Tablet (DYT) was observed and compared with the effect of those treated by CSDD alone (25 cases) or by DYT alone (18 cases) as the control groups. The total effective rate in the treated group was 94.29%, and that in the two control groups was 88.00% and 83.33% respectively. The markedly effective rate in the treated group was 62.86%, and that for the control group was 36.00% and 27.78% respectively. Ridit test showed significant difference among the effectiveness in the three groups, while chi 2 showed the difference of the total effective rate in the three groups was insignificant, but that of the markedly effective rate was significant. Serum IL-8 and plasma endothelin levels of 11 cases in the treated group were examined before and after treatment, the results showed that both the two parameters were reduced after the combination therapy. The effect of combination therapy of CSDD and DYT was better than that of CSDD or DYT alone, therefore, it is worth further studying and spreading.

SDZ ASM 981

SDZ ASM 981 is an anti-inflammatory macrolactam which binds with high affinity to macrophilin-12. The resulting complex inhibits calcineurin, thus blocking the synthesis of inflammatory cytokines. Twice daily application of topical SDZ ASM 981 1% cream was effective in the treatment of atopic dermatitis in adults and children in clinical trials. Summarised results from 260 patients with atopic dermatitis indicate that the efficacy of SDZ ASM 981 is dose dependent. The highest concentration evaluated (1% cream) was not as effective as betamethasone valerate 1% cream in this 3-week trial. The efficacy of SDZ ASM 981 and clobetasol ointments, used under occlusion, did not differ significantly in 10 patients with chronic psoriasis. Likewise, SDZ ASM 981 0.6% and betamethasone valerate 1% creams were similarly effective in 66 patients with allergic contact dermatitis. Concentrations of SDZ ASM 981 in the blood during topical treatment were invariably below 2.1 microg/L. Oral SDZ ASM 981 20mg or 30mg twice daily were effective in a dose dependent manner in the reduction of psoriasis in adults with no evidence of adverse effects. SDZ ASM 981 was well tolerated in the available trials, exhibiting no potential for systemic adverse reactions and no atrophogenic potential, a problem commonly associated with corticosteroid treatment.

Assessment of perforin expression in peripheral blood lymphocytes in psoriatic patients during exacerbation of disease.

There are very few data concerning the role played by cell-mediated cytotoxicity, particularly at the molecular level, in the course of psoriasis. Both cytotoxic T lymphocytes (CTL) and natural killer cells contain in their granules the cytolytic protein perforin, a mediator in cell-mediated cytotoxicity reactions. The aim of this study was to analyze perforin expression in various sets and subsets of perforin-positive peripheral blood lymphocytes in 17 patients with chronic psoriasis vulgaris in the exacerbation phase. The results were compared with those of an age- and sex-matched healthy control group (n = 21). Perforin (intracellular antigen) and cell surface antigens were detected using the simultaneous double-staining method. We found a significant increase in perforin (P) expression in the patient group for CTL (CD3+P+ cells), which are located mostly in the CD8+ population of T lymphocytes (CD8+P+).

Psoriatic eruption in Kawasaki disease

We describe 10 patients who developed a psoriatic skin eruption during either the acute or convalescent phase of Kawasaki disease. The skin eruption was pustular in 3 patients, but more typical psoriasiform skin lesions were seen in the remaining 7 patients. No patient has yet developed chronic psoriasis. (J Pediatr 2000;137:578-80)

Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds

Degradation of angiogenic mediators might be an underlying cause of chronic wounds. To test this hypothesis, we evaluated the expression and integrity of vascular endothelial growth factor, a potent angiogenic mediator, and its receptors, Flt-1 and KDR, in chronic venous leg ulcerations. Immunohisto- chemical, in situ hybridization, and semiquantitative reverse transcriptase polymerase chain reaction analyses all indicate that expression of vascular endothelial growth factor is elevated in ulcerative tissue, with vascular endothelial growth factor mRNA being especially pronounced in the hyperplastic epithelium of the wound margin. Flt-1 and KDR protein and mRNA were detected in the papillary vessels in close vicinity to the lesional epithelium of chronic wounds. Although increased expression of vascular endothelial growth factor protein was detected in the epidermis, the intensity of this staining was weak compared with the epidermal staining in psoriatic lesions and compared with the strong vascular endothelial growth factor mRNA signal in chronic wounds and psoriasis. To analyze whether this apparent decrease in immunoreactivity could be the result of degradation of vascular endothelial growth factor by proteolytic activities from the wound environment, we examined the stability of recombinant vascular endothelial growth factor in wound fluid from chronic leg ulcers. As demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, incubation of rVEGF165 with chronic, but not acute, wound fluid resulted in rapid proteolytic degradation of rVEGF165. Protease inhibitor studies indicate that serine proteases, such as plasmin, are involved in this degradation. Together, our data show that, although vascular endothelial growth factor expression is elevated in chronic wounds, increased proteolytic activity in this environment results in its degradation, which may contribute to an impaired wound healing response.

Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis

Objective No specific therapy exists for autoimmune diseases caused by self-reactive lymphocytes. As shown in experimental animals, which led to pilot clinical studies, elimination of self-reactive lymphocytes can be accomplished with high-dose chemoradiotherapy, followed by autologous stem cell transplantation, by re-establishment of unresponsiveness to self antigens of newly generated lymphocytes, due to a mechanism of central clonal deletion. We hypothesized that self-reactive lymphocytes causing autoimmune disease may be successfully eliminated by highly immunosuppressive yet not necessarily myeloablative conditioning in conjunction with allogeneic blood stem cell transplantation, since immunocompetent alloreactive lymphocytes of donor origin can effectively eliminate residual host-type hematopoietic cells, self-reactive lymphocytes included, by a mechanism that resembles graft-vs-leukemia (GVL) effects. The present report is an attempt to confirm the existence of graft-vs-autoimmunity (GVA) effects in parallel with amplification of the alloreactive potential of donor lymphocytes following allogeneic non-myeloablative stem cell transplantation (NST). Methods We identified a patient with severe psoriatic arthritis who also had Philadelphia (bcr/abl) positive chronic myelogenous leukemia and therefore was fully eligible for NST. Both diseases responded initially to non-myeloablative conditioning involving fludarabine 30 mg/m 2 × 6, anti–T-lymphocyte globulin 10 mg/kg × 4, and busulfan 4 mg/kg × 2. Results The initial NST procedure was uneventful and resulted in elimination of all signs of autoimmunity (psoriasis and arthritis). Recurrence of polyarthritis and exacerbation of psoriasis were observed in parallel with a significant increase in the proportion of male (host) DNA, and 5% of the mitoses were bcr/abl positive, indicating an increase in the clone of CML. Both bcr/abl-positive cells identified by RT-PCR and psoriatic arthritis were successfully eliminated following discontinuation of anti-GVHD prophylaxis with cyclosporine A (CSA), which resulted in activation of the alloreactive potential of donor T cells, accompanied by graft-vs-host disease (GVHD), suggesting the existence of GVA effects. RT-PCR for bcr/abl remains consistently negative for nearly 3 years, and all DNA remains donor type. Conclusions The response of autoimmune disease manifestations to GVA effects in parallel with elimination of all host-derived hematopoietic cells supports our working hypothesis that autoimmune diseases caused by self-reactive lymphocytes may be effectively treated by elimination of alloreactive self-reactive lymphocytes following induction of host-vs-graft tolerance, in analogy with replacement of malignant or genetically abnormal host cells following DLI. It is therefore suggested that intentional GVA effects may be inducible by DLI following a conventional or preferably safer non-myeloablative regimen in recipients with life-threatening autoimmune diseases resistant to conventional modalities. Adoptive immunotherapy of autoimmunity may thus involve a two-step procedure: first, inducing host-vs-graft and graft-vs-host transplantation tolerance through a transient stage of mixed chimerism; second, inducing controlled GVA effects, initially by discontinuation of CSA and then, if indicated, by late outpatient DLI to eradicate residual hematopoietic cells of host origin.

Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil

Mycophenolate mofetil (MMF), a widely used immunosuppressant in organ transplantation, is a recent addition to the therapeutic armamentarium of autoimmune and inflammatory skin disorders in dermatology. We describe 5 patients with moderate to severe chronic plaque psoriasis and 6 patients with psoriatic arthritis that was refractory to conventional systemic and/or topical antipsoriatic treatment who were treated with MMF monotherapy (2 g/d) in a 10-week study. Although MMF was tolerated well in all patients, only patients with moderate psoriasis and psoriatic arthritis improved with therapy, whereas patients with severe psoriasis did not respond to MMF. Although MMF seems to be effective and safe for blistering autoimmune diseases and pyoderma gangrenosum, our data do not allow optimistic statements on the use of MMF in severe plaque-stage psoriasis. However, MMF may develop into an interesting therapeutic alternative for patients with psoriatic arthritis. (J Am Acad Dermatol 2000;42:835-7.)

Medical history and risk of Hodgkin's and non-Hodgkin's lymphomas.

The relationship between a history of selected medical conditions and risk of lymphomas was investigated in a hospital-based case-control study conducted in Northern Italy on 429 incident, histologically confirmed cases of non-Hodgkin's lymphoma (NHL), 158 cases of Hodgkin's disease (HD) and 1157 controls admitted to hospitals for acute conditions. The odds ratios (OR) for NHL were above unity in patients with a history of infectious mononucleosis (OR 2.9), herpes zoster (OR 1.8), pyelonephritis (OR 4.9), tuberculosis (OR 1.8), malaria (OR 1.9), any chronic bacterial diseases (OR 1.7), rheumatoid arthritis (OR 1.7) and psoriasis (OR 2.5). With reference to HD, the ORs were 4.0 for infectious mononucleosis, 2.9 for herpes zoster, 3.3 for pyelonephritis, 2.3 for tuberculosis, 1.4 for chronic bacterial diseases, 2.4 for rheumatoid arthritis, 2.7 for psoriasis and 2.1 for diabetes. The association of NHL and HD with herpes zoster was restricted to the first ten years since the onset of the disease. The relationships between NHL and mononucleosis (OR 12.9), malaria (OR 2.8) and psoriasis (OR 14.0) were stronger for cases aged > or = 60 years, and that with tuberculosis (OR 3.5) was stronger for younger cases. For HD, the positive association was stronger for cases aged > or = 40 years for herpes zoster (OR 3.8) and diabetes (OR 2.6). An increased risk of NHL was found in association with poliomyelitis (OR 1.6) (restricted to cases aged > or = 60 years, OR 4.0) and BCG immunizations (OR 1.6), but not with vaccination against smallpox, tetanus and diphtheria; increased risks of HD were found in relation to poliomyelitis and BCG immunization in cases aged > or = 40 years (OR respectively 2.5 and 2.1), or > or = 50 years (OR 4.3 and 2.2). Thus, our results confirm the association between a history of several chronic infectious and inflammatory diseases and the risk of NHL or HD, and are compatible with a role of chronic immunological alterations in the aetiology of lymphomas.

Epinastine: An update of its pharmacology, metabolism, clinical efficacy and tolerability in the treatment of allergic diseases.

Epinastine is a potent antiallergic agent that has not only antihistaminic (H(1)) properties but also provides antileukotriene, anti-PAF and antibradykinin activities, which are associated with its antiallergic actions. Moreover, epinastine is very effective in inhibiting the release of chemical mediators from mast cells exposed to antigen. In addition, IL-8 release from eosinophils was inhibited by epinastine posttranscriptionally. Chemotatic movement of eosinophils was also blocked by epinastine. The increase in EEG power spectrum at low frequency region detected at frontal cortex is associated with drowsiness. No such change was induced by epinastine, while a marked increase was observed after ketotifen. In agreement with this, when the amount of H(1) blockers that penetrated through the BBB into the brain was estimated by means of PET, it was apparent that epinastine hardly penetrated the BBB. With regard to the current-voltage relationship of HERG currents, epinastine did not affect I(Kr), while a marked inhibition was seen after terfenadine or astemizole. These results indicated that epinastine does not suppress delayed rectifier potassium current of the heart and, consequently, no cardiotoxic action of epinastine was postulated. In man, epinastine is readily absorbed after oral administration and no significant change in pharmacokinetics was found during chronic administration. In teratological studies in rats, malformation and variation were not observed even at high doses of epinastine. In the clinical application of epinastine, it was shown that this drug is remarkably effective in the treatment of various dermatological diseases, such as chronic urticaria, psoriasis vulgaris and other pruritic dermatoses. Moreover, epinastine provides excellent clinical efficacy in the treatment of allergic rhinitis. Although efficacy of H(1) blockers in bronchial asthma is somewhat doubtful, the overall improvement rate in asthmatic patients was significantly higher in epinastine-treated patients (53.7%) compared to those treated with ketotifen (25%).

IL-12, Independently of IFN-γ, Plays a Crucial Role in the Pathogenesis of a Murine Psoriasis-Like Skin Disorder

AbstractThe onset of acute psoriasis and the exacerbation of chronic psoriasis are often associated with a history of bacterial infection. We demonstrate that while only few scid/scid mice develop disease when CD4+CD45Rbhigh T cells are transferred alone, coadministration of LPS plus IL-12 or staphylococcal enterotoxin B into scid/scid mice 1 day after CD4+CD45Rbhigh T cell transfer greatly enhances disease penetrance and severity. Most importantly, the skin lesions induced by this method exhibit many of the histologic hallmarks observed in human psoriasis. Skin infiltrating CD4+ T cells were predominantly memory/effector cells (CD45Rblow) and exhibited a highly polarized Th1 phenotype. To test whether the development of pathogenic T cells was dependent on their production of IFN-γ, we transferred IFN-γ−/− CD4+CD45Rbhigh T cells into scid/scid or into T, B and NK cell-deficient scid/beige mice. Surprisingly, the incidence of psoriasis was similar to scid/scid animals that received IFN-γ+/+ T cells, although acanthosis of the skin was attenuated. In contrast, the development of psoriasis was abolished if anti-IL-12 mAb was administered on day 7 and 35 after T cell transfer. Skin-derived IFN-γ−/− inflammatory cells, but not cells from anti-IL-12-treated animals, secreted substantial amounts of TNF-α, suggesting that the inflammatory effect of IFN-γ−/− T cells may be partly exerted by TNF-α and that the therapeutic effect of anti-IL-12 may depend on its ability to down-regulate both TNF-α and IFN-γ. Overall, these results suggest that IL-12, independently of IFN-γ, is able to induce pathogenic, inflammatory T cells that are able to induce psoriasiform lesions in mice.

Concentration of an epidermal growth factor in blood serum of males during topical treatment of psoriasis

Epidermal growth factor (EGF) is a mitogen that stimulates cell division of various cells of epidermal origin. The present study was undertaken to clarify whether the serum level of EGF is correlated with the disease activity during local therapy with dithranol in psoriasis. We examined serum EGF concentrations in acute and chronic psoriasis before and after topical treatment with dithranol and the correlation with Psoriasis Activity and Severity Index (PASI). Male patients were divided into two groups: acute psoriasis (AP, 18 cases) and chronic psoriasis (CP, 17 cases). A control group C consisted of 20 healthy male volunteers. Radioimmunoassay of EGF was performed using the reagent pack (Amersham, UK). In the CP group mean EGF was higher before treatment than in the AP and C groups, but not significantly. EGF concentration after local treatment was higher in the CP group than the AP group (P < 0.02); the AP group, however, showed statistically significant decrease of EGF after the treatment (P < 0.04). No correlation between EGF and PASI was found. Serum EGF concentration increased in 19/35 treated patients.

Concentration of an epidermal growth factor in blood serum of males during topical treatment of psoriasis

Epidermal growth factor (EGF) is a mitogen that stimulates cell division of various cells of epidermal origin. The present study was undertaken to clarify whether the serum level of EGF is correlated with the disease activity during local therapy with dithranol in psoriasis. We examined serum EGF concentrations in acute and chronic psoriasis before and after topical treatment with dithranol and the correlation with Psoriasis Activity and Severity Index (PASI). Male patients were divided into two groups: acute psoriasis (AP, 18 cases) and chronic psoriasis (CP, 17 cases). A control group C consisted of 20 healthy male volunteers. Radioimmunoassay of EGF was performed using the reagent pack (Amersham, UK). In the CP group mean EGF was higher before treatment than in the AP and C groups, but not significantly. EGF concentration after local treatment was higher in the CP group than the AP group (P<0.02); the AP group, however, showed statistically significant decrease of EGF after the treatment (P<0.04). No correlation between EGF and PASI was found. Serum EGF concentration increased in 19/35 treated patients.

Topical Calcipotriol Combined with Phototherapy for Psoriasis

Background: Calcipotrial has a well-documented effect in the treatment of psoriasis. Objective: To confirm the beneficial effect of the combination of calcipotriol and UVB and to demonstrate that the combination is safe and well tolerated. Methods: Data from two randomized right/left studies were analysed. Patients included in the studies had chronic stable plaque-type psoriasis with symmetrical lesions on the arms, the legs and/or the trunk. In one study, 101 patients were treated with calcipotriol on one side and calcipotriol + UVB on the other side of the body (open study). In the other study, 77 patients were treated with calcipotriol + UVB on one side and vehicle + UVB on the other side of the body (double-blind study). Calcipotriol ointment, 50 μg/g, was applied twice daily and UVB 3 times weekly for 8 weeks. UVB was increased from 0.7 MED before treatment in rapid steps up to the erythema threshold. Result: In both treatment series the therapeutic effect of the combination of calcipotriol and UVB was enhanced as compared to calcipotriol alone and UVB alone. In the first series there was a significant reduction of the psoriasis area and severity index (PASI) with the combination after 2 weeks as compared to calcipotriol alone. At the end of treatment significantly more sides were cleared after calcipotriol + UVB than after calcipotriol alone. In the other series there was a significantly faster onset of improvement on the sides treated with calcipotriol + UVB than on those treated with vehicle + UVB. After 2 weeks there was a significant difference in PASI in favour of calcipotriol + UVB. At the end of treatment, however, there was no difference between the treatments. There was a similar adverse event profile with either treatment. The addition of UVB to calcipotriol did not alter the tolerability or safety of topically applied calcipotriol. Conclusions: The result indicates a beneficial effect of combining calcipotriol and phototherapy. The findings are compared to other published studies.