Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.

BACKGROUND: Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. OBJECTIVES: To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. METHODS: Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas. RESULTS: Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect. CONCLUSIONS: Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

Properties of solubilized Fc gamma-receptors from psoriatic scales.

Extracts from psoriatic scales, prepared using Tris-HCl buffer containing ethylenediaminetetraacetatic acid (EDTA) and 2-mercaptoethanol (ME), agglutinated erythrocytes (E) sensitized with IgG antibodies (A) (EA), but not E or E sensitized with F(ab')2-fragments of IgG. The agglutination was inhibited by IgG and Fc fragments of IgG, but not by IgA, IgM or F(ab')2-fragments of IgG. Partially reduced and alkylated IgG did not inhibit the agglutination, indicating that an inter-heavy-chain disulphide-linked Fc region is required for binding of FcR. The extracts inhibited EA, but not E or EAC rosette formation with mononuclear cells. The results strongly indicated that the extract contained functionally active FcR. The agglutinating activity of the extract was not affected by treatment with periodic acid or formaldehyde, whereas heat reduced the activity. Using a monoclonal antibody (B1D6) a functionally active 40 kDa FcR with low affinity for native IgG was purified from the scale extract. The extracts also contained FcR activity not recognized by B1D6.

The distribution of Fc gamma RI, Fc gamma RII and Fc gamma R III on Langerhans' cells and keratinocytes in normal skin.

The distribution of Fc-receptors for IgG (FcR) on human epidermal cells (EC) was characterized in situ using monoclonal antibodies (MoAbs) by indirect immunofluorescence staining of cryosections. The results showed heterogeneity of FcR expression on Langerhans' cells (LC) and keratinocytes (KC). The MoAb IV.3 against FcR II (CDw32) gave granular staining of most LC whereas the MoAb 32.2 against FcR I (CD64) occasionally stained a few dendritic cells. 32.2 demonstrated weak granular staining along the outer aspect of KC in stratum spinosum and stratum basale and intense staining of stratum corneum and stratum granulosum. The MoAbs Leu 11b against FcR III (CD16) and B1D6 reacting with a placental FcR with low affinity for IgG gave intense linear membrane staining of KC. Leu 11b produced strongest staining of stratum granulosum and B1D6 the strongest staining of stratum spinosum and basale. The results confirm our previous observations of FcR in situ on LC and KC in normal skin using functional assays and demonstrate that these EC possess different types of low affinity FcR. The data support the contention of an immune function of KC. FcR may be mediators for interaction between KC and LC. The FcR activity in stratum granulosum may have an immune function as a barrier against microorganisms and other antigens.

In situ localization of interferons in psoriatic lesions.

An indirect immunofluorescence technique, using murine monoclonal antibodies (MoAbs) against human IFN-alpha and human IFN-gamma was used to study IFNs in cryostat sections from psoriatic skin lesions. The IFNs were more pronounced in sections from highly active psoriasis than in sections from stationary psoriasis. In highly active psoriatic lesions IFN-alpha was localized to keratinocytes is stratum basale, to some epidermal dendritic cells, probably Langerhans cells, and to some mononuclear cells in dermis. IFN-alpha was usually not detected in sections from stationary psoriasis. IFN-gamma was localized to stratum corneum, to keratinocytes around microabcesses and to mononuclear cells in the dermal cell infiltrates, predominantly in highly active psoriatic lesions. Both IFN-alpha and IFN-gamma were localized to some endothelial cells in the papillary dermis. The MoAbs did not stain sections from unaffected skin from patients with psoriasis or sections from healthy individuals. The findings indicate that the IFN system in the skin may be of significance in the pathophysiology of psoriasis.

Fc gamma-receptors and HLA-DR antigens on endothelial cells in psoriatic skin lesions.

Receptors for the Fc-part of IgG (FcR) and HLA-DR antigens on endothelial cells in normal and lesional skin from patients with psoriasis were studied in cryostat sections, using soluble immune complexes and monoclonal antibodies. FcR and HLA-DR antigens were detected on endothelial cells of dermal vessels both in sections of normal and lesional skin. The expression of FcR varied from one vessel to another and on endothelial cells within one and the same vessel. The expression of FcR and HLA-DR antigens was enhanced in sections of lesional skin compared with normal skin and most pronounced in lesional skin from active psoriasis. The enhanced expression may be mediated by interferon produced in psoriatic lesions. The presence of FcR and HLA-DR antigens on endothelial cells adds further evidence of he involvement of these cells in immune processes in the skin.

Fc gamma receptors on keratinocytes in psoriasis.

Epidermis in cryostat sections of skin biopsy specimens from patients with psoriasis and from healthy individuals bound bovine erythrocytes (E) sensitized with rabbit IgG antibodies (A)(EA). No binding occurred using E or E sensitized with IgM or F(ab')2 fragments of IgG. The binding of EA was inhibited by human IgG and by Fc fragments of IgG, whereas human IgA, IgM, albumin, and F(ab)2 fragments of IgG did not inhibit the binding, indicating the presence of receptors for the Fc part of IgG (FcR). EA bound mainly to stratum spinosum and most strongly above FcR-positive cell infiltrates in dermal papillae. The binding of EA to sections from patients with active psoriasis was stronger than to sections from patients with stationary psoriasis vulgaris. Sections of unaffected skin from patients with psoriasis and healthy individuals also bound EA, but the binding was weaker than to sections of psoriatic lesions. The receptors were sensitive to periodic acid, formaldehyde, and heat. Using immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP, the receptors were localized to the outer aspect of the keratinocytes and to the inflammatory cells in the microabscesses. The strongest binding occurred in the same areas which adhered EA most strongly. FcR on dendritic epidermal cells could not be demonstrated in situ. A monoclonal antibody against FcR also stained the outer aspect of most keratinocytes throughout the epidermis. FcR on keratinocytes support the assumption that these cells contribute to immune reactions in the skin.

Effect of UV radiation on interferon, immunoglobulins and complement components in serum from healthy individuals.

An infectivity inhibition micro-method was used to detect interferon (IFN) in sera from 20 healthy individuals before and after UVA irradiation, and in sera from 22 healthy individuals before and after UVB irradiation. The serum levels of IFN, immunoglobulins (Ig) and complement components (C) were examined before irradiation, after 10 and 20 exposures, and 4 weeks after irradiation. The median serum IFN level in both the UVA and the UVB group increased significantly during irradiation, most markedly during the 10 first exposures. Four weeks after irradiation the median IFN level was reduced in both groups, but had not reached the pre-irradiation levels. The IFN level was unchanged or reduced in 2 individuals in the UVA group and in 5 individuals in the UVB group. Characterization experiments indicated the presence of both acid-stable and acid-labile IFN-alpha and IFN-gamma. The mean serum IgG concentration was significantly reduced 4 weeks after UVA irradiation, whereas IgA, IgM, C3 and C4 were not affected. The mean serum concentrations of IgG and C4 were significantly reduced 4 weeks after UVB irradiation, whereas the mean concentrations of IgM and C3 were significantly increased. The concentration of IgA was not affected.

The effect of Goeckerman therapy on interferon in serum and suction blister fluid from patients with psoriasis.

An infectivity inhibition micromethod was used to detect interferon (IFN) in sera and suction blister fluids from 35 patients with untreated psoriasis vulgaris. IFN (greater than or equal to 16 units/ml) was detected in 56% of the sera (median 25 units/ml), in 77% of the suction blister fluids from lesional skin (median 35 units/ml) and 33% of the blister fluids from unaffected skin (median 10 units/ml). IFN levels were significantly higher in blister fluids from lesional skin than from unaffected skin (P less than 0.05) indicating local IFN production. Results of characterization experiments indicated the presence of both acid stable and acid labile IFN-alpha as well as IFN-gamma in sera and blister fluids. After Goeckerman therapy, IFN was detected in 91% of the sera (median 89 units/ml), in 90% of the blister fluids from lesional skin (median 50.5 units/ml) and in 72% of the blister fluids from unaffected skin (median 26.5 units/ml). The IFN levels in sera were significantly higher than in blister fluids from both lesional skin (P = 0.05), and unaffected skin (P = 0.001). Furthermore, after Goeckerman therapy the IFN levels in blister fluids from unaffected skin and in sera were significantly higher than those in untreated patients (P = 0.01 and P = 0.0001) respectively. The results indicate that UVB radiation induces systemic IFN production.

Interferon in suction blister fluid from psoriatic lesions.

Interferon (IFN) (at least 16 units/ml) was demonstrated in suction blister fluid obtained from lesional skin in nine of thirteen patients with psoriasis vulgaris and in two patients with allergic contact dermatitis, but not in blister fluid from unaffected skin. IFN was detected in only three of the sera from the patients with psoriasis. The difference in results between the blister fluid and the sera from these patients was statistically significant (P less than 0.025). Evidence was obtained which indicated that the activity was probably IFN-gamma (immune IFN), but the additional presence of IFN-alpha in some of the fluids could not be excluded. The data indicate that IFN is produced locally in the psoriatic lesions, most likely by activated T lymphocytes.

Pemphigus in rheumatoid arthritis treated with penicillamine.

The development of pemphigus foliaceus in three patients and pemphigus erythematosus in one patient with rheumatoid arthritis treated with penicillamine is described.

Basement membrane zone deposits of immunoglobulins and complement in a patient with pemphigus vulgaris.

A patient with pemphigus vulgaris is presented. In addition to the intercellular deposits of immunoglobulin and complement in the Malpighian layer which is consistent with pemphigus vulgaris, concomitant granular deposits of IgG and C3 were demonstrated at the dermal epidermal junction, similar to the findings in lupus erythematosus.

A study of Sézary cells in peripheral blood and skin lesions.

A patient with Sézary syndrome is presented. By phase contrast and scanning electron microscopy Sézary cells were demonstrated in peripheral blood and in skin tissue. Investigation of atypical mononuclear cells seen in the peripheral blood showed that these cells lack receptors for sheep erythrocytes. C3 and Fcgamma. Similarly, an examination of dermal mononuclear cell infiltrates showed that most of the cells lack receptors for sheep erythrocytes, C3 and Fcgamma.

Acquired epidermolysis bullosa treated with a gold compound.

A 20-year-old man with acquired epidermolysis bullosa of 3 years' duration was treated intramuscularly with gold sodium thiomalate. After a total dose of 1 000 mg gold sodium thiomalate, administered over a period of 9 months, the patient has shown an almost complete remission, without any apparent side effects of the chrysotherapy.

Epidermolysis bullosa acquisita and Crohn's disease.

A patient with epidermolysis bullosa acquisita (EBA) associated with Crohn's disease is presented. The clinical, histological and immunological findings were in keeping with previous reports. However, clinically normal skin and mucosa exhibited deposits of IgG and C3 in the basement-membrane zone. These deposits remained unchanged during the treatment period. It is therefore suggested that immunological mechanisms are implicated in pathogenesis of the disease.