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Efficacy and safety of oral retinoids in psoriasis.

With the advent of new biological agents, interest in the treatment of psoriasis has been renewed. Vitamin A and its derivatives (retinoids) have been used successfully in the treatment of psoriasis for over 30 years. In this paper, data on the efficacy and safety of oral retinoids for the treatment of various forms of psoriasis is reviewed. Studies have shown that retinoids are particularly effective in the treatment of pustular and palmoplantar psoriasis. When used in conjunction with ultraviolet therapy, retinoids appear to have a synergistic effect and can be used safely as long-term maintenance therapy. The most common side effects of oral retinoids are usually modest, treatable or reversible, and predominantly affect the liver, musculoskeletal and neurological systems. Potential teratogenicity remains the primary concern with use in women. Oral retinoids appear to be well tolerated in paediatric and HIV-infected patients.

Abnormalities, Drug-Induced↗

Addition of short-contact anthralin therapy to an ultraviolet B phototherapy regimen: assessment of efficacy.

The purpose of this study was to determine whether the addition of short-contact anthralin therapy to an ultraviolet B phototherapy regimen would result in more rapid resolution of psoriatic plaques. A bilateral paired comparison between an ultraviolet B phototherapy regimen with and without short-contact anthralin was completed in eleven patients. Only two of the patients responded faster on the anthralin-treated side. Our results do not support the routine addition of short-contact anthralin therapy to ultraviolet B phototherapy regimens, but this combination may be more effective in a minority of patients.

Anthracenes↗

[Ultraviolet blood irradiation therapy for the sudden deafness].

OBJECTIVE: In order to improve curative effect of sudden deafness. METHOD: We adopted ultraviolet blood irradiation (UBI) therapy added conventional pharmacotherapy to treat 70 cases of sudden deafness. RESULT: The general effective rate was 85.6% and there was no complication. In control group we adopted conventional pharmacotherapy only, the general effective rate was 65.7%. There was significant difference between experimental and control groups (P < 0.01). CONCLUSION: The results showed that the UBI is a safety, effective, simple and convenient therapy for the sudden deafness.

Adult↗

Phototoxicity and the cornea.

The cornea is sensitive to the effects of ultraviolet (UV) light and can suffer both acute and chronic toxicity. Ultraviolet keratitis is associated with relatively short exposures to light sources such as welding arcs or tanning lamps. The corneal effects are seen within a few hours following exposure and typically will resolve within 72 hours. Chronic exposure to environmental UV light may lead to a variety of ocular surface abnormalities that rarely resolve in the absence of therapy. Ultraviolet light, while potentially destructive, also can be used therapeutically. Recently, the photoablative properties of the excimer laser have been used in corneal refractive surgery. This laser uses UV light to break chemical bonds and remove tissue. Corneal phototoxicity is a reflection of the sensitivity of the ocular surface to photochemical injury. Fortunately, effective protection in the form of UV-blocking lenses is widely available.

Adult↗

[Growth-inhibiting effect of psoralen plus ultraviolet-A light therapy on K562 cells].

OBJECTIVE: To observe the effects of psoralen plus ultraviolet-A light (PUVA) on K562 cells and the relative mechanism. METHODS: The effects of psoralen, ultraviolet-A light and PUVA on K562 cells were assayed by monotetrazolium test (MTT). DNA content was analyzed by flow cytometry (FCM). The apoptotic rates of K562 cells treated with 40 and 80 microg/ml psoralen for 24 and 48 hours were assayed by Annexin-V-FITC/PI reagent kit on FCM respectively. The ultrastructures of apoptotic cells were observed by a transmission electron microscope (TEM). RESULTS: Either single psoralen therapy or single ultraviolet-A irradiation had inhibiting effect on K562 cells. The inhibiting effect of PUVA on K562 cells was stronger than that of the single psoralen therapy or single ultraviolet-A light irradiation (P<0.05). Apoptotic peak (AP) was detected by FCM. TEM test showed that K562 cells treated with PUVA were smaller, having condensed cell nucleus, assembled chromatin, disintegrated nucleus body and the majority of the cells appeared to be apoptotic conformation. CONCLUSION: Psoralen has inhibiting effect on K562 cells, and the effect of PUVA is more significant. It is suggested that 10 min irradiation and 40 microg/ml terminal concentration of psoralen be probably the best choice for PUVA. The inhibiting effect of PUVA is due to apoptosis.

Apoptosis↗

Ranitidine-induced photosensitivity.

We report the case of a 72-year-old male patient who developed a florid photosensitive eruption while on ranitidine therapy. Ultraviolet A sensitivity was detected by irradiation monochromator testing, suggesting drug-induced photosensitivity. Ranitidine was concluded to be the cause of his photosensitivity since the eruption resolved and the phototest abnormalities returned to normal following cessation of therapy. Similar cases have been reported to the Committee on Safety of Medicines but not published.

Aged↗

Delayed onset of bullous pemphigoid after PUVA and sunlight treatment of psoriasis.

The coexistence of bullous pemphigoid and psoriasis has previously been noted. In most patients, the bullous lesions start during PUVA or UVB therapy of psoriasis. We report on a psoriatic patient who developed bullous pemphigoid approximately three to four weeks after discontinuing PUVA treatment, and then three to four weeks after exposure to natural sunlight. Delayed induction of bullous pemphigoid has not been previously reported, and it raises the question of ultraviolet therapy inducing subclinical or latent bullous pemphigoid in psoriatic patients.

Humans↗

Antinuclear antibodies during psoralens plus ultraviolet A (PUVA) therapy--are they worthwhile?

From 1979 to 1985, 497 patients with psoriasis were started on psoralens plus ultraviolet A (PUVA) therapy at Northwestern University. Two hundred sixty-nine of these received therapy for greater than 3 months and had at least two antinuclear antibody (ANA) determinations. We have found that the difference between the number of significantly positive ANAs pre-PUVA therapy (4 of 269) compared to post-PUVA therapy (16 of 269) was not statistically significant. Furthermore, of the patients who did develop a significantly positive ANA, not one was found to have any symptoms, signs, or laboratory evidence of systemic lupus erythematosus. We therefore suggest obtaining ANAs prior to initiating PUVA therapy and obtaining follow-up ANAs only if the initial ANA is significantly positive. Patients with pre-PUVA--positive ANAs can be started on PUVA therapy if there is no evidence of lupus erythematosus.

Antibodies, Antinuclear↗

Studies on the effects of a high dose UVA-1 radiation therapy on surface markers and function of epidermal Langerhans cells.

Recently, high-dose UVA-1 therapy (340-400 nm) was introduced as an effective treatment of severe exacerbated atopic dermatitis. Since the target of this type of radiation in the skin is not known we investigated using the mouse model whether surface markers of the antigen-presenting function of epidermal Langerhans cells are affected by UVA-1 radiation. Even repeated high doses of UVA-1 radiation (up to 50 J/cm2) had no detectable effect on surface ATPase activity and Ia antigen expression on Langerhans cells. Also, the contact allergen oxazolone was presented normally in skin treated with UVA-1 radiation. In contrast, if the mice were injected 1 h before irradiation with 8-methoxypsoralen a dramatic reduction in ATPase activity and Ia antigen expression on Langerhans cells was observed and the induction of contact sensitivity was suppressed (PUVA effect). These results show that epidermal Langerhans cells are not impaired either in structure or function and that these cells probably do not represent the primary target of UVA-1 radiation in the skin. No side effects resulting from a diminished Langerhans cell function should result from high-dose UVA-1 therapy.

Adenosine Triphosphatases↗

The irritancy of anthralin is inhibited by repeat applications of a subirritant concentration.

Anthralin is a safe, effective treatment for psoriasis, but its efficacy is hampered by the side-effects of irritation and staining of the uninvolved skin. To avoid burning, it is customary to start at low concentrations and increase every 48-72 h until the therapeutically effective concentration is reached, which takes time and appears to prolong treatment. We felt that if the minimal erythema concentration (MEC) of anthralin could be determined initially in an individual, this ought to be near or at the final achievable therapeutic concentration. Hence, by analogy with ultraviolet therapy, treatment could start just below this concentration and thus avoid delay. A series of concentrations of anthralin in Lassar's paste was applied to the back for 3 h, and erythemal responses assessed at 24 and 48 h. MECs (0.015-0.03%) were far below those usually reached during normal therapy. To test the possibility that the skin was adapting to anthralin, we pretreated areas of skin with a subirritant concentration of anthralin (0.007%) for 3 h on 2 consecutive days prior to application of the full dose series. On the pretreated areas, the MEC increased fourfold from 0. 015% to 0.06% (P < 0.01); the concentration of anthralin required to produce the mid-point on the dose-response curve increased from 0. 06% to 0.25% (P = 0.01), demonstrating a clear adaptive response. One pretreatment produced a 52% reduction in erythema compared with control challenge, and maximal 61% inhibition was seen after three applications. Pretreatment with a subirritant concentration of a control irritant, croton oil, had no effect on the response to anthralin and vice versa. Pretreatment of skin with danthron, the non-irritant oxidation product of anthralin, had no effect, suggesting that the attenuation effect is specific to native anthralin. To see whether the attenuation might be due to modulation of xenobiotic metabolizing enzymes, skin was pretreated with inducers and inhibitors of the cytochrome P450 and NADPH-dependent quinone reductase (NDQR) enzyme systems. However, no effect was seen. In conclusion, we have shown that the irritant response to anthralin is attenuated by repeated applications of a subirritant concentration of anthralin; this is not a non-specific response to all irritants, but a specific property of native anthralin, and the enzymes P450 and NDQR are apparently not responsible for this effect.

Adaptation, Physiological↗

The use of ciclosporin in psoriasis.

Ciclosporin is a cyclic undecapeptide discovered in the 1970s to possess a potent inhibitory action on T lymphocytes. The subsequent discovery, in 1979, that it was remarkably effective in treatment of psoriasis transformed thinking about the nature of the disease, which subsequently became generally recognized as autoimmune in nature. Ciclosporin remains one of the most effective and rapidly acting treatments currently available for psoriasis. Virtually all the diverse manifestations of this disease can respond. The main side effects are nephrotoxicity and hypertension. There is considerable variation between individuals in susceptibility to these so careful monitoring is required. Ciclosporin should be used in single or intermittent short courses for all except the most severe cases as this is safer than continuous treatment. The rate of improvement depends very much on the dose, which ranges from 2 to 5.0 mg/kg/day. Ciclosporin can be combined with any topical treatment and a useful dose-sparing effect can be achieved in this way if patients are compliant. In severe cases ciclosporin is often used in combination with other systemic antipsoriatic drugs in order to spare the dose of each agent and reduce toxicity. Concurrent or intercurrent use of ultraviolet therapy is discouraged due to the increased risk of non-melanoma skin cancer. This article reviews the mode of action, pharmacokinetics, indications, contraindications, side effects, dosage regimens, pretreatment screening and monitoring, drug interactions, and use of treatment combinations with ciclosporin in the management of psoriasis.

Adult↗

Uremic pruritus.

Uremic pruritus and its treatment are reviewed. Pruritus affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis; symptoms usually begin about six months after the start of dialysis and range from localized and mild to generalized and severe. The mechanism underlying uremic pruritus is poorly understood; possibilities include secondary hyperparathyroidism and divalent-ion abnormalities; histamine, allergic sensitization, and proliferation of skin mast cells; hypervitaminosis A; iron-deficiency anemia; neuropathy and neurologic changes; or some combination of these. The cornerstone of therapy for uremic pruritus is regular, intensive, efficient dialysis. Other nonpharmacologic measures consist of the use of non-complement-activating dialysis membranes, compliance with dietary restrictions, electric-needle (acupuncture) therapy, and ultraviolet light therapy. Pharmacologic treatments that have been used include activated charcoal, antihistamines, capsaicin, cholestyramine, emollients and topical corticosteroids, epoetin, pizotyline, ketotifen, and nicergoline. Treatment results have been highly variable, and many of the clinical trials have been flawed. Phosphate-binding agents appear to be the most effective. Although enough is known to determine a reasonable set of steps in approaching a patient's uremic pruritus, more research is needed to understand the pathophysiology of this condition and to establish more reliable treatments. Pruritus is a common and sometimes severe complication of chronic renal failure. Efficient dialysis, dietary restrictions, phosphate-binding therapy, and phototherapy are the most effective treatments currently available.

Humans↗