Vasculitis in chronic urticaria: an immunopathologic study.

Forty-five patients with chronic urticaria were studied to determine: (1) the histologic incidence of leukocytoclastic vasculitis and (2) the clinical, laboratory and immunopathologic parameters that characterized this patient group. By histopathologic examination a spectrum of changes were noted as 9 patients showed leukocytoclastic vasculitis, 15 a dense perivascular infiltrate of lymphocytes and eosinophils, and 21 only a sparse lymphocytic perivascular infiltrate. Both the vasculitis and the dense infiltrate groups had an increased incidence of circulating immune complexes, as detected by Clq binding and monoclonal rheumatoid factor inhibition radioassays. Direct immunofluorescence showed blood vessel deposition of immunoglobulins, complement, and/or fibrin in 33% of the vasculitis group, 13% of the dense infiltrate group, and 9% of the sparse infiltrate group. These studies suggest that a meaningful number of patients with chronic urticaria have histologic and immunopathologic findings of vasculitis.

Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria and atopic dermatitis.

The subjects of this double-blind study were 59 patients with chronic idiopathic urticaria or atopic dermatitis randomly assigned to receive 10 mg of loratadine once daily and placebo twice daily (n = 20), 25 mg of hydroxyzine thrice daily (n = 20), or placebo thrice daily (n = 19). The patients (15 men, 44 women) were aged 18 to 65 years. Among the 18 patients with urticaria and 41 with atopic dermatitis, daily symptom scores decreased 43% and 57% in those receiving loratadine, 47% and 38% in those receiving hydroxyzine, and 0% and 33% in the placebo patients. The difference between the treated and placebo patients was significant among the urticaria patients. According to a global evaluation of treatment effects, more treated than placebo patients reported marked or complete symptom relief; among the patients with atopic dermatitis, the difference was significant between the loratadine and placebo patients. Somnolence or sedation during treatment was reported by one of the patients receiving loratadine, by eight of the hydroxyzine patients, and by two of the placebo patients; the difference between the loratadine and hydroxyzine patients was significant. It was concluded that loratadine is as effective as hydroxyzine in the treatment of urticaria and demonstrates a significant antipruritic effect in atopic dermatitis, but does not have the central nervous system effects of hydroxyzine.

Loratadine in the treatment of urticaria.

Urticaria is a common skin disease, which in its chronic form, is a very disturbing condition. Because histamine is the best-documented chemical mediator of urticaria, histamine-antagonists are the mainstay of therapy. First-generation antihistamines are limited by their tendency to produce sedation and anticholinergic side effects. Most of the newer second generation antihistamines compare well with the earlier agents in efficacy but are not limited by the same adverse side effects. Loratadine may be distinguished from other second-generation antihistamines by its pharmacodynamic profile, as well as its tolerability and safety.

Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study.

Topical corticosteroids and keratolytics are both used widely in the management of patients with psoriasis. A combination of the two types of agents may provide enhanced relief. The purpose of this study was to compare the efficacy and safety of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis vulgaris. A total of 408 patients were enrolled in this controlled, randomized, double-masked, parallel-group, multicenter comparison. Patients applied either mometasone furoate-salicylic acid ointment or mometasone furoate ointment alone to target lesions twice daily for 21 days. Severity of erythema, induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An evaluation of overall change in disease status of all treated lesions was performed at each follow-up visit. Adverse events were also monitored and scored, including signs of skin atrophy. Beginning on day 8, the combination of mometasone furoate-salicylic acid was significantly more effective than mometasone furoate alone, as indicated by the mean percentage of improvement in total disease scores, mean total disease sign scores, and the individual score for scaling. Similarly, the combination was more effective beginning on day 15, as indicated by the global evaluation of overall clinical response and individual scores for erythema and induration. Both treatments were well tolerated. Mometasone furoate-salicylic acid ointment provides more effective treatment of moderate-to-severe psoriasis than does mometasone furoate ointment alone and is safe and well tolerated.

Vitiligo associated with regional enteritis.

Although the cause of vitiligo is unknown, there is considerable evidence to indicate that autoimmunity plays a role. Much of this evidence is based on the increased associated occurrence of vitiligo in a number of diseases also believed to be autoimmune in origin. I have observed a case of almost simultaneous onset of vitiligo and regional enteritis. A search of the literature revealed no specific case report associating these two disorders. The association of these two disorders in the same person may be more than fortuitous, since both diseases may be autoimmune in origin.

Lupus band test.

The lupus band test (LBT) is a direct immunofluorescent technique for demonstrating a band of localized immunoglobulins at the dermal-epidermal junction in the skin of patients with lupus erythematosus (LE). Studies have shown immunoglobulins and complement at the dermal-epidermal junction in systemic (involved and uninvolved skin) and in discoid (involved skin only) LE. It is essential that the appropriate skin site be selected for biopsy; ie, involved or uninvolved skin, light-exposed or light-protected skin. The proper location of the biopsy site is determined by whether the LBT is intended for diagnostic or prognostic purposes. From a diagnostic standpoint, the LBT is a very sensitive and specific test for LE. In addition, this procedure has considerable value as a prognostic test for a patient with an established diagnosis of LE.

Urticaria. An updated review.

Urticaria can result from many different stimuli, and numerous factors, both immunologic and nonimmunologic, are involved in its pathogenesis. Most commonly considered of immunologic mechanisms is the type I hypersensitivity state mediated by IgE. Another immunologic mechanism involves the activation of the complement cascade, which produces anaphylatoxins that can release histamine. Immunologic, nonimmunologic, genetic, and modulating factors converge on mast cells and basophils to release mediators capable of producing urticarial lesions. In addition to the clinical and laboratory diagnosis and treatment regimens, we review such mediators as histamine, kinins, serotonin, slow-reacting substance of anaphylaxis, prostaglandins, acetylcholine, fibrin degradation products, and anaphylatoxins that increase vascular permeability and can thereby produce wheals. Special consideration is given to histamine and the factors that regulate is secretory release from mast cells and basophils, including the modulating role of intracellular levels of cyclic adenosine monophosphate.

Combined H1 and H2 antihistamine therapy in chronic urticaria.

Chronic urticaria is a frustrating problem for the patient and the physician. The cause is usually undetermined, and the therapy is directed toward controlling symptoms. Recent evidence that human skin blood vessels possess H2 receptors, as well as the commonly recognized H1 receptors, suggests a possible reason for the frequent failure of H1 antihistamines in controlling this disorder. Eighteen patients with refractory chronic idiopathic urticaria participated in a double-blind, cross-over study to evaluate the efficacy of combined H1 (hydroxyzine hydrochloride) and H2 (cimetidine) antihistamines vs H1 antihistamines alone. This study indicates that combined H1 and H2 antihistamine therapy is statistically more effective than H1 antihistamines alone in controlling the symptoms of chronic urticaria.

Treatment of urticaria.

In conclusion, although the treatment of urticaria, especially chronic urticaria, is often unsatisfactory, considerable progress has been made in this area over the past few years. As we learn more about the pathogenic mechanisms and mediators involved in the production of urticarial lesions, we will be better able to develop more effective treatment modalities. Currently, several medications exist to block the effects of already released histamine on the target organ receptor sites on the cutaneous blood vessels, to prevent the release of histamine from the mast cells, and to interfere with the release or production of other potential mediators of urticaria. Various combinations of these different therapeutic approaches will probably prove most helpful in treating different clinical patterns of urticaria.

A combination benzoyl peroxide and clindamycin topical gel compared with benzoyl peroxide, clindamycin phosphate, and vehicle in the treatment of acne vulgaris.

A topical gel combining 5% benzoyl peroxide and 1% clindamycin as phosphate was evaluated in a 10-week randomized double-blind trial involving 287 patients with moderate to moderately severe acne. The combination agent demonstrated significantly greater reductions in inflammatory lesions than either of its active constituents (5% benzoyl peroxide and 1% clindamycin) or vehicle when used alone. Significantly greater reductions in comedos and improvements, as measured by both physicians' and patients' global evaluations, were obtained with the combination agent than with clindamycin or vehicle. The reduction in comedos and the global improvements were similar between the combination agent and benzoyl peroxide. The combination agent was well tolerated; the incidence of dry skin was similar to that found with benzoyl peroxide, and other adverse events were similar to that with vehicle. The improved efficacy obtained with combination therapy was accompanied by a safety profile similar to that of either constituent used alone.

Desloratidine for the treatment of chronic urticaria.

Chronic urticaria is a common dermatologic condition that is idiopathic in most cases. Antihistamines are the mainstays of treatment for this condition. The newer, second and third generation antihistamines are the preferred agents because of their improved safety profile and comparable efficacy to the first generation antihistamines. Desloratadine is a new non-sedating H1-receptor agonist. Based on clinical studies, desloratadine is a valuable new addition to the available treatment options and should be considered as a first-line therapy for patients with chronic urticaria.

Nonsedating H1 antihistamines in chronic urticaria.

Histamine type 1 (H1) receptor antagonists are the principal therapy for chronic urticaria. Their usefulness, however, is sometimes compromised by undesirable central nervous system (CNS) side effects such as daytime sedation and anticholinergic side effects such as dry mouth. Second-generation, nonsedating antihistamines (terfenadine, astemizole, loratadine, and cetirizine hydrochloride) are just as effective as the potent first-generation antihistamines such as hydroxyzine. Yet they do not cause the CNS and anticholinergic side effects seen with the older agents. Cardiovascular side effects, which have been recently reported with terfenadine and astemizole, are dose related and rare, generally occurring in patients who overdose or who take concomitant medications that increase serum antihistamine levels. The second-generation antihistamines also offer twice daily and once daily dosage schedules, which are more convenient than the two- to four-times daily schedules of the older agents. They should therefore be considered first-line agents for the treatment of chronic urticaria. This article is a review of the role of the nonsedating antihistamines in the treatment of chronic urticaria.

Chronic urticaria: review of nonsedating H1 antihistamines in treatment.

Antihistamines are the drugs of choice in the symptomatic relief of chronic urticaria; however, the usefulness of classic antihistamines has been limited by side effects, especially daytime sedation. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less sedation. This review analyzes each of the new nonsedating antihistamines and evaluates its clinical efficacy, safety, and convenience in the treatment of chronic urticaria.

Urticarial vasculitis: an updated review.

Urticaria and vasculitis are two different reaction patterns in the skin. Both are caused by a wide variety of substances involving different pathogenic mechanisms. Recently isolated cases of "urticarial vasculitis" have been reported. These cases involve patients who present with a clinical picture of urticaria which, by skin biopsy, shows necrotizing vasculitis. The probable underlying pathogenic mechanism in this condition is one of immune complex deposition. This review will analyze the clinical, laboratory, and immunopathologic features of these patients and then will develop an overall concept of what constitutes "urticarial vasculitis."

The role of antihistamines in the treatment of chronic urticaria.

For many years, H1 antihistamines have been the primary management option for urticaria. However, undesirable side effects, particularly daytime sedation, have limited the usefulness of these classic antihistamines. A new class of peripherally acting, nonsedating antihistamines (e.g., terfenadine, astemizole, loratadine, and cetirizine) has proved to have clinical efficacy comparable with the classic antihistamines. In comparative trials between the various nonsedating agents, no significant difference in efficacy has been noted. All these agents have good safety profiles, although astemizole use has been correlated with increased appetite and weight gain in some patients, and cetirizine has caused slightly increased sedative effects compared with placebo. Although H1/H2 antihistamine combinations have been proposed as possible treatments for urticaria, studies have produced mixed results.

Appraisal of the validity of histamine-induced wheal and flare to predict the clinical efficacy of antihistamines.

Antihistaminic drugs have been used successfully for many years in the treatment of allergic diseases. Second-generation antihistamines have fewer sedating side effects than first-generation agents, and the number of newer drugs available for clinical use is growing. Various methods have been used to assess antihistaminic activity, the most popular of which is the epicutaneous histamine-induced wheal and flare. This test relies on the ability of epicutaneously injected histamine to bring about the wheal and flare, a neurovascular response that involves reflex vasodilation (flare) and local swelling caused by plasma extravasation (wheal). Antihistamines have been compared on the basis of their ability to block the histamine-induced wheal and flare in the skin. Results of these trials have been applied to predict the global antiallergic efficacy of various antihistamines. The review has examined the reliability of suppression of the histamine wheal and flare reaction in the skin to predict an antihistamine's clinical efficacy in two common allergic diseases seasonal allergic rhinitis and chronic idiopathic urticaria. Although histamine is one mediator in the allergic response in the skin and nasal mucosa, many other agents are important modulators of the allergic response. In addition, the major structural and functional differences that exist between the nasal mucosa and the skin affect the type of local response. These manifest themselves as differences between the responses to antigen and histamine challenge in the skin and the nose. The allergic responses in these tissues are not simply the consequence of one chemical but are the result of a cascade of interactions among various cells and mediators. The clinical manifestations of these complex interactions obviously cannot be fully replicated by injection of one chemical mediator, histamine, into the outer layer of the skin. Studies with antihistamines have shown that certain drugs, such as cetirizine, are more suppressive than others (loratadine, terfenadine) in controlling the histamine-induced wheal and flare reaction in the skin. When the clinical efficacy of these medications is compared in clinical trials in seasonal allergic rhinitis and chronic idiopathic urticaria, all are equally efficacious in controlling symptoms. Although the histamine-induced wheal and flare reaction can serve as a useful clinical pharmacologic test to assess dose-response relations for an antihistamine, its lack of correlation with clinical responses among antihistamines indicates that this model should not be used to predict or compare clinical efficacies of antihistamines in seasonal allergic rhinitis and chronic idiopathic urticaria.

Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria.

The efficacy and safety of a new non-sedating antihistamine, loratadine (Clarityn, CAS 79794-75-5) 10 mg q.d., was compared to the classical antihistamine, hydroxyzine 25 mg t.i.d. and placebo in a 4-week (optional 12 week) randomized, double-blind, multi-center study in 203 patients with chronic idiopathic urticaria. Efficacy evaluations included weekly physician and patient assessments of pruritus, overall disease condition, and therapeutic response to treatment. Loratadine and hydroxyzine were significantly more effective than placebo and clinically comparable to each other as measured by all efficacy evaluations at each visit. Loratadine was safe and well tolerated with sedation and dry mouth similar to placebo and significantly less than hydroxyzine.