Atopic dermatitis: a new treatment paradigm using pimecrolimus

Journal of Drugs in Dermatology, April, 2003 by Jeffrey M Weinberg, James G Bowerman, Stuart M Brown, David Gerstein, Kay S Kane, James Selevan, Sat Virdee

Abstract

Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation. Pimecrolimus is a novel steroid-free treatment for An. Consistently positive results have been found with pimecrolimus treatment in infants, children/adolescents, and adults. Its safety record is excellent, and studies have found no clinically relevant drug-related systemic adverse events. In this article, we first review atopic dermatitis and conventional treatment strategies. We then discuss various aspects of pimecrolimus, including pharmacologic properties, toxicology, short- and long-term studies, and safety and adverse events. Finally, we propose a new steroid-sparing treatment strategy for An.

Introduction

Atopic dermatitis (AD), often called eczema, is a disease characterized by intense pruritus, erythema, dry skin, and inflammation (1-3). The condition is chronic and relapsing, and often occurs in patients with a family history of the atopic triad (asthma, allergic rhinitis, and AD). The exact etiology of AD is not completely understood. Debate centers on whether AD is an allergic response or an immunoinflammatory process. Two main concepts have evolved to explain the pathogenesis of An: excessive T-cell activation in response to an antigen, and hyperstimulation of T-cells by atopic Langerhans cells (1,2,4).

Epidemiology

Prevalence of AD varies by geographic region. An analysis of AD among 155 collaborating centers in 56 countries reported prevalence rates ranging from < 1% to 20% (5). This worldwide assessment, performed by the International Study of Asthma and Allergies in Childhood (ISAAC), found that the United States ranked 17th in world AD prevalence at approximately 8% to 10%. One report concerning schoolchildren in Oregon found 17% had AD, suggesting a wide variation by locale (6). Approximately 49% to 70% of An cases occur in children at or below 6 months of age, while 80% to 90% present by 5 years of age (3). Males and females are affected in equal proportion, and no differences have been found among children of different racial and ethnic backgrounds (1).

Impact on the Family

AD has far-reaching consequences for the patient and the family. Pediatric AD has been shown to interfere with sports, sleep, social activities, and self esteem. A survey conducted by the National Eczema Association for Science and Education (NEASE) surveyed approximately 4000 pediatric patients and 2500 physicians who treat AD, of whom 429 pediatric patients and 303 physicians (99% dermatologists) responded (7). The survey assessed three major areas of concern regarding AD in children: the effects on quality of life, the safety of long-term use of corticosteroids, and differences in perceptions and concerns of parents vs. physicians. Of those patients responding, 35% had mild disease, 44% had moderate disease, and 21% had severe AD.

Pediatric patients reported serious consequences of their AD and its treatment. About half (55%) reported feeling embarrassed or self-conscious in public, 80% reported sleep disruption, and 60% reported a negative impact on daily activities (7). In addition, approximately one-third of patients (32%) rated their prescription medication as "not at all effective." Twenty-two percent of children experienced side effects severe enough to require medication withdrawal (7). These included burning (29%), loss of pigmentation (26%), and dryness (23%). The survey also found that physicians and patients/parents have concerns about the long-term adverse effects of corticosteroids. The NEASE survey also found that patients reported frequent disease flares and dependency upon steroid treatment.

Psychological problems are a concern in children with AD (7-9). Scratching, skin appearance, and facial involvement can negatively affect self-esteem and social development. Children and parents suffer the consequences of sleep deprivation, as well as feelings of being overwhelmed, guilt over not being able to cure the condition, and frustration with time-consuming treatments.

An Australian cross-sectional survey found that childhood AD has a profound impact on families (10). Investigators surveyed parents of 48 children with AD and 46 children with insulin-dependent diabetes mellitus. Results from the Impact on the Family Questionnaire indicated the impact of moderate-to-severe AD on the family was greater than the effect of childhood diabetes mellitus. Sleep deprivation and time taken to care for the child's AD were particularly disruptive. The authors concluded that "eczema is ... a major handicap with a considerable personal, social, and financial burden on the family." (10)

Conventional Treatment for Atopic Dermatitis

Treatment of AD in its initial stages focuses on skin care, patient/parent education, and elimination of trigger factors (1,2). Basic skin care includes the use of emollients for moisturizing the skin and proper bathing practices, such as taking lukewarm baths and patting the skin dry. Patients also need to avoid irritants such as wool, harsh soaps and detergents, aggravating environmental factors (e.g., dust, low humidity), and possible associated food allergies.