Richard D. Sontheimer

Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus

The 1982 ACR classification criteria have become de facto diagnostic criteria for systemic lupus erythematosus (SLE), but a review of the criteria is necessary to include recent diagnostic tests. The criteria were not developed with the help of dermatologists, and assign too much weight to the skin as one expression of a multiorgan disease. Consequently, patients with skin diseases are classified as SLE based mostly on skin symptoms. We discuss specific problems with each dermatologic criterion, but changes must await a new study. We suggest the following guidelines for such a study, aimed at revision of the criteria. 1) The SLE patient group should be recruited in part by dermatologists. 2) The study should evaluate an appropriate international ethnic/racial mix, including late onset SLE as well as pediatric patients. 3) All patients should have current laboratory and clinical evaluations, as suggested in the paper, to assure the criteria can be up-to-date. This includes anti-SS-A and anti-SS-B antibodies and skin biopsies for suspected cutaneous lupus erythematosus except for nonscarring alopecia and oral ulcers. 4) The study should be based on a series of transparent power calculations. 5) The control groups should represent relevant differential diagnoses in numbers large enough to assess diagnostic problems that might be specific to these differential diagnoses. In order to demonstrate specificity of the criteria with a 95% confidence interval between 90 and 100%, each control group of the above should have at least 73 patients.

Review of traditional and novel modalities that enhance the permeability of local therapeutics across the stratum corneum

Local therapeutic intervention has several major advantages, e.g. minimal systemic effects and the targeting of active areas of disease only. The nonviable uppermost layer of the epidermis, the stratum corneum, however, is an impediment to the delivery of many drugs at therapeutic levels. The stratum corneum is 10–15 cell layers thick over much of the body and, although routine histologic sections demonstrate wide separations between corneocytes (the so-called “basket-weave” appearance), this is an artifact and the cells are actually tightly opposed to each other (Fig. 1). The intercellular spaces between corneocytes are filled with stacked sheets of lipid bilayer membranes whose organization and unique chemical composition confer a high degree of water impermeability. It is these lipid lamellae that constitute the epidermal permeability barrier, both to water (which permits terrestrial life) and to other penetrants. The transport of medication across the stratum corneum is complex. The basic aspects of this transport mechanism, however, are controlled by three fundamental physiochemical parameters. Primarily, these consist of the partition ( K ), diffusion ( D ), and solubility ( C (s)) coefficients. 1 The solubility coefficient is a measure of how easily a particular gas dissolves in a liquid. The solubility coefficient can be used to calculate the partial pressure of a gas, and consequently determine the direction of diffusion of a gas through a liquid. Therefore, in order to enhance the transfer of a medication across the stratum corneum, these variables need to be manipulated and targeted. Synergism is often seen when the formulation influences more than one of these parameters. 1 This review aims to examine traditional and novel modalities for the promotion of transepidermal drug delivery (Fig. 2).

Practical and experimental consideration of sun protection in dermatology

Much is known regarding the deleterious effects of ultraviolet radiation (UV) on the skin. As more epidemiologic and basic research continues to characterize the impact of sun exposure and other sources of UV radiation upon the development of cutaneous neoplasm and a variety of photosensitive dermatoses, it is crucial for the dermatologist to promote sun protection among his/her patients as well as the primary care physician who has a greater reach of the community than the skin specialist. Practical steps to achieve optimal sun protection include avoidance of UV radiation, avoidance of photosensitizing drugs, use of photo‐protective clothing, and diligent application of broad‐spectrum sunscreens. In recent years, novel agents and experimental modalities with the potential to offer enhanced protective effects against deleterious sequelae of sun exposure have been elucidated, e.g. antioxidants, alpha‐MSH, polyphenol in green teas, genistein, NF‐kB decoy oligodeoxynucleotides, pTpT vaccination, and IL‐12. As these new photo‐protective tools are being developed by scientists around the world, greater concerted effort is needed to engage public health officials and the media to promote sun protection awareness throughout the general public.

Subacute Cutaneous and Systemic Lupus Erythematosus

Lupus erythematosus is a multi-organ autoimmune disease which presumably results from a complex interplay of genetic and environmental factors. The clinical phenotype of LE ranges in continuum from minor cutaneous lesions to life-threatening vital multi organ dysfunction. Throughout this continuum, skin manifestations are variable and common. There is a commonly accepted classification system that divides lesions into LE specific and LE non-specific cutaneous disease. LE specific cutaneous disease includes three clinically, immunologically and genetically distinct disorders: acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE) and chronic cutaneous LE (CCLE). Histopathological differentiation between especially the first two disorders can be difficult. SCLE is clinically characterized by non-scarring, non-indurated, erythematous, papulo-squamous and/or annular skin lesions occurring in a symmetric, photo distributed pattern. Patients with SCLE tend to exhibit milder systemic symptoms than those with unselected systemic LE (SLE). Although not mandatory for diagnosis, the majority of SCLE patients produce anti-Ro / SSA autoantibodies. In SLE, musculoskeletal symptoms such as arthritis and arthralgias are the most common systemic manifestations observed. Overall, most patients with SCLE tend to have mild systemic disease and it appears that isolated joint symptoms are a marker for milder disease. The clinical diagnosis of SCLE is not always obvious. Annular lesions can be confused with erythema annulare centrifugum, granuloma annulare, erythema gyratum repens, tinea corporis or erythema multiforme. Lesional photodistribution, characteristic histopathology and Ro/SS-A autoantibodies are useful in distinguishing SCLE from its differential diagnosis. Most SCLE patients tend to have intermittent recurrent skin lesions without significant disease progression, while some may experience permanent remissions. Approximately 15 percent of patients develop active SLE. The most common complaints other than skin lesions and photosensitivity were fatigue, arthralgias and Raynaud’s phenomenon. In addition, many patients had a subjective history of depression.The real prognosis of SCLE needs to be evaluated in a larger number of patients to more firmly establish its course, ANA and Ro/SS-A prevalence, overlap with other connective tissue diseases, as well as prognosis.