In studies of therapeutic efficacy, placebo-controlled trials are essential. This is especially true for diseases such as psoriasis in which the naturalcourse may vary considerably from patient to patient, with variations including chronic persistence of lesions as well as spontaneous and temporary or persistentremissions or exacerbations. Placebo effects influence treatment outcomes in up to 35% of patients. In this systematic review of randomized placebo-controlledtrials of systemic drugs for chronic plaque-type psoriasis, Spuls et al found considerable variation in treatment outcomes in placebo groups. Publicationbias and variations in study design and documentation may account for some of this variation.
The most common idiopathic photodermatosis, polymorphic light eruption(PLE), is characterized by a delayed abnormal reaction to UV radiation. Aftera critical review of the literature, van de Pas et al performed photoprovocation studies on 25 patients to develop a reliable provocation method for PLE. Thewavelength dependence of PLE remains unclear, and the action spectrum of the disease has been disparately reported to be in the UV-A range, the UV-B range,or both. In this study, solar-simulated radiation was found to be very effective in provoking PLE, which suggests that PLE may be most readily induced whenthe natural causes of the disease are simulated. Such a protocol could be particularly beneficial in the assessment of potential photoprotective agents.
Pemphigus vulgaris (PV) is an autoimmune, IgG autoantibody–mediated, mucocutaneous disease characterized by progressive blistering and nonhealingerosions. Corticosteroids remain the mainstay of therapy through immunosuppression as well as a direct blocking effect on IgG-induced acantholysis. Activationof keratinocyte cholinergic receptors mimics the antiacantholytic effects of corticosteroids, which prompted Nguyen et al to evaluate whether cholinomimeticagents may represent novel antiacantholytic therapy for this chronic disease. Using a mouse model of pemphigus, the authors demonstrate that the cholinergicagonist carbachol attenuated the effects of PV IgG on keratinocytes. The usefulness of pyridostigmine bromide in a single patient with PV is also discussed.
Psoralen–UV-A (PUVA) treatment of psoriasis is linked to an increased risk of cutaneous malignancy, but the precise causes are not well understood.In this study, Wolf et al demonstrate that PUVA may promote carcinogenesis by acting as a cofactor for tumorigenic viruses such as human papillomaviruses(HPVs). Using a nested polymerase chain reaction approach, the authors found a higher incidence of HPV in plucked hair follicles of patients with psoriasistreated with PUVA than in those of non–PUVA-treated patients. The high incidence of epidermodysplasia verruciformis HPVs, including HPV 38, in PUVA-treatedpatients may be directly involved in tumorigenesis.
Ultraviolet radiation can modify proteins and other organic molecules that may act as neoantigens to provoke an autoimmune reaction. On the otherhand, the cytokine balance in UV-exposed skin is shifted toward an immunosuppressive reaction in healthy individuals. A defect in UV-induced immunosuppressionmay explain the inflammatory reaction in the skin of patients with polymorphouslight eruption (PLE). Kölgen et al overexposed unaffected buttock skinof 6 patients with PLE and 5 healthy volunteers to UV-B and performed immunohistochemical staining on frozen skin sections for a number of cytokines. A reduced inductionof tumor necrosis factor α, which affects Langerhans cell migration, provides confirmation of a defect in UV-induced immunosuppression in PLE.
This Month in Archives of Dermatology. Arch Dermatol. 2004;140(3):271. doi:10.1001/archderm.140.3.271