Psoriasis A 25-year-old woman presents with a complaint of rash that has developed over the last several weeks

and seems to be progressing. On examination, she is noted to have several plaquelike lesions over the extensor surfaces of both upper and lower extremities as well as similar lesions on her scalp. The plaques are erythematous, with silvery scales, and are sharply marginated.
The lesions described are characteristic of psoriasis vulgaris. Psoriasis is both a genetic and an environmental disorder. A genetic origin is supported by several lines of evidence. There is a high rate of concordance for psoriasis in monozygotic twins and an increased incidence of psoriasis in the relatives of affected individuals. Furthermore, overexpression of gene products of class I alleles of the major histocompatibility complex (MHC) is seen in patients with psoriasis. However, psoriasis is not likely to be completely genetic in nature. Individuals with a genetic predisposition to the disorder appear to require environmental triggers, at least in some cases, such as trauma, cold weather, infections, and various medications. B. In psoriasis, there is shortening of the usual duration of the keratinocyte cell cycle and doubling of the proliferative cell population. This excessive epidermatopoiesis results in skin thickening and plaque formation. In addition to skin thickening, truncation of the cell cycle leads to an accumulation of cells within the cornified layer with retained nuclei. This pattern is known as parakeratosis and results in neutrophil migration into the cornified layer. Together these form the silvery scale characteristic of psoriasis. Finally, psoriasis induces endothelial cell proliferation, resulting in pronounced dilation, tortuosity, and increased permeability of the capillaries in the superficial dermis and causing erythema. C. Many immunologic abnormalities have been implicated in psoriasis, but the exact pathophysiologic mechanism remains unclear. As mentioned, psoriasis is associated with overexpression of MHC class I gene products. This suggests that CD8 T lymphocytes are involved, because the complex of MHC class I protein and antigen is the ligand of the Tcell receptor of CD8 cells. Also seen in psoriasis is overexpression of a large number of cytokines, particularly IL-2..

A. The major alternative diagnoses to consider are bullous pemphigoid and pemphigus, although other blistering diseases such as erythema multiforme and dermatitis herpetiformis should be considered as well. Bullous pemphigoid is characterized by subepidermal and pemphigus by intraepidermal vesiculation. The distinction is important because bullous pemphigoid has a more favorable prognosis. B. Microscopically, bullous pemphigoid lesions show a subepidermal cleft containing lymphocytes, eosinophils, neutrophils, and eosinophilic material, representing extravasated macromolecules such as fibrin. An inflammatory infiltrate of eosinophils, neutrophils, and lymphocytes is also present in the dermis beneath the cleft. C. Direct immunofluorescence microscopy demonstrates IgG and C3 bound in a linear distribution along the epidermaldermal junction. These autoantibodies are bound to a 230-kDa protein within the lamina lucida, known as the "bullous pemphigoid antigen." This antigen has been localized to the hemidesmosomal complex of the epidermal basal cell. Its role is not established. and C3 bound in a linear distribution along the epidermal-dermal junction. These autoantibodies are bound to a 230-kDa protein within the lamina lucida, known as the "bullous pemphigoid antigen." This antigen has been localized to the hemidesmosomal complex of the epidermal basal cell. Its role is not established. D. Blister formation is believed to begin with the binding of IgG to the bullous pemphigoid antigen, activating the complement cascade. Complement fragments then induce mast cell degranulation and attract neutrophils and eosinophils. The granulocytes and mast cells release multiple enzymes, resulting in enzymatic digestion of the epidermal-dermal junction and separation of the layers. It is also possible that the bullous pemphigoid antigen plays a vital structural role that is compromised when the autoantibodies bind, leading to cleavage of the epidermal-dermal junction.

A. The diagnosis is likely to be Rhus dermatitis ( and oak), a form of allergic contact dermatitis. The history of hiking in a heavily wooded area 2 days before onset of the rash is a helpful clue. However, the finding on physical examination of blisters arranged in straight lines helps make the diagnosis. Straight lines and angles suggest an exogenous cause for a skin eruption. In this case, poison ivy leaves traced a line across the skin as the patient walked through the brush, and she developed an allergic contact dermatitis in the pattern of the exposure. B. A common misconception regarding Rhus dermatitis is that blister fluid from broken blisters (or even touching the blistered area) causes the eruption to spread. In fact, once the eruption has developed, the allergen has been irreversibly bound to other proteins or has been so degraded that it cannot be transferred to other sites. In this case, the patient developed large blisters or bullae in response to the contactant at the original sites of contact, the legs. This means that she had a severe reaction to the allergen. Intense inflammation such as this can result in the autosensitization phenomenon, which in this case explains the development of ill-defined erythematous plaques with small papules and vesicles within the plaques seen on this patient's arms and trunk. Alternatively, inadvertent contact with contaminated clothes or other surfaces can induce new areas of dermatitis. The Rhus allergen is tremendously stable and can persist on unwashed clothing and remain capable of inducing allergic contact dermatitis for up to 1 year. C. If the allergen exposure is transient, the first exposure to a Rhus antigen often does not result in a reaction at the exposure site. However, a contingent of "armed and ready" memory T cells is now policing the skin, waiting for the allergen to reappear. The individual is said to be sensitized. When the person is exposed to the antigen again, the elicitation phase begins. Langerhans' cells process antigen and migrate to lymph nodes, but presentation and T-cell proliferation also occur at the site of contact with the allergen. Nonspecific T cells in the vicinity are recruited and stimulated by the inflammatory cytokines released by the specifically reactive T cells, and an amplification loop ensues, eventuating in clinically recognizable dermatitis. This complex series of events takes time to develop, resulting in the 24- to 48-hour delay between reexposure and rash eruption.