Erythema migrans: a spectrum of histopathologic changes.

Early cutaneous Lyme disease, erythema migrans, manifests as a gyrate erythema at the site of a tick bite. The standard histopathologic description is that of a superficial and deep perivascular lymphocytic infiltrate in which plasma cells are identified at the periphery of the lesion and eosinophils in the center. Deviation from these commonly accepted histopathologic findings may lead to an erroneous diagnosis. Herein, we describe 4 cases of erythema migrans, all biopsied at the periphery of the lesion and confirmed by serologic studies, demonstrating a variety of unconventional histopathologic patterns. These findings include eosinophils and neutrophils at the periphery of the expanding annular plaque of erythema migrans, focal interface change, spongiosis, involvement of the superficial vascular plexus alone, and an absence of plasma cells in all cases. These cases highlight the varied and nonspecific histopathologic changes that can be seen in erythema migrans, including the absence of plasma cells and the presence of focal interface change. Based on these findings, the dermatopathologist should always consider erythema migrans as a diagnostic possibility in a biopsy specimen from an expanding gyrate or annular erythema despite the presence of unusual features. In atypical clinical cases, serologic confirmation may be required for diagnosis in the presence of histopathologic findings considered unconventional for erythema migrans.

Barrier function of the skin: "la raison d'être" of the epidermis.

The primary function of the epidermis is to produce the protective, semi-permeable stratum corneum that permits terrestrial life. The barrier function of the stratum corneum is provided by patterned lipid lamellae localized to the extracellular spaces between corneocytes. Anucleate corneocytes contain keratin filaments bound to a peripheral cornified envelope composed of cross-linked proteins. The many layers of these specialized cells in the stratum corneum provide a tough and resilient framework for the intercellular lipid lamellae. The lamellae are derived from disk-like lipid membranes extruded from lamellar granules into the intercellular spaces of the upper granular layer. Lysosomal and other enzymes present in the extracellular compartment are responsible for the lipid remodeling required to generate the barrier lamellae as well as for the reactions that result in desquamation. Lamellar granules likely originate from the Golgi apparatus and are currently thought to be elements of the tubulo-vesicular trans-Golgi network. The regulation of barrier lipid synthesis has been studied in a variety of models, with induction of several enzymes demonstrated during fetal development and keratinocyte differentiation, but an understanding of this process at the molecular genetic level awaits further study. Certain genetic defects in lipid metabolism or in the protein components of the stratum corneum produce scaly or ichthyotic skin with abnormal barrier lipid structure and function. The inflammatory skin diseases psoriasis and atopic dermatitis also show decreased barrier function, but the underlying mechanisms remain under investigation. Topically applied "moisturizers" work by acting as humectants or by providing an artificial barrier to trans-epidermal water loss; current work has focused on developing a more physiologic mix of lipids for topical application to skin. Recent studies in genetically engineered mice have suggested an unexpected role for tight junctions in epidermal barrier function and further developments in this area are expected. Ultimately, more sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired.

Nephrogenic fibrosing dermopathy with systemic involvement.

BACKGROUND: There is a growing literature regarding sclerotic and panniculitic cutaneous conditions seen in patients with end-stage renal disease (eg, calciphylaxis and soft tissue calcification). Nephrogenic fibrosing dermopathy (NFD) is a recent designation to describe cutaneous findings in patients with end-stage renal disease who developed sclerotic plaques with scleromyxedema-like histologic features. Soft tissue calcification is rare in patients with NFD and systemic involvement has not been reported. OBSERVATIONS: We describe a patient with end-stage renal disease who developed diffuse indurated woody plaques consistent with NFD in association with soft tissue calcification with catastrophic sequelae. A deep excisional biopsy specimen from the patient revealed thickened collagen bundles in the reticular dermis, plump bipolar spindle cells, and increased mucin. Focally, there were zones of calcium deposition in dermal collagen without vessel calcification. Autopsy of the patient revealed extensive fibrosis and calcification of the diaphragm, psoas muscle, renal tubules, and rete testes. The patient died 11 months after developing NFD. CONCLUSION: A subset of patients with NFD may have significant systemic involvement.