Erythroderma associated with mixed lymphocyte-endothelial cell interaction and Staphylococcus aureus infection.

We report 11 consecutive cases of erythroderma, a high percentage of which were associated with the growth of Staphylococcus aureus in cultures from blood, joint fluid or skin. In biopsies from all the patients we found close morphological associations between lymphocytes and endothelial cells, with some of the lymphocytes showing features of blastoid transformation to T helper lymphocytes. In extreme cases, sheets of T cells, including T helper lymphocytes, formed a syncytium with endothelial cells in the dermis. Marked capillary proliferation was noted both on light and electron microscopy. We suggest that erythroderma is precipitated by antigens such as protein A, a potent T cell mitogen present on the cell surface of Staphylococcus aureus, or by drugs, such as phenytoin. These antigens induce antigen presentation by individual endothelial cells, leading to T helper transformation and lymphocyte proliferation. Endothelial proliferation resulting from lymphocyte-endothelial interaction results in the vascular proliferation associated with this syndrome.

Endothelial cell toxicity in leg ulcers treated with topical hyperbaric oxygen.

We report the clinical and electron-microscopic features of endothelial cell toxicity in patients treated with hyperbaric oxygen for prolonged periods for leg ulcers. The clinical manifestations include the appearance of depressed white areas within the bed of granulation tissue, which correlated with decreased vascularity under light microscopy. Electron-microscopic findings include endothelial cells with serrated nuclear membranes and degenerate mitochondria in the cytoplasm. These changes occurred in all patients subjected to at least 8 weeks of hyperbaric oxygen, even though an intermittent regimen was adopted. The changes reversed after 1-2 weeks of cessation of hyperbaric oxygen.

Significance and pathogenesis of basal keratinocyte herniations in psoriasis.

Using transmission electron microscopy, we studied, quantitatively, basal keratinocyte herniations (BKH) in relation to the other basement membrane zone changes in psoriatic lesions of varying clinical activity, and in psoriasiform skin diseases. BKH appears to correlate with disease activity. They do not occur passively as a result of the formation of gaps in the basal lamina. BKH in active psoriasis are associated with electron-lucent areas suggestive of proteolytic enzyme release. Their apparent association with Langerhans cells, neutrophils, macrophages, and endothelial cells may point to these cells as the source of proteolytic enzymes in psoriasis. BKH may prove to be a useful marker for clinical psoriasis.

Electron microscopic features in psoriatic patients with alpha 1-antitrypsin deficiency.

We studied the electron microscopic features of 7 psoriatic patients with alpha 1-antitrypsin deficiency and 14 psoriatic controls. We found a statistically significant difference in frequency of basal keratinocyte herniations (BKH) as well as of BKH with abnormal configuration (broad-based BKH, herniating through wide gaps in the basal lamina; and multipolypoid BKH) in the alpha 1-antitrypsin deficient group. The differences were more marked in the MZ phenotype than in the MS/SS phenotypes. These findings may reflect the changes resulting from defective inhibition of proteolytic enzyme activity in the psoriatic patients with alpha 1-antitrypsin deficiency, and support the concept that proteolytic enzyme release and activity may play a role in BKH formation.

Primary mucinous carcinoma of the skin with metastases to the lymph nodes.

Primary mucinous carcinoma is a rare sweat-gland neoplasm of the skin with a tendency to grow slowly. Although the neoplasm persists locally in nearly half of the cases after attempts at removal, metastases to regional lymph nodes and widespread metastases are uncommon. We present a case of primary mucinous carcinoma in an axilla with metastases to the axillary lymph nodes and propose a hypothesis explaining the slow rate of growth, based on our findings of a paucity of both blood vessels and macrophages in the neoplasm. Electron microscopy revealed mucin production by the dark cell and its extracellular secretion, which supports the theory of eccrine differentiation of the neoplasm.

Cell interactions in psoriasis.

Products of the HLA-D gene, the la or DR antigens, have been shown to control interactions between certain cells with immune functions. Three HLA-D alleles have been reported to be associated with a markedly increased relative risk in psoriatic individuals. We report the existence of apparently unique anatomic interactions between lymphocytes and basal keratinocytes, between Langerhans' cells and basal keratinocytes, and between Langerhans' cells and lymphocytes, deduced on the basis of (1) characteristic cytoplasmic processes extending from one cell into the cytoplasm of adjacent cells, with frequent absence of the intervening plasma membrane at the apexes of these processes, and (2) intimate apposition of the plasma membranes between the interaction cells over a large surface area. These interactions were noted in five of ten untreated psoriatic patients (three of four patients with Koebner's phenomenon) and in one of six treated psoriatic patients, but in none of 17 controls. Intercellular space abnormalities, probably secondary to excessive proteolytic enzyme release, and basal keratinocyte herniations in psoriasis may result from these anatomic interactions.

The sequence of events in psoriatic plaque formation after tape-stripping.

The sequence of events leading to the formation of a psoriatic plaque induced by tape-stripping was studied using light and electron microscopy. Among the earliest changes noted were increased mobility of the epidermal Langerhans cells across the basement membrane, evidence of Langerhans cell-lymphocyte interaction, and increased Langerhans cells 'activity' or 'cytotoxicity'. These changes were seen as early as 2 min after stripping and remained until the development of clinical psoriasis. Collections of epidermal lymphocytes showing the features of blastoid transformation while in contact with processes from activated Langerhans cells, suggest the involvement of Ia antigens in this process. We postulate that these findings are a manifestation of an increased immune responsiveness to trauma, controlled by genes located at the HLA-D locus of the major histocompatibility complex, and mediated by enhanced cellular interactions. The appearance of basal keratinocyte herniations (BKH) at 1-3 weeks after stripping, coincided with the development of clinical psoriasis. Neutrophils made their appearance at the same time as, or slightly before, the appearance of BKH, and are suspected to play a role in the development of these structures. We believe that BKH maintain epidermal proliferation through the persistence of the epidermal-stromal interaction.

Pathogenesis of papular urticaria.

The presence of immunoglobulin and complement deposits in the skin of three patients with papular urticaria suggests that these lesions may be due to a cutaneous vasculitis. These deposits were most frequently found in biopsy specimens taken from lesions within 24 hours of their development. The presence of granular deposits of Clq, C3, and IgM in the walls of the superficial dermal blood vessels suggests that immune complexes (IgM aggregates) may be primarily involved in the pathogenesis of these lesions, with complement activation initiated by Clq through the classical pathway.