Madalene C.Y. Heng

Lack of host cellular immune response in eruptive molluscum contagiosum.

A lack of cellular immunity on the part of the host has been incriminated as the cause of the persistence of the cutaneous lesions of molluscum contagiosum. We present a patient in the eruptive phase of the disease, confirming the absence of T-lymphocyte and natural killer cell subsets in the base of these typical lesions, using a panel of monoclonal antibodies. We also report the observation of lipid material ultrastructurally (confirmed by osmium staining on fresh-frozen tissue), as well as cross-reactivity immunocytochemically of the antigens on these molluscum bodies with antigens normally present on macrophages, as defined by DAKO-macrophage monoclonal antibodies. We have considered the possible role of these findings in the lack of host cellular responsiveness in the eruptive phase of the disease.

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 cell ‘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 la 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.

High endothelial venules in involved and uninvolved psoriatic skin: recognition by homing receptors on cytotoxic T lymphocytes.

We report the presence of tannic acid staining material in the intercellular spaces between adjacent endothelial cells of the high endothelial venules (HEVs) in psoriatic skin, which appears to be recognized by T8 (cytotoxic/suppressor) lymphocytes, as the presence of HEVs was found to be related to the presence of T8 lymphocytes in the epidermis. As HEVs with similar tannic acid staining material were also observed in peripheral lymph nodes, we suggest that this material may serve as a marker for HEVs recognized by the T8 lymphocyte subset. T8 + lymphocytes were found in the epidermis at 5 min and 1 h after tape‐stripping of uninvolved skin of psoriatic patients with active disease, but not until 24 h in a psoriatic patient in remission. The prior existence of HEVs in uninvolved psoriatic skin could account for the rapid egress of T8 lymphocytes from the vasculature to the epidermis in response to trauma.

Electron microscopic and immunocytochemical studies of the sequence of events in psoriatic plaque formation following tape‐stripping

Summary Electron microscopic and immunocytochemical studies were performed on sequential biopsies following the tape‐stripping of the uninvolved skin in 12 patients with psoriasis. In the biopsies taken after 5 min for up to 7 days during the pre‐psoriatic phase, there were initial lymphocyte‐Langerhans cell interactions as well as interactions between lymphocytes and keratinocytes. In biopsies taken after 6–8 weeks during the proliferative phase there were lymphocyte‐macrophage interactions. In the 24‐h and 7‐day biopsies there were close contacts between epidermal lymphocytes and keratinocytes via microvilli, with blebbing of the keratinocyte plasma membranes and granular cytoplasmic changes around these microvilli. Few basal keratinocyte herniations were noted during this phase. The 6–8‐week biopsies of Köbner‐positive patients were characterized by a marked increase in lymphocyte‐macrophage interactions via similar microvillous processes with associated electron‐lucent areas suggestive of cytotoxicity.

α1‐Antitrypsin deficiency in severe psoriasis

α1‐Antitrypsin phenotypes and trypsin‐inhibitory capacities were measured in fifty‐one patients with psoriasis. An increased number of variant phenotypes (MS, MZ, and SS) were found only in those patients with severe psoriasis (20% or more skin involvement) and not in those with lesser involvement. The psoriatic patients with variant phenotypes had an earlier disease onset than those psoriatic individuals (both mild and severe) without this association. Protease inhibitors may play a role in modifying disease activity in psoriasis.

Linear seborrheic keratoses associated with underlying malignancy

A clinical syndrome, consisting of eruptive linear seborrheic keratoses associated with adenomatous colonic polyps (malignant but without invasion of the stalk) and/or frankly invasive colonic adenocarcinomas, is described in five patients. Partial to almost complete regression of the cutaneous lesions over the succeeding months to years was noted after removal of the internal malignant tumors in all five patients. Resolving lesions were characterized by an accentuation of chronic inflammatory infiltrate both within the epidermis and dermis, suggesting perhaps that the regression of the skin lesions may be related to enhanced immunologic response concomitant with the removal of the underlying malignancy.

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 miroscopy. 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.

FOCAL ENDOTHELIAL CELL DEGENERATION AND PROLIFERATIVE ENDARTERITIS IN TRAUMA-INDUCED EARLY LESIONS OF NECROBIOSIS LIPOIDICA DIABETICORUM

Microangiopalhy is an essential component in diabetic vascular pathology. We report ultrastructural observations of ballooning degeneration involving isolated endo-thelial cells of cutaneous capillaries, while leaving adjacent cndothclial cells relatively intact in six diabetic patients with early lesions of necrobiosis lipoidica induced by trauma. Focal proliferation of cndothclial cells encroaching upon the vascular lumina (obliterative endar-tcritis) was also observed. Lectin studies on biopsy specimens of older lesíons of neerobiosis lipoidica revealed paucity of dermal blood vessels. These observations enable us to gain further insight into the pathophysiological mechanisms that underlie diabetic microvascular disease.

LOCAL HYPERBARIC OXYGEN ADMISTRATION FOR LEG ULCER

The side-effects of systemic oxygen therapy which include pulmonary and central nervous system toxicity, have been studied in man (Frank & Massaro, 1979; Morgan et al., 1963; Welch, Morgan and Clamann, 1963). Grand mal seizures have been reported to occur after exposure for 35-95 min at 3 atmospheres, and after 5 min at 7 atmospheres of oxygen tension (Morgan et al., 1963; Welch et al., 1963). Pulmonary oedema, atelectasis, consolidation, congestion, haemorrhage and fibrotic changes of the lung have been noted following systemic administration of oxygen (Frank & Massaro, 1979). Toxicity from systemic absorption of oxygen has led to consideration of local administration of oxygen for the promotion of wound healing. It has been shown that although hyperbaric oxygen at pressures of up to 3 atmospheres, administered percutaneously, did penetrate the superficial dermis, there was no penetration of oxygen into the deep dermis (Gruber et al, 1970b) with no resultant systemic toxicity (Gruber, Heitkamp & Amato, 1970a). Consequently, local percutaneous administration of hyperbaric oxygen has been successfully used by several investigators to heal ulcers, mainly those of ischaemic aetiology (Slack, Thomas & Dejode, 1966; Bass, 1971; Heng, Pilgrim & Beck, 1982) including decubitus ulcers (Gorecki, 1964; Rosenthal & Schurman, 1971; Fischer, 1970). However, there is no general agreement as to the optimum pressures of oxygen administered in the treatment of leg ulcers, and low pressures ranging from 5-15 mmHg above atmospheric pressure (Gorecki, 1964; Olejniczak, 1975) and intermediate pressures of 25-30 mmHg above atmospheric pressure (Heng, et al, 1982; Fischer, 1975) have been in vogue. High pressures of 2-3 atmospheres can only be generated in modified recompression chambers (Slack et al, 1966; Bass, 1971; Cooke, 1971), with attendant risks of systemic oxygen toxicity. Treatment times have likewise varied greatly, from 15-20 min (Gorecki, 1964; Olejniczak, 1975)and 1-2 h(Slacketa/., 19665Bass, 1971; Cooke, i97i)to4-6h(Heng,eja/., 1982;Fischer, 1966, 1975). It is believed that the best results might be obtained when periods of hyperbaric oxygen are interspersed with periods of tissue hypoxia when oxygen is withheld. Supporting this belief are observations, both in vivo and in vitro, that mild tissue hypoxia appears to be one of the more potent stimulators of tissue proliferation (Niinikoski, Heughan & Hunt, 1971; Goodson et al, 1979; Hunt, Zelderfeldt & Dunphy, 1968). It has been demonstrated, using rabbit ear chambers, that a hypoxic tissue gradient is necessary for angiogenesis during wound healing and that when the hypoxic gradient is removed, capillary growth ceases (Knighton, Silver & Hunt, 1981). Increased angiogenetic potential has been observed in malignant tissue (Folkman, 1974) and also in the corpus luteum (Gospodarowitz & Thakral, 1977) where high oxygen gradients have been noted to be associated with increased metabolic activity and demands. In patients with intermittent claudication and in atherosclerosis increased muscle capillary diameter and density has been observed (Hammarsten et al, 1980; Makitie, 1977). More clinical data is required to assess fully how these observations apply in patients with various types of leg ulcers. We have observed (Heng et al, 1982) that the ulcers treated with hyperbaric oxygen developed abundant granulation tissue which filled up the wound from the base towards the epidermal surface. It is known that in collagen synthesis, hydroxylation of lysyl and prolyl

Expression of the l‐fucose moiety on epidermal keratinocytes in psoriasis induced by the Koebner phenomenon: a sequential study

Summary The expression of Ulex europaeus agglutinin (UEA I) binding siteson cell‐surface glycoproteins has been used as a marker for terminaldifferentiation. Increased number of UEA I binding sites ofl‐fucose specificity have beendemonstrated in psoriatic epidermis. The results of lectin‐bindingstudies in a series of biopsies taken sequentially (0 min, 5min, 24h, 7 days and 8 weeks) after tape‐stripping of uninvolved skin in 12psoriatic patients (three of whom were taking diltiazem, a calciumblocker at the time of the study) and six controls are presented. UEAI binding sites, which were expressed on the granular layer and upperlayers of the stratum spinosum of pre‐tape stripped uninvolved skinin psoriatic individuals, were progressively more numerous, with theexpression of the l‐fucose moiety onthe lower stratum spinosum keratinocytes in the 7‐daypost‐tape‐stripping biopsies and 8‐week biopsies, correlating with amoderate and marked increase in the proliferative index, respectively. In the Koebner‐negative and non‐psoriatic individualswho failed to develop psoriasis after tape‐stripping, the UEA Ibinding sites were not expressed on keratinocytes of the lowerstratum spinosum in any of the biopsies, although a mild increase inthe proliferative index was noted in the 7‐day biopsies. Our datasuggest that the increased commitment of keratinocytes to terminallydifferentiate may be involved in the psoriatic process. There is someevidence that the signal initiating a series of events leading toterminal differentiation may be the influx of extracellularCa2+ into the keratinocyte cytosol. The failure of ourpsoriatic patients on diltiazem to develop psoriasis may providesupport for this concept.