R. Touraine

Sclerodermatous chronic graft-versus-host disease : analysis of seven cases

BACKGROUND Sclerodermatous chronic graft-versus-host disease is a disabling complication after allogeneic bone marrow transplantation from HLA-identical sibling donors. Only a few series of patients have been reported and the dermatologic features have never been extensively described. OBJECTIVE The purpose of the study was to describe clinical and biologic features of chronic sclerodermatous graft-versus-host disease and to compare them with scleroderma. METHODS We reviewed 196 patients grafted between April 1973 and July 1987 with survival times sufficient to be at risk of chronic graft-versus-host disease. Seven had the sclerodermatous form. RESULTS Most patients had disseminated sclerosis of the trunk and the proximal portions of the limbs. In two cases, atrophy of the skin was predominant, corresponding with a severe clinical evolution. Periorbital pigmentation was observed as an initial manifestation in three cases. Visceral manifestations resembled those observed in scleroderma but histologic and immunologic studies demonstrated clear differences. Response to therapy was variable. CONCLUSION Chronic sclerodermatous graft-versus-host disease may realize two different patterns. Major atrophy is associated with a more severe progression.

A routine immuno-electron microscopic technique for localizing an auto-antibody on epidermal basement membrane

A new diagnostic technique is described, in which 0.7 mm thick slices of skin are freshly cut, throughly washed, slightly fixed and directly incubated in peroxidase‐labelled antibodies. This easy technique allows routine immuno‐electron microscopic diagnosis of subepidermal auto‐immune bullous diseases, with excellent morphological results.

SJÖGREN-LIKE SYNDROME AFTER DRUG-INDUCED TOXIC EPIDERMAL NECROLYSIS

7 of 9 patients recovering from a drug-induced toxic epidermal necrolysis (TEN) which they had had 2 months to 4 years before had xerostomia, or keratoconjunctivitis sicca, or both. 5 patients had symptoms; 2 had severe visual impairment. In 5 cases there was lymphocytic infiltration of small salivary glands; in 2 patients this was identical to that of Sjögren syndrome. None of the patients had antinuclear antibody. TEN may occur during acute graft-versus-host disease (GVHD) and these observations are reminiscent of the sicca syndromes reported during chronic GVHD. They suggest that autoimmune mechanisms may be involved in drug-induced TEN and that Sjögren syndrome may occur as the result of a drug reaction.

Cellular events leading to blister formation in bullous pemphigoid

Cellular events occurring in eight patients with bullous pemphigoid were studied by light and electron microscopy. Sections (0.5 μm) of large surface area, overlapping blisters and surrounding skin, were examined and correlated ultrastructural studies were performed on selected areas. The peroxidase contained in granules of neutrophils, cosinophils and young macrophages was visualized by incubation with diaminobenzidine and hydrogen peroxide. This cytochemical reaction was used as a marker to study the release of granule enzymes from these inflammatory cells. The release of such enzymes from eosinophils and occasionally from macrophages on the epidermal basement membrane (more precisely in the lamina lucida) was demonstrated in the skin surrounding the blisters in four patients. The release of these enzymes was also observed in the floor of the blisters in all eight patients. It is well known that these granules contain several protcolytic enzymes. These observations are therefore consistent with the proposal that proteolytic enzymes of eosinophils play a pathogenic role during the initial stages of blister formation in bullous pemphigoid.

The collagen lattice: a model for studying the physiology, biosynthetic function and pharmacology of the skin

Until recently, changes in cell physiology following application of pharmacological agents have been studied in vivo or in vitro using monolayered cells. Although both approaches have unique advantages, both have shortcomings. Now the development of a skin-equivalent model has provided a system for studying cell responses at the tissue and organ levels in vitro (Bell, Ivarsson & Merrill, 1979; Bell et al., 1981a, b). The in vitro tissue model can be made simple or complex with respect to eel! type heterogeneity and matrix constitution; ideally, however, it should resemble skin as closely as possible. It has the special advantage, unlike skin, of being able to survive for long periods in vitro. In this paper we compare the model morphologically with skin and review some aspects of the biosynthetic output of cells in the tissue equivalent with that of monoiayered cells. Finally we illustrate in a pharmacological study that the model can be used to provide new information that in vivo studies or monolayer cell studies cannot yield.

Lymphopenia and abnormal balance of T-lymphocyte subpopulations in toxic epidermal necrolysis.

SummaryA lymphopenia (peripheral-blood-lymphocyte count <1,000/mm3) was observed in seven out of ten patients with toxic epidermal necrolysis (TEN). The enumeration of T-lymphocyte subsets with monoclonal antibodies showed a decreased number of pan T-lymphocytes (OKT3-positive), which was related to a profound depletion of OKT4-positive cells. In contrast, OKT8-positive cell counts were not significantly changed. This abnormal balance of T-lymphocytes was linked to the acute phase of the disease and was not found after recovery. The pathogenetic mechanisms of such T-lymphocyte abnormalities in TEN remain unclear.

Involvement of macrophages in the pathology of toxic epidermal necrolysis

In toxic epidermal necrolysis (TEN), as in the ‘epidermal type’ of erythema multiforme, the necrotic epidermis is infiltrated with mononuclear cells. We studied the epidermal infiltrate in seven cases of TEN. About half the cells obtained from pieces of cleaved epidermis dissociated by trypsin were non‐epithelial. On cytologic analysis, 80% of these foreign cells exhibited markers of macrophages, 15% were granulocytes and only 5% were lymphocytes (almost exclusively OKT8 T lymphocytes). Semi‐thin sections of early prenecrotic lesions showed exocytosis of mononuclear cells within the epidermis with features of satellite cell necrosis and formation of colloid bodies. Almost all these mononuclear cells were macrophages as evidenced by endogenous peroxidase‐positive granules. These findings suggest that some kind of macrophage‐mediated cytotoxicity may play a role in the necrosis of epidermal cells during TEN.

Plasma exchange in corticosteroid-resistant pemphigus

Plasma exchange produced excellent control for four steroid‐resistant cases of pemphigus, and appears to be useful therapy in severe forms of this disease.

A simple method for correlating observations on skin at the light and electron microscopic levels

A method is described which allows the embedding of 6 mm cutaneous punch biopsies for subsequent light and electron microscopic examination. Sections of 20 mm2 cut at 0.5–1 μ are stained for light microscopy. The subtle tinctorial affinities, which approach those achieved on haematological smears, and the preservation of cellular detail frequently make subsequent ultrastructural examination unnecessary. However, when required, a special technique for trimming and resectioning the tissue blocks allows a good correlation between light and electron microscopic observations.

Study of folate in psoriasis: blood levels, intestinal absorption and cutaneous loss.

Serum, red cell and squame folate content have been measured in fifty cases of psoriasis with extensive lesions. Reduced serum and red cell folate have been found in 44% of the patients. Folic acid absorption, studied in twenty‐six patients, was impaired in four and significantly increased in all the others.