Immunohistochemical and electron microscopic characterization of the cellular infiltrate in alopecia (areata, totalis, and universalis).

The inflammatory cell infiltrates in scalp skin of 35 patients, 20 with alopecia areata (AA), 7 with totalis, and 8 with universalis were characterized with the ANAE (alpha-naphthylacetate esterase) marker, monoclonal antibodies, and electron microscopy. As demonstrated by the ANAE staining, no clear difference in the main lymphocyte subclasses (T and B cells) or macrophages was seen between the different types of alopecia or as compared to control patients' scalp skin. However, T lymphocytes and macrophages were seen most frequently and in greater numbers perivascularly and infiltrating the hair bulb in those cases of AA where active hair loss took place. Using monoclonal OKT (OKT-3, -4, and -8) antibodies and the avidin-biotin immunoperoxidase method on frozen sections, a concentration of OKT-8 reactive cells (suppressor/cytotoxic T cells) was seen peribulbarly and invading the hair infundibulum. The cells affecting the hair infundibulum were further studied by electron microscopy. They could be classified into three main types: small lymphocytes (60%), macrophages (30%) and cells closely resembling large granular lymphocytes (LGL) (10%). LGL have previously been considered to be human natural killer (HNK) cells. Thus the hair follicle seems to be the target for the cellular immune response in alopecia. Whether HNK cells participate in the destruction of hair bulbs remains to be investigated.

Morphologic changes in epidermis of PUVA-treated patients with psoriasis with or without a history of arsenic therapy.

The uninvolved skin of patients with psoriasis was examined microscopically. Atypical nuclear features in keratinocytes and melanocytes were found in about half of the patients. The patients treated with psoralens and UV-A (PUVA) had significantly more of these changes than did patients without PUVA treatment, and the risk was dose dependent. Previous arsenic treatment and x-ray irradiation seemed to have a similar effect. The changes may have been due to the shortwave UV range of the light source.

Epidermolysis bullosa simplex associated with muscular dystrophy with recessive inheritance.

Epidermolysis bullosa with unusually severe clinical features was associated with progressive muscular dystrophy in two siblings. Light and electron microscopic examination revealed an intraepidermal cleavage confirming that this mechanobullous disease belonged to the epidermolysis bullosa simplex group. This may represent a new disease entity inherited in an autosomal-recessive fashion.

Epidermolysis bullosa simplex. A new histologic subgroup.

Two patients with a new mechanobullous disease are described. The trauma-induced bullae were present at birth. The nails were deformed in both cases. Both patients were isolated cases; so far, the inheritance pattern is not known. The histologic picture was unique. The keratinocytes were dyskeratotic, enlarged, and had atypical mitoses on light microscopy of neonatal biopsy specimens. Electron microscopically the defect occurred in the tonofilaments, which formed round clumps. The blister formation took place in the lower part of the epidermis.

Ichthyosis hystrix (Curth-Macklin). Light and electron microscopic studies performed before and after etretinate treatment.

Clinical and light and electron microscopic observations of a 16-year-old male patient suffering from ichthyosis hystrix (Curth-Macklin) are presented. The patient had no family history for this disease. The diagnosis was based on the distinct electron microscopic finding of continuous perinuclear tonofibril shells in the keratinocytes. About 10% of the keratinocytes were binucleate and one third contained conspicuous vacuoles. The steroid sulphatase activity in a skin biopsy was normal. Etretinate treatment proved beneficial during the first year of therapy. Later the treatment was less effective. The basic genetic defect persisted in the phenotype of the keratinocytes during etretinate therapy, but the exceedingly thick horny layer was considerably thinned.

Ultrastructure of human fetal sympathetic ganglia after permanganate fixation - absence of granular vesicles.

Midterm human fetal sympathetic ganglia were studied using the formaldehyde-induced fluorescence technique for demonstrating catecholamines, and after glutaraldehyde-OsO(4) or permanganate fixation for electron microscopy. The fluorescence technique indicated the presence of catecholamines in most of the developing neurons. After glutaraldehyde-OsO(4) fixation large granular vesicles were found in the perikarya, but a more specific technique for catecholamines, permanganate fixation, revealed no granular vesicles at this stage of development. This indicates that most of the catecholamines are loosely bound in a non-granular store during development.

Small, intensely fluorescent cells of human sympathetic ganglia.

Human sympathetic ganglia obtained from sympathectomies were studied using the formaldehyde-induced fluorescence (FIF) method and electron microscopy to identify the small, intensely fluorescent (Sif) cells. Microspectrofluorimetry was used to study the intensity of the emitted FIF and the emission spectra. The SIF cells were found in every ganglion studied, but they were very sparce. They occurred alone or in small clusters and were mostly situated close to the blood vessels. The SIF cells contained high amounts of catecholamines, as indicated by microspectrofluorimetry. Electron microscopy revealed granule-containing cells (GC) enveloped by satellite cells; the former cells contained osmiophilic granules 300--400 nm in diameter and synapses of the cholinergic type were frequently found on their surface.

Electron microscopy of epidermal and dermal Langerhans' cells in long-lasting allergy patch tests.

In rare cases, normal allergy patch tests persist for weeks or months. Here, seven biopsies from six patients with long-lasting allergy patch tests, taken 15-75 days after allergen challenge, were analysed by transmission electron microscopy. In accordance with clinical expression of the test site, fine structural evidence of persistent activity of immunocompetent cells in the epidermis and dermis was observed. Moderate numbers of exocytic lymphocytes and macrophages were seen in the epidermis. Langerhans' cells (LC) appeared active, and LCs with Birbeck granules were detected both in the epidermis and the dermis and were also seen to cross the dermoepidermal junction. LC-mononuclear cell contacts were more frequent in the epidermis than is normal in allergy patch tests. A strong infiltrate of lymphocytes, macrophages, fibroblasts, mast cells, and cells resembling LCs but devoid of Birbeck granules, i.e. indeterminate cells, was seen in the upper dermis. Less than 10% of the dermal cells showing the fine structural appearance of LCs had Birbeck granules, as seen in a single section. Both indeterminate cells and LCs were apposed by lymphocytes in the dermis, often in a rosette-like fashion. The present paper is descriptive but gives background to the understanding of events in long-lasting allergy patch tests. However, the reason for and the basic mechanisms of long-lasting allergy patch tests are not known. A defect in down-regulation of the contact hypersensitivity reaction and/or a constant antigen stimulation could be responsible for the persistence of these allergy patch test reactions.

A semiquantitative light and electron microscopic analysis of histopathologic changes in photochemotherapy-induced freckles.

Photochemotherapy(PUVA)-induced freckles were found in 25 patients (41%) who had received more than 1,000 J/cm2 of PUVA. The patients had been treated with PUVA for more than 2 years, with more than 150 exposures before PUVA lentigines appeared on the thighs, the upper arm, the mid-lower arm, the waist, and the buttocks. The histopathology of these freckles was analyzed by light and electron microscopy. Light microscopy showed an increased amount of pigment and melanophages and increased numbers and size of melanocytes. The keratinocytes often displayed atypical features such as enlarged nuclei, giant size, or fibrillar degeneration. Homogenization of the papillary dermis was observed in 11 patients. The activation of melanocytes was confirmed electron microscopically, and pathological features such as large amounts of lipid droplets and lysosome-melanosome complexes within the melanocytes were seen. The Langerhans cells were mostly normal, whereas the keratinocytes showed cytolytic changes, fibrillar degeneration, and vacuolization. A close follow-up of patients with prolonged PUVA treatment is recommended.

Pharmacokinetics of 8-methoxypsoralen in serum and suction blister fluid.

Micronized 8-methoxypsoralen (8-MOP), with a smaller crystal size, produced significantly higher serum level profiles than nonmicronized 8-MOP. Furthermore, the absorption of the micronized drug was more rapid, resulting in peak serum levels within 1 h in 75% of the patients. Our blister fluid studies suggest, however, that reduction of the photosensitizer concentration is slower in skin than in serum. This implies that despite markedly reduced 8-MOP serum level after 2 h the skin remains sufficiently sensitized up to that point of time.

Recessive ichthyosis congenita type II.

In the heterogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe ichthyosis, but good general health and no associated symptoms. This disorder has recently been named 'ichthyosis congenita type II' by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis 'lamellar ichthyosis'.

Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study.

The pathogenesis of a rare form of the ichthyotic diseases, ichthyosis hystrix Curth-Macklin, was investigated by immunohistochemistry and electron microscopy. Monoclonal antibodies (Mabs) against keratins expressed in normal basal cells (PKK2 and KA1), Mabs against keratins only present in normal fetal skin (PKK1), and Mabs against keratins 1, 2, 10, and 11 (KA5 and K8.60) were used. The Mabs reacting with normal basel cells showed an increased reaction with many cell layers. The Mab PKK1 distinctly reacted with the basal cell layer, suggesting an expression of fetal keratins. Electron microscopic study of both normal-looking and involved skin revealed the keratinization disorder characterized by tonofilament shells, perinuclear vacuoles, and binuclear keratinocytes. The results suggest that there is no prematurity of keratinization, but rather a pathological expression of specific keratin genes leading to expression of fetal keratins in this form of ichthyosis hystrix.

Clinical, light and electron microscopic features of recessive ichthyosis congenita type III.

The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the ichthyosis was variable, in contrast to other patients described under the heading recessive congenital ichthyosis.

Epidermodysplasia verruciformis. Clinical and light- and electron-microscopic observations during etretinate therapy.

Three patients with epidermodysplasia verruciformis (EV) were treated with etretinate for 9-13 months. The patients had lesions characteristic of EV, including flat warts, common genital warts, pityriasis-versicolor-like lesions and malignant changes such as actinic keratosis and Bowenoid cancer in situ. During etretinate treatment, some flattening of the warts was observed in all three patients, and the lesions on the chest and back became less red and scaling. However, none of the lesions disappeared completely, and when the treatment was discontinued, the lesions relapsed. No malignant changes were detected during the period of therapy. Electron microscopy revealed the presence of typical large, clear cells containing viral particles in the upper epidermis. Etretinate therapy induced the same type of fine-structural changes as those seen in keratinization disorders and genodermatoses. The clear cells and virus particles persisted throughout the treatment period. More long-term, controlled studies are necessary to make possible an estimate of the curative and cancer-inhibitory effect of etretinate treatment in patients with EV.

Occupational skin allergy in the dental profession.

Dental personnel are exposed to a high number of sensitizing chemicals such as acrylics, metals, anesthetics, fragrances, and antimicrobials. Although these chemicals usually cause allergic contact dermatitis, they also may cause immediate contact reactions. Usually the diagnostics involve patch testing, but prick testing needs to be performed to confirm immediate allergy. This article reviews the important causes and diagnostics of skin allergy in dental personnel. Special attention is given to the acrylates and methacrylates.

Long-lasting contact urticaria. Type I and type IV allergy from castor bean and a hypothesis of systemic IgE-mediated allergic dermatitis.

A unique urticarial type I patch-test reaction to castor bean that persisted for more than 48 hours and was followed by a delayed type IV reaction is described. Immunohistochemical and electron microscopic observations indicated involvement of eosinophils and IgE receptors on Langerhans' cells. The authors present a scheme for the role of Langerhans' cells in skin allergy.

Knuckle pads from boxing.

A 21-year-old man developed painful hyperkeratotic, fissured, callosities on his knuckles ("knuckle pads") after having boxed for five evenings a week for six months. Boxer's knuckle pads are one type of traumatic skin injury regularly found in athletes, such as "jogger's toe", "athelete's nodule", "jog-ger's nipple", "runner's rump", "runner's bump", "rower's rump", "tennis toe", "skier 's shin", "surfer's nodule" "black heel", "black palm", "jazz ballet bottom" and "stria distensae". These types of traumatic skin injuries are briefly reviewed here.

Allergic onycholysis and paronychia caused by cyanoacrylate nail glue, but not by photobonded methacrylate nails.

Artificial acrylic nails may induce side effects such as fingertip dermatitis, periungual dermatitis, onycholysis, paresthesiae, Raynaud's phenomenon, ectopic facial involvement, and allergic contact dermatitis. We present a patient who developed allergic onycholysis from a cyanoacrylate used in a nail adhesive. She was able to use photobonded sculptured nails because they contain methacrylates that do not cross-react with cyanoacrylates.

Allergic contact dermatitis from 2-hydroxyethyl methacrylate in an adhesive on an electrosurgical earthing plate.

A highly (meth)acrylate-allergic patient underwent surgery because of nodular struma. Three days after her operation she developed an itching dermatitis on her left thigh. She came to our attention 18 days after the operation, because of an oozing, highly pruritic dermatitis, 8 x 19 cm in width on her left thigh, at the site where an electrosurgical earthing plate had been used during the surgery. It was revealed that the pressure-sensitive adhesive of the pad contained 2-hydroxyethyl methacrylate (2-HEMA) to which the patient earlier had had an allergic patch test reaction. The patient was negative on patch testing to other (meth)acrylates present in the pad. Patients should be questioned about possible methacrylate sensitivity before methacrylate-containing electrosurgical earthing plates are used during surgery. Allergic contact dermatitis caused by acrylic adhesives is briefly reviewed.

Occupational allergic contact dermatitis from alkylammonium amidobenzoate.

Quaternary ammonium compounds are water-soluble antimicrobials which are widely used in disinfectants, sterilizers, skin cleansers and antiseptic creams. One quaternary ammonium compound, alkylammonium amidobenzoate (Osmaron B) has for decades been used in udder ointments. Here we present a ship technician with occupationally induced sensitization to alkylammonium amidobenzoate. The diagnosis was reached only when it emerged, after careful questioning, that the patient was exposed to a substance peculiar to his workplace but not to his occupation and was then patch tested for it. It turned out that an udder ointment had been used at the patient's workplace as a hand ointment. Patch testing was positive to the patient's hand ointment, and Osmaron B at 0.1-0.01% in petrolatum. Other sensitizing quaternary ammonium compounds, namely benzalkonium chloride, benzethonium chloride, benzoxonium chloride, N-benzyl-N,N-dihydroxyethyl-N-cocosalkyl-ammonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium bromide, chloroallylhexaminium chloride, dequalinium chloride, domiphen bromide, methylbenzethonium chloride and 2,3-epoxypropyl trimethyl ammonium chloride are reviewed briefly. The importance of patch testing to all materials in use by the patient is emphasized. It is also important to select non-allergenic hand creams for use at work places.