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We report the results of a study on 100 patients (aged 12-68) with vitiligo, who were treated by transplantation of cultured autologous melanocytes to the depigmented areas, after removal of the epidermis at the recipient site by dermabrasion. The melanocytes were cultured from a 2 x 3 cm2 superficial shave biopsy taken from pigmented buttock skin. After 2-3 weeks in culture, 700-1000 cells per mm2 were applied on 60-500 cm2 dermabraded areas, and occluded for 1 week. The repigmented portion of the total treated area amounted to 95-100% in 40 patients, 65-94% in 32, 20-64% in 22, and 0-19% in six. It was more difficult to achieve complete pigmentation on the fingers, elbows and knees. In the first few months following the procedure, the treated areas were often hypo- or hyperpigmented, but after 6-8 months they had acquired the same colour as the surrounding skin. No scarring or other side-effects occurred. The donor site had repigmented after 3-6 months in all but two patients, who also showed poor pigmentation in the transplanted areas. At follow-up after 1 and 2 years in 50 and 10 patients, respectively, the repigmented areas remained unchanged. The method is time-consuming, but the results obtained indicate that the procedure can be valuable in motivated patients, when the extent of vitiligo does not exceed 30% of the total body area, and when the areas to be treated are not actively extending.

A 71-year-old woman with chronic urticaria and vitiligo is reported who lacked eosinophil and basophil leukocytes in her blood, bone-marrow and skin. No IgE was detectable in serum. She had a low level of serum eosinophil cationic protein (ECP) which could indicate that some eosinophils had been formed but rapidly destroyed. There was, however, no ECP release when the patient's serum was mixed with heterologous eosinophils. Staining for eosinophilic proteins in white blood cells by monoclonal antibodies revealed no storage or secreted forms of ECP. The source of ECP in our patient therefore remains unknown.

The aim of this study was to test the usefulness of a melanocyte-enriched cell suspension for the treatment of leucoderma. After removal of a superficial (4-30 cm2) skin sample, the cells were mechanically separated in a trypsin-EDTA solution, centrifuged and washed in a melanocyte medium. The melanocyte-enriched epidermal cell suspension devoid of stratum corneum and stratum granulosum was then applied to the dermabraded depigmented skin. The 26 patients treated had piebaldism (three), vitiligo vulgaris (17), segmental vitiligo (three), halo naevi (one), naevus depigmentosus (one) and chemical leucoderma (one). In patients with widespread piebaldism we found that by diluting the cell suspension the recipient area could be increased to up to 10 times the size of the donor area with the same good results as without or with less dilution. In patients with vitiligo areas of between 50 and 90 cm2, the recipient areas were increased three- to fivefold in the donor area. Patients with piebaldism, segmental vitiligo and halo naevi healed completely, as did most patients with vitiligo. In naevus depigmentosus no effect was seen. Our new method for treatment of leucoderma has the advantage that cell culture is not needed and that it is more suitable than epidermal sheet grafts when several small areas are to be treated.

SUMMARY A morphological and biochemical analysis was made of cornified envelopes isolated from patients with different congenital disorders. Nomarski contrast microscopy of the envelopes showed that their morphology was not greatly altered in several types of keratoderma and parapsoriasis, but it was grossly modified in ichthyotic disorders. The various types of ichthyoses, keratoderm -lysine isopeptide bonds. In the epidermis two morphologically distinct types of CEs have recently been identified:4 a polygonal rigid type (CEr) and an irregularly shaped type with a fragile appearance (CEf) which, in healthy skin, is only present in the lower part of the stratum corneum. These two types possibly represent two successive steps of CE maturation. The stratum corneum of normal subjects contains mainly CEr, whereas the scales in psoriasis contain a much higher proportion of CEf. Keratinocytes in submerged cultures are only able to form CEf4

Deep-seated lipomas can present with symptoms very different from those of the common subcutaneous variety. Rapid growth and nerve encroachment may cause suspicion of malignancy. The case histories as well as the clinical and radiographic findings of 2 patients with alarming symptoms from deep-seated lipomas of hand and forearm, respectively, are described. By means of CT an accurate preoperative diagnosis could be made, and surgery planned accordingly.

Urticaria is a well-known disease entity; however, with an increasing understanding of the molecular mechanisms involved in its pathogenesis, there is also growing evidence for a heterogeneity of urticaria. Currently it is sometimes difficult to compare divergent data reported by different centers researching urticaria due to a lack of precisely described patient populations. A consensus definition and classification of the disease and its subtypes, taking into account new developments, are therefore needed. In addition, this consensus report provides a guideline for diagnostic procedures in different subtypes of urticaria.

We describe a 20-year-old man with naevus anaemicus on the chest where, after dermabrasion of the epidermis, enlarged teleangiectatic dark-red vessels were seen within the previously pale area. They were clearly different from those seen on dermabrasion at this site in normal skin and in patients with vitiligo where the area is lighter red with only small punctual bleedings from arterial capillaries. The naevus anaemicus and a port-wine stain (naevus flammeus) in the same location is a phenomenon of vascular twin spotting, which was revealed when the epidermis was removed. The area was transplanted with thin epidermal grafts and healed within 2 weeks. One year later the naevus looked the same as before grafting. Much thicker grafts than those used by us will be needed, but they are not cosmetically acceptable.

PSR handles the vast majority of malpractice injuries in Sweden. PSR is a claims handling company which settles claims for malpractice on behalf of the insurance company owned by the Swedish county councils: the County Councils Mutual Insurance Company. A central issue in the law regulating patient injuries in Swedish health care is to define injuries that could have been avoided if a certain therapeutic/diagnostic procedure or a more appropriate method had been utilized. PSR arranged a multiprofessional conference regarding guidelines to decrease the number of malpractice injuries in the treatment of distal radius fractures. Among the most important issues defined were: To improve and standardize diagnostic imaging Patient information Early decision making in surgery and physical/occupational therapy A more well-defined indication for surgery, in which type of trauma, biological age and functional demands are considered in addition to radiographs Less stereotyped thinking in follow-up Controlled randomized trials.

The aim of this study was to test the usefulness of a melanocyte-enriched cell suspension for the treatment of leucoderma. After removal of a superficial (4-30 cm2) skin sample, the cells were mechanically separated in a trypsin-EDTA solution, centrifuged and washed in a melanocyte medium. The melanocyte-enriched epidermal cell suspension devoid of stratum corneum and stratum granulosum was then applied to the dermabraded depigmented skin. The 26 patients treated had piebaldism (three), vitiligo vulgaris (17), segmental vitiligo (three), halo naevi (one), naevus depigmentosus (one) and chemical leucoderma (one). In patients with widespread piebaldism we found that by diluting the cell suspension the recipient area could be increased to up to 10 times the size of the donor area with the same good results as without or with less dilution. In patients with vitiligo areas of between 50 and 90 cm2, the recipient areas were increased three- to fivefold in the donor area. Patients with piebaldism, segmental vitiligo and halo naevi healed completely, as did most patients with vitiligo. In naevus depigmentosus no effect was seen. Our new method for treatment of leucoderma has the advantage that cell culture is not needed and that it is more suitable than epidermal sheet grafts when several small areas are to be treated.

The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.

Thin epidermal sheets, obtained by a high-speed air-driven dermatome, were used to repigment white areas in 19 patients with vitiligo and one boy with piebaldism. In the depigmented skin to be treated the epidermis was removed by a rotating diamond fraise under topical and/or local anaesthesia injections. The method was used on most parts of the body, including the eyelids and genitalia. The maximum total area treated on each occasion was 190 cm2. Excellent results could be obtained if the vitiligo had been stable and had not increased anywhere during the last 2 years. Lack of immobilization could explain a poor result in some areas. The donor area on the buttocks healed quickly without depigmentation. In the transplanted area milia were observed in the first 6 months. No scarring was seen. The technique has a niche in the treatment of depigmented skin, especially in larger areas.

Because of the abundance of hyaluronan in skin, interest was early focused on variation in the content of the polysaccharide in various pathological conditions of this tissue. A large amount of early work utilized histological techniques of insufficient specificity but recent developments of specific analytical and staining methods for hyaluronan have supplied new data on its presence and possible role in skin disorders.

This is a randomized, double-blind, parallel-group, multicenter study involving 120 patients comparing the safety and tolerability of two midpotency topical preparations, fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, in the treatment of moderate-to-severe eczema. Safety of the study medications was determined over a twelve-week period using laboratory tests for selected fasting blood chemical levels, hematologic analysis, urinalysis, and morning plasma cortisol levels, and by analyzing both the nature and frequency of reported adverse events. Efficacy was evaluated during the first four weeks of the study. None of the fluticasone-treated patients experienced any severe drug-related adverse events, but one hydrocortisone-17-butyrate-treated patient's eczema was severely exacerbated by drug therapy. Plasma cortisol monitoring revealed minimal hypothalamic-pituitary-adrenal axis suppression. Overall, the nature of drug-related adverse events in patients as young as 12 years old treated with fluticasone propionate cream, 0.05%, indicates this topical application was safe and well tolerated throughout the twelve-week study. Fluticasone cream was also found to be similar in efficacy to hydrocortisone-17-butyrate cream.

Histochemical stainings of frozen sections of human normal and psoriatic skin were used to study the localization of hyaluronan (HA) and intercellular adhesion molecule 1 (ICAM-1). HA staining was found in all areas of the skin, with the exception of the stratum corneum, in both normal and psoriatic cases without any apparent quantitative differences between the conditions. The staining for ICAM-1 was detected in vessels in normal skin and at lower levels in normal areas of the skin in patients with psoriasis. However, in these patients the staining increased to about the same level as in normal skin after hyaluronidase treatment of the sections prior to staining. In psoriatic lesions, distinct staining for ICAM-1 was localized mainly to vessels and infiltrating leukocytes. Treatment of the sections with hyaluronidase increased the staining of vessels only slightly, but more strongly around leukocytes. These findings show that ICAM-1 is predominantly free from bound HA on vessel endothelium in psoriasis lesions but not on vessels in normal areas of the skin, and suggests that systematically administered HA, previously shown to reduce chronic inflammation in animal models, might have a beneficial effect in psoriasis via blocking of endothelial ICAM-1 and thereby causing a reduced invasion of leukocytes into the skin.

Juhlin L. A comparison of the pharmacodynamics of H1-receptor antagonists as assessed by the induced wheal-and-flare model.

We have developed a technique through which we can multiply melanocytes in culture from a small specimen of normally pigmented buttock skin and reimplant them into depigmented sites of vitiligo. To date, 90 patients have benefited in our hands from such autologous transplantation of pigment cells. Often we have an excess of cells which we would like to store for later use in the event a patient requires further treatment. We report here on 4 cases in which we have cryostored cultured melanocytes for 6-12 months, reimplanted them into vitiliginous sites of the donor after one week of reculture, and obtained optimal repigmentation. We now routinely freeze melanocytes left over after treatment.

The area of UV erythema produced by a small beam head was found to increase with increasing doses. The aim was to investigate whether measurement of the area could be a more useful indicator of UV-induced damage than classic visual grading. Topical pretreatment with all-trans retinoic acid (tretinoin) and betamethasone valerate was used to test the applicability of the method in pharmacological studies. We used a round outlet head (5 mm2) connected by optical fibre to a monochromatic irradiator, and doses ranging from 0.05 to 0.2 Joule of 300 mm UV light were applied to the skin of 6 healthy subjects. Erythemal area was calculated by the measurement of two diameters, and intensity was graded visually (0-6 scale). The area of the erythema correlated with the increase in intensity up to score 6. Area measurement was less subject to intra-investigators' variability than the intensity score. By multiplying intensity by area, a good indicator of UV-induced reactivity was obtained. Pretreatment with betamethasone valerate decreased the area of erythema, as did tretinoin 12 h after irradiation. Thus, area measurement of erythema is a useful adjunct to visual grading of UV-induced skin reactions.

A murine monoclonal antibody, BC12, was obtained after immunization against suprabasal human keratinocytes. In the epidermis of normal human skin, the antigen recognized by BC12 (BC12 antigen) is located at the apex of keratinocytes in the upper stratum spinosum and stratum granulosum but is absent in other layers. The BC12 antigen is also present in hair follicles. Immunoblotting performed on keratinocyte subpopulations confirmed the presence of the BC12 antigen in differentiated keratinocytes only. Two-dimensional immunoblotting showed that the BC12 antigen corresponds to a set of polypeptides with an apparent molecular weight of approximately 33kD. In keratinocyte cultures, the antigen is present only in stratified areas. The distribution of the BC12 antigen, as studied by indirect immunofluorescence and immunoelectron microscopy, and its presence in certain subcellular fractions of epidermal cells suggest that it is a component of membrane coating granules (MCGs) or that it is associated with these structures. Strikingly, in psoriasis, eczema and many other diseases, the BC12 antibody does not label the epidermis, but vessels in dermal papillae. The BC12 antibody may thus be a useful tool in the study of keratinocyte differentiation and MCG physiology, and, also, in pathology.

The inhibition of erythema by drugs applied topically after irradiation with 0.2-0.8 J of 313 nm has been studied in healthy volunteers. Indomethacin and piroxicam markedly inhibited the erythema at 6 to 24 h after irradiation but erythema reappeared at 45 h. The results reported suggest that the UVB response is biphasic with an early phase responsive to nonsteroid anti-inflammatory drugs and a late phase which is not responsive. No effect on the intensity of the erythema was seen with betamethasone chloroquine and cetirizine. Oral intake of aspirin before and/or after irradiation did not influence the UV response.

Biopsies of normal and diseased skin were immunohistochemically investigated for the presence of parathyroid hormone-related protein (PTH-rp). In normal skin and several skin disorders a monoclonal antibody against the 34-68 sequence of PTH-rp was found to be exclusively located in the granular layer. PTH-rp could not be detected in untreated psoriatic plaque lesions even when a granular layer was present. Psoriatic lesions improving after 1-2 weeks' treatment with betamethasone or vitamin D3 analogue revealed PTH-rp reactivity just above the granular layer. These findings substantiate a possible role for PTH-rp as a growth inhibitor. In the dermis the granular layer in the upper part of the hair follicles was stained for PTH-rp and the dermal infiltrates in 5 of 10 patients were stained with mycosis fungoides.

The effects of one week's daily treatment with dexchlorpheniramine (3 + 3 mg x 2) and loratadine (10 mg x 2) on the cutaneous reactions to putative mediators of urticarial reactions were studied in healthy subjects and in patients with chronic urticaria. Biopsy specimens were taken from skin with delayed reactions and studied immunohistochemically for the presence of eosinophilic cationic protein (ECP). In healthy subjects both antihistamines significantly decreased the weal and flare induced by histamine and the histamine releaser compound 48/80. They also reduced the flare seen after injection of PAF (platelet activating factor) and kallikrein. In patients with chronic urticaria the delayed reactions to PAF and kallikrein were larger than in healthy subjects. The immediate flare seen after injection of histamine, 48/80 and PAF, and the delayed reaction to 48/80, were significantly decreased by treatment with loratadine. No correlation was found between the clinical response and test reactions. In the group of healthy subjects, eosinophils were increased in the skin of all subjects after intradermal injection of 100 micrograms of PAF and in 50% after 1 microgram of PAF, but no eosinophils were seen after injection of 1 ng of PAF. In patients with chronic urticaria the eosinophils were increased at all sites where 1 ng of PAF had been injected and also at a limited number of sites of injection of histamine, 48/80, kallikrein and saline. Treatment with the antihistamines had no effect on the influx of eosinophils in the skin.

Given the variability of patient problems, it is difficult to construct a single drug therapy regimen for treatment of chronic urticaria. However, the following regimen should prove to be a useful outline to follow for most cases. The first line of therapy will usually be antihistamines. In general, antihistamines should be always used on a regular basis and not only after hives occur. If drowsiness or anticholinergic adverse symptoms limit the use of one drug in effective doses, other H1-blockers should be tried. For day-time use, the newer, less sedating antihistamines are preferred. If antihistamines fail to control symptoms when used at full doses, addition of glucocorticosteroids can be tried for short periods. Most patients respond to doses equivalent to 40 mg of prednisone daily. The end point of use of corticosteroids is to reach quickly an effective low, alternate-day dose followed by their discontinuation.

The effects of oral cetirizine on spontaneous and provoked urticaria were evaluated in two studies. In a double-blind crossover trial, 30 patients with idiopathic urticaria received 10 or 20 mg of cetirizine or placebo. Cetirizine was significantly more effective than placebo in reducing the incidence of erythema, wheals, and pruritus. No serious side effects were reported. In the second study of ten patients with chronic urticaria, immediate and delayed reactions to injected autologous serum, histamine, kallikrein, and synthetic platelet-activating factor (PAF)-acether were inhibited by 10 mg of cetirizine. These results suggest that the mechanism of action of cetirizine may involve inhibition of PAF-induced influx of eosinophils.

In atopic subjects, intradermal injection of platelet-activating factor (PAF), 40 and 400 ng, resulted in an immediate edema reaction markedly blocked by cetirizine, 10 mg twice a day. PAF challenge also induced a significant eosinophil accumulation evidenced by a skin window technique at 2, 4, 8 and 24 h. This inflammatory phenomenon was significantly inhibited by cetirizine. In patients with chronic urticaria, PAF, 100 μg intradermally, induced immediate and late cutaneous reactions (LCR) also blocked by cetirizine, 10 mg twice a day. These LCR were accompanied by an infiltration of the deep dermis by degranulated eosinophils. The pathophysiological mechanism of the PAF-induced skin reactions is discussed as well as the mechanism of action of cetirizine.

Eutectic Mixture of Local Anesthetics (EMLA) containing 5% lidocaine and prilocaine in a cream was found to give effective topical analgesia in normal and diseased skin, making it useful for superficial surgery and various other clinical procedures. To be effective, an adequate amount must be applied under occlusion and at the right time before the intervention.

The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.

Possible connections between carpal tunnel syndrome (CTS) and exposure to vibrating handheld tools, repetitive wrist movements, and heavy manual work were examined in a case-referent study. The cases were 38 men operated on for CTS between 1974 and 1980. For each case, two referents were drawn from among other surgical cases (hospital referents) and two further referents from the population register and telephone directory, respectively (population referents). Thirty four of 38 cases (89%) and 143 of 152 referents (94%) were interviewed by telephone. An increased prevalence of obesity, rheumatoid disease, diabetes, or thyroid disease was observed among the cases but most did not suffer from any of these disorders. CTS was significantly correlated with exposure to vibration from handheld tools and to repetitive wrist movements but showed a weaker correlation with work producing a heavy load on the wrist. A cause-effect relation between CTS and exposures to handheld vibrating tools and to work causing repetitive movements of the wrist seems probable. Some differences between hospital and population referents indicate that a case-referent study of this type could be biased by inappropriate selection of referents.

35 individuals showing reactions to penicillin of anaphylactic shock, angioedema or urticaria were investigated. Their skin sensitivity was analysed using 16 different penicillin derivatives. In addition, the content of circulating reagins against the penicilloyl structure in the patient’s sera were analysed using RAST. 17 of the patients had negative skin reactions and RAST results to all substances tested. The other 18 were skin test-positive to at least one derivative but showed markedly heterogeneous patterns of skin reactivity. 14 had positive reactions against penicilloyl structures accompanied by anti-penicilloyl reagins. Four patients showed doubtful reactions only to penicillin or penicilloate and/or penilloate. These patients also had very low levels of reagins against penicilloyl in their sera. Positive skin test results using monovalent penicillin derivatives such as penicillin, penicilloate, penilloate, penicilloyl amide, penicilloyl-formyl-lysine, penicillamine, which cannot form a multivalent antigen with penicillyol specificity, indicated formation of other derivatives of importance in penicillin allergy, e. g., penicillamine protein conjugates. Three patients showed skin reactions to ampicillin polymer and two to benzyl-penicillin polymer. The skin tests performed with the penicillin derivatives used do not seem to give more information on the sensitivity of the patiens than does the RAST using penicilloyl structures.

A 48-year-old woman with generalized scleroderma of the acrosclerosis type developed several lesions clinically, histologically and ultrastructurally, which were characteristic of necrobiosis lipoidica. The lesions were located to scar tissue. An increased collagen synthesis is suggested as a possible explanation.

SUMMARY Plasma from patients with active psoriasis has been shown to induce the formation of stellate fibrin-fibronectin microclots in vitro around cultured keratinocytes and fibroblasts. Such a stellate radiation of fibronectin and fibrin was also demonstrated around monocytes from patients with psoriasis. The phenomenon was not observed in healthy subjects but has been found in various disorders.

The time-course of cutaneous inflammatory responses to LTB4 and PGE2 both alone and in combination has been studied in 10 healthy volunteers. LTB4 induced a transient wheal and flare response in some subjects, maximal at 15 minutes and succeeded by an erythematous, indurated lesion at 2-4 hours. PGE2 elicited a wheal and erythema response which resolved within 1-2 hours. Combination of LTB4 and PGE2 produced acute wheal and erythema responses which did not differ significantly from the summation of responses to the individual constituents of the mixture or from responses to a two-fold increase in the concentration of either component. Wheal and erythema responses persisted, however, with significant potentiation of responses 4 hours after injection. As both leukotrienes and prostaglandins are generated in acute allergic reactions, the effects of these mediators in combination could contribute to persisting and late-onset responses to allergen, in both the skin and lung. In particular, sustained responses to the combination of LTB4 and PGE2 might be important in the pathogenesis of inflammatory skin diseases such as psoriasis.

The effects of the cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine in their base form) were studied in volunteers. When tested by pin-prick, EMLA cream 2.5% and 5% produced analgesia of the area tested, the cream being most effective if left in contact with the skin for 60 min. The pain produced by the insertion of an i. v. cannula was successfully blocked by the application of this formulation, especially if applied to the antecubital area. Temporary blanching of the skin areas was frequently observed on removal of the occlusive tape bandages, but prolonged, or repeated, application of 5% EMLA cream did not produce local skin reactions. Tests for delayed hypersensitivity reactions were negative. Plasma concentrations of lignocaine and prilocaine were low after a standard application.