Acta dermato-venereologica. Supplementum

Published by Society for Publication of Acta Dermato-Venereologica
The purpose of the present manuscript is to review the chemical and physical properties of epidermal lipids and to relate these properties to the formation and function of the permeability barrier of the skin. Lipids accumulate in small organelles known as lamellar granules as epidermal keratinocytes differentiate. This lipid is extruded into the intercellular spaces where it undergoes enzymatic processing to produce a lipid mixture consisting of ceramides, cholesterol and fatty acids. This intercellular lipid is uniquely organized into a multilamellar complex that fills most of the intercellular space of the stratum corneum. The barrier properties of the stratum corneum are related to the phase behavior of the intercellular lipids. It has been proposed that a structurally unusual acylglucosylceramide is thought to be involved in assembly of the lamellar granules, and a related acylceramide may have a major influence on the organization of the lamellae in the stratum corneum.
The childhood spectrum of non-bullous, non-syndromic ichthyosis (a) a collodion baby who later developed a mild congenital ichthyosis with fine or focal scaling (CIFS) phenotype (i.e. 'self-healing collodion baby'), (b) a newborn baby with congenital ichthyosiform erythroderma (CIE) (EM type I and no TGM1 mutations'– see Fig. 6 and Table I for explanation), (c) a case of harlequin ichthyosis 5 days after birth, (d) a 6- month-old baby with lamellar ichthyosis (LI) due to TGM1 mutations (EM type II), (e) a prematurely born baby with CIFS (EM type IV), (f) a 7- month-old baby with clumped fingers and toes (harlequin-like EM picture), (g) a 2-month-old baby with LI due to TGM1 mutations (EM type II), (h) a 4-year-old girl with LI due to TGM1 mutation (EM type II), and (i) a 10-year-old boy with TGM1 mutation and a focal appearance of LI (EM type II).  
Clinical spectrum of syndromic ichthyosis: (a) a newborn girl with Sjögren-Larsson syndrome (SLS); note the thick scales on the scalp and face (picture by Dr L. Bergfelt, Borås County Hospital), (b) right flank of an adult male with SLS, (c) a newborn boy with Netherton's syndrome, (d) a 10-day-old baby with the same syndrome; note severe erythroderma of the arms, (e) girl with keratitis-ichthyosis-deafness (KID) syndrome and typical ichthyotic plaques on the cheek, (f) the neck of an adult woman with suspected KID syndrome, (g) the face of the same boy as in (c), although 8 years later, (h) right thigh of a girl with erythrokeratodermia variables, and (i–j) the feet and fingers of a man with Vohwinkel's syndrome showing mutilating keratoderma and constriction bands (pseudoainhum) around the finger.  
Histopathologic abnormalities in various types of congenital ichthyosis (a-d: van Gieson staining; e-h: immunoperoxidase staining using antibodies against transglutaminase 1 (Tgase1)). (a) Epidermolytic hyperkeratosis (bullous ichthyosis) showing acanthosis, suprabasal cytolysis and massive hyperkeratosis, (b) lamellar ichthyosis (LI) showing mild hyperkeratosis and acanthosis, (c) congenital ichthyosiform erythroderma (CIE) with hyperkeratosis, acanthosis and dermal inflammation, (d) x-linked recessive ichthyosis with mild orthohyperkeratosis, (e) no Tgase1 expression in severe LI due to homozygous TGM1 mutations, (f) weak expression in a milder type of LI also due to TGM1 mutations, (g) normal expression in LI without TGM1 1 mutations, and (h) overexpression of Tgase 1 in CIE without TGM1 mutations.
Electron microscopy (EM) analysis of superficial epidermis in various types of congenital ichthyosis showing: (a) clumping of tonofilaments around the nuclei in bullous ichthyosis (epidermolytic hyperkeratosis), (b) numerous intra-corneocyte droplets in congenital ichthyosisform erythroderma (CIE) of unknown cause (EM type I), (c) aggregates of "cholesterol clefts" in lamellar ichthyosis (LI) due to TGM1 mutations (EM type II), (d) elongated intra-corneocyte membranes (arrowheads) in LI of unknown cause (EM type III), (e) lentiform areas in stratum corneum filled with membrane inclusions (arrowheads) in "prematurity ichthyosis" (EM type IV), (f) densely packed corneocytes with well-developed cell envelopes (arrows) in x-linked ichthyosis, (g) abnormally wide intercorneocyte spaces (x) in Sjögren-Larsson syndrome (picture by Dr H. Nordlinder), and (h) dispersed keratohyaline in KID syndrome, previously reported also in hystrix-like ichthyosis with deafness (7).
The adult spectrum of non-bullous, non-syndromic ichthyosis. Examples a–e are cases due to TGM1 mutations: (a) a man with severe, nontreated lamellar ichthyosis (LI), (b) a woman with a LI-congenital ichthyosiform erythroderma (CIE) overlap (EM type II), (c) a mild LI in an adolescent girl, (d) keratoderma in association with LI (EM type II), (e) women with severe LI and total alopecia (EM type I), (f) female with LI (EM type III), (g) a man with severe CIE, note abnormal fingers (harlequin-like EM picture), (h) a woman with moderate CIE (EM type I), (i) a woman with mild LI, and (j) a man with KLICK syndrome (keratosis linearis, ichthyosis congenita and keratoderma) and striate hyperkeratosis in the flexures  
Congenital ichthyosis comprises a rare group of usually monogenetic diseases that present at birth as a collodion phenotype or as variable degrees of ichtHyosiform erythroderma, with or without superficial blisters. Depending on which gene mutation causes the disease, the skin problems later in life may range from a severe lamellar or bullous ichthyosis to mild or only focally expressed hyperkeratotic lesions. It is obviously important, but sometimes painstakingly difficult, to make a correct diagnosis already in infancy. Fortunately, recent advances in our understanding of the molecular genetics of ichthyosis have led to several new diagnostic tools that are continuously being updated. Based on this development, and on our own 5 years of experience in a national genodermatosis centre, we describe 127 cases of congenital ichthyosis examined in childhood or adulthood. Applying a combination of phenotypic and genotypic criteria, the patients were classified into three main groups: 1) Bullous ichthyosis (epidermolytic hyperkeratosis) and related disorders due to keratin mutations (n = 21); 2) Non-bullous ichthyosiform erythroderma and lamellar ichthyosis mainly due to transglutaminase 1 mutations (n = 80); 3) Syndromic ichthyosis, i.e. systemic (multi-organ) diseases due to many different causes (n = 26). Each group could be further stratified into 4-11 entities using mutation analysis, electron microscopy of epidermis and various other techniques. Our findings are discussed in relation to recent data in the literature emphasizing the clinical usefulness of various diagnostic procedures for ichthyosis.
Clinical experience obtained in the management of 138 patients of psoriatic arthritis is reported. The correct recognition of arthritic subtype (according to Moll and Wright classification) always resulted essentially in the choice of the therapy. Our programme included rehabilitative, pharmacologic and surgical approaches. Our data suggest that psoriatic arthritis is a mild articular disease when compared to other affections such as rheumatoid arthritis or ankylosing spondylitis. Notwithstanding an accurate therapeutical programme, it is necessary to control atypical cases which not infrequently can occur.
In a prospective computerized study on atopic dermatitis (AD) several basic and minor clinical features in patients with AD (n = 110) and a sample of the normal population (n = 527) was studied systematically and analysed statistically with regard to their diagnostic importance. On basis of chi-square values a diagnostic score system was constructed which might help to establish a firm diagnosis of AD in patients with ambiguous cutaneous inflammatory disease. Based on this score system patients with more than 10 points should be considered atopic, patients with 6 to 10 points are suspected to be atopics. An association between serum IgE and the amount of atopic points was found. Seven percent of the normal population sample proved to be obviously atopic, another 19% were suspected to be atopics.
Microbial findings were analyzed from a group of 167 patients with psoriasis in an attempt to discover specific associations. Positive findings include associations between Malassezia ovalis and scalp/ear/face psoriasis and between bacteria and bodyfold, nailfold, and gluteal/rectal psoriasis.
The efficacy and tolerability of acitretin (etretin) in severe psoriasis was compared with that of etretinate in a double-blind randomized study for 12 weeks. A total of 127 patients received acitretin and 41 received etretinate. The initial daily dose was 40 mg/day over 4 weeks and was subsequently adjusted according to individual response. From week 5-12 the mean daily dose was 42.9 mg of acitretin (0.58 mg/kg) versus 49.2 mg of etretinate (0.65 mg/kg). Acitretin gave a PASI score reduction from baseline of 70.5% and etretinate a reduction of 68.4% (mean values). Acitretin tended to give more discomfort than etretinate, particularly with regard to hair loss and peeling of palms and soles. The differences found between acitretin and etretinate may be related to higher maximum plasma concentrations of acitretin. The considerably shorter half-life of acitretin, gives it a great advantage over etretinate with regard to risk of teratogenicity after cessation of treatment.
The changes in disease pattern in a Danish skin clinic during the period 1947 to 1977 is reported. The data rest upon comparisons from patient registrations taken with ten years interval. The study also comprises comparison of frequencies of positive patch tests between 1947 and 1977. The data show, that the disease pattern was far from stable. An increased frequency was registered in atopic dermatitis, allergic contact dermatitis, drug eruptions, urticaria, skin cancer, psoriasis and viral diseases. While reductions were found in all other infectious diseases, seborrheic dermatitis, and so called "non classified eczema". The changes are postulated to be of a multifactorial origine. Environment was supposed to be the main factor in regard to contact dermatitis and some infections and to be of great importance to skin cancer, while better therapeutic posibilities seem to have influenced the frequency of most of the remaining disease groups. Pronounced changes were also registered among the ten most commonly detected contact allergens. It is stated that preventive measures are extremely important within this area. The decrease in contact allergy to balsam of Peru is used as an example of the effects of good preventive medicine.
The paper presents the results of a cooperative, retrospective study of mycosis fungoides in Norway, in 112 patients diagnosed histologically between 1960-80. The study includes an analysis of incidence, clinicopathological findings, survival, mortality and autopsy findings. In addition, other factors, such as occupation, the incidence of cancer, associated illnesses and contact allergies are reviewed. The significant prognostic variables with regard to survival included, age at diagnosis, stage of the disease at diagnosis and occupation. Industrial workers showed the highest incidence of MF and the poorest prognosis in terms of survival after biopsy. In 59% of deceased MF patients, the cause of death was related to MF.
55 cases of neurosyphilis, probably all that has been disclosed in Denmark in the nine year period 1971 to 1979 are submitted. 55 case histories and 10 tables illustrate the variegated clinical features and the differential diagnoses, the serological data, and CSF findings, the treatment and its results. As the symptomatology of the series fits well into the classification of neurosyphilis of the past our cases are classified accordingly in five clinical groups with seven subgroups. Penicillin treatment was applied to all the patients in current dosages and proved beneficial in most patients with regard to clinical symptoms and to laboratory parameters. The outcome here registered seem, however, to be related more to the character of the disease than to the types or amounts of penicillin. Eleven of the patients had a history of previous positive serology and two of them had been treated with penicillin for early syphilis but their neurosyphilis was evidently due to an untreated reinfection. Ten of the patients had aortitis.
All causes of occupational skin diseases seen during a 10-year period (1974-1983) at the Institute of Occupational Health in Helsinki were analyzed, and certain important groups of occupational dermatosis diagnosed at the Institute during 1974-1988 underwent further, detailed study. A total of 1,082 cases of occupational dermatoses were diagnosed between 1974 and 1983. Contact eczema was the most common diagnosis, comprising 1,052 cases (97%), of which 542 cases (52%) were allergic and 510 cases (48%) irritant eczema. The five most frequent causes of allergic eczema were metals (154 cases = 28%), plastic materials (150 cases = 28%), rubber and rubber chemicals (108 cases = 20%), formaldehyde (31 cases = 6%), and colorants (16 cases = 3%). When the statistics compiled by the Institute in 1946-1972 were compared to the data of the present study, allergy to plastic materials and rubber had increased considerably, accounting for 8% and 11% of cases in the first statistics, and for 28% and 20% of cases, respectively, in the latter. Chromium, which had previously ranked first of all allergens, fell to third place. Turpentine is no longer one of the main allergens, whereas formaldehyde still remains one of the most common causes of occupational allergic eczema. Rubber gloves caused two-thirds of all cases of rubber eczema diagnosed during 1974-1983. Rubber gloves represented 93%, whereas plastic gloves represented only 7% of all allergic glove dermatoses during that 10-year period. Acrylates, which are both skin irritants and sensitizers, were the fourth most common cause of eczema due to plastics during the same 10-year period. Textile, leather and fur dyes were the main causes of occupational eczema due to colorants during the 10-year period of 1974-1983. The present study also found that formaldehyde is a common cause of occupational allergic eczema, and a rare cause of occupational urticaria. The most common sources of formaldehyde allergy were glues, washing agents, textiles, formaldehyde solutions, and dust containing formaldehyde resins. All patients were allergic to 1% formaldehyde in water, and a positive dilution series confirmed the result. A provocation test commonly used when formaldehyde asthma is suspected is recommended to confirm the diagnosis of formaldehyde urticaria.
Trends of N. gonorrhoeae (1975-1991) and C. trachomatis (1988-1991) infections in Norway were analysed by the National Institute of Public Health (SIFF) using data reported by physicians. The validity of the reporting system was evaluated by comparing reported data from the three northernmost counties and particularly the Kautokeino community to SIFF with confirmed positive specimens analysed by the two microbiological laboratories serving this area. The incidence of gonorrhoea in Norway has declined continuously from 300 cases per 100,000 annually in 1976 to 15 in 1991, whereas C. trachomatis infections with annual rates of 300 cases per 100,000 during the last 4 years has shown no significant decrease. The incidence of gonorrhoea in the county of Finnmark has shown the same declining trend as for the rest of the country, but is still four times higher than the national average. C. trachomatis infections show no obvious declining tendency in any part of the country and is three to four times higher in Finnmark than the average for the country. Kautokeino experienced a dramatic decrease in gonococcal infections from more than 1000 cases per 100,000 in 1976 to almost eradication in 1991, whereas C. trachomatis infections show a four times higher annual incidence than the national average. Although gonorrhoea is almost eradicated in Norway, C. trachomatis infections remain an important public health problem. This study indicates that young, sexually active individuals need to be targeted for effective health education in order to modify behaviour patterns which put them at risk of acquiring STDs.
The present work is the first epidemiological study carried out by the Spanish Contact Dermatitis Research Group during 1977. During this year 2806 patients were studied with patch test among 30873 dermatological patients. The 60-62% of the totality had reactivity to one or more patches. Four major groups of allergens were able to consider, following the incidence in their power of sensitize. First group with strong incidence include: Nickel, Chromate, Cobalt, T.M.T.D.,P.P.D.A., Mercapto mix., and Wood tars. Second and third groups with medium incidence contain: Caines, Carbonates, Neomycin, Balsam of Peru, Mercury, Lanolin, Naphtyl mix., Formaldehyde, Benzalkonium chloride, P. P. D. A. mix, and Turpentine. Four group show very low incidence substances, as: Epoxi, Sulfonamides, Etilendiamine, Parabens, Chinoform, Colophony and Cinnamon oil. Few comments about age and occupations are included.
Of a total of 3731 patients investigated between 1974 and 1990, 1844 (49.4%) had an occupational skin disease. Of them 142 (7.7%) had an occupational skin disease caused by epoxy compounds--135 patients (95%) had allergic contact dermatitis, five had irritant contact dermatitis, and two had contact urticaria. Apart from dermatoses, two patients had IgE-mediated asthma from exposure to DGEBA epoxy resins. Thus epoxy compounds are one of the main causes of occupational allergic contact dermatoses and can be considered potential causes of occupational asthma. The most frequent causes were epoxy resin compounds, which together induced 93% (132 cases) of all epoxy compound dermatoses. The three most common causative products were epoxy paints and their raw materials (31%, 41 cases), epoxy resin compounds used in electrical insulation (29%, 38 cases) and epoxy glues (18%, 24 cases). Fewer cases were caused by products containing epoxy acrylate and EPTMAC. The present study found that, in addition to contact allergy to DGEBA epoxy resins, contact allergy to epoxy hardeners, non-DGEBA resins and reactive diluents is common. Polyamine hardeners, most frequently MDA, DETA and TETA, rarely IPDA, tris-DMP, EDA, TMD and XDA, were the second commonest causes of contact allergy induced by epoxy resin compounds, after DGEBA epoxy resins. Cycloaliphatic epoxy resins and other non-DGEBA epoxy resins, including heterocyclic dimethyl hydantoin, phenol novolak and brominated epoxy resins, were the third commonest causes, and reactive diluents the fourth commonest cause of allergic dermatitis due to epoxy resin compounds. Most patients sensitized to reactive diluents were allergic to PGE, ortho-CGE, HDDGE and BDDGE, whereas fewer patients were sensitized to AGE, NPGDGE and BGE. Cross-sensitization between reactive diluents was common. Cardura E 10 and Epoxide 8 provoked no reactions. The present study also indicated that DGEBA epoxy resins with a high average MW ought to be regarded as potential sensitizers, and organic solvents probably promote sensitization to DGEBA, even if the amount of DGEBA is low in the causative products. When contact dermatitis induced by epoxy compounds is suspected, an accurate diagnosis is made with the use of detailed data on the patient's exposure and extensive patch testing, including tests with the patient's own products. No chemical can be used alone to screen for sensitization to all different contact allergens of epoxy compounds.(ABSTRACT TRUNCATED AT 400 WORDS)
We report the initial results arising from analysis of a prospective computerized study of infantile atopic dermatitis in which, among other factors, the criteria of severity of the dermatitis was considered for the first time. Besides providing informations on the natural history of childhood AD, this study showed that onset of asthma was significantly earlier in children affected with severe AD.
The aim of this study was to evaluate the long-term effects of intermittent Cyclosporin A treatment of severe plaque psoriasis. For this purpose we considered the clinical records of 26 patients who had been intermittently treated with Cyclosporin A for 2 to 4 years. All 26 patients had severe plaque-type psoriasis (PASI score > 18) that was unresponsive to conventional treatment. The initial Cyclosporin A dosage was 5 mg/kg/day in 8 cases and 3 mg/kg/day in 18 cases. In all patients, Cyclosporin A treatment was prolonged until complete or nearly complete remission of psoriasis (mean 2 months; range 1-4 months). All patients subsequently underwent a 2-4 months maintenance treatment with Cyclosporin A dosages that were gradually reduced until tapering off. In order to maintain clinical improvement after Cyclosporin A withdrawal, patients were treated with topical steroids, topical tar, emollients and UVA exposure and/or eliotherapy. Cyclosporin A treatment (2.5-3 mg/kg/day) was reintroduced only when clinical relapses reached a PASI score of 12 or more. Duration and dosages of Cyclosporin A cycles were always adapted for the purpose of obtaining an improvement acceptable to the patient (PASI < 8) rather than total clearance of psoriasis. So far, the 26 patients have undergone 3-5 cycles of therapy with low doses of Cyclosporin A. None of these 26 patients interrupted Cyclosporin A treatment because of side effects. In conclusion, in our experience cyclic CyA treatment is effective for the long-term treatment of psoriatic patients.
Xenotransplanted human melanoma was investigated by measuring the increase in tumour volume and in final tumour weight (macroscopical parameters) and histomorphological parameters of cell proliferation: Mitotic index (MI) and autoradiographic [3H]thymidine labelling index (LI). A total of 87 tumours, derived from a human melanoma metastasis and a primary nodular melanoma respectively, were analysed by these methods in two series. Topical treatment of the tumours with azelaic acid cream resulted in a statistically significant reduction in the increase in tumour volume and, in the first series, in a clear decrease in final tumour weight and in the MI, as compared with controls. The LI was decreased only in the superficial region of the tumours, i.e. at the site of treatment. Subtumoral injection of azelaic acid (disodium salt solution) was the second route of local therapy. It was followed by a significant reduction in the increase in tumour volume, of final tumour weight (first series) and in the MI. The average LI was clearly smaller than in the controls, especially at the tumour base, which was the site of injection (local effect). Systemic (intravenous) injection of azelaic acid (same concentration of the disodium salt solution) had no negative effect on the increase in tumour volume or final tumour weight, but was followed by a clear reduction of the MI. The average LI of this group was significantly smaller than in the controls as well. This effect was most impressive in the perivascular regions of large and small vessels, which fact can be interpreted as a sort of local effect via the blood stream after systemic application of azelaic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
PTFE ¯ow-through permeation cell.
E2 (A) and NETA ¯ux (B). The curves contain the average ¯ux data from all ten permeation cells (2, 4, 8, 16 and 24 hr, in duplicate). Black squares mark the predetermined hours where each time two permeation cells were disassembled to prepare the skin samples for visualization studies. E2 (C) and NETA (D) cumulative penetrated mass and surface related steroid contents. 3 H-E2 (E) and 3 H-NETA (F) silver grain densities (divided by the autoradiography exposure time) over stratum corneum and viable epidermis.
Developing transdermal therapeutic systems for estradiol and norethindrone acetate raised questions about the steroids penetration pathway across and retention in the skin. This paper describes the distribution of 3H-estradiol and 3H-norethindrone acetate in human stratum corneum after topical application to dermatomed skin in vitro. The study involved (a) permeation experiments to determine the steroid flux, (b) autoradiographical visualization of the steroid distribution in the same skin samples, and (c) a correlation between flux and skin distribution in time. On correlating the steroid flux with intraepidermal steroid distribution, it was concluded that both permeants were bound in the skin tissue. The steroids were preferentially located in or close to the intercellular lipids of the stratum corneum, indicating that both transport and binding occurred via this domain of the stratum corneum. This study demonstrated the importance of correlating drug flux with intraepidermal drug distribution as a function of time.
The aim of this study was to define the prevalence and clinical features of Juvenile Psoriatic Arthritis (JPsA). According to the definition by Ansell and Bywaters, we identified the population at risk of JPsA in 425 patients with psoriasis with onset occurring before the age of 31. Among these, 85 were younger than 16 years. Five patients with JPsA were found (prevalence 1.0%). All had a family history of psoriasis and onset of skin disease in the age range 10 to 20 years. Arthritis preceded psoriasis in two cases, while in the remainder the converse occurred. The interval between the onset of cutaneous and articular involvement never exceeded 8 years. Previous studies reported the low frequency of JPsA among juvenile arthritides. Our data appear to underline the rarity of the arthritic form.
It is well known that genetic heterogeneity and/or the complex interaction of several MCH-linked risk factors can explain the onset and the broad spectrum of Psoriatic Arthritis (PsA) from the clinical point of view. Fifty-eight patients with PsA (Moll and Wright criteria), 35 men and 23 women, mean age of 45, 14, were studied; all the patients were assessed by both clinical and radiological examination, with particular attention to the sacroiliac joints. HLA typing of the patients confirmed the association between PsA and HLA-B39 (p = 0.0008) and Cw6 (p = 0.0011). In addition a significant increase in DQ2 antigen (p = 0.004) has been found. No correlation of any particular HLA antigen with clinical subsets (oligo-polyarticular peripheral PsA, axial PsA and axial with peripheral PsA) or erosive incidence of joint involvement-generally related to the duration of the disease--was found.
The mol wt of the extracted tonofilaments was estimated from the results obtained by both sodium dodecylsulfate acrylamide gel electrophoresis and gel filtration in 6 M guanidine hydrochloride. Monomer (60,000), dimer (120,000) and polymer were apparent in the gel filtration study and the monomer consisted of 2 major and 4 minor subunits (43,000 to 71,000) on the electrophoretic analyses in the presence of 0.1% sodium dodecylsulfate.
Calcipotriol, a non-calcemic vitamin D3 analogue, inhibits the proliferation and is necessary for final differentiation of keratinocytes. The aim of the present study was to determine the efficacy and tolerability of calcipotriol ointment in patients treated for 6 weeks. Twenty patients with chronic plaque-type psoriasis were treated twice daily with calcipotriol ointment 50 ng/g. After 6 weeks' treatment there was a marked and statistically significant decrease in the PASI score values for 17 patients, no improvement was seen in 1 patient and local adverse events occurred in 2. Hypercalcemia or other laboratory abnormalities did not develop in any patient.
Ninety-six persons, living in Gothenburg, Sweden, on the first of January 1978 and known by the health services as cases of neurofibromatosis, were investigated concerning clinical and genetic aspects of the disease. Close relatives were also interviewed and examined. The diagnostic criteria were operationally defined according to number of café-au-lait spots and/or neurofibromas. The prevalence of neurofibromatosis was estimated to be 0.02%. The following findings were made in the patients: axillary freckling (48%), neurological symptoms (30%), epilepsy (3-9%), sarcoma (4%), pheochromocytoma (3%), osseous dysplasias (12%), subnormal intelligence (45%) and psychiatric symptoms (33%). The genetic analysis revealed a dominantly inherited disease with full penetrance and a very high mutation frequency, at least 4.3 X 10(-5). Questions commonly encountered during counselling are discussed.
The HLA-ABC antigens were investigated in 29 patients with pure atopic dermatitis and 43 patients with atopic dermatitis combined with atopic respiratory disease (ARD). Furthermore, the DR antigens were studied in 10 patients with dermatitis alone and in 24 patients with combined atopic disease. The frequencies of antigens and the HLA phenotypes A1, B8 and A3, B7 in the entire group of patients and in two subgroups did not differ significantly from those in controls, when correction was made for the number of comparisons made. However, the frequency of HLA-DR7 was strikingly low, but this observation needs confirmation. IgE levels were measured in eight patients with pure dermatitis and in 24 patients with dermatitis combined with ARD and found equally increased in both groups compared to controls.
A variety of abnormalities of the uninvolved skin have been reported in psoriasis, but there are few studies in which abnormalities of the stratum corneum (SC) have been investigated. In this study we have examined the intracorneal cohesion and structural detail of corneocytes of the SC from involved and uninvolved sites in 24 patients with psoriasis and 10 controls. We have found that intracorneal cohesion is increased in the involved and uninvolved skin of psoriatic patients compared to controls and that there are abnormalities of stratum corneum and corneocyte structure as determined by scanning electron microscopy. The changes in the uninvolved sites may well be due to the increased rate of epidermal cell production in these areas.
Having found an inability of patients with atopic eczema to distinguish different levels of iontophoretically applied histamine concentrations, as shown by their diminished vascular reactions and itch responses, and reviewing this result in the light of our new findings of smaller flare reactions and weaker itch sensations following different concentrations of intradermally injected substance P, we have concluded that unmyelinated afferent skin nerve fibres in these patients seem to be affected by the pathophysiological mechanism of atopic eczema. We therefore suspect that a down-regulation of histamine receptors at nerve endings compensates for elevated histamine release from cutaneous mast cells in patients with atopic eczema.
Exposure of normal mononuclear leukocytes (MNL) to histamine causes heterologous desensitization accompanied by beta adrenergic receptor alterations and increased cyclic AMP-specific phosphodiesterase (PDE) activity. We have demonstrated similar abnormalities in MNL from patients with atopic dermatitis (AD). Considering that these dual changes might be due to altered phosphorylation, we have studied cyclic AMP-dependent protein kinase (PK-A) in untreated and histamine-treated normal MNL and in AD cells. We found that basal or endogenous phosphorylative activity was two-fold higher in preparations from patients with AD. The activity ratios of protein kinase increased significantly in normal MNL after histamine exposure. In contrast, cells from patients with AD failed to show this increase. These findings correlate with similarly increased PDE activity after histamine stimulation of normal, but not AD cells. The increased PK-A activity in both atopic and histamine-desensitized MNL correlates with membrane receptor changes and elevated PDE activity. This enchaned phosphorylation may account for the varied physiological and immunological abnormalities that have been described in AD.
Top-cited authors
Thomas L Diepgen
  • Universität Heidelberg
Manigé Fartasch
  • Ruhr-Universität Bochum
Birgitta Meding
  • Karolinska Institutet
Magnus Sven Ågren
  • University of Copenhagen
Finn Schultz Larsen
  • Odense University Hospital