[Skin of the aging human being]. / Huden hos den åldrande människan.

Cutaneous aging includes true aging and photo-aging due to sun exposure. A decrease in epidermal turnover rate results in epidermal atrophy and delayed wound-healing. A reduction in the number of epidermal Langerhans' cells is responsible for a decrease in delayed immune responsiveness in skin observed in the elderly. Reduced numbers of fibroblasts and mast cells are typical histologic findings in aging human dermis. Collagen bundles become fragmented, less elastic and more brittle. Telomere shortening at the end of chromosomes is probably the major mechanism of cellular senescence in skin. Common skin tumors and other major age-related changes in the skin of the elderly are described.

Microdialysis of histamine in the skin of patients with mastocytosis.

Mastocytosis represents a group of disorders characterized by the proliferation and accumulation of mast cells in tissue. The aim of the present study was to examine whether the interstitial histamine concentration in the skin is increased in mastocytosis patients and whether it correlates with the number of mast cells, the amount of metabolite N-methyl-imidazole acetic acid in the urine and the tryptase in serum. In 7 mastocytosis patients on a standardized diet, the analysis of histamine was performed on microdialysates obtained from catheters positioned intracutaneously in involved and uninvolved skin. N-methyl-imidazole acetic acid in the urine was collected for 24 h. Biopsies for analyses of mast cells were taken from skin adjacent to the microdialysis catheters. The histamine concentrations were 42+/-14, 12+/-3 (P<0.05) and 8+/-2 nmol/l (mean+/-SEM, n=7) in skin eruptions, non-lesional skin and plasma respectively. Mean N-methyl-imidazole acetic acid in the urine (9.7+/-3.5 mmol/mol creatinine) and mean tryptase (124+/-54 microg/l) had increased in all patients. In the present study, no linear correlation was found between these parameters and interstitial histamine in lesional skin. This finding corresponds to the fact that the concentration of histamine metabolites and tryptase derives from the entire mast-cell population, while interstitial histamine in the dermis represents the local tissue concentration before metabolic transformation. The microdialysis of histamine in the skin of mastocytosis patients could be used as a tool to investigate the effects of dermal mast-cell histamine release in different kinds of treatment regimen.

Cytogenetic studies in patients with mastocytosis.

Chromosomal aberrations in hematopoietic cells are common in malignant hematological disorders and have also been reported in some patients with mastocytosis. In this study, 34 patients with either urticaria pigmentosa or systemic mastocytosis were investigated by cytogenetic analysis of bone marrow cells. A follow-up investigation was performed in 22 patients. Clones with chromosome abnormalities were found in 32% of the patients at the first examination and in 27% at the second examination; in total, 41% of the patients had an abnormal clone in at least one examination. No clinical correlation was found with regard to cytogenetic results, with the exception of four patients who had an associated hematological disease and poor prognosis. In the second examination, only 6 patients had an unchanged chromosome pattern, and 4 of the patients with an initial normal pattern had appearance of abnormal clones; however, in 7 patients, the initial abnormal cells disappeared. The abnormalities were, among others, deletions of chromosomes 5, 7, 11, and 20. The proportion of cells with structural or numerical chromosome changes was higher in comparison with reported control groups. The frequency and type of chromosome abnormalities in bone marrow cells from patients with mastocytosis was about the same as observed in other chronic myeloproliferative disorders and myelodysplastic syndromes, diseases which also developed in 4 of our patients. An association between malignant hematological disorders and mastocytosis have been suggested by us and others. The chromosome abnormalities maybe reflect a genetic instability of the hematopoietic cells in mastocytosis.

Serum tryptase measured with B12 and G5 antibody-based immunoassays in mastocytosis patients and its relation to histamine turnover.

Serum tryptase was measured with the B12 and G5 antibody-based immunoassays in 25 adult patients with mastocytosis and in 18 controls. Twelve patients had uncomplicated cutaneous mastocytosis (urticaria pigmentosa) and 13 had urticaria pigmentosa with systemic symptoms. Tryptase levels were compared with histamine turnover estimated as urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid. Elevated B12 tryptase levels (> 20 microg/L) were found in most mastocytosis patients, including five of eight patients with only cutaneous manifestations who had a low urinary histamine metabolite excretion. This indicated a higher sensitivity for diagnosing mild mastocytosis on the basis of levels of serum tryptase as opposed to urinary methylimidazoleacetic acid. However, the serum B12 tryptase assay could not differentiate between urticaria pigmentosa patients with and without systemic disease: the measurement of histamine metabolite excretion probably reflects the mast cell burden more accurately. Serum G5 tryptase levels were generally low in both controls and mastocytosis patients.

PUVA in early mycosis fungoides may give long-term remission and delay extracutaneous spread.

We report a follow-up for 3-18 years of 24 patients with the non-infiltrated patch and infiltrated plaque stage of mycosis fungoides, treated with psoralen photochemotherapy (PUVA) and on resistant infiltration or development of tumours also with fractionated radiation therapy. All patients with patch and limited plaques showed complete remission after initial PUVA therapy. Half of the patients with patch stage mycosis fungoides and also half of the patients with plaque stage mycosis fungoides were in complete remission when the study ended. Most of them had remission periods for years after early PUVA treatment. Patients with more advanced mycosis fungoides needed repeated periods of PUVA therapy. Two patients with extensive infiltrated plaques did not reach complete remission at all during the study but progressed and finally died of their T-cell lymphoma. Another 4 patients with extensive plaque stage mycosis fungoides died after initial complete remission for a maximum of 3 years. In this investigation the clinical evaluation was made by one dermatologist and the histopathological evaluation by one pathologist. This is of importance since in the early stages of mycosis fungoides the diagnosis is challenging and may require a combination of clinical, histopathological and molecular evaluations. The identification of early disease is crucial for the rapid implementation of adequate treatment. The study shows that early PUVA therapy may delay extracutaneous spread and possibly also in some cases be curative.

Bone density, bone markers and bone radiological features in mastocytosis.

We examined the association between severity of disease in mastocytosis and skeletal manifestation and bone markers in 16 patients varying in extent of mastocytosis as determined by the urine excretion of methylimidazoleacetic acid. Both osteoporosis and osteosclerosis were found. Bone density in the hip was significantly higher (p < 0.05) in both men and women with an enhanced histamine metabolite excretion. Patients with only moderately increased mast cell mass had low bone mineral density in the hip, osteoporosis and vertebral fractures. The different skeletal disease patterns in mastocytosis might be the effect on osteoblasts and osteoclasts of biologically active substances. Mast cells release a number of vasoactive substances, including histamine which promotes osteoblasts and heparin and prostaglandin D2 which induce bone resorption by activation of osteoclasts. Systemic mastocytosis is a rare disease characterized by multi-organ infiltration by mast cells and with varying skeletal manifestations including osteoporosis. Treatment with bisphosphonates may be beneficial in arresting osteoporosis in this disorder.

Indications of a considerable decrease in the death rate in mycosis fungoides by PUVA treatment.

PUVA therapy has its roots in ancient India and Egypt and began to come into general use in the highly developed countries in the middle of the 1970's (1). The first reports of PUVA treatment of mycosis fungoides were published in 1976 (2); these were followed by several other studies in the two following years (3-7). Some of the early work on PUVA therapy was carried out in Sweden (8,9), and the modality was in general use in most major clinics by 1977. The dramatic effect on mycosis fungoides of PUVA therapy is well known, but whether the death rate is influenced is not known. For ethical reasons no controlled clinical studies have been performed. Sweden is a highly organized country with reliable death statistics at least for diseases as conspicuous as mycosis fungoides. The purpose of the present study was to provide data on the death rate in mycosis fungoides in Sweden from 1961 to 1990, which we think is relevant to the question whether PUVA treatment decreases the death rate in mycosis fungoides.

No relationship between histamine release measured as metabolite excretion in the urine, and serum levels of mast cell specific tryptase in mastocytosis.

To test the hypothesis that histamine release in mastocytosis patients generally occurs without activation of the mast cells, histamine turnover, measured as histamine metabolite excretion in the urine, was compared with the serum level of mast cell specific tryptase, which is released only during active discharge of mast cell granular contents. Twenty mastocytosis patients with a wide range of histamine turnover rates were investigated. Slightly increased levels of tryptase were found in seven patients with no obvious relationship to histamine metabolite excretion. In contrast, there seemed to be a connection between the tryptase level and the severity of symptoms. These results strengthen the view that histamine in mastocytosis is predominantly released from the mast cells without any accompanying active release process. This does not exclude the possibility that, in some mastocytosis patients, a limited number of mast cells, or a subpopulation, may be actively secreting histamine together with tryptase.

A follow-up study of bone marrow chromosomes and in vitro colony growth in patients with mastocytosis.

Proliferation of mast cells can give rise to many clinical manifestations in patients, and an association with hematological disorders has been pointed out. The study was initiated to determine whether patients with mastocytosis show a clinical progression in relation to bone marrow cell parameters analyzed. During a median follow-up period of 5.5 years, 10 patients with mastocytosis were re-examined with regard to clinical symptoms, urine histamine metabolites (U-MeImAA), bone marrow cells examined with chromosome analyses, and in vitro stem cell growth for CFU-GM. Seven patients showed a clinical progression with increase of either symptoms, bone marrow infiltrates of mast cells or U-MeImAA. One patient with a myeloproliferative bone marrow morphology had a malignant course. Four of the 7 patients showed an increased colony growth, while 3 showed a decreased growth, in the second examination compared with the first examination. One patient had a persistent clone with the chromosome aberration 9p+. A variable pattern was observed in the other patients, in resemblance with findings in chronic myeloproliferative disorders. Our conclusion is that mastocytosis belongs to the myeloproliferative disorders.

Clinical, immunological and bacteriological evaluation of adverse reactions to skin-penetrating titanium implants in the head and neck region.

Between 1977 and October 1989, 445 patients have been treated with bone-anchored skin-penetrating titanium implants for anchorage of facial prostheses or bone-conducting hearing aids, at the Ear, Nose and Throat Department at Sahlgren's Hospital in Gothenburg. The majority of patients had no adverse skin reactions, while a few patients were responsible for the majority of the adverse reactions. The aim of our study was to analyse differences between these groups. We started a clinical study on 9 patients with a clinical history of adverse skin reactions around the titanium implants and 9 patients without adverse skin reactions were used as controls. None of the patients had delayed hypersensitivity to titanium. Microbiological analyses showed that when there was clinical irritation, Staphylococcus aureus could be isolated.

Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides.

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.

Allergic contact dermatitis from diphenylthiourea in Vulkan heat retainers.

11 cases of contact dermatitis from Vulkan heat retainers are reported. The skin eruptions started on days 1-11 after the 1st day of exposure. The clinical picture varied from eczema through urticaria to purpura. In some cases, the symptoms were severe. Patch testing was performed in 10 individuals and all reacted positively to the heat retainer and/or the rubber glue used in the heat retainer. A series of rubber chemicals was patch tested in 7 patients and all showed positive reactions to diphenylthiourea (DPTU), and all but one to ethylene thiourea (ETU). TLC examination revealed a spot with the same RF-value as DPTU in extracts of the adhesive, but no spot corresponding to ETU. There were no indications of impurities in the test preparations of DPTU and ETU. By HPLC, the content of DPTU in the adhesive was determined as 0.6% w/w.

Serum levels of neutrophil and eosinophil chemotactic activities in mastocytosis.

Neutrophil and eosinophil chemotactic activities (NCA and ECA) were measured in serum from twenty-two patients with urticaria pigmentosa or systemic mastocytosis. NCA was also measured after heating serum to 56 degrees C (heat-stable NCA). Although these factors were increased in about half of the patients there was no correlation with histamine release as estimated by the excretion of the main histamine metabolite methylimidazoleacetic acid (MelmAA) in urine. A significant increase in heat-stable NCA, however, was found in patients with pruritus and abnormal high values of MelmAA. It is concluded that only heat-stable NCA is a specific mast cell mediator, but that the heat-labile NCA and ECA are dependent on mast cells for their production by a different cell, tentatively identified as the macrophage.

Trichophyton rubrum abscesses in immunocompromised patients. A case report.

A 72-year-old immunocompromised man with myelodysplastic syndrome who developed multiple erythematous, scaly abscesses like lesions on his left foot and lower leg is described. He also had dry scaly lesions on his soles and lesions on several toe nails. A punch biopsy showed abscesses with fungal elements and Trichophyton rubrum was cultured from skin scales and the biopsy. A diagnosis of T. rubrum abscesses should be suspected in all immunocompromised patients with signs of superficial dermatophyte infection.

Cytogenetic studies and in vitro colony growth in patients with mastocytosis.

Cytogenetic analysis of bone marrow cells and in vitro growth for bone marrow granulocytic-macrophage stem cells have been performed in 13 patients with mastocytosis, six with systemic mastocytosis, and seven with urticaria pigmentosa. Clones with chromosome abnormalities were found in five patients. The number of clusters and/or colonies after seven days in culture was increased in seven patients, compared with the growth in a control group. Three patients with chromosome abnormalities showed an abnormal growth pattern, yet exhibited normal peripheral blood values. Two patients with systemic mastocytosis had clones with chromosome abnormalities and some abnormal hematological values. The proportion of patients with chromosome abnormalities and an abnormal growth pattern was higher among these patients with mastocytosis than in healthy control subjects. These results may be of interest when discussing the origin of mast cell disorders and indicate an association with the myeloproliferative disorders.

Oculomotor dysfunction in patients with syphilis.

Four patients with syphilis or, in two instances, possibly some other treponematosis, underwent oculomotor and audiological tests. The oculomotor test result was abnormal in all four patients. Three had abnormal smooth pursuit eye movements and two of them had hypometric voluntary horizontal saccades, which indicate that the central nervous system (CNS) was affected. Moreover, one of the patients had pathological auditory brain stem responses, which indicate brain stem dysfunction. Another patient had signs of Menière's syndrome in one ear.