Biomedical subjects
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We present a 47-year-old Caucasian female who initially presented with mild discoid lupus erythematosus that evolved into systemic lupus erythematosus with subacute cutaneous LE and treatment-recalcitrant lupus panniculitis. Conventional therapy with antimalarials, systemic steroids, azathioprine, cyclophosphamide, methotrexate, and pulse doses of methylprednisolone did not control the course of the disease. Cyclosporin-A treatment led to clinical improvement and maintained remission.
We investigated in vivo the relationship between the degree of peripheral blood lymphocyte apoptosis and circulating dendritic cells (DC) as well as the immunological status in 45 patients with systemic lupus erythematous (SLE). Apoptosis was detected by phosphatidylserine externalization and assays to detect caspase activation. The total DC count (tDC) and their myeloid, mDC1 (BDCA1+) and mDC2 (BDCA3+), and plasmacytoid, pDC (BDCA3+), subtypes were assessed. Moreover, several immunological parameters, such as complement proteins, interferons (IFN), tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-6 levels were assessed. There were no significant differences in both the intensity of apoptosis and DC counts between active and inactive SLE as well as between untreated patients and those treated with steroids. The incidence of lymphocyte apoptosis correlated positively with T-cell count, both T-helper (p=0.004) and cytotoxic T cells (p=0.001), but not with B or natural killer (NK) cells. The intensity of apoptosis enhanced along with the increase in complement C3 (p=0.016) and decrease in IFN-gamma (p=0.040) levels. The apoptotic cell count correlated with tDC (p=0.031), mDC1 (p=0.007), and pDC (p=0.039) counts. Both tDC and mDC1 counts correlated positively with antinuclear antibody (ANA) titers (p=0.017 and 0.032, respectively). Moreover, tDC correlated with C4 (p=0.039) and pDC with both C3 (p=0.032) and C4 (p=0.007) levels. The DC counts correlated inversely with IFN-gamma (tDC, p=0.038; mDC1, p=0.009), IL-6 (mDC2, p=0.031), or serum IgG levels (tDC, p=0.006; mDC1, p<0.001; mDC2, p=0.001). We found a positive correlation between lymphocyte apoptosis and peripheral blood DC count as well as the level of complement proteins in patients with SLE. The enhanced lymphocyte apoptosis was accompanied by the decrease in concentration of some cytokines, such as IFN-gamma or IL-6, as well as serum IgG level. This finding may reflect pathogenetic events during development of the disease, which include a persistent signal derived from circulating apoptotic lymphocytes, mobilizing the complement system, and attracting peripheral blood DC.
Fibroblasts have been implicated in psoriatic inflammatory processes. The aim of the study was to evaluate soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6), and interleukin 8 (IL-8) plasma levels in psoriatic patients and IL-6 and IL-8 levels in fibroblast culture supernatants. Cytokines levels in plasma and supernatants were measured by ELISA. Plasma sIL-2R, IL-6, and IL-8 levels were higher before the treatment in comparison to healthy controls (P < 0.001) and decreased after treatment. Fibroblasts from healthy controls, psoriatic lesional skin, and noninvolved psoriatic skin, when stimulated with tumor necrosis factor alpha, released considerable amounts of IL-6 and IL-8. No significant difference between healthy controls and psoriatic fibroblasts was observed. Monitoring plasma sIL-2R levels could be employed as a reliable method of psoriasis activity. IL-8 and IL-6 plasma levels seem to reflect psoriasis activity, and treatment response, respectively. Fibroblasts are not a major source of increased IL-6 and IL-8 production in psoriasis.
Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid DC (PDC) and two myeloid subsets--MDC1 and MDC2. Several studies revealed the presence of both MDC and PDC in blood of healthy subjects, however no precise literature data exist on the number and distribution of BDC in the skin. The aim of our study was to assess the number and distribution of BDC and their subtypes in the healthy skin. The-study included 30 healthy volunteers (age 18-51). Punch biopsies were taken from the buttock skin from each subject, and immunofluorescent staining was performed using monoclonal mouse IgG1 antibodies directed against BDCA-1, BDCA-2, BDCA-3 and BDC-4. The BDC were present both in the epidermis and dermis. PDC were detected mainly in the dermis (mean 1.2 cells per field). Myeloid subtypes were observed mainly in the middle layers of the epidermis and in the upper part of the dermis (mean 1.8 cells per field). The detection of blood dendritic cells in the skin proves their role in immune cutaneous surveillance.
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease which pathogenesis is associated with destruction of the basement membrane components and the anchoring fibers. The binding of autoantibodies to antigens localized in the basement membrane of the epidermis activates a series of immunological and enzymatic phenomena that lead to blister formation. There are some data that MMPs are involved in the development of skin lesions in BP, however their exact role in this process is not fully understood. We aimed to investigate whether MMPs and their inhibitors (TIMPs), assessed by their tissue expression, are involved in the pathogenesis of BP. The localization and expression of collagenase (MMP1), gelatinase (MMP2), 92 kD gelatinase (MMP9) and stromelysin 2 (MMP10) and TIMP1, 2, 3 were examined by immunohistochemistry in skin biopsies as well as in normal human skin specimens. The study included 21 patients with BP at an active stage of the disease. The MMPs and TIMPs serum levels were measured by ELISA method. Expression of MMP1, MMP2, MMP9 and MMP10 was observed either in the whole epidermis or in the basal keratinocytes. Most of the enzymes examined, apart from TIMP3, were detected in dermal part of the blister. Expression of the majority of the enzymes examined was observed in blister fluid however, the most intense signal was noted for MMP10. In cellular infiltrate we found expression of all the MMPs and TIMPs, the most distinct for MMP1, MMP2, MMP10 and for TIMP2. In all biopsies obtained from healthy volunteers only single basal keratinocytes gave positive, weak signal for the examined proteins. The MMPs and TIMPs serum levels in the control group were normal while in some cases of BP patients they were increased. Based on the results we conclude that imbalance between these enzymes really occurs in BP and it is likely to take important part in the pathogenesis of the disease.
Researches on quality of life have been undertaken from dozens of years. However, there are few information about quality of life among people suffering from systemic lupus erythematosus (SLE). The aim of this study was to set predictors making possible quality of life anticipation. The participants of the studied group were 42 patients with inactive illness stage (disease severity were estimated by SLAM scale). Quality of life was measured by own questionnaire. Personal resources, which are the base of anticipation, were estimated by standardized tests (AIS, LOT, GSES). The results indicated that two of examined variables became the quality of predictors: helpless/hopeless strategy and illness acceptation.
Acne rosacea is a common skin disorder which affects adults, usually women. Erythema, papules, pustules and telangiectases, the main clinical manifestations of the disease are located on the face. Currently opinions dealing with pathogenesis and clinical forms of rosacea are presented. As the clinical picture might be confusing, similar to other illnesses, differential diagnosis with other dermatoses like acne vulgaris, erysipelas, seborrhoeic and contact eczema as well as systemic diseases like lupus erythematosus, dermatomyositis, scleroderma, sarcoidosis and leukemia were discussed.
Dermatitis herpetiformis (DH) is a subepidermal autoimmune disease characterized by skin and intestinal lesions consistent with coeliac disease. There are also some data that metalloproteinases (MMPs) are involved in the development of skin lesions in DH, however their exact role in this process is not fully understood. The aim of the study was to investigate whether MMPs and their inhibitors are involved in pathogenesis of DH. Skin biopsies were taken from 13 patients with active DH and from 10 healthy subjects. The localization and expression of MMPs and TIMPs were examined by immunohistochemistry. MMPs expression was detected in basal keratinocytes and in the whole epidermis in all of the DH subjects. Neutrophils in microabscesses and in blister fluid were also positive for MMPs. Expression of TIMPs was moderate or weak in all examined biopsies. Our results allow us to conclude that imbalance between these enzymes takes an important role in the pathogenesis of DH.
The aim of our study was to compare serum concentration of IL-1beta, IL-6, IL-8, IL-10, and TNF-alpha in 105 healthy volunteers before and after exposure to UVR: 25 subjects (10 days of UVB), 55 (10 days of UVB or solar-simulated radiation, followed by acute UVB dose), and 25 (local high dose of UVB). In all the individuals blood samples were analyzed before and after final irradiation by chemiluminescence assay. After 10 days of UVB irradiation a statistically significant increase in serum concentration only in IL-8 (P<.05) and strong tendency in TNF-alpha (P=.05) were observed. The applied schedules of irradiation have minor impact on serum cytokine level and still a threshold dose of UVR causing systemic immune impairment is unknown.
Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic sclerosis (SSc) may lead to dysfunction of the above organs or even patients death. Recent studies point out the role of angiogenesis and fibrosis disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF), endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P < .05). Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P < .05). The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis.
Although it is generally recognised that UV radiation (UVR) can induce suppression of contact hypersensitivity (CHS) in human subjects, most protocols to date have not tested the effect of low daily doses of solar simulated radiation (SSR). In the present study, healthy individuals, divided into four groups each consisting of approximately 34 subjects, were whole-body irradiated with 1.2 standard erythema doses of SSR for 2, 10 or 30 consecutive days, or were unirradiated. They were sensitised with diphenylocyclopropenone (DPCP) on one exposed body site 24 h after the final UVR. The occurrence and severity of the primary allergic response were noted, and both parameters were shown to be significantly lowered in the group irradiated for 30 days compared with the unirradiated group. Elicitation of CHS was undertaken 3 weeks after the sensitisation, using a range of concentrations of DPCP on a UV-protected body site. The extent of the CHS at 48 h was assessed by the clinical score, by an erythema meter and by histological examination of a biopsy taken from the site challenged with one selected concentration of DPCP. Although erythema and pigmentation did not differ between the groups, a significant negative correlation was found between the clinical CHS score and the number of days of UV exposure, at the lowest challenge dose of DPCP. In addition a significant negative correlation was revealed between the intensity of spongiosis (intraepidermal oedema and vesicles, as evaluated by histology) and the number of days of UV exposure. Thus small daily doses of SSR induce suppression of CHS in human subjects and the effect is cumulative, indicating that there is no adaptation to the immunomodulating effects of UVR, at least over the test period of 30 days.
Although there has been a steady decline in the incidence of tuberculosis in recent years, it persists in some regions, and where AIDS is especially prevalent, the number of new cases has been increasing. Thus, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multidrug-resistant pulmonary tuberculosis. Lupus vulgaris has been and remains the most common form of cutaneous tuberculosis. Cutaneous manifestations of disseminated tuberculosis are unusual, being seen in less than 0.5% of cases. Scrofuloderma, tuberculosis verrucosa cutis and lupus vulgaris comprise most cutaneous tuberculosis cases. Bacillus Calmette-Guerin (BCG) is derived from an attenuated strain of Mycobacterium bovis and is employed beneficially as a relatively safe vaccination in Poland and other countries in which the prevalence of tuberculosis is high. However, BCG vaccination may produce complications, including disseminated BCG and lupus vulgaris, the latter seen in one of our two patients in whom lupus vulgaris at the inoculation site followed a second vaccination with BCG 12 years after the initial one. A similar phenomenon has been described after immunotherapy with BCG vaccination. Re-infection (secondary) inoculation cutaneous tuberculosis may also occur as a result of BCG vaccination, producing either lupus vulgaris or tuberculosis verrucosa cutis, probably depending upon the patient's degree of cell-mediated immunity. However, most lupus vulgaris cases are not associated with vaccination with BCG, as occurred in our first patient. For those who do develop lupus vulgaris, it can be persistent for a long period, in some cases for many decades. In the second patient we describe a lengthy duration and cutaneous reactivation at distant sites after more than 40 years.
BACKGROUND/PURPOSE: Dendritic cells (DC) play a major role in the afferent immune response. They are found as a minor cell population in the blood as three main subtypes that can be distinguished phenotypically: plasmacytoid DC (PDC), and myeloid DC1 and 2 (MDC1 and 2). The aim of the study was to examine the effect of repeated whole-body suberythemal ultraviolet (UV) B irradiation on the percentages of DC subsets in the blood and skin, and to test for photoadaptation by the subsequent administration of a local erythemal UV dose. METHODS: Thirty subjects in each group were irradiated with either 0.7 personal minimal erythema dose (MED) UVB daily for 10 days (whole body), or for the 10 days followed by a single three MED UVB exposure of a local body site, or with the single three MED UVB exposure of a local body site only. Blood was collected before and after the exposures and the percentage of DC and DC subtypes assessed by flow cytometry. Skin biopsies were collected at the same times, and the number and position of the DC subsets examined by immunofluorescent microscopy. RESULTS: The whole-body repeated UVB irradiations did not result in a change in the blood DC (BDC) or the subsets percentages in the blood, except that there was a small but significant rise in the percentage of the MDC2 subset. No alteration occurred following the local erythemal UVB exposure. The total number of BDC in the skin was small, with the PDC being located mainly in the dermis and the myeloid subtypes mainly in the epidermis. No change in cutaneous numbers or distribution was revealed following the irradiation protocols. CONCLUSIONS: Repeated whole-body suberythemal UVB irradiation does not cause a change in BDC or BDC subsets in the blood or skin, except for a small increase in the percentage of MDC2 in the blood. Local erythemal UVB irradiation does not alter the BDC subsets in blood or skin.
Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disorder characterised by autoantibodies production. The diagnosis of disease requires evidence of 4 out of 11 clinical and/or laboratory symptoms proposed by American College of Rheumatology. For many years attention has been drawn to the problem of finding a valid and sensitive tool for measuring SLE activity and more than 60 different methods have been proposed. Unfortunately none of them has been generally accepted. Amongst the most frequently used are SLEDAI scale and its modifications, BILAG and SLAM. The systems have been validated in prospective studies, and their reproducibility, validity and sensitivity have been compared. At present they are widely used in clinical practice. In this review currently accepted methods of SLE activity evaluation are presented.
Systemic lupus erythematosus is an autoimmune, multiorgan disease, in the course of which central nervous system (CNS) disturbances are usually observed. Pathomechanism of CNS changes is complex and not fully investigated. Neuropathological alterations are often not characteristic, usually caused by vasculopathy, infarction, hemorrhages or infection. Vascular changes are generally disseminated and develop in different time period, sometimes they precede clinical symptoms. Currently applied diagnostic methods and their usefulness in diagnosis of CNS involvement in lupus patients, especially single photon emission computed tomography (SPECT), are presented.
UNLABELLED: We present a case of a 31-year old man with a 17 year history of Raynaud's symptom and contractures of the both hands' interdigitalis joints, progressive skin sclerosis of the arms, forearms and hands, telangiectases on the face skin. Because of the painful leg ulcers on the outer surface of both shins and on the dorsal part of the right foot (they appeared almost 10 years ago) the patient finally was admitted to our Department. Physical examination revealed hepatosplenomegaly, in laboratory tests leukopenia, mild thrombocytopenia, elevated ESR, elevated serum levels of IgG, IgM, IgA, creatine kinase level and hypergammaglobulinaemia were found. Neither anti-HBV or anti-HCV or antiphospholipid antibodies were present. Immunofluorescence test (HEP-2 cells) revealed the presence of antinuclear antibodies in a titer of 1:2560 (homogenous and partially speckled pattern) and by immuno-diffusion-anti-Ro antibodies. Hepatosplenomegaly was diagnosed by USG examination. Endocrinological, neurological, surgical and pulmonological examinations gave no abnormalities. Liver biopsy showed features of chronic inflammation and autoimmune hepatitis was diagnosed. COMMENT: the presence of scleroedematous lesions of the skin accompanying chronic hepatic inflammation enabled us to establish the diagnosis of scleroderma-like lesions in the course of long lasting mild autoimmune hepatitis.
The evaluation of contact hypersensitivity (CHS) reaction is one of the methods used in the assessment of the immune status of an organism after UV radiation. The aim of the study was to compare usefulness of visual scoring system and histological morphometry in the assessment of CHS response after exposure of humans to solar simulated radiation (SSR). The study included 140 healthy volunteers, 33 people were irradiated for 2 days, 34 - for 10 days and 33 - for 30 days with SSR. Forty non-irradiated individuals served as controls. All the volunteers were sensitized with diphenylocyclopropenone (DPCP) 24 h after final exposure. Statistical analysis comparing intensity of CHS reaction based on visual score between irradiated groups and non-irradiated group revealed no differences (p>0.05). We found a significant difference in epidermal thickness between healthy skin and irradiated groups (p<0.05) and a positive correlation between intensity of spongiosis and clinical score for CHS response at 3.2 DPCP site (p<0.000001). A negative correlation between time of irradiation and spongiosis score was revealed (R=-0.28; p<0.001). We conclude that histological examination of biopsies taken from one of the series of elicitation sites is a reliable and sensitive method in the evaluation of CHS response after UVR.