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Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented.
To determine the diagnostic use of different markers of acute parvovirus B19 infection, serum specimens obtained from 128 persons with erythema infectiosum were tested for specific immunoglobulin G (IgG), IgA, and IgM antibodies by capture enzyme immunoassay (EIA) using Chinese hamster ovary (CHO) cell-expressed B19 antigen, and tested for circulating B19 DNA by polymerase chain reaction (PCR). A significant rise in specific IgG and IgA antibodies was detected in 87% and 77%, respectively, of persons from whom acute- and convalescent-phase serum specimens were available. Specific IgA antibodies were detected in single serum specimens from 90% of cases and were present in 22 (18%) of 120 persons from a control group without a history of recent exposure to B19. Specific IgM antibodies were detected in 97% of cases and one person (1%) from the control group. B19 DNA was detected in 94% of cases and was absent in 20 persons from the control group positive for both IgG and IgA antibodies. Serum specimens obtained between 4 and 6 months after onset of illness from six additional persons were also tested. All had specific IgG antibodies, four (67%) had IgA, five (83%) had IgM, and none had detectable B19 DNA. Our data indicate that 1) specific IgA antibodies are too persistent to be a useful indicator of recent B19 infection; 2) specific IgM antibodies are the most sensitive indicator of acute B19 infection in immunologically normal persons but can persist up to 6 months; and 3) B19 DNA can often be detected up to 2 months after onset of illness even in immunologically normal hosts and might be a useful adjunct test for diagnosis of acute B19 infection.
We report the findings on a skin biopsy taken from a child acutely infected with parvovirus B19 showing the typical exanthematous rash. By indirect immunofluorescence with a monoclonal antibody to B19, viral capsid proteins were detected in epidermal cells localized mainly in the stratum basale. Additionally, B19 DNA was detected in epidermal cells of the stratum basale by in situ hybridization using a Dig-labelled B19 DNA probe. The detection of viral capsid proteins and viral DNA suggests the presence of complete viral particles. It is therefore concluded that B19 plays a direct role in the formation of the exanthematous rash in erythema infection.
A localized skin reaction occurred within 4 weeks following IV administration of mitomycin C and 5-FU. Erythematous papules appeared proximal to the forearm site used for drug administration that histologically resembled an erythema multiforme-like drug reaction. A localized hypersensitivity reaction to mitomycin C is suspected.
BACKGROUND AND OBJECTIVES: Objective evaluation of the pigmentation index (PI) and the eythema index (EI) of human skin is a prerequisite for successful optimization of laser- and intense-pulsed-light (IPL)-based treatment modalities in dermatology. STUDY DESIGN/MATERIALS AND METHODS: We describe a three-wavelength technique for determining PI and EI as well as its particular implementation using LEDs operating at wavelengths of 560, 650, and 710 nm and a large-area photodiode. The instrument has been evaluated both in vitro and in vivo. RESULTS: In vitro, good correlation between the measured indices and results obtained with commercially available techniques has been observed. In addition, linearity of the PI with melanin concentration in the phantom medium up to 7 x 10(-3) nm(-1) (defined as a slope of the optical density spectrum) has been established. In vivo, feasibility of using the technique for predicting the minimal erythema dose (MED), minimal phototoxic dose (MPD), and the threshold of epidermal damage in a photothermal treatment has been demonstrated. CONCLUSIONS: The data suggest that the technique has a substantial potential as a method of pre-treatment diagnostics for photochemical and photothermal procedures.
The production of tumor necrosis factor (TNF) by Mycobacterium leprae-stimulated phagocyte cells, isolated from lepromatous leprosy patients (LL) and normal individuals, was evaluated, using the highly TNF-sensitive mouse fibrosarcoma cell line WEHI164cl13. Mononuclear cells, isolated from all individuals studied, showed a low level of spontaneous TNF production, except for patients undergoing erythema nodosum leprosum (ENL), in which we found significantly higher levels of TNF. Addition of M. leprae to the phagocyte cell culture enhanced TNF production in all groups studied, except in the group with untreated leprosy patients. Strongest M. leprae-induced TNF release was found in mononuclear cell cultures derived from ENL patients. Patients in the postreactional state showed significantly higher TNF levels than healthy controls. These findings support the idea that TNF plays a key role in the complex symptomatology of ENL.
A polymerase chain reaction (PCR) assay was developed for the detection of Borrelia burgdorferi-specific DNA in the urine of patients with erythema migrans (EM). The target for the PCR was a specific region of the flagellin gene, and DNA was extracted from urine by Chelex resin. The detection limit was 1-10 genomes of B. burgdorferi, B. garinii or B. afzelii. A prospective study was performed with 12 consecutively diagnosed patients with EM, to evaluate the PCR assay on clinical samples. Borrelia burgdorferi-specific DNA could be detected in urine specimens from the 12 patients with EM before antibiotic therapy. Five weeks after therapy all the patients were negative by PCR of urine. Results of the present study confirm that the described PCR assay is sensitive and that this sort of test allows monitoring of the efficacy of therapy in patients with early Lyme borreliosis.
Epidemiological characteristics of 892 adult patients with typical Erythema migrans (Em), registered at Lyme borreliosis Outpatients' Clinic, Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia, in 1993, are presented. Data were gathered prospectively by means of a questionnaire. All the patients were seen by at least one of the four authors of this report. There were 57% females and 43% males aged from 15 to 91 years (median value 44 years, mean 44.4 +/- 14.3 years). The highest number of patients was found in age groups from 30 to 59 years. 73% of the patients quoted a tick bite at the site of later Em and 6% an insect bite; 21% didn't remember any bite. 212 out of 638 patients with a tick bite were able to assess the maximal possible duration of tick attachment: two-thirds quoted 24 hours or less. Interval from a tick bite to the appearance of skin changes was one day to six months (median value 15 days, mean 20.3 +/- 20.6 days) and from the beginning of Em to registration one day to 10 months (median value eight days, mean 17.1 +/- 24.2 days). More than half of the patients were registered in June, July and August. The majority of patients with Em resided in the region of Ljubljana. They were bitten by ticks predominantly near their homes but some of them also quite far away. Slovenia is an endemic region for Lyme borreliosis. The number of cases presented in our report is most likely only a fraction of the real number of patients with Em in the region of Ljubljana and is even further underestimated for other parts of Slovenia.
Infection with herpes simplex virus (HSV) is the most common precipitating factor in the development of erythema multiforme (EM). It is not known why only a few of the many individuals who experience recurrent HSV infection also develop herpes-associated EM (HAEM), although a difference in the HSV-specific immune response has been postulated. The purpose of this study was to compare the HSV-specific immune response of individuals with HSV infection alone with that of individuals with HAEM. There were 21 patients in each of the two groups. Four parameters of the HSV-specific immune response were examined: (1) anti-HSV IgG titers were measured by ELISA; (2) antibody neutralization was assessed using a plaque assay; and (3) antibody-dependent complement-mediated cytotoxicity, and (4) antibody-dependent cellular cytotoxicity were investigated using a previously described in vitro HSV-specific cytotoxicity assay. No statistically significant differences were detected between the two patient groups. Thus, a difference in these HSV-specific immune mechanisms does not explain the development of HAEM in some individuals with recurrent HSV infection.
A previous study using the hairless mouse model demonstrated that diets containing a fish-oil lipid source, which contained high levels of omega-3 fatty acids, markedly increased the minimum erythema dose (MED) when compared with diets containing other polyunsaturated fatty acids. To determine whether fish oil supplementation could produce a similar effect in humans, 20 subjects were randomized into two groups, a placebo group and a group receiving fish-oil supplements over a 4-week period. Results showed a small, but statistically significant, increase in MED in patients whose diet was supplemented with fish oil. Cholesterol and prostaglandin E2 levels were unchanged, while triglyceride levels were significantly decreased in the fish oil group. No significant changes in any of these parameters occurred in the placebo group.
Vitiliginous patients undergoing photochemotherapy with TMP were less susceptible to a sun burn. To investigate this point, the MED for UV-B was measured before, 2 h, and 24 h after oral intake of TMP in 10 healthy volunteers. There was an increase of MED when UV exposure had taken place 2 h after TMP intake (P < 0.01). This was no longer detectable when the exposure had taken place 24 h after intake. MED increase was 11.8% for 0.19 mg/kg TMP, 21.0% for 0.37 mg/kg, and 23.7% for 0.74 mg/kg. This dose-dependence was significant (P < 0.01). The protective effect of TMP against UV-B erythema seemed related to UV absorption by the drug while it was in the blood stream.
Influence of antioxidants on two phototoxic effects of 8-methoxypsoralen (8-MOP) was studied: erythema and changes in mechanoelectrical properties of skin. alpha-Tocopherol and its analogs with shortened lateral hydrocarbon chains at C2-atoms of chromane groups (chromanols) were used as antioxidants. alpha-Tocopherol and its analogs inhibited both phototoxic effects of 8-MOP. Inhibition was observed only if antioxidants were present in skin during irradiation. When applied after irradiation these antioxidants produce no inhibitory effect. The antioxidant antierythemal action depends greatly on their concentration. The protective effects is maximal at antioxidant concentrations 2.5 . 10(-10) - 5 . 10(-9) mol . cm-2 of skin, at concentrations higher than 5 . 10(-9) mol . cm-2 the protective action is decreased. The protective effect of antioxidants depends on the irradiation dose.
1. A typical case of Erythema elevatum diutinum (E.e.d.) with extracellular cholesterosis is described clinically and histologically in a 48-year-old woman. The disease had a course of 15 years. 2. Electron microscopy confirmed the histological and immunfluorescent findings of leucocytoclastic vasculitis. In older lesions, histiocytes/macrophages predominate. Intra- and extracellular lipid depositions showed a variety of ultrastructural characteristics which differed from electron microscopical findings described in other disorders associated with lipid deposition. 3. The findings are in accordance with the hypothesis that the primary event in E.e.d. is a special type of chronic leukocytoclastic vasculitis. Subsequently, the damage of the vessel walls and focal necrosis may lead to secondary lipid deposition.
A leukocytoclastic vasculitis was induced by intracutaneous injection of streptococcal antigen in a patient with erythema elevatum diutinum (E.e.d.). The immunoelectronmicroscopical demonstration of C3 was performed by use of the peroxidase-antiperoxidase multistep technique 24 h after the injection of the antigen. Deposits of C3 were found between endothelial cells, on the outer surface of endothelial cells, pericytes, and smooth muscle cells, as well as within the multilayered basal lamina of small vessels. Intact and disintegrating neutrophils accumulate within the vessel walls and in their surroundings. Necrosis and fibrin deposition are present in advanced stages. The findings demonstrate the sequence of events in leukocytoclastic vasculitis at the ultrastructural level. They also support the hypothesis that in E.e.d. an Arthus type reaction induced by bacterial antigens may be of pathogenetic significance.
Paraproteinaemia (IgGkappa) was observed in a 68 year-old patient with erythema elevatum diutinum. The association of this skin disease with paraproteinaemia as already reported by other authors may indicate a pathogenetic relationship.
An indirect immunofluorescence technique for the determination of antibodies against ixodid tick spirochetes is described. Differences in the reactivity between Ixodes ricinus spirochete and Ixodes dammini spirochete antigens were not observed. Cross-reacting antibodies against Treponema pallidum and Treponema phagedenis can be eliminated by quantitative absorption with T. phagedenis. Cross-reactions with leptospira were not observed by immunofluorescence. In the IgM test, false negative reactions caused by high-titered specific IgG antibodies or false positive reactions caused by rheumatoid factor occur. This can be avoided by testing the IgM fraction (19S-IgM-test) or using sera previously treated with anti-IgG serum. Significantly elevated antibody titers against ixodid tick spirochetes were observed in 45% of 44 cases with erythema migrans disease, in 72% of 29 cases of lymphocytic meningoradiculitis, in all of nine patients with acrodermatitis chronica atrophicans and in all of four investigated patients with lymphocytoma (lymphadenosis benigna cutis).
To determine whether early dissemination of Borrelia burgdorferi to the central nervous system occurs in stage I of Lyme borreliosis, neurological and cerebrospinal fluid examination was performed in 48 consecutive patients in whom the only sign of infection was a solitary erythema migrans lesion. Long-term follow-up after treatment with tetracycline was carried out by telephone interview. At presentation, neurological findings were normal in all 48 patients. Cerebrospinal fluid samples were obtained from 29 (60%) patients. Mild pleocytosis and mild impairment of the blood-brain barrier were present in four and one of these patients, respectively. No significant amount of tumor necrosis factor or interleukin 6 was found in the cerebrospinal fluid samples. Culture results of 13 cerebrospinal fluid samples were negative. Borrelia burgdorferi DNA was only detected by the polymerase chain reaction in one of two aliquots of the cerebrospinal fluid sample of one patient. None of 46 patients who were interviewed 12 to 51 (median 25) months after antibiotic treatment developed manifestations consistent with disseminated or chronic Lyme borreliosis. Thus, no compelling evidence was found for the presence of asymptomatic central nervous system involvement in patients with clinically localized Lyme borreliosis.
Twelve non-steroidal anti-inflammatory agents (NSAI's) and one steroidal anti-inflammatory agent, dexamethasone, were examined in the carrageenan edema test (CET) in the rat and in the ultraviolet light-induced erythema test (UVE) in the guinea pig to evaluate the correlation between those models of inflammation and the clinical dose of the NSAI's in the treatment of rheumatoid arthritis. The regression of the logarithm of the clinical dose with the logarithm of the ED50 for UVE gave a slope of 0.54 implying a non-parallelism of assays and a difference in mechanism. Dexamethasone failed to inhibit the UVE thereby corroborating this point. The parallelism of the logarithm of the clinical dose with the logarithm of the ED50 for the CET was substantially better (slope = 0.86). Dexamethasone was active in CET and its dose would be predicted by the CET regression. When only one variable was used for a prediction, log(CET) was a better predictor of log (clinical dose) than log(UVE). Standard methods for best regression selection indicated that even when both predictor variables were considered, log(CET) alone gave the best regression equation for predicting clinical dose. The view that inhibition of prostaglandin biosynthesis is the primary anti-inflammatory mechanism of NSAI's in rheumatoid arthritis is discussed in terms of these findings.