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The effect of systemically and topically applied drugs on ultraviolet-induced erythema in the rat.

1. Exposure of the skin of rats to u.v. light (greater than 295 nm) for 30 s or longer elicited a delayed erythema response, the rate of onset increasing with period of irradiation. The erythema was still present at 24 h and was replaced by scab formation in 48 hours. 2. Both topically applied steroidal and non-steroidal anti-inflammatory drugs reduced the erythema formation when administered immediately after u.v. exposure. Propyl gallate, an antioxidant with sun screening properties in man, also possessed topical anti-erythemic activity. 3. Both steroidal and non-steroidal anti-inflammatory drugs, systemically administered 1 h before u.v. exposure, reduced and erythema. However, the steroidal compounds were less effective than the non-steroids and reduced the intensity of erythema by less than 50%. Antagonists of 5-hydroxytryptamine (5-HT) reduced the erythema but several other drugs with different pharmacological activities were ineffective. 4. Neither topical nor systemic treatments of any of the drugs examined suppressed the scab formation at 48 hours. 5. These results and those using other selective blocking agents indicate that in the mediation of the erythema reaction prostaglandins may play a major role and 5-HT perhaps a minor one but that H1 histamine receptors and alpha- and beta-adrenoceptors have no significant role.

Administration, Oral↗

IgM anti-phenolic glycolipid I and IgG anti-10-kDa heat shock protein antibodies in sera and immune complexes isolated from leprosy patients with or without erythema nodosum leprosum and contacts.

The aim of the present work was to evaluate the levels of anti-PGL-I and anti-10-kDa heat shock protein antibodies in serum and immune complexes isolated from leprosy patients, convivients and controls. Leprosy patients with erythema nodosum leprosum or without it were included and a comparative study was done to investigate intergroup differences. Immune complexes were precipitated from serum by polyethylene glycol 3.5%; antibody levels were measured in sera and in dissociated immune complexes by ELISA. Serum antibody levels were then correlated with immune complex-associated antibody levels. The results showed that the erythema nodosum leprosum group differed from controls, contacts and non-erythema patients in their immune complex levels. IgM anti-PGL-I and IgG anti-10-kDa heat shock protein antibodies were constituents of the immune complexes in patients with erythema nodosum leprosum, who exhibited a significant difference in their immune complex composition compared with controls, contacts and non-erythema patients; while free antibody levels (anti-PGL-I and anti-10-kDa) did not differentiate between erythema and non-erythema patients, the measurement of immune complex-associated antibodies demonstrated a significant difference between the two clinical conditions. Furthermore, the measurement of immune complex-associated anti-PGL-I IgM made it possible to differentiate between contacts and controls. The significance of these results is discussed.

Adolescent↗

Quantification of allergic and irritant patch test reactions using laser-Doppler flowmetry and erythema index.

The laser-Doppler blood flow and erythema index were assessed in 16 patch test reactions caused by irritants (1% aq. sodium lauryl sulphate and 1% aq. benzalkonium chloride) and in 13 varied allergic reactions, at 2 or 4 days. Both irritant and allergic responses produced statistically significant increases in laser-Doppler flow index and erythema index compared to control sites (p less than 0.05 or less, using the Wilcoxon rank-sum test). A disproportionately greater increase in erythema index than in laser-Doppler flow was seen in mild irritant reactions, compared to allergic, though the two could not be reliably distinguished by these tests. 2 non-allergic nickel sulphate sites produced an increase in both blood flow and erythema without any clinical change. Petrolatum alone produced no significant change in either measurement. The laser-Doppler flow showed an overall correlation with the erythema index (product moment method; r = 0.55, p less than 0.001), but there was little correlation between these indices and patch test reactivity as judged clinically by conventional scoring. Generally, allergic and irritant patch test reactions could not be differentiated on the basis of laser-Doppler flow or erythema index. However, the disproportionate increase in erythema index over laser-Doppler flow index for mild irritant responses warrants further study in other irritant models.

Allergens↗

Erythema-multiforme-like eruption due to topical contactants: expression of adhesion molecules and their ligands and characterization of the infiltrate.

Erythema-multiforme-like reactions are a rare manifestation of allergic contact sensitivity, the pathomechanisms of which and their possible relationship to erythema multiforme remain unclear. We present our histopathological and immunohistochemical findings regarding the expression of several adhesion molecules and immunophenotypic markers of the infiltrate in skin biopsy specimens from 2 cases of erythema-multiforme-like reactions due to contact sensitizers and 3 cases of typical post-herpetic erythema multiforme. The histopathological pattern of erythema-multiforme-like reactions was characterized by an upper-dermal perivascular lymphoid infiltrate with exocytosis and keratinocyte necrosis; in 1 of the cases, there were foci of spongiosis and an admixture of eosinophils in the infiltrate. In comparison with biopsy specimens from cases of typical erythema multiforme, in both cases of erythema-multiforme-like reactions, the epidermal expression of ICAM-1 was more prominent, the % of CD4+ cells in the infiltrate was higher and the % of CD69+ cells was lower. There were no other significant differences in the cell phenotype of the infiltrate or in adhesion molecule expression in biopsy samples from both disorders.

Adult↗

Altered skin blood perfusion in areas with non blanchable erythema: an explorative study.

Non blanchable erythema, i.e. stage I pressure ulcer, is common in patients in acute and geriatric care and in nursing homes. Research has shown that this type of lesions is prone to develop into more severe pressure ulcers. The peripheral skin blood perfusion is of major importance for the development of pressure ulcers. The aim of this study was to explore the peripheral skin blood perfusion over time, in areas with non blanchable erythema and in corresponding undamaged areas on the opposite side of the body. A total of 19 measurements were performed, over time, using a laser Doppler perfusion imager. The blood flow distribution profiles over areas with non blanchable erythema and undamaged skin were found to be different. As the area of the non blanchable erythema decreased, the blood perfusion distribution profiles gradually became more heterogeneous; an area of high blood perfusion in the centre of the lesions was seen and the perfusion successively decreased closer to the edge. These results indicate that there are differences in blood perfusion between skin areas of non blanchable erythema and undamaged skin. The results also indicate that the visible redness in areas with non blanchable erythema is related to altered blood perfusion. The skin blood perfusion also seems to increase in relation to the size of the non blanchable erythema.

Aged↗

Erythema nodosum and pyoderma gangrenosum in 50 patients with Crohn's disease.

Erythema nodosum and pyoderma gangrenosum may occur in Crohn's disease. In the present evaluation of consecutive patients with Crohn's disease spanning more than two decades, erythema nodosum was seen in 45 patients and pyoderma gangrenosum was seen in seven patients. Forty-one of 566 women (7.2%) and nine of 449 men (2.0%) were affected. Of these, 45 (4.4%) had erythema nodosum and seven (0.7%) had pyoderma gangrenosum, including two (0.2%) with both dermatological disorders at different times during their clinical courses. Recurrent erythema nodosum was also detected in nine patients (20%) including eight women, while recurrent pyoderma gangrenosum was seen in two patients (28.6%). There was an age-dependent effect on the appearance of erythema nodosum in women, with the highest percentages seen in those younger than 20 years of age. Detection rates for erythema nodosum in women only approached the low men's rates in Crohn's disease at older than 40 years of age. Most patients with these dermatological disorders had colonic disease with or without ileal involvement as well as complex disease, usually with penetrating complications. The present study documents a sex-based and age-dependent effect on the clinical expression of erythema nodosum in Crohn's disease. This suggests that some components of the inflammatory process in Crohn's disease may be modulated by estrogen-mediated events, particularly in adolescents and young adults.

Adult↗

Establishing a minimal erythema concentration of methyl nicotinate for optimum evaluation of anti-inflammatories.

Topical administration of chemicals such as methyl nicotinate that induce erythema have been employed to measure the effectiveness of formulations containing anti-inflammatory agents. Prior studies have utilized a single concentration of methyl nicotinate, between 36.5 and 100 mM, for all test subjects in evaluations of topical formulations. However, individuals have different thresholds of response to methyl nicotinate; thus, a single concentration may not be appropriate for all individuals and could result in the apparent lack of anti-inflammatory activity of the formulation being evaluated. In the current study, we evaluated the use of a minimal erythema concentration (MEC) of methyl nicotinate, defined as the lowest concentration that produces a complete and even erythema at the test site, compared with a 36.5-mM concentration of methyl nicotinate. Hydroalcoholic gels containing the nonsteroidal anti-inflammatory drug ibuprofen were compared with placebo. Diffuse reflectance spectroscopy was employed to measure differences in cutaneous inflammatory response between the control (placebo)-treated group and the ibuprofen-treated group. When chemical erythema was induced using an MEC of methyl nicotinate, greater reductions in erythema were seen in ibuprofen-treated sites compared with sites treated with a 36.5-mM concentration of methyl nicotinate. In conclusion, for an accurate assessment method of erythema induced by methyl nicotinate, consideration should be given to determining the extent of response of an erythema-producing agent on an individual basis. An MEC of methyl nicotinate should be determined and employed for each individual to obtain more consistent and reliable efficacy results of anti-inflammatory activity.

Administration, Topical↗

Erythema toxicum neonatorum is an innate immune response to commensal microbes penetrated into the skin of the newborn infant.

Erythema toxicum neonatorum is a common rash of unknown etiology affecting healthy newborn infants. In this study, we postulated that the rash reflects a response to microbial colonization of the skin at birth, and that the hair follicle constitutes an "easily opened door" for microbes into the skin of the newborn. We collected microbial cultures from the skin of 69 healthy, 1-d-old infants with and without erythema toxicum to identify the colonizing flora and correlate culture results with clinical findings. We also analyzed biopsies from lesions of erythema toxicum with scanning and transmission electron microscopy in the search for microbes. Finally, each infant's body temperature was measured as a sign of acute phase response. We found that 84% of 1-d-old healthy infants, with and without erythema toxicum were colonized with coagulase-negative staphylococci. In all lesions of erythema toxicum, TEM identified cocci-like bacteria localized in the hair follicle epithelium and into recruited immune cells surrounding the hair follicle; morphology and dimension supported their identification as belonging to the genus Staphylococcus. SEM revealed 10 times more hair structures per skin surface unit in newborns compared with adults. Infants with erythema toxicum also had higher body temperature. In erythema toxicum, commensal microbes gain entry into the skin tissue, most probably through the hair canal. This triggers the local immune system and a systemic acute phase response, including an increase in body temperature. We speculate that early microbial exposure to the newborn may be important for the maturation of the immune system.

Body Temperature↗

An intraindividual study of the characteristics of erythema induced by bath and oral methoxsalen photochemotherapy and narrowband ultraviolet B.

We compared the characteristics of psoralen and ultraviolet A (PUVA) erythema in skin photosensitized by bath or oral methoxsalen in 20 subjects. Erythema was assessed visually and with a reflectance instrument at 24 h intervals for 7 days. In addition, narrowband ultraviolet B (TL-01 UVB) erythema was examined in 19 of these subjects at 4, 8, 12, 24, 48 and 72 h and in another nine subjects at 12, 15, 18, 21 and 24 h. Both bath and oral PUVA exhibited broad erythemal peaks beyond 72 h. For topical PUVA the lowest minimal phototoxic dose (MPD) occurred at 120 and 144 h (P = 0.01 and 0.03 compared with 72 h). Oral PUVA erythema peaked earlier at 96 h: the MPD was significantly lower at 96, 120 and 144 h compared with 72 h (P = 0.001, 0.01 and 0.02, respectively). At 120 h, bath PUVA had a significantly steeper slope compared with oral PUVA. The TL-01 UVB minimal erythema dose was significantly lower at 12 h compared with 24 h (P = 0.019). The majority of subjects were at maximal erythema at 12 h (22 of 28) and 15 h (eight of nine). Our results suggest that peak erythema for bath PUVA, oral PUVA and TL-01 UVB occurs at 120, 96 and 12-15 h, respectively.

Administration, Oral↗

Objective measurement of minimal erythema and melanogenic doses using natural and solar-simulated light.

Very little information exists on the amount of natural and artificial UV light required to cause sunburn and tanning in individuals with very pale skin who are at the greatest risk of developing skin cancer. We have investigated minimal erythema dose (MED) and minimal melanogenic dose (MMD) in a group of 31 volunteers with Fitzpatrick skin types I and II using an Oriel 1000 W xenon arc solar simulator and natural sunlight in Sydney, Australia. We measured the erythemal and melanogenic responses using conventional visual scoring, a chromameter and an erythema meter. We found that the average MED measured visually using the artificial UV source was 68.7 +/- 3.3 mJ/cm2 (3.4 +/- 0.2 standard erythema doses [SED]), which was significantly different from the MED of sunlight, which was 93.6 +/- 5.6 mJ/cm2 (P < 0.001) (11.7 +/- 0.7 SED). We also found significant correlations between the solar-simulated MED values, the melanin index (erythema meter) and the L* function (chromameter). The average MMD (obtained in 16 volunteers only) using solar-simulated light was 85.6 +/- 4.9 mJ/cm2, which was significantly less than that measured with natural sunlight (118.3 +/- 8.6 mJ/cm2; P < 0.05). We mathematically modeled the data for both the chromameter and the erythema meter to see if we were able to obtain a more objective measure of MED and differentiation between skin types. Using this model, we were able to detect erythemal responses using the erythema index function of the erythema meter and the a* function of the chromameter at lower UV doses than either the standard visual or COLIPA methods.

Adolescent↗

Erythema infectiosum in children. A Clinical study.

Erythema infectiosum is a childhood illness characterized by mild constitutional symptoms and a blotchy or maculopopular lacy rash on the cheeks (slapped - cheek) spreading primarily to the extremities and trunk. The disease is caused by human parvovirus B19. Erythema infectiosum epidemics occur in a cyclic fashion, mostly during winter and spring months. The diagnosis of erythema infectiosum is usually based on the appearance and pattern of the rash. The aim of our study was to establish the frequency and clinical characteristics of erythema infectiosum in children, in the period between 2000 and 2004 at the Institute of Child and Youth Health Care, Department of Dermatology, Novi Sad There were 0.23% of children with a clinical picture of infectious erythema. There was an outbreak of erythema infectiosum from December 2001 to September 2002. The highest number of cases was detected in April and May of 2002 from 2003 to 2004, no cases with infekctious erythema were diagnosed. The average age of injected children was 7.38. Female children were affected slightly more often than male (56.41% : 43.58%). Pruritus was detected in 10.26% of children. The most constant clinical sign was reticular exanthema on the limbs, present in 100% of cases, jollowed by 89.74% of cheek exanthema, while limb and trunk exanthema was present in 7.68% of children. Adenopathies and mild constitutional symptoms were present in 5.12% of children. No complications were recorded in any of the cases.

Adolescent↗

Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans.

BACKGROUND: Lyme disease has a wide spectrum of clinical manifestations. Diagnosis is usually based on the clinical and serologic picture rather than on microbiological confirmation. OBJECTIVE: To examine the clinical presentation and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. DESIGN: Observational cohort study. SETTING: 31 university-based or clinician-practice sites in 10 endemic states. PARTICIPANTS: 10 936 participants enrolled in a phase III trial of Lyme disease vaccine; 118 participants had erythema migrans in which Borrelia burgdorferi was detected by culture or polymerase chain reaction. MEASUREMENTS: Clinical characteristics and treatment outcome were noted. Skin biopsies of erythema migrans were performed for culture and detection of B. burgdorferi by polymerase chain reaction; serologic responses were determined by Western blot. RESULTS: The 118 patients with microbiologically confirmed erythema migrans presented a median of 3 days after symptom onset. Early erythema migrans commonly had homogeneous or central redness rather than a peripheral erythema with partial central clearing. The most common associated symptoms were low-grade fever, headache, neck stiffness, arthralgia, myalgia, or fatigue. By convalescence, 65% of patients had positive IgM or IgG antibody responses to B. burgdorferi. Most patients responded promptly to antibiotic treatment. CONCLUSIONS: In major endemic areas in the United States, Lyme disease commonly presents as erythema migrans with homogeneous or central redness and nonspecific flu-like symptoms. Clinical outcome is excellent if antibiotic therapy is administered soon after symptom onset.

Adolescent↗

Has the presence or absence of Borrelia burgdorferi sensu lato as detected by skin culture any influence on the course of erythema migrans?

The aim of this prospective study was to compare epidemiological and clinical data in patients with a positive Borrelia burgdorferi sensu lato culture and culture-negative erythema migrans skin lesions. Of the 546 adult patients with erythema migrans seen at our institution in 1997 in whom a skin biopsy was performed and the specimen cultured for the presence of B. burgdorferi sensu lato, 235 (43%) had a positive and 311 (57%) a negative skin culture. More women than men were present in both groups and women were also significantly older than men. Tick bites resulting in culture-positive erythema migrans predominated in May (p = 0.012), while in August and September tick bites with subsequent culture-negative skin lesions were more common (p = 0.018 and 0.011, respectively). Similarly, erythema migrans lesions noticed by our patients in May were significantly more often Borrelia culture positive than negative (p = 0.004), while lesions appearing in October were significantly more often culture negative (p = 0.004). In addition to these seasonal differences, the comparison of the large number of Borrelia skin culture-positive and -negative patients with erythema migrans also revealed differences in several clinical parameters including a larger diameter of skin lesions in the culture-positive group (p = 0.007 at presentation, and p = 0.039 at registration, respectively), a lesser number of multiple skin lesions (7/235 versus 27/311, p = 0.006), and a lower frequency of signs/symptoms (p = 0.039) associated with erythema migrans lesions in culture-positive than in culture-negative patients. We have no plausible explanation for the majority of these rather unexpected findings. Of the 59 patients who, prior to biopsy, had received brief courses of antibiotics known to be effective in the treatment of erythema migrans, 12 (20.3%) were culture positive. As anticipated, the ratio of culture positivity in pretreated patients was significantly lower (p < 0.001) than in those without antecedent antibiotic therapy.

Adolescent↗

[Erythema multiforme in children versus Stevens-Johnson syndrome].

UNLABELLED: 30 children treated between 1984-98 for erythema multiforme (versus SJS) in Department of Allergology at the Children's Memorial Health Institute in Warsaw. 25 children suffered from erythema multiforme minor and 5 suffered from Stevens-Johnson Syndrome. Before symptoms of the illness 13 children had been treated with antibiotics and 27 children demonstrated different symptoms of infections, mostly viral. Drug therapies and viral or bacterial infections probably induce symptoms in patients susceptible to erythema multiforme or severe versus Stevens-Johnson Syndrome. CONCLUSION: 1. Erythema multiforme (EM) rather seldom occurs in children. The Most commonly its course is benign (EM minor). In another type of erythema multiforme--Stevens-Johnson Syndrome (EM major), in which mucous membranes are involved, the course of disease and the prognosis are always severe. 2. Both viral and bacterial infections as well as administered drugs play the important role in the etiopathogenesis of erythema multiforme. 3. The treatment of erythema multiforme in children is symptomatic (general and local). In Stevens-Johnson Syndrome early administration of glicocorticoids is recommended. Children with bacterial infection (contagion, contamination) should be treated with antibiotic.

Adolescent↗

Erythema multiforme.

Erythema multiforme is a cutaneous reaction pattern manifested by well-demarcated plaques on the trunk and extremities. Target, or "iris," lesions, with central clearing, are characteristic of this disorder. Erythema multiforme may be a mild condition (erythema multiforme minor), or it may be a severe, possibly life-threatening condition (erythema multiforme major or Stevens-Johnson syndrome). Toxic epidermal necrolysis, manifested by widespread epidermal desquamation, is the most severe form of this disorder. The three most common triggers for erythema multiforme are herpes simplex infection, mycoplasma infection and drug reactions. Drugs that can precipitate erythema multiforme include sulfonamides, penicillins, phenylbutazone and phenytoin. The appearance of the characteristic lesion is usually diagnostic. However, conditions such as tinea corporis, lupus erythematosus, herpetic gingivostomatitis, Behçet's disease and erosive lichen planus, among others, may mimic erythema multiforme. For mild cases, treatment is supportive, with antibiotics used for secondary skin infections. For severe causes, many physicians use systemic corticosteroids, although this treatment is not universally endorsed.

Adrenal Cortex Hormones↗

The effect of topical indomethacin on ultraviolet-radiation-induced erythema.

Indomethacin inhibits UVB erythema but is thought not to influence UVA erythema. We have examined the wavelength dependence of the effect of indomethacin on ultraviolet radiation (UVR) erythema. Duplicate sites on the back were irradiated with a series of doses at 300 and 320 nm, or single doses at 330, 340, 350 or 370 nm. Indomethacin 1% was applied to sites on one side of the back after irradiation, occluded for 2h and erythema measured at 24h with a reflectance instrument. Indomethacin inhibited 300 and 320 nm (UVB) erythema, had no effect at 330 and 340 nm (UVA2), but augmented 350 and 370 nm (UVA1) erythema. There appears to be a varied response of UVR erythema to cyclo-oxygenase inhibition at different wavelengths across the UVR spectrum. This mechanism may be deranged in certain photosensitive disorders.

Adult↗

[Tissue oxygenation and microcirculation in dermatoliposclerosis with different degrees of erythema at the margins of venous ulcers. A contribution to hypodermitis symptoms].

BACKGROUND: In patients with chronic venous insufficiency erythematous areas in indurated skin (hypodermitis) and non erythematous areas of lipodermatosclerosis were examined. METHODS: In 13 patients with venous ulcers a total of 32 localizations in more or less erythematous and indurated ulcer edges were measured. The amount of erythema was taken as an indicator for the extent of hypodermitis. The parameters examined were erythema (a-value), skin temperature (t), laser Doppler flow (LDF), transcutaneous (tcpO2) and intracutaneous oxygen tension (icpO2). According to the amount of erythema the different localizations were separated into two groups: areas with a-values lower than 14,2 were classified as lipodermatosclerosis without or with little erythema, are-as with a-values higher than 14,2 were classified as areas of lipodermatosclerosis with extensive erythema. Identical measurements were also performed in healthy looking skin below the knee. RESULTS: Skin temperature and LDF were higher in areas with much erythema compared to those with little or no erythema. TcpO2, measured with an electrode temperature of 44 degrees C, was lower in areas with inflammation; tcpO2-values at 37 degrees C and icpO2-values showed no differences in ulcer edges with different amounts of inflammation. CONCLUSION: The results show differences of microcirculation between areas of lipodermatosclerosis with and without hypodermitis. These differences did not influence the actual tissue oxygenation in deeper parts in the dermis.

Aged↗

[Erythema nodosum: 112 cases. Epidemiology, clinical aspects and histopathology].

In a retrospective study we analyzed the cases of 112 patients with erythema nodosum treated during the period 1983-1993 in the Department of Dermatology, University Hospital of Basel, Switzerland. The aim of the study was to investigate the epidemiology, incidence of different etiologies, relevance of laboratory investigations and the histopathologic features in our patients, 83% of whom were females. The peak incidence occurred between the ages of 18 and 34 years. The commonest cause of erythema nodosum was infection. Other etiologic factors were adverse drug reactions, sarcoidosis, Crohn's disease, non-Hodgkin lymphoma, pregnancy, discoid lupus erythematosus, Sharp syndrome and aspartame. Only 47% of patients showed the classic bilateral distribution of the nodes on the extensor surface of the lower extremities. 77% of infection-induced erythema nodosum healed after 7 weeks, the longest course being 18 weeks. In contrast, 30% of idiopathic erythema nodosum lasted more than 6 months. Patients in whom erythema nodosum was associated with non-Hodgkin lymphoma had an extremely protracted course. Erythema nodosum associated with non-Hodgkin lymphoma may precede the diagnosis of lymphoma by months. In 4 cases erythema nodosum was the initial sign of sarcoidosis. In 30% of biopsies we found single vessels with leukocytoclastic vasculitis. The histologic pattern failed to provide etiologic pointers.

Adolescent↗