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PubMed2001

Suppression of UVB-induced cutaneous erythema by a previous UVB exposure.

People who vacation in sunny places are exposed to the sun on multiple occasions at least on a daily basis. The clinical assessment of sun exposure is erythema in the first 48 h after exposure and pigmentation at times greater than 3-5 days. The purpose of this investigations was to determine the extent to which consecutive erythemogenic exposures result in additive erythema responses. Studies were conducted in which volunteers were first exposed to a graded series of fluences of UVB radiation and then on subsequent days (1-3 days) the same sites along with the surrounding unexposed skin were challenged with varying fluences of UVB radiation. The erythema reactions were assessed clinically and were objectively documented with diffuse reflectance spectroscopy. The sites that received two exposures always showed a reduced erythema response compared to a single erythemogenic exposure. The suppression of erythema was more pronounced when the second exposure was given 48 h after the first. The erythema suppression was maximal when the first exposure was at 1.3 minimum erythema dose (MED). The pigment response to the first exposure was completely suppressed for fluences less than 1.5 MED. We thus provide evidence for a decoupling of the classical sequence of erythema-pigmentation response. We also show that the erythema induced by a second exposure may be substantially suppressed by an earlier exposure, and that this cannot be due to melanin photoprotection or due to substantial thickening of the stratum corneum. We propose that the cause may be some diffusible element of yet unknown origin.

Adult↗
PubMed1956

Systemic manifestations of erythema nodosum.

The systemic manifestations accompanying erythema nodosum can be differentiated from those associated with the precipitating infectious process and from coincident disease processes. Erythema nodosum itself is characterized by (a) skin lesions at pressure sites, (b) malaise, fever and occasionally chills, (c) arthritis (70 per cent) and (d) over-reactivity of tissue. Tissue hypersensitivity is most pronounced at sites of trauma, at sites of specific skin testing, and in the lymphoid system draining infections in the pharynx and lung. Common infections of the respiratory tract most often antedate attacks of erythema nodosum. In New England, a beta-hemolytic streptococcus infection is a common causative factor, and tuberculosis is an unusual causative factor. In endemic areas, coccidioidomycosis is a common cause of erythema nodosum. The most important coincidental disease process is rheumatic heart disease. Rarely is it a sequel of erythema nodosum. Other "collagen diseases" may coexist with erythema nodosum. Erythema nodosum is its own most common complication. Follow-up studies indicate that over half of the patients have a subsequent attack, and a certain number have recurrent episodes for months to years. The management of erythema nodosum is expectant. In each case the cause should be found and treated. Steroid treatment is rarely justified, and should be used only after tuberculosis and other treatable entities have been ruled out.

Arthritis↗
PubMed2002

Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study.

BACKGROUND: It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions. OBJECTIVE: To evaluate the validity of this clinical separation. DESIGN: Case-control study. SETTINGS: Active survey from 1989 to 1995 of 1800 hospital departments in Europe. PATIENTS: A total of 552 patients and 1720 control subjects. METHODS: Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome-toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups. RESULTS: Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme. CONCLUSIONS: This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.

Adult↗
PubMed1995

A placebo controlled clinical trial investigating the efficacy of a homeopathic after-bite gel in reducing mosquito bite induced erythema.

A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One bite was treated with the homeopathic after-bite gel, another bite with a placebo gel which was identical in appearance and smell to the homeopathic after-bite gel, and the third bite remained untreated. Immediately after the bites and 1, 3, 6, 26 and 31 hours post-bite, the length and width of the erythema were measured with a calliper, and photographs were taken of the bite sites from which the size of the erythema was subsequently determined. This was followed by assessment of the extent of itching with a verbal analogue scale, and finally treatment took place. For each spot the total erythema was calculated as the area under the plotted curve of the erythema at different time points (mm2*h) and the total sum of the itch scores was determined. For the bites treated with the homeopathic after-bite gel the median total erythema was 10.500 mm2*h. For the spots treated with the placebo gel and the untreated spots the median total erythema was 12.900 mm2*h and 13.300 mm2*h, respectively. The difference between the spots treated with the homeopathic after-bite gel and the untreated spots came close to significance (two-tailed P = 0.06), which was not the case for the difference between the spots treated with the homeopathic after-bite gel and the spots treated with placebo gel (P = 0.13). After pooling the data of a very similar previous pilot study and the present study (ntotal = 83), the homeopathic after-bite gel was significantly superior to no treatment (two-tailed P = 0.003) as well as to placebo gel (two-tailed P = 0.03). Comparing itching after the three treatments, no significant differences could be demonstrated. The extent of itching was positively correlated with the area of the erythema (r = 0.63). Treatment of mosquito bites with the homeopathic after-bite gel will reduce the erythema compared to no treatment. Comparison with the placebo gel suggests it is the plant extracts which are the active components of this gel.

Adult↗
PubMed2006

Electrocardiographic findings in children with erythema migrans.

OBJECTIVE: To assess electrocardiographic findings in children with erythema migrans and to compare them with findings obtained in a healthy control group of comparable age and with a similar proportion of boys and girls. METHODS: Electrocardiograms were carried out in 147 children under the age of 15 years before treatment with antibiotics for erythema migrans (solitary 68 patients, multiple 79 patients) and in the control group of 148 healthy children. RESULTS: Abnormal electrocardiographic findings were detected more often in healthy children than in patients (14% versus 5%; P = 0.0303) and among patients more often in boys than in girls (10% versus 0%; P = 0.0107). Electrocardiographic abnormalities characteristic for Lyme borreliosis, such as atrioventricular blocks, were rare: in patients with erythema migrans only one child had first-degree atrioventricular block; in the control group one child had first-degree and another had second-degree atrioventricular block. Patients with erythema migrans had shorter PR and RR intervals and lower R and S wave voltages in V1 than the healthy children. Comparison among patients with solitary and multiple erythema migrans did not reveal significant electrocardiographic differences. The frequency of electrocardiographic abnormalities in patients with erythema migrans was not associated with the presence of systemic symptoms, or with the presence of meningitis or the isolation of Borrelia burgdorferi sensu lato from the blood. CONCLUSIONS: Electrocardiographic abnormalities in children with erythema migrans are mild, nonspecific and rare. The presence of clinical signs and symptoms indicative or suggestive of disseminated Lyme borreliosis is not associated with higher frequency of such abnormalities. Comparison of findings in patients with erythema migrans and healthy children revealed several distinctions, some of which might have been interpreted as a result of altered activity of the autonomic nervous system.

Adolescent↗
PubMed1995

Misdiagnosis of erythema migrans.

BACKGROUND: Erythema migrans is a clinical diagnosis that carries possible long-term repercussions. Despite widespread awareness of the clinical presentation of erythema migrans, incorrect diagnosis occurs. PATIENTS AND METHODS: We describe 13 cases in which erythema migrans was misdiagnosed and discuss some pitfalls in diagnosis. These cases were seen at a tertiary referral center in Connecticut, a state where Lyme disease is endemic. The patients selected for inclusion were those who most clearly illustrate potential difficulties involved in making the diagnosis of erythema migrans. RESULTS: The diagnosis of erythema migrans was missed in 5 patients due to atypical presentations. Eight patients with skin eruptions closely mimicking erythema migrans were incorrectly diagnosed with erythema migrans. CONCLUSIONS: There are pitfalls associated with the diagnosis of erythema migrans that may result in overdiagnosis or underdiagnosis.

Adult↗
PubMed2002

Quantification of erythema using digital camera and computer-based colour image analysis: a multicentre study.

BACKGROUND/PURPOSE: Colour measurements obtained from digitized images have been proposed as a simple and cost-effective way to evaluate skin colour and the activity of treatments. The main disadvantage of the method is the fact that it is highly dependent on ambient light: even if an accurate control of subjects' illumination is provided, readings remain not comparable among different laboratories. The purpose of this study was to develop a highly reproducible system for computerized colour image analysis of skin erythema, making it possible to compare readings from different environmental light conditions. PATIENTS AND METHODS: Three hundred and forty-eight Caucasian adult healthy subjects (age range: 18-60 years) of both sexes (14% males, 86% females), were enrolled in the study by 49 dermatologists distributed all over Italy. They were recruited among patients who required aesthetic treatments involving skin erythema, like chemical peeling and laser epilation. Once the treatment was administered, clinical evaluations and pictures were taken at the level of treated areas. Visual assessment of erythema was done on the basis of conventional clinical grades (0 = absent; 1 = slight; 2 = moderate; 3 = intense). The clinicians participating in the study were asked to put a standard colour marker (red, green and blue coloured self-adhesive ring) in the photographed skin area. The difference between r, g, b values of photographed colour markers on the skin of single patients participating in the study and the r, g, b values obtained photographing the colour marker in fixed illumination conditions was used to adjust skin colour measurements. Then erythema index (E.I) on digitized images was calculated subtracting red value to green one by averaging procedure of different pixels. RESULTS: Erythema index. average value among the groups divided according to the conventional clinical score increased progressively from score 0-2, while it decreased from score 2 to score 3. The differences in E.I. mean values among the score groups (0 vs. 1, 1 vs. 2, 2 vs. 3) were statistically significant (P < 0.05). CONCLUSION: We developed a method for the measurement of skin erythema using digital camera, normalized r, g, b colour co-ordinate system and computerized calculation of E.I. Clinical usefulness of our method for absent, slight and moderate erythema, was demonstrated. For intense erythema lesions we did not find a correspondence between clinical and computerized evaluation, probably due to other factors involved in skin inflammation (e.g. oedema).

Adolescent↗
PubMed1997

The geographical distribution of tick bites and erythema migrans in general practice in The Netherlands.

BACKGROUND: Lyme disease is caused by Borrelia burgdorferi which is transmitted in Europe by the tick ixodes ricinus. Erythema migrans is a skin lesion which is pathognomonic of Lyme disease. A retrospective study was carried out to determine the geographical distribution of the occurrence of tick bites and erythema migrans in the Netherlands and to identify ecological risk factors. METHODS: In April 1995, all general practitioners (GPs) in the Netherlands were asked to complete a postal questionnaire on the number of tick bites and erythema migrans case-patients seen in 1994 and the size of the practice. Reminders were sent to non-responders. Information on ecological risk factors by local government area was obtained from a geographical information system. RESULTS: The response rate was 79.9%. In 1994, GPs reported seeing approximately 33,000 patients with tick bites and 6500 with erythema migrans. The incidence rate of erythema migrans was estimated at 4.3 per 10,000 population. Ecological risk factors for both tick bites and erythema migrans were the proportion of the area covered by woods, sandy soil, dry uncultivated land, the number of tourist-nights per inhabitant and sheep population density. The cattle population density was a risk factor for erythema migrans. CONCLUSIONS: Using simple methods, a crude estimate of the incidence rate of erythema migrans was obtained rapidly, and high risk areas were identified. Lyme disease appears to be an important problem in the Netherlands.

Animals↗
PubMed1994

Histopathological features of recalcitrant erythema of the face in adult patients with atopic dermatitis.

Recalcitrant erythema on the face of 21 adult patients with atopic dermatitis was histologically examined. All patients had been applying topical corticosteroids to the facial erythema for three years or more. The histopathology of the recalcitrant facial erythema was not homogeneous. Thus, the facial erythema was roughly classified into three categories: 1) erythema which mainly showed eczematous changes, 2) erythema which mainly showed steroid-induced rosacea-like changes, and 3) erythema which showed both eczematous changes and steroid-induced rosacea-like changes. The majority (75%) of recalcitrant facial erythema belonged to the third category.

Adult↗
PubMed1982

Erythema and skin blood content.

We have studied the inflammatory response produced by painting pigs and hairless mice with anthracene and subsequently exposing the skin to fluorescent blacklight lamps. Erythema and oedema appeared in pig skin shortly after the onset of irradiation; oedema but no erythema was evident in mouse skin. The response in both animals became increasingly severe as long as irradiation continued, and began to resolve when irradiation ceased. Hyperaemia (increased tissue blood content) was quantified by the increased in 51Cr-RBC content (c.p.m./wet weight) of the skin. Erythema (appearance of redness) was assessed by the use of an 'erythema grading scale' consisting of red gelatin filters of increased red saturation sandwiched between clear acrylic sheets. Mouse skin responded with a nine-fold hyperaemia compared with unirradiated skin, although no erythema was produced. In contrast, pig skin responded with intense erythema with no corresponding increase in hypaeremia. It is apparent that a stimulus which produced hyperaemia will not necessarily produced erythema, and erythema can develop without hyperaemia.

Animals↗
PubMed1993

Immunological evaluation of erythema nodosum in tularaemia.

During two tularaemia outbreaks in the Bursa region of Turkey in 1991, a total of 98 patients were diagnosed and evaluated. Thirteen of these patients had erythema nodosum, which is accepted as a secondary skin manifestation. The patients with erythema nodosum, 21 patients without any skin lesions, and 20 healthy controls were studied. Comparable elevations of levels of IgG, IgA, and IgM were detected in the two tularaemia groups. There was no difference in complement C3c and C4 levels between the groups. All of the patients with erythema nodosum had elevated circulating immune complex (CIC) levels, when compared with the patients without skin lesions and the control group. The acute phase response (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) of the erythema nodosum group was significantly higher than the patients with normal skin, and healthy controls (P < 0.001). Serum transferrin levels were significantly decreased in both of the tularaemia groups (P < 0.001). Serum soluble interleukin-2 receptor levels (SIL-2R) were significantly elevated in both tularaemia groups (P < 0.001), and the elevation was more marked in the erythema nodosum group (P < 0.05). Histopathological evaluation of biopsies from two patients with erythema nodosum showed dermal oedema, a perivascular lymphocytic infiltrate, and panniculitis. No immunoglobulin or complement deposits were detected on immunofluorescence. Erythema nodosum in the course of tularaemia is associated with many immunological changes, although it is not clear whether these findings are related to the increased tissue response, or whether they play a role in the pathogenesis of the erythema nodosum.

Adolescent↗
PubMed2004

Minimal erythema dose after multiple UV exposures depends on pre-exposure skin pigmentation.

BACKGROUND/PURPOSE: Phototherapy consists of multiple ultraviolet (UV) exposures. Most previous studies have focused on erythema following a single UV exposure in fair-skinned persons. Although it is well known that phototherapy lowers the daily UV-threshold dose for erythema in clinical practice, this is insufficiently documented under controlled experimental conditions. The purpose of this study was to quantify the change in the daily threshold for a dose specific erythema grade after 1-4 consecutive daily UV exposures. METHODS: Forty-nine healthy volunteers (skin type II-V) with varying pigmentation quantified by skin reflectance. Two UV sources were used: a narrowband UVB (Philips TL01) and a Solar Simulator (Solar Light Co.). Just perceptible erythema after 24 h was chosen as the minimal erythema dose (+); besides + and ++ were assessed. RESULTS: We found a positive and significant exponential relationship between skin pigmentation and UV dose to elicit a specific erythema grade on the back after 1-4 UV exposures. After repetitive UV exposures the UV dose had to be lowered more in dark-skinned persons compared with fair-skinned persons to elicit a certain erythema grade. This applied to both UV sources and all erythema grades. CONCLUSION: In the dark-skinned persons the daily UV dose after the 4 days UV exposure should be lowered by 40-50% to avoid burns compared with the single UV exposure. For the most fair-skinned persons essentially no reduction in the daily UV dose was needed. Our results indicate that the pre-exposure pigmentation level can guide the UV dosage in phototherapy.

Adult↗
PubMed2006

Melanin differentially protects from the initiation and progression of threshold UV-induced erythema depending on UV waveband.

BACKGROUND/PURPOSE: This study aimed to determine the relationship between various measures of constitutive skin pigmentation and erythema caused by solar-simulated UV (ssUV), 290 and 310 nm UV. METHODS: Skin pigmentation was assessed clinically by skin typing as well as objectively by measurement of the melanin index (MI) by reflectance spectroscopy. Subjects having Fitzpatrick skin types I-IV were exposed to graded doses of ssUV and either narrowband 310 nm (n=70) or 290 nm (n=69) UV, and assessed 24 h after exposure. Minimal erythema dose (MED) was assessed visually as the lowest dose that caused minimally perceptible erythema. Susceptibility to further development of erythema with higher exposure doses was measured by the gradient of erythema dose-response curves. This was determined by linear regression using reflectance spectrometry data beyond the MED. RESULTS: Although there was considerable variation within each skin type, MI and ssUV MED increased with increasing Fitzpatrick skin type. MI correlated with ssUV MED and 310 nm UV MED, but not 290 nm UV MED. There was also a significant negative correlation between MI and erythema dose-response gradients caused by ssUV, 310 and 290 nm UV. CONCLUSION: Melanin situated near the basal epidermis may not protect from the initial development of threshold erythema caused by 290 nm UV because it penetrates poorly past the stratum corneum and is not well absorbed by melanin in vivo compared with 310 nm UV. Higher erythemal 290 nm UV doses may reach basal epidermal melanin, which may then afford protection against further 290 nm UV erythema.

Adult↗
PubMed2006

Should macular erythema reactions be counted as positive allergic patch-test reactions?

BACKGROUND: Positive allergic patch-test results are generally described as erythematous papules, vesicles, or a spreading reaction with crust and ulceration. This description excludes milder reactions, including macular erythema. OBJECTIVE: Our aim was to investigate the prevalence and relevance of reactions graded as macular erythema at Mayo Clinic. METHODS: Between January 2001 and June 2004, patients suspected of having allergic contact dermatitis were patch-tested with our institution's standard patch test, a screening series of 68 to 72 allergens. In total, 2,823 patients were patch-tested with 193,530 allergen applications. Reactions were interpreted with the North American Contact Dermatitis Group scale, including and excluding reactions graded as macular erythema. Irritant reactions were excluded from calculations. For this study, scores for current, questionable, and past relevance were combined. RESULTS: On day 5, with the exclusion of reactions graded as irritant, 7,274 allergen applications were associated with reactions, including 3,082 (42.4%) that were graded as macular erythema. Of the macular erythema reactions, 2,430 (78.8%) were graded as relevant. The rate of reaction in our patients was 2.2% if macular erythema was excluded, 3.8% if all macular erythema reactions were included, and 3.4% if only those macular reactions deemed relevant were included. CONCLUSION: Patch-test reactions rated as macular erythema are common and may be of clinical relevance. For the purposes of patient education, they should not be disregarded. Consideration should be given to including these reactions when reporting patchtest results.

Allergens↗
PubMed1992

Erythema: does it indicate infection in a peritoneal catheter exit site?

The definition of a peritoneal catheter exit site infection varies from one dialysis center to another. A review of abnormal appearing exit sites (n = 334 in 169 patients) from 1/83 to 3/91 was done to compare outcome in exit sites presenting with erythema (39, 12%) to those with drainage plus erythema (72, 22%) or drainage alone (223, 67%). Resolution of the abnormality occurred in 48% of those exit sites with drainage, 62% with erythema and drainage, and 79% with erythema alone (p < 0.005). S. aureus was present in 62% of the cultured exit sites which had erythema alone, 64% with erythema plus drainage, and 41% with drainage alone, while Gram negative rods were present in 13%, 12%, and 35%, respectively (p < 0.005). Twenty-three of the 39 exit sites with erythema were not initially treated with antibiotics; 87% resolved compared with 69% of those treated immediately with antibiotics (p = ns). Seven of the 8 erythematous exit sites that did not resolve progressed to tunnel infection and/or peritonitis and required catheter removal, despite the addition of antibiotics in the three initially untreated. Six of the 8 unresolved erythematous exit sites were due to S. aureus. These results indicate that, although drainage is the commonest exit site abnormality and has the worst prognosis, peri-catheter erythema is not always benign, representing an early sign of infection in some cases.

Catheterization↗
PubMed2005

Comparison of erythema and induration as results of tuberculin tests.

SETTING: Schoolchildren, tuberculosis (TB) patients, and hospital employees in Tokyo, Japan. OBJECTIVE: To compare erythema and induration resulting from tuberculin tests among TB patients, normal children, and hospital employees with and without evidence of atopy. DESIGN: The distributions of diameters of erythema and induration were compared among three groups: 951 TB patients, 6139 first-grade and 6185 seventh-grade children, and 97 volunteer employees classified as atopic or non-atopic on the basis of skin tests and serum immunoglobulin E (IgE) concentrations. RESULTS: Erythema and induration were highly correlated. The distribution of erythema diameters was unimodal, and the distribution of induration diameters was bimodal. Erythema was considerably greater than induration among persons classified as being atopic. CONCLUSION: Both erythema and induration appear to be adequate indices of tuberculin sensitivity. However, because most of the world uses induration as the index and virtually all studies of tuberculin sensitivity rely on induration, there are advantages in the use of induration. It would be desirable to initiate a large prospective study to see whether erythema or induration is the better predictor of subsequent tuberculous disease, and to confirm our finding that erythema is more likely to be confounded by atopy than induration.

Adult↗
PubMed1990

[Bazin's erythema induratum: obsolete concept and terminology].

In 1855 Ernest Bazin, who had noted hard, deep and violaceous nodules on the legs of young women, created his famous "erythema induratum" classified among the "erythematous benign scrofulides". Some forty years later, identical lesions were observed associated with tuberculosis; Colcott-Fox called them "érythème induré de Bazin", and ever since that time erythema induratum has been presumed to be of tuberculous origin. In 1900, Darier spoke of "tuberculids" for erythema induratum, and Bazin's "scrofulides" were abusively translated as "tuberculids". In the early 20th century many authors described such skin lesions without any evidence of tuberculosis and later on many papers tried to deny this "systematic" association, but the idea that erythema induratum is caused by tuberculosis still lingers on in 1990. There are many arguments against a tuberculous aetiology, but although very few cases in large series are really associated with tuberculosis many patients have been treated with specific antituberculous agents. For numerous authors, erythema induratum in "tuberculous by definition". In 1945 Montgomery et al. created the "nodular vasculitis" concept. The clinical features are very similar to those of erythema induratum but the disease is certainly not of tuberculous origin. This new pathology has been well developed by French and Spanish authors (Bureau, Duperrat, Vilanova). Despite repeated efforts to separate these two "entities" no clinical or histological data are available to distinguish between erythema induratum and nodular vasculitis. The real meaning of "erythema induratum" is far from being clear: in old publications and sometimes in recent textbooks one can find the same name followed by of Bazin, Whitfield or Hutchinson. Some authors call the disease tuberculids, and other believe it is a true cutaneous tuberculosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗
PubMed1985

Gyrate erythema.

The gyrate erythemas consist of a nonspecific group (often called erythema annulare centrifugum) for which the cause is usually unknown, and three specific types (erythema marginatum rheumaticum, erythema chronicum migrans [Lyme disease], and erythema gyratum repens). The first specific type, erythema marginatum rheumaticum, has become extremely rare with the decline of its associated disease, rheumatic fever. The second specific type, erythema chronicum migrans, is caused by a spirochete transmitted by the I. ricinus complex of ticks. The third specific type, erythema gyratum repens, is uncommon, morphologically distinctive, and an indicator of serious disease, usually internal malignancy, in almost every instance.

Anti-Bacterial Agents↗