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Is erythema toxicum neonatorum a mild self-limited acute cutaneous graft-versus-host-reaction from maternal-to-fetal lymphocyte transfer?

Erythema toxicum neonatorum (ETN) is a common, self-limited neonate dermatosis affecting worldwide about 50% of newborns--mostly second and later deliveries--irrespective of sex and race. Its etiology still remains obscure: some reaction of the skin of the newborn in adapting to its new environment is the favorite hypothesis to date. A suggested viral or allergic nature could not be confirmed by adequate agent or antigen isolation respectively. In this paper a hypothesis is presented that ETN is a self-limited acute cutaneous graft-versus-host reaction (GVHR) caused in the transiently immunosuppressed newborn by maternal lymphocytes transferred shortly prior to or during delivery.

Erythema↗

Erythema nodosum following a jellyfish sting.

At least 100 of the approximately 9,000 species of coelenterates are dangerous to humans. The most common syndrome following an envenomation is an immediate intense dermatitis, with characteristic skin discoloration, local pain, and systemic symptoms. In this case report, we describe a case of erythema nodosum with articular manifestations following envenomation with an unknown jellyfish. Serological testing of the victim revealed marked elevation of immunoglobulins G and M directed against Physalia physalis, the Portuguese man-of-war. The patient's condition did not respond to conventional topical therapy for coelenterate envenomation, but was successfully managed with systemic corticosteroid therapy. This case demonstrates that the emergency physician should consider a delayed reaction to a marine envenomation in any victim who presents with an acute dermatological disease following immersion in marine coastal waters.

Animals↗

Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990-1992): structure and results of a population-based registry.

The severe skin reactions erythema exsudativum multiforme majus (EEM with mucosal involvement, EEMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) are difficult to study as they are very rare diseases with an incidence of about two cases per 1 million inhabitants per year. We report on the structure of a registry with the aim of ascertaining all hospitalized cases of EEMM, SJS, and TEN in western Germany and Berlin. The registry is structured as an intensive reporting system, regularly contacting more than 1500 departments including 100% of the burn units (n = 34), departments of pediatrics (n = 241), departments of dermatology (n = 106), and 100% of all internal medicine departments in hospitals with intensive care facilities or with more than 200 beds (n = 1161). With a coverage rate up to 95% based on the number of responding departments between April 1, 1990 and December 31, 1992, from a total of 767 reported cases 353 patients with EEMM, SJS, and TEN were finally included in the registry. Most of these patients were directly reported to the registry; only 2.54% (9 of 353) were primarily registered by the German spontaneous reporting systems. Assuming an average population of 64.5 million for western Germany and Berlin an incidence up to 1.89 per 1 million inhabitants per year could be calculated for SJS and TEN.

Epidemiologic Methods↗

[Benign cutaneous lymphocytoma of the breast areola and Erythema chronicum migrans: a pathognomonic association of Lyme disease].

BACKGROUND: Clinical manifestations of Lyme disease are mainly cutaneous, neurologic, cardiac and/or located joints. Some dermatologic manifestations are more specific. CASE REPORT: An eight year-old-girl was examined because she suffered from a nodular lesion located on the left breast areola which appeared 3 months earlier. This lesion was associated with an expanding erythematous annular lesion located on the anterior face of thorax and left axillary area, without any lymphadenopathy. The association of this cutaneous lymphocytoma and erythema chronicum migrans was suggestive of Borellia infection despite absence of previous tick bite. Serologic tests (indirect immunofluorescence) were negative, but both lesions disappeared within 2 weeks with ceftriaxone, 50 mg/kg/day. CONCLUSIONS: This association is pathognomonic of Lyme disease; serologic tests may be found negative in the early stages of disease.

Breast↗

UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo.

Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.

Adult↗

Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance.

Erythema migrans (EM) develops at the site of the tick bite in 77-90% of Lyme borreliosis (LB) patients and is therefore a common manifestation of early disease. Clinical treatment failures have been reported in early LB cases for almost every suitable antimicrobial agent. The exact risk of resistance to antibiotic treatment in patients with EM, however, is not known and there are few published cases of culture-proven treatment failure. Moreover, currently available diagnostic techniques cannot reliably discriminate between possible reinfection, true endogenous relapse and co-infection with other tick-borne pathogens. These drawbacks together with the phenomenon of resistance to therapy in individual patients undoubtedly contribute to the inconsistencies surrounding the optimal treatment regimens for LB and are often misinterpreted and misused to support prolonged antibiotic treatment regimens. The question for the underlying mechanisms of possible antimicrobial resistance in Borrelia burgdorferi sensu lato remains unresolved but a better understanding of such genetic or phenotypic mechanisms would be helpful for the treatment of LB and other spirochetal diseases. Investigations on this issue, at best, should start with borrelial isolates cultured from patients before the start of antibiotic therapy and again after the conclusion of treatment. This task, however, remains challenging insofar, as culture is rarely successful under routine laboratory conditions after antimicrobial therapy. Here, we review recent clinical and experimental data on treatment resistance in EM patients suggesting that, although rare, borrelial persistence does occur at the site of the infectious lesion after antibiotic treatment. Borrelial persistence, however, is unlikely to result from acquired resistance against antimicrobial agents that were used for initial specific chemotherapy.

Adult↗

Poison ivy: an underreported cause of erythema multiforme.

The relationship between herpes simplex virus (HSV) and erythema multiforme (EM) has been well described. Many authors contend that EM (excluding Stevens-Johnson syndrome and toxic epidermal necrolysis) occurs almost exclusively as a response to HSV infection. During the past year, however, we have observed several cases of EM complicating severe Rhus allergic contact dermatitis. Although this association has been previously documented, the paucity of cases in the literature, along with our experience, suggests that this is an underreported phenomenon. We describe 4 of our cases.

Adolescent↗

Severe erythema multiforme responding to interferon alfa.

Erythema multiforme (EM) is a targetoid eruption with interface pathology often triggered by a hypersensitivity response to a variety of infections, most commonly herpes simplex virus. Hepatitis C virus is rarely associated with EM. We present a 37-year-old man with an 8-year history of severe EM unresponsive to valacyclovir, acitretin, and cyclosporin, and marginally responsive to high-dose prednisone. The eruption had cleared 6 years previously during treatment with interferon for his concurrent hepatitis C virus. Although his viral titer was undetectable, we initiated therapy with interferon and ribavirin. The patient responded dramatically within 2 months and remained clear of EM after 1 year of continued interferon therapy. This is the third case reported in the world literature documenting a response of EM to interferon, and the first case in which hepatitis C virus was undetectable in serum prior to interferon therapy.

Adult↗

Necrolytic acral erythema: a cutaneous sign of hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is globally epidemic. Several mucocutaneous diseases are well established in association with HCV infection. Few case reports describe the recently recognized HCV-related skin disorder termed necrolytic acral erythema (NAE). METHODS: Thirty patients with NAE were identified in a university-based dermatology clinic in Cairo, Egypt. These patients were observed over time to document the clinical and histologic findings of this disorder. RESULTS: All patients were infected with HCV. Erythematous papules arose most commonly on the dorsal aspect of the feet, particularly the dorsal surface of the great toe. Progression resulted in confluence into erythematous dusky plaques with adherent scale and central erosion. The eruption extended to involve the lower leg and other regions in some patients but never affected palms or soles, the nail bed, nail plate, or mucous membranes. Skin biopsy specimens from fully evolved lesions displayed psoriasiform changes in association with more characteristic findings of keratinocyte necrosis and papillomatosis. LIMITATIONS: We did not perform a prospective review of patients known to be infected with HCV. Patients were identified from a general clinic population and then assayed for HCV serology. CONCLUSIONS: NAE is a distinctive skin disorder associated with HCV infection in all cases reported to date. Recognition of this disease should alert practitioners to the need for viral testing and appropriate counseling of patients.

Adolescent↗

Early congenital syphilis and erythema multiforme-like bullous targetoid lesions in a 1-day-old newborn: detection of Treponema pallidum genomic DNA from the targetoid plaque using nested polymerase chain reaction.

A 1-day-old male newborn was born with respiratory distress, low birth weight, hepatosplenomegaly, and bullous targetoid skin lesions over the face, back, buttocks, and extremities. A diagnosis of early congenital syphilis was made based on a treponemal serologic test. Pathologic examination of the skin lesion showed scattered dyskeratotic cells in the epidermis and interface dermatitis consistent with erythema multiforme. No spirochete could be found in the skin sections staining with Warthin-Starry stain. Using nested polymerase chain reaction, treponemal genomic DNA fragments encoding DNA polymerase I were detected.

Biopsy↗

Instrumental assessment of atopic eczema: validation of transepidermal water loss, stratum corneum hydration, erythema, scaling, and edema.

BACKGROUND: Quantification of skin diseases can be carried out in many ways. Clinical scores are widely used in atopic eczema (AE), and noninvasive instruments are a relevant supplement. OBJECTIVE: Our purpose was to validate 5 noninvasive instruments in quantification of AE severity. METHODS: In all, 101 patients with AE and 30 control subjects were assessed twice in a clinical cross-sectional examination. Assessment of transepidermal water loss, stratum corneum hydration, erythema, scaling, and subepidermal edema was assessed on 3 predetermined skin sites. RESULTS: The methods discriminated among various severity degrees and correlated significantly with objective assessment of disease severity. High correlations were found among instruments assessing acute symptoms of AE. Threshold values for transepidermal water loss and capacitance were found. LIMITATIONS: No gold standard exists for severity assessment of atopic eczema. Therefore, the methods used cannot be validated in relation to such a standard. Furthermore, atopic eczema is a generalized disease and the methods used assess target lesions. By assessing target lesions, information about the disease is reduced. CONCLUSION: Noninvasive instruments are valuable in quantification of disease severity in a mixed group of patients with active AE. Assessment with ultrasound has contributed new information about the pathophysiology in AE.

Adolescent↗

Quantitative assessment of skin erythema due to radiotherapy--evaluation of different measurements.

BACKGROUND AND PURPOSE: Visual assessment is the most common clinical investigation of skin reactions in radiotherapy. Due to the unquantitative and subjective nature of this method additional non-invasive methods are needed for more accurate evaluation of the visible acute adverse skin reactions due to radiotherapy. The purpose of this study was to evaluate a new objective measure with regard to reliability and validity and compare it with an established objective measure and a visual assessment. PATIENTS AND METHODS: A sample of 53 consecutive patients commencing curative tangential radiation therapy to the breast parenchyma were included in the study. The skin area of the treated breast was divided into five sections and assessed individually at 0, 24 and 50 Gy. The RTOG scoring system was used for the visual assessment of the skin reactions. The first objective measure included reflectance spectrometry (DermaSpectrometer) measures at fixed points within the treatment area. For the second objective measure digital images (Camera) were taken with a system using a digital camera and software. The images were analyzed using the Adobe Photoshop 5.0 software program. RESULTS: The results provided significant evidence of the test-retest reliability of the camera. The correlation between the objective measures proved to be significant as the treatment progressed. CONCLUSIONS: The results suggest that the camera may be used in a reliable and valid way to measure skin erythema due to radiotherapy.

Adult↗

The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans.

BACKGROUND: The diagnosis of erythema migrans (EM), the characteristic rash of early Lyme borreliosis, is based primarily on its clinical appearance since it often occurs prior to the development of a specific antibody response. Other skin disorders, however, may be confused with EM. METHODS: Between June 1991 and September 1993, a prospective study was conducted at the Lyme Disease Diagnostic Center of the Westchester County Medical Center to isolate Borrelia burgdorferi systematically from patients with Em, and to characterize the clinical manifestations of patients with culture-documented infection. Skin biopsies and/or needle aspirates of the advancing margin of primary lesions, and blood specimens from adult patients were cultured for B burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. RESULTS: B burgdorferi was recovered from 79 patients (49 [62%] males) ranging in age from 16 to 76 years old (mean, 43 +/- 14 years old). Maximum EM diameter (mean, 16 +/- 10 cm; range, 6-73 cm) was a function of EM duration (mean 6.7 +/- 6.4 days; range, 1-39 days) (correlation coefficient = 0.7; P < 0.001). Twenty (25%) patients had noted a tick bite at the site of the primary lesion a mean of 10 days (range, 1-27 days) before onset. Multiple EM lesions (range, 2-70) were present in 14 (18%) patients. Systemic symptoms were present at the time of culture in 54 patients (68%) including fatigue (54%), arthralgia (44%), myalgia (44%), headache, (42%), fever and/or chills (39%), stiff neck (35%), and anorexia (26%). Thirty-three patients (42%) had at least one objective finding on physical examination in addition to EM, including 18 (23%) with localized lymphadenopathy, 13 (16%) with fever (t > or = 37.8 degrees C), seven (9%) with tender neck flexion, six (8%) with joint tenderness, and 1 each with joint swelling, nuchal rigidity, and facial nerve palsy. No patient had new electrocardiogram evidence of atrioventricular block. Liver function assays were abnormally elevated in 37% of patients. Thirty-four percent of patients were seropositive by enzyme-linked immunosorbent assay at presentation. Most others rapidly seroconverted so that 69 of 78 evaluable patients (88%) were seropositive at some point during the first month after diagnosis. CONCLUSIONS: We describe the largest group of culture-positive patients with EM from the United States to date. Although systemic symptoms were present in most patients, objective evidence of advanced disease was uncommon. Our patients with culture-confirmed EM were less sick than those described in the days before culture confirmation was possible. The ability to isolate B burgdorferi from lesional skin of large numbers of patients with EM should make culture-positive patients the standard by which to define manifestations of early Lyme borreliosis associated with this rash. Microbiologic documentation of Lyme borreliosis will help delineate the manifestations of this illness, and should form the framework for research directed at pathophysiology, diagnosis, treatment, and prevention.

Adolescent↗

Erythema migrans and early Lyme disease.

Erythema migrans (EM) must be distinguished from other entities including streptococcal and staphylococcal cellulitis, hypersensitivity reactions to arthropod bites, plant dermatitis, tinea, and granuloma annulare. Although EM lesions may be pruritic or painful, these complaints are generally mild. Central clearing may be absent in > 50% of patients. Multiple lesions, formerly present in 50% of U.S. patients, now occur in approximately 20%. EM develops days to 1 month after a tick bite (median 7-10 days), and lesion diameter increases with duration. Most patients have associated complaints, with fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), and fever and/or chills (39%) being the most common. Respiratory and gastrointestinal complaints are infrequent. Symptoms may begin prior to the onset of, concomitant with, or after resolution of the rash. The incidence of viral-like illness due to Lyme disease without EM is unknown. Antibodies to Borrelia burgdorferi are absent in up to 50% of patients at presentation, with initial seropositivity most likely in those with EM of longer duration. The vast majority of patients will become seropositive within the first month of illness, even with treatment. Although there is evidence that B. burgdorferi can spread to the blood and central nervous system soon after onset of infection, oral therapy is highly effective in preventing objective extracutaneous complications of Lyme disease. The most appropriate choice, route of administration, and duration of therapy require further study. Because of variations in the etiologic agent between North America and Europe, comparisons of disease manifestations, treatment, and prognosis of Lyme disease must be made cautiously.

Borrelia burgdorferi Group↗

Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy.

Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.

Amyloidosis↗

Acarbose-induced generalised erythema multiforme.

A 58-year-old man with diabetes mellitus was treated with acarbose 300 mg daily. 13 days after the start of treatment with acarbose, generalised erythema multiforme developed with blood eosinophilia. Tissue eosinophilia was also found histologically. A challenge test for acarbose confirmed allergic reaction clinically and histologically.

Acarbose↗

Cicatricial pemphigoid and erythema multiforme.

Cicatricial pemphigoid (CP) and erythema multiforme (EM) are bullous diseases that involve the skin and mucous membranes including the conjunctiva. Of all the bullous diseases, CP and EM not only involve the conjunctiva most frequently but also cause the most severe conjunctival disease. A chronic, progressive disease, CP is characterized by shrinkage of the conjunctiva, symblepharon, entropion, trichiasis, dry eye, and finally reduced vision from corneal opacification. It is primarily a disease of the elderly that affects more women than men and is characterized by blisters or bullae in a subepithelial location and immunoglobulins and complement bound to the basement membrane zone of skin and mucous membranes including the conjunctiva. Circulating antibodies to the basement membrane zone can be demonstrated occasionally. Treatment includes artificial tears, topical antibiotics, correction of entropion and trichiasis, therapeutic soft contact lenses, and systemic immunosuppressive therapy including corticosteroids. An acute, generally self-limited, inflammatory disorder of the skin and mucous membranes, EM occurs primarily in young, healthy individuals. The most frequent precipitating factors are (1) drugs and (2) infections caused by Mycoplasma pneumoniae and herpes simplex. Conjunctival involvement ranges from a mild catarrhal conjunctivitis which terminates without sequelae to membranous conjunctivitis which may heal leaving scarring, symblepharon, and even ankyloblepharon. Histopathologic findings include subepithelial bullae and perivascular mononuclear cell infiltrates. Patients with EM have circulating immune complexes and immunoreactant deposition in the blood vessel walls of the dermis. After the acute episode has subsided, they may require artificial tears, topical antibiotics, correction of entropion and trichiasis, therapeutic soft contact lenses, tarsorrhaphy, and mucous membrane grafts.

Anti-Bacterial Agents↗