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High incidence of chemotherapy-induced acral erythema in female patients with non-Hodgkin's lymphoma treated with the VACOP-B regimen.

Seven patients, all females out of 29 with non-Hodgkin's lymphoma (NHL) (16 males and 13 females) treated with the VACOP-B regimen utilizing granulocyte-colony-stimulating factor (G-CSF) support developed chemotherapy-induced acral erythema (CAE). In contrast, none of 32 patients with NHL who were treated with CHOP, MACOP-B, or biweekly CHOP regimens without G-CSF developed CAE. Total dose intensities of VACOP-B regimen were higher than those of the three other regimens. However, no significant difference in dose intensities of each drug in the patients treated with the VACOP-B regimen was found between male and female patients and between female patients with or without CAE. The cause of the high incidence of CAE (7/13) in the female patients treated with VACOP-B regimen remains unknown. However, female sex hormones may increase susceptibility to CAE. Since the occurrence of CAE interrupts intensive chemotherapy and reduces the cure rate, high risk patients for CAE should be carefully monitored for early symptoms and signs of CAE and should be treated early and appropriately.

Antineoplastic Combined Chemotherapy Protocols↗

Successful treatment of chronic erythema nodosum with vitamin B12.

A 38-year-old woman presented with painful lesions on both shins that first appeared a few days earlier. Physical examination revealed multiple red tender nodules on both legs. The patient had been treated with nonsteroidal anti-inflammatory drugs for having a few months without any improvement. The patient was referred to a dermatologist and a rheumatologist, who confirmed our diagnosis of chronic erythema nodosum (EN). She returned to the clinic 3 months later complaining of having numbness in the soles of her feet for a few weeks. Her serum vitamin B12 level was 118 pg/mL (normal range 135 to 911). After 4 weeks of twice weekly injections of vitamin B12 at a dose of 1000 mcg, there was a clear alleviation of the numbness, and the EN completely resolved without evidence of recurrence on follow-up. Because it seems that vitamin B12 caused resolution of EN in this case, we recommend that physicians consider testing for vitamin B12 deficiency in patients with EN.

Adult↗

Serologically diagnosed Lyme disease manifesting erythema migrans in Korea.

Lyme disease is a vector-borne infection, primarily transmitted by Ixodes ticks, and caused by Borrelia burgdorferi. It has a wide distribution in the northern hemisphere. In Korea, however, only one human case has been reported, although B. burgdorferi was isolated from the vector tick I. persulcatus in the region. A 60-year-old male and a 45-year-old female developed the clinical sign of erythema migrans. Each patients were bitten by a tick four weeks and five weeks, respectively, before entering the hospital. On serologic examination, significantly increased IgM and IgG antibody titers to B. burgdorferi were observed in consecutive tests performed at an interval of two weeks. They responded well to treatment with tetracycline.

Erythema Chronicum Migrans↗

Clinical constellation of annular erythema associated with anti-Ro/La autoantibodies.

Annular erythema (AE) associated with anti-Ro (SSA) and/or La (SSB) autoantibody in patients with Sjögren syndrome (SS) or with SS/systemic lupus erythematosus overlap syndrome (SS/SLE), has recently been described in Orientals, and it may be a counterpart of annular skin lesion of the subacute cutaneous LE seen mostly in Caucasians. The author examined five Korean AE patients in respect to dinical diversity. In this small-sample study, subtle differences appeared between individual cases regarding the serologic features and the diagnoses of the disease. Among the five cases, four had circulating anti-Ro and anti-La antibodies, and one had only anti-La. Regarding the diagnosis, one was SS/SLE, two were primary SS, and the remaining two were only "AE associated with anti-Ro/La antibody". There seem to be a wide clinical spectrum in the disease expression of AE associated with anti-Ro/La autoantibody than previously thought.

Adolescent↗

Taking aim at erythema multiforme. How to spot target lesions and less typical presentations.

Erythema multiforme is a distinct cutaneous condition characterized by target lesions. Most cases are associated with HSV infection, which may be subclinical. When the classic target lesions are absent, skin biopsy may be necessary to confirm the diagnosis. Treatment is directed at suppressing outbreaks of HSV infection and controlling symptoms during acute episodes.

Erythema Multiforme↗

Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans.

We used multiparameter flow cytometry to characterize leukocyte immunophenotypes and cytokines in skin and peripheral blood of patients with erythema migrans (EM). Dermal leukocytes and cytokines were assessed in fluids aspirated from epidermal suction blisters raised over EM lesions and skin of uninfected controls. Compared with corresponding peripheral blood, EM infiltrates were enriched for T cells, monocytes/macrophages, and dendritic cells (DCs), contained lower proportions of neutrophils, and were virtually devoid of B cells. Enhanced expression of CD14 and HLA-DR by lesional neutrophils and macrophages indicated that these innate effector cells were highly activated. Staining for CD45RO and CD27 revealed that lesional T lymphocytes were predominantly Ag-experienced cells; furthermore, a subset of circulating T cells also appeared to be neosensitized. Lesional DC subsets, CD11c(+) (monocytoid) and CD11c(-) (plasmacytoid), expressed activation/maturation surface markers. Patients with multiple EM lesions had greater symptom scores and higher serum levels of IFN-alpha, TNF-alpha, and IL-2 than patients with solitary EM. IL-6 and IFN-gamma were the predominant cytokines in EM lesions; however, greater levels of both mediators were detected in blister fluids from patients with isolated EM. Circulating monocytes displayed significant increases in surface expression of Toll-like receptor (TLR)1 and TLR2, while CD11c(+) DCs showed increased expression of TLR2 and TLR4; lesional macrophages and CD11c(+) and CD11c(-) DCs exhibited increases in expression of all three TLRs. These results demonstrate that Borrelia burgdorferi triggers innate and adaptive responses during early Lyme disease and emphasize the interdependence of these two arms of the immune response in the efforts of the host to contain spirochetal infection.

Adult↗

Short report: erythema nodosum leprosum lymphadenitis.

A case of isolated erythema nodosum lymphadenitis involving the paravertebral, intercostal, and cervical lymph nodes without concomitant skin involvement is reported in a 62-year-old male patient under treatment for lepromatous leprosy.

Erythema Nodosum↗

Erythema infectiosum ("slapped cheeks" syndrome): a little-known entity.

Erythema infectiosum is an uncommon, benign, self-limited disease with a distinctive clinical picture, occurring mainly in children. An inquiry showed that most doctors who deal with children are not familiar with it, and the disease is therefore seldom diagnosed. As recognition has connotations which may sometimes be important, the disease is briefly reviewed, and three cases are reported.

Child, Preschool↗

Thalidomide's effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood.

Thalidomide is well documented as being an effective drug in the treatment of erythema nodosum leprosum (ENL). The mechanism of action of thalidomide in ENL as well as the pathogenesis of ENL are yet to be fully determined. Lepromatous leprosy patients experiencing ENL have been reported to have an increase in the ratio of CD4+ to CD8+ cells in their blood and ENL skin lesions. Thalidomide has been shown to cause a decrease in the ratio of CD4+ to CD8+ lymphocytes in the blood of healthy males. This decrease was due to a significant reduction in the numbers of Cd4+ lymphocytes and an apparent increase in the numbers of CD8+ lymphocytes. In this study, thalidomide's effectiveness in halting chronic ENL and arresting a relapse into ENL was consistently associated with a decrease in the numbers of CD4+ lymphocytes in the blood of 2 male lepromatous leprosy patients.

Adult↗

Dysregulation of IL-4 expression in lepromatous leprosy patients with and without erythema nodosum leprosum.

In order to increase our understanding of the immunological basis of erythema nodosum leprosum (ENL), we studied Th-like cytokine profiles in 130 leprosy patients, employing both the conventional and a novel, real-time, fluorogenic reverse transcriptase-based PCR (RT-PCR). The concomitant expression of both Th-like cytokines, interferon-gamma and IL-4, and the regulatory cytokines, IL-10 and IL-12, was studied in the peripheral blood cells of leprosy patients with and without ENL. In the conventional RT-PCR, varied cytokine profiles were observed in individual patients of all clinical types. Fifty-three percent of lepromatous patients without ENL and 59% of tuberculoid leprosy patients showed co-expression of IFN gamma and IL-4, indicating a non-polarized Th 0 pattern. Of the 36 patients with ENL, 58% demonstrated a polarized Th 1 pattern, with only 30% expressing both cytokines. Semiquantitative RT-PCR indicated a lower expression of IL-4 compared to that of IFN gamma in the lepromatous patients without ENL; the difference was even greater among those with ENL. The sensitive, real-time PCR confirmed the down-regulation of IL-4 and IL-10, with absence of IL-4 in half of the patients, resulting in skewing of the cytokine response toward a Th 1-like profile.

Cytokines↗

Erythema chronicum migrans and Lyme arthritis. The enlarging clinical spectrum.

Thirty-two patients with the onset of erythema chronicum migrans, Lyme arthritis, or both in mid-1976 were studied prospectively. The skin lesion (24 patients) typically lasted about 3 weeks, beginning as a red macule or papule that expanded to form a large ring with central clearing. Associated symptoms ranged from none to malaise, fatigue, chills and fever, headache, stiff neck, backache, myalgias, nausea, vomiting, and sore throat. Three patients had been bitten by ticks at the site of the initial lesion 4 to 20 days before its onset. Nineteen patients suddenly developed a monoarticular or oligoarticular arthritis 4 days to 22 weeks (median, 4 weeks) after onset of the skin lesion; eight developed arthritis without a preceding skin lesion. Seven of these 27 experienced migratory joint pains. Arthritis attacks, most commonly in the knee, were typically short (median, 8 days) but sometimes persisted for months. Other manifestations included neurologic abnormalties, myocardial conduction abnormalities, serum cryoprecipitates, elevated serum IgM levels, and elevated erythrocyte sedimentation rates. The diagnostic marker is the skin lesion; without it, geographic clustering is the most important clue.

Adult↗

An electron microscopic study of oral lesions in erythema multiforme.

The ultrastructure of oral lesions in 6 patients with erythema multiforme (EM) and of one apparently clinically healthy oral mucosa in one patient with recurrent EM during remission is described. Alterations were observed in epithelium, basal lamina and lamina propria. Both intercellular and intracellular oedema, intracellular vacuolization, decreased numbers of desmosomes, and also loss of cytoplasmic organelles and occasional nuclei were noted in the epithelium. Inflammatory cells--mainly lymphocytes--were found intra-epithelially. Several discontinuities together with some evidence of duplication of the basal lamina were seen in five of the six lesional mucosa specimens. The inflammatory infiltrate in the lamina propria consisted mainly of lymphocytes, although plasma cells, neutrophilic and eosinophilic leukocytes, macrophages and mast cells were also found. Some of the mast cells were partly degranulated. The apparently clinically healthy oral mucosa in the patient with EM in remission showed mild inflammatory changes. The changes observed in the lesional mucosa in EM are thus according to our study mostly non-specific inflammatory alterations and are not pathognomonic for EM.

Adolescent↗

Herpes simplex virus antigens and inflammatory cells in oral lesions in recurrent erythema multiforme. Immunoperoxidase and autoradiographic studies.

Herpes simplex virus (HSV) antigens were sought in 15 biopsy specimens from both lesional mucosa and clinically healthy looking oral mucosa between attacks in patients with erythema multiforme (EM). Four of the eight biopsy specimens obtained from lesional EM mucosa stained positively with HSV-1-and/or HSV-2-specific antisera applied in direct immunoperoxidase staining. Of the 16 tissue specimens used as controls, two displayed positive staining with HSV-1 and/or HSV-2. Five of the seven biopsy specimens from macroscopically healthy oral mucosa obtained between attacks from patients with recurrent EM stained positively with HSV-1 and/or HSV-2. Of the six tissue specimens used as controls, three stained positively. Most of the local inflammatory mononuclear cells belonged to the T cell series, mainly to the CD-4 subset. A small proportion of the local T cells were blast transformed as assessed by CD-25 expression and [3H]thymidine incorporation. This, together with the findings showing a lower degree of activation in the biopsy from macroscopically healthy looking mucosa between attacks suggest an active role of the cell-mediated immune response in the genesis of oral lesions in EM. The persistence of HSV antigens, and the well-established role of HSV as a precipitating factor in recurrent EM, suggest that HSV may be involved, but since HSV seems to be present in other mucosal lesions as well as in clinically healthy mucosa, quite frequently an additional, hitherto unknown factor must be present in order that EM may occur.

Antigens, Viral↗

Clinical and biological characteristics of immunopathological disease-related erythema nodosum in children.

We report a series of 22 children with idiopathic, drug unrelated erythema nodosum (EN) admitted to our Department. In 5 of them an history of streptococcal pharyngitis was referred; the remaining patients came to us with a diagnosis of "EN of unknown origin". Acute phase reactants, immunoglobulins, stool alpha1 antitrypsin, ANA, anti dsDNA antibodies and ANCA assay, chest roentgenogram, tuberculin test, and ophthalmologic assessment were performed in all patients. Etiologic diagnosis was made in 16 patients: Streptococcal pharyngitis (5 cases), chronic inflammatory bowel disease, IBD (3 cases), Behçet syndrome (2 cases), Yersinia enteritis (2 cases), infectious mononucleosis, atypical mycobacterial infection, immunodeficiency related infection, and SLE-like syndrome due to C4 deficiency (1 case each). We found oral/scrotal aphthae in 3 cases, gastrointestinal symptoms in 5 cases, arthritis in 3 cases. Acute phase reactants were positive in 16 patients without correlation to the underlying disease. Conversely, the increased alpha1 antitrypsin stool excretion and IgA serum concentration seemed to represent helpful indicators of IBD and Behçet syndrome, respectively. Proinflammatory cytokine pattern showed increased IL6 serum concentrations both in infectious and in non infectious disease-related EN, whereas a minor involvement of TNF was found in these patients.

Adolescent↗

Erythema infectiosum (Fifth disease) and pregnancy.

QUESTION: One of my patients is currently 14 weeks pregnant. She is a teacher in grade 1, and there is an epidemic of Fifth disease in the school where she teaches. Can this disease affect her pregnancy and how should I care for her? ANSWER: Erythema infectiosum (Fifth disease) is usually a benign disease for children and mothers, but might have serious consequences for a fetus due to hemolytic anemia, although the risk is very low. You should evaluate the mother's immune status. If she is already immune (IgG positive), the risks are nil. If she is not immune (although the risk of the fetus's being affected is very low), fetal surveillance by repeated ultrasonographic examination and immune status reevaluation has been recommended. If a fetus is found to be affected, intrauterine evaluation and treatment are available at tertiary care centres.

Adult↗

[Erythema multiforme. A heterogeneous pathologic phenotype].

The term Erythema Multiforme (EM) include actually a wide range of clinical expressions, from exclusive oral erosions (Oral EM) to mucocutaneous lesions (EM Minor), sometimes with severe involvement of multiple mucosal membrane (EM major, Stevens-Johnson syndrome [SJS]) or with involvement of a large area of the total body surface (toxic epidermal necrolysis [TEN]). However, this terminology is not worldwide accepted and often the various clinical categories show some overlapping features. Among the great number of suspected etiological factors, herpes simplex virus is involved in many cases of EM minor whereas SJS and TEN are caused in 80% of cases by systemic drugs, mainly by anticonvulsivants, sulfonamides, nonsteroidal anti-inflammatory drugs and antibiotics. Several oral EM seem idiopathic, but data on this topic are very few. There is no specific or consistent microscopic and immunopathologic pattern of EM and the diagnosis should be done by excluding other similar diseases. The treatment include the use of antivirals for EM minor, mainly if recurrent, and of immunosuppressants (especially systemic corticosteroids) for SJS. TEN patients require adequate supportive care and often they have to be treated in emergency departments. Finally, patients with exclusive oral lesions may be treated with both topical and systemical corticosteroids.

Adolescent↗