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HLA DQB1*0301 allele is involved in the susceptibility to erythema multiforme.

Erythema multiforme (EM) is an acute, episodic inflammatory disorder of the skin and mucous membranes of various etiology that could be related to immunologic hypersensitivity response. EM has been previously reported to be associated with serologically defined HLA-DRw53 and DQw3 antigens. In this report, we reevaluate the role of HLA class II alleles in EM manifestations. With use of the polymerase chain reaction, followed by sequence-specific oligonucleotide hybridization, 35 unrelated Caucasian EM patients and 80 randomly selected healthy subjects were studied, and the DRB3, DRB4, DQA1, and DQB1 alleles were analyzed. The comparison of frequencies of these alleles indicates that (i) susceptibility to EM disease is more associated with the HLA-DQ than the HLA-DR subregions and (ii) that the DQB1*0301 is the most frequent allele among EM patients. Sixty-six percent of the patients had the DQB1*0301 allele compared to 31% of the controls (RR = 4.1; p less than 0.001). An even stronger DQB1*0301 association was found in the patient group with herpes-associated EM (76%; RR = 6.5; p less than 0.001). Our data demonstrate a clear association between an HLA-DQB1 allele and susceptibility to EM.

Adolescent↗

UVA erythema in skin: is it a sunburn?

Specimens obtained from human skin following the induction of erythema responses with long ultraviolet (UVA) and with middle ultraviolet (UVB) radiation alone were compared histologically to determine whether the effects of these two portions of the electromagnetic spectrum were the same. It was found that, except for similar dermal inflammatory changes, the effects of UVA were not the same as those of UVB; characteristic epidermal sunburn damage was induced by the latter, but not by the former.

Erythema↗

Detection of viral DNA within skin of healed recurrent herpes simplex infection and erythema multiforme lesions.

The polymerase chain reaction (PCR) was used to detect HSV DNA in genomic DNA extracted from skin biopsies obtained from healed skin of five patients with hyperpigmented macules following recurrent cutaneous HSV infections and from eight patients with HSV-associated erythema multiforme (EM). A 92-bp HSV-1 DNA fragment was found in all the skin biopsies from the site of recurrent HSV infection and in five of eight (62%) biopsies from the EM patients. Virus DNA was not found in tissues distant from the site of HSV recurrence or from a patient without a history of HSV infection. These findings confirm the presence of HSV in healed skin from the site of recurrent HSV disease and are consistent with the concept that HSV is involved in EM pathogenesis.

Adolescent↗

Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascular permeability and angiogenesis associated with many malignant tumors. In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis. In this study, we investigated the expression of VPF/VEGF in three bullous diseases with subepidermal blister formation that are characterized by hyperpermeable dermal microvessels and pronounced papillary dermal edema. The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization. Epidermal labeling was particularly intense over blisters, but strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters. Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF (138-238 pM) were detected in blister fluids obtained from five patients with bullous pemphigoid. Addition of blister fluid to human dermal microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bullous diseases, leading to papillary edema and fibrin deposition and contributing to the bulla formation characteristic of these disorders.

Adult↗

Perturbation of experimental ultraviolet light-induced erythema by passive transfer of serum from subacute cutaneous lupus erythematosus patients.

Several lines of investigation have implicated anti-Ro/SS-A antibody in the pathogenesis of photosensitive forms of cutaneous lupus erythematosus such as neonatal lupus erythematosus and subacute cutaneous lupus erythematosus. To further explore this possibility, we have developed a quantitative, experimental system for examining the effect of passively transferring anti-Ro/SS-A antibody-containing and antibody-deficient subacute cutaneous lupus erythematosus patient sera on one aspect of cutaneous photoreactivity, UV-induced erythema. Laser-Doppler velocimetry was used to quantitate the microvascular flow rates in normal control, disease control (rheumatoid arthritis, discoid lupus erythematosus), and subacute cutaneous lupus erythematosus serum-injected guinea pig skin test sites before and after combined ultraviolet B and A radiation from a solar simulator. Results, expressed as change in milli-electron voltage (perturbed milli-electron volts after irradiation minus baseline milli-electron volts before irradiation), revealed that subacute cutaneous lupus erythematosus serum injections consistently resulted in greater UV-induced microvascular flow rates than those elicited by normal or disease control serum injections. Anti-Ro/SS-A containing subacute cutaneous lupus erythematosus sera produced the greatest flow rates observed in this study. Earlier studies have suggested that the pathogenesis of lupus photosensitivity is very likely multifactorial. Our current data suggest that anti-Ro/SS-A autoantibody or other closely related humoral elements should also be considered among the factors which might contribute to this clinical phenomenon.

Acute Disease↗

Erythema chronicum migrans in three soldiers.

Three cases of erythema chronicum migrans in soldiers who had returned from active duty in Central Europe were seen within a ten-week period in San Franciso. Typically, the lesions cleared in less than five days with penicillin in two cases and erythromycin in another.

Adult↗

CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments to the skin of patients with erythema multiforme (HAEM).

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.

Adult↗

Palpable arciform migratory erythema in an HIV patient, a CD8+ pseudolymphoma.

BACKGROUND: Palpable arciform migratory erythema (PAME) is characterized by large, elevated, reddish annular lesions localized on the upper trunk. As its infiltrate consists predominantly of dense infiltrates of CD4+ lymphocytes with polyclonal T-cell receptor (TCR) gene rearrangement, it has been grouped as a rare member of the T-cell pseudolymphomas. METHODS: We performed histology, immunophenotyping, and TCR-gamma gene rearrangement studies in an human immunodeficiency virus (HIV)-positive patient, CDC stage IIIB, who showed a clinically typical PAME. RESULTS: While TCR-gamma gene rearrangement studies showed a polyclonal infiltrate confirming a pseudolymphoma, 85% of skin-infiltrating lymphocytes were CD8+ T cells. CONCLUSION: PAME may also occur in HIV-positive patients with CD4+ deficiency. Our case demonstrates that regular CD4 counts and immunocompetence are not necessary for its pathogenesis.

Adult↗

Mycobacteria other than Mycobacterium tuberculosis are not present in erythema induratum/nodular vasculitis: a case series and literature review of the clinical and histologic findings.

Erythema induratum (EI)/nodular vasculitis (NV) is characterized by recurrent crops of tender oedematous nodules on the lower legs. A lobular panniculitis with granulomatous inflammation, vasculitis, focal necrosis and septal fibrosis is present. Mycobacterium tuberculosis DNA has been detected in some lesions by means of polymerase chain reaction (PCR). Ten cases of EI/NV were found. H&E slides were reviewed. PCR assays for M. tuberculosis and mycobacteria other than M. tuberculosis (MOTT) were performed. PCR did not reveal M. tuberculosis (0%) or MOTT (0%) DNA, with positive controls, indicating the reliability of the assays. Among the MOTT, cutaneous infections are most commonly caused by M. marinum. Subcutaneous tuberculoid granulomas may be seen with M. kansasii, M. marinum, M. scrofulaceum and M. avium complex. M. gordonae, M. szulgai and M. malmoense rarely cause cutaneous infections. M. simiae, M. gastri and M. asiaticum are probably not cutaneous pathogens. M. tuberculosis and MOTT DNA was not found in EI/NV. EI/NV has diverse aetiologies with varying pathogeneses leading to similar histologic changes. The cases analysed may not have had an infectious aetiology. However, in EI/NV, performance of PCR for MOTT as well as M. tuberculosis complex may still be beneficial, particularly in cases from immunocompromised hosts.

Adolescent↗

Histopathologic spectrum of erythema nodosum.

Erythema nodosum (EN) is the most common panniculitis and histologically represents the prototype of a septal panniculitis. However, the histologic findings can be quite variable. We describe four patients with EN who each underwent two consecutive biopsies. In each case, the first biopsy showed histopathologic features that fall outside the usual spectrum of disease. Two cases showed predominantly neutrophilic infiltrates with focal suppuration as well as vasculitis of medium-sized arteries. The areas of suppuration were more extensive in the first case prompting special stains for microorganisms that were all negative. The third case demonstrated a lobular panniculitis with a predominantly lymphohistiocytic infiltrate. Special stains were negative in this case as well. The fourth case revealed vasculitis of a medium sized artery, small vessel vasculitis, and a mixed septal and lobular panniculitis with a polyclonal population of atypical lymphocytes. In all patients, the clinical course and the subsequent biopsy were classic for EN. We conclude that lobular neutrophilic panniculitis with suppuration, small vessel vasculitis, and even medium vessel arteritis may rarely occur in EN. There are few clues in these unusual cases that allow for a specific diagnosis from the start, and often, a second biopsy is required.

Acute Disease↗

The level of angiotensin-converting enzyme as indicator of 2-year prognosis in untreated pulmonary sarcoidosis without erythema nodosum.

In order to evaluate the prognostic significance of elevated serum angiotensin-converting enzyme (SACE) in pulmonary sarcoidosis, the 2-year prognosis was studied in 33 untreated patients without erythema nodosum. Elevated SACE was found in 19 patients among whom total regression or improvement was noted in 42%, against 86% in 14 patients with normal SACE in serial measurements. The groups with and without elevated enzyme levels were not different with respect to sex, age, pulmonary changes, or extrathoracic manifestations. Thus, the findings of elevated SACE in this category of sarcoidosis patients may have some prognostic significance, pointing toward a greater risk of a chronic course.

Acute Disease↗

Erythema multiforme in children: unusual clinical features with seasonal occurrence.

Eighty-six cases of erythema multiforme (EM) were studied based on the distribution of skin lesions. Twenty-nine patients had distinct facial skin lesions as well as lesions on the extremities (Group A) and 57 patients had skin lesions only on the extremities (Group B). Patients in Group A were younger than those in Group B; the average ages being 7.5 and 25.2 years, respectively. In Group A, the disease occurred mainly in winter, while, in Group B, it began most frequently in summer. Preceding ulcerated pernio was seen in 11 patients of Group A, but only one of Group B. Histopathologically, both groups are compatible with a diagnosis of EM, although the seasonal occurrence of facial involvement in Group A may suggest a specific etiological relationship to cold.

Adolescent↗

Necrolytic migratory erythema in glucagonoma syndrome.

A 32-year-old female Chinese presenting with typical features of necrolytic migratory erythema due to glucagonoma syndrome is reported. The clinical, biochemical, histopathological, and electron-microscopic findings are described. Various different aspects of this rare entity are discussed.

Adult↗

The relationship of sun protection factor to minimal erythema dose, Japanese skin type, and skin color.

The relationship of sun protection factor (SPF) to minimal erythema dose (MED), Japanese skin type, and skin color was investigated on the unexposed backs of 48 healthy subjects. SPF of a UVB-sunscreen was determined using sun lamps as a light source. A significant correlation was found between SPF and MED; subjects with lower MED showed higher SPF. The average SPF decreased with increasing skin type. There was no significant correlation between SPF and skin color (L*a*b* color system).

Adult↗

Palmar erythema ab igne without detectable type IV collagen at the basement membrane zone.

A 42-year-old baker had hyperkeratotic lesions on reticular erythema of his palms and volar digits. Attachment between the epidermis and the dermis was loose at the hyperkeratotic sites, but no blisters had formed. After he stopped work for 2 months, the skin lesions disappeared, leaving a slight scar. Immunofluorescence studies showed a normal distribution of type VII collagen and laminin, but there was almost no fluorescence for type IV collagen in the basement membrane zone. Disappearance of cytoplasmic organelles and aggregated tonofibrils was evident under electron microscopy in the basal cells which appeared shrunken under light microscopy. The structures of lamina lucida, basal lamina and anchoring fibrils were disarranged. The loose dermo-epidermal attachment is probably due in part to this disorganized basement membrane structure lacking type IV collagen, which may have been digested by heat-activated matrix metalloproteinases. In addition, his work-related chronic heat exposure might have caused hyperproliferation of keratinocytes.

Adult↗

Erythema nodosum leprosum in histoid leprosy: a case report.

A 28-year-old married female developed histoid papules and nodules de novo over her face, extremities, back, buttocks and thighs. She had developed erythema nodosum leprosum lesions without any antileprosy treatment. Histopathology from a histoid nodule showed well defined nodular collections of plump, spindle-shaped histiocytes. A few globi were also seen with Ziehl Neelson staining. Leucocytoclastic vasculitis was present in the ENL lesion. The CD4:CD8 ratio was 1.5:1.

Adult↗

An erythema multiforme-like eruption caused by exposure to 1-chloromethylnaphthalene.

A young male patient developed an erythema multiforme-like eruption following an accidental exposure to 1-chloromethylnaphthalene (1-CMN). In addition to the skin lesion, he suffered from liver involvement and tear insufficiency. Positive results of a patch test with 1-CMN and an in vitro lymphocyte transformation test suggested that direct exposure of the skin to chemical compounds was the probable cause of his symptoms.

Administration, Topical↗