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.     

Yersinia lipopolysaccharide and its biological activity

The data on the structure and biological activity of the lipopolysaccharide (LPS) of Yersinia as an important virulence factor are analyzed. The biological effects of LPS are characterized by dose dependence: small doses stimulate the intensity of phagocytosis, while large doses decrease phagocytic activity and produce cytotoxic effect. Yersinia LPS plays an important role in the development of such consequences of yersiniosis as reactive arthritis, erythema nodosum, Reiter's syndrome. Yersinia LPS is a widespread component for the diagnostics of yersiniosis and pseudotuberculosis.     

Erythema nodosum associated with pregnancy and oral contraceptives.

Erythema nodosum recurred in a woman during each of her four pregnancies and every time she was started on oral contraceptives. The lesions always disappeared in the fifth month of gestation or when contraceptives were withdrawn. Erythema nodosum is mediated by immune mechanisms, and both pregnancy and oral contraceptive use can interfere with the immune system. The concentrations of oestrogen and progesterone or the ratio between them may be critical to the development of erythema nodosum. The observation that the lesions spontaneously resolved in the fifth month of pregnancy supports this hypothesis.     

Lepromatous leprosy in Saudi female from central region

Leprosy is an uncommon disease in Saudi population. Lepromatous leprosy is a most contagious form of leprosy. Erythema nodosum leprosum is an unusual complication of leprosy. We report an unusual case of leprosy from the central region of Saudi Arabia presenting as erythema nodosum leprosum.     

Erythema nodosum caused by ascariasis and Chlamydophila pneumoniae pulmonary infection – a case report

Erythema nodosum belongs to a group of relatively common hypodermal inflammations. It occurs mainly among women, particularly young women. The etiology of the disease is not clear. Most frequently, changes appear on the surface of the frontal part of the shins. Initially, red nodules change in color to dark brown and then to yellow and green. There is neither dissolution nor cicatrization of the exanthema. Regression is frequent. We present a case of erythema nodosum caused by Ascaris lumbricoides infection as well as by an early Chlamydophila pneumoniae infection, whose etiology has rarely been described in the literature. We were not able to confirm which factor was responsible for the occurrence of the skin changes as treatment of both infections was effective and all skin changes later disappeared completely. Particular attention should be paid to the fact that precise diagnosis of a patient and the search for etiologic factors, even rare ones, are crucial to obtain good results with treatment of erythema nodosum.     

Controlled Clinical Trial of Clofazimine in Untreated Lepromatous Leprosy

A comparison of clofazimine and dapsone in the management of untreated lepromatous leprosy showed no significant differences between the two drugs in terms of morphological and bacterial indices. The incidence of erythema nodosum leprosum was similar in the two groups. Since dapsone is cheaper than clofazimine it remains the drug of choice for the routine management of untreated lepromatous leprosy.     

Characterization of a Superantigen Produced by Yersinia pseudotuberculosis

Abstract

Yersinia species are Gram-negative coccobacilli consisting of three pathogenic species, Y. pestis, Y. pseudotuberculosis, Y. enterocolitica, and five nonpathogenic species, Y. kristensenii, Y. frederiksenii, Y. intermedia, Y. rohdei, and Y. aldovae. The former three species are primary pathogens of wild and domestic animals and birds. In the human, Y. pestis causes plague, or black death, while Y. pseudotuberculosis and Y. enterocolitica produce milder forms of disease varying from diarrhea and abdominal pain to more systemic symptoms such as fever, scarlatiniform skin rash, conjunctivitis, erythema nodosum, and lymphadenopathy (1–3). Complications of reactive arthritis, acute uveitis, coronary aneurysms, and acute renal failure are not infrequently reported after the latter two Yersinia infections (4–8). The mechanisms by which these organisms mediate these complicated symptoms are poorly understood. However, the preferential avidity for lymphoid tissues seen in these species and the characteristic histopathological finding of lymphoid hyperplasia mainly seen in mesenteric lymph nodes (9–10) suggest that the stimulation of a large proportion of T lymphocytes may be involved in the pathogenesis of this infection.     

Population structure of the Yersinia pseudotuberculosis complex according to multilocus sequence typing

Multilocus sequence analysis of 417 strains of Yersinia pseudotuberculosis revealed that it is a complex of four populations, three of which have been previously assigned species status [Y.?pseudotuberculosis sensu stricto (s.s.), Yersinia pestis and Yersinia similis] and a fourth population, which we refer to as the Korean group, which may be in the process of speciation. We detected clear signs of recombination within Y.?pseudotuberculosis s.s. as well as imports from Y.?similis and the Korean group. The sources of genetic diversification within Y.?pseudotuberculosis s.s. were approximately equally divided between recombination and mutation, whereas recombination has not yet been demonstrated in Y.?pestis, which is also much more genetically monomorphic than is Y.?pseudotuberculosis s.s. Most Y.?pseudotuberculosis s.s. belong to a diffuse group of sequence types lacking clear population structure, although this species contains a melibiose-negative clade that is present globally in domesticated animals. Yersinia similis corresponds to the previously identified Y.?pseudotuberculosis genetic type G4, which is probably not pathogenic because it lacks the virulence factors that are typical for Y.?pseudotuberculosis s.s. In contrast, Y.?pseudotuberculosis s.s., the Korean group and Y.?pestis can all cause disease in humans.     

Acute Necrotizing Lepromatous Lymphadenitis: an Erythema-nodosum-leprosum-like Reaction in Lymph Nodes

Histological examination of lymph-node biopsy specimens in 12 patients with erythema nodosum leprosum showed almost complete replacement of the node by lepromatous granuloma, together with considerable polymorph infiltration. Ziehl-Neelsen staining demonstrated numerous Mycobacterium leprae present in the nodes. The majority of these patients were very ill, and responded to prednisolone or corticotrophin.It is suggested that the histological appearances may represent an intensive inflammatory response in the lymph nodes followed by avascular aseptic necrosis.     

The yersiniae--a model genus to study the rapid evolution of bacterial pathogens

Yersinia pestis, the causative agent of plague, seems to have evolved from a gastrointestinal pathogen, Yersinia pseudotuberculosis, in just 1,500-20,000 years--an 'eye blink' in evolutionary time. The third pathogenic Yersinia, Yersinia enterocolitica, also causes gastroenteritis but is distantly related to Y. pestis and Y. pseudotuberculosis. Why do the two closely related species cause remarkably different diseases, whereas the distantly related enteropathogens cause similar symptoms? The recent availability of whole-genome sequences and information on the biology of the pathogenic yersiniae have shed light on this paradox, and revealed ways in which new, highly virulent pathogens can evolve.     

Increased Expression of IL-22 Is Associated with Disease Activity in Behcet’s Disease

Objective

Interleukin (IL)-22 has been reported to be involved in the development of autoimmune diseases. This study aimed to analyze the expression and potential role of IL-22 in the pathogenesis of Behcet’s disease (BD).

Methods

The levels of IL-22 in patient sera or supernatants of cultured peripheral blood mononuclear cells (PBMCs) and CD4⁺T cells were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to evaluate the frequency of IL-22–producing CD4⁺ T cells. IL-22 mRNA from erythema nodosum skin lesions was examined using real time quantitative RT-PCR.

Results

BD patients with active uveitis showed a significantly higher expression of IL-22 in the supernatants of stimulated PBMCs and CD4⁺T cells compared with BD patients without active uveitis and normal controls. An increased frequency of IL-22-producing CD4⁺T cells was also found in BD patients with active uveitis. IL-22 mRNA expression was elevated in erythema nodosum skin lesions. In BD patients, a high IL-22 level in the supernatant of stimulated PBMCs correlated with the presence of retinal vasculitis and erythema nodosum.

Conclusions

IL-22 was associated with disease activity in BD and correlated with the presence of small vessel inflammation, suggesting that it may be involved in its pathogenesis.     

Fatal case of erythema nodosum and histoplasmosis

Summary In the post mortem examination of a patient, erythema nodosum of the upper extremities with fibrinoid arteritis was found in presence of primary pulmonary histoplasmosis with hematogenous dissemination. Sudden death is believed to have been the result of hypersensitivity to acute fungous spread.Prof. Titul. Direct. Inst. Anat. Patol., Universidad de los Andes, Merida Venezuela, Sen. Res. Assoc., Clinical Laboratories, Jewish Hospital, Cincinnati, Ohio (Dr.Jan Schwarz).     

The gene identification of bacterial species and serovariants by the polymerase chain reaction with universal oligonucleotides: the reidentification of earlier isolated strains of Yersinia pseudotuberculosis]

Genetic analysis of 19 standard strains belonging to 6 Yersinia species (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica, Y. kirstensenii, Y. frederiksenii, Y. intermedia) revealed that gene typing by the method of polymerase chain reaction (PCR) with the use of universal primers permitted the identification of species in bacterial cultures by PCR patterns and the determination of Y. pseudotuberculosis serovars within 4 hours. By this method 23 Y. pseudotuberculosis strains (serovar 1), earlier isolated in different regions of the USSR from humans and rodents, were studied. The study showed that out of 14 strains of human origin only two strains could actually be classified with serovar 1, while the remaining strains were reidentified as belonging to serovar 5. Among 9 strains isolated from rodents those of serovar 1 prevailed (8 strains). The authors suppose that strains of serovar 5 cause outbreaks and sporadic cases of pseudotuberculosis, occurring considerably more often than it is commonly believed in the USSR.     

`Silk Route Disease' (Beh?et's Disease)

Behçet''s disease is a multisystem disorder in which orogenital ulceration is associated with troublesome generalized uveitis, erythema nodosum, pyoderma, dermatographism, seronegative arthritis, and neurologic and cardiovascular symptoms. There is no diagnostic laboratory test; the diagnosis is based on the disorder''s multisystem clinical features. A points scoring system is helpful in distinguishing it from other multisystem disorders that mimic it. It occurs most frequently in an area coinciding with the old Silk Route, between latitudes 30° and 45° north, in Asian and Eurasian populations, and it has an HLA-B51 affinity. The cause remains unknown, but a postulated trigger factor is a herpesvirus with cofactors that include ethnic group, human leukocyte antigen affinities, T-cell and autonomic imbalance, circulating immune complexes, autoimmunity, blood viscosity, decreased fibrinolysis, and zinc deficiency. Treatment includes administering corticosteroids, azathioprine, chlorambucil, cyclosporine, and colchicine, and fibrinolytic therapy.     

Complete genome sequence of Corynebacterium pseudotuberculosis strain Cp267, isolated from a llama

In this work we report the genome of Corynebacterium pseudotuberculosis strain 267, isolated from a llama. This pathogen is of great veterinary and economic importance, as it is the cause of caseous lymphadenitis in several livestock species around the world and causes significant losses due to the high cost of treatment.     

Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren’s syndrome

Introduction: Macrophage migration inhibitory factor (MIF) has been shown to be a key regulator in innate and adaptive immune responses. A single nucleotide polymorphism in the 5′ region of the MIF gene, MIF -1731G/C, is associated with increased MIF protein production, in vivo and in vitro. Associations have been shown between the minor MIF -173C allele and sarcoidosis patients with erythema nodosum (EN). Löfgren’s syndrome is an acute and usually self-remitting phenotype of sarcoidosis. It is defined as having an acute onset with bilateral hilar lymphadenopathy (BHL), fever, erythema nodosum (EN) and/or arthritis.The aim of this study was to investigate whether MIF -173G/C associates with the susceptibility to and the clinical manifestations, i.e. arthritis or EN, of Löfgren’s syndrome.A total of 171 patients with Löfgren’s syndrome and 313 controls were genotyped for a single nucleotide polymorphism at position -173 of the MIF gene (SNP rs755622), using a PCR and a restriction enzyme technique.Results: There were no significant differences found in the MIF -173C allele frequencies between patients with Löfgren’s syndrome and controls. In patients with Löfgren’s syndrome with only EN, a significantly increased frequency of the C minor allele was observed compared to patients with arthritis only (p = 0.0095; OR 3.08, CI: 1.28–7.39).Patients with only EN compared to patients with EN and arthritis showed a significantly increased frequency of the minor C allele (p = 0.044; OR 1.97, CI: 1.01–3.85). But patients with only arthritis compared to patients with EN and arthritis did not show a significant difference in C allele frequency (p = 0.270; OR 0.64, CI: 0.29–1.42).Conclusions: The MIF -173C allele is associated with erythema nodosum in Löfgren’s syndrome, but not with susceptibility to sarcoidosis. This indicates a role for MIF after antigen presenting to the T cell has taken place and the sarcoid inflammatory response has begun.     

Use of a genetically labelled strain for the analysis of Yersinia pseudotuberculosis population dynamics in natural soils

The Rifr mutant of Y. pseudotuberculosis, capable of producing pure cultures in media with a high content of rifampicin, has been used for an accurate quantitation of this microorganism in various kinds of natural (nonsterile) soil in controlled laboratory and field experiments. The main biological characteristics of the mutant have been identical to those of the parent strain. The first experiments have shown that the initially high concentration of Y. pseudotuberculosis in the soil gradually decreases in 2 months. The share of this microorganism in the natural microflora of the soil seems to be rather small, which probably explains the cause of low indices of spontaneous contamination of the soil in nature.     

Double-Blind Controlled Clinical Trial of Clofazimine in Reactive Phases of Leprotamous Leprosy

A double-blind controlled trial in 24 lepromatous leprosy patients in reaction showed that clofazimine (Lamprene) controlled symptoms of erythema nodosum leprosum reaction in lepromatous leprosy better than prednisolone. Clofazimine also appeared to be significantly superior in preventing recurrence once the reaction had been controlled. There was a statistically significant rise in serum albumin among inpatients on clofazimine as compared with patients on prednisolone, but no difference in terms of neurological status, bacterial index, morphological index, and renal functions. Red/black hyperpigmentation was seen among practically all patients on clofazimine. No other side-effects or deleterious systemic effects were observed.     

Serum neopterin as a marker for reactional states in leprosy

Reactions, a relatively common phenomenon among leprosy patients in treatment, require early detection and proper management to prevent serious sequelae. It is generally accepted that reactional states are immunologically mediated and, as such, usually improve with immunomodulatory treatments such as corticosteroids or thalidomide. Neopterin, a product of gamma-interferon-activated macrophages, is a marker for cell-mediated immune activation and may be useful to detect reactional states in leprosy. Here, we compared neopterin levels in single serum samples from leprosy patients with and without reaction with untreated controls and, when available, serial samples among patients with and without reaction. Levels in the single sample measurements, conducted in 22 patients with a reversal reaction (mean 14.5 nmol l(-1), S.D. 8.7) and 13 with erythema nodosum leprosum (mean 16.9 nmol l(-1), S.D. 13.6), were significantly higher (P=0.02 and P=0.001, respectively) than levels in 26 untreated patients (mean 9.1 nmol l(-1), S.D. 7.3). Values above the upper limit of normal (10 nmol l(-1)) were found in seven of 26 untreated patients, 14 of the 22 reversal reaction patients (P=0.01) and 10 of the 13 ENL patients (P=0.003). Serial serum samples, obtained from six patients that developed reactions and 14 that remained free of reaction, indicated that reversal reaction or erythema nodosum leprosum paralleled a concomitant increase in the serum neopterin level. Neopterin levels generally declined upon corticosteroid therapy. Neopterin may be a useful marker for reactional states in leprosy by providing a laboratory parameter to assess the onset, progression, response to therapy and resolution.     

Genotyping of Yersinia pseudotuberculosis isolated in Siberia and Far East

Genotypic characteristics based three main factors of pathogenicity (presence of resident plasmids [pYV, pVM], gene of toxin-superantigen ypm and nine genes for high pathogenicity island [HPI]) of 212 strains of Y. pseudotuberculosis isolated in Siberia and Far East were studied. It was shown that strains of Y. pseudotuberculosis with one of two variants of plasmids 82:47 MDa and 47 MDa (60.8% and 31.6% respectively) are predominated. Gene ypmA was detected in 96.2% of isolated strains. Eight strains had none of the ymp gene variants. HPI were detected in 96.2% of isolated strains. Obtained characteristics of Y. pseudotuberculosis allowed to determine the dominating genogroup pWYV+, ypmA+, HPI- (95.8% of strains) that cause systemic infection.