Guttate psoriasis triggered by perianal streptococcal infection

The association of guttate psoriasis (GP) with streptococcal pharyngitis is well accepted. However, less is known about the association with perianal streptococcal infection. We report a case of a 19‐month‐old boy with GP after a preceding perianal streptococcal dermatitis, with no clinical signs of a streptococcal pharyngitis. Treatment with phenethicillin was given together with mometasone ointment. After 4 weeks, the perianal redness was reduced and the psoriasis had improved significantly. A review of the literature revealed nine previous case reports, comprising a total of 15 patients. In all cases, the perianal dermatitis and the GP improved after treatment with oral antibiotics, sometimes in combination with topical corticosteroids. We conclude that in cases of GP in children, the perianal area must be examined for streptococcal infection.     

Restricted T-cell receptor Vβ gene usage in the skin of patients with guttate and chronic plaque psoriasis

A strong association between acute guttate psoriasis and group A, β-haemolytic streptococcal infections is well established. Furthermore, streptococcal M proteins and toxins have been shown to act as superantigens, stimulating subpopulations of T lymphocytes expressing particular Vβ families. We have therefore studied the possible role of streptococcal superantigens in psoriasis by staining peripheral T lymphocytes and skin sections from patients with guttate or chronic plaque psoriasis for the expression of nine TCR Vβ families, using a range of monoclonal antibodies. A marked over-representation of Vβ2⁺ T lymphocytes was observed in the dermis and epidermis of patients in both groups, when compared with T lymphocytes in their peripheral blood. A less marked dermal increase in Vβ5.1⁺ T lymphocytes was also observed in these patients. These findings are consistent with the involvement of a superantigen, possibly streptococcal, in the pathogenesis of psoriasis.     

Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study

BACKGROUND: Guttate psoriasis has a well-known association with streptococcal throat infections but the effects of these infections in patients with chronic psoriasis remains to be evaluated in a prospective study. OBJECTIVES: To determine whether streptococcal throat infections are more common in and can cause exacerbation in patients with chronic psoriasis. METHODS: Two hundred and eight patients with chronic plaque psoriasis and 116 unrelated age-matched household controls were followed for 1 year. At recruitment all patients were examined, their disease severity scored and throat swabs taken. Patients and corresponding controls were then re-examined and tested for streptococcal colonization whenever they reported sore throat or exacerbation of their psoriasis during the study period. RESULTS: The psoriasis patients reported sore throat significantly more often than controls (61 of 208 vs. three of 116, P < 0.0001), and beta-haemolytic streptococci of Lancefield groups A, C and G (M protein-positive streptococci) were more often cultured from the patients than the controls (19 of 208 vs. one of 116, P = 0.003). A significant exacerbation of psoriasis (P = 0.004) was observed only if streptococci were isolated and the patients were assessed 4 days or later after the onset of sore throat. No difference was observed between groups A, C or G streptococci in this respect. CONCLUSIONS: This study confirms anecdotal and retrospective reports that streptococcal throat infections can cause exacerbation of chronic plaque psoriasis. It is concluded that psoriasis patients should be encouraged to report sore throat to their physician and that early treatment of streptococcal throat infections might be beneficial in psoriasis. A controlled trial for assessing potential benefits of tonsillectomy in patients with severe psoriasis should also be considered.     

Peripheral blood lymphocytes from psoriatic patients are hyporesponsive to β-streptococcal superantigens

The strong association of acute guttate psoriasis and streptococcal throat infection, together with the preferential use of T cells expressing a particular T-cell receptor, has suggested a role for bacterial superantigens in the pathogenesis of psoriasis. We examined the proliferative responses of peripheral blood lymphocytes (PBLs), obtained from patients with psoriasis and from healthy controls, to streptococcal superantigens, cytoplasmic membrane-associated protein (CAP) and secretion-type CAP (SCAP), isolated from group A, β-haemolytic streptococci. PBLs from patients with psoriasis showed significantly less response to SCAP and CAP than those from healthy controls. Because there was no difference between psoriatic patients and controls in the proliferative response of PBLs to staphylococcal enterotoxin A or E (SEA, SEE) or the mitogen phytohaemagglutinin (PHA), these findings strongly suggest that the reduced reactivity to the streptococcal superantigens seems to reflect anergy of a population of PBLs to the superantigens. As the CAP used in the present study stimulates Vβ8 T cells selectively, we further examined the proliferation of Vβ8 T cells after such stimulation using flow cytometry. Vβ8 T cells obtained from three of four psoriatic patients failed to proliferate in the presence of CAP, whereas they proliferated vigorously in the presence of SEE, which activates Vβ8 T cells, confirming the specific hyporesponsiveness of PBLs from psoriatic patients to streptococcal superantigens. We then determined the effects of serum factors on the suppressed response of PBLs to the streptococcal superantigens with SCAP or CAP. It was partially restored when PBLs were cultured with sera obtained from healthy subjects, although the responses were still significantly lower than those of the healthy controls. In contrast, psoriatic sera markedly suppressed the proliferative response of PBLs from healthy controls to CAP or SCAP, but showed no suppression of the proliferative response of PBLs to SEA. Because these findings suggest the presence of specific inhibitory factors in psoriatic sera, we examined whether the inhibitory effect was caused by antisuperantigen antibody. However, no significant increase was detected in antibody titre to CAP in psoriatic sera, as has been noted in sera from patients with poststreptococcal glomerulonephritis. The present results show for the first time the hyporesponsiveness of PBLs to streptococcal superantigens and the presence of serum inhibitors that specifically inhibit T-cell response to the superantigens in psoriatic patients. These findings suggest a pathological role for streptococcal infections in the pathogenesis of psoriasis.     

云南汉族与链球菌感染有关的银屑病患者HLA-DR易感基因研究

目的：发现云南汉族与链球菌感染相关的银屑病患者易感基因，探讨银屑病与感染和遗传的关系。方法：用多聚酶链反应技术及序列特异性引物（PCR-SSP），对36例咽部致病性链球菌培养阳性银屑病患者进行HLA-DR基因分型，并与28例云南汉族正常人HLA-DR分型结果比较。结果：银屑病患者HLA-DR7基因频率比正常人显著增高，HLA-DR15基因频率也增高；20例HLA-DR15阳性患者有19例与HLA-DR7连锁，而正常组无DR7与DR15连锁。结论：云南汉族与链球菌感染有关银屑病患者易感基因与HLA-DR7及DR15关联，推测这两个位点的等位基因连锁以共同对链球菌感染相关银屑病易感性发挥作用。     

Perianal streptococcal dermatitis in adults

Summary Perianal streptococcal dermatitis is an uncommon superficial cutaneous infection of the perianal area almost exclusively described in children. We report here four adult cases. Beta-haemolytic streptococcus group A was detected in the perianal areas of all the patients. Systemic erythromycin gave complete resolution. The incidence of perianal streptococcal dermatitis in adults is probably underestimated, and culture from the affected area should always be performed in patients with persistent perianal erythema.     

Necrotizing Fasciitis Due to Group A Streptococci: A Clinicopathological Study of Six Patients

The recent worldwide appearance of invasive group A streptococcal infections has again called attention to streptococcal necrotizing fasciitis. However, in contrast to polymicrobial necrotizing fasciitis, the streptococcal form has not been thoroughly studied clinically. The objective of the study was to elucidate the characteristic features of recent cases of necrotizing fasciitis due exclusively to pure group A streptococci. We encountered six patients with these criteria at a single hospital in Japan during the last 12 years. A clinicopathological analysis was performed in these six patients. In three patients, the clinical signs and the laboratory findings were characteristic of systemic toxicity. In this group, the clinical presentation was a pale or blue-gray lesion associated with severe intravascular coagulation histologically involving the vessels in the lesion. In the three patients without signs of systemic toxicity, a swollen, erythematous skin lesion persisted for as long as one week; histologically, the intravascular coagulation within these lesions was mild. In clinicopathological terms, the entity in these six patients could be clearly classified as either fulminant or subacute. In the fulminant type, immediate surgical debridement of necrotic fascia is required; in the subacute type, incision and drainage alone are sufficient.     

The role of streptococcal infection in the initiation of guttate psoriasis.

BACKGROUND AND DESIGN--Although the association between streptococcal infection and guttate psoriasis is well known, to date there has been little information on whether only limited groups and/or serotypes of beta-hemolytic streptococci are involved. One hundred eleven patients with a sudden onset or deterioration of psoriasis were investigated for evidence of streptococcal infection. Of these patients, 34 had acute guttate psoriasis, 30 had a guttate flare of chronic psoriasis, 37 had chronic plaque psoriasis, and 10 had other types of psoriasis. RESULTS--Serologic evidence of recent streptococcal infection was present in 19 (58%) of 33 patients with acute guttate psoriasis compared with seven (26%) of 27 patients with guttate exacerbations of chronic psoriasis. Streptococcus pyogenes was isolated from 19 (17%) of all 111 patients (9 [26%] of 34 with acute guttate psoriasis, four [13%] of 30 with guttate exacerbations of chronic psoriasis, and five [14%] of 37 patients with chronic psoriasis) compared with seven (7%) of 101 of a control population of patients being seen for treatment of viral warts. Other beta-hemolytic streptococci were found with equal frequency in the study and control populations. Thirteen isolates of 10 different streptococcal serotypes were obtained from the 64 patients with guttate psoriasis. These serotypes were similar in distribution and prevalence to those present in the local community. CONCLUSIONS--This study confirms the strong association between prior infection with S pyogenes and guttate psoriasis but suggests that the ability to trigger guttate psoriasis is not serotype specific.     

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

Background

The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. In vitro data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients.

Methods

We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping. The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test.

Results

Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls. The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively.

Conclusion

These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.     

Erythema nodosum and associated diseases. A study of 129 cases

Background Erythema nodosum (EN) is associated with many infectious diseases. The purpose of this study was to evaluate the relative prevalence of associated diseases in a large series of EN, and to review the previously described causes of EN. Materials and methods A total of 157 inpatients with a diagnosis of EN made in Strasbourg, France between 1960 and 1995 were studied retrospectively, but only 129 patients with confirmed EN were evaluated. A biopsy was taken in 30 patients with atypical clinical symptoms. Chest radiography, blood cell count, throat swab, and anti-streptolysin dosage were performed systematically. Viral investigations and serodiagnoses for various bacterial infections were carried out in approximately half of the patients. All investigations were analyzed retrospectively and compared with the world literature. Results The female : male ratio was 5 : 1 and the mean age was 31 years. We found 28% confirmed streptococcal infections, 11% sarcoidosis, 1.5% enteropathies, 1.5% Chlamydia infections, 0.8% Mycoplasma infections, 0.8% Yersinia infections, 0.8% hepatitis B, and 0.8% tuberculosis (one case). The causative factor could not be determined in 55% of patients. Conclusions Our data confirm the predominance of streptococcal infections and sarcoidosis among patients with EN. Tuberculosis has virtually disappeared, since the last case was observed in 1962. Various viral or bacterial diseases are rarely associated with EN, but all patients were not thoroughly investigated. A large and prospective study should be performed in order to determine the true prevalence of associated diseases in EN. In the absence of specific symptoms, exhaustive investigations are not cost-effective.     

Unspecific increase of antistreptolysin-O titer in acute guttate psoriasis

An acute streptococcal infection is well-known to be a predisposing factor in acute guttate psoriasis. This study also revealed a high ASO titer in 11 of 13 patients at first examination. However, a non-specific ASO increase due to non-immunological reaction of serum lipoproteins with antistreptolysin-O, was found in 5 of these patients who visited our clinic at the evolving phase, 2 or 3 weeks after onset of the eruption but was no longer observed at 5-6 weeks and thereafter. On the other hand, specific ASO increase, which was not related to lipoproteins, was observed first in some patients at 3-4 weeks and at 7-10 weeks in all patients examined. These observations suggest the role of streptococcal lipoprotein alteration in the occurrence of this disease.     

Skin CD4+ T cells produce interferon-gamma in vitro in response to streptococcal antigens in chronic plaque psoriasis

Recently, we have demonstrated that group A streptococcal antigen reactive T cells are present in the skin lesions of chronic plaque psoriasis. To determine the cytokine profile (interferon-gamma, interleukin-4 and interleukin-10) of these T cells in response to streptococcal antigens, T cell lines were cultured from untreated lesional skin of 13 patients with chronic plaque psoriasis and 12 patients with other inflammatory skin diseases. T cell lines were incubated with or without a sonicated heat-killed mixture of group A streptococcal isolates for 18 h in the presence of a transport inhibitor, stained for surface CD4 or CD8 and intracellular cytokine expression, and analyzed by flow cytometry. Psoriatic T cell lines were grown from 10 of 13 patients and were predominately CD4+ (64%-85%) with 10%-32% CD8+ T cells. Variable numbers of CD4+ T cells produced interferon-gamma (0.8%-35%, median 13.9) in eight of 10 T cell lines (p < 0.02). In contrast, CD4+ T cells in five of 12 T cell lines obtained from disease controls did not produce or produced minimal interferon-gamma in response to group A streptococcal isolates; this was significantly different from the psoriatic T cell lines (p < 0.05). Small numbers of interleukin-10 positive (0.8%-1.3%) and interleukin-4 positive (2.1%-2.5%) CD4+ T cells induced by group A streptococcal isolates were also present in two out of five and three out of five psoriatic T cell lines, respectively. This was significantly less in each case than the numbers of CD4+/interferon-gamma+ T cells (p < 0.05). Cytokine-positive CD8+ T cells were rarely observed. These findings demonstrate that a subpopulation of CD4+ T cells in chronic plaque psoriasis skin lesions produces interferon-gamma in response to streptococcal antigens and may be relevant to the pathogenesis of psoriasis.     

银屑病患者血清中链球菌抗体的研究

为了进一步证实链球菌感染与银屑病的关系,我们应用免疫印迹法测试了银屑病患者血清中抗链球菌、抗金黄色葡萄球菌及抗白念珠菌抗体含量.发现点滴型银屑病患者的抗链球菌抗体含量不仅显着高于正常人对照组(P<0.01),亦高于慢性斑块型银屑病患者(P<0.05);但其抗金黄色葡萄球菌、抗白念珠菌抗体含量与对照组相比,结果均无显着性差异(P>0.05).本研究证明了链球菌感染与点滴型银屑病密切相关.     

Decreased IL-10 production by psoriatic peripheral blood mononuclear cells stimulated with streptococcal superantigen

The strong association of acute guttate psoriasis and streptococcal throat infection has suggested a role for streptococcal antigens in the pathogenesis of psoriasis. We have reported that psoriatic peripheral blood mononuclear cells (PBMCs) showed significantly lower responses to cytoplasmic membrane-associated protein (CAP) isolated from group A beta-hemolytic streptococci, a kind of streptococcal superantigen. The objectives were to evaluate the abnormal cytokine production by psoriatic PBMCs to streptococcal superantigen, CAP. We compared the production of four different cytokines, i.e. IL-4, IL-5, IL-10, and IFN-gamma, by PBMCs between psoriatic patients and healthy controls after stimulation with CAP or two different staphylococcal superantigens, staphylococcal enterotoxin A (SEA) or E (SEE). When PBMCs were stimulated with CAP, the production of IL-10 was significantly lower by psoriatic PBMCs than by those from healthy controls, whereas those of IL-4, IL-5, or IFN-gamma were not different between the two groups. Such a significant decrease in IL-10 production by psoriatic PBMCs was not observed when they were stimulated with staphylococcal superantigens. Flow cytometric analysis of intracytoplasmic IL-10 demonstrated defective IL-10 production by psoriatic PBMCs in both CD3+ T cells and CD14+ monocytes. There was a significant positive correlation between IFN-gamma production by PBMCs and the proliferation of Vbeta8+ T cells preferentially stimulated by CAP. These data demonstrating the defective IL-10 production by psoriatic PBMCs stimulated with streptococcal superantigen seem to explain why only psoriatic patients evolve sustained and Th-1 deviated skin lesions after streptococcal upper respiratory infection.     

An investigation of antistreptococcal antibody responses in guttate psoriasis

In two-thirds of patients with guttate psoriasis (GP), there is good evidence that the eruption is triggered by a streptococcal throat infection. We attempted to determine if a specific epitope of the bacterial pathogen was associated with the humoral immune response in GP patients. Antibody titres against beta-haemolytic streptococci (BHS) extracts in sera from 14 patients with GP, 10 healthy controls and 10 chronic plaque psoriasis (CPP) patients were determined by ELISA. Antibody BHS reactivity was investigated using immunoblotting, followed by epitope mapping using peptide-phage display. The highest GP antibody titres (10,000-25,000) were found in sera that had a matching streptococcal isolate, three sera had high (5,000-12,500) and seven had raised titres (500-5,000). In the healthy control group, three had relatively high and seven lower titres. All the CPP sera had very low titres (<500). In the immunoblots, three major bands were recognised by all the GP sera, and, to a lesser extent, by four healthy controls. No GP-specific protein was identified. Epitope mapping identified 10 phage clones that specifically bound 2 or 3 GP sera, displaying five different peptide sequences that were not streptococcal in origin. These findings suggest that the antigen specificity of the humoral response to BHS in GP does not differ from that of non-psoriatic individuals.     

IgG class antibodies to heat shock-induced streptococcal antigens in psoriatic patients

BACKGROUND: Psoriasis is a chronic inflammatory skin disease. Probably autoimmune in nature, and associated with streptococcal throat infections as a triggering factor. Although many groups have associated the disease with other pathogens, Streptococcus pyogenes seems to be the most important microorganism related to this disease. Therefore, it is necessary to identify the streptococcal antigens involved in the process. METHODS: In this work IgG class antibodies to soluble antigens obtained from Staphyloccus aureus, Candica albicans or S. pyogenes before and after heat shock induction, were analyzed by ELISA in 28 psoriatic patients and 30 healthy donors. RESULTS: In all cases, the patients and the controls had IgG class antibodies to the four antigens. Nevertheless, the IgG levels to the heat shock-induced S. pyognes were statistically different between the patients and the controls (P < 0.001). There was no difference between the groups when the IgG antibodies to the other antigens, including the noninduced streptococcal extract, were analyzed. Additionally, anti-streptolysin O titers and throat cultures were carried out in all patients and controls. No differences between ASO titers were found but the patients were more frequently colonized by pyogenes. CONCLUSION: Results obtained in this study suggest that heat shock-induced proteins from S. pyogenes are associated with psoriasis.     

Immunoregulatory mechanisms and stress hormones in psoriasis (part 1)

Background In an earlier paper, the author noted that psoriatic eruptions may be produced in phases of humoral and cellular immunodeficiency and in the presence of streptococcal antigen-releasing inflammatory foci. In this study it was investigated as to whether stress hormones glucocorticoids, catecholamines) are substantially involved in the activity phases (eruptions) of psoriasis.
Methods During a series of investigations over two years, the following were determined for 70 chronic psoriasis patients and 50 controls: cortisol-adrenaline serum levels, polyclonal serum immunoglobulins IgM, IgG, IgA, total serum IgE, complements C3, C4, T-cells and subpopulations, streptococcal antibody titres ASO/ADNase B.
Results Phases of clinical inactivity are associated with a mechanism called immunologic regulation: elevated antibacterial titres and unremarkable findings for all other parameters. Phases of clinical activity (in 25/70 patient) showed absolutely elevated serum cortisol levels, absolutely decreased serum epinephrine levels, deficient serum IgM or IgG and IgE levels, increased C3, decreased C4 and T4:T8 ratio, and significantly elevated streptococcal titres.
Conclusions The greatly elevated serum cortisol levels indicate that glucocorticoids are produced in excess via the pituitary adrenal axis and are significantly involved in the triggering of immunosuppressive phases (eruptions) in psoriasis.     

Perianal Streptococcal Dermatitis

Eight patients were treated for perianal streptococcal dermatitis. The condition previously was described as perianal cellulitis, a term that is confusing in light of the clinical features and distinctive appearance of the disorder.     

DNase Ⅰ消化前后的链球菌抗原对寻常性银屑病外周血单一核细胞增殖反应的影响

目的 观察DNA酶（DNaseⅠ）消化前后的链球菌抗原对寻常性银屑病患者外周血单一核细胞（PBMC）增殖反应的影响。方法 寻常性银屑病患者15例，正常人10例。取外周抗凝血，分离并培养PBMC，分别使用A型β溶血型链球菌全菌抗原（SA）和DNaseⅠ消化后的链球菌抗原（DNaseⅠ-SA）刺激PBMC，72 h后采用3H-TdR掺入法检测并比较PBMC增殖反应的差异。结果 DNaseⅠ-SA与SA比较，无论在高浓度还是低浓度时，前者刺激患者PBMC增殖反应的能力均明显低于后者（P < 0.01）；在正常人，高浓度时DNaseⅠ-SA对PBMC刺激的增殖反应与SA比较差异无统计学意义（P > 0.05），但在低浓度时DNaseⅠ-SA刺激后细胞增殖反应的能力低于SA（P < 0.05）。进一步比较患者和正常人对SA和DNaseⅠ-SA刺激后增殖反应的差异，发现当抗原浓度为25 μg/mL时，患者PBMC对SA刺激后的增殖能力显著高于正常人（P < 0.05）；患者PBMC对DNaseⅠ-SA三种剂量刺激后的增殖反应与正常人比较差异无统计学意义（P > 0.05）；同时，患者对SA和DNaseⅠ-SA刺激后增殖反应的差值高于正常人，差异有统计学意义（P < 0.05）。结论 链球菌DNA可能参与了感染诱发银屑病的发生。     

HLA Cw*06 is not essential for streptococcal-induced psoriasis

BACKGROUND: Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. OBJECTIVES: To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. METHODS: The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n=41). RESULTS: The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. CONCLUSIONS: Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined.