Rita Bunikowski

Prevalence and role of serum IgE antibodies to the StaphylococcuS aureus–derived superantigens SEA and SEB in children with atopic dermatitis

BACKGROUND The skin of patients with atopic dermatitis exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus. In this context it has been previously shown that S aureus-derived superantigens could function as classic allergens, inducing production of functionally relevant specific IgE antibodies. OBJECTIVE The aim of this study was to determine the prevalence and the role of circulating staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE antibodies in children with atopic dermatitis. METHODS In a cross-sectional study of 58 children with atopic dermatitis, the presence of IgE antibodies to SEA and SEB was correlated with the severity of the disease and the total and other unrelated allergen-specific IgE titers and density of colonization with S aureus strains on atopic skin and episodes of superficial S aureus skin infections. RESULTS Twenty of 58 children (34%) were sensitized to superantigens (45% to SEB, 10% to SEA, 45% to SEA and SEB). In this group, severity of atopic dermatitis and levels of specific IgE to food and air allergens were significantly higher. The degree of disease severity correlated to a higher extent with the presence of SEA/SEB-specific antibodies than with total serum IgE levels. Density of colonization with superantigen-secreting S aureus strains was higher in the superantigen IgE-positive group. Sixty-three percent of these children experienced repeated episodes of superficialS aureus skin infections. CONCLUSIONS Sensitization to S aureus-derived superantigens may be involved in disease exacerbation. The presence of SEA/SEB-specific antibodies had additional explanatory value for disease severity and therefore may be helpful in the characterization of children with severe atopic dermatitis.

Role of T Cells in Atopic Dermatitis

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease. Influx of activated T cells into the skin lesions represents a hallmark in AD. Recent results indicate a dynamic T-cell-derived cytokine production in AD. In addition to the well-known TH-2 component, chronic lesions and late-phase allergic responses are characterized by an TH-1/TH-0 cytokine pattern. Although there is no doubt that aeroallergens can contribute to the elicitation of acute- and late-phase allergic responses in AD, their role in the immunopathogenesis is controversally discussed. Recent attention has been given to the long-known phenomenon of persistent colonization of AD skin with S. aureus and the potential role of S. aureus-derived superantigens. Evidence from several in vitro and in vivo studies suggests that such bacterial superantigens have the potency to trigger chronic T-cell-mediated skin inflammation. Although these data are certainly suggestive, further clinical studies are required to elucidate the role of bacterial superantigens in initiation, maintenance and, especially, chronicity of skin inflammation.

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis : Clinical and immunological effects

Cyclosporin A (CsA) is an effective and well‐tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low‐dose CsA in childhood AD with respect to clinical outcome and modulation of T‐cell dysregulation. In an open prospective study, 10 children (age: 22–106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non‐responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine‐producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T‐cell numbers were measured by fluorescence‐activated cell sorter (FACS) analysis. Twenty healthy age‐matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low‐dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4‐week follow‐up period. At baseline the percentage of interleukin‐4 (IL‐4), IL‐13, and human leucocyte antigen (HLA)‐DR‐positive CD3+ cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon‐γ (IFN‐γ), IL‐2, IL‐4, IL‐13, and HLA‐DR‐positive CD3+ cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T‐lymphocyte cytokine production, and regulates T‐cell activation.

Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis.

Background: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). Objective: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. Methods: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of ≧35% was achieved (‘treatment response’). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-α) from patients’ PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. Results: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients’ PBMC produced more IL-6, IL-8 and TNF-α than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-α levels were unchanged by CyA in all patients. Conclusions: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-α by PBMC.

Extraordinarily high serum IgE levels and consequences for atopic phenotypes

BACKGROUND IgE plays a central role in allergic diseases. Recent studies have postulated an association between serum IgE levels and bronchial asthma. OBJECTIVE To examine the differences of atopic phenotypes in a group of individuals with extraordinarily high serum IgE levels (>10,000 kU/L) compared with children with moderately elevated IgE levels (400-1,000 kU/L). METHODS We investigated 20 children with serum IgE levels greater than 10,000 kU/L and compared them with 56 age-matched children with serum IgE levels of 400 to 1,000 kU/L regarding prevalences of atopic dermatitis, bronchial asthma, allergic rhinoconjunctivitis, allergic sensitization, and history of anaphylaxis. RESULTS The mean eczema severity score as determined by the Severity Scoring of Atopic Dermatitis Index was 56 vs 18 (P < 0.003), and anaphylactic reactions were reported in 20% of the group with very high serum IgE levels vs 7% in the group with moderate levels (P < 0.02). Sensitization to both aeroallergens and food allergens was detected in 80% of the group with very high serum IgE levels vs 32% of the group with moderate levels (P < 0.001). CONCLUSIONS Our results indicate that children with very high serum IgE levels are at risk for anaphylactic reactions and more severe atopic dermatitis.

Contribution of Bacterial Superantigens to Atopic Dermatitis

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease manifested from the atopic syndrome. We propose in addition to classical environmental allergens bacterial antigens play an important role in AD [1]. Several observations support the hypothesis for an important role of Staphylococcus aureus colonization in AD: (1) S. aureuscan be isolated from skin lesions in about 95% of all AD patients; (2) S. aureuscolonization can reach up to 10 7 colony-forming units per square centimeter on lesional skin; (3) S. aureuscolonization can cause severe exacerbation of the disease and anti-staphylococcal therapy is beneficial in severe cases. Despite this cirumstantial evidence, a clear causal relationship has not yet been established. Since some S. aureusstrains secrete superantigens (e.g. SEB), we examined the potential roe of S. aureus -derived superantigens in AD.

Effect of oral cyclosporin A in children with Staphylococcus aureus-colonized vs. S. aureus-infected severe atopic dermatitis

Atopic dermatitis (AD) is frequently associated with skin colonization or infection with Staphylococcus aureus strains producing exotoxins. The aim of this investigation was to evaluate the effect of oral cyclosporin A (CsA) on disease severity and bacterial counts in colonized and infected patients. Eleven children with severe AD (SCORAD index >50, mean objective SCORAD score >40) were treated for 8 weeks with 2.5–5 mg/kg CsA. In five patients, the skin was only colonized with S. aureus whereas the remaining six patients presented clinically relevant suppurative S. aureus skin infections characterized by small pustules, crustings, pus and increased pruritus in the presence of S. aureus as determined by contact sampling and culture which regularly resulted in the indication for antibiotic treatment. Clinical and microbiological investigations were performed before and after CsA therapy. Clinical signs and symptoms of AD improved in all patients with a reduction in mean SCORAD index from 74 to 29 (p < 0.001). However, disease severity and bacterial counts were more reduced by CsA in the colonized patients compared with the patients with clinical overt infections. In conclusion, treatment with CsA resulted in an improvement of clinical symptoms in children suffering from severe AD. However, anti‐infective treatment administered before immunomodulatory therapy is likely to be decisive for the long‐term therapeutic effect.

Mollusca contagiosa generalisata bei einem afrikanischen Kind mit Aids

ZusammenfassungBei einem Kind aus Zaire mit fortgeschrittener Aids-bedingter Immundefizienz (CDC: P2D1) traten generalisierte Mollusca contagiosa von ungewöhnlicher Größe auf. Während die Molluscum-contagiosum-Infektion bei Immunkompetenten meist selbstlimitiert ist, treten bei fortgeschrittener Immundefizienz disseminierte und persistierende Infektionen auf. Histologisch und immunhistochemisch zeigte sich eine starke Verminderung der Langerhans- und T-Zellpopulationen, die der Disseminierungstendenz zugrunde liegen können. Wegen ihrer klinischen Ähnlichkeit mit Mollusca contagiosa und, aufgrund einer vorausgegangenen systemischen Kryptokokkose im Laufe der Grunderkrankung der Patientin, mußte eine kutane Kryptokokkose differentialdiagnostisch berücksichtigt werden. Als weitere Differentialdiagnosen waren kutane Manifestationen der amerikanischen und afrikanischen Histoplasmose, kutane Toxoplasmose und Pneumocystis-carinii-Infektion sowie kutane Mykobakteriosen in Betracht zu ziehen.SummaryA 12-year-old girl from Zaire with Aids (CDC: P2 D1) presented with a generalized molluscum contagiosum infection. She had suffered from systemic cryptococcosis and from cryptosporidiosis several months before admission. While molluscum contagiosum infection is usually a self-limiting disease in immunocompetent persons, a fulminant appearance and persistence of giant mollusca occurs with advanced immunodeficiency. Histological and immunohistological examinations showed a severe diminution of Langerhans and T cell populations that might enhance the dissemination of the infection. Molluscum-like lesions of cryptococci have been described, and cutaneous cryptococcosis is the main condition to be considered in the differential diagnosis. Further differential diagnoses should include American and African histoplasmosis, and the cutaneous manifestations of mycobacterial infections, of toxoplasmosis and of Pneumocystis carinii infection.