Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2.

BACKGROUND: Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs). OBJECTIVES: We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release. METHODS: Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays. RESULTS: Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro. CONCLUSION: Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.

Genetics of atopic dermatitis.

Atopic dermatitis (AD) is a multifactorial disease, with a strong genetic predisposition. Genome-wide studies as well as candidate gene studies revealed several susceptibility loci. Since the observation of a strong association of "loss of function" mutations in the filaggrin gene with AD, the epidermal barrier was rediscovered as important pathophysiological co-factor of this disease.

Superimposed linear lichen planopilaris: another polygenic disorder exemplifying a new genetic concept.

In a few cases, polygenic skin diseases show a segmental arrangement of the lesions and at the same time a milder non segmental involvement. This phenomenon has been described as superimposed segmental manifestation. Here, we report a patient who had developed itching papules on the right side of the trunk and neck together with a scarring alopecia of the scalp. Additionally, the patient showed perifollicular papules on the abdomen leading to truncal alopecia. The histopathological analyses of skin biopsies taken from the scalp and abdomen revealed a lichen planopilaris. Interestingly, the involvement of the scalp and the chest followed the lines of Blaschko, whereas the abdominal skin lesions did not show a segmental distribution, so that a superimposed lichen planopilaris could be diagnosed. This is to our knowledge the first described case of a superimposed lichen planopilaris.

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis.

BACKGROUND: Trafficking of dendritic cell (DC) subtypes to and from the skin plays a pivotal role in atopic dermatitis (AD). OBJECTIVES: We sought to determine the CCR pattern of epidermal DC subtypes and CCL expression in relation to the state of AD. METHODS: Shave biopsy specimens were taken from patients with AD before and after 24 and 72 hours of atopy patch testing and from the skin of patients with chronic AD, skin of patients with psoriasis, and healthy skin. CCR expression of epidermal DCs was studied by using flow cytometry, and chemokine mRNA levels in the skin were quantified by means of real-time PCR. RESULTS: The total number of CD1a(+) epidermal DCs increased and the proportion of Langerin-positive CD1a(+) DCs decreased whereas the percentage of Langerin-negative CD1a(+) DCs increased after allergen application. Expression of CCR5 and CCR6 of Langerin-negative CD1a(+) DCs was characteristic for acute AD. Expression of CCL1, CCL3, CCL4, and CCL11 mRNA was greater in patients with acute AD versus that seen in patients with chronic AD. Only a strong increase of CCLs, in particular CCL1, CCL17, and CCL18, went along with eczema development, and increased CCL1, CCL13, CCL17 and CCL18 expression was specific for patients with chronic AD compared with those with psoriasis. CONCLUSION: Modified recruitment and differentiation of DCs from their dermal and blood precursors occurs in the acute phase of AD. A boost in the amplitude of CCLs after allergen application goes along with eczema development.

Molecular pathogenesis and clinical implications of eczema herpeticum.

A subgroup of patients with atopic dermatitis develops one or more episodes of a severe viral skin infection caused by herpes simplex virus superimposed on eczematous skin lesions. This condition is named atopic dermatitis complicated by eczema herpeticum. Characteristic features of patients developing eczema herpeticum include an early age of onset of atopic dermatitis with a persistent and severe course into adulthood, predilection for eczematous skin lesions in the head and neck area, elevated total serum IgE levels and increased allergen sensitisation. Deficiencies at the level of both the innate and the adaptive immune system, which have been identified in atopic dermatitis, are much more pronounced in this subgroup. Predisposing cellular factors include a reduced number of plasmacytoid dendritic cells in the epidermis and a modified capacity of these cells to produce type I interferons after allergen challenge. In addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis patients, resulting in part from a Th2-prone micromilieu, contribute to the lack of an effective defence against viral attack. In this review, we summarise the current knowledge of the molecular pathogenesis of eczema herpeticum.

Flushing and increase of serum tryptase after mechanical irritation of a solitary mastocytoma.

Solitary mastocytomas are infiltrates of mast cells in the upper corium, appearing at any side of the body as brownish-reddish plaques in the first months of life. Their course is benign with a spontaneous regression in most cases. A 5-month-old boy presented a 5 x 3 cm sized brownish-yellow plaque on the back of his right hand. His parents reported repeated episodes of swelling and blistering of the skin lesion as well as recurrent systemic flush-reactions. General laboratory parameters were without pathological findings including a normal serum tryptase (5.5 microg/L). A few minutes after rubbing, the lesion became urticarially swollen and the infant developed a general flush reaction accompanied by a bilateral miosis and asthma-like symptoms which disappeared completely after oral administration of 7 drops of dimentinden. Assessment of the serum tryptase two hours after the provocation revealed a more than 5-fold increase (29.3 microg/L) compared to the basic value. We conclude that uncontrolled stroking of mastocytomas should be avoided in patients with a systemic reaction in their history, since this case demonstrates that despite its limited size, mechanical irritation of a solitary mastocytoma may induce strong systemic symptoms as witnessed by transient increase of the serum tryptase, which to our knowledge has not been described in the literature before.

Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis?

House dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD.