Photodynamic therapy as an alternative treatment for cutaneous sarcoidosis

Sarcoidosis is a systemic granulomatous disease. In more than 90% of the cases, sarcoidosis affects the lung with bilateral hilar adenopathy, while skin involvement occurs in about 25% of the cases. Whereas sarcoidosis of the lung is often successfully treated with oral corticosteroids, therapy of cutaneous sarcoidosis is frequently frustrating because some of the lesions may be refractory to treatment or recur quickly after resolution. We report two cases of cutaneous sarcoidosis successfully treated with photodynamic therapy, which represents an effective alternative therapy with fewer side effects.     

The role of membrane fusion activity of a whole inactivated influenza virus vaccine in (re)activation of influenza-specific cytotoxic T lymphocytes

Induction of cytotoxic T lymphocyte (CTL) activity against conserved influenza antigens, e.g. nucleoprotein (NP) could be a step towards cross-protective influenza vaccine. The major challenge for non-replicating influenza vaccines aiming for activation of CTLs is targeting of antigen to the MHC class I processing and presentation pathway of professional antigen presenting cells, in particular dendritic cells (DCs). Intrinsic fusogenic properties of the vaccine particle itself can enable direct cytosolic delivery of the antigen by enhancing release of the antigen from the endosome to the cytosol. Alternatively, the vaccine particle would need to possess the capacity to activate DCs thereby triggering cell-intrinsic mechanisms of cross-presentation, processes that do not require fusion. Here, using fusion-active and fusion-inactive whole inactivated virus (WIV) as a vaccine model, we studied the relative contribution of these two pathways on priming and reactivation of influenza NP-specific CTLs in a murine model. We show that activation of bone marrow-derived DCs by WIV, as well as reactivation of NP-specific CTLs in vitro and in vivo were not affected by inactivation of membrane fusion of the WIV particles. However, in vivo priming of naive CTLs was optimal only upon vaccination with fusion-active WIV. Thus, DC-intrinsic mechanisms of cross-presentation are involved in the activation of CTLs upon vaccination with WIV. However, for optimal priming of naive CTLs these mechanisms should be complemented by delivery of antigen to the cytosol mediated by the membrane fusion capacity of the WIV particles.     

Transforming growth factor-beta1 regulates the expression of the high-affinity receptor for IgE on CD34 stem cell-derived CD1a dendritic cells in vitro

It has been reported that monocytes, Langerhans cells (LC) and other dendritic cells (DC) express the high-affinity receptor for IgE (FcepsilonRI) in patients with atopic diseases. These cells may be instrumental in the control of the immune response and the allergic inflammation. In this context, transforming growth factor beta 1 (TGF-beta1) has been highlighted as a key cytokine involved in the mechanisms aimed to orchestrate tolerance and has been suggested as a candidate gene in atopic diseases. In this report, we investigate the putative role of TGF-beta1 in the regulation of FcepsilonRI on cord blood CD34+ stem cell-derived CD1a+ DC (CD34-derived CD1a+ DC). Kinetic experiments show that FcepsilonRI spontaneously appears on the surface of CD1a+ DC, but decreases when exogenous TGF-beta1 is added at high doses (10 ng per mL) or when endogenous TGF-beta1 is neutralized in the culture conditions. In contrast, low-dose TGF-beta1 (0.5 ng per mL) stabilizes surface FcepsilonRI expression on DC. Increasing TGF-beta1 concentrations leads to the generation of LC-like DC showing an augmentation in stimulatory capacity towards allogeneic T cells. In view of these data, a picture emerges that FcepsilonRI+ on DC is finely modified by the TGF-beta1 concentration in the microenvironment and could be of primary relevance in the context of atopic diseases.     

Benigne symmetrische Lipomatose Launois-Bensaude Typ II mit ausgeprägter Systembeteiligung und Psoriasis

Benign symmetric lipomatosis of the pseudoathletic type was identified in a woman with a positive family history for the disorder and a past history of alcohol abuse. She had an exceptionally high number of additional diseases such as arthropathy with degenerative osteoporosis, hyperuricemia, hyperlipidemia, psoriasis, neuropathy, muscular atrophy, arteriosclerosis and increased cardiovascular risk factors.     

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.     

Systemic therapeutic options for severe atopic dermatitis

Systemic therapy of severe atopic dermatitis (AD) is difficult in some cases, because the use of immunosuppressive agents such as cyclosporine A, mofetil mycophenolate, tacrolimus, and azathioprine is limited by adverse reactions or contraindications. Recent reports suggest a helpful role for biologics, methotrexate, anti‐IgE antibodies, and immunotherapy. We review the modes of action, as well as advantages and disadvantages of current and new systemic therapeutic options for severe AD.