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Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.

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Background: Leg ulcers are an important cost factor in health care systems. It has been shown that a telemedical wound care consultation can improve quality of care and help reduce costs. In this study, we evaluated the feasibility of telemedical wound care using a new generation of mobile telephones with integrated cameras.Observations: Three physicians separately evaluated 61 leg ulcers for the following 9 variables: epithelialization, fibrin, necrosis, and granulation tissue at the center and normal border, erythema, cyanosis, eczema, and hyperpigmentation at the periphery. One physician performed the face-to-face consultation (gold standard), and 2 others performed the remote evaluation. The image was obtained with the mobile telephone and immediately sent via e-mail. To measure the agreement of the evaluation among the 3 physicians, we used Cohen statistics. Overall, the agreement between the remote and face-to-face evaluations was very good, with values of up to 0.94 The image quality was judged to be good in 36 cases (59%) and very good in 12 (20%). The participants felt comfortable making a diagnosis based on the pictures in 50 cases (82%). Conclusion:Although this study was performed with the first generation of these devices, we were able to demonstrate the feasibility of such a telemedical wound care consultation.

Rituximab therapy of CBCL appears to have a potential advantage in cases where lesions are localized in sites that are difficult to treat with radiotherapy or surgery and in which secondary scarring or alopecia is likely. Intralesional injections of rituximab allow the use of considerably smaller doses compared with intravenous treatment, with similar response rates and tolerance. However, within a 12-month follow-up period, relapse of CBCL with new lesions at distinct sites was frequently observed after intralesional treatment.

Background: High-dose intravenous immunoglobulins (IVIGs) are increasingly used to treat inflammatory and/or autoimmune disorders. In dermatology, they provide therapeutic benefit in Kawasaki disease and certain cases of dermatomyositis. While most adverse effects following IVIG treatment are not severe, occasionally more severe adverse effects occur, including anaphylactic reactions and acute, usually transient, renal failure. Observations:We report 4 cases of a characteristic severe extensive eczematous reaction that occurred approximately 10 days after IVIG infusion for polyradiculoneuritis. In all cases, onset was characterized by dyshidrotic lesions on the palms, rapidly followed by pruriginous maculopapular lesions involving the whole body. All patients were treated with topical and/or systemic ste-roids, and complete resolution of skin lesions was observed within 1 month. To date, 33 cases of cutaneous rash following IVIG infusion have been reported in the literature, mostly in neurology journals, and the features are identical to those reported herein.Conclusions: Severe eczematous skin reaction with a characteristic initial localization to the palms and/or soles that then extends to the rest of the body is a rare but characteristic adverse effect of high-dose IVIG therapy. Although the precise mechanism of this cutaneous eruption remains to be elucidated, its occurrence within days of IVIG infusion, its characteristic distribution at onset, and its clinical course should be recognized by dermatologists.

Background:Stevens-Johnson syndrome (SJS) is a severe cutaneous drug reaction associated with considerable morbidity, possible transition to toxic epidermal necrolysis (TEN) and death in certain cases. Objective: To determine whether treatment with high-dose IVIG in SJS patients may improve outcome. Methods: Data from 12 patients (collected between January 1997 and November 2000 from7 university dermatology centers in Europe and North America) diagnosed with SJS according to a recent consensus definition was analyzed retrospectively. All patients had progressive ongoing epidermal detachment at the time of treatment initiation. Patients with overlap syndromes and TEN were excluded. Tolerance, survival at 45 days after onset and total healing time were assessed. Results: Twelve SJS patients (mean age 44 years) were treated with IVIG at a mean dose of 0.6g/kg/day for an average of 4 days. An objective response to IVIG infusion was observed in all patients within a mean of 2 days, and the overall survival rate was 100%. Total skin healing occurred, on average, within 8.3 days. Time to total healing was shorter in a group of patients with fewer severe underlying diseases who had received IVIG infusion rapidly after the onset of skin lesions. Conclusion: High-dose IVIG may be effective in blocking the progression of SJS and reducing the time to complete skin healing.

We report the case of an 80-year-old patient who had intense pruritus which did not respond to a 3-month treatment with topical corticosteroids. On dermoscopy examination of the excoriations, we found the typical dermoscopic aspect of the scabies mite at a distance. Dermoscopy allows identifying a triangular structure which corresponds to the anterior section of the mite including the mouth part and the 2 pairs of front legs. This aspect has been described as resembling a jetliner with its trail, a delta glider or a spermatozoid. Traditional diagnostic methods for scabies failed in this case because the mites were at a distance from the burrows. This was due to the fact that the reaction to the mite was less pronounced and the diagnosis is frequently missed. Dermoscopy is a useful tool for the diagnosis of scabies either as a diagnostic test or to guide the traditional diagnostic tests.