Palmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics1-3. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK (OMIM #148600), we report heterozygous loss-of-function mutations in AAGAB, encoding alpha- and gamma-adaptin binding protein p34, at a previously linked locus on 15q22. p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicative of a role in membrane traffic. Ultrastucturally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of p34 in keratinocytes led to increased cell division, which was linked to greatly increased epidermal growth factor receptor (EGFR) protein expression and tyrosine phosphorylation. We hypothesize that p34 deficiency may impair endocytic recycling of growth factor receptors such as EGFR, leading to increased signaling and proliferation.

SUMMARYIt is suggested that CD30 and CD26 are surface molecules expressed on activated Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26 (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The plasma levels of both sCD30 and sCD26 were significantly higher in AD patients than in controls, both in exacerbation status and after conventional treatment. Multiple regression analyses showed that plasma sCD30 was a much better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the area and the score of AD eruption than sCD26, although elevated levels of both sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly, sCD30 plasma levels decreased significantly in AD patients after conventional treatment, while no significant transition was noted in the concentration of sCD26. Moreover, a significant reduction of sCD30 levels was observed in the group of patients whose eruption score was reduced . 50%, whereas it was not in those , 50%. These findings provide evidence that the successful treatment of AD is associated with down-activation of Th2.

SUMMARY Matrix metalloproteinases and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), contribute to inflammation‐induced tissue destruction and subsequent remodeling for maintenance of tissue homeostasis. Since the production of these enzymes and their inhibitors is regulated by mediators such as proinflammatory cytokines and growth factors, elevated levels of serum TIMPs and/or MMPs have been documented in patients with several inflammatory disorders. In this study, we examined the role of TIMPs and MMPs in the pathogenesis of atopic dermatitis (AD) by evaluating the serum levels of TIMP‐1 and MMP‐3 in 40 patients with AD and 20 control subjects by ELISA. The serum TIMP‐1 levels were significantly higher in AD patients in exacerbation status than in nonatopic subjects, whereas serum MMP‐3 levels were not significantly different between them. As a result, AD patients revealed significantly elevated TIMP‐1/MMP‐3 ratios. The levels of serum TIMP‐1 were significantly reduced in AD patients following conventional treatments. Significantly higher values of peripheral eosinophil counts, serum levels of IgE and lactate dehydrogenase, eruption score, and eruption area were noted in the AD patients with elevated TIMP‐1 levels when compared with those with normal values. Moreover, the points of chronic eruptions such as lichenification and prurigo were significantly higher in the patients with elevated TIMP‐1 levels than those with normal TIMP‐1, while those of acute lesions such as oozy/microvesicles and oedema were not different between these groups. Serum TIMP‐1 level may be a useful marker to estimate the long‐term disease activity of AD.

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Interstitial lung disease (ILD) frequently accompanies polymyositis (PM) and dermatomyositis (DM) and is a major cause of mortality. The rapid diagnosis of ILD is paramount. However, the early changes of presymptomatic ILD are difficult to detect. We present a patient with DM who had positive uptake in the lung of FDG-PET/CT as well as 'mechanic's hands' appearance, increased serum ferritin and serum anti-CADM-140 antibody, all before the detection of ILD by CT. Although aggressive treatment was initiated, the patient died of diffuse alveolar damage. These observations suggest that the pulmonary uptake of 18 F-FDG predicts rapidly progressive ILD in DM.