Subject(s)
Burns/complications , Skin Diseases, Vesiculobullous/etiology , Skin/injuries , Administration, Cutaneous , Biopsy , Burns/diagnosis , Burns/drug therapy , Female , Glucocorticoids/administration & dosage , Humans , Middle Aged , Prednisolone/administration & dosage , Skin/drug effects , Skin/pathology , Skin Diseases, Vesiculobullous/diagnosis , Skin Diseases, Vesiculobullous/drug therapy , Time Factors , Treatment Outcome , Upper Extremity , Wound HealingABSTRACT
Palmoplantar keratodermas (PPKs) are a group of disorders that are diagnostically and therapeutically problematic in dermatogenetics. Punctate PPKs are characterized by circumscribed hyperkeratotic lesions on the palms and soles with considerable heterogeneity. In 18 families with autosomal dominant punctate PPK, we report heterozygous loss-of-function mutations in AAGAB, encoding α- and γ-adaptin-binding protein p34, located at a previously linked locus at 15q22. α- and γ-adaptin-binding protein p34, a cytosolic protein with a Rab-like GTPase domain, was shown to bind both clathrin adaptor protein complexes, indicating a role in membrane trafficking. Ultrastructurally, lesional epidermis showed abnormalities in intracellular vesicle biology. Immunohistochemistry showed hyperproliferation within the punctate lesions. Knockdown of AAGAB in keratinocytes led to increased cell division, which was linked to greatly elevated 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 cellular proliferation.
Subject(s)
Adaptor Proteins, Vesicular Transport , Carrier Proteins/genetics , Haploinsufficiency , Porokeratosis/genetics , Adaptor Proteins, Vesicular Transport/genetics , Adaptor Proteins, Vesicular Transport/metabolism , Chromosome Mapping , Cytosol/ultrastructure , ErbB Receptors/genetics , ErbB Receptors/metabolism , Gene Expression Regulation , HeLa Cells , Humans , Keratinocytes/metabolism , Keratinocytes/pathology , Pedigree , Porokeratosis/metabolism , Protein Binding , Proteins/genetics , Proteins/metabolismABSTRACT
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.
Subject(s)
Dermatomyositis/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Aged , Dermatomyositis/complications , Dermatomyositis/diagnosis , Disease Progression , Early Diagnosis , Fatal Outcome , Female , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Humans , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnosis , Multimodal Imaging , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, X-Ray ComputedSubject(s)
Agaricus , Allergens/adverse effects , Cheilitis/diagnosis , Dermatitis, Allergic Contact/diagnosis , Plant Extracts/adverse effects , Cheilitis/chemically induced , Cheilitis/pathology , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/pathology , Diagnosis, Differential , Fruiting Bodies, Fungal , Humans , Male , Middle Aged , Patch TestsSubject(s)
Pemphigus, Benign Familial/pathology , Scabies/complications , Aged , Biopsy, Needle , Female , Humans , Immunohistochemistry , Pemphigus, Benign Familial/etiology , Pemphigus, Benign Familial/physiopathology , Prognosis , Recurrence , Risk Assessment , Scabies/diagnosis , Severity of Illness IndexABSTRACT
In patients with atopic dermatitis (AD), it is debatable whether clinically normal-appearing skin is equal to non-atopic normal skin. The aim of this study was to quantitatively evaluate the characteristics of normal-appearing skin of AD. We examined the value of skin surface morphological changes using a new, simple, computer-assisted method with a video microscope. We also investigated the physiological function as represented by transepidermal water loss (TEWL) levels in 44 patients with AD and 15 normal controls. The morphological changes were represented by a variation coefficient score that reflected the irregularity of skin ridges, named the surface irregularity index (SII). There were significant differences between the normal-appearing skin of AD and non-atopic normal skin in both SII (P<0.001) and in TEWL (P<0.01). Especially for the SII, there were significant differences between AD subgroups subdivided by peripheral blood eosinophil count (Eo), serum lactate dehydrogenase level, and clinical score. TEWL values were significantly higher in the high-Eo AD group (n=15) than in the low-Eo AD group (n=29) (P<0.05). These findings indicate that clinically normal-appearing skin of AD patients with high disease activity differs from non-atopic normal skin in both surface morphology and physiology and that these changes reflect the current disease activity.
Subject(s)
Dermatitis, Atopic/physiopathology , Water Loss, Insensible , Adolescent , Adult , Case-Control Studies , Female , Humans , Image Processing, Computer-Assisted , Male , Microscopy, Video , Middle Aged , Severity of Illness Index , Skin Physiological PhenomenaABSTRACT
The clinical characteristics of patients in whom an IgE-mediated reaction against house dust mite (HDM) antigens that contribute to the pathogenesis of atopic dermatitis (AD) remain unclear. This study attempted to elucidate the characteristics of patients who exhibit a positive reaction 48 hr or later against HDM in scratch tests. The reactions after epi-cutaneous application of the allergen to skin with prior scratching were observed for one week in sixteen AD patients showing positive immediate-type hypersensitivity reactions for HDM. Fifty percent of the patients demonstrated positive reactions at 48 hours after epi-cutaneous application of HDM. Significantly higher values were demonstrated in the group positive for HDM after 48 h in serum total IgE, specific IgE for Der f 1, and lactate dehydrogenase, peripheral eosinophil counts, eruption score, and the area of eruption than in the group negative for HDM after 48 h. Domestic exposure to Der f 1 was also higher in the group positive for HDM after 48 h than in the negative group. These results indicate that the patients in whom the HDM-induced reaction continuing more than 48 h and contributing to their real eczematous eruptions are characterized by considerably increased levels of specific IgE for HDM antigens, high disease activity in AD, and increased exposure to domestic HDM.
