An Update on the Pathogenesis of Skin Damage in Lupus.

PURPOSE OF REVIEW: Lupus erythematosus (LE) is characterized by broad and varied clinical forms ranging from a localized skin lesion to a life-threatening form with severe systemic manifestations. The overlapping between cutaneous LE (CLE) and systemic LE (SLE) brings difficulties to physicians for early accurate diagnosis and sometimes may lead to delayed treatment for patients. We comprehensively review recent progress about the similarities and differences of the main three subsets of LE in pathogenesis and immunological mechanisms, with a particular focus on the skin damage. RECENT FINDINGS: Recent studies on the mechanisms contributing to the skin damage in lupus have shown a close association of abnormal circulating inflammatory cells and abundant production of IgG autoantibodies with the skin damage of SLE, whereas few evidences if serum autoantibodies and circulating inflammatory cells are involved in the pathogenesis of CLE, especially for the discoid LE (DLE). Till now, the pathogenesis and molecular/cellular mechanism for the progress from CLE to SLE are far from clear. But more and more factors correlated with the differences among the subsets of LE and progression from CLE to SLE have been found, such as the mutation of IRF5, IFN regulatory factors and abnormalities of plasmacytoid dendritic cells (PDCs), Th1 cells, and B cells, which could be the potential biomarkers for the interventions in the development of LE. A further understanding in pathogenesis and immunological mechanisms for skin damage in different subsets of LE makes us think more about the differences and cross-links in the pathogenic mechanism of CLE and SLE, which will shed a light in predictive biomarkers and therapies in LE.

Discoid lupus erythematosus of the eyelids associated with staphylococcal blepharitis and Meibomian gland dysfunction.

Lower eyelid involvement occurs in 6% of patients with discoid lupus erythematosus (DLE). Eyelid lesions are rarely the initial manifestation of DLE. We describe a 25-year-old woman presenting with discoid lesions of the lower eyelids, staphylococcal blepharitis and Meibomian gland dysfunction, who later developed a discoid lesion on the chin. Histopathological and immunofluorescence studies of a biopsy specimen from this lesion established the diagnosis of DLE. We are unaware of any previously reported cases of DLE presenting with discoid eyelid lesions associated with staphylococcal blepharitis and Meibomian gland dysfunction. DLE should be considered as a differential diagnosis in chronic blepharitis that persists despite usual medical management and eyelid hygiene. Misdiagnosis may lead to eyelid margin deformities, necessitate a complicated full-thickness biopsy, and delay diagnosis of systemic lupus.

Histologic observations of coccoid forms suggestive of cell wall deficient bacteria in cutaneous and systemic lupus erythematosus.

The cutaneous lesions of seven consecutive patients with cutaneous lupus erythematosus (LE), two patients with systemic LE, and a patient with both dermatomyositis and cutaneous LE, were studied bacteriologically and microscopically for the presence of bacteria. The study was prompted by the previous reports of variably acid-fast and non-acid-fast bacteria in other collagen diseases, and also by recent reports confirming the presence of cell wall deficient (CWD) bacteria (staphylococci, streptococci, and corynebacteria) within the hematologic elements of both "normal" and diseased individuals. Staphylococcus epidermis was isolated from four cases. Propionibacterium acnes from two cases, and Corynebacterium sp. from one case. Three cases were bacteriologically negative. Basophilic- and eosinophilic-stained coccoid forms, suggestive of CWD bacteria, were identified in the microscopic sections of all the cases, as were non-acid-fast coccoid forms. Definite acid-fast coccoid forms were observed in vivo in two cases of cutaneous LE. The complex bacteriology of LE is discussed, as well as the possibility that variably acid-fast CWD microbes might be the long sought-after etiologic agent or agents in the production of LE.

Virus-like structures in lupus erythematosus discoides.

Biopsy specimens from typical skin lesions of DLE patients were studied by means of electron microscopy. Virus-like structures were discovered in the cytoplasm of fibrocytes, endothelial cells and keratinocytes. After prolonged chloroquine treatment a decrease in the frequency and size of these structures was observed.

Vascular changes of chronic lupus erythematosus. Electron microscopic studies.

Vascular changes in the course of chronic lupus erythematosus were mainly characterized by a large, yet varying degree of proliferation of endothelial cells. In all cases examined the presence of tubular forms similar to paramyxoviruses was noted. The vascular basal membrane was noted to be either widened, segmentally separated or absent in places. Collagen fibres in these cases adhered directly to the endothelial cells. In the nuclei of endothelial cells of the infiltrate, "nuclear bodies" could be observed. In area surrounding capillaries oval concentrations of fibrilles 80 A in diameter were noticed.