Discoid lupus erythematosus (DLE) classically affects sun‑exposed areas, such as the face, scalp, and ears. Involvement of the lower extremities is uncommon, and presentation of DLE in association with systemic lupus erythematosus (SLE) in a male patient is relatively rare. This case report describes a 34‑year‑old man who presented with chronic, scaly, dyspigmented plaques confined to both the lower legs, which prompted further evaluation and led to the diagnosis of SLE. Histopathological evaluation supported the diagnosis of DLE, while serologic workup revealed high‑titer antinuclear antibodies (ANAs), anti‑double‑stranded DNA (anti‑dsDNA), anti‑Smith antibodies, and hypocomplementemia, supporting a diagnosis of SLE with chronic cutaneous lupus involvement. Following treatment with strict photoprotection, topical corticosteroids, and weight‑based hydroxychloroquine, the patient showed marked clinical and serologic improvement at the 12‑week and 9‑month follow‑ups. This case highlights the importance of evaluating for systemic involvement in patients with biopsy‑supported DLE, particularly when lesions occur in atypical anatomical locations and in populations traditionally considered at lower risk.

Apolipoprotein E (ApoE) is highly expressed in the central nervous system (CNS) where it plays a critical role in lipid homeostasis and in the etiology of Alzheimer's disease (AD) and related diseases. ApoE associates with lipids to form discoidal and spherical lipoproteins that carry lipid and protein cargo throughout the brain. In this review, we focus on the significance of ApoE as a lipoprotein and how this impacts the function of ApoE in homeostasis and disease. In the CNS, ApoE is primarily secreted by astrocytes, though other cells, including microglia, secrete ApoE under certain conditions. ApoE lipoproteins (LpE) secreted by different cell types carry unique lipids and proteins which alter its function. The lipidation state of ApoE alters its conformation and binding to different receptors and, consequently, its ultimate impact on AD pathology. Most dramatically, nonlipidated ApoE has minimal binding to the low density lipoprotein receptor (LDLR), while lipidation of ApoE restores high affinity binding to LDLR. Furthermore, the degree of ApoE lipidation also impacts ApoE receptor binding through changes in protein conformation and stoichiometry of ApoE molecules per lipoprotein. The lipidation state of ApoE also alters its interaction with amyloid-β and tau, the proteins involved in forming amyloid plaques and neurofibrillary tangles, the pathological hallmarks of AD. LpE also carry lipids and proteins that alter the function of ApoE. Understanding how the lipid and protein content of LpE interacts with the conformational changes that occur with lipidation and maturation are essential to mechanistically understanding the role of ApoE in homeostasis and disease pathogenesis. In this review, we highlight the current understanding of LpE biology in the CNS and delineate important areas of future research.

Patients treated with TNF-α antagonists may develop psoriasis-like skin lesions. Clinical manifestations include palmoplantar, inverse, localized or generalized guttate, plaque-type, eczematous, and pustular lesions; deep inflammatory nodes; and nonscarring alopecia, often with overlapping reaction patterns. They are classified as paradoxical psoriasis and interpreted as an inflammatory reaction resulting from the disturbed maturation of plasmacytoid dendritic cells, with overproduction of type I interferons due to tumor necrosis factor α (TNF-α) inhibition. Management frequently necessitates discontinuation of therapy. Here, we review the clinical presentation of six patients who were initially diagnosed with paradoxical psoriasis during TNF-α blockade due to the development of corresponding skin lesions. Dermatologic examination revealed that the lesions were impetigo contagiosa, ecthyma, folliculitis decalvans, ostiofolliculitis, nummular microbial eczema, or abscessing furunculosis-all caused by Staphylococcus aureus, likely spreading from the colonized nasal mucosa to the skin. The cutaneous symptoms resolved with topical antimicrobial therapy and systemic antibiotic treatment. We conclude that many cases diagnosed as paradoxical psoriasis may, in fact, represent generalized abscessing staphyloderma resulting from impaired antimicrobial immunity under TNF-α blockade. The diagnosis of paradoxical psoriasis should therefore be critically re-evaluated on a case-by-case basis. Identification and eradication of S. aureus may substantially improve the prognosis for patients experiencing paradoxical psoriasis-like manifestations during treatment with TNF-α antagonists.