Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making.

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that can result in substantial morbidity and mortality. Diagnosis and treatment of SLE are clinical challenges. Patient presentation and response to therapy are heterogeneous because of the complex immune dysregulation that results in SLE disease pathogenesis. An intricate interplay between genetic risk and skewing of adaptive and innate immune system responses leads to overproduction of type I interferons and other cytokines, complement activation, immune-complex deposition, and ultimately inflammation and tissue damage. Here, we review the classification criteria as well as standard and emerging diagnostic tools available to identify patients with SLE. We then focus on medical management, including novel therapeutics, nonpharmacologic interventions, and comorbidity management. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

Intraorbital aneurysm of the ophthalmic artery is a very rare condition. Duke-Elder (I952) mentioned seven reports, some of which lack anatomical verification; these were written between I823 and 19I4 when angiographic studies were not available and the verifications when done were post mortem studies.Dempsey (I886) reported a saccular aneurysm of the ophthalmic artery at the back of the globe associated with a fusiform aneurysm of the internal carotid artery. The patient died and these aneurysms were found post mortem.Wheeler and Baker (I964) found three aneurysms of the ophthalmic artery in 57 cases in which angiography was performed for ocular pathological studies. Only one of these was intraorbital.Di Chiro (I96I) stated that aneurysms of the ophthalmic artery were rarely seen. Lombardi (i967), in 370 intracranial aneurysms seen before I964, found none in the ophthalmic artery. Parkinson, Jain, and Blair-Johnson (i96I) were unable to trace previous reports of saccular aneurysms arising from the ophthalmic artery. Case reportA 55-year-old white man was first seen in I963, when the external examination of his eyes anid ophthalmic investigations were negative apart from presbyopia. PREVIOUS MEDICAL HISTORYHe had had an injury to the head during the second world war with uneventful recovery. At times he heard "blowing" noises in the head. FAMILY HISTORYA brother had died from a ruptured intracranial aneurysm, and the patient's only child had died at birth with a suspected intracranial haemorrhage. RECENT MEDICAL HISTORYOn November 14, I968, at 8 a.m. the patient coughed and developed a "haemorrhage and protrusion" of the right eye. An intramuscular injection of pethidine 50 mg. was given by his general practitioner, and he was examined (by L. M.) at I I a.m. on the same morning.There was marked proptosis, a large subconjunctival haemorrhage, and a haemorrhage that had suffused into the lids and periorbital tissues ( Figs I and 2, overleaf). The pupil was fixed and dilated and in the mid-position. There was no perception of light.

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