Neuropsychiatric systemic lupus erythematosus associated with unique lymphoplasmacytic skin lesions

Summary: Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) may be the least understood manifestation of lupus. NPSLE has been associated with increased morbidity and mortality, and it is considered a major diagnostic and therapeutic challenge in systemic lupus erythematosus (SLE). SLE patients with positive anti-P have been found to have an earlier onset age and are more prone to skin involvement and proteinuria, it can be used as an important indicator of skin and kidney damage in SLE as is supported by our case. Anti-ribosomal-P antibodies can induce the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and IL-8, which can cause inflammation of the BBB, further allowing the entrance of auto-antibodies to the brain. Animal studies have demonstrated that anti-ribosomal-P may interact with neuronal surface-P antigen on the surface of hippocampal neurons, leading to apoptosis. Currently, we do not fully understand its pathogenesis, the spectrum of disease manifestations is debated, and strong research is lacking on diagnostics and treatment. Case Presentation: We present a 51 y/o male with no past medical history who presented with confusion, anorexia and a diffuse eczematous rash with ulcers concerning for infectious process. Upon neurologic evaluation, he was minimally responsive to commands, lethargic, and AAOx0. Brain imaging demonstrated partial thrombosis of left transverse sinus, sigmoid sinus and proximal left internal jugular vein. CT-chest revealed bilateral axillary lymph node enlargement. Lumbar puncture was obtained showing low glucose, high protein and negative cultures. Additional infectious workup was also negative. EEG revealed moderate encephalopathic findings. His labs demonstrated pancytopenia as well as proteinuria and a workup for autoimmune causes was obtained. This revealed an anti-nuclear antibody of 1:2560 homogenous, a positive anti-Smith antibody, low C3/C4 levels, and a positive anti-ribosomal P antibody. Labs were negative for Lupus Anticoagulant, Cardiolipin antibodies and B2-glycoprotein. A renal biopsy showed mesangial proliferative lupus nephritis class 2. Given his clinical picture and these findings, a diagnosis of neuropsychiatric lupus was made, and he received pulse dose steroids, IV Cyclophosphamide, and Hydroxychloroquine which lead to clinical improvement. A skin biopsy had also been obtained, which was negative for infectious organisms and demonstrated a perivascular lymphoplasmacytic infiltrate in the dermis with prominent edema present in the deep dermis. Discussion: While our patient responded clinically to typical NPSLE management, his presentation was quite atypical. To our knowledge, this is the first case describing cutaneous lupus manifesting as widespread ulcerative skin lesions with a lymphoplasmacytic infiltrate and edema on biopsy. In SLE, biopsy typically demonstrates interface dermatitis with a perivascular lymphocytic infiltrate. While cutaneous ulceration has rarely been reported in SLE, none have demonstrated a lymphoplasmacytic infiltrate or been associated with NPSLE. Our case is also atypical given that <1% of lupus patients develop venous sinus thrombosis, and this is typically associated with antiphospholipid antibodies, which were absent in our patient. Venous sinus thrombosis has been reported in the spectrum of neuropsychiatric lupus, but it is not yet clear if his cutaneous findings will correlate with neuropsychiatric disease or represent a separately occurring disease manifestation. Conclusions: A case like ours is unique as to our knowledge, it is the first reported in medical literature that present NPSLE with atypical cutaneous manifestations of lymphoplasmacytic infiltrates and presence of venous sinus thrombosis in absence of antiphospholipid antibodies. It would be helpful to have additional cases reported on in the future.