Keratoderma in Systemic Lupus Erythematosus: An Unusual Cutaneous Manifestation of Disease?

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, with the skin being the second most affected organ after the joints. We present a unique case of a 44-year-old female who presented with an acute flare of SLE and the concurrent onset of keratoderma on both lower limbs. She presented with high-grade fever, arthralgia, and generalized edema of four months duration. A general physical examination revealed pallor and scaly hyperpigmented plaques on both lower limbs, which was confirmed to be keratoderma on histopathological examination. Blood investigations revealed pancytopenia, elevated erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP), and positive titers for anti-nuclear antibody (ANA) and anti-Po ribosomal P proteins (RPP) antibodies. Immunosuppressive medications and topical keratolytics were used to treat her successfully. Post medical management, she showed significant improvement in her symptoms. On follow-up, the patient had a complete resolution of the symptoms and remained well. This case demonstrates keratoderma as a rare incidental finding in a patient with SLE flare. Understanding SLE's various cutaneous manifestations are critical for holistically diagnosing and treating the disease.

Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism.

Human neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson's disease (PD) are also observed in other neurodegenerative diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis. Here, we show that fumble (fbl), the human PANK2 homolog in Drosophila, interacts with PINK1 genetically. fbl and PINK1 mutants display similar mitochondrial abnormalities, and overexpression of mitochondrial Fbl rescues PINK1 loss-of-function (LOF) defects. Dietary vitamin B5 derivatives effectively rescue CoA/acetyl-CoA levels and mitochondrial function, reversing the PINK1 deficiency phenotype. Mechanistically, Fbl regulates Ref(2)P (p62/SQSTM1 homolog) by acetylation to promote mitophagy, whereas PINK1 regulates fbl translation by anchoring mRNA molecules to the outer mitochondrial membrane. In conclusion, Fbl (or PANK2) acts downstream of PINK1, regulating CoA/acetyl-CoA metabolism to promote mitophagy, uncovering a potential therapeutic intervention strategy in PD treatment.