We present a case of a 48-year-old man with an approximately 30-year history of spiny projections on the palms, which were histopathologically consistent with spiny keratoderma. Spiny keratoderma is a rare entity of unknown etiology that has been described with both hereditary and acquired variants. The hereditary form, which is most likely the diagnosis in our patient, manifests at a younger age and is benign. The acquired variant, which presents in older adults, has been associated with a variety of systemic diseases and malignant conditions. In patients suspected of having acquired spiny keratoderma, an evaluation for malignant conditions may be warranted.

Objectives

Susceptibility source-separation (χ-separation) MRI provides in-vivo proxy of myelin (diamagnetic susceptibility, χ_dia) and iron concentrations (paramagnetic susceptibility, χ_para) in the central nervous system, potentially uncovering myelin- and iron-related pathology in multiple sclerosis (MS) lesions (e.g., demyelination, remyelination, and iron-laden microglia/macrophages formation). This study aims to monitor longitudinal changes in χ_para and χ_dia signals within MS lesions using χ-separation and evaluate the association between lesional iron and remyelination capability.

Methods

Fifty participants with MS (pwMS) were followed annually over a mean period of 3.3 years (SD = 1.8 years) with MRI, including χ-separation, and clinical assessments. To monitor lesions from their early stage (lesion age < 1 year), we identified newly-noted lesions (NNLs) and contrast-enhancing lesions (CELs), and tracked their longitudinal changes in χ_para and χ_dia signals.

Results

Twenty-three pwMS were detected with NNLs and/or CELs (38 NNLs, 31 CELs;7 overlapped). Among these lesions (62 lesions in total), 27 exhibited χ_para hyperintensity, termed hyper-paramagnetic sign (HPS), indicating iron deposition "throughout" the lesion (not confined to rim sign). Early-stage HPS correlated with future remyelination failure detected by χ_dia myelin signals (P < 0.001). After adjustment, lesions with early HPS demonstrated an annual loss in myelin signal (-1.94 ppb/year), whereas those without early HPS exhibited annual recovery (+0.66 ppb/year). Participants with confirmed disability improvement (CDI) had fewer HPS-positive lesions at baseline than those without CDI (P < 0.001).

Conclusion

The presence of HPS is associated with impaired remyelination capacity and a lack of disease improvement in pwMS. Identifying HPS may help demarcate lesions more amenable to myelin repair therapies.

Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading-vertical growth and radial expansion-were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared with Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated proinflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated proinflammatory cytokines were lower in Western large plaque psoriasis, whereas T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T-cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes.