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The article discusses a case of a 34-year-old man with antiphospholipid syndrome (APS) who developed multiple subcutaneous nodules known as reactive angioendotheliomatosis (RAE). The patient had a history of pulmonary embolism and APS, with contrast-enhanced computed tomography revealing numerous subcutaneous nodules in his trunk and thighs. The histopathological features of the nodules were consistent with RAE, characterized by endothelial cell proliferation and fibrin thrombi within capillary-sized vessels. This case highlights the importance of considering RAE in patients with APS, even when skin changes are not present, and emphasizes the need for appropriate diagnostic tests and monitoring techniques. [Extracted from the article]

The interleukin (IL)‐1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL‐1 superfamily, IL‐36 plays a pivotal role in both innate and adaptive immune responses. Of the four IL‐36 isoforms, three have agonist activity (IL‐36α, IL‐36β, IL‐36γ) and the fourth has antagonist activity (IL‐36 receptor antagonist [IL‐36Ra]). All IL‐36 isoforms bind to the IL‐36 receptor (IL‐36R). Binding of IL‐36α/β/γ to the IL‐36R recruits the IL‐1 receptor accessory protein (IL‐1RAcP) and activates downstream signalling pathways mediated by nuclear transcription factor kappa B and mitogen‐activated protein kinase signalling pathways. Antagonist binding of IL‐36Ra to IL‐36R inhibits recruitment of IL‐1RAcP, blocking downstream signalling pathways. Changes in the balance within the IL‐36 cytokine family can lead to uncontrolled inflammatory responses throughout the body. As such, IL‐36 has been implicated in numerous inflammatory diseases, notably a type of pustular psoriasis called generalized pustular psoriasis (GPP), a chronic, rare, potentially life‐threatening, multisystemic skin disease characterised by recurrent fever and extensive sterile pustules. In GPP, IL‐36 is central to disease pathogenesis, and the prevention of IL‐36‐mediated signalling can improve clinical outcomes. In this review, we summarize the literature describing the biological functions of the IL‐36 pathway. We also consider the evidence for uncontrolled activation of the IL‐36 pathway in a wide range of skin (e.g., plaque psoriasis, pustular psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis and pyoderma gangrenosum), lung (e.g., idiopathic pulmonary fibrosis), gut (e.g., intestinal fibrosis, inflammatory bowel disease and Hirschsprung's disease), kidney (e.g., renal tubulointerstitial lesions) and infectious diseases caused by a variety of pathogens (e.g., COVID‐19; Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pneumoniae infections), as well as in cancer. We also consider how targeting the IL‐36 signalling pathway could be used in treating inflammatory disease states. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase–signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI. [ABSTRACT FROM AUTHOR]

The corneocyte lipid envelope, composed of covalently bound ceramldes and fatty adds, Is Important to the Integrity of the permeability barrier in the stratum corneum, and its absence is a prime structural defect in various skin diseases associated with defective skin barrier function. SDR9C7 encodes a short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7) recently found mutated in ichthyosis. In a patient with SDR9C7mutation and a mouse Sdr9c7-KO model, we show loss of covalent binding of epidermal ceramides to protein, a structural fault in the barrier. For reasons unresolved, protein binding requires lipoxygenase-catalyzed transformations of linoleic acid (18:2) esterified in [omega]-O-acylceramides. In [Sdr9c7.sup.-/-] epidermis, quantitative liquid chromatography-mass spectometry (LC-MS) assays revealed almost complete loss of a species of [omega]-Oacylceramide esterified with linoleate-9,10-trons-epoxy-11E-13-ketone; other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed [NAD.sup.+]-dependent dehydrogenation of linoleate 9,10-trons-epoxy-11E-13-alcohol to the corresponding 13-ketone, while ichthyosis mutants were inactive. We propose, therefore, that the critical requirement for lipoxygenases and SDR9C7 is in producing acylceramide containing the 9,10- epoxy11E-13-ketone, a reactive moiety known for its nonenzymatic coupling to protein. This suggests a mechanism for coupling of ceramide to protein and provides important insights into skin barrier formation and pathogenesis., Introduction During the evolutionary process, when our ancestors left the aquatic environment, our integument developed a robust protective structure in the uppermost epidermis, the stratum corneum, and adjusted to the [...]

Hydroxyurea (HU) is a chemotherapeutic agent used for the treatment of myeloproliferative disorders such as chronic myeloid leukemia, polycythemia vera, and essential thrombocytosis. We describe a 69-year-old man who had essential thrombocytosis and developed amyopathic dermatomyositis after long-term HU therapy. He presented with Gottron papules and heliotrope erythema. The former has been described in all cases of HU-induced dermatomyositis; the latter has been seen in a few cases of that disorder.