Cutaneous Manifestations of Systemic Disease

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Background

Clinical dermatologists rightfully consider the skin as a critical window on internal disease processes due to the high frequency of association between cutaneous manifestations and systemic disease. Skin signs are sometimes specific to diseases, especially when a shared immunopathogenesis or histology is recognized, while other times they may be suggestive of multiple associated systemic conditions. Skin findings are central manifestations in rheumatologic disorders, infective diseases – especially viral infections – and endocrine syndromes. In oncology, paraneoplastic dermatoses may be the first sign of a previously unnoticed malignancy or an early warning of tumour recurrence after treatment. Moreover, skin changes – especially pigmentary lesions – appear very early in patients with genetic neurocutaneous disorders, enabling dermatologists to raise clinical suspicion for diagnosis in many cases. Finally, treatments can cause adverse manifestations involving the skin; some are widely documented while others are novel and related to emerging treatments, in both dermato-oncology and immunology.

The broad concept that skin is a mirror of internal disease may be approached from three different angles. Firstly, disease-related skin lesions that may occur in association with different systemic conditions, including endocrinopathies, infections, rheumatologic and autoimmune disorders, and malignancy. Secondly, disease-specific skin manifestations. Here there is a special focus on genodermatoses which is motivated by the necessity for early recognition of these hereditary cancer syndromes, that require life-long clinical and instrumental surveillance for malignancy. Lastly, cutaneous adverse effects of systemic treatment. Kinase inhibitors and, more recently, immunotherapy with checkpoint blockade revolutionized cancer treatment and confronted dermato-oncologists with novel side-effects and immune-related adverse events targeting the skin. Similarly, Janus kinase inhibitors and other small molecule inhibitors are the latest additions to the therapeutic armamentarium of immune-mediated skin disorders and have been associated to peculiar skin manifestations, such as acne with upadacitinib.

While a detailed description of all cutaneous manifestations related to systemic disease is clearly beyond the scope of this topic, all contributions presenting the latest updates and future perspectives are welcome in form of: Original Research, Systematic Review (conforming to accepted reporting guidelines), Review, Mini Review, Hypothesis and Theory, Perspective, Clinical Trial, Case Report (carefully following the CARE guidelines), Brief Research Report, Opinion.

Contributions to the recognition and management of the cutaneous side effects of systemic treatment are particularly valuable to the practicing clinician. Finally, while cutaneous tropism is characteristic of several viruses, an in-depth understanding of the skin manifestations reported with SARS-CoV-2 is currently lacking as to their relatedness and pathogenesis.

Keywords: Cutaneous, Systemic Disease, Malignancy

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