ABSTRACT
BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).
Subject(s)
Cholecalciferol , Exanthema , Adult , Humans , Cholecalciferol/pharmacology , Double-Blind Method , Treatment Outcome , Exanthema/chemically induced , Exanthema/drug therapy , Inflammation/drug therapySubject(s)
Ankle , Skin Abnormalities , Ankle/diagnostic imaging , Humans , Tomography, X-Ray ComputedSubject(s)
Ki-1 Antigen/analysis , Mycosis Fungoides/diagnosis , Sezary Syndrome/diagnosis , Skin Neoplasms/diagnosis , Aged , Bexarotene/administration & dosage , Humans , Ki-1 Antigen/metabolism , Male , Middle Aged , Mycosis Fungoides/blood , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Photopheresis , Sezary Syndrome/blood , Sezary Syndrome/drug therapy , Sezary Syndrome/pathology , Skin Neoplasms/blood , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , T-Lymphocytes/metabolism , Treatment Outcome , Vorinostat/administration & dosageABSTRACT
Recently, several cutaneous manifestations of coronavirus disease 2019 (COVID-19) have been reported. However, there is a paucity of published images. Those that have been published so far tend to fall under distinct morphologic categories. We present a 52-year-old patient with an ill-defined skin eruption that preceded mild gastrointestinal (GI) symptoms and without respiratory symptoms who tested positive for COVID-19. With this case report, we widen the spectrum of the cutaneous manifestations of COVID-19 infection. Consequently, we propose an expansion of the criteria for COVID-19 testing when skin findings are associated with relatively mild GI symptoms.
