Project description:Hereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma prekallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1β (IL-1β) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.
Project description:Olaparib is recently approved as an anti-tumor agent for several cancers, including castration-resistant prostate cancer, which inhibits poly (adenosine diphosphate-ribose) polymerase, a DNA repair factor. Since olaparib is a newly approved drug, there are few reports of skin disorders that may be triggered by olaparib administration. In this report, we present a case with an olaparib-induced drug eruption presenting multiple purpuras on the patient's fingers and fingertips. The present case suggests that olaparib might induce purpura as nonallergic drug eruption.
Project description:Lichenoid drug eruption (LDE) is a rare form of delayed-type drug eruption. Among anti-tuberculosis (Tb) agents, cycloserine (CS) has been reported as a rare cause of LDE. Positive results on the lymphocyte transformation test (LTT) have not been reported in patients with LDE. In the present case, we performed LTT and a patch test, and successfully proved CS as the offending drug in this patient, who had been treated with multiple anti-Tb drugs. These observations suggest that CS should be considered a possible cause of LDE and that LTT can be an option for the diagnosis of LDE.
Project description:A 58-year-old man with a history of hypertension and psoriasis presented with acute-onset heart failure with an ejection fraction of 25%-30%. During the work-up, cardiac magnetic resonance imaging showed a pattern of inflammation consistent with sarcoidosis, which was confirmed with (18)F-fluorodeoxyglucose positron emission tomography . The patient was recently initiated on ixekizumab for psoriasis, which was then discontinued. This discontinuation resulted in complete resolution of cardiac sarcoidosis, with establishment of normal ejection fraction. This result suggests a potential causal association of ixekizumab-induced cardiac sarcoidosis, which is a rare phenomenon. Elucidation of the mechanism behind the effect of ixekizumab may provide insights into the possible mechanism(s) behind cardiac sarcoidosis.
Project description:Statins, an example of the most commonly prescribed medications to the elderly, are not without side effects. Dermatologic events are often overlooked as arising from medications, particularly those which are taken chronically. Moreover, elderly patients are prone to pharmacologic interactions due to multiple medications. In this report, we describe a case of a statin-induced eczematous dermatitis with a psoriasis-like clinical presentation and review the skin manifestations that may arise from statin therapy.An 82-year-old man with gout and hypercholesterolemia presented to dermatology clinic with new onset of pruritic, scaly erythematous plaques bilaterally on the extensor surfaces of his arms. He had never had similar lesions before. Despite various topical and systemic treatments over several months, the rash continued to evolve. The patient was then advised to discontinue his long-term statin, which led to gradual resolution of his symptoms. He was subsequently diagnosed with statin-induced eczematous dermatitis.This case report describes an adverse cutaneous reaction to statins that is rarely reported in the literature. Medications, including longstanding therapies, should be suspected in cases of refractory dermatologic lesions.
Project description:Telaprevir used as a protease inhibitor against hepatitis C virus is frequently associated with cutaneous adverse reactions. To explore a histological biomarker of cutaneous adverse events induced by telaprevir, we systematically searched for genes that were dysregulated by telaprevir in normal human epidermal keratinocytes (NHEKs). Microarray analysis and real-time polymerase chain reaction (PCR) revealed the significant increase in the expression of S100 calcium-binding protein A2 (S100A2) gene following treatment of NHEKs with telaprevir. Immunohistochemical analysis demonstrated that the expression of S100A2 was dominant in the spinous layer of the epidermis in patients with telaprevir-mediated severe-type drug eruptions and limited to the basal layer of the epidermis in healthy subjects. Furthermore, S100A2 expression increased after treatment with trichloroethylene and other medications, and the degree of S100A2 expression correlated with the severity of cutaneous adverse events. S100A2 expression also significantly increased in the skin of patients with atopic dermatitis and psoriasis. Taken together, S100A2 is highly expressed in the epidermis under inflammatory conditions and drug eruptions and may serve as a marker for keratinocyte damage in response to any inflammatory or toxic condition.
Project description:With recent increase in the use of direct oral anticoagulants (DOACs), several new cases of adverse drug reactions (ADRs) have been identified in pharmacovigilance surveys. These ADRs can result in significant mortality and morbidity if not identified and treated promptly. It is important for physicians to recognize that immunologically mediated delayed hypersensitivity reactions, although rare in occurrence, can have significant impact on patient's quality of life. To the best of our knowledge, we report the first case of lichenoid eruption associated with apixaban. We further provide evidence of tolerance to rivaroxaban in the same patient.Plain language summaryApixaban-induced lichenoid eruption Well documented case reports, although providing evidence of probable causal relationship between a drug and specific adverse drug reactions (ADRs), can increase awareness amongst clinicians treating patients with direct oral anticoagulants (DOACs), especially with its rapid utilization. Rare ADRs are difficult to detect as clinical trials of DOACs lacked enough patient sample, making post-marketing reporting of such events important so both patients and clinicians can be vigilant to help with prompt recognition of such symptoms. We report the first case of lichenoid eruption hypersensitivity reaction associated with apixaban in patient with tolerance to rivaroxaban.