RESUMO
BACKGROUND: Scleroderma and adult onset Still's disease (AOSD) are both uncommon autoimmune disorders. These two disorders have rarely been documented to occur simultaneously. In fact, after a thorough literature review, we discovered only one prior case report in a pregnant individual. Here, we describe the first documented case of scleroderma and AOSD in a postmenopausal patient. CASE PRESENTATION: The patient is a 61-year-old Caucasian female with a past medical history significant for peptic ulcer disease, mitral valve prolapse, chronic idiopathic pancreatitis, and limited cutaneous scleroderma with sclerodactyly, Raynaud's, and calcinosis. She was sent to the emergency room by her primary care physician due to one-week history of intermittent spiking fevers (Tmax 101°F), sore throat, myalgias, arthralgias, and non-pruritic bilateral lower extremity rash. Diagnostic evaluation in the hospital included complete blood count, comprehensive metabolic panel, respiratory viral panel, antinuclear antibody panel, bone marrow biopsy, and imaging with computerized tomography. Our patient fulfilled Yamaguchi Criteria for AOSD and all other possible etiologies were ruled out. She was treated with a steroid taper and methotrexate was initiated on post-discharge day number fourteen. Clinical and biochemical resolution was obtained at three months. CONCLUSIONS: In this report, we describe the first ever documented case of scleroderma and AOSD in a postmenopausal patient. The clinical presentation, diagnostic work up, and management discussed herein may serve as a framework for which rheumatologists and other physicians may draw upon in similar future encounters.
RESUMO
Increased IFN-α signaling is a heritable risk factor for systemic lupus erythematosus (SLE). IFN induced with helicase C domain 1 (IFIH1) is a cytoplasmic dsRNA sensor that activates IFN-α pathway signaling. We studied the impact of the autoimmune-disease-associated IFIH1 rs1990760 (A946T) single nucleotide polymorphism upon IFN-α signaling in SLE patients in vivo. We studied 563 SLE patients (278 African-American, 179 European-American, and 106 Hispanic-American). Logistic regression models were used to detect genetic associations with autoantibody traits, and multiple linear regression was used to analyze IFN-α-induced gene expression in PBMCs in the context of serum IFN-α in the same blood sample. We found that the rs1990760 T allele was associated with anti-dsDNA Abs across all of the studied ancestral backgrounds (meta-analysis odds ratio = 1.34, p = 0.026). This allele also was associated with lower serum IFN-α levels in subjects who had anti-dsDNA Abs (p = 0.0026). When we studied simultaneous serum and PBMC samples from SLE patients, we found that the IFIH1 rs1990760 T allele was associated with increased IFN-induced gene expression in PBMCs in response to a given amount of serum IFN-α in anti-dsDNA-positive patients. This effect was independent of the STAT4 genotype, which modulates sensitivity to IFN-α in a similar way. Thus, the IFIH1 rs1990760 T allele was associated with dsDNA Abs, and in patients with anti-dsDNA Abs this risk allele increased sensitivity to IFN-α signaling. These studies suggest a role for the IFIH1 risk allele in SLE in vivo.
