Assessment of patient-reported symptoms and distress in IgG4-related disease (IgG4-RD): Development, clinical validation, and content validation of the IgG4-RD Symptom Severity Index.

OBJECTIVE: IgG4-related disease (IgG4-RD), a multi-organ autoimmune disease, causes diverse manifestations that can lead to symptoms and distress. We developed and validated the Symptom Severity Index (SSI) to assess symptom burden. METHODS: A pilot SSI was tested in n = 5; several gaps were identified. Twenty semi-structured qualitative interviews were performed to expand the item set and identify missing symptoms. Subsequent changes resulted in the current SSI; it was administered with quality of life (QOL) measures to n = 136. We assessed symptom burden and the construct validity of the SSI. A distress score for each symptom is calculated by multiplying symptom frequency ("Never" [0 points] to "Every Day" [3 points]) by associated distress ("None" [0 points] to "Very Much" [4 points]). Each distress score is summed to calculate a total SSI score. RESULTS: The SSI assesses the frequency and distress of 24 symptoms. Among n = 136 with ≥ 1 SSI, 90% experienced ≥ 1 symptom and 88% had distress. The median SSI score was 6.5 (IQR 3.0, 18.0). Fear of more severe disease was observed in 49%. The SSI inversely correlated with the SF-36 (r= - 0.51, p<0.001), the feeling thermometer (r= - 0.28, p<0.001), and the EQ-5D (r= - 0.28, p<0.001). The median SSI score was higher during active vs non-active disease among n = 52 who completed >1 SSI (15 [6, 26] vs. 3 [2, 14], p = 0.008). CONCLUSIONS: Symptoms and distress are common in IgG4-RD and associated with worse health-related QOL. The SSI has face, content, and construct validity; it corresponds with QOL measures.

Impact of vaccination on postacute sequelae of SARS CoV-2 infection in patients with rheumatic diseases.

OBJECTIVE: Vaccination decreases the risk of severe COVID-19 but its impact on postacute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC. METHODS: We prospectively enrolled patients with SARD from a large healthcare system who survived acute infection to complete surveys. The symptom-free duration and the odds of PASC (any symptom lasting ≥28 or 90 days) were evaluated using restricted mean survival time and multivariable logistic regression, respectively, among those with and without breakthrough infection (≥14 days after initial vaccine series). RESULTS: Among 280 patients (11% unvaccinated; 48% partially vaccinated; 41% fully vaccinated), the mean age was 53 years, 80% were female and 82% were white. The most common SARDs were inflammatory arthritis (59%) and connective tissue disease (24%). Those with breakthrough infection had more upper respiratory symptoms, and those with non-breakthrough infection had more anosmia, dysgeusia and joint pain. Compared with those with non-breakthrough COVID-19 infection (n=164), those with breakthrough infection (n=116) had significantly more symptom-free days over the follow-up period (+21.4 days, 95% CI 0.95 to 41.91; p=0.04) and lower odds of PASC at 28 and 90 days (adjusted OR, aOR 0.49, 95% CI 0.29 to 0.83 and aOR 0.10, 95% CI 0.04 to 0.22, respectively). CONCLUSION: Vaccinated patients with SARDs were less likely to experience PASC compared with those not fully vaccinated. While we cannot rule out the possibility that findings may be due to intrinsic differences in PASC risk from different SARS-CoV-2 variants, these findings support the benefits of vaccination for patients with SARDs and suggest that the immune response to acute infection is important in the pathogenesis of PASC in patients with SARDs.