Building on previous work in Phenotype Phebruary 2022
Phenotype Phebruary Day 6 - Systemic Lupus Erythematosus (SLE)
Ah, remember the old days, say, February 2022, when the phenotype development process in OHDSI was in its early adolescence? Well, it’s grown up a lot in the past year thanks to a lot of work by phenotype development scientists like @Gowtham_Rao and @Azza_Shoaibi . Last year I submitted my phenotypes for SLE as four separate algorithms: two sensitive algorithms for incident and prevalent cases and two specific algorithms requiring a second code for SLE within 31-365 days post index. This year I’m going to reduce the algorithms down to one for easier review. The single algorithm, which can be viewed in the OHDSI Phenotype Library shiny app as phenotype 119:
The algorithm is incident, using the first code for SLE, with up to 90 day index date reclassification.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin. Clinical manifestations include fatigue, arthropathy, and involvement of nearly all organ systems, particularly cardiac and renal.(Jump et al, Greco et al 1, Miner et al 1, Danila et al 1) A review by Stojan and Petri 1 of research on multi-country incidence rate estimates found the incidence rate of SLE to be between 1-9 cases per 100,000 person-years (PY).
Clinical Description
Overview: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology that may involve any organ system with a wide range of severity. It is characterized by periods of exacerbation and relative quiescence and occurs predominantly among women of child-bearing age.
Presentation: SLE presents with symptoms such as fatigue, rash (usually malar), arthritis, anemia, and nephritis and occasionally may be life threatening.
Assessment: Anti-nuclear antibodies (ANA) presence is highly sensitive but not specific to SLE. Under specialist care, testing includes measurement of anti-double-stranded DNA (ds-DNA) antibodies, a more specific version of ANA. When someone with SLE features tests ANA+, testing then includes measurement of complement (C3, C4) as well as ds-DNA. Diagnosis of SLE is difficult and often delayed especially in the early stages. For many patients, true disease onset may be when symptoms, treatment, or testing started for SLE which may be weeks or months prior to an SLE diagnosis
Plan: Conservative treatment includes sun protection, NSAIDS, anti-malarial drugs such as hydroxychloroquine and chloroquine, and methotrexate. More life-threatening states may be managed by systemic glucocorticoids and cytotoxic or immunosuppressive agents.
Prognosis (from UpToDate): Systemic lupus erythematosus (SLE) can run a varied clinical course, ranging from a relatively benign illness to a rapidly progressive disease with fulminant organ failure and death. The five-year survival rate in SLE has dramatically increased since the mid-20th century, from approximately 40 percent in the 1950s to greater than 90 percent since 1980s. The improvement in patient survival is probably due to multiple factors including increased disease recognition with more sensitive diagnostic tests, earlier diagnosis or treatment, the inclusion of milder cases, increasingly judicious therapy, and prompt treatment of complications. Despite these improvements, patients with SLE still have mortality rates ranging from two to five times higher than that of the general population. Based on mortality data from the United States Centers for Disease Control and Prevention (CDC) from 2000 to 2015, SLE ranked among the top 20 leading causes of death in females between the ages of 5 and 64. In another large population-based study in the United States, mortality risk from SLE was higher among women, African Americans, and residents of the South.
Designated Medical Event - MedDRA PT terms: Granulocytopenia, Has neutropenia as a component: Aplastic anemia, Bone marrow failure, Pancytopenia; Neutropenic colitis, Neutropenic infection, Neutropenic sepsis
Phenotype development:
Submission:
As discussed last year, after reviewing the literature and finding recommendations from PHOEBE (thanks again @aostropolets), we decided on the following concept set:
We then began building our cohort definitions. We knew from prior literature that SLE often takes a long period to diagnose so we looked for signs, symptoms, and indicative treatment to determine if we should include index date reclassification.
We found the following for signs and symptoms:
And for prior indicative treatment:
We submit the cohort definition # 119 to the OHDSI phenotype library which is currently in peer review status.
Phenotype evaluation:
Here are the incidence rates across several databases:
SLE is more prevalent in females than males.
And tends to peak in the 50-59 YO age group.
The results from PheValuator are:
We see good sensitivity among those with a 365 day lookback period, with a mean of around 94% across the 7 databases tested. Positive predictive value (PPV) was fair, with a mean of around 69%. Remember from last year we found that adding a second code 31-365 days post-index increased the PPV with a concomitant decrease in sensitivity.
While I am limiting this year’s algorithm to one, this algorithm can be easily converted for other uses such as a conversion to a prevalent cohort by removing the requirement for a 365 day look-back.
- thanks for catching this.