Lymphomas that occur in the setting of IgG4-related disease (IgG4-RD) are uncommon. Most reported cases derive from Asia and are MALT lymphomas occurring in orbital IgG4-RD. The spectrum of lymphomas ...among IgG4-RD patients in the Western world remains poorly defined. The aim of this study was to report our experience with lymphomas occurring in IgG4-RD. Eight cases were identified from the pathology and consultation files. The median age was 61 years (range 22–68) at IgG4-RD diagnosis and 63.5 years (range 33–79) at lymphoma diagnosis, with a M:F ratio of 4:4. The diagnosis of lymphoma and IgG4-RD was concurrent in three cases and asynchronous in five (interval 4.3–16.4 years). Concurrent cases included a MALT lymphoma and a diffuse large B cell lymphoma (DLBCL) occurring with IgG4-related sialadenitis and a follicular lymphoma occurring with orbital IgG4-RD. Asynchronous cases included a lymphoplasmacytic lymphoma with large cell transformation and intervening IgG4-related pancreatitis, a MALT lymphoma after lacrimal IgG4-RD, two DLBCLs after multiorgan IgG4-RD, and a DLBCL after IgG4-related sialadenitis. Our findings suggest that lymphomas in IgG4-RD are more varied in location and type than the experience reported from Asia to date. Pathologists should be aware of the potential for lymphoma to develop in patients with IgG4-RD and should have a high degree of suspicion when lymphadenopathy or extranodal masses persist despite appropriate therapy for IgG4-RD. The co-occurrence of IgG4-RD and lymphoma that is reported here and previously suggests a possible etiologic association.
IgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought ...to identify key IgG4-RD phenotypes.
We used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.
In the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1-3 (316, 178 and 445 mg/dL, respectively, p<0.001).
We identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.
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.
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).
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).
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.
Purpose of Review
Patients on disease-modifying anti-rheumatic drugs (DMARDs) remain concerned about potential risks of severe COVID-19 outcomes. Meanwhile, several DMARDs have been proposed as ...COVID-19 therapies.
Recent Findings
In patients with autoimmune diseases, baseline glucocorticoid use is associated with severe COVID-19. While classes of DMARDs (e.g., conventional synthetic, targeted synthetic, and biologic) do not appear to be associated with higher risk, specific medications such as rituximab and sulfasalazine may be associated. Randomized clinical trials (RCTs) show that glucocorticoids reduce mortality in severe COVID-19. RCTs suggest other agents, such as baricitinib, may improve COVID-19 outcomes in certain populations.
Summary
Baseline glucocorticoid use raises the risk of severe COVID-19 in patients with autoimmune diseases, but glucocorticoids are an effective treatment for those with severe COVID-19. Further research is needed to inform DMARD management in autoimmune disease patients during the pandemic and the role of DMARDs in COVID-19 treatment.
Abstract IgG4-related systemic disease (IgG4-RD) is an inflammatory condition of unknown etiology that has been identified as the cause of tumefactive lesions in a number of tissues and organs. The ...role of the IgG4 remains to be clarified fully, but the histopathologic diagnosis hinges upon the finding of IgG4-bearing plasma cells in addition to characteristic morphologic features, with or without elevated seum IgG4. We present a 56-year-old man with orbital pseudotumor in whom, after 30 years of intractable disease, biopsy showed IgG4-RD involving the lacrimal gland, extraocular muscles, intraconal fat, and trigeminal nerve. Six months after initiating treatment with rituximab, his disease remained dormant, with improvement in his proptosis and normalization of serum IgG4 levels. We review the differential of idiopathic orbital inflammatory disease, including IgG4-RD, and emphasize the need for biopsy for accurate diagnosis and to guide appropriate treatment.
Objective
The etiology of IgG4‐related disease (IgG4‐RD) is unknown, and there has been controversy over the significance of allergic conditions in IgG4‐RD. We examined the prevalence of lifetime ...allergy symptoms in IgG4‐RD and the association between these and IgG4‐RD.
Methods
We identified IgG4‐RD patients and non‐IgG4‐RD controls without autoimmune conditions seen at a single center. IgG4‐RD patients were classified using the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria. Allergy symptoms were ascertained by questionnaire. We assessed the association of IgG4‐RD features with allergy symptoms. We compared the proportion of cases and controls with allergy symptoms using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) after matching cases and controls 1:1 by age and sex.
Results
Lifetime allergy symptoms were reported by 165 (71%) of 231 IgG4‐RD patients. Aeroallergen symptoms were most commonly reported (n = 135, 58%), followed by skin allergy symptoms (n = 97, 42%) and food allergy symptoms (n = 47, 20%). IgG4‐RD cases with a history of allergy symptoms were more likely to have head and neck involvement (OR 2.0 95% CI 1.1–3.6) and peripheral eosinophilia (OR 3.3 95% CI 1.2–9.0) than those without allergy symptoms. The prevalence of any allergy symptoms was similar between cases and controls (OR 0.7 95% CI 0.4–1.1); this remained consistent after stratifying by head and neck involvement.
Conclusion
Lifetime allergy symptoms are common in IgG4‐RD but are not reported more often in IgG4‐RD compared to non‐IgG4‐RD patients without autoimmune conditions. These findings suggest that allergies are not uniquely associated with the pathogenesis or presentation of IgG4‐RD.
Objective
Prior authorizations (PAs) are commonly used by health payers as cost‐containment strategies for expensive medications, including infused biologics. There is scarce data about the effect of ...PA requirements on patient‐oriented outcomes.
Methods
We included patients for whom an infusible medication was prescribed for a rheumatologic condition. The exposures of interest were a PA requirement and whether or not the PA was denied. The primary outcome was the difference in days from medication request to infusion. Secondary outcomes included the proportion of denied PAs and differences in glucocorticoid exposure following a PA request.
Results
Of the 225 patients, the infusible medications of 160 (71%) required a PA. PAs were associated with a greater number of days to infusion compared to cases in which no authorization was required (median 31 days interquartile range (IQR) 15–60 days versus median 27 days IQR 13–41 days; P = 0.045), especially among the 33 patients (21%) whose PA was denied initially (median 50 days IQR 31–76 days versus median 27 days IQR 13–41 days; P < 0.001). PA denials were associated with greater prednisone‐equivalent glucocorticoid exposure in the 3 months following the request than when a PA was not required (median 605 mg IQR 0–1,575 versus median 160 mg IQR 0–675; P = 0.01). Twenty‐seven of the 33 PA requests that were initially denied (82%) were eventually approved. Thus, 96% of all PAs were ultimately approved.
Conclusion
PA requirements are associated with treatment delays and denials are associated with greater glucocorticoid exposure. Because the great majority of PA requests are ultimately approved, the value of PA requirements and their impact on patient safety should be reevaluated.
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