The guidance aims to address delays in recognition and improve timely initiation of treatment in this rare condition.
The European Reference Network for Rare Connective Tissue Diseases has released guidance for clinicians to consider IgG4-related disease in a bid to promote earlier diagnosis and treatment.
Recognising these red flags in primary and secondary care is crucial for early referral to specialists, especially given the potential for significant organ damage, such as fibrosis or loss of organ function, early detection and appropriate treatment can prevent irreversible damage.
European researchers published the guidance in The Lancet Rheumatology this month, describing it as the “first set of red flags for IgG4-related disease”.
“These red flags are based on expert opinion rather than on established evidence and highlight an important knowledge gap in the field of IgG4-related disease,” they wrote.
“These red flags require validation in longitudinal cohorts. Although the absence of evidence in support of our results prevents them from being conclusive, this work provides important recommendations for future research and represents an opportunity to increase disease awareness among non-specialists.”
The researchers said primary care physicians and specialists might not regularly encounter IgG4-RD, but it was important to remain vigilant for these red flags, especially when a patient presents with unexplained swelling, organ dysfunction, or other symptoms that do not fit a common diagnostic pattern.
The five red flags are:
- Swelling in one or more organ systems such as the salivary glands, lymph nodes, pancreas and kidneys. This is one of the most common and earliest signs of IgG4-RD.
- Pancreatic involvement, sometimes presenting as autoimmune pancreatitis; and biliary tree involvement, such as sclerosing cholangitis.
- Increased serum IgG4 levels: this is not specific to the condition but should prompt further investigation.
- IgG4-positive plasma cell tissue infiltration. This can be seen on biopsy samples from affected organs, thought this may not always be feasible in early stages.
- Obliterative phlebitis: inflammation and fibrosis of small veins in organs such as the pancreas or retroperitoneum is a key histopathological feature of IgG4-RD and can help distinguish it from other conditions.
The authors said raising suspicion of IgG4-related disease would “foster early referral to tertiary care centres for diagnostic confirmation and timely treatment with effective therapies”.
“Further studies should include analysis of primary care data from patients ultimately diagnosed with IgG4-related disease,” they concluded.
“This information would help to identify the reasons for the consultation that eventually led to the suspicion of IgG4-related disease and uncover knowledge gaps, resource constraints, and organisational barriers in this specific setting.
“Future potential red flags are likely to change as further evidence of sociodemographic and risk factors emerge.”
