What is the recommended initial therapy for IgG4‑related disease involving the parotid gland?

Treatment of IgG4-Related Disease Involving the Parotid Gland

Begin oral prednisolone at 0.6 mg/kg/day (approximately 40 mg daily) for 2–4 weeks as first-line therapy for IgG4-related disease of the parotid gland. 1

Initial Glucocorticoid Induction

• Start prednisolone at 0.6 mg/kg/day (typically 40 mg daily for most adults) and continue this dose for the full 2–4 weeks before any tapering. 1, 2

• For elderly patients or those with contraindications to high-dose steroids (insulin-dependent diabetes, severe osteoporosis), consider a lower initial dose of 10–20 mg daily, which retrospective data suggest may achieve comparable effectiveness. 1

• Assess treatment response after 2–4 weeks by evaluating clinical improvement (reduction in parotid swelling, resolution of sialadenitis symptoms), normalization of inflammatory markers, and radiological reduction of lesions. 1, 3

• If no objective radiological improvement occurs by weeks 4–8, reconsider the diagnosis—this suggests either misdiagnosis or a fibrotic, non-inflammatory disease phase rather than true steroid failure. 1

Glucocorticoid Tapering Protocol

• After the initial 2–4 week induction period, taper prednisolone by 5 mg weekly over 8–12 weeks to reach a maintenance dose of 2.5–5 mg/day within 2–3 months. 1, 2

• Do not taper before completing the full 2–4 weeks of initial therapy—premature tapering substantially increases relapse risk. 1

Mandatory Steroid-Sparing Immunosuppression

• Because at least 60% of patients relapse after stopping steroids entirely, add a steroid-sparing immunosuppressant during the prednisolone taper for virtually all patients. 1, 4

• Initiate azathioprine (approximately 2 mg/kg/day), 6-mercaptopurine, or mycophenolate mofetil as the prednisolone dose is being reduced. 5, 1

• Continue immunosuppressive therapy for up to 3 years (potentially longer in multiorgan disease) to sustain disease control and prevent relapse. 1

• Alternatively, maintain low-dose prednisolone at 5–7.5 mg/day as monotherapy, which reduces the 3-year relapse rate to approximately 23% compared with 58% when steroids are completely withdrawn. 5, 1

Rituximab for Refractory or Relapsing Disease

• For patients who fail to respond to initial glucocorticoids or who experience disease flare after steroid withdrawal, rituximab is the preferred second-line agent, achieving >95% clinical response rates. 5, 1, 6

• Administer rituximab as two infusions of 1,000 mg given 15 days apart, repeated every 6 months for maintenance therapy. 1, 6

• Premedicate with methylprednisolone and antihistamines to reduce infusion-related reactions. 1

• Rituximab is especially indicated in multisystem disease or in patients who are steroid-dependent. 5, 1

• Repeated courses of rituximab maintain effectiveness and result in progressive declines in serum IgG4 concentrations. 6

Monitoring and Relapse Prevention

• Do not use serum IgG4 concentrations alone to direct treatment decisions or monitor response, although decreasing levels may parallel clinical improvement. 1

• Higher baseline serum IgG4 levels, involvement of more organs, and re-elevation of IgG4 during follow-up are associated with increased relapse risk. 4

• Patients with multiorgan involvement have particularly high relapse rates and require sustained maintenance immunosuppression. 5, 1

Specialist Referral

• Refer patients with complex multiorgan involvement, suspected malignancy, or refractory disease to a multidisciplinary team experienced in IgG4-related disease for optimal management. 5, 1

Critical Pitfalls to Avoid

• Never discontinue all immunosuppressive agents after an initial response—relapse rates exceed 60% without maintenance therapy. 1, 4

• Never taper steroids before completing 2–4 weeks of initial therapy at full dose—premature tapering increases relapse risk. 1

• Never rely on serum IgG4 levels alone for diagnosis or treatment monitoring—clinical and radiological assessment are essential. 1

• Never assume lack of radiological improvement at 4–8 weeks means treatment failure—consider fibrotic phase or misdiagnosis before escalating therapy. 1

• IgG4-related disease frequently mimics infectious, inflammatory, and neoplastic diseases, so confirm the diagnosis histopathologically before committing to long-term immunosuppression. 3, 2