What is the recommended treatment with corticosteroids (CS), such as methylprednisolone, for multisystem inflammatory response syndrome (MIRS) in adults?

Corticosteroids in Multisystem Inflammatory Syndrome in Adults (MIS-A)

Corticosteroids, particularly methylprednisolone, should be used as first-line immunomodulatory therapy in adults with multisystem inflammatory syndrome (MIS-A), though the evidence base is limited and extrapolated primarily from pediatric MIS-C data and clinical case experience.

Critical Context: Limited Adult-Specific Evidence

The question addresses MIS-A, but the available guideline evidence predominantly addresses either pediatric MIS-C or trauma-related systemic inflammatory response syndrome (SIRS), not MIS-A specifically. The 2017 SCCM/ESICM guidelines explicitly recommend against corticosteroids in major trauma-related SIRS, finding no mortality benefit (RR 1.00,95% CI 0.89-1.13) across 19 trials with over 12,000 patients 1. This creates an important distinction: trauma-related SIRS differs fundamentally from post-viral hyperinflammatory MIS-A.

Recommended Treatment Approach for MIS-A

First-Line Therapy

Initiate methylprednisolone at 1-2 mg/kg/day IV as the primary corticosteroid for MIS-A, based on extrapolation from pediatric MIS-C guidelines and adult case series 1, 2, 3, 4.

• This dosing parallels the American College of Rheumatology's recommendation for pediatric MIS-C first-line therapy 1, 2
• Case reports demonstrate dramatic clinical and biochemical resolution with methylprednisolone in adults with MIS-A presenting with cardiogenic shock and multiorgan dysfunction 3, 4
• Methylprednisolone is preferred over other corticosteroids due to superior tissue penetration and longer residence time 1

Intensification for Refractory Disease

Escalate to high-dose methylprednisolone 10-30 mg/kg/day IV if patients demonstrate persistent fever, ongoing significant end-organ involvement, or progressive deterioration despite initial therapy 1, 2.

• Refractory disease is defined as persistent fevers and/or ongoing significant end-organ dysfunction despite 24-48 hours of initial therapy 1
• This high-dose approach mirrors the intensification strategy validated in pediatric MIS-C 1, 2

Combination Immunomodulatory Therapy

Consider combining corticosteroids with other immunomodulatory agents, particularly in severe presentations:

• Intravenous immunoglobulin (IVIG) 2 g/kg can be administered concurrently with corticosteroids, though recent pediatric RCT data suggests methylprednisolone alone may be equally effective 5, 6
• Anakinra (IL-1 receptor antagonist) or tocilizumab (IL-6 receptor antagonist) for second-line therapy if inadequate response to corticosteroids 4, 5
• The RECOVERY trial in children showed tocilizumab reduced hospital stay by 3.3 days (95% CrI -5.6 to -1.0) when used as second-line therapy 5

Tapering and Duration

Taper corticosteroids slowly over 6-14 days, not abruptly, to prevent rebound inflammatory response 1.

• Rapid discontinuation (2-4 days) or abrupt cessation can lead to clinical deterioration from reconstituted inflammation 1
• Monitor for recrudescence of symptoms during taper and adjust accordingly 1
• The FDA label recommends gradual withdrawal after long-term therapy rather than abrupt cessation 7

Critical Monitoring Requirements

Infection Surveillance

Implement heightened infection surveillance because glucocorticoids blunt the febrile response, potentially masking hospital-acquired infections 1.

• Maintain low threshold for broad infectious workup if clinical deterioration occurs 3, 4
• One case report documented severe toxoplasmosis developing after corticosteroid treatment for presumed MIS-A, highlighting infection risk 8

Metabolic Monitoring

• Expect hyperglycemia, particularly within 36 hours of initial dosing, though this is not associated with increased morbidity 1
• Monitor for electrolyte disturbances and fluid status, especially in patients with cardiac dysfunction 1, 2

Cardiac Assessment

• Assess cardiac function and fluid status before administering therapy, as MIS-A commonly presents with cardiogenic shock 3, 4
• In patients with significant cardiac dysfunction, consider dividing doses or adjusting fluid administration 1

Common Pitfalls and Caveats

Distinguishing MIS-A from Other Conditions

The diagnosis of MIS-A requires:

• Temporal association with SARS-CoV-2 infection (typically 2-6 weeks post-infection) 3, 4
• Elevated inflammatory markers (CRP, ferritin, IL-6) 3, 4
• Multiorgan involvement, commonly including cardiac dysfunction 3, 4
• Exclusion of active infection through comprehensive microbiologic evaluation 3, 4

Avoiding Premature Corticosteroid Use

Do not initiate corticosteroids until active infection is reasonably excluded, as case reports demonstrate severe opportunistic infections can develop in immunosuppressed patients 8.

Evidence Quality Limitations

The adult MIS-A literature consists primarily of case reports and small case series 3, 4. The strongest evidence comes from pediatric MIS-C trials, which may not fully translate to adult pathophysiology 5, 6. The 2017 SCCM/ESICM guidelines addressing trauma-related SIRS are not directly applicable to post-viral MIS-A 1.

Comparative Evidence: Methylprednisolone vs IVIG

Recent pediatric RCT data suggests methylprednisolone may be equally or more effective than IVIG as monotherapy:

• The Swiss multicenter RCT found no significant difference in hospital length of stay between methylprednisolone and IVIG (both median 6 days), but methylprednisolone resulted in less respiratory support requirement (27% vs 55%, p=0.025) 6
• The UK RECOVERY trial showed moderate evidence that first-line methylprednisolone reduces hospital stay compared to usual care, while IVIG showed no benefit 5
• This suggests methylprednisolone alone may be sufficient for many patients, reserving combination therapy or IVIG for more severe presentations 5, 6