What are the treatment options for rheumatological emergencies, such as severe flare-ups of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE)?

Rheumatological Emergencies: Treatment Approach

For life-threatening SLE emergencies such as diffuse alveolar hemorrhage, severe neuropsychiatric manifestations, or severe hematologic crises, immediate aggressive immunosuppression with high-dose intravenous glucocorticoids combined with cyclophosphamide is the first-line treatment, with rituximab, therapeutic plasma exchange, or intravenous immunoglobulin reserved for refractory cases or specific clinical scenarios. 1

Life-Threatening SLE Emergencies

Diffuse Alveolar Hemorrhage (DAH)

• Initiate intravenous glucocorticoids plus cyclophosphamide immediately as the mortality rate is extremely high and early aggressive intervention is mandatory 1
• Alternative or adjunctive therapies include therapeutic plasma exchange (TPE) and/or rituximab, which can be used simultaneously without prioritizing one over another given the life-threatening nature 1
• Cost and availability typically favor glucocorticoids plus cyclophosphamide over other combinations 1

Severe Neuropsychiatric Manifestations

• Use glucocorticoids plus cyclophosphamide as first-line therapy for acute severe neurologic manifestations including seizures, psychosis, myelitis, peripheral neuropathy, brain stem disease, and optic neuritis 1
• Glucocorticoids plus rituximab is an alternative, but cyclophosphamide has better quality evidence and rituximab was only evaluated in refractory patients 1
• The certainty of evidence favors cyclophosphamide over rituximab for initial treatment 1

Severe Hematologic Emergencies

Life-Threatening Hemolytic Anemia (Hemoglobin ≤8 g/dL)

• Start with high-dose glucocorticoids alone for severe hemolytic anemia 1
• Add rituximab for life-threatening hemolytic anemia or when high-dose glucocorticoids fail, despite moderate infection risk 1
• Immunosuppressants may be substituted for rituximab based on cost and availability, though evidence is lacking 1

Severe Thrombocytopenia (Platelet Count ≤30 x10⁹/L)

• Begin with high-dose glucocorticoids as initial therapy 1
• For refractory cases, life-threatening bleeding, pre-surgical patients, or those with infections, use intravenous immunoglobulin with/without glucocorticoids or rituximab plus glucocorticoids 1
• Intravenous immunoglobulin has smaller harmful effects (infusion reactions) compared to rituximab (increased infections) 1
• In life-threatening situations, both intravenous immunoglobulin and rituximab provide critical platelet count elevation 1

Severe RA Flares (Not Truly Life-Threatening)

Important Distinction

While severe RA flares cause significant morbidity, they are not true medical emergencies that compromise life, unlike the SLE emergencies described above 2, 3

Immediate Management of Severe RA Flares

• Optimize methotrexate to 20-25 mg weekly (oral or subcutaneous) before declaring treatment failure 4, 5
• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) for rapid symptom relief, using the lowest dose for the shortest duration (less than 3 months) 4, 6
• Provide intra-articular glucocorticoid injection for isolated joint inflammation 1

Escalation Strategy for Inadequate Response

• For patients on DMARD monotherapy: initiate triple-DMARD therapy (methotrexate + hydroxychloroquine + sulfasalazine) before advancing to biologics 4, 5
• For patients already on biologics: either discontinue the biologic and start triple-DMARD therapy, or switch to an alternative biologic with different mechanism of action 1, 7
• For seropositive RA patients (RF-positive, anti-CCP positive, or elevated IgG), rituximab demonstrates superior response rates compared to other biologics 5, 8

Treatment Targets and Monitoring

• Target clinical remission (SDAI ≤3.3 or CDAI ≤2.8) or low disease activity (SDAI ≤11 or CDAI ≤10) 4, 5
• Assess disease activity every 1-3 months during active treatment adjustment 4, 5
• If no improvement after 3 months, adjust therapy; if target not reached by 6 months, change to alternative mechanism 4, 5

Critical Pitfalls to Avoid

SLE Emergencies

• Never delay aggressive immunosuppression in diffuse alveolar hemorrhage as the mortality rate is extremely high and requires immediate intervention 1
• Do not use glucocorticoids alone for severe neuropsychiatric manifestations—always combine with cyclophosphamide or rituximab 1
• Recognize that rituximab increases infection risk; weigh this against potential benefits in hematologic emergencies 1

RA Management

• Do not continue ineffective therapy beyond 6 months as this leads to irreversible joint damage 5, 9, 10
• Avoid prolonged corticosteroid use beyond 1-2 years due to increased risk of cataracts, osteoporosis, fractures, and cardiovascular disease 4, 5
• Do not use NSAIDs or corticosteroids alone as they provide only symptomatic relief without disease modification 4
• Recognize that RA causes progressive radiographic damage, severe functional deterioration, and premature mortality comparable to cardiovascular or neoplastic disease—treat aggressively from diagnosis 11

Monitoring Requirements

• For rituximab use: screen for hepatitis B virus reactivation which can result in fulminant hepatitis, hepatic failure, and death 8
• Monitor for progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab 8
• Administer rituximab only with appropriate medical support to manage severe infusion-related reactions, as approximately 80% of fatal reactions occur with first infusion 8