What is the optimal treatment plan for a 44-year-old female with biopsy-proven lupus and dermatomyositis, presenting with itchy rash, swelling in hands, iron deficiency, and vitamin D deficiency, currently on hydroxychloroquine and mycophenolate?

Treatment Plan for Cutaneous Lupus and Dermatomyositis Overlap Syndrome

Given the biopsy-proven dermatomyositis findings, positive PM/Scl-100 antibody, and persistent cutaneous disease despite hydroxychloroquine and mycophenolate, the planned addition of rituximab 1000 mg at weeks 0 and 2, then every 6 months is appropriate, but hydroxychloroquine should be discontinued immediately due to the high risk of cutaneous adverse reactions in dermatomyositis patients. 1

Critical Medication Safety Issue

Hydroxychloroquine paradoxically worsens cutaneous disease in approximately 31% of dermatomyositis patients and should be stopped. 2, 3, 4

• Patients with anti-SAE-1/2 antibodies have an 8-fold increased risk of hydroxychloroquine-induced skin eruptions (50% vs 16.5% in those without this antibody) 4
• The itchy rash on legs and calves that persists despite topical triamcinolone and tacrolimus may represent hydroxychloroquine-induced exacerbation rather than disease progression 3
• Cutaneous reactions typically occur within 2 weeks to 9 months of starting hydroxychloroquine, with resolution taking 6 weeks to 6 months after discontinuation 3
• While hydroxychloroquine is universally recommended for SLE 5, dermatomyositis represents a specific exception where it can cause harm 2, 4

Immunosuppressive Treatment Algorithm

Continue mycophenolate mofetil as the steroid-sparing agent and proceed with rituximab for severe/refractory disease. 1

Current Appropriate Medications:

• Mycophenolate mofetil: Effective for refractory cutaneous disease and dermatomyositis, target dose 2-3 g/day 1, 5
• Rituximab 1000 mg weeks 0,2, then every 6 months: Appropriate for severe disease with dermatomyositis features and inadequate response to conventional immunosuppression 1

Corticosteroid Management:

• For severe dermatomyositis with organ involvement, high-dose methylprednisolone pulse therapy (15-30 mg/kg/dose for 3 consecutive days) followed by oral prednisone 1-2 mg/kg/day is recommended 1
• Given the elevated ESR (57), low C4 (8), and persistent symptoms, a short course of higher-dose corticosteroids may be needed before rituximab initiation 1
• Taper corticosteroids aggressively once rituximab takes effect, targeting <7.5 mg/day for maintenance 5

Management of Cutaneous Disease

After discontinuing hydroxychloroquine, intensify topical therapy and optimize systemic immunosuppression. 5

• Continue topical triamcinolone for localized lesions 5
• Continue topical tacrolimus (calcineurin inhibitor) for facial/sensitive areas 5
• Strict photoprotection is essential given photosensitivity 5
• If cutaneous disease persists 6 weeks after stopping hydroxychloroquine, consider adding methotrexate 15-20 mg/m² weekly subcutaneously as it is effective for both cutaneous lupus and dermatomyositis 1, 5

Addressing Comorbidities

Iron Deficiency:

• Continue IV iron infusions with hematology as planned 5
• Monitor hemoglobin as anemia is a predictor of poor outcomes in lupus 1

Vitamin D Deficiency (level 21.2 ng/mL):

• Increase vitamin D supplementation to achieve levels >30 ng/mL 1
• Adequate calcium and vitamin D intake reduces corticosteroid-related bone loss 1

Hand Swelling:

• This likely represents inflammatory arthritis from lupus/overlap syndrome 5
• Should improve with rituximab and optimized immunosuppression 1
• Monitor with patient-reported outcomes and joint examination at each visit 1

Suspected Mast Cell Activation Syndrome:

• Continue OTC cetirizine (Zyrtec) and fluticasone (Flonase) 5
• This does not contraindicate immunosuppressive therapy 5

Monitoring Strategy

Regular monitoring every 2-4 weeks initially, then every 3-6 months once stable. 1, 5

At Each Visit Monitor:

• Blood pressure, weight 1
• Complete blood count (watch for rituximab-related cytopenias) 1
• Serum creatinine, eGFR (currently normal at 112) 1
• Urinalysis with microscopy, protein/creatinine ratio (currently 100 mg/g, borderline) 1
• C3 (currently normal at 129), C4 (currently low at 8) 1, 5
• Anti-dsDNA (currently negative) 5
• ESR/CRP (ESR currently elevated at 57) 1
• Liver enzymes (ALT 48, AST 45 - mildly elevated, likely from mycophenolate) 1

Additional Monitoring:

• Creatine kinase remains normal (74), but recheck if weakness worsens 1
• Consider repeat muscle biopsy or MRI if weakness progresses despite treatment 1

Critical Pitfalls to Avoid

• Do not continue hydroxychloroquine in dermatomyositis patients with worsening rash - this represents a unique population where standard lupus recommendations do not apply 2, 3, 4
• Do not delay rituximab - the combination of dermatomyositis features, positive PM/Scl-100, and inadequate response to hydroxychloroquine/mycophenolate indicates severe disease requiring biologic therapy 1
• Monitor for rituximab-related infections - patients with SLE have increased infection risk, compounded by immunosuppression 5
• Watch for myocarditis - dermatomyositis can involve cardiac muscle, which would be life-threatening and require urgent high-dose corticosteroids 1