What is the diagnosis and recommended treatment for a 37-year-old female patient with a 1-year history of non-specific symptoms, including sore mouth and throat, muscle pain and weakness, intermittent joint swelling, pelvic pain, and bilateral symmetrical intermittent paresthesia in arms and legs, with positive Extractable Nuclear Antigen (ENA) with Ribonucleoprotein-A (RNP-A), and negative Electromyography (EMG), Cerebrospinal Fluid (CSF) testing, and infectious panel?

Diagnosis: Mixed Connective Tissue Disease (MCTD)

This patient's presentation of positive anti-RNP antibodies (RNP-A 4.7) combined with multisystem involvement including arthritis, myalgia, Raynaud's phenomenon (suggested by paresthesias), and mucosal symptoms is diagnostic of Mixed Connective Tissue Disease (MCTD). 1, 2

Diagnostic Confirmation

The presence of anti-RNP antibodies is the serological hallmark of MCTD, occurring in 100% of cases, and distinguishes this condition from other connective tissue diseases 3. This patient's clinical constellation fits the Alarcon-Segovia criteria for MCTD 1:

• Anti-RNP antibodies (positive) - the defining serological marker 2, 3
• Arthritis/arthralgias - intermittent joint swelling 2, 4
• Myositis features - muscle pain and weakness 2
• Raynaud's phenomenon - likely manifesting as bilateral symmetrical paresthesias 1, 2
• Mucosal involvement - sore mouth and throat 4

Critical Diagnostic Workup Still Needed

Immediate laboratory testing should include:

• Creatine kinase (CK) levels to distinguish true myositis from myalgia-like syndrome; MCTD patients with myositis typically show CK >2650 IU/L, while polymyalgia-like presentations have normal CK 5
• Complete metabolic panel with creatinine to assess for renal involvement, though this is less common with anti-RNP positivity 3
• Pulmonary function tests and high-resolution chest CT to screen for interstitial lung disease, which carries the worst prognosis and highest mortality in MCTD 2, 1
• Echocardiogram to evaluate for pulmonary hypertension, a life-threatening complication 2

Additional autoantibody testing:

• Anti-dsDNA and complement levels (C3, C4) to assess for SLE overlap features 6
• Anti-Sm antibodies to differentiate from pure SLE (present in 32% of SLE but not typically in MCTD) 3

Treatment Recommendations

Initial therapy should consist of systemic corticosteroids as the foundation, with early addition of disease-modifying agents given the multisystem involvement. 1, 2

First-Line Treatment Protocol

Corticosteroids:

• Prednisone 0.5-1 mg/kg/day (approximately 30-60 mg daily for this patient) for moderate-to-severe disease with multisystem involvement 6
• Taper slowly over 4-6 weeks based on clinical response, aiming for maintenance dose <10 mg/day 6

Disease-Modifying Antirheumatic Drug (DMARD):

• Methotrexate 15-25 mg weekly should be initiated early as a steroid-sparing agent, particularly given the arthritis and myositis features 1, 6
• Hydroxychloroquine 200-400 mg daily can be added for mucocutaneous and articular manifestations 2

Monitoring for Treatment Response

Serial assessments every 4-6 weeks should include:

• CK levels and inflammatory markers (ESR, CRP) to track disease activity 5, 6
• Muscle strength testing using standardized manual muscle testing scores 7
• Joint examination with 28-joint count assessment for synovitis 8

Escalation Strategy for Refractory Disease

If inadequate response after 4-6 weeks or inability to taper prednisone below 10 mg/day:

• Add mycophenolate mofetil 1000-1500 mg twice daily for severe organ involvement, particularly if pulmonary or renal disease develops 2
• Consider rituximab or other biologic agents (anti-TNF therapy such as infliximab) for refractory cases 1
• Avoid IL-6 inhibitors (tocilizumab) if any gastrointestinal involvement is present due to perforation risk 6

Critical Pitfalls to Avoid

Do not delay treatment pending complete workup - the presence of anti-RNP antibodies with compatible clinical features is sufficient to initiate therapy, as MCTD can progress rapidly with life-threatening complications 1, 2

Do not assume benign course - while early descriptions suggested good response to low-dose steroids, this is not universal; pulmonary involvement carries high mortality and requires aggressive monitoring 2

Do not attribute all symptoms to MCTD without excluding infection - the extensive negative infectious panel is reassuring, but ongoing vigilance is needed, especially once immunosuppression begins 2

Distinguish true myositis from myalgia syndrome - if CK is normal despite muscle symptoms, this represents polymyalgia-like syndrome rather than inflammatory myositis, which has different treatment implications and prognosis 5, 6

Prognosis and Long-Term Management

The prognosis varies significantly in MCTD, with outcomes ranging from complete remission to life-threatening complications 1. The development of pulmonary disease (interstitial lung disease or pulmonary hypertension) is the most important prognostic factor and leading cause of mortality 2. This patient's lack of respiratory symptoms is favorable, but serial monitoring is essential.

Rheumatology referral is mandatory for ongoing management of this complex autoimmune condition 8. The negative EMG and CSF testing help exclude alternative diagnoses such as primary neurologic disease or CNS vasculitis 6.