What is the diagnosis and recommended management for a 35-year-old female with a history of asthma, Attention Deficit Hyperactivity Disorder (ADHD), hepatitis C, treated Post-Traumatic Stress Disorder (PTSD), anxiety, sinus tachycardia, and Lyme disease, currently taking metoprolol (Lopressor) 25 mg, Qelbree (viloxazine) 200mg, and Vyvanse (lisdexamfetamine) 60 mg, presenting with raised irritated follicles on the head, posterior cervical lymph node enlargement, chronic sinus pain and pressure, cobblestoning of the posterior throat, fatigue, possible Raynaud's phenomenon, and worsening libido?

Likely Diagnosis: Systemic Autoimmune/Connective Tissue Disease with Drug-Induced Component

This patient's constellation of symptoms—Raynaud's phenomenon, posterior cervical lymphadenopathy, fatigue, cobblestoning throat, scalp folliculitis, and reticular rash—strongly suggests an underlying systemic autoimmune or connective tissue disorder, potentially triggered or exacerbated by her CNS stimulant medications (Vyvanse and Qelbree). 1, 2

Critical Medication-Related Concerns

CNS Stimulants and Autoimmune Phenomena

• Vyvanse (lisdexamfetamine) and viloxazine (Qelbree) can induce Raynaud's syndrome and potentially systemic sclerosis (SSc). 1, 2
• Methylphenidate and amphetamine derivatives have documented associations with Raynaud's phenomenon that can progress to systemic sclerosis with skin changes, positive ANA, and pathological capillaroscopy. 2
• Symptoms typically appear and worsen over months following CNS stimulant use and may subside after cessation. 2
• The combination of Raynaud's phenomenon with reticular skin changes (likely livedo reticularis) in a patient on stimulants raises serious concern for drug-induced connective tissue disease. 1, 2

Cardiovascular Monitoring

• Long-term ADHD medication use (>3 years) is associated with increased cardiovascular disease risk, particularly hypertension and arterial disease. 3
• Her sinus tachycardia may be exacerbated by the combination of Vyvanse 60mg and metoprolol 25mg (which may be inadequate beta-blockade for stimulant-induced tachycardia). 3

Differential Diagnosis Priority

Primary Considerations

1. Drug-induced systemic sclerosis/scleroderma spectrum disorder - Most urgent given CNS stimulant exposure with Raynaud's and skin changes 2
2. Systemic lupus erythematosus (SLE) - Explains lymphadenopathy, fatigue, Raynaud's, photosensitivity, and potential livedo reticularis 2
3. Mixed connective tissue disease (MCTD) - Can present with overlapping features 2
4. Undifferentiated connective tissue disease (UCTD) - Early presentation before full criteria met 2

Secondary Considerations

1. Chronic viral reactivation (EBV, HHV-6) - Given hepatitis C history and lymphadenopathy 4
2. Allergic/vasomotor rhinitis with systemic features - Explains cobblestoning and sinus symptoms but not Raynaud's or lymphadenopathy 5

Immediate Diagnostic Workup

Essential Laboratory Studies

• Complete autoimmune panel:

  • ANA with reflex to specific antibodies (anti-dsDNA, anti-Smith, anti-RNP, anti-Scl-70, anti-centromere)
  • Rheumatoid factor and anti-CCP
  • Complement levels (C3, C4)
  • ESR and CRP
  • Complete blood count with differential
  • Comprehensive metabolic panel 2

• Raynaud's-specific evaluation:

  • Nailfold capillaroscopy (pathological findings support SSc) 2
  • Cold stimulation test if diagnosis unclear 1

• Infectious workup for lymphadenopathy:

  • Hepatitis C viral load (given history)
  • HIV testing (risk factor for atypical presentations) 6
  • EBV serologies (VCA IgM/IgG, EBNA)
  • Lyme disease serology confirmation (Western blot if not previously done) 4, 6

Imaging and Specialized Testing

• Lymph node evaluation: Ultrasound of posterior cervical nodes to assess size, architecture, and vascularity; nodes >1cm warrant close observation or biopsy if concerning features present 4
• Chest X-ray: Rule out hilar lymphadenopathy or interstitial lung disease (SSc complication) 2
• High-resolution CT chest (if pulmonary symptoms develop): Early SSc can affect lungs 2

Rhinitis-Specific Evaluation

• Allergy testing (skin prick or specific IgE): To differentiate allergic from non-allergic rhinitis and guide targeted therapy 5, 7
• Nasal endoscopy: Evaluate cobblestoning, rule out polyps, assess for vasomotor vs allergic changes 5, 7

Immediate Management Algorithm

Step 1: Address Medication-Induced Risk (URGENT)

Temporarily discontinue or significantly reduce Vyvanse dosage in consultation with prescribing psychiatrist, given strong association between CNS stimulants and progressive Raynaud's/SSc. 1, 2

• Monitor for 2-4 weeks to assess if Raynaud's symptoms improve with drug cessation 2
• Consider alternative ADHD management: atomoxetine has rare RS association but lower risk than stimulants; behavioral therapy; or lowest effective stimulant dose if symptoms improve 1
• Qelbree (viloxazine) continuation requires careful monitoring as it's a newer agent with less data on vascular effects 1

Step 2: Symptomatic Management While Awaiting Workup

For Raynaud's phenomenon:

• Avoid cold exposure, use hand warmers, dress warmly
• Consider calcium channel blocker (nifedipine extended-release 30-60mg daily) if symptoms severe and not contraindicated by metoprolol 1
• Discontinue metoprolol if switching to calcium channel blocker for Raynaud's management 1

For rhinitis symptoms:

• Initiate intranasal corticosteroid (fluticasone propionate 2 sprays each nostril daily or mometasone furoate 2 sprays each nostril daily) as first-line therapy for chronic nasal symptoms, cobblestoning, and sinus pressure 5, 8
• Add oral second-generation antihistamine (cetirizine 10mg or loratadine 10mg daily) for sneezing/itching if allergic component confirmed 5, 9
• Nasal saline irrigation (twice daily) for symptomatic relief and to clear secretions 9, 8

For scalp folliculitis:

• Topical antibacterial (mupirocin ointment or benzoyl peroxide wash)
• Consider seborrheic dermatitis treatment if scalp is also scaly (ketoconazole shampoo)

Step 3: Lymphadenopathy Observation Protocol

• Observe posterior cervical lymphadenopathy for 2-4 weeks if nodes are mobile, soft, and <2cm 4
• Immediate referral for biopsy if: nodes are rock hard, rubbery, fixed, >2cm, or in supraclavicular region 4
• Re-examine after autoimmune workup and stimulant discontinuation 4

Step 4: Specialist Referrals

Rheumatology (URGENT):

• Refer immediately given Raynaud's phenomenon with skin changes and potential drug-induced SSc 2
• Rheumatologist should perform nailfold capillaroscopy and interpret autoimmune panel 2

Allergy/Immunology:

• Refer for comprehensive allergy evaluation and management of rhinitis symptoms 5, 7
• Consider immunotherapy if specific allergens identified and pharmacotherapy inadequate 5

Otolaryngology:

• If rhinitis symptoms persist despite medical management or if structural abnormalities suspected 5

Management of Comorbid Conditions

Asthma Monitoring

• Viral URIs and untreated rhinitis can trigger asthma exacerbations 9, 8
• Ensure patient has appropriate rescue inhaler (SABA) and assess need for controller therapy 9
• Intranasal corticosteroids may improve both rhinitis and asthma control 8

Chronic Sinusitis Consideration

• Despite negative CT scan, patient has chronic sinus pain/pressure and cobblestoning suggesting chronic rhinosinusitis 5, 8
• Up to 60% of patients with recurrent/chronic sinusitis have underlying allergic rhinitis 8
• Treatment of allergic rhinitis with intranasal corticosteroids improves sinus symptoms 8

Libido and Quality of Life

• Decreased libido may be multifactorial: PTSD/anxiety medications, chronic illness, untreated rhinitis affecting sleep quality 5
• Allergic rhinitis significantly impacts sexual quality of life, which improves with appropriate treatment 5
• Fatigue from untreated autoimmune disease or chronic rhinitis affects overall functioning 5

Critical Pitfalls to Avoid

1. Do not dismiss Raynaud's phenomenon as benign in a patient on CNS stimulants - this can progress to systemic sclerosis with serious complications including digital ulceration and gangrene 1, 2

2. Do not continue stimulant medications without rheumatologic evaluation when Raynaud's and skin changes are present 2

3. Do not attribute all symptoms to rhinitis/sinusitis when systemic features (lymphadenopathy, Raynaud's, fatigue, rash) suggest connective tissue disease 5, 2

4. Do not delay lymph node biopsy if nodes develop concerning features (hard, fixed, >2cm, supraclavicular location) 4

5. Do not overlook medication interactions - metoprolol may mask tachycardia from stimulants but doesn't address underlying cardiovascular stress 3

6. Do not assume negative sinus CT rules out chronic rhinosinusitis - clinical diagnosis based on symptoms and examination findings 5, 8