In a 16‑year‑old female with diffuse poorly localized pain, a history of postural orthostatic tachycardia syndrome, and visible stretch marks, what is the most likely diagnosis and recommended evaluation and management?

Diffuse Pain in 16-Year-Old Female with POTS and Stretch Marks

Most Likely Diagnosis

The most likely diagnosis is joint hypermobility syndrome (Ehlers-Danlos syndrome hypermobility type) presenting with diffuse musculoskeletal pain in the context of known POTS. 1, 2

Clinical Reasoning

This presentation represents a classic triad that strongly suggests connective tissue disorder:

• POTS and joint hypermobility syndrome frequently coexist, with joint hypermobility being one of the most common comorbidities in POTS patients 1, 3, 2
• Stretch marks (striae) in an adolescent without obesity or rapid growth are a hallmark sign of connective tissue fragility, particularly in Ehlers-Danlos syndrome 4
• Diffuse, poorly localized pain is characteristic of joint hypermobility syndrome, often affecting multiple body regions and worsening with activity 4, 2

The pathophysiologic link is well-established: connective tissue abnormalities lead to both vascular compliance issues (contributing to POTS) and musculoskeletal instability (causing pain) 2, 5.

Recommended Evaluation

Immediate Clinical Assessment

• Perform Beighton score assessment (≥6/9 points diagnostic in pre-pubertal children; ≥5/9 in adolescents post-puberty) to quantify joint hypermobility 1, 3
• Document skin findings: assess for hyperextensibility, atrophic scarring, easy bruising, and the quality/distribution of striae 4
• Detailed pain characterization: location, timing, relationship to activity, and any joint instability or subluxations 4

Essential Laboratory Testing

• Complete blood count and inflammatory markers (ESR, CRP) to exclude inflammatory arthritis
• Thyroid function tests to rule out hyperthyroidism as a POTS mimic 1, 3
• Iron studies (ferritin, transferrin saturation) as iron deficiency contributes to hypovolemic POTS and may worsen symptoms 1, 3
• Celiac disease screening (tissue transglutaminase antibodies) given the association with hypermobility disorders 3

Specialized Testing When Indicated

• 12-lead ECG to exclude cardiac arrhythmias or conduction abnormalities 1, 3
• Consider autoantibody testing if post-viral onset or autoimmune features are present 3
• Baseline serum tryptase only if multisystem symptoms suggest mast cell activation syndrome (flushing, urticaria, gastrointestinal symptoms) 3

Management Approach

First-Line Non-Pharmacologic Interventions

• Physical therapy focused on joint stabilization and proprioceptive training is essential for hypermobility-related pain 4
• Graduated exercise reconditioning program starting with recumbent exercises (rowing, swimming) to address POTS deconditioning 1, 6
• Compression garments (20-30 mmHg waist-high stockings) to improve venous return 1, 6
• Increased fluid intake (2-3 liters daily) and salt supplementation (6-10 grams daily) for POTS management 1, 6

Pain Management Strategy

• Avoid NSAIDs if possible due to potential for easy bruising in connective tissue disorders 4
• Consider gabapentin or pregabalin for neuropathic-type pain, which is common in hypermobility syndromes 4
• Low-dose tricyclic antidepressants (amitriptyline 10-25 mg at bedtime) may address both pain and POTS-related sleep disturbance 6

POTS-Specific Pharmacotherapy (If Non-Pharmacologic Measures Insufficient)

• Beta-blockers (propranolol 10-20 mg twice daily, titrated) if hyperadrenergic features predominate 6, 5
• Midodrine (2.5-10 mg three times daily) for neuropathic POTS with inadequate vasoconstriction 6, 5
• Fludrocortisone (0.1-0.2 mg daily) for hypovolemic POTS phenotype 6, 5

Critical Diagnostic Pitfalls to Avoid

• Do not dismiss pain as "just anxiety" or malingering in POTS patients—musculoskeletal symptoms are real and often indicate underlying hypermobility 4, 2
• Avoid extensive imaging for pain without clear trauma history, as hypermobility-related pain is typically functional rather than structural 4
• Do not order broad autoimmune or food allergy panels without specific clinical indication, as false positives complicate management 3
• Recognize that mast cell activation testing should be reserved for patients with multisystem allergic-type symptoms, not routine POTS evaluation 3

Multidisciplinary Coordination

• Establish care with a primary physician experienced in autonomic disorders for ongoing POTS management 7
• Refer to physical medicine/rehabilitation for structured exercise program and bracing if needed 4
• Consider genetics referral if clinical features strongly suggest Ehlers-Danlos syndrome for formal classification and family counseling 4, 2
• Screen for mental health comorbidities (depression, anxiety) which are common and require targeted treatment 1, 3

Special Perioperative Considerations

If any surgical intervention becomes necessary, be aware that POTS patients with hypermobility require specialized anesthesia planning due to increased risk of complications including dysautonomia during anesthesia, excessive bleeding from tissue fragility, and poor wound healing 4.