What is the differential diagnosis for dry eyes, fatigue, and suprapubic discomfort?

Differential Diagnosis: Dry Eyes, Fatigue, and Suprapubic Discomfort

Primary Consideration: Sjögren's Syndrome

The combination of dry eyes, fatigue, and suprapubic discomfort (suggesting bladder/urinary symptoms or interstitial cystitis) strongly suggests Sjögren's syndrome as the unifying diagnosis, which requires immediate serological workup and rheumatology referral. 1

Why Sjögren's Syndrome is the Leading Diagnosis

• Approximately 10% of patients with clinically significant aqueous tear deficiency dry eye have underlying Sjögren's syndrome 1
• Sjögren's syndrome should be suspected particularly in non-elderly women with rapid onset and/or marked severity of tear production deficiency 1
• The female-to-male ratio is 20:1, making this especially relevant if the patient is female 1
• Fatigue is a cardinal systemic symptom of Sjögren's syndrome that often accompanies the sicca features 1
• Suprapubic discomfort may represent interstitial cystitis or bladder dysfunction, which are well-recognized extraglandular manifestations of Sjögren's syndrome 1

Immediate Diagnostic Workup Required

Order the following serological tests immediately for any patient with dry eyes plus systemic symptoms like fatigue:

• Anti-SSA/Ro antibody (scores 3 points in diagnostic criteria) 1
• Anti-SSB/La antibody (part of diagnostic panel) 1
• Rheumatoid factor 1
• Antinuclear antibody (ANA) 1
• Consider point-of-care testing that includes additional biomarkers (SP1, CA6, PSP) 1

Diagnostic criteria for Sjögren's syndrome require a weighted score ≥4 from:

• Anti-SSA/Ro positivity (3 points) 1
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² (3 points) 1
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4 (1 point) 1
• Schirmer test ≤5 mm/5 minutes without anesthesia (1 point) 1
• Unstimulated salivary flow rate ≤0.1 mL/minute (1 point) 1

Critical Prognostic Implications

This diagnosis is potentially life-threatening and requires urgent attention:

• Primary Sjögren's syndrome has the strongest association with lymphoid proliferative malignancy among autoimmune diseases 1
• Patients with decreased C4 levels at diagnosis have higher risk of developing lymphoma 1
• Risk of potentially life-threatening vasculitic disorders exists 1
• Ocular complications include scleritis, sterile keratitis, and uveitis 1

Mandatory Rheumatology Referral

All patients with suspected or confirmed Sjögren's syndrome must be co-managed with a rheumatologist due to multiple possible comorbid systemic conditions 1

Secondary Differential Considerations

Other Autoimmune/Systemic Causes of Dry Eye with Fatigue

• Rheumatoid arthritis - associated with dry eye and systemic fatigue 1
• Systemic lupus erythematosus - can cause dry eye, fatigue, and urinary symptoms 1
• Sarcoidosis - multisystem disease with dry eye, fatigue, and potential genitourinary involvement 1
• Graft-versus-host disease (GVHD) - if patient has transplant history 1

Medication-Induced Dry Eye

Review all medications, particularly:

• Antidepressants (including duloxetine/Cymbalta which specifically causes dry eye syndrome) 2
• Antihistamines - anticholinergic effects reduce tear production 1
• Diuretics - can worsen dry eye 1
• Beta-adrenergic antagonists 1
• Any medication with anticholinergic effects 1

Isolated Dry Eye Disease

If serologies are negative and no systemic disease identified:

• Meibomian gland dysfunction is the most common cause of evaporative dry eye 1
• Age and female gender are major risk factors for primary dry eye 1
• Environmental factors (low humidity, air conditioning, screen time) worsen symptoms 2

Suprapubic Discomfort Alternative Causes

If not related to Sjögren's syndrome, consider:

• Urinary tract infection
• Interstitial cystitis (can occur independently)
• Bladder dysfunction
• Gynecological pathology in females

Clinical Pitfalls to Avoid

• Do not dismiss dry eye as a benign condition when accompanied by systemic symptoms - this combination mandates workup for autoimmune disease 1
• Ocular fatigue is a major symptom of dry eye (71.3% of symptomatic dry eye patients report ocular fatigue), so do not attribute fatigue solely to systemic causes without addressing the dry eye 3
• Poor correlation exists between dry eye symptoms and objective signs - patients may have severe symptoms with minimal findings 4, 5
• Do not delay rheumatology referral - early diagnosis and treatment of Sjögren's syndrome may be lifesaving given malignancy risk 1

Immediate Management While Awaiting Workup

• Artificial tears/ocular lubricants for symptomatic relief 2
• Environmental modifications (humidifiers, reduced screen time, avoid direct air flow) 2
• Lid hygiene if meibomian gland dysfunction present 1
• Ophthalmology referral if moderate-to-severe symptoms, lack of response to lubricants, or progressive vision changes 2