What is the differential diagnosis for a 75‑year‑old woman with chronic dry cough, modestly elevated C‑reactive protein, longstanding bilateral leg edema, left wrist and hand pain with tenderness over the dorsal base of the thumb and grip weakness, normal blood pressure, clear lungs, normal heart sounds, negative Tinel’s and Phalen’s tests, former smoker, diabetes on medication, and currently taking celecoxib?

Differential Diagnosis for This 75-Year-Old Woman

The differential diagnosis should prioritize three distinct clinical problems: (1) chronic dry cough with elevated CRP, (2) bilateral leg edema, and (3) left wrist/hand pain with weakness—each requiring separate diagnostic consideration.

Chronic Dry Cough with Elevated CRP

The most likely causes are upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD), which account for 92-100% of chronic cough cases in nonsmoking adults with normal chest examination 1.

Primary Considerations:

• Upper Airway Cough Syndrome (UACS) is the most common single cause and can be completely "silent" without nasal symptoms 1, 2. The morning phlegm production (yellow sputum) strongly suggests postnasal drainage 2.
• Asthma or cough-variant asthma is the second most common cause and may present with cough as the only symptom, without wheezing or dyspnea 1.
• GERD is the third most common cause and can be "silent GERD" without heartburn, with cough as the sole manifestation 1.
• Drug-induced cough must be considered—specifically, diabetes medications should be reviewed. If she is taking an ACE inhibitor for diabetic nephropathy or hypertension, this could explain the chronic cough that started with diabetes medication 3, 1.

Important Caveat:

Up to 25% of patients have multiple contributing diagnoses, so all three common causes must be considered regardless of symptoms 1. The character, timing, or productivity of cough has no diagnostic value and should not be used to rule in or rule out any diagnosis 1.

Uncommon but Important Consideration:

• Giant cell arteritis (GCA) should be considered in this 75-year-old with unexplained elevated CRP and chronic dry cough 4. Dry cough occurs in 13.6% of GCA patients and correlates with inflammatory markers (mean CRP 153.8 mg/L in patients with dry cough versus 94 mg/L without) 4.
• Sarcoidosis presents with chronic cough in 40-80% of symptomatic patients and should be considered with elevated CRP 3.
• Nonasthmatic eosinophilic bronchitis (NAEB) is an increasingly recognized cause that responds predictably to inhaled corticosteroids 1, 5.

Bilateral Leg Edema

The most probable cause in a 75-year-old is chronic venous insufficiency, followed by heart failure 6.

Primary Considerations:

• Chronic venous insufficiency is the most common cause of bilateral leg edema in older patients 6. The several-year history without cellulitis or new skin changes supports this diagnosis.
• Heart failure is also common, though the normal heart sounds on examination make this less likely 6.
• Drug-induced edema from celecoxib (NSAID) is a significant consideration, as NSAIDs can cause leg edema 3, 6.

Less Likely but Important:

• Renal disease or liver disease are much rarer causes but should be evaluated with basic laboratory tests 6.

Left Wrist and Hand Pain with Weakness

The clinical presentation—dorsal wrist tenderness at the base of the thumb, pain with fine movements, grip weakness, and negative Tinel's/Phalen's tests—strongly suggests de Quervain's tenosynovitis or first carpometacarpal (CMC) joint osteoarthritis rather than carpal tunnel syndrome.

Primary Considerations:

• De Quervain's tenosynovitis: Tenderness over the dorsal wrist at the base of the thumb, pain with fine movements (picking up pen, holding coffee cup), and weakness are classic features.
• First CMC joint osteoarthritis: Common in elderly women, presents with base-of-thumb pain, weakness with pinch and grip, and difficulty with fine motor tasks.
• Inflammatory arthritis (rheumatoid arthritis): Given the elevated CRP, this must be considered 3. However, the unilateral presentation and lack of small joint swelling make this less typical. RA typically involves metacarpophalangeal joints, proximal interphalangeal joints, and wrists bilaterally 3.

Important Diagnostic Point:

The negative Tinel's and Phalen's tests effectively rule out carpal tunnel syndrome as the primary diagnosis.

Consideration of Systemic Disease:

• Polymyalgia rheumatica or giant cell arteritis: The combination of elevated CRP, chronic cough, and joint pain in a 75-year-old warrants consideration of these conditions 4.
• Celecoxib response: The fact that celecoxib is helping the hand pain suggests an inflammatory component, supporting osteoarthritis or inflammatory arthritis 3.

Critical Next Steps

A systematic approach requires:

1. Review all medications for ACE inhibitors (causing cough) and NSAIDs (causing edema) 1, 6.
2. Laboratory evaluation: ESR, RF, anti-CCP antibodies (for RA), and basic metabolic panel (for renal causes of edema) 3, 6.
3. Empiric treatment trial for UACS with first-generation antihistamine-decongestant combination 1, 2.
4. Consider temporal artery evaluation (ESR, temporal artery ultrasound, or biopsy) if CRP remains significantly elevated, given age and symptom constellation 4.