What systemic conditions can cause diffuse palmoplantar keratoderma in a 60‑year‑old man?

Systemic Conditions Causing Palmoplantar Keratoderma

Acquired diffuse palmoplantar keratoderma in a 60-year-old man should prompt immediate evaluation for internal malignancy, particularly lung and esophageal carcinomas, as this paraneoplastic presentation carries a poor prognosis. 1

Life-Threatening Causes Requiring Immediate Action

Malignancy-Associated PPK:

• Non-small-cell lung carcinoma is the most critical systemic cause to exclude, as PPK associated with malignancy carries poor prognosis 1
• Esophageal carcinoma also presents with acquired diffuse PPK 1
• Obtain chest radiography and sputum cytology immediately in any adult with new-onset diffuse PPK 1
• Frequent medical surveillance is mandatory once malignancy-associated PPK is identified 1

Infectious Systemic Causes

Tick-Borne Illnesses:

• Rocky Mountain spotted fever presents with maculopapular rash spreading to palms and soles 2-4 days after fever onset, with 5-10% mortality if untreated 2
• Initiate doxycycline immediately if fever, palmar rash, and tick exposure are present—do not wait for confirmation 2
• Ehrlichiosis involves palms/soles in 30% of adults and 60% of children, with 3% case-fatality rate 2

Other Infectious Causes:

• Syphilis can cause palmoplantar hyperkeratosis 3
• Tuberculosis may present with PPK 3
• Human papillomavirus infection causes palmoplantar keratosis 3
• Mycoses and scabies are additional infectious etiologies 3

Inflammatory Systemic Conditions

Psoriasis:

• Palmoplantar psoriasis affects 40% of psoriasis cases, presenting with well-demarcated erythematous plaques with thick silvery scale and marked hyperkeratosis 4
• Treat with topical clobetasol solution, oral acitretin 25mg daily, or soak PUVA for severe disease 2

Eczematous Conditions:

• Hyperkeratotic hand-foot eczema shows vesicles, scaling, erythema, and fissuring with yellow-white scaling, affecting 31% of cases 4
• Dyshidrotic eczema requires moderate-to-high potency topical corticosteroids (prednicarbate 0.02% or betamethasone valerate 0.1%) twice daily for 2 weeks 2

Lichen Planus:

• Common inflammatory cause of acquired PPK 3

Toxic and Environmental Causes

• Arsenic poisoning causes palmoplantar hyperkeratosis 3
• Polycyclic aromatic hydrocarbons exposure leads to PPK 3
• Irritant contact dermatitis from frequent hand washing (>10 times daily) causes acute lipid loss and barrier disruption, particularly with water temperature >40°C 2

Drug-Induced PPK

Chemotherapy-Associated:

• Chemotherapy-induced hand-foot syndrome causes redness, marked discomfort, swelling, and tingling in palms 2
• For Grade 1-2, continue drug and apply topical low/moderate steroid 2
• For Grade ≥3, interrupt treatment until Grade 0/1, use oral doxycycline 100mg twice daily for 6 weeks, topical steroids, and consider systemic corticosteroids 2

BRAF/MEK Inhibitors:

• Palmoplantar keratoderma occurs in 1-2% of patients on dabrafenib/trametinib or vemurafenib/cobimetinib combinations 5

Other Medications:

• Investigate all prescription, over-the-counter pharmaceuticals, and herbal remedies through careful medication history 2

HIV-Associated Disease

• HIV-associated pruritus with palmar involvement responds better to indomethacin 25mg three times daily than sedating antihistamines, though gastric intolerance may occur 2

Pregnancy-Related Cause

• Intrahepatic cholestasis of pregnancy presents with palmar pruritus and requires serum bile acid measurement due to stillbirth risk 4

Diagnostic Algorithm for a 60-Year-Old Man

1. Assess for systemic symptoms: fever, malaise, weight loss, night sweats to exclude life-threatening infectious or malignant causes 2
2. Obtain chest radiography and sputum cytology to exclude lung carcinoma 1
3. Detailed exposure history: recent tick exposure, travel history, medication use (including chemotherapy), occupational exposures to arsenic or hydrocarbons 2, 3
4. Laboratory evaluation: CBC, liver function tests, lipid panel before systemic therapy 4
5. Consider HIV testing if risk factors present 2

Critical Pitfalls

• Never dismiss fever with palmar rash as simple dermatitis—Rocky Mountain spotted fever mortality increases dramatically with delayed doxycycline treatment 4
• Acquired diffuse PPK in an adult without family history mandates malignancy workup, as prognosis is poor when PPK is paraneoplastic 1
• The disproportionate impact of palmoplantar disease on quality of life justifies systemic therapy when topical treatments fail 4