What causes a skin lesion on the hand with oral ulcers?

Differential Diagnosis of Skin Lesions on Hand with Oral Ulcers

The combination of hand skin lesions with oral ulcers most commonly suggests Behçet's disease, pemphigus vulgaris, erythema multiforme, or hand-foot-and-mouth disease, with the specific diagnosis depending on lesion morphology and distribution. 1

Primary Diagnostic Considerations

Behçet's Disease

• Behçet's disease classically presents with recurrent oral ulcers combined with skin lesions including papulopustular lesions, erythema nodosum, and pathergy (skin hyperreactivity to minor trauma). 1
• Look for bipolar aphthosis—simultaneous oral and genital ulcers—which strongly suggests this diagnosis. 2
• The hand lesions in Behçet's may appear as papulopustular eruptions or nodular lesions. 1
• Pathergy testing (positive skin reaction to needle prick) supports the diagnosis. 1

Pemphigus Vulgaris

• Pemphigus vulgaris typically begins with painful oral ulcers (in 50-70% of cases) followed weeks to months later by flaccid bullae on the skin that rupture easily, leaving erosions. 1, 3
• The hand can be affected with characteristic flaccid blisters that demonstrate a positive Nikolsky sign (skin separates with gentle lateral pressure). 1
• Oral lesions appear as painful erosions after bullae rupture, often affecting the buccal mucosa, palate, and gingiva. 1, 3
• Diagnosis requires skin biopsy with direct immunofluorescence showing intercellular IgG deposition. 1, 3

Erythema Multiforme

• Erythema multiforme presents with acute-onset target lesions on the hands (classic distribution) accompanied by oral erosions. 4, 5
• The hand lesions are distinctive targetoid papules with central clearing or dusky centers. 4
• Oral involvement shows hemorrhagic crusting of lips and erosions. 4, 5
• Often triggered by herpes simplex virus infection or medications. 4, 5

Inflammatory Bowel Disease

• Crohn's disease commonly causes oral ulceration that may coincide with cutaneous manifestations including pyoderma gangrenosum or erythema nodosum affecting the extremities. 1, 2
• Inquire specifically about abdominal pain, diarrhea, and weight loss. 1
• The oral ulcers in Crohn's may be aphthous-like or linear "knife-cut" ulcers. 1

Essential Diagnostic Workup

Initial Laboratory Testing

• Obtain full blood count, fasting glucose, HIV antibody, syphilis serology, and nutritional markers (vitamin B12, folate, iron) before proceeding to biopsy. 2
• These tests exclude contraindications to biopsy and provide diagnostic clues for systemic diseases. 1, 2
• Elevated glucose suggests risk for deep fungal infections presenting with oral ulcers. 1, 2

Biopsy Indications

• Any oral ulcer persisting beyond 2 weeks or hand lesion of unclear etiology requires biopsy for histopathologic examination. 1, 6, 2
• For suspected pemphigus, obtain perilesional skin for direct immunofluorescence in addition to routine histology. 1, 3
• Ensure adequate biopsy depth—superficial biopsies miss diagnostic features. 1, 6
• If initial biopsy shows only nonspecific inflammation, consult superior pathologists or repeat the biopsy. 1

Specialized Testing

• Consider serum antibodies (Dsg1, Dsg3 for pemphigus; BP180, BP230 for pemphigoid) when autoimmune blistering disease is suspected. 1
• Direct immunofluorescence is essential for diagnosing pemphigus vulgaris and other autoimmune bullous diseases. 1, 3
• Pathergy testing may support Behçet's disease diagnosis. 1

Critical Red Flags Requiring Urgent Evaluation

• Solitary chronic ulcers >2 weeks must be biopsied to exclude squamous cell carcinoma or lymphoma. 1, 2, 4
• Atypical features suggesting malignancy include indurated borders, lack of pain, and progressive growth. 1, 2
• Widespread erosions with positive Nikolsky sign suggest pemphigus and require urgent dermatology referral. 1
• Constitutional symptoms (fever, weight loss, night sweats) with oral ulcers raise concern for lymphoma or systemic infection. 1

Specialist Referral Algorithm

• Refer to oral medicine or dermatology for any oral ulcer lasting >2 weeks or not responding to 1-2 weeks of empiric treatment. 1, 6
• Oral medicine specialists can perform specialized diagnostic procedures and coordinate multidisciplinary care. 6
• For suspected Behçet's disease, rheumatology consultation is appropriate. 1
• Gastroenterology involvement is needed when inflammatory bowel disease is suspected. 1, 6

Common Diagnostic Pitfalls

• Relying solely on topical treatments without establishing definitive diagnosis delays identification of malignancy or systemic disease. 6, 2
• Overlooking medication history misses NSAID-induced ulceration or drug-induced pemphigus. 2
• Inadequate biopsy technique (too small or superficial) yields nondiagnostic results. 1, 6
• Failing to inquire about genital ulcers misses the diagnosis of Behçet's disease. 1, 2
• Not examining for skin lesions elsewhere on the body limits diagnostic accuracy. 4, 7