This presentation may overlap with inherited palmoplantar keratodermas (PPK), and be confused with them in the absence of personal and family history. In this section, the inherited keratodermas will not be addressed. Clinical differential diagnosis includes
Tinea , psoriasis and CHE may involve the soles of the feet.

Rarely, a patient with the above clinical presentation may be harboring mycosis fungoides (MF) and much more rarely a paraneoplastic disorder (paraneoplastic palmoplantar keratoderma). Patients with pityriasis rubra pilaris (PRP) and papulosquamous-secondary syphilis who have palmoplantar involvement are easily diagnosed on the basis of having other manifestations of PRP and syphilis .

The most common differential diagnosis submitted with a biopsy specimen from the palm or sole is dermatitis, tinea , and psoriasis. If there are coexisting pustules the differential diagnosis is palmoplantar pustular psoriasis and tinea, and less frequently dermatitis with secondary bacterial infection. Clinical Clues

Tinea is strongly suspected if the hand involvement is unilateral, especially in the presence of bilateral plantar involvement (the so-called two-foot, one-hand tinea). Palmoplantar tinea varies in clinical morphology from fine scaling and desquamation (a common presentation in asymptomatic patients) to redness and scaling to pustules and bullae. An active inflammatory border may be seen. Some nails, especially toenails, may show evidence of onychomycosis.Plaque psoriasis of the palms and soles is very close in clinical appearance to that of plaque psoriasis on other parts of the skin surface. Occasionally, patients with palmoplantar plaque psoriasis may have mild lesions on the elbows, knees, or scalp which they may not be aware of. If present, characteristic nail changes are helpful in confirming the diagnosis of psoriasis.