Multiple Minute Digitate Hyperkeratoses Differential Diagnoses
- Author: Annie Wester, MS; Chief Editor: Dirk M Elston, MD more...
Several entities are often confused in the literature and on clinical examination. Note the following:
Punctate porokeratosis: Unlike multiple minute digitate hyperkeratosis (spiny hyperkeratosis), nearby epidermal alterations are generally noted, including dyskeratosis and hypogranulosis. Overall, keratinocyte changes do not exist under the cornoid lamellalike spines of minute digitate hyperkeratosis (spiny hyperkeratosis). Porokeratosis and multiple minute digitate hyperkeratosis are often confused in the literature.
Hyperkeratosis lenticularis perstans (also known as Flegel disease): Unlike multiple minute digitate hyperkeratosis, histopathology can show hypogranulosis. Furthermore, the hyperkeratosis in Flegel disease is not punctate in nature.
Follicular spicules: This is a paraneoplastic presentation of myeloma. The spines are commonly located on the nose and sometimes the ears. In these situations, the spicules are composed of immunoglobulin G-lambda accumulations. Furthermore, the lesions clear with remission of the neoplasm. The clinical presentation is almost identical to minute digitate hyperkeratosis (spiny hyperkeratosis). 
Lichen spinulosus: Lichen spinulosus: This is a follicular digitate keratosis that mainly affects the trunk and limbs. Follicular hyperkeratotic papules are grouped into 2- to 6-cm plaques, which aids in the diagnosis. It is frequently associated with atopic conditions, including asthma, allergies, and hay fever. 
Punctate keratoderma (often palmar or plantar): This appears as verrucalike papules that are depressed and contain a central horny plug. They are sometimes described as spicules and thus confused with minute digitate hyperkeratosis (spiny hyperkeratosis). These tiny keratoses may involve the entire palmoplantar surface or may be restricted to certain locations such as the crease. It is autosomal dominant in African Americans. Punctate keratoderma should not be confused with the name punctate keratosis used in a different entity.
Trichodysplasia spinulosa  : This condition is associated with immune suppression and polyomavirus infection. Less often used terms for this are pilomatrix dysplasia and cyclosporine-induced folliculodystrophy. This is a rare condition with follicular spiny projections. Like the spicules in myeloma, these also tend to appear on the face. Characteristic histological features include dilated hair follicles; hyperplastic hair bulbs; hyperplasia of inner root sheath cells with many large, eosinophilic, trichohyalin granules; and hypercornification (all thought to be abnormally maturing anagen follicles). It has been noted in patients with cancer and immune suppression and is considered to be secondary to a viral infection.  Electron microscopy studies have found 40-nm intranuclear polyhedral inclusions suggestive of polyoma viruses, a double-stranded DNA virus. Treatment with immune suppression reduction and/or antiviral medications often is effective.
Keratosis pilaris: This is a perifollicular process. Presentation is often in teen and preteen years. With a late-onset presentation, perform a biopsy to rule out the other keratotic differential diagnoses.
Multiple minute digitate hyperkeratosis is typically generalized; the only other conditions with widespread multiple keratoses are lichen spinulosus and phrynoderma. Multiple minute digitate hyperkeratoses differs from these in that its horns are nonfollicular and tend to be taller/thinner/rodlike. Furthermore, lichen spinulosus horns are typically grouped into discrete plaques, which can also help in differentiating it from multiple minute digitate hyperkeratoses.
Phrynoderma has a predilection for the dorsal thighs and forearms. It is rare in developed countries, as it is caused by various nutritional deficiencies, most commonly vitamin A.
A variety of rare disorders can produce localized digitate keratoses, as opposed to the generalized keratoses of multiple minute digitate hyperkeratoses. Multiple digitate keratoses of the palms and/or soles suggest spiny keratoderma or arsenical keratoses. Spiny keratoderma is histopathologically indistinguishable from multiple minute digitate hyperkeratoses but exhibits a completely different (palmoplantar) distribution.
Although some authors have proposed a relationship between sporadic multiple minute digitate hyperkeratoses and malignancy and/or inflammatory disorders, this contention was based on a broad definition of multiple minute digitate hyperkeratoses that included disorders that are now recognized as distinct from multiple minute digitate hyperkeratoses. These include the paraneoplastic facial hyperkeratotic spicules described above, as well as postirradiation digitate keratoses and palmoplantar spiny keratoderma. Adopting the more stringent criteria proposed by Caccetta et al, if they become more broadly accepted and cited, will greatly assist in clarifying the literature on this condition.
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