Multiple Minute Digitate Hyperkeratoses

Updated: Jun 19, 2018
Author: Annie Wester, MD, MS; Chief Editor: Dirk M Elston, MD 

Overview

Background

Multiple minute digitate hyperkeratosis (MMDH) or spiny hyperkeratosis (SH) is a rare nonfollicular digitate keratosis affecting the trunk and limbs.[1, 2]  Although some confusion has existed in past terminology, more recent works have emphasized the separation of multiple minute digitate hyperkeratosis (spiny hyperkeratosis) from any association with porokeratosis. Keratosis pilaris[3]  also is often confused with multiple minute digitate hyperkeratosis (spiny hyperkeratosis) in clinical diagnosis.[4] Note the following important clarification of the most often interchanged terms in the literature:

  • Spiny hyperkeratosis - Synonym for multiple minute digitate hyperkeratosis

  • Spiny keratoderma - Different process that is included in the palmoplantar keratoderma disease group[5]

  • Music box spines - Term applied to multiple conditions, including multiple minute digitate hyperkeratosis (spiny hyperkeratosis)

  • Follicular spicules - Most often used to describe the myeloma-associated process; also used in keratosis pilaris and multiple minute digitate hyperkeratosis (spiny hyperkeratosis); multiple minute digitate hyperkeratosis (spiny hyperkeratosis) is not commonly follicular, as is described below; follicular spicules should not be confused with trichodysplasia, which can also be seen in myelomas and is described in more detail in Diagnostic Considerations

  • Porokeratosis and orthokeratosis - Most classically associated with premalignant lesions and actinic processes; however, have also been used to describe multiple minute digitate hyperkeratosis (spiny hyperkeratosis)

A list of other similar-appearing entities that are easily confused can be found in Diagnostic Considerations.

Pathophysiology

The exact cause of multiple minute digitate hyperkeratosis (spiny hyperkeratosis) is not known, although cases have been associated with autosomal dominant genetic inheritance, postinflammatory changes, and sporadic occurrence.

As more reports of multiple minute digitate hyperkeratosis (spiny hyperkeratosis) are published, it will be confirmed whether the reported associations with systemic disease are real or whether they represent chance occurrences. It is also important to note that many of the above divisions may be associated with similar presenting clinical conditions and larger studies are required to validate such classifications before broad adoption of these concepts occurs.[6] So many of these proposed divisions/classifications are based on case reports, and the validity of use is still hard to determine.

Etiology

No one cause of minute digitate hyperkeratosis (spiny hyperkeratosis) is known. The exact cause of multiple minute digitate hyperkeratosis (spiny hyperkeratosis) is not known, though cases have been associated with autosomal dominant genetic inheritance, postinflammatory changes, and sporadic occurrence.

Epidemiology

Frequency

Multiple minute digitate hyperkeratosis (spiny hyperkeratosis) is a rare chronic disorder of keratinization. The incidence and prevalence have not yet been determined.

Race

No race predilection has been reported for minute digitate hyperkeratosis (spiny hyperkeratosis) in the evidence-based literature.

Sex

A slight male prevalence has been noted for minute digitate hyperkeratosis (spiny hyperkeratosis).[7]

Age

No age predilection has been reported for minute digitate hyperkeratosis (spiny hyperkeratosis) in the evidence-based literature. However, multiple minute digitate hyperkeratosis appears to be most reported in the second and third decades of life and in the fifth and sixth decades of life.

Classification

One group has proposed a classification based on certain characteristics of the multiple minute digitate hyperkeratosis presentation.[8, 9]

Familial form of multiple minute digitate hyperkeratosis

These are considered autosomal dominant in the majority of cases. The most common age at presentation is the second and third decade.

Postinflammatory/insult form of multiple minute digitate hyperkeratosis

This type is reported after various skin insults, including radiotherapy, sun damage, and use of systemic or topical drugs (eg, cyclosporin, simvastatin, etretinate). This category brings to light the question of trauma as a trigger or facilitator of multiple minute digitate hyperkeratosis, as is noted in other diseases of keratinization.

Sporadic multiple minute digitate hyperkeratosis

Patients with this form tend to present in the fifth and sixth decade. Sporadic multiple minute digitate hyperkeratosis may be associated with internal malignancy or other systemic disease. In particular, it is possible that the myeloma-related spicules are a variation of multiple minute digitate hyperkeratosis (spiny hyperkeratosis), although this differentiation is elaborated on in the sections below.

Prognosis

No reports in the evidence-based literature have examined the prognosis of minute digitate hyperkeratosis (spiny hyperkeratosis). However, the lesions themselves are believed to be benign in nature.

The larger unanswered question is the role of associated findings that may occur with minute digitate hyperkeratosis (spiny hyperkeratosis). Currently, multiple minute digitate hyperkeratosis appears to be found inconsistently with other disease processes. Any further associations would require a larger series of patients or pathogenic, molecular, or genetic studies to correlate the somewhat random findings noted to date. Anecdotal and clinical observations have suggested early-onset/congenital multiple minute digitate hyperkeratosis (spiny hyperkeratosis) differs from late-onset/acquired forms. Although not backed by a large body of evidence, the late-onset multiple minute digitate hyperkeratosis (spiny hyperkeratosis) is presumed to have an increased association with inflammatory or malignant disease in some cases. However, the evidence for these associations is anecdotal.[7, 10]

 

Presentation

History

Patients with minute digitate hyperkeratosis (spiny hyperkeratosis) report multiple tiny spiky hyperkeratotic projections on the trunk or limbs. Sometimes, small domed papules can be seen. Patients rarely report any other symptomatology.

Physical Examination

Lesions of minute digitate hyperkeratosis (spiny hyperkeratosis) are white, yellow, brown, or flesh colored nonfollicular spicules, as shown in the image below. They are occasionally flat-topped, dome shaped, or crateriform papules. They generally measure 0.5-5 mm long and 0.3-3 mm in diameter. Most reported cases note presence on the trunk and limbs, with sparing of the face and palmoplantar surfaces. However, no evidence-based review has been performed on the location of multiple minute digitate hyperkeratosis.

Multiple minute digitate hyperkeratosis. Published Multiple minute digitate hyperkeratosis. Published with permission granted from and with copyright retained by the American Medical Association. Clark JL, Davis G, Bennett DD. Arch Dermatol. 2008 Aug;144(8):1051-6.
 

DDx

Diagnostic Considerations

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). [4]
  • 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. [1]
  • 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 [11] : 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. [1]  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.[1]

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.[12]

Workup
 

Workup

Laboratory Studies

The extent of examination and laboratory tests ordered in cases of minute digitate hyperkeratosis (spiny hyperkeratosis) should be guided by the history and physical examination findings. Some physicians recommend a CBC count, a comprehensive metabolic panel, and age-appropriate cancer screening for sporadic cases. Many reported associations exist, including chronic lymphocytic leukemia. However, none is proven to be beyond coincidental co-occurrence.[13]

Imaging Studies

Age- and symptom-appropriate appropriate examinations should be ordered in the workup of minute digitate hyperkeratosis (spiny hyperkeratosis). The finding of multiple minute digitate hyperkeratosis alone may be incidental. In current practice, multiple minute digitate hyperkeratosis findings do not indicate the need for specific imaging tests.

Other Tests

No other tests are needed for minute digitate hyperkeratosis (spiny hyperkeratosis).

Procedures

Skin punch or shave biopsy may be needed to diagnose and differentiate minute digitate hyperkeratosis (spiny hyperkeratosis) from other similar-appearing punctate keratoses.

Histologic Findings

Histopathology reveals compact orthokeratotic hyperkeratotic projections that may be perifollicular but overall should be a non-follicular process. This focal column of hyperkeratosis resembles a cornoid lamella.[14] Of note, some reports in the literature list parakeratosis as a finding, rather than orthokeratosis.

The granular layer appears intact and no changes are noted in the epidermis other than the hyperkeratosis. Some reports have described granular layer changes that include increased or decreased granulation, but these may be a distinct histoclinical entity. The dermis shows no major alterations.

A clinicohistologic-based classification has been proposed, although it is not yet universally established.[15] It is divided as follows:

  • Type I minute digitate hyperkeratosis (spiny hyperkeratosis) (parakeratotic columns): It is referred to as type Ia if it is palmoplantar and type Ib if it is disseminated. Rather than random number assignment, it may be more clear and simple to name it using its description. For example, Ia could best be called palmoplantar parakeratotic columnar.

  • Type II minute digitate hyperkeratosis (spiny hyperkeratosis) (orthokeratotic columns): It is referred to as type IIa if it is palmoplantar and type IIb if it is disseminated.

  • Type III minute digitate hyperkeratosis (spiny hyperkeratosis) (porokeratotic eccrine ostial and dermal duct nevus): This type is clinically linear in presentation and histologically shows parakeratosis associated with sweat duct structures.

This proposed classification brings to light the lack of clarity in the literature on this disease process. Types I-III may be related, or they may be different entities that have somewhat similar appearances. At this point, the literature does not yet favor the use of the criteria proposed above. In fact, new criteria and algorithms are regularly proposed.[12]

Other proposed divisions include the following[16] :

  • Disseminated orthokeratotic

  • Disseminated parakeratotic

  • Palmoplantar orthokeratotic

  • Palmoplantar parakeratotic

Immunoglobulin G deposits have been noted in multiple minute digitate hyperkeratosis associated with paraproteinemia, but these lesions do not typically occur on the extremities.[17] These lesions may also be a different entity known as spicules, which is seen in myeloma patients.

The finding of hyperkeratosis has also been described in 2 manners, as either spiked/digitiform or as columns. The authors proposed a potential difference in etiology and pathologic trigger based on the difference in histology. The most probable explanation is that the spiked/digitiform type is a different process altogether and not actual multiple minute digitate hyperkeratosis.

Ultrastructural studies show smaller-than-normal keratohyalin granules. Lamellar (Odland) bodies are normal.[18] Desmosome and basement membrane density is not known to be altered but has not been studied in detail. See the image below.

Multiple minute digitate hyperkeratosis. Published Multiple minute digitate hyperkeratosis. Published with permission granted from and with copyright retained by the American Medical Association. Clark JL, Davis G, Bennett DD. Arch Dermatol. 2008 Aug;144(8):1051-6.

Staging

Staging may be needed if an associated pathology is noted, as indicated in Pathophysiology.

 

Treatment

Medical Care

No large studies on treatment options for minute digitate hyperkeratosis (MMDH) (spiny hyperkeratosis) have been performed. Improvement in minute digitate hyperkeratosis (spiny hyperkeratosis) has been reported with treatment using the following agents:

  • Topical keratolytics combined with topical emollients

  • Tretinoin cream and oral vitamin A

  • Topical 5-fluorouracil cream

Resolution without treatment has also been reported.[19]

Surgical Care

The lesions of minute digitate hyperkeratosis (spiny hyperkeratosis) can be trimmed or clipped as needed.

Diet

Nutrition is an important consideration when evaluating keratinization disorders. A review of nutritional status should be performed.

Long-Term Monitoring

Follow patients on a yearly basis because of the rarity of minute digitate hyperkeratosis (spiny hyperkeratosis). In particular, an annual skin examination and follow up by a primary care physician for age-appropriate screenings are recommended.