Nevus Comedonicus

Background

In 1895, Kofmann^[1] described the first case of nevus comedonicus. It manifests as groups of closely set, dilated follicular openings with dark keratin plugs resembling comedones. The majority of cases are isolated. However, nevus comedonicus may be part of nevus comedonicus syndrome in association with skeletal or central nervous system anomalies, ocular abnormalities, and cutaneous defects.^{[2, 3, 4]}

See the image below.

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Nevus comedonicus. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/lesions/com-naev1.jpg).

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Pathophysiology

Many consider nevus comedonicus to be a hamartoma deriving from a failure of the mesodermal part of the folliculosebaceous unit to develop properly, with subsequent abnormal differentiation of the epithelial portion. The follicular structures that result are unable to form terminal hair or sebaceous glands and are capable only of producing soft keratin, which accumulates in the adnexal orifices and produces the comedonelike lesions observed in persons with this condition. Another view is that nevus comedonicus is an epidermal nevus involving hair follicles or an appendageal nevus of sweat ducts. Lesions that extend onto a palm or sole typically demonstrate sweat duct dilatation with keratin in the volar portion of the lesion. See Epidermal Nevus Syndrome for more information.

The etiology of nevus comedonicus is unclear. Why some nevus comedonicus patients present late in life is not known, although a genetic mosaicism has been proposed. While the majority of cases are sporadic, several families with this condition have been documented. Only one report has described nevus comedonicus occurring in homozygous twins.^[5]

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Etiology

The etiology is unknown. However, whole-exome sequencing in nevus comedonicus identified somatic NEK9 mutations, each affecting highly conserved residues within its kinase or RCC1 domains.^[6] All mutations were gain of function, resulting in increased phosphorylation at Thr210, a hallmark of NEK9 kinase activation. The authors found that comedo formation in nevus comedonicus is marked by loss of follicular differentiation markers, expansion of keratin-15‒positive cells from localization within the bulge to the entire sub-bulge follicle and cyst, and ectopic expression of keratin 10, a marker of interfollicular differentiation not present in normal follicles. These findings suggest that NEK9 mutations in nevus comedonicus disrupt normal follicular differentiation and identify NEK9 as a potential regulator of follicular homeostasis.^[6]

Another study of two families with nevus comedonicus found an up-regulation of ABCA12 in the sebaceous glands of affected individuals compared with controls. This same gene is altered in keratosis pilaris.^[7]

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Epidemiology

Frequency

Exact figures are lacking. Nevus comedonicus is considered relatively rare. One dermatology department found 12 cases in 100,000 skin biopsy specimens. Another department reported an incidence of 1 case per 45,000 dermatology visits. The incidence of nevus comedonicus syndrome is even more difficult to estimate; it is considered less common than nonsyndromal nevus comedonicus.

Race

No racial predilection is recognized.

Sex

Males and females are equally affected.

Age

Approximately 50% of cases of nevus comedonicus are evident at birth, with the other 50% developing during childhood, usually before age 10 years. A few case reports describe onset later in life, including in the seventh decade. These cases usually occur after some form of trauma^[8] or a rash.

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Prognosis

Most patients are asymptomatic. Uncommonly, the lesions become repeatedly inflamed and infected, leading to painful cysts, abscesses, fistula formation, and scarring. Additionally, patients may be distressed over the cosmetic appearance of the lesions. Spontaneous resolution has not been described. All lesions persist unless treated. They often enlarge during puberty.

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History

The lesions are typically present at birth or develop in early childhood. They are usually asymptomatic. However, one case report described itching as an accompanying symptom. Patients usually seek help for cosmetic reasons. The lesions grow as the patient does and often grow faster at puberty. Patients may be able to express keratinaceous material from the pores.

With the inflammatory form, repeated bacterial infections, drainage, cysts, fistula and abscess formation, and scarring may develop.^{[9, 10, 11]} Reports from 2015 and 2016 describe nevus comedonicus syndrome complicated by hidradenitis suppurativa‒like lesions.^{[12, 13]}

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Physical Examination

The lesion appears as a collection of discrete, dilated follicular ostia plugged with pigmented keratinaceous material.^{[14, 15]} Dermoscopy displays multiple, well-defined structureless brown homogenous circular pores with keratin plugs.^[16] They can be single or multiple, usually unilateral, and range in size from a few centimeters to involving half of the entire body.

Nevus comedonicus is typically found on the face, trunk, neck, and upper extremities.^{[17, 18, 19, 20]} Rarely, it has been described on the palms^[21] and soles, scalp,^{[22, 23]} or penis.^[24] When it occurs on the elbows and knees, it can appear as verrucous nodules. When it occurs in the intertriginous zones, the mechanical stress can produce hidradenitis suppurativa–like lesions.^[25]

Nevus comedonicus may be linear, interrupted, unilateral, bilateral, present in a dermatomal distribution, following the lines of Blaschko, or segmental.^{[11, 26, 27, 28, 29, 30, 31]}

Nevus comedonicus syndrome is the association of nevus comedonicus with abnormalities in the central nervous system, skeletal system, skin, and eyes as follows:

• Central nervous system - Epilepsy, electroencephalogram abnormalities, transverse myelitis, microcephaly
• Skeletal system - Scoliosis, hemivertebrae, spina bifida occulta, foot deformities, absent fifth finger, syndactyly, supernumerary digits
• Skin - Ichthyosis, trichilemmal cysts, leukoderma, white hairs, Sturge-Weber syndrome, hemangiomas, linear basal cell nevus
• Eye - Congenital cataracts (unilateral and bilateral)^[32]
• Other - Bilateral oligodontia,^[33] multiple basal cell carcinomas, rare systemic malignancies

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Complications

Persons with inflammatory nevus comedonicus can develop cysts, recurrent bacterial infections, fistulae, and abscesses, and these may subsequently heal with scarring. Treat these lesions with appropriate antibiotics or surgical drainage. Infections may be recurrent.

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Laboratory Studies

Many cases have been reported in which extensive laboratory evaluation has yielded no abnormalities. No particular laboratory test is specifically indicated.

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Imaging Studies

Perform imaging studies of obvious bony abnormalities if nevus comedonicus syndrome is suspected. The abnormalities described can be seen on routine radiographs of the area.

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Procedures

Skin biopsy may be performed to confirm the diagnosis.

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Histologic Findings

Typically, closely positioned dilated follicular infundibula with prominent orthokeratotic plugging are present, sebaceous elements are rudimentary or absent, and mature hair follicles are absent. The follicular walls are lined by epithelium that often appears atrophic, and it is composed of a few layers of keratinocytes. Epithelial follicular budding may be seen. The interfollicular epidermis is often normal but may appear papillomatous or hyperkeratotic. No apocrine glands are seen. Several reports of nevus comedonicus show epidermolytic hyperkeratosis in the follicular epithelium. On volar surfaces, eccrine ducts are involved.

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Medical Care

Asymptomatic lesions may be left untreated or therapy may be implemented for cosmetic concerns. Some lesions improve with topical retinoic acid,^[34] salicylic acid, or ammonium lactate lotion.^[35]

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Surgical Care

As nevus comedonicus is an asymptomatic benign condition, no treatment is required. Surgical excision of small lesions can be curative and should be considered in consultation with a dermatologic/plastic surgeon. Incomplete excision may result in recurrence of the lesion.^{[36, 37]}

Laser surgery has been tried. Carbon dioxide laser has been used as an ablative technique in eradicating extensive nevus comedonicus; however, this can cause significant scarring and may require grafts if the treatment area is large.^[38]

Treatment using a 1450-nm diode laser in conjunction with a topical retinoid has been documented to show improvement in the lesion. In 2019, a case report described some improvement of lesions with a microneedling fractional radiofrequency device.^[39]

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Consultations

If defects associated with a nevus comedonicus syndrome are found, consult the appropriate specialist, as follows:

• Neurologist for seizure disorders
• Ophthalmologist for cataracts
• Orthopedist for skeletal deformities

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Medication Summary

Both topical and oral therapies have been tried. Improvement may occur with the use of topical retinoic acid, salicylic acid, or ammonium lactate lotion. Isotretinoin (Accutane) is not usually recommended because of the long-term treatment requirement, but it may be beneficial in preventing cyst formation.

In cases complicated by hidradenitis suppurativa, treatment for hidradenitis can be initiated. It may help with cysts that develop in the nevus comedonicus lesions.^[40]

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Tretinoin topical (Avita, Retin-A)

• Dosing, Interactions, etc.

Clinical Context:  Tretinoin inhibits microcomedo formation and eliminates lesions present. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. Tretinoin is available as 0.025, 0.05, and 0.1% creams and 0.01 and 0.025% gels.

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Class Summary

Topical retinoids are known to have effects on keratinocyte proliferation and differentiation. This is believed to loosen comedones and facilitate extraction.

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Ammonium lactate lotion (AmLactin, Lac Hydrin)

• Dosing, Interactions, etc.

Clinical Context:  Ammonium lactate lotion contains lactic acid, an alpha-hydroxy acid that has keratolytic action, thus facilitating release of comedones. It comes in 5-12% strengths.

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Class Summary

Keratolytic agents cause cornified epithelium to swell, soften, macerate, and then desquamate.

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