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Nevus Comedonicus
Introduction
Nevus comedonicus (NC), first described by Kofmann in 1895, is a rare condition considered to be a type of epidermal nevus. Nevus comedonicus presents as grouped, dilated follicular openings with dark keratin plugs. Kofmann initially had suggested labeling the condition 'comedo nevus.' [1]
Etiology
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Etiology
The exact etiology has not been clarified. Nevus comedonicus is considered to be an epidermal nevus developing from the hair follicle. The other opinion is that it is a hamartoma derived from the mesodermal part of the pilosebaceous unit. Genetic mosaicism has been proposed to be part of etiology of nevus comedonicus.[2][3]
Epidemiology
The prevalence has been reported to be between 1 in 45,000 to 1 in 100,000. There is no specific gender predilection; males and females can be equally affected. No increased incidence within a specific ethnicity has been reported. Most of the cases develop before the age of ten years.[4][5][6]
Pathophysiology
A mutation of Fibroblast Growth Factor Receptor 2 (FGFR2) along with increased expression of interleukin-1-alpha is considered an important factor in the pathogenesis. Other possible factors include gamma-secretase and filaggrin. Recent studies have highlighted the importance of somatic mutations in NEK 9 in nevus comedonicus. NEK9 has been postulated to be important in the regulation of follicular homeostasis. The NEK 9 mutations are associated with increased phosphorylation at Thr210, indicating activation of NEK9 associated kinase. The formation of the comedones in nevus comedonicus also has been associated with other changes such as loss of markers of follicular differentiation and ectopic expression of keratin 10. A recent study has suggested a role for upregulation of ABCA 12 in nevus comedonicus.[2][1][3]
Histopathology
skin biopsy shows the typical features of comedones -dilated follicular ostia filled with keratin.[4][1]
History and Physical
NC develops shortly after birth in about half of patients, and most patients develop the lesions before the age of ten years. The most common affected sites are the face, neck, upper arms, chest, and abdomen. Sites such as the scalp are affected quite rarely. Other rare but reported sites of involvement include the palms and the glans penis. The usual presentation is in the form of a single group of dilated and plugged follicular ostia in a honeycomb pattern. Other patterns seen include linear, segmental, or Blaschkoid. The lesions may rarely be bilateral. Two specific subtypes have been described: (1) a non-pyogenic type and (2) a type associated with the formation of cysts, pustules, and abscesses. Nevus comedonicus can occur in isolation or in combination with systemic abnormalities in the central nervous system, skeletal system, another skin manifestation, or ocular and dental abnormalities. Combination subtypes are known as nevus comedonicus syndrome. [1][7][4] [8] [9][10]
Evaluation
The diagnosis is usually clinical. Detailed evaluation of the central nervous system, skeletal system, and the eyes is required in suspected cases of NC syndrome. A skin biopsy shows the typical dilated follicular ostia filled with keratin. Immunohistochemistry studies have shown an increased expression of proliferating cell nuclear antigen, intercellular adhesion molecule-1 (ICAM-1), HLA-DR, and CD68. Electron microscopy has shown an increased number of Langerhans cells. Usually the clinical diagnosis is quite obvious with the history of early age of onset and the typical morphology, but in case of atypical presentations other conditions to consider as differentials include atypical acne (e.g., segmental acne and other mosaic acneiform conditions), other acneiform conditions such as chloracne, Favre- Racouchot syndrome (i.e., nodular elastosis with cysts and comedones), and familial dyskeratotic comedones. This last is a relatively rare, autosomal dominantly inherited condition characterized by hyperkeratotic, comedonal lesions. Histological examination shows comedones with associated dyskeratosis. [11]
Recently, dermoscopy has been reported to be useful in the diagnosis of nevus comedonicus. Dermoscopy highlights the typical comedonal lesions. The typical dermoscopy findings described include multiple light and dark brown, circular or barrel shaped homogenous areas with prominent keratin plugs.[12][13]
Treatment / Management
Spontaneous resolution of nevus comedonicus has not been described; however, aggressive treatment is not recommended as nevus comedonicus is essentially a benign condition. Treatment is mainly reserved for cosmetic reasons or when there are complications such as the formation of cysts or abscesses. Cosmetic treatment for the post-inflammatory scarring also might be required. Treatment options include topical and systemic retinoids. These sometimes are combined with topical steroids for their anti-inflammatory action, salicylic acid, or 12% ammonium lactate. Surgical excision and ablative lasers have been tried in NC. Newer treatment avenues being explored include FGFR inhibitors, interleukin-1-alpha inhibitors, and anti-gamma-secretase drugs. Successful treatment of the keratin plugs with a pore strip has been described. Lasers have been described to be effective in the treatment of nevus comedonicus. Ultrapulse carbondioxide lasers and erbium-YAG lasers have been reported to effectively treat lesions of nevus comedonicus. A recent report has mentioned the use of a 1450 nm diode laser in treating nevus comedonicus. It is postulated that sublesional collagen stimulation by the laser might lead to a reduction of the epidermal invaginations leading to an improvement in the skin texture.[14][15][16][1][17][18](B3)
Differential Diagnosis
- Acne neonatorum
- Acne vulgaris
- Angiokeratomas
- Chloracne and acne conglobata with extensive comedones
- Epidermal nevus
- Epidermoid cyst
- Familial dyskeratotic comedones
- Favre-Racouchot syndrome
- Infantile acne
- Keratosis pilaris
- Lichen striatus
- Nevus sebaceus
- Tuberous sclerosis
Pearls and Other Issues
Several associations have been reported along with nevus comedonicus and as part of the nevus comedonicus syndrome. Nevus comedonicus syndrome refers to nevus comedonicus presenting with extra cutaneous manifestations usually involving the central nervous system, skeletal system, teeth, and eyes. Common central nervous system abnormalities reported include- seizure disorders, delayed mental development, electroencephalogram abnormalities, microcephaly and transverse myelitis. Skeletal abnormalities include syndactyly, supernumerary digits, scoliosis, and spina bifida. The most common ocular manifestation described is a cataract. Oligodontia is the most reported dental abnormality. Nevus comedonicus syndrome is considered to be a part of the epidermal nevus syndrome which covers extra cutaneous manifestations occurring in association with conditions like nevus comedonicus, verrucous epidermal nevus, and nevus sebaceus. The other syndromes considered to be part of the group of epidermal nevus syndromes include Schimmelpenning syndrome, phacomatosis pigmentokeratotica, angora hair nevus syndrome, and Becker nevus syndrome.[19] [1][20][21][22]
Hidradenitis suppurative can occur along with nevus comedonicus. Hidradenitis suppurative-like lesions complicating nevus comedonicus have been described and mechanical stress has been postulated as a trigger for their development. Other rare systemic associations reported with nevus comedonicus include Alagille syndrome, spinal dysraphism, hypothyroidism, and Paget bone disease. Primary dermatological conditions occurring in association with nevus comedonicus include basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, linear morphea, lichen striatus, accessory breast tissue, epidermolytic hyperkeratosis, nevoid hyperkeratosis of areola, hidradenoma papilliform, syringocystadenoma papilliform, epidermoid cysts, cutaneous horns, hemangiomas, ichthyosis, leukoderma, pilar sheath tumor, dilated pore of Winer, trichoepithelioma, and other epidermal nevi.[23][24][25]
Enhancing Healthcare Team Outcomes
It is important to look for features of nevus comedonicus syndrome in any patient presenting with lesions suggestive of nevus comedonicus. Patients must be counseled regarding the possibility of intermittent flares. As of now there are no clear randomized control trials to clearly predict treatment success with any particular modality, but patients must be made aware of all available options so that an informed decision can be made.
Media
(Click Image to Enlarge)
Nevus comedonicus over the forehead
Contributed by Feroze Kaliyadan, MD
References
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Level 3 (low-level) evidence