The authors have declared that no competing interests exist.
Nevus comedonicus (NC) was initially described by Kofmann in1895 and scripted as a “comedo nevus”. Nevus comedonicus is cogitated as an exceptional subtype of epidermal nevus engendered from the hair follicle and a lesion predisposition for face and neck. Nevus comedonicus syndrome with constituent nevus comedonicus was initially coined by Engber in 1978. Delayed milestones and deferred neonatal development can ensue with nevus comedonicus or nevus comedonicus syndrome
Nevus comedonicus (NC) was initially described by Kofmann in1895 and scripted as a “comedo nevus”. Nevus comedonicus is cogitated as an exceptional subtype of epidermal nevus engendered from the hair follicle and a lesion predisposition for face and neck. Nevus comedonicus syndrome with constituent nevus comedonicus was initially coined by Engber in 1978. Delayed milestones and deferred neonatal development can ensue with nevus comedonicus or nevus comedonicus syndrome
Nevus comedonicus is a condition of obscure aetiology, a category of epidermal nevus or an origin as a hamartoma primarily derived from mesodermal segments of the pilosebaceous unit. Genetic mosaicism can be proposed as an aetiological factor for emergent nevus comediconus
Estimated prevalence of nevus comedonicus varies from 1 : 45000 to 1 : 100,000 individuals. The condition is devoid of a specific gender or racial predilection and male to female proportion of disease emergence is equivalent. Nevus comedonicus can emerge as a congenital condition or within the neonatal period in an estimated 50% subjects and majority of instances are discerned prior to 10 years
Chromosomal mutation of fibroblastic growth factor receptor 2 (FGFR2) along with enhanced enunciation of interleukin 1- alpha are cogent factors within the pathogenesis of nevus comedonicus. Gamma- secretase and filaggrin are also incriminated. Inter-relation of fibroblastic growth factor (FGF) and fibroblastic growth factor receptor 2 (FGFR2) is a critical component of mesenchymal- epithelial interaction, particularly in the genesis of pilo-sebaceous unit. FGFR is composed of a family of tyrosine kinase receptors wherein FGFR2b is singularly situated within the epithelial cells, especially epidermal keratinocytes and sebocytes. Activation of FGFR2 signalling pathway in association with enhanced manifestation of interleukin 1- alpha is delineated with the occurrence of nevus comedonicus
Somatic mutations within NEK9 are implicated in the genesis of nevus comedonicus, a gene which significantly regulates follicular homeostasis. Genomic mutations of NEK9 are accompanied by an enhanced phosphorylation at Thr 210 position, thereby indicating the activation of NEK9 associated kinase
Configuration of comedones in nevus comedonicus are associated with adjunctive modifications such as decimated markers of follicular differentiation and ectopic enunciation of keratin 10 besides an upregulation of ABCA12
Nevus comedonicus is frequently asymptomatic and usually represents grouped, distended, follicular apertures delineating dark-staining keratin plugs, commonly situated upon the face, neck, upper arms, chest and abdomen whereas scalp, palms, soles and genital region as with glans penis are infrequently incriminated. Generally, a singular group of dilated, closely arranged, adjacent and plugged follicular ostia are exemplified within a honey comb pattern. Nevus comedonicus typically enunciates dilated, follicular apertures plugged with keratinous material which recapitulate classical comedones
Aggregated, dilated, plugged follicular ostia predominantly configure a honey comb pattern. Plugged ostia are impacted with lamellated, keratinaceous substance, the superficial surface of which simulates black dots, wherein keratinous substance is resistant to mechanical extraction, in contrast to acne comedones
Nevus comedonicus delineates specific subtypes such as a) a non pyogenic form with acne-like characteristics, additionally delineated as Munro’s acne nevus, which can be considered as a condition distinct from nevus comedonicus
b) a category demonstrating the articulation of cysts, pustules, papules and abscesses in diverse stages of configuration.
Nevus comedonicus can occur as a solitary lesion or in concurrence with systemic anomalies of the central nervous system, skeletal system, ocular or dental aberrations and associated cutaneous manifestations. Diverse combinations of aforesaid clinical manifestations configure the nevus comedonicus syndrome
Nevus comedonicus syndrome is defined as a neuro-cutaneous disorder with nevus comedonicus occurring in association with extra-cutaneous manifestations such as skeletal, ocular, tooth and central nervous system anomalies. Frequently encountered are features such as cataracts, scoliosis, fused vertebrae, spina bifida and delayed mental development. Additionally, seizures, paresis, dysgenesis of corpus callosum, aberrant electroencephalogram, microcephaly, transverse myelitis, limb deformities as with the absence of fifth finger, polysyndactyly or clinodactyly, syndactyly, supernumerary digits and oligodontia as a common dental aberration are exhibited in nevus comedonicus syndrome
Nevus comedonicus syndrome as a constituent of epidermal nevus syndrome accompanies disorders such as Schimmelpenning syndrome, phacomatosis pigmentokeratotica, angora hair nevus syndrome and Becker nevus syndrome, in concurrence with adjunctive syndromic manifestations wherein a genetic component remains unestablished.
Exceptional, systemic syndromes associated with nevus comedonicus are constituted by Alagille’s syndrome, spinal dysraphism, hypothyroidism and Paget’s bone disease
Sufficient mechanical stress is contemplated as a trigger for the occurrence of hidradenitis suppurativa in concurrence with nevus comedonicus.
Primary dermatological disorders accompanying nevus comedonicus are basal cell carcinoma, squamous cell carcinoma, keratoacanthoma, linear morphea, lichen striatus, accessory breast tissue, epidermolytic hyperkeratosis, nevoid hyperkeratosis of aerola, hidradenoma papilliferum, syringocystadenoma papilliferum, epidermoid cysts, cutaneous horns, haemangiomas, ichthyosis, Sturge- Weber syndrome, haemangiomas, inverse acne leukoderma, pilar sheath tumour, dilated pore of Winer, trichoepithelioma and adjunctive epidermal nevi.
Subjects with nevus comedonicus require appropriate evaluation for nevus comedonicus syndrome. Intermittent disease flares can be observed
A cogent tissue specimen demonstrates typical features of comedones as follicular ostia distended and impacted with keratin. Significant histological manifestations are the occurrence of enlarged, grouped, distended follicular ostia demonstrating an absence of hair shafts along with impaction of laminated keratin. Base of the follicular invaginations may or may not delineate singular, rudimentary glandular structures. Miniature cysts, cystic invaginations and occasional enlarged cysts can be encountered. Cystic articulations are diverse and preponderantly layered by keratinizing, stratified squamous epithelium. Hyperkeratosis or epidermolytic hyperkeratosis and acanthosis of superimposed epidermis can concur although the lesion is devoid of parakeratosis or dyskeratosis
Immune histochemical evaluation depicts an enhanced expression of proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule 1 (ICAM-1), histocompatibility antigens (HLA- DR) and CD68.
Nevus comedonicus demonstrates immune reactivity to cytokeratin, simulating the expression of normal cutaneous surfaces. Generally encountered within the granular epidermal layer, immune reactivity for filaggrin is demonstrable within the entire epidermal thickness of closed comedones, a molecular which can be implicated in the genesis of nevus comedonicus
Atypical representations of nevus comedonicus require a demarcation from adjunctive conditions such as atypical acne, segmental acne or associated mosaic acneiform disorders such as chloracne and Favre- Racouchot syndrome, denominating nodular elastosis with cysts and comedones. Disorders such as familial dyskeratotic comedones mandate a segregation from nevus comedonicus and are cogitated as exceptional, autosomal dominant, inherited conditions with characteristic emergence of hyperkeratotic comedonal lesions. Histological assay demonstrates the occurrence of comedones with associated dyskeratosis
Generally, a clinical discernment of nevus comedonicus is adequate on account of preliminary age of disease onset and a typical morphology. Systematic evaluation of central nervous system, skeletal system and ocular structures are necessitated to exclude nevus comedonicus syndrome
Employment of a contemporary diagnostic modality such as dermoscopy is beneficial in determining nevus comedonicus. Typical comedonal lesions are highlighted by dermoscopy which characteristically demonstrates multiple, light and dark brown, spherical and barrel shaped, homogenous zones embedded with prominent keratin plugs
Spontaneous resolution of nevus comedonicus is unknown. Frequently, the superimposed epithelium is hyperkeratotic and occasionally acanthotic, thus extraction of a comedo is difficult, in contrast to removal of acne comedones.
The essentially benign nevus comedonicus may not mandate the adoption of aggressive treatment modalities, except in complex instances or for aesthetically pleasing outcomes
Treatment is primarily adopted for cosmetic reasons or for alleviation of complications such as configuration of cysts or abscesses. Cosmetic management for post- inflammatory scarring may be necessitated.
Topical and systemic retinoids can be adopted singularly or in combination with topical steroids for inciting anti-inflammatory functions.
A pore strip can be successfully employed to treat keratin plugs
Conservative therapeutic options comprise of application of emollients and moisturizers, topical corticosteroids in inflammatory lesions and keratolytics as salicylic acid or 12% ammonium lactate solution. Conservative treatment modalities can enhance cosmetic outcomes in certain subjects. As retinoids are efficacious in treating acne, the agents can be administered in nevus comedonicus. Application of topical tretinoin produces limited outcomes. Application of topical tazarotene as monotherapy or in combination with topical mometasone furoate or calcipotreine can produce superior outcomes in nevus comedonicus
Administration of FGFR inhibitors with cogent anti-vascular activity can be considered. Contemplated contemporary treatment modalities are comprised of administration of fibroblastic growth factor receptor (FGFR) inhibitors, interleukin 1- alpha inhibitors and anti gamma -secretase agents.
Interleukin 1- alpha inhibitors are classified into receptor inhibitors such as anakinra and monoclonal antibodies against the interleukin molecule and can be adopted for treating nevus comedonicus, although the outcomes are insufficiently detailed
Administration of gamma- secretase, especially stimulators of aforesaid enzymes such as general control nonderepressible 2 (GCN2), a subunit of eukaryotic translation factor 2 kinase, can be contemplated as a future therapeutic option
Surgical extermination of lesions of nevus comedonicus can be advantageous. Focal lesions of nevus comedonicus can be extracted with a cogent surgical eradication and demonstrates superior aesthetic outcomes, in contrast to adoption of manoeuvers such as superficial shaving, comedo extraction and techniques of dermabrasion.
Surgical eradication of linear nevus comedonicus situated upon the limbs mandate a concomitant, complex decongestive therapy, especially manual lymphatic drainage and employment of compression garments, wherein aforesaid measures enhances wound healing. Enlarged lesions require cutaneous and soft tissue transplantation for closure of surgical defects. Alternatively, repetitively-mobilizing or self-mobilizing osmotic tissue expanders can be utilized to obtain surplus skin for closure of discontinuous wounds
Erbium YAG laser therapy is frequently followed by delayed relapse of the lesion. In contrast to application of ablative lasers, 1450-nm diode laser can shrivel sebaceous glands and diminish seborrhoea. Combined 1450-nm diode laser and 1550-nm erbium- doped fibre laser can be employed to treat nevus comedonicus
Nevus Comedonicus | Tricho-folliculoma | Dilated port of Winer | Pilar sheath acanthoma | Folliculo-cystic and collagen comedo hamartoma | Hair Cortex | |
Site | Head | - | - | - | Head | Head |
Face | Face | Face | Face | - | ||
Neck | - | - | - | - | Neck | |
Trunk | Trunk | - | - | Trunk | Trunk | |
Limbs | - | - | - | - | - | |
Follicles | Numerous open follicles | Open “mother” follicles | Open “mother” follicles | - | Numerous open follicles | Solitary lesion |
Cysts | Present | Present | Present | |||
Hair shafts | - | Vellus shafts | - | - | - | - |
Lamellated keratin | Present | - | - | - | - | |
Others | - | - | - | Massive epithelial proliferations without follicles | Abundant collagen formation | - |