Acne keloidalis nuchae: Pathogenesis, clinical manifestations, and diagnosis

INTRODUCTION — Acne keloidalis nuchae (AKN) is a common, chronic disorder involving inflammation and scarring of the hair follicles, with the subsequent development of keloid-like papules and plaques and scarring alopecia (picture 1A-G). The characteristic site of involvement is the posterior scalp and neck. Infrequently, other areas of the scalp are affected.

AKN most often occurs in Black males but also occasionally develops in females and other populations. AKN may be pruritic, painful, or cosmetically disfiguring, contributing to negative effects on quality of life.

The pathogenesis, clinical features, and diagnosis of AKN will be reviewed here. The management of AKN and the general approach to diagnosis of hair and scalp disorders are reviewed separately.

●(See "Acne keloidalis nuchae: Management".)

●(See "Evaluation and diagnosis of hair loss".)

TERMINOLOGY — Although the term "acne keloidalis nuchae" is commonly used, there are other historical and contemporary descriptors for AKN. Historical terms for this condition include "sycosis framboesiformis" and "dermatitis papillaris capillitii" [1,2]. Contemporary alternative names for AKN include "folliculitis keloidalis" [3], "folliculitis nuchae" [4], and "folliculitis keloidalis nuchae" [5,6]. In addition, because of the occasional extension to other areas of the scalp, some authors eliminate "nuchae" from "acne keloidalis nuchae" and refer to the disorder as "acne keloidalis."

Multiple authors have suggested that the name "acne keloidalis nuchae" is a misnomer, since the lesions are neither pathologically acne nor keloids [7]. In contrast to true acne, comedones are never present in AKN [8]. The scar-like lesions, though they resemble keloids, do not typically recur following excision, like keloids often do [9], and patients typically do not have keloids elsewhere.

EPIDEMIOLOGY — The frequency of AKN varies across populations. Black males with tightly curled hair are the predominant population at risk, although there are reports of other populations, such as White and Asian patients [10-13]. In a study of 453 male football players (aged 14 to 27 years), AKN was present in 14 percent of Black players compared with 0 percent of White players [14]. Studies performed in North America, the Caribbean, and Africa have found AKN to represent between 0.45 and 9 percent of diagnoses among Black patients evaluated in dermatology clinics [7,15-19].

AKN is infrequent in other populations [10-13]. A Korean study found a prevalence of 0.007 percent for AKN in approximately 254,000 new patients evaluated over a 12-year period in a single institution [11]. AKN may still be a relevant form of cicatricial alopecia in some populations in which the diagnosis is uncommon. A retrospective case series conducted in Taiwan that included 89 patients with pathology-confirmed primary scarring alopecia found 12 percent had AKN [12].

AKN affects males far more frequently than females, although females occasionally develop AKN [20,21]. A 20:1 ratio of affected males to females is commonly quoted [22]. In a community-selected group in South Africa, 11 percent of 267 males versus 0.3 percent of 597 females had AKN [23].

Onset of disease typically follows adolescence and is rare after age 50 [24]. The predilection for the onset of AKN after adolescence was demonstrated in a study of 1042 South African school children (age 6 to 21 years). The prevalence of AKN was 0.67 percent overall, but among students in the final year of high school, the prevalence of AKN was 4.7 percent [23].

PATHOGENESIS — As evidenced by a multitude of proposed theories with variable levels of evidence, the cause of AKN has not been definitively established. Pathogenic mechanisms related to skin injury and aberrant immune responses to common antigens are among the cited theories:

●Skin injury – Some theories of causality focus on chronic irritation or occlusion of the follicles due to hair cutting practices (eg, close shaves or close clipping), trauma, friction (eg, rubbing from shirt collars or helmets), heat, or humidity as a predisposing or exacerbating factor [16,25-28]. Whether the tool used for hair cutting might influence risk for AKN is unclear. In a South African study, the prevalence of AKN did not appear to differ with the use of razors versus clippers [23]. Frequent and traumatic haircuts have also been proposed as potential contributors, though further study is necessary to determine whether these are relevant factors [15,23].

External insults are unlikely to be the sole cause of AKN, given the disproportionate number of cases that occur in Black males. The findings of a study of 453 male football players supports this; in contrast to the increased prevalence of AKN noted in Black players, acne mechanica (an acneiform eruption induced by friction, occlusion, and heat [29]) occurred on the posterior neck at similar rates in Black and White players [14].

A role for the tightly curled hair type in AKN has been suggested based upon the increased prevalence in the Black population, possibly related to the curvature and morphology of this type of hair. Although penetration of curved hair into the skin has been proposed as a potential mechanism [22], this theory has been questioned by authors who have found no clinical or pathologic evidence of hairs curving and re-entering the skin [30,31].

●Aberrant immune reaction – Another proposed pathogenic theory is based upon consideration of AKN as a form of primary cicatricial (scarring) alopecia stimulated by an immune response in the skin [32]. (See "Evaluation and diagnosis of hair loss", section on 'Cicatricial alopecia'.)

The following sequence of events for the development of AKN as a primary scarring alopecia has been proposed [32]:

•Intrafollicular antigens (particularly those that are more prevalent after puberty) attract inflammatory cells to the follicle at the level of the isthmus (figure 1). Proposed antigens include Demodex, skin flora (eg, bacteria or fungal spores), cosmetics, sebum, and desquamated keratinocytes.

•The sebaceous gland is either an early target for inflammation or is destroyed secondarily as a result of the inflammatory process.

•The follicular wall is weakened by the perifollicular inflammation, resulting in spongiosis and a mild, lymphocytic exocytosis.

•The weakened follicular wall allows increased leakage of intrafollicular antigens, resulting in greater inflammation.

•The process continues with development of concentric lamellar fibroplasia, with the hair shaft eventually penetrating the follicular wall and entering the dermis, resulting in intense inflammation and epithelial destruction, further resulting in a follicular scar.

•Hypertrophic scarring develops due to the presence of hair shaft fragments and degenerating, epithelial components in the dermis.

●Other – Other potential contributory factors proposed based upon limited data include autoimmunity [30], excess androgens or increased sensitivity to androgens [18,33], seborrhea [18], and medications (eg, cyclosporine [34-36], tacrolimus [37], sirolimus [37], or diphenylhydantoin and carbamazepine [38]). As with other proposed contributors, a role for these factors remains to be confirmed.

CLINICAL MANIFESTATIONS — AKN presents with variable degrees of inflammation and keloid-like (keloidal) scarring on the posterior lower scalp and nape of the neck. Occasionally, involvement extends onto the vertex or other areas of the scalp (picture 2) [39].

Active inflammation in AKN manifests as inflamed papules or pustules (picture 1A-G). Inflammation may be acute, demonstrating marked erythema, inflamed papules, or papulopustules. Alternatively, a combination of acute inflammation and chronic inflammation (manifesting as pink to dusky red papules without pustules or discharge) may be present. The degree of inflammation ranges from mild to severe and can vary to some extent between episodes of flare in a given individual. Crusting or excoriation may be evident. In severe cases, draining sinus tracts or suppuration may be present.

Scarring is typically present by the time patients present for medical evaluation. Scarring is manifested by variably sized, keloidal papules, plaques, or nodules at the site of previously involved hair follicles (picture 1G-K). The keloidal papules of AKN are typically dome shaped (picture 3). In the later stages of AKN, patients may present with chronic scarring or scarring alopecia without active inflammation (picture 2). Tufted "doll hairs," multiple hairs emerging from a single follicular orifice, may be present (picture 1K).

AKN may be asymptomatic or symptomatic. Pruritus or pain may accompany the skin lesions, particularly if pustules are present [7,22,25,30].

CLINICAL COURSE — AKN is a chronic disease with episodic flares of worsening inflammation. Effective treatment typically requires a maintenance regimen with therapeutic adjustments as needed for flares. With time (usually over a variable number of years), the disease tends to become less active in terms of inflammation. However, keloidal papules and plaques usually persist unless treated. (See "Acne keloidalis nuchae: Management".)

ASSOCIATED DISORDERS — Potential associations between AKN and other disorders have been reported:

●Metabolic syndrome – Increasing data suggest an association of AKN with metabolic syndrome and its component disorders (eg, obesity, diabetes mellitus/type 2 diabetes, hypertension, and dyslipidemia) [13,40-43].

One of the largest studies, a retrospective study of 2677 patients with AKN and 13,190 controls, found a higher prevalence of metabolic syndrome in patients with AKN compared with controls (16.1 versus 6.6 percent, odds ratio [OR] 2.72, 95% CI 2.40-3.08, p<0.001) [43]. Obesity had the strongest association with AKN (OR 3.00, 95% CI 2.75-3.28), followed by type 2 diabetes (OR 2.47, 95% CI 2.20-2.77), hypertension (OR 1.82, 95% CI 1.63-2.05), and dyslipidemia (OR 1.60, 95% CI 1.46-1.75). In addition, a retrospective study of 43 patients with AKN found patients with chronic scalp folliculitis, any component disease of the metabolic syndrome, or hypertension specifically more likely to have more extensive AKN (lesions extending beyond the nape of the neck and occipital scalp) [40].

●Hidradenitis suppurativa – A cross-sectional study of 2677 patients with AKN and over 13,000 control patients found a higher incidence of hidradenitis suppurativa in the AKN group compared with the control group (1 versus 0.3 percent, adjusted OR 3.6, 95% CI 2.1-5.9). The association was particularly strong for patients under the age of 20 years and females [44].

●Keratosis follicularis spinulosa decalvans – AKN has been reported in patients with keratosis follicularis spinulosa decalvans, an X-linked genetic disorder that predisposes patients to the development of follicular hyperkeratosis and inflammation [45,46]. (See "Keratosis pilaris atrophicans", section on 'Keratosis follicularis spinulosa decalvans'.)

HISTOPATHOLOGY — Histopathologic findings vary based on the stage of the disease and the specific clinical features present in the immediate area of the biopsy. Typically, however, AKN is characterized by the presence of acute and chronic folliculitis, ruptured pilosebaceous units, and dense dermal (cicatricial-type) fibrosis (picture 4A-E) [11,47]:

●Early stages – Dense, follicular and perifollicular, inflammatory infiltrate of lymphocytes and neutrophils. The dermal fibrosis resembles the collagen fibers seen in typical scar tissue more than the fibrosis seen in keloid scars [22].

●Later stages – Disrupted and fractured hair follicles are surrounded by granulomatous inflammation, perifollicular abscess formation, and dermal fibrosis [48].

Additional findings that may be present include plasma cells, marked lamellar fibroplasia at the level of the isthmus, destruction of sebaceous glands, and thinning of the follicular epithelium at the level of the isthmus [32]. The "spade sign," a thin, dilated space resembling the shape of a balloon or spade symbol at the lower isthmus, was identified in 8 of 15 patients with AKN in a retrospective study from Taiwan [47].

DIAGNOSIS — The diagnosis of AKN can usually be made based upon the clinical findings. Biopsy is rarely necessary. The clinical findings that raise suspicion for a diagnosis of AKN are firm, keloidal papules or plaques on the lower posterior scalp or upper posterior neck, with or without inflamed, follicular papules or papulopustules:

●Patient history – The patient history allows the clinician to collect information that may aid in supporting or negating a diagnosis of AKN, determining the best approach to management, and assessing the response to treatment. Knowledge of the following is useful:

•Age of onset (postadolescence to middle age is typical for AKN)

•Disease duration and rate of progression

•Symptoms (eg, pain, pruritus, drainage)

•Hair care practices (hair cutting and shaving)

•Exacerbating factors

•Prior treatments (including response to each treatment)

●Physical examination – The entire scalp should be examined. In typical AKN, the area of disease (inflammatory papules, pustules, and keloidal papules or plaques) is limited to the lower posterior scalp and nape of the neck. Crusting, excoriation, and, in severe cases, suppuration may be present.

Although AKN occasionally extends to other areas of the scalp [39], findings of follicular papules, inflammation, suppuration, or scarring on other areas of the scalp should prompt consideration of alternative diagnoses, such as folliculitis decalvans, dissecting cellulitis of the scalp, lichen planopilaris, follicular cutaneous T cell lymphoma (CTCL), tinea capitis, or another disorder. (See 'Differential diagnosis' below.)

Reported dermoscopic findings include perifollicular pustules and a white halo surrounding hair follicles in early-stage disease and tufted hairs in later-stage AKN [49]. (See "Overview of dermoscopy of the hair and scalp".)

●Biopsy – Biopsy is usually unnecessary unless the presentation is atypical. If a biopsy is necessary for diagnosis, a 4 mm punch biopsy should be performed. A 4 mm punch size, in addition to providing a larger surface area for evaluation, allows for comparison with standardized histopathologic values, including typical hair follicle count, ratio of vellus to terminal hairs, and ratio of anagen to telogen hairs. (See "Skin biopsy techniques", section on 'Punch biopsy'.)

Vertical sectioning of the pathology specimen is usually sufficient for recognizing pathologic characteristics of AKN and is regarded as the preferred technique.

It is essential that the biopsy be of sufficient depth to include the base of the follicle. It is also important to include a suspected keloidal papule. Biopsy solely of areas of severe inflammation or frank suppuration in the absence of keloidal papules may not be helpful.

●Other tests – If superinfection is a possibility (extensive erythema, suppuration, pain, drainage, odor, or systemic symptoms such as fever), bacterial culture should be obtained. The need for other tests is determined by the differential diagnosis. For example, if tinea capitis is suspected, a potassium hydroxide (KOH) preparation or fungal culture is indicated. (See "Acne keloidalis nuchae: Management", section on 'Secondary infection' and 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The diagnosis of AKN is usually straightforward, based on the clinical appearance and location of lesions. However, there are several disorders that may merit consideration if faced with an atypical presentation of AKN, such as acne mechanica, infections, primary scarring alopecia, and cutaneous T cell lymphoma (CTCL):

●Skin trauma:

•Acne mechanica – Acne mechanica is a frictional or traumatic folliculitis. The disorder may present on the nape of the neck or in any hair-bearing area subject to rubbing or friction. Unlike AKN, acne mechanica is usually transient and does not present with keloidal papules or plaques. Often, a specific trigger may be identifiable (eg, shaving, friction, or trauma from clothing or other apparel such as a hat or helmet).

●Infections:

•Bacterial folliculitis – Bacterial folliculitis may occur due to bacterial colonization in the setting of minor trauma (eg, shaving) or follicular occlusion followed by secondary infection. Patients present with multiple follicle-based, inflammatory papules and pustules (picture 5). Unlike AKN, keloidal papules should not be present. (See "Infectious folliculitis".)

•Molluscum contagiosum – Molluscum contagiosum presents with skin-colored papules that may resemble small, keloidal papules (picture 6A-B). The nape of the neck is an uncommon location for molluscum contagiosum. However, infection in this site could occur due to transmission via infected hair clippers or self-inoculation from other areas of the body.

Close examination may help to differentiate molluscum contagiosum lesions from keloidal papules; molluscum lesions frequently exhibit central umbilication and are likely to be accompanied by lesions elsewhere on the body. Inflammation is usually minor or absent, unless molluscum become inflamed or secondarily infected. Biopsy findings should easily differentiate molluscum from AKN [7]. (See "Molluscum contagiosum", section on 'Clinical features'.)

•Tinea capitis – Tinea capitis may present with kerion, an acute, inflammatory reaction to tinea capitis that presents as a localized plaque with erythema, pustules, alopecia, and boggy induration (picture 7A-B). Cervical lymphadenopathy is usually present.

In most cases, the clinical distinction between AKN and fungal infection should be straightforward. Kerion presents acutely, and keloidal papules are not a feature of tinea capitis. A fungal culture should be obtained if kerion is a possibility. (See "Tinea capitis".)

●Primary scarring alopecia:

•Folliculitis decalvans – Folliculitis decalvans is an uncommon form of cicatricial alopecia that typically presents with one or more confluent areas of scarring alopecia and multiple pustules that are often located at the periphery of the areas of alopecia (picture 8A-B). Tufted hairs may be present. Unlike AKN, multifocal involvement of the scalp is common, and keloidal papules and plaques are not features of this disease. (See "Folliculitis decalvans".)

•Dissecting cellulitis of the scalp – Dissecting cellulitis of the scalp is an uncommon form of cicatricial alopecia in which patients develop follicular papules, pustules, fluctuant nodules, and abscesses on the scalp that result in scarring (picture 9A-B). Young Black males are most frequently affected. Keloidal papules and plaques are not a feature of dissecting cellulitis of the scalp. (See "Dissecting cellulitis of the scalp".)

•Lichen planopilaris – Lichen planopilaris should be easy to distinguish from AKN. Affected patients present with fine, perifollicular papules with scale and erythema at the base of affected hairs. The perifollicular papules are smaller than those typically seen in AKN. Macules or patches of alopecia may be present (picture 10). Pustules should not be present, nor should there be keloidal papules or plaques. Lichen planopilaris can be located anywhere on the scalp. (See "Lichen planopilaris", section on 'Clinical presentation'.)

Although a variant of lichen planopilaris, frontal fibrosing alopecia, typically affects the frontal and temporal hairline with variable extension to the crown and temporoparietal scalp, the lower posterior scalp would not typically be affected in the absence of lesions elsewhere on the scalp. (See "Frontal fibrosing alopecia: Pathogenesis, clinical manifestations, and diagnosis".)

●Malignancy:

•Follicular cutaneous T cell lymphoma (CTCL) – Follicular CTCL may present with follicular papules with alopecia, alopecic patches or plaques with hyperkeratotic papules, keratosis pilaris-like lesions, or comedonal or milia-like lesions. Conventional lesions of mycosis fungoides may or may not be present [50]. Alternate presentations include papules, plaques, and nodules on the head and trunk [51]. If follicular CTCL is a concern, biopsy for definitive diagnosis is essential. Multiple biopsies may be helpful in this clinical scenario. (See "Variants of mycosis fungoides", section on 'Folliculotropic mycosis fungoides'.)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Acne keloidalis nuchae (AKN) is a common, chronic disorder characterized by inflammation and keloid-like scarring on the posterior scalp or posterior upper neck. Most cases of AKN occur in postadolescent Black males. Less frequently, other individuals develop AKN. (See 'Epidemiology' above.)

●Pathogenesis – The cause of AKN is unclear. Proposed contributory factors have included possession of tightly curled hair, close shaving or clipping of hair, and factors that may irritate or occlude hair follicles on the posterior scalp and neck. Some authors consider AKN a form of primary scarring alopecia. Associations between AKN and other disorders have been described. (See 'Pathogenesis' above and 'Associated disorders' above.)

●Clinical manifestations – The major clinical findings of AKN include inflammatory papules, pustules, and keloid-like papules or plaques on the posterior scalp and nape of the neck (picture 1A-G). The severity of involvement varies widely. Patients may be asymptomatic or symptomatic. Symptomatic patients may experience pain or pruritus. (See 'Clinical manifestations' above.)

●Diagnosis – The diagnosis of AKN can usually be made based upon the clinical evaluation. Clinical findings that strongly suggest a diagnosis of AKN include firm, keloid-like papules or plaques on the lower posterior scalp or nape of the neck, with or without inflamed papules or pustules. Biopsy is not typically necessary but can be useful for confirming the diagnosis in atypical cases. (See 'Diagnosis' above.)