A systematic approach to the evaluation of alopecia allows for more effective management. Below is a step-by-step approach that can be used in scarring alopecia:
Initial classification of alopecia type
Applying scarring alopecia terminology based on clinical features
Using histology findings to further support/define the diagnosis
Providing an overall evaluation/diagnosis with treatment options
Initial classification
The initial determination of alopecia type usually begins with the establishment of alopecia as either a scarring (cicatricial) alopecia or nonscarring alopecia. Nonscarring alopecias tend to have preserved follicular ostia. No clinically visible inflammation is noted in most presentations, although histologic inflammation may be present. The most common nonscarring alopecias include alopecia areata and telogen effluvium.
Scarring alopecias have loss of follicular ostia, or atrophy. Clinical inflammation is frequently, but not always, present. Histologic inflammation may be present. Ultimately, histologic confirmation is the best method to confirm the presence of a fibrosing/scarring process with loss of hair follicles.
Many alopecia types are biphasic. For example, androgenetic alopecia eventually results in loss of ostia and thus may appear like a scarring alopecia. This article focuses on the alopecia types that are believed to be due to an inflammatory response with rapid secondary scarring if not controlled.
Scarring alopecia terminology based on clinical features
Once the patient is determined to have scarring alopecia, establishing and clarifying the diagnostic options and terminology is important to assist in confirming the diagnosis, initiating treatment, and suggesting a prognosis. Several manuscripts have examined and attempted to clarify the literature findings,[1, 2, 3] as summarized below.
Also important to note is that examination alone cannot be the final step; the literature is filled with examples of misdiagnosis and diagnostic mimics in alopecia.[4, 5, 6, 7] This includes patients presenting with nonscarring, noninflammatory alopecia that is later found to be scarring and inflammatory.[8] Even amongst the scarring alopecia presentation, it is sometimes debated as to the role of immune alteration versus pure external factors that cause the scarring alopecia. Much of the confusion is often based in the similarities of clinical presentation, which emphasizes again the importance of not basing diagnosis purely on clinical examination findings alone.[9]
Diagnoses in which lymphocytes predominate are as follows:
Lichen planopilaris
The diagnosis of lichen planopilaris (LPP) is confirmed by a combination of clinical and histologic features. The following subtypes are recognized[10] :
Frontal fibrosing alopecia (FFA): This is a potential clinical variant of lichen planopilaris, with similar histologic features. Frontal fibrosing alopecia has been associated with the postmenopausal state (ie, postmenopausal frontal fibrosing alopecia), although not all patients with this diagnosis are postmenopausal. Note the image below.
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End-stage scarring alopecia (ESSA) with prior history of itching and burning, along with a receding hairline. Started as the lichen planopilaris varia....
Fibrosing alopecia in pattern distribution (FAPD): This also is a potential clinical variant of lichen planopilaris, with similar histologic features. Additionally, fibrosing alopecia in pattern distribution has some histologic/clinical overlap with androgenetic alopecia. Fibrosing alopecia in pattern distribution may also be an overlap of lichen planopilaris with androgenetic alopecia.
Graham-Little syndrome: This entity is also a possible overlapping condition, with features of lichen planopilaris and other alopecia types.
Central centrifugal cicatricial alopecia (CCCA)
CCCA is a diagnostic category adopted by the North American Hair Research Society to encompass terms such as hot comb alopecia, follicular degeneration syndrome, pseudopelade in African Americans, and central elliptical pseudopelade in whites.[10] Despite the many attempts to clarify and unify the terminology of central CCCA patterns of scarring alopecia, CCCA is not clearly a diagnostic entity in and of itself.
Pseudopelade
Pseudopelade is a term used to describe a clinically noninflammatory patchy alopecia. The most common condition to produce this appearance is lichen planopilaris. The term “idiopathic pseudopelade” refers to a distinct fibrosing alopecia characterized by a thin dermis, with dense eosinophilic dermal collagen and thick recoiled elastic fibers. The fibrous tracts are broad and may contain granulomas, but the surrounding elastic sheath is preserved.
Traction alopecia
As the name implies, traction alopecia is alopecia secondary to physical traction. Variant presentations exist with terminology that is optional for differentiating purposes. This includes alopecia linearis frontalis (ALF), more commonly known as marginal alopecia, and chignon alopecia, which is when a tight hair bun causes the traction changes.
Secondary systemic scarring alopecia
Secondary systemic scarring alopecia is a term used when the alopecia is a feature of a systemic disease (eg, scleroderma, discoid lupus erythematosus). Discoid lupus erythematosus is often a cause of alopecia. In the classic lupus classifications scheme, discoid lupus erythematosus is one of the chronic cutaneous lupus types (along with tumid lupus and lupus panniculitis).
Trichotillomania
Trichotillomania is a nonscarring psychiatric alopecia that can have a scarring clinical presentation. Trichotillosis is an alternative term that some physicians believe is more acceptable to patients.[11]
Chemotherapy alopecia
Chemotherapy alopecia is often thought of as nonscarring alopecia; however, reports of permanent alopecia suggest that hair stem cells can be permanently destroyed. Note the image below.
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Alopecia due to primary cutaneous follicular center cell lymphoma. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morza....
Alopecia mucinosa
Follicular mucinosis can exist by itself or can be a manifestation of mycosis fungoides.
Keratosis pilaris atrophicans
Keratosis pilaris atrophicans involves a spectrum of conditions that resemble keratosis pilaris, but result in hair loss.
Diagnoses in which neutrophils predominate are as follows:
Folliculitis decalvans: Folliculitis decalvans presents with recurrent crops of follicular pustules that result in permanent epilation. Staphylococci are often cultured from pustules, but this condition does not respond the standard antibiotic regimens. The best results are obtained by long-term use of topical corticosteroids together with an oral tetracycline.
Perifolliculitis capitis abscedens et suffodiens: Other terms used for perifolliculitis capitis abscedens et suffodiens include dissecting cellulitis and Hoffman disease. It resembles hidradenitis suppurativa and the 2 often occur together.
Tufted hair folliculitis: Tufted hair folliculitis often contains Staphylococcus aureus, but it is unclear if a preexisting abnormality predisposes to staphylococcal infection. Clinically, 5-20 hairs emerge from a common dilated follicular orifice, producing a clinical resemblance to doll hair. This is often seen as a reactive pattern present in multiple types of scarring alopecia and even as a reaction to medications.[12]
Diagnoses in which a mix of cell types predominate are as follows:
Acne keloidalis: Others terms used for this condition include acne keloidalis nuchae, dermatitis papillaris capillitii, sycosis nuchae, and folliculitis keloidalis. Patients present with pustules, alopecia, and hypertrophic scarring on the posterior neck. Many plasma cells are typically present in the infiltrate.
Acne necrotica: Acne necrotica is sometimes also called folliculitis necrotica. This condition is rare and exists in 2 variants. The first is acne necrotica varioliformis, which is a distinctive necrotizing disorder of the hair follicle that heals with varioliform scars. The second is acne necrotica miliaris, which is a nonscarring folliculitis.
Erosive pustular dermatosis of the scalp: This condition often follows surgery or other trauma. It presents with an expanding patch of crusts and pustules.[13] It has been reported to respond to potent topical corticosteroids, tacrolimus, and light therapy.
Diagnoses for which the least evidence-based characterization is available are as follows:
Pressure alopecia: Pressure alopecia is due to constant pressure to the region. Often described as a nonscarring reversible alopecia, it has also been reported to result in permanent scarring. This may be more accurately termed externally traumatic alopecia or iatrogenic alopecia.[14] As in chemotherapy alopecia, the rapidly growing hair follicle and hair cell source (bulge and associated regions) may be especially susceptible to antimetabolic insult, such as lack of blood flow.
Lipedematous alopecia: Lipedematous alopecia is a rare condition with unknown scarring potential. It is also referred to as lipedematous scalp.
Senescent alopecia: Senescent alopecia is also known as senile alopecia, a diffuse thinning due to decreased terminal hairs but without increased miniaturization.[15] It is thought to affect people aged 40-50 years or older with no family history or evidence of pattern balding. Senescent alopecia is not a primary diagnosis in all clinics and often is debated as a diagnosis as actually being late-onset androgenetic alopecia.[16]
Keratosis follicularis atrophicans
Possible variants include keratosis pilaris decalvans, an X-linked and sporadic condition, and folliculitis spinulosa decalvans, which is autosomal dominant.
The etiology for most forms of scarring alopecia is largely unknown and represents a fertile area for research.
One study suggested an autosomal dominant pattern of inheritance with CCCA, with hairstyling and gender as strong contributing factors.[17] A population study of environmental and medical risk factors for CCCA development described a possible correlation between the clinical presentation of CCCA and the finding of diabetes. The study also reminds us that traction makes alopecia, including CCCA worse; hot comb use does not necessarily play a role.[18] The major limitations of this study should be acknowledged and include the lack of biopsies and the reliance on self-reporting. Clinical CCCA does not always translate into histological CCCA because clinical mimics are common in alopecia.
For lichen planopilaris, related entities include frontal fibrosing alopecia and fibrosing alopecia in pattern distribution. Research has suggested that dysfunction in the PPAR receptor plays a role in the pathophysiology of lichen planopilaris. The dysfunction results in toxic fatty acid buildup.[19]
Studies have also show a significantly higher ratio of Langerhans cells to T lymphocytes in lichen planopilaris compared with that seen in traction alopecia.[9]
Sebaceous gland damage is also believed to be more common in scarring alopecia and can be a histologic clue to scarring.[20] Although it is not clear if a difference exists between external trauma–induced scarring alopecia and internal dysfunction, such as in lichen planopilaris. Nevertheless, it can be a good clue to differentiate from clinical mimics that can be seen in nonscarring alopecia.
Scarring alopecia can also result from rather unexpected causes. In particular, epidermal growth factor receptor inhibitors and chemotherapy-induced scarring/permanent alopecia have been reported.[21]
Traction alopecia is believed to be related directly to external factors, such as traction or trauma resulting from activities such as break dancing.[22]
Epidemiology studies are mostly from clinics dedicated to alopecia. Within the alopecia population, the prevalence of scarring alopecia is believed to be approximately 7%.[23] The relative prevalence of each type of scarring alopecia varies by different reports and is highly clinic dependent.[23]
No large evidence-based medicine studies are available to report the epidemiology of lichen planopilaris, central centrifugal cicatricial alopecia, or pseudopelade in the general population.
Traction alopecia is most commonly seen in the African American population because of the practice of styling the hair in tight braids or the use of chemical hair straighteners. Female athletes who pull their hair back tightly have been found to develop from this problem. Traction alopecia is also reported in nurses who secure their nurse's caps to their scalp with bobby pins.[14, 15] The exact frequency of traction alopecia in the United States has yet to be documented.
International
Traction alopecia is seen worldwide. Its frequency usually depends on cultural customs. Japanese women who wear a traditional hairdo, Sikh men in India, and others who wear ponytails are examples of individuals who may be affected.
Population studies show a prevalence of 17.1% in African schoolgirls (6-21 y) and of 31.7% in women (18-86 y).[24] This is by far one of the most frequent types of scarring alopecia presentations.
Scarring alopecia prevalence studies are otherwise still lacking. Partial hindrance of such data production is based on the lack of well-established diagnostic criteria. Prevalence from specialty clinics has been estimated, although extrapolation to the general population is still difficult.[25]
Race
Large race-based studies are not yet available. Central centrifugal cicatricial alopecia is believed to be predominant in African Americans, while lichen planopilaris occurs mostly in lighter-skinned patients.
Sex
The sex distribution of scarring alopecia is anecdotally believed to be predominantly favoring the female population.
Age
Traction alopecia is initially seen in children and young adults. Traction alopecia is an uncommon overall cause of hair loss in adults. However, in the African American population, this entity is a significant cause of alopecia. The exact frequency has yet to be documented in children, young adults, and adults.
Age distribution on the other scarring alopecia types has not been well studied. The majority of case reports suggest these conditions present in persons older than 20 years.
The natural history of scarring alopecia has not been extensively validated in the literature. The morbidity of alopecia has been reviewed.[26] In addition is psychiatric morbidity; the correlation of scarring alopecia with systemic disease may be important and is becoming a larger focus of research.
Instruct patients to discontinue hairstyling practices that cause traction alopecia.
Evaluation and follow up should be emphasized, even if patient is disappointed that the physician does not have a quick fix for the problem or cannot reverse its course. At the very least, halting progression is often possible and a point to highlight.
History findings for the various types of scarring alopecia are as follows:
Lichen planopilaris: Common symptoms include itching, burning, and pain.[2] Some authors report a co-occurrence of androgenetic alopecia in up to 30% of patients with lichen planopilaris.
Central centrifugal cicatricial alopecia: Patients report slow onset of hair loss without symptoms.
Pseudopelade: Patients report slow onset of hair loss without symptoms.
Traction alopecia: Patients report slow onset of hair loss without symptoms.
Lipedematous alopecia: Patients report slow onset of hair loss without symptoms.
Alopecia mucinosa: Patients report dyshidrosis and dysesthesia.
Chemotherapy alopecia: Alopecia may occur accompanied by a sensation of tingling. Cytotoxic effects on hair follicles result in temporary hair loss starting within 4 weeks of treatment initiation. This does not resolve until the telogen phase is complete and a new hair cycle begins, typically within 6 months.[27] Permanent chemotherapy-induced alopecia is defined as decreased or no regrowth 6 months after the end of therapy.[27] This alopecia is often reversible and is due to hair follicle cycle inhibition by the chemotherapy agents. This altered cycle and shedding is often called anagen effluvium. Reports of permanent alopecia typically follow high-dose chemotherapy and often also include subsequent bone marrow transplantation. Busulphan is the most common agent cited to cause permanent chemotherapy-induced alopecia.[27]
Discoid lupus: Patients often have a history similar to persons with cutaneous discoid lupus, which may include a sensation of itchiness and tenderness in the region. Also see Lupus Erythematosus, Discoid.
Acne keloidalis: Patients report of itching, burning, and tenderness.
Acne necrotica: Patients report of itching, burning, and tenderness.
Erosive pustular dermatosis: Patients often have no symptoms. If the scalp region is tender, suspect malignancy.
Pressure alopecia: Patients usually report itching and dandruff. Note the image below.
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Recalcitrant scarring pressure alopecia several years after an ICU stay. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD,....
Senescent alopecia: Patients often have a normal full head of hair through age 40 years. A dramatic, diffuse thinning is then noted. No regional augmented area of alopecia is noted, as in androgenetic alopecia. Mild superimposed androgenetic alopecia may also be present.[28]
A hair-pull test can assist in the evaluation of all types of alopecia. An excess of loose anagen hairs can be indicative of active disease. All types of scarring alopecia show loss of follicular ostia. This is most easily seen with a magnification light or dermatoscope.
As detailed below, a full review of systems and a skin examination help in finding subclinical and atypical disease presentations.
Lichen planopilaris
The classic presentation of lichen planopilaris includes perifollicular erythema, perifollicular hyperkeratosis, and scalp erythema. Extracranial disease may be noted in up to 30% of patients. Signs of scalp inflammation can precede hair loss by many months, thus emphasizing the need for a thorough skin examination that includes a scalp examination.[28]
Graham-Little syndrome is another variant characterized by patchy cicatricial alopecia of the scalp, nonscarring alopecia of the axillary and pubic areas, and grouped spinous follicular papules that resemble lichen spinulosus or keratosis pilaris on the trunk and extremities.
Central centrifugal cicatricial alopecia
Signs of inflammation are not noted on physical examination. Although central centrifugal cicatricial alopecia classically is described to start on the crown and spread centrifugally, the discovery of cicatricial pattern hair loss as a possible alternate presentation indicates this is not the only course of progression.
Pseudopelade
Signs of inflammation are not noted on physical examination. Unlike central centrifugal cicatricial alopecia, pseudopelade often presents as small patches of scarring in the scalp. Some have suggested use of the term pseudopelade should be avoided.
Traction alopecia and trichotillomania
The scalp may have perifollicular erythema, scales, pustules, or a more subtle seborrheic picture. However, active inflammation is not required for the diagnosis. Broken hairs are common.
The region affected is determined by the etiology. With chignon alopecia, hair loss may be in the occipital area. With corn-rowing, the area most commonly affected is adjacent to the region that is braided. In patients who tie their beards into knots, areas of alopecia can be detected along the sides of the mandible. Note the image below.
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Traction alopecia.
In alopecia linearis frontalis, the distribution of hair loss follows a characteristic pattern in the temporal scalp, starting in the periauricular area and extending forward in a triangular manner. The involved area is approximately 1-3 cm in width in most cases.
With the long-term application of tensile forces, an irritant type of folliculitis develops. Follicular scarring and permanent alopecia may result. In some cases, peripilar hair casts form. The casts are fine, yellowish-white keratin cylinders smaller than 1 cm in diameter that ensheathe the hair follicle. Often, peripilar hair casts occur in isolation; however, they have also been known to occur in association with hyperkeratotic scalp disorders. The hair-loss pattern entirely depends on the specific grooming pattern of each patient. Marginal and nonmarginal types may be seen.
Awareness of trichotillomania mimics is also important. This diagnosis can easily mimic other conditions such as patchy alopecia areata, especially if history findings do not suggest otherwise. Often, examination and differentiation can be difficult.[7]
Alopecia mucinosa
Hair-bearing areas in the head and neck region are commonly involved. Examination findings include alopecia, prominent follicles, and indurated plaques with fine scale. The physical presentation can be one of many polymorphous types, with no specific pattern recognized. In fact, reports have included mimics of ophiasis, alopecia areata patches, and frontal fibrosing alopecia. Furthermore, because affected hair shafts are fragile and break easily, alopecia mucinosa can present with the now less-specific “black dots” sign of tinea capitis. Thus, no clinical criteria exist for differentiation of patients with benign alopecia mucinosa from those with malignancy-associated alopecia mucinosa.
Keratosis pilaris atrophicans
Keratosis pilaris decalvans involves widespread follicular hyperkeratosis with variable progression to atrophy, cicatricial alopecia of the scalp, and photophobia.
In folliculitis spinulosa decalvans, scalp pustules develop after puberty, often with bacterial infection. This condition may be related to a mutation in MBTPS2.[29]
In keratosis pilaris atrophicans faciei, follicular hyperkeratosis develops on the eyebrows but spares the scalp.
With atrophoderma vermiculata, follicular hyperkeratosis involves the cheeks but spares the scalp. Close examination is required in less dramatic cases in order to rule out nonfollicular mimics such as multiple minute digitate hyperkeratosis (also known as spiny hyperkeratosis) and other differential diagnoses related to spiny diseases.
Chemotherapy alopecia
Chemotherapy-induced alopecia can be diffuse or focal. Clinical signs of inflammation are lacking.[30]
Discoid Lupus
In adults, discoid lupus erythematosus affects females more often than males. An increased prevalence among African Americans has been reported in the United States.[31] The onset of disease is typically between ages 20 and 40 years. Approximately 10% of adults with discoid lupus erythematosus develop systemic lupus erythematosus (SLE); the likelihood is significantly higher in children and adolescents (26%-31%).[32] Similarly, 10% of systemic lupus erythematosus patients develop discoid lupus erythematosus. The course of systemic disease is often severe, with renal or neurologic involvement. However, when systemic lupus erythematosus precedes the onset of discoid lupus erythematosus, systemic disease tends to be relatively mild.[32]
Involvement of the scalp is common in adults with discoid lupus erythematosus (approximately 50%), and half the patients have the initial onset on the scalp.[33]
Patients often report pruritus. The initial erythematous papule or plaque undergoes centrifugal spread and a coin-shaped (discoid) erythematous plaque forms, with follicular plugging and adherent scale. The “carpet tack” sign may be elicited with retraction of the scale. Eventually, erythema diminishes and atrophy, telangiectases, hypopigmentation or depigmentation, and loss of follicular ostia become prominent.
If disease is localized, spontaneous remission occurs within 4 years in approximately 50% of affected persons. Intralesional recurrences are common, along with other complications such as aggressive squamous cell carcinoma with a high metastatic rate.
Folliculitis decalvans
Folliculitis decalvans often starts with a pinpoint erythematous follicular pustule or papule with pain or pruritus. Multiple lesions soon appear, with formation of a large abscess. Clinical findings may include round- to irregularly-shaped, atrophic, flesh-colored or ivory-white areas of scarring alopecia. These areas spread peripherally and can be multifocal. The course is chronic and slowly progressive. Tufted folliculitis may be present.
Perifolliculitis capitis abscedens et suffodiens
Papules progress to painful, bulbous, firm or fluctuant nodules. Pressure on affected sites can result in expression of seropurulent exudate. Long-standing, untreated disease progresses from nonscarring to scarring alopecia. Lymphadenopathy may be present. Perifolliculitis capitis abscedens et suffodiens can resemble and be confused with kerion.
Acne keloidalis
Acne keloidalis is often noted along the posterior hairline and neck. It is mainly found in nonwhite males, although females and whites are also affected. Onset occurs after adolescence. Pinpoint, smooth, follicular papules are evident early in disease and may be crusted, umbilicated, or pustular and contain hair. These papules may coalesce to nodules or keloidal plaques. Abscesses, sinuses, polytrichia, tufted hair folliculitis, foul-smelling discharge, and pain are possible findings.
Acne necrotica
The varioliformis variant is a chronic, relapsing disorder of the adult anterior hairline. Similar findings may be noted in a seborrheic distribution. Examination findings include pruritic, tender, reddish-brown papules or pustules that umbilicate and then undergo central necrosis. These lesions ultimately leave a round hemorrhagic crust that eventually sheds. Varioliform scars result, appearing as focal areas of cicatricial alopecia. A few lesions typically appear with each outbreak. Aggravation in the summer has been reported.
The miliaris variant is not often seen intact because pruritus can lead to near-neurotic excoriation of the lesions.
Erosive pustular dermatosis
Patients develop large, asymptomatic or tender, well-demarcated, boggy, crusted plaques with exudative erosions and pustules. Episodic pustular flares, with slow enlargement over years, are common. Cicatricial alopecia is common, as is bacterial colonization.
Depending on the presentation, it may be prudent to (1) evaluate the patient for potential mimics (eg, syphilis), (2) draw bacterial/fungal cultures if infection is suspected, (3) rule out overlap conditions that may be autoimmune or stress based (thyroid, anemia), and (4) consider problems with systemic correlation.[26]
Studies have also suggested a role for evaluating zinc and vitamin D levels in alopecia patients. Although the correlation may exist, it has not yet been established if they are directly associated. Nevertheless, such testing is relatively inexpensive.[36, 37]
With regard to scalp biopsy, the site chosen for the specimen is crucial for proper yield of pathologic information. Ideally, the site should be clinically active.[3]
The chosen biopsy site should be representative of clinically active disease, with primary morphologic features and a positive pull test (if present). Symptomatic sites are often helpful in selecting the location for obtaining the biopsy specimen. Examination of a sample taken from end-stage disease/balding areas is usually not productive. In the absence of clinical inflammation, biopsy of a hair-bearing site with a relative paucity, but not complete lack, of follicular ostia may suffice. The direction of the biopsy should be in line with the follicle course in the scalp. This will help obtain complete follicles for histologic examination.
Dermatoscope evaluation has been reported in a small series. Validation in large randomized studies is pending. At this time, findings reported are as follows[38] :
Discoid lupus - White patches, branching capillaries, and keratin plugs
Lichen planopilaris - Perifollicular scales and white dots
Aside from white dots, blue-grey dots were also described and may be on the spectrum of variants of inflammatory and postinflammatory changes of scarring, especially in darker-skinned patients.
All findings showed the expected reduced follicle ostia.
Scalp biopsy has been shown to be especially effective when samples are submitted for both transverse and horizontal sectioning. In nonspecific presentations, with continued progression, serial biopsies may be required. Horizontal and vertical samples and a combination called HoVert (HOrizontal VERTical) have been proposed to be of use.[39, 40]
In nonspecific presentations with continued progression, serial biopsies may be required. The current literature on histologic features of scarring alopecia only consists of small case reports or series. Features believed to be specific to one condition (eg, hair casts in traction alopecia and alopecia areata)[41] often occur in several other conditions.
Typical scarring alopecia demonstrates perifollicular concentric fibrosis, mild perifollicular and perivascular lymphoid cell infiltrate (if of the lymphocytic scarring type), destruction of the follicular epithelium, naked hair shafts in giant cells, and, in terminal phases, follicular dropout. Numerous end-stage fibrous tracts replaced by amorphous connective tissue, consistent with follicular scars, are seen in the subcutaneous tissue. The loss of sebaceous glands is believed to be a helpful hint to indicate scarring alopecia.[20]
Note one example of a histologic division of the scarring alopecias based on data from the North American Hair Research Society (NAHRS).
Lymphocytic entities are as follows:
Chronic cutaneous lupus erythematosus
Lichen planopilaris
Graham-Little syndrome
Classic pseudopelade (Brocq)
Central centrifugal cicatricial alopecia
Alopecia mucinosa
Keratosis follicularis spinulosa decalvans
Neutrophilic entities are as follows:
Folliculitis decalvans
Dissecting cellulitis/folliculitis (perifolliculitis capitis abscedens et suffodiens)
Mixed entities are as follows:
Folliculitis (acne) keloidalis
Folliculitis (acne) necrotica
Erosive pustular dermatosis
Classic histologic patterns
The following are histologic patterns that are used by many pathologists in horizontal sections of a 4-mm punch biopsy sample. Understanding the patterns and the differentials assists in diagnosis of the alopecia biopsy sample.
Normal hair biopsy findings are as follows:
Total number of hairs - 30-45 (can be half this number in African Americans)
Telogen hairs - Less than 15%
Terminal hairs - Vellus hairs ratio: 2:1
Follicular units - 12-14, each with 4-6 hairs
Lichen planopilaris
Lichenoid dermatitis is present in lichen planopilaris (and its clinical variants, regardless of presentation) at the level of the infundibulum and can easily be missed in transverse sections. These are mostly CD8 cells. Concentric lamellar perifollicular fibrosis can develop.
Staining with Verhoeff–van Gieson elastin stain may be of value in differentiating advanced cases of discoid lupus erythematosus, lichen planopilaris, and pseudopelade of Brocq, which often have overlap features on routine pathologic examination but display distinct patterns on elastic tissue staining. End-stage lichen planopilaris shows loss of elastic fibers in a superficial dermal wedge-shaped scar, which is better demarcated with elastic stain. Discoid lupus erythematosus elastin stain shows a more diffuse broad dermal scar pattern.[42]
Direct immunofluorescence highlights the presence of colloid bodies in the peri-infundibular area after staining with immunoglobulin M (less frequently with immunoglobulins G, A and C3). A linear band of fibrin deposition is present along the basement membrane zone of affected follicles, while the interfollicular epidermis is negative for immunoreactants.
In the frontal fibrosing variant, reports have noted histopathologic features of lichen planopilaris and some authors believe this variant preferentially affects the miniaturized secondary vellus hairs in those with androgenetic alopecia.[43]
No large studies have validated direct immunofluorescence results as sensitive or specific for this alopecia variant.
Central centrifugal cicatricial alopecia
The findings are variable, as this does not appear to represent a single condition and at this time may be a clinical pattern of scarring alopecia.
Some authors have suggested that central centrifugal cicatricial alopecia has unique histology findings.[3] These findings include premature desquamation of the inner root sheath below the isthmus and eccentric thinning of the follicular epithelium. Whereas desquamation of the inner root sheath is a feature normally observed at the isthmus, its early presence below this level indicates pathology. Further, premature desquamation of the inner root sheath can be found in other inflammatory conditions of the scalp, including lichen planopilaris. Thus, to distinguish these diagnoses, it has been suggested that central centrifugal cicatricial alopecia has this finding in otherwise normal hair follicles without otherwise showing lymphocytic inflammation or structural alteration. In vertical sections, thickened dermal elastic fibers in a hyalinized dermis have been reported.[3]
Pseudopelade of Brocq
In advanced disease, elastin stains reveal dense elastic tissue cuffing a broad, fibrotic follicular tract, unlike the characteristic pattern seen in advanced discoid lupus erythematosus and lichen planopilaris. Other histologic findings are nonspecific; concentric lamellar fibroplasia around the upper follicle, sebaceous gland loss, and, ultimately, complete destruction of the pilosebaceous unit are noted. End-stage disease is marked by follicular longitudinal fibrous tracts extending into the subcutis, which often are found in association with hair-shaft granulomas.
Traction alopecia
In early traction alopecia, a subacute perifollicular inflammation is accompanied by mild-to-moderate hyperkeratosis. In cases of prolonged traction, decreased hair follicle and sebaceous gland density, perifollicular fibrosis, and vertical bands of follicular scarring are seen. However, blood vessels and eccrine sweat glands remain unaffected. Trichomalacia and pigment casts may be found but are not specific. Histologic pattern can be very similar to normal biopsy with variance by timeline (ie, less follicles and more streamers/telogen hairs in advanced disease).
Chemotherapy alopecia
Various patterns of inflammation have been noted. None is well proven enough to be specific to this type of permanent alopecia.[30]
Alopecia mucinosa
Intrafollicular mucin deposition is seen. A perivascular and perifollicular lymphocytic infiltrate is seen, often with eosinophils. Careful examination should be performed to investigate for findings of cutaneous T-cell lymphoma.
Keratosis pilaris atrophicans
A few reports have noted compact hyperkeratosis and hypergranulosis of the upper follicular epithelium. Superficial intrafollicular and perifollicular edema, as well as perivascular lymphocytes and neutrophils, may be present with acute disease or progression.
Discoid lupus
Discoid lupus erythematosus presents with vacuolar interface dermatitis, with a few dyskeratotic keratinocytes, cytoid bodies, and a variably dense periadnexal and superficial/deep perivascular lymphocytic infiltrate with dermal mucin.[44] Perifollicular inflammation can surround any part of the mid and upper follicle. Sebaceous glands can be atrophied or absent. Distention of follicular ostia with laminated keratin can be prominent (ie, follicular plugging histology). When stained with Verhoeff–van Gieson stain, advanced discoid lesions reveal diffuse loss of elastic fibers. This is compared with lichen planopilaris, which has a wedge-shaped scar in the area of the infundibulum that can often be found with a loss of elastic fibers only in that area.
Use of direct immunofluorescence for diagnosis and differentiation from other primary lymphocytic cicatricial alopecias can be helpful. To optimize the yield, the lesion chosen for biopsy should be untreated for at least 2-4 weeks and should be at least 3 months old. Diagnostic features of discoid lupus erythematosus on direct immunofluorescence are deposition of immunoglobulin G, immunoglobulin M, and C3 in a granular bandlike pattern at the dermal interface.
At times, differentiation of lichen planopilaris from discoid lupus erythematosus can be challenging in older lesions or those that are not fully developed. However, perieccrine inflammation, deep perivascular inflammation, and dermal mucin are not found in lichen planopilaris.
Atypical, linear presentations of lupus alopecia have also been reported. These show clinical similarity to alopecia areata but histologic findings of lupus.[45]
Acne keloidalis
The biopsy demonstrates scarring, ingrown hairs, and suppurative folliculitis. Many plasma cells are present in the dermis.
Acne necrotica
Histology studies show lymphocytic exocytosis, spongiosis, and sporadic necrosis of keratinocytes in the upper pilosebaceous unit. A dense perifollicular and perivascular lymphocytic infiltrate are present.[46] Eventually, formation of confluent necrosis of the follicular epithelium and adjacent epidermis/dermis is noted. Neutrophils may be present.
Erosive pustular dermatosis
Histology findings are nonspecific, and direct immunofluorescence results are often negative. A dense, chronic mixed inflammatory cell infiltrate and foreign body giant cells may be found but are not folliculocentric. Fibrosis and follicular unit loss eventually ensue.
Pressure alopecia
Classic diagnostic features on histology have not been determined.
Folliculitis decalvans
Histology studies show acneiform infundibular dilatation and intrafollicular and perifollicular neutrophilic infiltrate around the upper and mid follicle. With disease of long duration, the infiltrate may be mixed with neutrophils, lymphocytes, and plasma cells and extends into the deeper dermis. Abscess formation is less prominent than in perifolliculitis capitis abscedens et suffodiens and no sinus tracts are found. Granulomatous inflammation with foreign body giant cells around naked hair shafts may be seen.
Perifolliculitis capitis abscedens et suffodiens
Histology findings show infundibular acneiform distension with intrafollicular and perifollicular neutrophilic infiltration. Follicular perforation results in abscesses of neutrophils, lymphocytes, and plasma cells. The abscesses may become partially lined by squamous epithelium, forming a sinus tract.
Senescent alopecia
Telogen counts can be normal. Inflammation is often absent. Follicles are not as long or as wide as expected, but they are not miniaturized, as in androgenetic alopecia. In a 4-mm biopsy specimen, the total number of hairs would be 20-35 (normal count, 30-45). Unlike androgenetic alopecia, the terminal-to-vellus ratio is a normal 2:1.[28]
Few large, randomized, blinded, controlled studies are available. Most treatments are considered off label. Stimulating hair growth using options often considered for nonscarring alopecia has been attempted with mixed results, and these include finasteride, minoxidil topically, and bimatoprost injections.[47] In general, with both scarring and nonscarring alopecia, early intervention is best.[48]
Lichen planopilaris
Primary treatment is focused on anti-inflammatory modulation. More common medications used are monthly intralesional triamcinolone acetonide at 3-10 mg/mL, prednisone, and systemic retinoids, although hydroxychloroquine and other immune suppressants (particularly mycophenolate mofetil) are also used. Evidence suggests good results with mycophenolate mofetil. Evidence also suggests that while hydroxychloroquine may suppress symptoms, it may not prevent disease progression.[49] Novel approaches include attempting PPAR modulation.[19]
Central centrifugal cicatricial alopecia
No large randomized blinded controlled studies are available. Symptoms or histologic evidence of inflammation has been reported to improve with daily use of a potent topical corticosteroid and tetracycline.
Traction alopecia
Patient education and behavioral modification are most critical.
Discoid lupus
Sun avoidance is a common suggestion for lupus patients. Whether sun exposure plays a role in discoid lupus erythematosus is not clear because several authors have noted no correlation in discoid lupus erythematosus prevalence and patients with previous alopecia avoiding sun exposure.
Two randomized and controlled studies are available. These studies showed that class II corticosteroid creams are more efficacious than class VII preparations, and approximately half the patients have improvement with hydroxychloroquine. Acitretin has also shown good results, although with increased adverse effects.
Several other treatment modalities have been advocated. These include concurrent topical class I or class II steroids along with intralesional triamcinolone acetonide (10 mg/mL every 4-6 wk). Hydroxychloroquine is also commonly used as part of the treatment regimen. Clinical improvement is often seen within 4-8 weeks, with the full extent of benefit not evident for several months. Despite its good safety profile, prior to initiating therapy, a baseline ophthalmologic examination should be conducted, and patients who smoke should be encouraged to quit because cigarette smoking has been shown to reduce therapeutic responsiveness in a dose-dependent fashion. A bridge of anti-inflammatory prednisone orally is sometimes used for the first 3 months.
With recalcitrant disease, oral retinoids (acitretin or isotretinoin) have been used with good-to-excellent results. Immune-suppressing medications have been used for treatment of discoid lupus erythematosus, with largely mixed outcomes.
Acne keloidalis
Early disease can be controlled with topical steroids and topical antibiotics. Intralesional steroids, laser ablation, and retinoids have also been used. Surgical excision can also be effective.
Acne necrotica
Empiric oral tetracyclines or antistaphylococcal agents, antibacterial shampoos, and even oral retinoids may produce results.
Erosive pustular dermatosis
Topical steroids have been reported to be effective. Reports of treatment and aggravation have been noted with phototherapy. Traumatic manipulation also often aggravates the lesions. Topical psoriatic medications have been reported to be effective.
Pressure alopecia
No large randomized blinded controlled studies are available.
Trichotillomania
Psychiatric behavioral modulation is an option.
In a double-blind, placebo-controlled trial, N -acetylcysteine improved trichotillomania in adults (n = 50) with compulsive behavior. The dosage ranged from 1200-2400 mg/d. N -acetylcysteine restores extracellular glutamate concentration in the nucleus accumbens and therefore may be effective in reducing compulsive behavior. This study is thought to be the first to examine the effect of a glutamatergic agent for the treatment of trichotillomania.[50]
Alopecia mucinosa
Age-appropriate cancer screening should be undertaken. Small reports have included use of topical, intralesional, and oral corticosteroids; antibiotics; and topical/oral retinoids.
Keratosis pilaris atrophicans
Pustular flares should prompt bacterial cultures. Anecdotal reports have noted use of topical/oral steroids, topical/oral retinoids, and dapsone. Baseline and routine ophthalmologic examination may be warranted.
Folliculitis decalvans
Combination antibiotic treatment including rifampin can sometimes produce sustained disease-free remission. Rifampin (600 mg twice daily) and clindamycin (150-300 mg twice daily) are commonly used together. Sustained relief can also be obtained through the use of topical corticosteroids together with an oral tetracycline.
Perifolliculitis capitis abscedens et suffodiens
Oral antibiotics (eg, tetracyclines) and intralesional triamcinolone acetonide are most effective if used in combination. The response to oral isotretinoin is often disappointing, but some reports describe a response to the more potent antitumor necrosis factor biologic agents.
Incision and drainage of painful nodules or excisional carbon dioxide laser treatment with secondary-intention healing are among several surgical techniques advocated.
Despite the lack of multiple medical options for the treatment of end-stage scarring alopecia, achieving cosmetically acceptable correction of alopecia by means of surgical hair transplantation procedures (eg, punch grafting, flap rotation) is possible.[51]
However, koebnerization of the disease may occur. Additionally, surgical correction of alopecia should not be performed if the patient has any active scalp disease or inflammation.
Recent advances in follicle unit extraction have also led to improved survival and more natural outcomes in scarring alopecia patients.[52, 53, 54]
Finally, scalp reduction can be used in small areas (usually ≤1 cm).
Stress and psychiatric morbidity are common considerations to evaluate. Often, consultation with a psychiatrist is of assistance. Patients often refuse this suggestion.
Sufficient levels of iron and protein in the diet may help promote normal hair growth. The exact role of diet with scarring alopecia has not been evaluated extensively in the medical literature. Diet and vitamins such as vitamin D are an established factor in normal hair growth and development but have not yet been strongly correlated with scar formation and inflammation.[55]
Clinical Context:
Triamcinolone can be used topically or injected intralesionally. It decreases inflammation by suppressing the migration of PMN leukocytes and reversing capillary permeability.
These agents are used for their anti-inflammatory properties, but they must be used with caution because they have local and systemic side effects. In most cases pustular folliculitis respond to topical corticosteroids.
Clinical Context:
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions. It suppresses mRNA expression of T helper type 2 (Th2) cytokines (interleukins 4 and 13) in peripheral blood mononuclear cells.
Clinical Context:
Pimecrolimus cream is used for short-term treatment or for intermittent, long-term treatment in unresponsive or intolerant cases. It is available in a 1% cream.
Clinical Context:
Isotretinoin is an oral retinoid indicated for recalcitrant, nodulocystic acne. It addresses all four pathogenic factors involved the development of acne: follicular hyperkeratinization, inflammation, sebum production, and Propionibacterium acnes growth. Treatment is weight-based, usually dosed initially 0.5 mg/kg and increased to 1 mg/kg in 2 divided doses for 15-20 weeks. Once-daily dosing is not recommended. One may adjust the dose to administer up to 2 mg/kg/day. Patients must be registered into the government-regulated iPledge program in order to receive the medication.
Clinical Context:
Acitretin is a retinoic acid analog, like etretinate and isotretinoin. Etretinate is the main metabolite and has demonstrated clinical effects close to those seen with etretinate. Its mechanism of action is unknown.
These agents stimulate cellular retinoid receptors and help normalize keratinocyte differentiation and are comedolytic. In addition, they have anti-inflammatory properties. Oral isotretinoin also reduces sebum production in the skin.
Clinical Context:
Hydroxychloroquine may allow partial or complete control of the disease. Anecdotal evidence has suggested that morbilliform drug reactions are more common in patients with dermatomyositis than in those with other collagen vascular diseases. Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.
Antimalarial agents may be used as steroid-sparing agents to treat skin disease. Hydroxychloroquine is preferred; chloroquine and quinacrine (100 mg/day) are second-line agents. Quinacrine may suppress bone marrow and is distributed by the Centers for Disease Control and Prevention (CDC); blood cell counts should be obtained regularly.
Clinical Context:
Tetracycline inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunit(s). Tetracycline has anti-inflammatory activity. One may administer 250-500 mg orally twice daily.
Clinical Context:
Doxycycline is a broad-spectrum antibiotic with excellent gram-positive coverage, including most resistant staphylococcal organisms. It inhibits protein synthesis and, thus, bacterial growth, by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Clinical Context:
Clidamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Clidamycin is commonly used topically, but it can be given orally. Oral monotherapy administration should be avoided to reduce the risk of antibiotic resistance. One may administer 150-300 mg twice daily.
Clinical Context:
Rifampin is for use in combination with at least one other antituberculosis drug. It inhibits DNA-dependent bacterial RNA polymerase but not mammalian RNA polymerase. Cross-resistance may occur. One may administer 600 mg twice daily.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting. Antibiotic treatment for rosacea include tetracyclines and metronidazole. Dapsone is used in the treatment of eosinophilic pustular folliculitis.
Basil M Hantash, MD, PhD, MBA, Medical Director, Advanced Skin Institute
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Jaggi Rao, MD, FRCPC, Clinical Professor of Medicine, Division of Dermatology and Cutaneous Sciences, Director of Dermatology Residency Program, University of Alberta Faculty of Medicine and Dentistry, Canada
Disclosure: Nothing to disclose.
Mayla T Carlos, PA-C, MPH, MSPAS, Physician Assistant for Dermatology Practice, Advanced Skin Institute
Disclosure: Nothing to disclose.
Rashid M Rashid, MD, PhD, Director, Mosaic Clinic Hair Transplant Center of Houston
Disclosure: Nothing to disclose.
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School
End-stage scarring alopecia (ESSA) with prior history of itching and burning, along with a receding hairline. Started as the lichen planopilaris variant, frontal fibrosing alopecia. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Alopecia due to primary cutaneous follicular center cell lymphoma. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Recalcitrant scarring pressure alopecia several years after an ICU stay. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Traction alopecia.
Traction alopecia.
Alopecia due to primary cutaneous follicular center cell lymphoma. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Recalcitrant scarring pressure alopecia several years after an ICU stay. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
End-stage scarring alopecia (ESSA) with prior history of itching and burning, along with a receding hairline. Started as the lichen planopilaris variant, frontal fibrosing alopecia. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Dissecting scalp cellulitis. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Armpit scarring alopecia in lichen planopilaris variant. Patient presented with frontal fibrosing alopecia. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Acne keloidalis. A misnomer term based on clinical examination findings. Used with permission, rights retained, courtesy of Rashid M. Rashid, MD, PhD, Morzak Research Collaborative.
Lichen planopilaris in its active stage presenting in a lighter-skinned patient. Courtesy of Rashid M Rashid, MD, PhD, and Ronald Rapini, MD.
Alopecic and aseptic nodules of the scalp (AANS) is a new entity reported first in Japan as "pseudocyst of the scalp." The main location of the nodules was the occiput. The associated alopecia was nonscarring. Histology is nonspecific but often shows deep granulomas. AANS reponds to tetracyclines. Photo courtesy of Sami Abdennader, MD (rights retained).
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