Acne vulgaris, an inflammatory disease of sebaceous follicles, is a common disorder that affects a large proportion of the teenage population.^{15.16.17.18. and 19.} Acne vulgaris also affects people with skin of color.^{20. and 21.} The incidence in a recent survey of Asian teenagers in Singapore was 88%. ²² The incidence is low in non-westernized populations. ²³ It is usually a mild affliction which improves spontaneously after adolescence. ²⁴ In a small proportion, it produces considerable disfigurement. Severity can impact on the quality of life of the affected individual.^{25.26.27.28. and 29.} Acne can also be found in some neonates, infants, and adults.^{30.31.32.33. and 34.} Infantile acne may be the initial sign of an adrenocortical tumor. ³⁵ Infantile acne has a male predominance. ³⁶ It may result in considerable scarring. ³⁷ Late-onset acne appears to be a special group in which endogenous factors play a major role. ³⁸ A high proportion of female acne is of late onset.^{39. and 40.}

In a study published in 2006, but based on 2004 data, which was a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology, acne was the second most costly skin disease after skin ulcers and wounds, accounting for $2.5 billion annually in direct medical costs. ⁴¹ Of this amount, $1.74 billion was expended on prescription drugs, and this figure does not include specialty pharmaceuticals, which are often used in the treatment of acne. Incidentally, the prevalence was estimated to be 50.2 million persons. ⁴¹

Acne is a polymorphic disorder with such diverse lesions as comedones, papules, pustules, cysts, sinuses, and scars. ¹⁵ Scarring can be minimized by early effective treatment.^{42. and 43.} An attempt has been made to classify the scars into several subtypes. ⁴⁴ The comedones may take the form of tiny white papules known as ‘whiteheads’ (closed comedones) or small papules with a central core, the surface of which is black. These lesions are known as ‘blackheads’ (open comedones). Comedones are not confined to acne, being found in senile skin, ⁴⁵ in a rare congenital form, ⁴⁶ in nevus comedonicus, and following exposure to certain chemicals such as coal tar. ⁴⁷ Only a few inflammatory lesions are present at any one time in mild acne, although comedones may be present and dormant for years. ⁴⁸ A recent study has confirmed the comedomal origin of the majority of inflammatory acne lesions. ⁴⁹ However, quite a few cases (28%) appear to arise from normal skin, although some microcomedones may be difficult to visualize. ⁴⁹

Acne affects the face and, less frequently, the upper part of the trunk. These are sites of maximum density of sebaceous follicles. ¹⁶ In one report, acne presented in a zosteriform distribution (‘acne nevus’). ⁵⁰ In another, the acneiform rash was localized to the site of previous herpes zoster infection. ⁵¹ Acne is uncommon in the scalp, suggesting that terminal follicles may have a protective function. ⁵²

Acne fulminans is a rare, acute form of acne, found usually in young adult males.^{179. and 180.} There is a sudden onset of painful, ulcerated, and crusted lesions accompanied by fever, musculoskeletal pain, and leukocytosis.^{179. and 181.} Lytic lesions of bone develop in 25% of cases.^{179.182.183. and 184.} A subgroup without systemic features has been reported. ¹⁸⁵ Acne fulminans has been reported in association with Crohn’s disease, ¹⁸⁶ erythema nodosum,^{187. and 188.} and the use of testosterone. ¹⁸⁹ It has also been precipitated by the use of isotretinoin in the treatment of acne vulgaris. ¹⁹⁰ Familial cases have been reported. ¹⁹¹

The etiology of this condition is unknown, although there is speculation that immune mechanisms are involved. ¹⁸² This is supported by the response that occurs to systemic corticosteroid therapy.^{181. and 192.}

Acne fulminans, or another pustular dermatosis such as acne conglobata, palmoplantar pustulosis, hidradenitis suppurativa or pustular psoriasis, may occur as the cutaneous manifestation of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis).^{193.194. and 195.}

Systemic corticosteroids are the mainstay of therapy for acne fulminans. The use of adjuvant oral retinoids is controversial, as their use for acne vulgaris may precipitate the condition. ¹⁹⁰ Cyclosporine (ciclosporin), methotrexate, and infliximab have all been used as single adjuvants with corticosteroids. ¹⁹⁴

Chloracne is an acneiform eruption caused by systemic poisoning by halogenated aromatic compounds.^{197.198. and 199.} Although the brominated compounds tend to be more toxic, the term ‘chloracne’ stems from the chlorinated version. ²⁰⁰ Industrial exposure is the usual source of the chloracnegens, although exposure to defoliants containing dioxin was encountered in the Vietnam War.^{201.202.203. and 204.} Cutaneous lesions may persist for long periods after the last exposure to the offending chemical.

Chloracne is distinct from other forms of acne. ¹⁹⁷ It most often involves the malar crescent, the retroauricular region, and the scrotum and penis. Erythema and pigmentation of the face may also occur. ¹⁹⁷ The primary lesion is the comedo, which is intermingled with small cysts. ¹⁹⁷ Inflammatory lesions are sparse. Dioxins have also produced areas resembling granuloma annulare and atrophoderma vermiculatum. ¹⁹⁷

Acute superficial folliculitis, also known as impetigo of Bockhart, is characterized by small pustules developing around follicular ostia and frequently pierced by a hair.^{205. and 206.}Staphylococcus aureus has been implicated in the etiology.

There have been several reports of a pustular folliculitis of the face and upper part of the trunk following exposure to sunlight.^{208.209.210.211. and 212.} The lesions usually appear 4–6 hours after the exposure. ²¹³ The mechanism by which exposure to ultraviolet light results in folliculitic lesions remains to be elucidated, although the condition may be related to acne vulgaris and acne estivalis. ²¹⁰

Acne necrotica (acne varioliformis) is a rare dermatosis of adults, consisting of crops of erythematous, follicle-based papules that become superficially necrotic, umbilicated, and crusted, with subsequent healing which produces a depressed varioliform scar.^{214.215. and 216.} Only a small number of active lesions may be present at any time. They develop on the frontal hairline, forehead, and face and sometimes on the upper part of the trunk.

Acne necrotica miliaris has been regarded as a pruritic, non-scarring variant of acne necrotica in which follicular vesiculopustules develop on the scalp. ²¹⁴ This condition has been regarded as nothing more than neurotic excoriations superimposed on a bacterial folliculitis, an etiology that has also been proposed for acne necrotica itself. ²¹⁷

A necrotizing folliculitis is a rare cutaneous manifestation of the acquired immunodeficiency syndrome (AIDS) or its prodromes. ²¹⁸

Eosinophilic (pustular) folliculitis is a heterogeneous group of disorders with several clinical subsets:

The classic form, eosinophilic pustular folliculitis (Ofuji’s disease), is a rare, chronic dermatosis, first described in the Japanese^{220.221. and 222.} but now reported occasionally in white and other races.^{223.224.225.226.227. and 228.} There are recurrent, sterile, follicular papules and pustules with a tendency to form circinate plaques.^{229.230. and 231.} These may show central clearing with residual hyperpigmentation. ‘Seborrheic areas’, such as the face, trunk, and extensor surface of the proximal part of the limbs, ²³² are usually involved but in 20% of cases the non-hair-bearing palms and soles may also be involved. ²²⁹ For this reason, the designations ‘eosinophilic pustular dermatosis’²³³ and ‘sterile eosinophilic pustulosis’ have been suggested as more appropriate titles. There is a male preponderance. ²²⁸ The mean age at presentation in one series was 35 years. ²³⁴ A peripheral leukocytosis and eosinophilia are often present. A case that was exacerbated by pregnancies has been reported. ²³⁵ Another case was associated with pathergy. ²³⁶

The condition reported in two brothers as ‘circinate eosinophilic dermatosis’ has some similarities. ²³⁷

The etiology of eosinophilic pustular folliculitis is unknown. Interestingly, a similar lesion has been reported in dogs. ²³⁸ Various immunological abnormalities have been reported in some patients, but this is not a constant feature.^{239. and 240.} Circulating antibodies to basal cell cytoplasm, ²⁴¹ and intercellular antigens have been noted. ²⁴² Chemotactic factors have also been isolated from the skin. ²⁴³ More recently it has been suggested that the production of nitric oxide by eosinophils may have a pathogenetic role. ²⁴⁴

HIV-associated (immunosuppression-associated) eosinophilic pustular folliculitis has been regarded as a subset of the pruritic papular eruption of human immunodeficiency virus infection.^{231.245.246.247.248.249.250.251.252. and 253.} It differs from the classic form (Ofuji’s disease) by the severe pruritus, the absence of circinate and palmoplantar lesions, and the less frequent involvement of the face. ²⁵⁴ Coexisting follicular mucinosis has been reported in some patients.^{255. and 256.} It has been suggested that HIV-associated eosinophilic folliculitis is an autoimmune disease with the sebocyte or some constituent of sebum acting as the autoantigen. ²⁵⁷ Immunohistochemistry shows increased expression of interleukin-4, and -5, as well as eotaxin. ²⁵⁸ In one patient, the eruption appeared to be related to the use of foscarnet therapy. ²⁵⁹ Although the onset of eosinophilic folliculitis may be initiated by antiretroviral therapy, eosinophilic folliculitis may respond favorably to treatment with this therapy. ²⁶⁰

Pediatric (childhood) eosinophilic pustular folliculitis is usually confined to the scalp, although grouped aggregates of follicular pustules can occur on the face, extremities, and trunk in some patients.^{261.262.263. and 264.} Onset can be as early as the first day of life. ²⁶⁵ It is seen most frequently in white people but Japanese cases occur. ²⁶⁶ It usually has a self-limited course. This condition is no longer regarded as a variant of eosinophilic folliculitis as interfollicular inflammation is sometimes the predominant feature. Eosinophilic pustulosis appears to be an appropriate designation for these cases. Ziemer and Böer have questioned the existence of this variant, stating that previously reported cases encompass a spectrum of eosinophil-rich dermatoses including scabies and other bite reactions. ²⁶⁷

Fungal eosinophilic folliculitis is usually a localized disease, characterized by erosive and pustular plaques.^{268. and 269.}Trichophyton rubrum can produce a folliculitis that is histologically identical to eosinophilic pustular folliculitis. ²⁷⁰ Larva migrans, Toxocara canis, and scabies may be associated with an eosinophilic folliculitis.^{271. and 272.}

The miscellaneous group includes patients in whom bacteria, such as Pseudomonas, have been isolated and patients with myeloproliferative or other hematological disorders.^{273.274.275. and 276.} It has been reported in association with pulmonary eosinophilia, ²⁷⁷ and following allogeneic peripheral blood stem cell transplantation. ²⁷⁸ Nine HIV-negative patients with an atopic diathesis have been reported with ulcerative and/or nodular plaques mainly on the face and/or extremities, sometimes in an annular configuration. Other necrotizing variants have been reported.^{279. and 280.} The histology was that of a necrotizing eosinophilic folliculitis. These cases appear to be the ‘eosinophilic equivalent’ of sterile neutrophilic folliculitis with perifollicular vasculopathy (see p. 410). Drugs such as allopurinol, carbamazepine, and minocycline have been associated with an eosinophilic folliculitis.281.^{282. and 283.} It has also followed the use of a fentanyl-TTS patch, ²⁸⁴ and chemotherapy. ²⁸⁵ Rarely, pemphigus vegetans may present as an eosinophilic folliculitis. ²⁸⁶ A case associated with the nevoid basal cell carcinoma syndrome resolved after removal of the jaw cyst associated with the syndrome. ²⁸⁷

Infundibulofolliculitis is mentioned here for completeness, although it is discussed in further detail with the spongiotic tissue reaction (see p. 99). The histopathological changes are those of follicular spongiosis. A few neutrophils may be found in the spongiotic infundibulum or in the keratin plug which is sometimes present in the involved follicle. A variable mononuclear cell infiltrate usually surrounds the upper dermal portion of the hair follicle.^{302. and 303.}

A furuncle (boil) is a deep-seated infection centered on the pilosebaceous unit. ³⁰⁵ Boils commonly occur at sites of friction by clothing such as the back of the neck, the buttocks and inner aspect of the thighs. The lesion begins as a painful, follicular papule with surrounding erythema and induration. ³⁰⁵ The center usually becomes yellow, softens and discharges pus. A rim of desquamation often surrounds the infected hair follicle. ³⁰⁶ Healing takes place with minimal scarring. A carbuncle is a coalescence of multiple furuncles which may lead to multiple points of drainage on the skin surface. There are often constitutional symptoms.

Staphylococcus aureus is the organism most often involved. ³⁰⁷

Pseudomonas folliculitis is usually caused by Pseudomonas aeruginosa. It presents as an erythematous follicular eruption which may be maculopapular, vesicular, pustular, or polymorphous.^{309. and 310.} It usually involves the trunk, axillae, and proximal parts of the extremities. There may be constitutional symptoms. ³¹¹ Lesions develop 8–48 hours after recreational exposure to the organism, which is found in contaminated sponges, whirlpools, and hot tubs.^{312.313.314. and 315.} Organisms other than Pseudomonas may be responsible for hot tub (spa bath) folliculitis. ³¹⁶ Spontaneous clearing usually occurs within a week. Sporadic cases, without recreational exposure, also occur. ³¹⁷

A folliculitis caused by Gram-negative bacteria may occur as a complication of prolonged antibiotic therapy in patients with acne vulgaris. ³¹⁸ Most of these infections are caused by a subgroup of lactose-fermenting bacteria, resulting in superficial pustules grouped around the nose. Pseudomonas aeruginosa has also been implicated in this clinical setting. ³¹⁹ In others, deep nodular and cystic lesions occur as a result of infection by species of Proteus. ³¹⁸Citrobacter diversus, Acinetobacter baumanii, ³²⁰Klebsiella sp., ³²¹Escherichia coli, and Enterobacter sp. have also been implicated.^{322. and 323.} In immunocompromised patients, organisms which are not usually pathogens, such as Micrococcus, have been involved. ³²⁴

Bacteria, possibly complicating the application of various oils to the skin, have been implicated in a pustular eruption of the legs seen in parts of Africa and India and known as dermatitis cruris pustulosa et atrophicans. ³²⁵

Salmonella dublin was isolated from one case of widespread folliculitis. ³²⁶

The pilosebaceous follicle may be infected with herpes simplex virus type I. Vesicular or pustular lesions may not be obvious clinically. ³²⁷ Recently it has been shown that infections with varicella zoster virus (VZV) are more common as a cause of a folliculitis than herpes simplex virus. ³²⁸ A granulomatous folliculitis has been reported as a manifestation of post-herpetic isotopic response.^{329. and 330.}

Viral-associated trichodysplasia (pilomatrix dysplasia, cyclosporine-induced folliculodystrophy, ³³³ virus-associated trichodysplasia spinulosa^{334. and 335.}) is a recently described follicular dystrophy of presumptive viral origin associated with immunosuppression.^{336.337. and 338.} The patients present with numerous, disfiguring, papular, and spiny lesions, predominantly affecting the central face. ³³⁹ Alopecia may be present elsewhere on the body. ³⁴⁰ Ultrastructurally, there are intranuclear viral particles consistent with polyoma virus. ³³⁴ There are anecdotal reports that topical cidofovir, an antiviral agent, has resulted in improvement in the condition. ³³⁹

Fungal elements may be seen on or within the hair shafts in certain dermatophyte infections, particularly tinea capitis. Various organisms may be involved, particularly Trichophyton tonsurans, Microsporum canis, and M. audouinii. ³⁴² Sometimes an inflamed boggy mass, known as a kerion, develops.

Pityrosporum folliculitis, resulting from infection of the follicle by Malassezia sp. (Pityrosporum), has been described on page 593. The small oval yeast responsible can be seen within the inflamed follicle and may be found in the adjacent dermis following rupture of the follicle.

Folliculitis decalvans is a chronic form of deep folliculitis that usually occurs on the scalp as oval patches of scarring alopecia at the expanding margins of which are follicular pustules.^{205. and 343.} Any or all of the hairy areas of the body may be involved. Folliculitis barbae (lupoid sycosis) is a related condition confined to the beard area, while epilating folliculitis of the glabrous skin is the name used in the earlier literature for a related condition involving the legs. ³⁴⁴ Folliculitis decalvans has been reported in identical twins. ³⁴⁵

Folliculitis decalvans usually runs a prolonged course of variable severity. The development of squamous cell carcinoma is a rare complication. ³⁴⁶ The etiology is unknown, although Staphylococcus aureus is sometimes cultured from the lesions. ³⁴⁷ It appears that early lesions are characterized by an infiltration of activated T-helper cells. IL-8 and ICAM-1 may contribute to the infiltration of neutrophils. ³⁴⁸

The very existence of this entity has been questioned, although the author still uses this diagnosis. Ackerman states that it is best to eschew the term, ³⁴⁹ while Sperling believes that most cases represent a highly inflammatory form of central centrifugal cicatricial alopecia. ³⁵⁰

Tufted hair folliculitis (see p. 430) has been regarded as a clinicopathological variant of folliculitis decalvans, ³⁵¹ but as it can be associated with other disease processes, it is best regarded as a distinct process. ³⁵²

Folliculitis keloidalis nuchae, also known as acne keloidalis, is a rare, idiopathic, inflammatory condition of the nape of the neck, restricted almost exclusively to adult males.^{353.354.355. and 356.} About 90% of patients are below the age of 40 years. ³⁵⁷ It is a form of primary scarring alopecia of the occipital and nuchal region. ³⁵⁸ It is more common in blacks of African origin. There are follicular papules and pustules which enlarge, forming confluent, thickened plaques, sometimes with discharging sinuses.^{353. and 359.} The lesions have caused secondary cutis verticis gyrata in affected persons.^{360. and 361.} Scarring results from this chronic inflammatory process. Surgery is sometimes required to manage the condition, when treatment with topical corticosteroids/antibiotics and oral antibiotics fails.^{362. and 363.}

The pathogenesis of this condition and the reasons for its occipital localization are not known. Postulated mechanisms include a seborrheic constitution, incurving hairs resulting from recurrent low-grade trauma (for example, by football helmets),^{356. and 364.} the use of antiepileptic drugs or cyclosporine,^{365. and 366.} and an increase in mast cell numbers in the occipital region.^{367.368. and 369.} Tinea capitis was the cause in one case. ³⁷⁰

Acne inversa (hidradenitis suppurativa) is a chronic, relapsing, inflammatory disorder involving the terminal hairs of one or more apocrine gland-bearing areas, which include the axillae, groins, pubic region, and perineum.^{376.377.378.379.380.381. and 382.} The author has responded to pleas to abandon the term hidradenitis suppurativa because it is a misnomer, in favor of acne inversa, ³⁸³ which may be another. ³⁸⁴ The term hidradenitis suppurativa appears to be the preferred one in Europe. ³⁸⁵ The prevalence estimate is 1 : 300. ³⁸⁶ There are recurrent, deep-seated inflammatory nodules, complicated by draining sinuses and subsequent scarring. The disease causes a high degree of morbidity; pain is often a problem.^{387. and 388.} The development of squamous cell carcinoma is a late and rare complication.^{389.390.391.392. and 393.} The tumors arise from the sinus tracts. ³⁹⁴ Other clinical features include the presence of comedones in retroauricular and apocrine sites, ³⁹⁵ a female predominance,^{396. and 397.} and a genetic predisposition.^{398.399. and 400.} Recently one Chinese family with the disease was mapped to chromosome 1p21.1–1q25.3. ⁴⁰¹ Interestingly, frequent losses in chromosomal region 1p21–p22 have been associated with diffuse malignant peritoneal mesothelioma, a rare neoplasm reported recently in association with acne inversa. ⁴⁰¹ Prepubertal onset is rare. ⁴⁰² Associations with lithium therapy, ⁴⁰³ Dowling–Degos disease, ⁴⁰⁴ cigarette smoking,^{405.406. and 407.} obesity, ³⁸⁵ and Crohn’s disease have been reported.^{408.409. and 410.} Host defense mechanisms are usually normal, except in some severe cases, where a reduction in T lymphocytes, and the presence of dysfunctional neutrophils have been documented.^{411. and 412.} Monocytes secrete less TNF-α and IL-6 than do cells from healthy controls, ⁴¹³ but toll-like receptor 2 is strongly expressed. ⁴¹⁴ There is now good evidence that acne inversa is an androgen-dependent disorder,^{415.416.417.418. and 419.} although how this relates to the poral occlusion by keratinous material is uncertain. ⁴²⁰ This occlusion is followed by an active folliculitis with, in some cases, a secondary apocrinitis and apocrine destruction. Apoeccrine glands, which drain directly onto the epidermal surface, appear to be uninvolved. ⁴²¹ Coagulase-negative staphylococci are the most common isolate; ⁴²² however, the microbiological flora is not constant. ⁴¹⁰ It is possible that an abnormal immune response against bacteria, colonizing the follicular infundibulum, may be one of the initial events leading to acne inversa. ⁴²³

Dissecting cellulitis of the scalp, also known as perifolliculitis capitis abscedens et suffodiens (Hoffmann’s disease), is an extremely rare disease characterized by the appearance of tender, suppurative nodules with interconnecting draining sinuses and subsequent scarring.^{442.443. and 444.} Patchy alopecia usually overlies the lesions, which have a predilection for the vertex and occipital scalp. There is a predilection for young adult black males. ⁴⁴⁵ Familial occurrence has been reported. ⁴⁴⁶ Dissecting cellulitis may occur alone or in association with the other follicular occlusion diseases – hidradenitis suppurativa and acne conglobata. ³⁷⁵ It has also been associated with an arthropathy, which may be axial, ⁴⁴⁷ and a marginal keratitis. ⁴⁴⁸ The development of squamous cell carcinoma is a rare complication. ⁴⁴⁹

The etiology is unknown, but follicular occlusion is presumed to play a role. Bacterial superinfection appears to be a secondary event.^{450. and 451.} Harsh trauma was implicated in one case. ⁴⁵²

Treatment with oral isotretinoin has been successful in several cases.^{445.453. and 454.} Quinolone antibiotics may be used as adjuvant therapy. ⁴⁵¹ Electron beam radiation, ⁴⁵⁵ and an 800 nm pulsed diode laser have also been used. ⁴⁵⁶ A recent report documents the successful use of infliximab, a monoclonal antibody to TNF-α. ⁴⁵⁷

Acne conglobata is an uncommon dermatosis, occurring almost exclusively in males and commencing after puberty. There are small and large, tender, inflamed nodules, cysts, and discharging sinuses that eventually heal, leaving disfiguring scars. ⁴⁵⁹ Lesions may develop in any hair-bearing area, particularly the trunk, buttocks, and proximal parts of the extremities. ⁴⁶⁰ The lesions frequently become secondarily infected with bacteria. ⁴⁶¹ The distribution is much wider than in hidradenitis suppurativa. Acne conglobata has been reported in association with lichen spinulosus in a man seropositive for the human immunodeficiency virus (HIV). ⁴⁶² There is also an eruption resembling pityriasis rubra pilaris in these HIV-positive patients. ⁴⁶³ It has also followed pregnancy. ⁴⁶⁴ Malignant degeneration can develop in lesions of acne conglobata of long standing. ⁴⁵⁹

Isotretinoin, often in conjunction with prednisone, is the preferred treatment for severe acne conglobata. Doxycycline or oral trimethoprim-sulfamethoxazole is used for secondary infections. There is a recent report on the use of infliximab in this disease. Results were good. ⁴⁶¹

Pseudofolliculitis is a common disorder of adult black males. It is usually confined to the beard area of the face and neck, ⁴⁷² but rarely the scalp, ⁴⁷³ pubic area, ⁴⁷⁴ and legs⁴⁷⁵ may be involved. Pseudofolliculitis barbae (‘razor bumps’) refers to lesions of the beard area. ⁴⁷⁶ Hypertrophic pseudofolliculitis barbae has been reported in renal transplant recipients receiving cyclosporine. ⁴⁷⁷ Pseudofolliculitis consists of papules and pustules in close proximity to hair follicles. Scarring and keloid formation sometimes result. ⁴⁷⁸

Pseudofolliculitis is an inflammatory response to an ingrown hair. Hair shafts in black people have a tendency to form tight coils and, following shaving, the sharp ends may pierce the skin adjacent to the orifice of the follicles. ⁴⁷³ Dermoscopy has been used to confirm the diagnosis. ⁴⁷⁶

The treatment of pseudofolliculitis is challenging. Behavioral changes with a minimization of overshaving may assist. ¹⁷⁷ Benzoyl peroxide, clindamycin, and retinoids have been used. Surgical or laser depilation may be necessary. ⁴⁷⁶ The neodymium:yttrium aluminum garnet (YAG) laser is a safe and effective option for reducing hair and subsequent papule formation. ⁴⁷⁹

Pruritic folliculitis of pregnancy is a rare dermatosis in which pruritic, erythematous papules develop in a widespread distribution in the latter half of pregnancy. ⁴⁸⁰ The lesions clear spontaneously at delivery or in the postpartum period. There is no adverse effect on fetal well-being. ⁴⁸¹ The etiology is unknown, but on the basis of a case with elevated androgens, it has been suggested that this condition is a ‘form of hormonally induced acne’. ⁴⁸² This finding has not been confirmed in a subsequent study. ⁴⁸¹Malassezia yeasts do not appear to be the cause either.^{483. and 484.}

Perforating folliculitis is manifested by discrete, keratotic, follicular papules with a predilection for the extensor surfaces of the extremities and the buttocks. ⁴⁸⁶ It may persist for months or years, although periods of remission often occur. Disease associations have included psoriasis, ⁴⁸⁷ juvenile acanthosis nigricans, HIV infection, ⁴⁸⁸ primary sclerosing cholangitis,^{489. and 490.} and renal failure, often in association with hemodialysis.^{486. and 491.} It has recently been reported following the use of the inhibitors of tumor necrosis factor-α, infliximab and etanercept. ⁴⁹²

The features of perforating folliculitis associated with renal failure (see p. 324) may overlap those of reactive perforating collagenosis and Kyrle’s disease⁴⁸⁶ (the latter disease has been regarded by some as a variant of perforating folliculitis). ⁴⁹³ Lesions associated with renal failure are often pruritic, in contrast to the asymptomatic lesions of the majority of cases. ⁴⁹⁴

The etiology of perforating folliculitis is unknown, although minor mechanical trauma may play a role. It has been suggested that perforation of the epithelium is the primary event and that it is not a primary disorder of transepithelial elimination. ⁴⁹⁴

The term ‘follicular toxic pustuloderma’ has been used for an acute pustular eruption with follicular localization. Most cases have been associated with the ingestion of drugs, particularly antibiotics, although in others an enterovirus infection has been incriminated. ⁴⁹⁷ As the lesions are not always follicle-based, the terms ‘toxic pustuloderma’ and ‘acute generalized exanthematous pustulosis’ are now used (see p. 132).

The term ‘sterile neutrophilic folliculitis with perifollicular vasculopathy’ was coined by Magro and Crowson for a distinctive cutaneous reaction pattern, usually accompanying systemic diseases such as inflammatory bowel disease, Reiter’s disease, Behçet’s disease, hepatitis B, and various connective tissue diseases. ⁴⁹⁸ It may present clinically as a folliculitis or a vasculitis or with vesiculopustular or acneiform lesions, predominantly on the legs, arms, and upper back. Arthritis, fever, and malaise are often present.

Pseudolymphomatous folliculitis is a subset of cutaneous lymphoid hyperplasia that is found at all ages and in both sexes. ⁴⁹⁹ It is almost exclusively a solitary lesion on the face measuring approximately 1 cm in diameter. ⁵⁰⁰ The lesions often regress after incisional biopsy.

A review of 55 cases of cutaneous lymphoid hyperplasia (‘pseudolymphoma’) from Japan revealed 19 cases that were reclassified as pseudolymphomatous folliculitis. ⁵⁰¹

Trichorrhexis nodosa is characterized by one or more small, beaded swellings along the hair shaft, corresponding to sites that fracture easily. Scalp hair is most often involved although the genital region may also be affected. ⁵¹⁸ Trichorrhexis nodosa may be generalized or localized. ⁵¹⁹ Alopecia may result because the hairs fracture easily.

The basic cause of trichorrhexis nodosa is prolonged mechanical trauma or chemical insults, although a contributing factor in some instances is an inherent weakness of the hair shaft. This weakness may result from a specific pilar dystrophy such as pili torti, monilethrix or trichorrhexis invaginata, or from an inborn error of metabolism affecting the hair such as citrullinemia (OMIM 2157000), ⁵²⁰ arginosuccinic aminoaciduria (OMIM 207900), ⁵²¹ Menkes’ syndrome (OMIM 309400), ⁵²² or trichothiodystrophy (see below).^{510.518.523.524.525. and 526.} This latter group of abnormalities is quite rare but they usually form the basis of hereditary cases of trichorrhexis nodosa. ⁵¹⁸ Trichorrhexis nodosa is also associated with other rare syndromes such as one that also includes intractable diarrhea of infancy, dysmorphism, and cirrhosis. ⁵²⁷ Neurocutaneous features may accompany the trichorrhexis nodosa syndrome (OMIM 275550).

Trichothiodystrophy (OMIM 601675) refers to a rare group of autosomal recessive disorders that have in common short brittle hair with a sulfur content less than 50% of normal.^{518.528.529.530.531. and 532.} This results from a deficiency of the sulfur-containing aminoacid cystine in the cuticle and cortex.^{533.534. and 535.} A defect in excision repair of ultraviolet damage in fibroblasts has been detected in many patients. Unlike xeroderma pigmentosum, in which this defect also occurs, there is no increase in skin cancer.^{536. and 537.} Most patients exhibit mutations on the two alleles of the XPD (ERCC2) gene, mapped to 19q13.2, although rarely a mutated XPB (ERCC3) gene, mapped to 2q21, or TTDA gene may be involved.^{538. and 539.} Further information is provided in an excellent review by Itin and colleagues. ⁵³⁰ Trichothiodystrophy is often associated with brittle hair, impaired intelligence, decreased fertility and short stature (BIDS syndrome – OMIM 234050), sometimes combined with ichthyosis (IBIDS syndrome),^{533. and 540.} osteosclerosis (SIBIDS syndrome), ⁵⁴¹or photosensitivity (PIBIDS syndrome).542. ^{and 543.} It has been suggested, and confirmed in mutant (TTD) mice, that the neurological features seen in some of these related syndromes are due to thyroid hormone deficiency resulting from XPD mutations. ⁵³⁸

Trichoschisis is a clean transverse fracture of the hair shaft through the cuticle and cortex. ⁵⁰³ It is usually seen in the brittle hair associated with trichothiodystrophy (see above).

There is a transverse or oblique fracture of the shaft with irregular borders and a cuticle which is partly intact. ⁵⁰³ As such it resembles a greenstick fracture. ⁵⁰³ It does not indicate any specific underlying systemic disease, but rather it may follow trauma to the hair or be associated with pili torti, monilethrix, or other hair shaft abnormalities (see below).

Trichorrhexis invaginata (bamboo hair) is a rare but unique abnormality of the hair shaft in which there are nodose swellings that give the hair an appearance reminiscent of a bamboo stem. ⁵⁴⁶ The scalp hair is usually short, dull and friable and the eyebrows and eyelashes may be sparse. ⁵²⁸ It is one of the hair anomalies associated with Netherton’s syndrome (OMIM 256500), an autosomal recessive disorder in which there is also ichthyosis linearis circumflexa or some other ichthyosiform dermatosis (see p. 253).^{537. and 546.} This hair shaft anomaly is seen less characteristically as a sporadic change following trauma or in association with other hair shaft abnormalities.^{503. and 546.}

Trichorrhexis invaginata may result from a transient defect of keratinization of the hair shaft due to incomplete cystine linkages, leading to softness of the cortex at the point of disruption. ⁵⁴⁶

Tapered fractures refer to a progressive narrowing of the emerging hair shaft as a result of inhibition of protein synthesis in the hair root. ⁵⁰³ Fracture of the shaft may occur near the skin surface. Tapered fractures (‘pencil-pointing’) are seen in anagen effluvium caused by cytotoxic drugs. ⁵⁰³

Trichoptilosis refers to longitudinal splitting or fraying of the distal part of the hair shaft as a result of persistent trauma. ⁵⁴⁸ It results from separation of the longitudinal cortical fibers following loss of the cuticle from wear and tear. ⁵⁰³ A rare variant with the split in the center of the hair and reconstitution of the shaft distal to this has been reported.^{549. and 550.} Other hair shaft abnormalities may also be present.

Trichoteiromania is self-inflicted damage to the hair resulting from rubbing of the hair. ⁵⁵¹ This causes splitting and breaking of the hairs and discrete patches of alopecia. ⁵⁵¹

Pili canaliculati et trianguli (pili canaliculi – OMIM 191480), a rare disorder of the hair shaft, is also known as the uncombable hair syndrome,^{553. and 554.} cheveux incoiffables, ⁵⁵⁵ and the spun-glass hair syndrome.^{556.557. and 558.} The hair is drier, glossier and lighter and it is unmanageable in that it does not lie flat when combed.^{559. and 560.} It may be sparse. ⁵⁶¹ The condition derives its name from the longitudinal canalicular depression in one side of the shaft and its triangular or kidney shape in cross-section.^{555. and 559.} For clinical change to be apparent, approximately 50% of hairs must be affected with this abnormality. ⁵⁶² It may result from a disorder of keratinization of the hair. ⁵¹⁰ This hair shaft abnormality has been reported in patients with ectodermal dysplasia.^{563. and 564.} This has been called Bork syndrome (OMIM 191482).

Straight hair nevus, a localized disorder in which the involved hairs are short and straight, in contrast to the usual woolly hair of black people, in whom this condition has been described, has been regarded as a localized form of uncombable hair. ⁵⁶⁵ However, it should be noted that in straight hair nevus there may be an associated epidermal nevus; furthermore, the hairs are normal in cross-section, in contrast to pili canaliculati et trianguli. ⁵⁶⁶ It has also followed the use of interferon-α and ribavirin in the treatment of hepatitis C infection. ⁵⁶⁷

In the condition known as pili bifurcati, hairs show intermittent bifurcations of the shaft which subsequently rejoin further along the shaft to form a normal structure. ⁵⁷⁰ Unlike trichoptilosis, which it superficially resembles, each ramus of the bifurcated segments is invested by its own cuticle. ⁵⁷⁰ This abnormality has been regarded as a restricted form of pili multigemini. ⁵⁰³

Pili multigemini is a rare malformation of the pilary apparatus associated with the emergence of multiple hairs from a follicular canal which in turn is composed of as many papillae as there are hairs.^{571. and 572.} These multigeminate follicles may arise on the face or the scalp. It differs from tufted-hair folliculitis in which distinctive tufts of multiple hairs emerge from a single follicular orifice into which several complete follicles open (see p. 430).

Trichostasis spinulosa presents either as asymptomatic, comedone-like lesions on the nose⁵⁷³ or as mildly pruritic hyperkeratotic papules on the upper trunk or arms.^{503.574.575. and 576.} With a hand lens, multiple vellus hairs can sometimes be seen protruding from the patulous follicles. There is retention of telogen hairs within the follicles, although the reason for this is unknown. ⁵⁷⁴ Widespread trichostasis spinulosa has been reported in a patient on hemodialysis for chronic renal failure. ⁵⁷⁷ There is also a possible association with the prolonged topical application of a corticosteroid cream. ⁵⁷⁸

The condition of pili annulati (ringed hairs – OMIM 180600) is a rare, familial (autosomal dominant) or sporadic anomaly in which there are alternating light and dark bands along the shaft, when viewed by reflected light.^{526.579. and 580.} Axillary hair is occasionally affected. An association with alopecia areata has been reported. ⁵⁸¹ In one case, there was clinical disappearance of the disorder in the regrown hair following an episode of alopecia areata, although banding was still present in 20% of the hairs on light microscopy. ⁵⁸²

The light bands are due to clusters of abnormal, air-filled cavities which appear to result from insufficient production of the interfibrillar matrix.^{579. and 583.} Various weathering patterns may be seen in involved hair shafts. ⁵⁸⁴

The term ‘pseudopili annulati’ refers to the presence of light and dark bands when slightly flattened or twisted hair is examined under reflected light.^{585. and 586.} It is thought to be a variant of normal hair and to have no clinical significance. ⁵⁰³

In monilethrix (OMIM 158000) the hairs have a beaded or moniliform appearance as a result of a periodic decrease in the diameter of the hair.^{591. and 592.} Inheritance is usually as an autosomal dominant trait with high gene penetrance but variable expressivity (see below). ⁵⁰³

The hair is susceptible to fracture at the narrower internodal regions, leading to short hair and hair loss. ⁵⁹³ The occipital region is usually involved soon after birth and the affected area slowly extends. ⁵¹⁰ Other hairy areas may also be involved. Some improvement occurs with age and occasionally there is spontaneous remission at puberty. ⁵²⁸

The defect leading to monilethrix may result from a periodic dysfunction of the hair matrix.^{591.594. and 595.} Abnormalities also exist in the inner root sheath adjacent to the zones of abnormal shaft thinning. Transmission electron microscopy has shown an abnormal cortex with areas of homogeneous non-fibrillar material and a deviated axis of some microfibrils. ⁵⁹⁶

The gene responsible for monilethrix maps to the region on chromosome 12 (12q13) containing the type II keratin cluster, which includes the basic type II trichocyte keratins.^{597. and 598.} The defect may involve one of three keratin genes KRTHB6, KRTHB1, and KRTHB3.^{599. and 600.} Several different mutations have been found.^{601. and 602.} Nail defects appear common with KRTHB1 defects. ⁶⁰⁰ Monilethrix may be associated with keratosis pilaris, and with various ectodermal anomalies. These other syndromes are not well characterized. ⁶⁰³

Pseudomonilethrix (OMIM 177750) is characterized by irregularly placed nodes at irregular intervals along the hair shaft. It may be an autosomal dominant disorder producing hypotrichosis of the entire scalp, or just the occipital area, an acquired condition associated with various hair fragility disorders, and an iatrogenic condition. ⁶⁰⁴ The latter form may be the result of the compression of normal or fragile hairs between glass slides, prior to their microscopic examination. ⁶⁰⁵

Tapered hairs can arise in the same way as tapered fractures and they may also occur in association with other abnormalities of the hair shaft. ⁵⁰³ Several distinct variants have been described. The Pohl–Pinkus mark is an isolated narrowing of the hair shaft which coincides with a surgical operation or some other traumatic episode. ⁵⁰³ This narrowing is not as abrupt in the bayonet hair, which may possibly be a form of the Pohl–Pinkus mark. ⁵⁰³ Newly growing anagen hairs often have a tapered, hypopigmented top.

Bubble hair is a rare abnormality characterized by a large cavity in the shaft on scanning electron microscopy and an unusual ‘bubble’ appearance on light microscopy. ⁶⁰⁷ It presents with a localized area of brittle, easily broken hairs on the scalp. ⁶⁰⁸ The abnormality can be reproduced by heat, suggesting that hair dryers that overheat may be responsible.^{454.609.610. and 611.}

Trichomegaly (OMIM 190330) refers to an enlargement and hypertrichosis of the eyelashes. It may be associated with more generalized hypertrichosis or with involvement of the eyebrows as well. There is a congenital and an acquired form. Interest in this condition has followed its association with various drugs such as interferon-α 2a and 2b, topiramate, cyclosporine, latanoprost, and the epidermal growth factor receptor (EGFR) inhibitor gefitinib.^{140.612. and 613.} A variant associated with mental retardation and retinal degeneration (OMIM 275400) also occurs.

Pili torti (OMIM 261900) result from a structural defect in which the hair shaft is twisted on its axis at irregular intervals, with flattening of the hair at the sites of twisting. ⁶¹⁴ This leads to increased fragility, particularly in areas subjected to trauma. ⁵¹² There are several clinical settings in which pili torti can occur. ⁵⁰³

The rare congenital (Ronchese) type presents at birth or soon after, with a localized area of alopecia or short hair which gradually spreads. ⁵⁰³ Sites other than the scalp may be affected. Pili torti may occur alone or in association with other syndromes, particularly of ectodermal type. ⁵¹¹ These include Bazex’s, Crandall’s, and Bjornstad’s syndromes^{615. and 616.} as well as hypohidrotic ectodermal dysplasia. ⁵¹² They also occur in citrullinemia (OMIM 215700) ⁶¹⁴ and in Menkes’ kinky hair syndrome.^{510. and 528.} Bjornstad’s syndrome (OMIM 262000) combines pili torti with congenital hearing loss.^{617. and 618.} The responsible gene maps to chromosome 2q34–q36. There is a mutation in the BSC1L gene, which encodes an ATPase required for the assembly of a mitochondrial complex. ⁵²⁰ Crandall’s syndrome combines pili torti, hearing loss, hypogonadism, and rarely, mental retardation. ⁵²⁰ In Menkes’ syndrome (OMIM 309400) the hair may show defects other than pili torti, including trichorrhexis nodosa, trichoclasis, and irregular twisting. ⁶¹⁹ The gene maps to chromosome Xq13.

Postpubertal onset has also been recorded (Beare type). ⁵¹² Involvement of multiple hair-bearing sites and mental retardation are usually features of this variant. An acquired form of pili torti has been described as a result of trauma, associated with cicatricial alopecia, following the use of synthetic retinoids (isotretinoin), ⁶²⁰ and on the abdomen and thighs of hirsute males and females. ⁶²¹ It has also been reported in anorexia nervosa. ⁶²² Pili torti of early onset may improve with age.

‘Corkscrew’ hairs, an exaggeration of pili torti, have been reported in patients with ectodermal dysplasia.^{623. and 624.} The presence of a longitudinal groove on the hair shaft has led to ‘corkscrew’ hairs being called pili torti et canaliculi. ⁶²⁴ This abnormality can also be seen in hereditary congenital hypotrichosis of Marie–Unna (see p. 420).

Woolly hair is very curly hair that is difficult to style. It is normal in most black races but in white races it occurs in several different clinical settings.^{503.526.625. and 626.} These include an autosomal dominant form (OMIM 194300) which affects the entire scalp (the hereditary type) for which no gene has been elucidated, an autosomal recessive form (the familial type – OMIM 278150) due to a mutation in the PKRY5 gene at 13q14.12–q14.2, a diffuse partial form where shorter, finer, curly hair is interspersed with normal hair, ⁶²⁵ and a well-demarcated localized form (woolly hair nevus) which may be associated with an ipsilateral epidermal nevus.^{627.628.629.630. and 631.} Acquired progressive kinking of the hair (see below) is sometimes included as a variant of woolly hair. ⁵¹⁰ Woolly hair has been reported in association with loose anagen hair, ⁶³² hair-shaft fragility, ⁶³³ and skin fragility (OMIM 607655) due to a mutation in the desmoplakin gene (see p. 125). Woolly hair has also been associated with hypotrichosis, an everted lip and malformation of the ear (OMIM 278200), and several ectodermal dysplasias, usually including palmoplantar keratoderma as well.^{634. and 635.} Specific associations include Naxos disease (OMIM 601214) – see p. 258, Noonan syndrome (OMIM 163950), cardiofaciocutaneous syndrome (OMIM 115150), and keratosis pilaris (OMIM 604093) and its variant ulerythema ophryogenes (see p. 433). ⁶³⁶

Acquired progressive kinking of the hair shaft is rare. It is sometimes considered to be a variant of woolly hair, but is best regarded as a distinct entity on the basis of its onset at or after puberty, the involvement of certain regions of the scalp rather than the entire scalp, and the tendency for affected hair to resemble pubic hair both in texture and color.^{637.638.639. and 640.} Acquired progressive kinking of the hair tends to occur in males who subsequently develop a male pattern alopecia of fairly rapid onset.^{637.641.642. and 643.} ‘Whisker hair’, which occurs not uncommonly about the ears, is probably a variant.^{503.637.643. and 644.}

Curly hair, in which there are large loose spiral locks, can be seen in many genetic syndromes including trichodentoosseous (TDO) syndrome (OMIM 190320), ⁵³⁹ Costello’s syndrome (OMIM 218040), CHAND (curly hair, ankyloblepharon, and nail dysplasia) syndrome (OMIM 214350), and Noonan’s syndrome (OMIM 163950). ⁵²⁰ The TDO syndrome is due to a mutation in the DLX3 gene on chromosome 17q21. It is a homeobox gene important for embryonic development. ⁵²⁰

Trichonodosis (knotted hair) is usually an incidental finding in individuals with various lengths and types of scalp hair, particularly those with curly or kinky hair.^{646. and 647.} Knots are very common in curly African hair, leading to fracturing and breaking when combed. African hair length is less than that of white people, possibly because of the hair loss associated with the combing of knotted hair. ⁶⁴⁸ There may be a single or a double knot. Various hair shaft abnormalities of a secondary nature may be present in and adjacent to the knots. ⁵⁰³

Multiple large knots involving body hairs have been reported. The hairs show an unusual twisting and matting. ⁶⁴⁹

Hair matting is a rare acquired condition characterized by irreversible tangling of hair. It has many causes other than trichonodosis. They include hair density and coiling, chemical and physical treatments to the hair, including the use of conditioners, ⁶⁵⁰ frequent combing, ⁶⁵¹ and neglect.^{652. and 653.} The original term plica neuropathica is sometimes used for this condition.^{654. and 655.}Plica polonica refers to the same phenomenon. ⁶⁵⁶

Circle hair presents as a black circle related to hair follicles as the result of a hair shaft becoming coiled into a circle under a thin transparent roof of stratum corneum.^{657. and 658.} The cause of this abnormality is unknown but it may be seen in middle-aged men on the back, abdomen, and thighs. ⁶⁵⁷ The case reported as pili migrans has some similarities (see p. 411).

Rolled hair (the term is sometimes used interchangeably with circle hair) refers to a common disorder of hair growth in which the hairs are irregularly coiled but do not form a perfect circle. ⁶⁵⁹ It is usually associated with some other disorder such as keratosis pilaris.

Whorled hair, in which multiple whorls are present, is probably a related disorder. ⁶⁶⁰ This phenomenon may be associated with anomalies in brain development. ⁶⁶⁰

In tinea capitis, fungal elements may be found on the surface of the hair shaft (ectothrix) or within the substance of the hair (endothrix). ⁵⁰³ In both cases the affected hairs are fragile and break near the skin surface.

The condition known as piedra occurs in two forms, white piedra and black piedra. ⁵⁰³ They are characterized by the formation of minute concretions on the affected hair (the Spanish word piedra means stone).

White piedra (trichosporonosis, trichosporosis)^{661. and 662.} is a rare superficial infection of the terminal part of the hair caused by the yeast-like fungus Trichosporon beigelii (cutaneum). It occurs particularly in South America, parts of Europe, Japan, the Middle East, and the United States.^{663. and 664.} There are numerous discrete or coalescing cream-colored nodules, just visible to the naked eye, forming sleeve-like concretions attached to the hair shaft.^{665. and 666.} White piedra may affect hairs on the face, scalp, or scrotum. ⁶⁶⁵ Fracture of the hair shaft may result. A synergistic coryneform bacterial infection is sometimes present. ⁶⁶⁷

Black piedra, which is caused by the ascomycete Piedraia hortae, consists of gritty black nodules which are darker, firmer, and more adherent than those found in white piedra. ⁶⁶⁶ Black piedra is prevalent in tropical climates. A case of black piedra due to Trichosporon asahii has been reported. ⁶⁶⁸

The treatment of white piedra is an area of therapeutic frustration. ⁶⁶⁹ Shaving the hair is one recommended treatment, but this is not acceptable in some societies. Itraconazole has been used successfully in one series with a low failure rate, but with some recurrences on cessation of treatment. ⁶⁶⁹ Antifungal shampoos have also been used, alone, ⁶⁶⁷ or in combination with an oral azole antifungal agent. ⁶⁷⁰

In trichomycosis axillaris, there are tiny, cream to yellow nodules attached to axillary or pubic hair (Fig. 15.15). ⁵⁰³ It is not a mycosis but the result of infection by a species of Corynebacterium.

Nits are small white to brown ovoid structures attached to the hair shaft. ⁵⁰³ They are the eggs of the lice responsible for pediculosis capitis (see p. 658).

Hair casts (peripilar casts, pseudo-nits) are firmish, yellow-white concretions, 3–7 mm long, ensheathing hairs and movable along them. ⁶⁷³ Two types of hair casts exist.^{674.675.676.677. and 678.} The more common type (parakeratotic hair cast) is associated with various inflammatory scalp disorders such as psoriasis, seborrheic dermatitis, and pityriasis capitis. ⁶⁷⁴ The second type (peripilar keratin cast), which is quite uncommon, occurs predominantly in female children without any underlying disease as a diffuse disorder of scalp hair. ⁶⁷⁵ Hair casts appear to be nothing more than portions of root sheath pulled out of the follicle by a hair shaft itself. ⁶⁷⁹ Tight plaiting of the hair, leading to local scalp ischemia and consequent damage to the root sheaths of the follicle, may be responsible for the formation of hair casts.^{676.677. and 678.} Hair casts have also been associated with the use of a deodorant spray; ⁶⁸⁰ usually they cause small deposits (see below).

Various substances may become adherent to hair shafts, causing an unusual appearance on microscopy. ⁵⁰³ These include paint, hair spray, lacquer, and glue. Hair lacquer and gel can produce hair beads. ⁶⁸² Microscopy reveals that the deposits are not inherent parts of the hair shaft. ⁵⁰³

Alopecia universalis congenita (alopecia congenitalis, universal congenital alopecia – OMIM 203655) refers to cases of congenital alopecia without associated defects.^{528. and 736.} It is a heterogeneous group. Hair loss occurs at birth or shortly after in one subgroup with autosomal recessive inheritance, while in those with one form of autosomal dominant inheritance the hair is normal until mid childhood.^{737. and 738.} The autosomal recessive form is linked to the human hairless gene (HR) at 8p21.2.^{739. and 740.} Misdiagnosis as alopecia areata occurs. ⁷⁴¹ Another autosomal dominant form has been called hypotrichosis simplex (OMIM 146520). ⁷⁴² It is of early onset and without associated abnormalities. The gene for this condition, the corneodesmosin (CDSN) gene, has been mapped to chromosome 6p21.3.^{743.744. and 745.} Autosomal recessive transmission and a sporadic case have also been reported. ⁷⁴⁶ The variant linked to a short anagen phase has now been reclassified as short anagen syndrome (see p. 420). ⁷⁴⁷

Hypotrichosis with juvenile macular dystrophy (OMIM 601553) is a rare autosomal recessive disorder characterized by sparse and short hair and progressive degeneration of the retinal pigment epithelium leading to blindness by the second decade of life. It is due to a mutation in CDH3, a gene encoding P-cadherin, a major component of adherens junctions, located at 16q22.1. ⁷⁴⁸

A related disorder, also due to a CDH3 mutation, also causes ectodermal dysplasia, ectrodactyly, and macular dystrophy – EEM (OMIM 225280). Hypotrichosis and hypodontia are also present. ⁷⁴⁸

Other hypotrichosis syndromes are: an autosomal recessive localized form (OMIM 607903) due to a mutation in the desmoglein 4 (DSG4) gene on chromosome 18q12; another localized form (OMIM 611452) due to a mutation in the P2RYS gene at 13q14.12–q14.2; ⁷⁴⁹ a total hypotrichosis caused by a mutation in the lipase H (LIPH) gene (OMIM 604379) on 3q27–q28; ⁷⁵⁰ a hypotrichosis–lymphedema–telangiectasia (OMIM 607823) form due to a mutation in the SOX18 gene at 20q13.33; ⁷⁵¹ and focal hypotrichosis occurring in Gomez–Lopez–Hernandez syndrome (OMIM 601853), also known as cerebello-trigeminal-dermal dysplasia. ⁷⁵²

Hereditary hypotrichosis (Marie–Unna type – OMIM 146550) presents with short, sparse hair at birth and hair growth in childhood that is coarse and wiry. ⁷⁵⁶ There is progressive loss of hair resembling androgenetic alopecia, commencing during adolescence. ⁵²⁸ It is an autosomal dominant condition associated with a defect in chromosomal region 8p21. One study mapped the gene to 8p21.3. ⁷⁵⁷ This is close to, but distinct from, the human hairless gene (HR) responsible for atrichia with papular lesions (see below).^{758.759. and 760.} There appears to be genetic heterogeneity. ⁷⁶¹

The association of Marie–Unna hypotrichosis with onycholysis and cleft lip/palate has been given the OMIM number of 609250. It is not related to the gene that causes Marie–Unna hypotrichosis.

Atrichia with papular lesions (OMIM 209500) is a rare disorder in which progressive shedding of scalp and body hair occurs in the first few months of life.^{763.764.765. and 766.} The eyelashes are typically spared. Numerous small, milia-like cysts develop on the face, neck, scalp, and extremities in childhood and early adult life. ⁷⁶⁷ It is an autosomal recessive condition in which mutations occur in the human hairless gene (HR), a putative single zinc-finger transcription factor protein which has been mapped to chromosome 8p21.2.^{739.768. and 769.} Numerous mutations have been described.^{770.771.772. and 773.} Compound heterozygosity has also been reported. ⁷⁷⁴ Mutations in this gene are also responsible for alopecia congenitalis (universal congenital alopecia), which differs by having no papular lesions (see above).^{739. and 775.}

Atrichia with papules also occurs in the clinical setting of vitamin D-dependent rickets type IIA (OMIM 277440), resulting from mutations in the vitamin D receptor (VDR) gene on chromosome 12q13.1.^{776.777.778. and 779.} The clinical findings of the two types are strikingly similar.

Keratosis pilaris atrophicans refers to a group of clinically related syndromes in which inflammatory keratosis pilaris leads to atrophic scarring (see p. 433). This condition is mentioned here because it is regarded as a congenital follicular dystrophy.

The Hallermann–Streiff syndrome (mandibulo-oculofacial dyscephaly – OMIM 234100) is a branchial arch syndrome which combines a characteristic bird-like facies with ocular abnormalities and alopecia, which may have an unusual sutural distribution on the scalp.^{781. and 782.} Atrophic patches of skin, which may be limited to the areas of alopecia, also occur. ⁷⁸¹ Most cases appear to occur as new mutations. ⁷²⁴

The trichorhinophalangeal syndrome (OMIM 190350) is a rare autosomal disorder with sparse and slow-growing hair, facial dysmorphism, and bone deformities. ⁷⁸³ It is due to mutations in the TRPS1 gene on chromosome 8q24. It encodes a zinc finger transcription factor. ⁷⁸⁴

This recently described anomaly is characterized by ‘hair that never needs cutting’. It has probably been underreported. ⁷⁴⁷ There is short, fine scalp hair with normal body hair and eyelashes. ⁷⁸⁶ Only 24% of hairs were in anagen in one hair pull study. ⁷⁸⁶ A biopsy, with vertical and not horizontal sections, appeared unremarkable. Thai and Sinclair have reported a case with persistent synchronized scalp hair growth associated with short anagen duration. ⁷⁸⁷ A patient with two localized areas of short anagen (‘short anagen hair nevus’) responded to treatment with 5% topical minoxidil. ⁷⁸⁸

Trichotillomania is a rare form of alopecia resulting from the deliberate, although at times unconscious, avulsion of hairs by patients who may be under psychosocial stress.^{792. and 793.} In adults it is more common in women; in children there has been no sex predilection in some series. In children, eating the plucked hair may lead to the formation of trichobezoar (hair balls). ⁷⁹⁴ It has been claimed recently that the term ‘trichotillomania’ is outdated, pejorative, and offensive to patients. ⁷⁹⁵ The term ‘neuromechanical alopecia’ has been suggested as a replacement. ⁷⁹⁵

Although the crown and occipital scalp are primarily affected, other areas of the scalp, as well as the eyebrows, trunk and pubic areas, ⁷⁹⁶ may also be involved. Isolated involvement of the eyebrows and eyelashes has been reported.^{797. and 798.} Similar features can result from traction of hair associated with hairstyles and from prolonged pressure. ⁷⁹⁹ Pressure appears to be involved in the occipital alopecia that occurs in children and some adults after surgery of prolonged duration.^{800. and 801.} The term ‘traumatic alopecia’ can be applied to such cases, including trichotillomania.^{802. and 803.} Clinical differentiation from alopecia areata can be difficult.

A related disorder involving the nails is called onychotillomania in which patients neurotically pick or injure their nails until they are permanently altered. ⁸⁰⁴

If trauma (such as traction) is repeated, prolonged and severe, then additional features, including scarring, will develop. This is best called traction alopecia with scarring, but it is also known as ‘hot comb’ alopecia and follicular degeneration syndrome (see p. 430). ⁸⁰⁵

The management of patients with trichotillomania involves psychiatric and support services beyond the scope of this book. Guidelines for the management of trichotillomania were published in 2002. ⁸⁰⁶ Traction alopecia is best managed by advice to the patient on the underlying mechanism of their alopecia.

Telogen effluvium is an abnormality of hair cycling that results in excessive loss of telogen hairs. It has been regarded as a syndrome and as a non-specific reaction pattern, rather than as a disease sui generis.^{789.814.815. and 816.} It is nevertheless a useful term to apply to those cases of diffuse hair loss in which various stressful circumstances precipitate the premature termination of anagen. It is one of the most common causes of diffuse hair loss. ⁸¹⁷ Telogen effluvium can follow febrile illness, parturition, systemic illnesses, chronic infections (including HIV infection), ⁸¹⁸ allergic contact dermatitis of the scalp, ⁸¹⁹ air travelers’ ‘jet lag’, psychogenic illnesses, ‘crash diets’, iron deficiency,^{820. and 821.} and sudden severe stress. ⁸²² It may also be associated with an internal cancer, ⁶⁸⁶ cytotoxic drugs, ⁸²³ and with the eosinophilia-myalgia syndrome. ⁸²⁴ Loss of hair in the newborn is a physiological example of this process. ⁷⁸⁹ Exceptionally, drugs such as heparin, clofibrate, gentamicin, niacin (nicotinic acid), nitrofurantoin, salicylates, oral contraceptives, anticonvulsants, pramipexole, ⁸²⁵ excess vitamin A, and the antihypertensive agent minoxidil⁸²⁶ have been implicated in the etiology of telogen effluvium.^{689.827. and 828.} Headington has defined five different functional types of telogen effluvium. ⁸²⁸

Telogen effluvium presents as a diffuse thinning of the scalp hair, although the hair loss is not always obvious clinically. Hair loss usually occurs about 3 months after the precipitative event. Sometimes this hair loss unmasks small areas of alopecia, of other causes, which had previously gone unnoticed.

In chronic telogen effluvium (defined as shedding that persists beyond 6 months) there is hair shedding of abrupt onset followed by a fluctuating course in which there is diffuse thinning all over the scalp, frequently accompanied by bitemporal recession.^{822. and 829.} There is no frontoparietal hair loss and these women characteristically present with a full, thick head of hair. ⁸³⁰ It is more common in postmenopausal women, ⁸³¹but it has been seen in men. ⁸³² It must be distinguished from female pattern hair loss, which often has overlapping features.^{833. and 834.} Both conditions may have trichodynia. ⁸³⁵ Hair shedding in this condition appears to be self-limiting.

Alopecia areata (OMIM 104000) is a relatively common condition affecting individuals of any age, but particularly those between the ages of 15 and 40.^{837.838.839. and 840.} Its incidence is 0.1–0.2%, ⁸⁴¹ and the lifetime risk is approximately 2%. More than 4.5 million people in the United States are affected. ⁸⁴² Although mild cases may escape clinical detection, alopecia areata usually has a sudden onset with the development of one or more discrete, asymptomatic patches of non-scarring hair loss on the scalp. ⁸⁴³ Exclamation mark hairs are found near the advancing margins. ⁸⁴³ The clinical course is variable. ⁸⁴⁴ There may be spontaneous remission, sometimes followed by exacerbations, or there may be relentless progression to involve the entire scalp (alopecia totalis) and, uncommonly, all body hair (alopecia universalis).^{845. and 846.} Progression to alopecia totalis is more likely in children.^{847.848. and 849.} In one study 7% of patients with alopecia areata progressed to alopecia totalis or universalis. ⁸⁵⁰ HLA-DR11, HLA-DR4, and HLA-DQ7 are significantly increased in frequency in patients with alopecia totalis/alopecia universalis in contrast to patients with patchy alopecia areata.^{851. and 852.} Alopecia universalis may be a manifestation of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome (OMIM 304790) due to a mutation in the FOXP3 gene at Xp11.23–q13.3. ⁸⁵³ It also occurs as a manifestation of Satoyoshi syndrome (OMIM 600705) in which there are intermittent painful muscle spasms and malabsorption. Other HLA profiles may be increased in some ethnic groups. ⁸⁵⁴

A family history of alopecia areata is present in 8–50% of affected individuals.^{837.847.855.856.857.858.859. and 860.} Inheritance is polygenic, ⁸⁶¹ but there appears to be an association with HLA class II genes.^{768.862.863. and 864.} More specific genetic associations have now been reported. It has been associated with a genetic variant in the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene. ⁸⁶⁵ In another study four susceptibility loci were found on chromosomes 6, 10, 16, and 18. ⁸⁴² The locus on chromosome 6 was in the region of the major histocompatibility complex locus. ⁸⁴² The chromosome 16 locus has been given an OMIM number of 610753, a gene map locus of 16q11–q22 and the title of alopecia areata type 2. There is a 55% concordance rate in identical twins. ⁸⁶⁶ Congenital alopecia areata is exceedingly rare.^{867. and 868.}

Regeneration is heralded by the development of fine white or tan hair. ⁸⁴³ Most times the depigmented hair regrowth lasts one hair cycle, but persistent depigmented hair does occur. ⁸⁶⁹ In one such case only pigmented hairs were lost in the initial hair loss phase leading to completely white hair after treatment and regrowth. ⁸⁷⁰ In another case, graying hairs were spared. ⁸⁷¹

There are conflicting data on the clinical associations of alopecia areata. Many reports have documented an increased incidence of autoimmune diseases such as Hashimoto’s thyroiditis, Addison’s disease, idiopathic primary hypophysitis, ⁸⁷² thrombocytopenia, ⁸⁷³ vitiligo, ⁸⁷⁴ and lupus erythematosus, but not others.^{843.845. and 875.} Children with alopecia areata have an increased family history of autoimmunity. ⁸⁷⁶ Autoantibodies to various thyroid antigens,^{877.878. and 879.} gastric parietal cells, ⁸⁵⁵ and smooth muscle⁸⁸⁰ have been reported, ⁸⁸¹ although not all of these findings have been confirmed by others. ⁸⁸² There are also conflicting results on the various cell-mediated functions in alopecia areata, but this may in part reflect the different techniques that have been used and the heterogeneous nature of this condition.^{879. and 883.} Other clinical associations have included atopic states,^{858. and 884.} Down syndrome,^{885. and 886.} Turner’s syndrome, ⁸⁸⁷ the use of rifampin (rifampicin), ⁸⁸⁸ efalizumab, ⁸⁸⁹ adalimumab, ⁸⁹⁰ infliximab,^{889. and 891.} cyclosporine, ⁸⁹² etanercept, ⁸⁹³ and interferon alpha, ⁸⁹⁴ hypomagnesemia, ⁸⁹⁵ HIV infection, ⁸⁴⁸ psychiatric comorbidity, ⁸⁹⁶ CMV infection, ⁸⁶⁶ Epstein–Barr virus infection, ⁸⁹⁷ pili annulati, ⁸⁹⁸ the regression of cutaneous melanoma, ⁸⁹⁹ the sparing of areas with psoriasis, ⁹⁰⁰ and with a congenital nevus, ⁹⁰¹ and following vasectomy. ⁹⁰² Various nail changes have been reported in 10–25% of patients.^{859. and 903.} Reduced sweating has also been documented. ⁹⁰⁴ Rarely it may masquerade as other alopecias such as trichotillomania⁷⁹⁸ and frontal fibrosing alopecia. ⁹⁰⁵ Migratory poliosis may be a forme fruste of alopecia areata. ⁹⁰⁶ Although eyebrow loss may occur in alopecia areata, diffuse eyebrow loss can occur in a familial setting in the absence of scalp hair loss. ⁹⁰⁷

Alopecia areata incognita is a variant of alopecia areata characterized by acute diffuse shedding of telogen hairs in the absence of typical patches. ⁹⁰⁸ Clinically it has the features of telogen effluvium. Scalp dermoscopy shows characteristic round or polycyclic yellow dots and numerous short regrowing hairs. ⁹⁰⁸ Fine depigmented hair may be present. ⁹⁰⁹

Androgenetic alopecia (common baldness, androgenic alopecia) is a physiological event which may commence in males soon after puberty.^{978. and 979.} It occurs less often in females and its onset is a decade or so later than in males. It has been said to affect at least 50% of men by the age of 50 years, ⁹⁸⁰ and 80% at the age of 70 years, ⁹⁸¹ while it affects about 40% of women aged 70 years and over. ⁹⁸² The hair loss is more obvious in men. Clinically there is progressive replacement of terminal hairs by fine, virtually unpigmented vellus hairs, with hair loss in distinct geographical areas of the scalp. ⁹⁸³ Hair diameter diversity is an important clinical sign that reflects the underlying follicular miniaturization characteristic of this condition. ⁹⁸⁴ Increased shedding of hairs is usually noted. ⁹⁷⁸ In females, there may be features of hyperandrogenism such as hirsutism and acne. ⁹⁸⁵ However, it has been reported in a female with hypopituitarism, indicating that it is not always androgen dependent. ⁹⁸⁶ Cigarette smoking may predispose to androgenetic alopecia, ⁹⁸⁷ although this was not confirmed in another study. ⁹⁸¹

In males, the hair loss is patterned and involves the frontal, central, and temporal regions. Uncommonly, there is sparing of frontoparietal hairline in men. ⁹⁸⁸ Various categories of male baldness have been defined, based on which of the above areas are involved.^{978. and 989.} Hair loss may have an important psychological effect, particularly in younger males.990. ^{and 991.}

In females, three distinct patterns of hair loss have been recognized.^{992.993.994. and 995.} The most common type is a diffuse frontovertical thinning without temporal recession. ⁹⁸⁵ The second type is similar to that seen in the male (male pattern alopecia). It is often associated with virilism, although in one study it was found in a significant number of normal postmenopausal women. ⁹⁹⁶ The third pattern is diffuse thinning confined to the vertex and developing after the menopause. ⁹⁹² A midline part will reveal a characteristic decrease in hair density from the vertex to the front of the scalp. ⁹⁹⁷ In endocrinologically normal females, the rate of progression of the alopecia is very slow. However, it should always be kept in mind that androgenetic alopecia, in both sexes, may be accompanied or unmasked by other forms of hair loss such as alopecia areata, telogen effluvium, or the hair loss associated with hypothyroidism and even with iron deficiency.^{821. and 998.} The term ‘female pattern hair loss’ is preferred by some workers in this field for female patients, rather than the term androgenetic alopecia. ⁹⁹⁹

A new classification of pattern hair loss, applicable to both men and women, has been devised. ¹⁰⁰⁰ It has considerable merit, but it will not be discussed in detail, because it is yet to gain acceptance. ¹⁰⁰⁰

Androgenetic alopecia results from a progressive diminution in the size of terminal follicles with each successive cycle and their eventual conversion to vellus follicles.^{978. and 1001.} This vellus conversion occurs under the influence of androgenetic stimulation or in individuals with genetic predisposition. ⁹⁸⁵ The actual mechanism of this miniaturization has never been clearly elucidated. Whiting has postulated an abrupt process with a reduction in cell numbers of the dermal papilla. ¹⁰⁰² Rebora has postulated three mechanisms: an androgen-induced acceleration of the mitotic rate of the matrix that leaves less and less time for differentiation; an increased telogen shedding; and the increased number and duration of the lag phase (kenogen), the true resting period of the follicle after telogen. ⁷¹⁷ Other studies support the notion that the dermal papilla cells represent the androgen target within the hair follicle. ¹⁰⁰³ The androgen receptor coactivator ARA70/ELE1 is reduced in androgenetic alopecia. ¹⁰⁰⁴

The method of inheritance has not been clearly defined. It is probably polygenic. No relationship with the 5α-reductase gene or the human hairless gene has been found.^{1005.1006.1007. and 1008.} The microsomal enzyme steroid 5α-reductase is responsible for the conversion of testosterone into the more potent androgen dihydrotestosterone. ¹⁰⁰⁹ Androgenetic alopecia is common in adrenoleukodystrophy, an X-linked recessive condition. ¹⁰¹⁰ In contrast, it is uncommon in patients with Kennedy’s disease (OMIM 313200), a neurodegenerative disease due to a mutation in the androgen receptor (AR) gene on chromosome Xq11–q12. ¹⁰¹¹ Racial influences also play a part. ⁹⁸⁵ The age-specific prevalence in certain Asian countries is lower than that seen among white people.^{987.999. and 1012.}

Elevated urinary¹⁰¹³ and sometimes serum dehydroepiandrosterone levels have been noted in male pattern alopecia. ¹⁰¹⁴ Hair follicles from sites involved with baldness have shown altered levels in the activity of the enzyme responsible for the conversion of certain androgens to their more active metabolites. ¹⁰¹⁵ Hyperandrogenism has been detected in approximately 40% of females with the diffuse type of alopecia.^{992. and 1016.} Sebum excretion is not increased in females. ¹⁰¹⁷ Polycystic ovaries are frequently the cause of this hyperandrogenetic state. ¹⁰¹⁶ Ovarian hyperthecosis may also cause androgenetic alopecia in postmenopausal women. ¹⁰¹⁸ Antiandrogen therapy (see below) will result in some improvement in up to 50% of patients, but this is usually confined to a decreased rate of hair loss. ¹⁰¹⁹ The insulin growth factor 1 (IGF-1) axis may be important in the etiology of patterned hair loss in males.^{1020. and 1021.} Increased expression of IGF-1 messenger RNA levels in the dermal papilla of patients with androgenetic alopecia is associated with response to finasteride, ¹⁰⁰³ a selective inhibitor of type 2 5α-reductase, which appears to be capable of reversing the miniaturization of follicles in androgenetic alopecia of younger males, but not in postmenopausal women.^{1022. and 1023.}

Temporal triangular alopecia consists of a triangular patch of alopecia with its base extending to the frontotemporal hairline.^{1054.1055.1056. and 1057.} Most cases develop during the first few years of life; the original designation ‘congenital triangular alopecia’ is a misnomer.^{1058. and 1059.} It is usually unilateral. Fine vellus hairs are often present in the area. ¹⁰⁵⁵ It has been misdiagnosed clinically as refractory tinea capitis. ¹⁰⁶⁰

It has been reported in association with colonic polyposis, eye defects, mental retardation and phakomatosis pigmentovascularis, and also with congenital heart and other anomalies.^{1061.1062. and 1063.} It has also occurred in combination with androgenetic alopecia. ¹⁰⁶⁴ The pathogenesis remains unknown. ¹⁰⁶⁵

Loose anagen (hair) syndrome (OMIM 600628) is a recently delineated entity of childhood in which anagen hairs are easily pulled from the scalp of affected individuals, who present with diffuse hair loss.^{1066.1067.1068.1069. and 1070.} It results from a disorder of adhesion of anagen hairs between the hair cuticle and inner root sheath cuticle leading to impaired anchorage of hairs to their follicle.^{1071. and 1072.} It may sometimes be mimicked by alopecia areata. ¹⁰⁷³ Some improvement in the alopecia occurs with increasing age. Children usually present with slow-growing hair that seldom requires cutting. ¹⁰⁷⁴ Short anagen syndrome also presents in this way. ⁷⁸⁶ Adult onset has been recorded.

The hair-pluck trichogram shows a high proportion of loose anagen hairs, but the hair-pull test varies over time. ¹⁰⁷¹ There are even periods when no hairs can be obtained. ¹⁰⁷¹

Trichotillomania, probably related to child abuse, has been superimposed on this syndrome, increasing the hair loss. ¹⁰⁷⁵

The syndrome has been associated with ectodermal dysplasia, with woolly hair, ¹⁰⁷⁶ and with a Noonan-like syndrome (OMIM 607721). ¹⁰⁷⁷ A mutation in the hair keratin gene K6HF (now KRT86) has been found in a few cases. ¹⁰⁷⁴

Alopecia induced by drugs usually presents as diffuse, non-scarring hair loss that is reversible upon withdrawal of the drug.^{1079.1080. and 1081.} It is a common complication of the various antimitotic agents used in the chemotherapy of cancer, ¹⁰⁸² but it may also occur as a rare complication of other therapeutic drugs. ¹⁰⁸³ It is now being described with the epidermal growth factor receptor (EGFR) inhibitors.^{1084. and 1085.} They may affect both growth and hair texture. A nationwide outbreak of alopecia has been reported in the United States, associated with the use of a commercial hair-straightening product. ¹⁰⁸⁶ The low pH of the product may have been responsible. Hair care products are widely used, and although sometimes implicated as a cause of hair loss, this complication is exceedingly rare, if it happens at all. ¹⁰⁸⁷

Drugs may interfere with hair growth in a number of different ways. For example, thallium, ¹⁰⁸⁸ excess vitamin A, retinoids, and certain cholesterol-lowering drugs interfere with the keratinization of the hair follicle.^{1079.1089. and 1090.} The antimitotic drugs interfere with hair growth in the anagen phase by interrupting the normal replication of the hair matrix cells. ¹⁰⁸⁰ Other drugs induce telogen effluvium and the follicles remain in the resting phase.

Besides those already listed, drugs that may induce alopecia include anticoagulants, antithyroid drugs, chemicals used in straightening hair,^{1086. and 1091.} anticonvulsants, hormone-related substances such as clomiphene, heavy metals such as lead, bismuth, arsenic, gold, mercury and lithium, antibacterial agents such as gentamicin, nitrofurantoin and ethambutol, and non-steroidal anti-inflammatory or antihyperuricemic agents such as naproxen, ibuprofen, allopurinol, probenecid and indomethacin.^{1079.1080. and 1092.} The anticonvulsant valproate may cause depigmentation of hair, rather than alopecia. ¹⁰⁹³ Drugs that have been incriminated rarely include amphetamines, vasopressin, ¹⁰⁹⁴ beta-blocking agents, cimetidine, levodopa, methysergide, penicillamine, bromocriptine, borates, ¹⁰⁹⁵ quinacrine (mepacrine), selenium, and tricyclic antidepressants. ¹⁰⁸⁰ Localized alopecia has been reported at the injection site of interferon alfa-2b. ¹⁰⁹⁶ A detailed listing is contained in the review article by Pillans and Woods. ¹⁰⁸¹

Idiopathic scarring alopecia (fibrosing alopecia,^{683. and 971.} alopecia cicatrisata, pseudopelade) is a rare, asymptomatic form of scarring alopecia in which there is patchy hair loss not accompanied by any clinical evidence of folliculitis, lichen planus, lupus erythematosus, or any of the specific diseases listed above. ¹¹¹⁶ The term ‘idiopathic scarring alopecia’ is preferred to the more commonly employed name pseudopelade, which has been used in the past in a variety of contexts:^{1117.1118. and 1119.} it has been applied to end-stage scarring alopecias following known dermatoses such as lichen planus and lupus erythematosus.^{1120. and 1121.} It is conceded that the term ‘pseudopelade’ has some use in a clinical setting to refer to a scarring alopecia, the cause of which is not yet known, but it should not be used to refer to a clinicopathological entity. ¹¹²² The term ‘idiopathic scarring alopecia’ is used infrequently these days.

Idiopathic scarring alopecia tends to affect females over the age of 40 years. It has an insidious onset and a chronic, usually slowly progressive course. It results in slightly depressed patches of irreversible hair loss which may occur singly or in groups that have been described as resembling ‘footprints in the snow’. ⁶⁸⁶ The small patches may coalesce to form larger patches of scarring alopecia. Both the scalp and beard area were involved in one patient. ¹¹²³ As the designation ‘idiopathic’ implies, the etiology is unknown.

Fibrogenic cytokines (IL-4, IL-6, fibroblast growth factor (bFGF), and TGF-β) were demonstrated in all scarring alopecias tested in one series. ¹¹²⁴

The term ‘traction alopecia with scarring’ is used in preference to ‘hot comb’ alopecia, central progressive alopecia in black females, and the follicular degeneration syndrome, for a form of scarring alopecia involving predominantly the crown of the scalp.^{1129. and 1130.} Hairs at the periphery of the scalp are spared. It primarily affects black women. ¹¹³¹ Traction alopecia was present in 22.6% of African adults (n = 874) examined in Cape Town; its prevalence was higher in women than men. ¹¹³² It also occurs in African schoolchildren. ¹¹³³ Relaxers, chemicals used to straighten African hair, can produce a similar clinicopathological picture. ¹¹³⁴ Traction alopecia can be reduced/prevented by avoiding hairstyles with traction especially to chemically processed hair. ¹¹³⁵

While minor degrees of traction can produce hair loss without significant scarring, as in trichotillomania (see p. 421), prolonged and recurrent severe traction can result in scarring. Recently, Ackerman and colleagues have presented a detailed study of this entity, pointing out that there is no follicular degeneration in these cases, and that the use of this term is no longer justified. ⁸⁰⁵

Pressure (postoperative) alopecia is a related disorder seen rarely in patients who have undergone a major surgical procedure.^{695. and 1136.} A few weeks later there is nearly total hair loss from the pressured area with sharp demarcation. The occipital area is commonly involved. Scarring also results in some of these cases.

The term ‘postmenopausal frontal fibrosing alopecia’ has been used for a progressive frontal scarring alopecia associated with perifollicular erythema.^{1137. and 1138.} The eyebrows and axillary hair are lost in some cases, ¹¹³⁹ leading to the suggestion that it is related to the Graham Little–Piccardi–Lassueur syndrome. ¹¹⁴⁰ Kossard and colleagues have reported 16 cases, suggesting that it is more common than the paucity of reports would suggest. ¹¹⁴¹ The histological features are generally thought to be indistinguishable from those seen in lichen planopilaris, but Tosti and colleagues have stated that unlike lichen planopilaris the lymphocytic infiltrate and fibrosis affect selectively the intermediate and the vellus-like follicles. ¹¹⁴² Others have reported more apoptosis in frontal alopecia than in lichen planopilaris and less follicular inflammation. ¹¹⁴³ The absence of lesions of lichen planus elsewhere in most cases led to the suggestion that these cases might represent a unique follicular destruction syndrome mediated by lymphocytes and triggered by postmenopausal events. ¹¹³⁷ However, it has now been reported in a premenopausal woman with cutaneous lichen planus. ¹¹⁴⁴ It is best regarded as a variant of lichen planopilaris with selective involvement of certain androgen-dependent areas (see p. 43).^{1141. and 1142.} It has followed hair transplantation for androgenetic alopecia. ¹¹⁴⁵ Dermoscopy can be used to distinguish the condition from alopecia areata. ¹¹⁴⁶ Loss of orifices is seen in all cases, but there are no yellow dots characteristic of alopecia areata. ¹¹⁴⁶

In some patients who have been treated with finasteride the condition has not progressed, which suggests that androgens may be partly responsible. ¹¹⁴² Intralesional and topical corticosteroids may also stop the progression of the disease. ¹¹³⁹

Fibrosing alopecia in a pattern distribution appears to be another variant of lichen planopilaris in which the immune reaction is directed against miniaturized follicles of androgenetic alopecia. ¹¹⁴⁷ That is, these persons develop inflammatory scarring alopecia affecting only the balding central scalp. ¹¹⁰² The lichenoid infiltrate targets the upper follicle. Late lesions resemble end-stage lichen planopilaris. ¹¹⁴⁷

Folliculitis decalvans is sometimes considered to be a primary scarring alopecia. However, because inflammation of the follicle is a major feature, it has been considered with the folliculitides on page 406. Hair straightening and other cosmetic practices are a common cause of this condition in African-American women. ¹¹⁴⁸ Sperling believes that folliculitis decalvans in most cases represents a highly inflammatory form of central centrifugal cicatricial alopecia. ³⁵⁰

Tufted-hair folliculitis is characterized by areas of scarring alopecia with tufts of 10–20 hairs emerging from single follicular openings.^{1149.1150. and 1151.} There is a predilection for the parietal and occipital areas. ¹¹⁵² It is most likely a consequence of bacterial folliculitis involving the upper and mid follicle with rupture and scarring. It may complicate folliculitis decalvans,351. ^{and 352.} folliculitis keloidalis nuchae (acne keloidalis), and pemphigus vulgaris.^{1153.1154. and 1155.} It has followed the use of cyclosporine. ¹¹⁵⁶

Antibiotics, both topical and systemic, are commonly used treatments, but complete cure is rare. ¹¹⁵² A combined therapy of oral rifampicin and oral clindamycin for 10 weeks has been used. ³⁵² It was effective in about one-half of the cases. ³⁵²

Lipedematous alopecia, an acquired condition of unknown etiology, is characterized by a thick, boggy scalp with varying degrees of hair loss, occurring predominantly in adult black females.^{1158. and 1159.} It is associated with a non-scarring but permanent alopecia. ¹¹⁶⁰ Irritation and pruritus are often present. ¹¹⁶¹ It has been reported in association with discoid lupus erythematosus. ¹¹⁶² There is doubling of the scalp thickness due to expansion of the subcutaneous fat layer. ¹¹⁶³ The term ‘lipedematous scalp’ has been used for cases without hair loss. ¹¹⁶⁴ The diagnosis can be confirmed by ultrasound.

Surgical debulking has been described as a method of management. ¹¹⁶⁵

Hypertrichosis refers to the growth of hair on any part of the body in excess of the amount usually present in persons of the same age, race, and sex. ¹¹⁷¹ Androgen-induced hair growth (hirsutism) is not included in this definition. ¹¹⁷² Several distinct clinical forms exist. ¹¹⁷³

Congenital hypertrichosis lanuginosa is an exceedingly rare familial disorder, often inherited as an autosomal dominant trait, in which there is excessive growth of lanugo hair. ¹¹⁷⁴ Dental and eye abnormalities may also be present. ¹¹⁷⁵ Sporadic cases also occur. ¹¹⁷⁶

Terminal and lanugo hairs are present in the hypertrichosis associated with gingival fibromatosis (OMIM 135400), a rare autosomal dominant syndrome.^{1177. and 1178.}

Acquired hypertrichosis lanuginosa is usually generalized, except for the palms and soles. An important cause is an underlying cancer, usually of epithelial type, ¹¹⁷⁹ although rarely a lymphoma is present. ¹¹⁸⁰ Hair growth may antedate the appearance of the tumor by months to several years.^{1181. and 1182.} There may be rapid resolution after treatment of the malignancy. ¹¹⁸³ The pathogenesis is unknown. Vellus hairs, intermediate forms, and terminal hairs may also be increased in paraneoplastic cases, ¹¹⁷⁶ as well as in cases of porphyria, malnutrition and brain injury and, usually reversibly, in patients taking streptomycin, phenytoin (diphenylhydantoin), corticosteroids, penicillamine, psoralens, benoxaprofen, the vasodilators diazoxide and minoxidil, ¹¹⁸⁴ and cyclosporin A (cyclosporine).^{1171.1185. and 1186.} Minoxidil-induced hypertrichosis may be limited to the face. ¹¹⁸⁷

Localized areas of hypertrichosis can be seen in congenital pigmented nevi, Becker’s nevus, overlying a neurofibroma, scrotal hair, ¹¹⁸⁸ hairy pinnae, hairy elbows (OMIM 139600),^{1178. and 1189.} anterior and posterior cervical hypertrichosis (OMIM 239840),^{1178.1190. and 1191.} nevoid hypertrichosis,^{1192. and 1193.} spinal dysraphism (‘faun-tail’),^{1194. and 1195.} ectopic cilia, ¹¹⁹⁶ and in depigmented hypertrichosis following Blaschko’s lines. ¹¹⁹⁷ Nevoid hypertrichosis is a congenital circumscribed patch of terminal hair without other abnormalities. It is usually solitary. ¹¹⁷³ It may be linear. ¹¹⁹⁸ Nevoid hypertrichosis has been successfully treated with the alexandrite laser. ¹¹⁹⁹

Moderate hypertrichosis of the lower extremities has been reported in a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS syndrome). ¹²⁰⁰ Other congenital syndromes associated with hypertrichosis¹²⁰¹ are listed in the review of this subject by Wendelin et al in 2003. ¹¹⁷³ A new entity reported since this review is the H syndrome (OMIM 612391), a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with numerous systemic manifestations including short stature, cardiac anomalies, hypogonadism, and hepatosplenomegaly. ¹²⁰²

Hypertrichosis may develop at sites of persistent friction and irritation in association with plaster casts and at sites of inflammation, including insect bites. ¹²⁰³ Trauma may explain the paradoxical hypertrichosis that followed laser epilation. ¹²⁰⁴ It has also developed at the site of measles immunization, ¹²⁰⁵ and in association with a verruca vulgaris. ¹²⁰⁶ It developed on the glans penis in an adult male, but no etiology was apparent. ¹²⁰⁷ Facial hypertrichosis has been induced by efalizumab¹²⁰⁸ and by cetuximab. ¹²⁰⁹ Hypertrichosis of the eyelashes can be caused by drugs that lower intraocular pressure such as latanoprost and bimatoprost. ¹²¹⁰

There is extensive clinical evidence for the effectiveness of laser and light-based treatments in the removal of unwanted hair. ¹²¹¹ Their mechanism of action is unknown. A study of follicular stem cells following laser treatment showed thermally altered hair shafts but intact stem cells, suggesting that functional alteration, rather than their destruction, may underlie the clinical efficacy of this treatment. Alternatively, completely different mechanisms may be involved. ¹²¹¹

Keratosis pilaris (OMIM 604093) is a disorder of keratinization involving the infundibulum of the hair follicle. It is a common condition, being found in up to 5% of adult males and in 30% of females, particularly those showing hyperandrogenism and obesity. ¹²¹³ These figures obviously include cases of keratosis pilaris rubra (see below) that has not always been distinguished from keratosis pilaris itself. It is also increased in patients with insulin-dependent diabetes mellitus. ¹²¹⁴ The lesions, which vary from subtle follicular excrescences to more prominent follicular spikes, are found most often on the posterior aspect of the upper part of the arms and on the lateral aspect of the thighs and buttocks. ¹²¹⁵ Unilateral involvement has been reported. ¹²¹⁶ Onset is usually in childhood with remission in adulthood in some patients. ¹²¹⁷ Follicular keratotic plugs resembling keratosis pilaris may be found in keratosis pilaris rubra, keratosis pilaris atrophicans (see below), lichen spinulosus (see p. 434), pityriasis rubra pilaris, ichthyosis, psoriasis, some eczemas, lithium therapy, ¹²¹⁸ and uremia.^{1213.1219. and 1220.} Keratosis pilaris itself has also been reported in the ectodermal dysplasias,^{1216.1221. and 1222.} and in association with woolly hair. Large follicular keratotic plugs are seen in the amputation stumps of some patients with lower limb amputations and ill-fitting prostheses;^{1223. and 1224.} they have also been seen as an idiopathic phenomenon. ¹²²⁵ Follicular keratosis of the chin also appears to be due to prolonged pressure and friction. ¹²²⁶

Keratosis pilaris rubra is characterized by substantial erythema, widespread involvement, and persistence after puberty. ¹²¹⁷ There is no atrophy or hyperpigmentation as seen in the atrophic variants. ¹²¹⁷ Erythema is sometimes present in keratosis pilaris, but it is usually mild and limited to the perifollicular skin.

It is thought that androgenic stimulation of the pilosebaceous follicle may result in the hyperkeratinization of the infundibulum. ¹²¹³ Flushing by autonomic dysregulation may have a role in the rubra variant. ¹²¹⁷

Numerous treatments have been used, reflecting the lack of a consistent response to any therapy. They include emollients, various keratolytics, or a combination, topical corticosteroids, pulsed-dye laser, and retinoids, both topical or systemic. ¹²¹⁷

The term ‘keratosis pilaris atrophicans’ refers to a group of three related disorders in which keratosis pilaris is associated with mild perifollicular inflammation and subsequent atrophy, particularly involving the face.^{1230. and 1231.} Differences in the location and the degree of atrophy have been used to categorize these three conditions. Fortunately most cases cease to progress after puberty.

Treatment is usually unsuccessful. Emollients may be used. Antibiotics have no effect. Keratolytics and oral retinoids have also been used with mostly disappointing results. ¹²³¹

Keratosis pilaris atrophicans faciei is manifest soon after birth by follicular papules with an erythematous halo involving the lateral part of the eyebrows.^{1232. and 1233.} It may later involve the forehead and cheeks. Pitted scars and alopecia usually result. ¹²³³ Keratosis pilaris of the arms, buttocks, and thighs is often present. Less common clinical associations include atopy, mental retardation, ¹²³³ woolly hair, ¹²³⁴ cardiofaciocutaneous syndrome,^{1235. and 1236.} Rubinstein–Taybi syndrome (OMIM 180849), ¹²³⁷ Cornelia de Lange syndrome (OMIM 122470), ¹²³⁸ Noonan’s syndrome (OMIM 163950),^{1239.1240.1241. and 1242.} Bazex–Dupré–Christol syndrome (OMIM 301845), ¹²⁴³ and a low serum vitamin A level. ¹²³³ Some reports suggest an autosomal dominant inheritance. ¹²³³ A gene in the 18p region may be involved. ¹²⁴⁴

Keratosis follicularis spinulosa decalvans (OMIM 308800) is another exceedingly rare condition which begins in infancy with diffuse keratosis pilaris associated with scarring alopecia of the scalp and eyebrows.^{1245.1246.1247. and 1248.} ‘Moth-eaten’ scarring of the cheeks usually results. Associations include atopy, acne keloidalis nuchae, ¹²⁴⁹ photophobia, corneal abnormalities, Down syndrome, ¹²⁵⁰ palmoplantar keratoderma, ¹²⁵⁰ woolly hair, ¹²⁵¹ and other ectodermal defects. ¹²⁵² The gene maps to Xp21.1–p22.2. ¹²⁵³ It is probably the SAT-1 gene which encodes spermidine/spermine NI-acetyltransferase. ¹²⁵¹ Females can be involved. ¹²⁵⁴ Some cases are sporadic, while other cases appear to be autosomal dominant. ¹²⁵⁵ On histological examination there is hyperkeratosis, follicular keratotic plugging, mild perifollicular chronic inflammation, and focal scarring. ¹²⁵⁶ Biopsies from the scalp show a scarring alopecia with some features of folliculitis decalvans. ¹²⁵⁷ A variant with autosomal dominant inheritance and inflammation that begins at puberty has been called ‘folliculitis spinulosa decalvans’. ¹²³⁰

Treatment failure is the usual outcome. Oral isotretinoin is sometimes effective. ¹²⁴⁹

Atrophoderma vermiculata (folliculitis ulerythematosa reticulata)^{1258. and 1259.} involves the preauricular region and cheeks.^{1260.1261.1262.1263. and 1264.} It may follow Blaschko’s lines. ¹²⁶⁵ It develops in late childhood with the formation of horny follicular plugs which are later shed. This is followed by a reticulate atrophy with some comedones and scattered milia. Inheritance is autosomal dominant in type. Rare clinical associations include Marfan’s syndrome, ¹²⁶⁶ leukokeratosis oris, ¹²⁶⁷ and trichoepitheliomas with basal cell carcinomas (ROMBO syndrome – see p. 683).^{1268. and 1269.} Keratosis pilaris of the limbs is quite commonly present. A condition described in the literature as atrophia maculosa varioliformis cutis (OMIM 601341) affects a similar location on the cheeks^{1270.1271.1272. and 1273.} but there is no mention in these cases of a preceding stage with follicular plugging. ¹²⁷⁰ Extrafacial involvement also occurs. ¹²⁷⁴ Familial cases of this variant have been reported.^{1275. and 1276.} It appears to be autosomal dominant. ¹²⁷⁷ A disorder of elastin has been suggested. ¹²⁷⁸ Another variant has been called ‘hereditary perioral pigmented follicular atrophoderma’ (OMIM 603587). It is associated with milia and epidermal cysts. ¹²⁷⁹

All three conditions are regarded as congenital follicular dystrophies with abnormal keratinization of the superficial part of the follicles. A fourth condition, erythromelanosis follicularis faciei et colli, has minute follicular papules resulting from small keratin plugs associated with red-brown pigmentation and fine telangiectases.^{1280.1281.1282.1283.1284.1285.1286.1287. and 1288.} Lesions are usually confined to the face and neck, but there may be extension onto the upper trunk. ¹²⁸⁹ This rare disease appears to be another follicular dystrophy but is usually not considered with the other three conditions because it lacks any atrophy. Familial cases have been reported.^{1290.1291. and 1292.} In one of these families keratosis pilaris was also present. ¹²⁹¹ It has also been present in many of the non-familial cases. ¹²⁸⁹

Follicular spicules with a horny appearance have been reported on the face of patients with multiple myeloma and cryoglobulinemia.^{1295.1296. and 1297.} The spicules are composed of eosinophilic, compact, homogeneous material which is largely the monoclonal protein of the underlying gammopathy. ¹²⁹⁶

Lichen spinulosus is a rare dermatosis of unknown etiology characterized by follicular keratotic papules that are grouped into plaques, 2–6 cm in diameter. ¹²⁹⁸ The horny spines protrude 1–2 mm above the surface. Lesions are distributed symmetrically on the extensor surfaces of the arms and legs and on the back, chest, face, and neck. Onset of the disease is in adolescence. It has been described in an HIV-positive man¹²⁹⁹ and in an elderly female with Crohn’s disease. ¹³⁰⁰ It is commonly seen in patients with an atopic diathesis.

Emollients and/or salicylic acid have been used successfully to treat this condition. ¹³⁰¹ The combination of tretinoin gel, 0.04%, applied nightly and hydroactive adhesive applications daily can also be used. ¹³⁰¹