Continuing Education Activity

Hypertrichosis is defined as excessive hair growth anywhere on the body in either males or females. It is important to distinguish hypertrichosis from hirsutism, which is a term reserved for females who grow an excessive amount of terminal hairs in androgen-dependent sites. This activity explains when this condition should be considered on a differential diagnosis, articulates how to properly evaluate for this condition, and highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Review the etiology of hypertrichosis.
• Describe the presentation of a patient with hypertrichosis.
• Summarize the treatment options for hypertrichosis.
• Outline the importance of enhancing care coordination among the interprofessional team to ensure proper evaluation and management of hypertrichosis.

Introduction

Hypertrichosis is defined as excessive hair growth anywhere on the body in either males or females. It is important to distinguish hypertrichosis from hirsutism, which is a term reserved for females who grow an excessive amount of terminal hairs in androgen-dependent sites.[1][2][3]

There are several ways of classifying hypertrichosis. These are based on the distribution (generalized vs. localized), the age of onset (congenital versus acquired), and the type of hair (vellus versus terminal).

Forms of generalized hypertrichosis include, but are not limited to, congenital generalized hypertrichosis (which is further divided into congenital hypertrichosis lanuginosa, universal hypertrichosis, and hypertrichosis universalis congenita), prepubertal hypertrichosis, acquired generalized hypertrichosis, and acquired hypertrichosis lanuginosa. They each differ in their etiology and clinical findings.[4][5][6][7][8]

Forms of localized hypertrichosis include, but are not limited to, congenital localized hypertrichosis (congenital nevi, plexiform neurofibromas, Becker melanosis/nevus, nevoid hypertrichosis, spinal dysraphism, and the hair collar sign), localized hypertrichosis in hereditary and acquired systemic disease, and acquired localized hypertrichosis.[9][10][11][12][13]

An understanding of lanugo, vellus, and terminal hair is integral in evaluating a patient with presumed hypertrichosis. Lanugo hair is fine, non-pigmented hair that covers the normal fetus. It is often several centimeters long. By the first few weeks of life, lanugo hair should be replaced by vellus hair on the body and terminal hair on the scalp.  Vellus hair is lightly pigmented, fine, short hair, often referred to as “peach fuzz” that is found on the face, arms, stomach, and legs. Terminal hair is coarse, thick hair that is found on the scalp, underarms, and pubic area. In men, terminal hair is also found on the face. During puberty, vellus hair is replaced with terminal hair in androgen-dependent sites under the influence of testosterone.[1]

Etiology

Congenital generalized hypertrichosis is a feature of several rare inherited syndromes in which genetic errors result in the dysfunction of proteins involved in the development of the hair follicle.[10] There is some evidence to support that exposure to medications such as minoxidil in utero may predispose to congenital generalized hypertrichosis.[14]

Prepubertal hypertrichosis is linked to elevated levels of free and total testosterone in some patients.[7][15]

Drugs most often cause acquired generalized hypertrichosis.

• Antibiotics such as streptomycin
• Anti-inflammatory drugs such as benoxaprofen and corticosteroids
• Vasodilators (diazoxide, minoxidil, prostaglandin E1)
• Diuretics (acetazolamide)
• Anticonvulsants (phenytoin)
• Immunosuppressives (cyclosporine, mycophenolate mofetil)
• Psoralens (methoxypsoralen, trimethylpsoralen)
• Antiseptic agents (hexachlorobenzene) 
• Chelators (penicillamine)
• Interferon-alpha
• Fenoterol
• EGFR inhibitors (cetuximab, panitumumab, erlotinib, gefitinib)

Although drugs are usually the culprit, acquired generalized hypertrichosis can also be seen in traumatic brain injuries, juvenile hypothyroidism, juvenile dermatomyositis, acromegaly, malnutrition, and advanced HIV infection.[16][17][16]

Acquired hypertrichosis lanuginosa is considered to be a paraneoplastic phenomenon, and in certain instances precedes the diagnosis of cancer.[18][19] The most common malignancies that it is associated with include lung, colon, and breast cancers. It is sometimes seen in concert with other paraneoplastic dermatoses such as acanthosis nigricans, palmoplantar keratoderma, Leser-Trelat sign, and acquired ichthyosis.

Several forms of congenital localized hypertrichosis including hypertrichosis cubiti (hairy elbow syndrome), hairy palms and soles, hypertrichosis of the auricle, hypertrichosis of the nasal tip, and anterior or posterior cervical hypertrichosis are inherited in an autosomal dominant fashion.[20] Trichomegaly of the eyelashes is the exception, as it is an autosomal-recessive disorder.[21][22]

Congenital melanocytic nevi are often associated with hypertrichosis that becomes apparent during the infantile period of childhood. Plexiform neurofibromas, lesions pathognomonic for neurofibromatosis type I, also have associated hypertrichosis.[23]

Nevoid hypertrichosis has a variable etiology.

• Primary nevoid hypertrichosis occurs in the absence of extracutaneous associations.
• Secondary nevoid hypertrichosis is associated with lipodystrophy, hemihypertrophy, scoliosis, and abnormalities of the underlying vasculature.[24][25]

There are several hereditary and acquired systemic diseases that present with localized hypertrichosis. Cornelia de Lange syndrome, caused by autosomal dominant or X-linked dominant mutations can present with synophrys (unibrow), as well as hypertrichosis over the forehead, lateral face, shoulders, and back.[26] Rubinstein-Taybi syndrome is due to autosomal-dominant mutations and leads to hypertrichosis over the lateral face, shoulders, and back.[27] Porphyria cutanea tarda is a cause of hypertrichosis in sun-exposed areas.[28][29] Lipodystrophy syndromes, such as Berardinelli-Seip syndrome caused by AGPAT2, BSCL2, CAV1, CAVIN1/PTRF gene mutations, can present with hypertrichosis as well.[30]

Acquired localized hypertrichosis is caused by repetitive trauma, friction, irritation, or inflammation. For example, localized hypertrichosis is often observed on the back of sack carriers, over a fractured limb after plaster casting, and over the posterior neck in weightlifters.  It can also be seen within vaccination sites and varicella scars.[10] Hypertrichosis at sites of wart removal and laser epilation has also been reported in the literature. Acquired localized hypertrichosis can also be iatrogenic; it has been described following PUVA therapy, topical corticosteroids, tacrolimus, creams containing mercury or iodine, anthralin, and prostaglandin F-2 alpha analogs (latanoprost, bimatoprost).[31]

Epidemiology

In the majority of hypertrichosis cases, men and women are equally affected, with a few exceptions. Prepubertal hypertrichosis is common in healthy, Mediterranean, or South Asian infants and children. Hypertrichosis of the auricle and hypertrichosis of the nasal tip,  types of hereditary hypertrichosis, primarily affect males.[32][33]

Pathophysiology

The pathophysiology of hypertrichosis varies depending on the etiology. Genetic abnormalities underlie several types of hypertrichosis, and the pathogenesis of increased hair growth is unknown.

Histopathology

On histopathology, hypertrichosis appears as an increased number of terminal or vellus hairs, depending on the etiology of the hypertrichosis.

History and Physical

History and physical exam findings for hypertrichosis differ between types of hypertrichosis. In generalized forms of hypertrichosis, the patient will present with lanugo hair, vellus hair, or terminal hair covering a majority of their body. Transformation of terminal hair to lanugo hair can be seen.[34]

There are several disorders characterized by congenital generalized hypertrichosis. Congenital hypertrichosis lanuginosa presents rather dramatically; the entire body surface, except for the palms, soles, dorsal hands and feet, and prepuce are covered with fine, silver-gray to blond lanugo hair. Hair may grow up to 10 centimeters in length, giving a "werewolf" appearance. Congenital hypertrichosis lanuginosa may present with dental anomalies, glaucoma, pyloric stenosis, and photophobia.[35]

Universal hypertrichosis, another form of congenital generalized hypertrichosis, presents with thick, long hair on the back, proximal extremities, and preauricular areas. It is often thought of as "exaggerated normal hairiness."[36]

Hypertrichosis universalis congenita sometimes referred to as Ambras syndrome, presents with fine, silky, light-colored long hair primarily involving the face, ears, shoulders, and nose. It is associated with minor facial dysmorphism, supernumerary nipples, and dental anomalies.[37][38]

Patients with prepubertal hypertrichosis typically present with widespread, diffuse involvement that becomes obvious and bothersome during childhood. Hair growth favors the face (especially the forehead, temples, and preauricular area), proximal extremities, and back. It is described as having an "inverted fir tree" pattern. It also features thick, bushy eyebrows and a low anterior hairline.[7]

Acquired generalized hypertrichosis presents with the reversible, slow growth of terminal hairs over the forehead, temples, flexors, and trunk. Patients will report a history of frequently implicated medications traumatic brain injury, or systemic disease (see etiology section for a complete list).

In acquired hypertrichosis lanuginosa, fine lanugo hairs rapidly develop over the entire body. Mild forms localized to the face exist. Patients may report a history of malignancy.[19]

Several forms of congenital localized hypertrichosis exist. Hypertrichosis cubiti (hairy elbow syndrome) presents anywhere from birth to early childhood with hypertrichosis over the forearms and antecubital fossa. It is occasionally associated with short stature. Hairy palms and soles syndrome presents at birth. Hypertrichosis of the auricle presents during childhood or adolescence and favors males. Hypertrichosis of the eyebrows and nasal tip appear in adolescence. Anterior cervical hypertrichosis presents from birth to early childhood and is associated with sensory and motor neuropathy, mental retardation, and hallux valgus. Posterior cervical hypertrichosis appears at birth and is associated with kyphoscoliosis.[39]

Becker melanosis (nevus) presents as a patch of hyperpigmentation with irregular borders on the upper trunk. Typically, hyperpigmentation appears during childhood, with hypertrichosis developing later in the second decade of life. Patients with Becker melanosis may have associated asymmetry of the extremities and hyperplasia or hypoplasia underlying the affected areas; ipsilateral mammary hypoplasia is a common finding in women). There are reports of Becker melanosis arising in the context of genitourinary abnormalities (SNUB syndrome; supernumerary nipples, uropathies, and Becker melanosis). Becker melanosis can also be associated with hemimaxillofacial dysplasia, which presents as unilateral maxillary enlargement manifesting as facial asymmetry, gingival hyperplasia, and hypoplastic teeth.[40]

Nevoid hypertrichosis presents as a well-circumscribed area of overgrowth of terminal hairs. Primary nevoid hypertrichosis refers to an isolated finding with no extracutaneous associations. Secondary nevoid hypertrichosis is often seen in conjunction with lipodystrophy, hemihypertrophy, scoliosis, and vasculature abnormalities.[24]

Localized areas of hypertrichosis may be a sign of defects underlying the patch of hair, such as spinal dysraphism. The faun tail sign is a patch over the lumbosacral area signifying the presence of spina bifida occulta or diastematomyelia (split spinal cord). The hair collar sign is a ring of hypertrichosis that surrounds aplasia cutis or ectopic brain tissue.[12]

Porphyrias such as porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP) can present as hypertrichosis within sun-exposed areas. Patients will present with other symptoms of porphyria. The hypertrichosis associated with PCT often favors the lateral face. Patients will present with other stigmata of PCT including a blistering photosensitive eruption.[41]

Acquired localized hypertrichosis will present as hypertrichosis, hyperpigmentation, and epidermal hyperplasia at a site of friction. Patients will report a history of mechanical or iatrogenic insult to the area. It is important to note that there are several reports of localized hypertrichosis overlying areas of lupus panniculitis and morphea.[10][42]

Evaluation

When a patient presents with generalized hypertrichosis, the first step in evaluation is to determine whether it is a congenital or acquired problem. This can generally be determined by patient history. 

If the hypertrichosis appears to be of congenital origin, the next step is to determine whether fine, lightly colored lanugo hairs predominate (suggesting a diagnosis of congenital hypertrichosis lanuginosa), or if pigmented/terminal hairs predominate. If there is a predominance of pigmented/terminal hairs, the patient should be evaluated for a family history of hypertrichosis, maternal drug or alcohol intake, and orofacial, skeletal, ocular, or neurologic abnormalities that may suggest a rare genetic syndrome such as X-linked hypertrichosis, congenital generalized hypertrichosis with or without gingival dysplasia, hypertrichotic osteochondrodysplasia, Zimmerman-Laband syndrome, Coffin-Siris syndrome, Schinzel-Giedion midface retraction syndrome, Gorlin-Chaudry Moss syndrome, adducted thumbs syndrome, Barbar-Say syndrome, Amaurosis congenita, or CAHMR (cataracts, hypertrichosis, and mental retardation) syndromes.[35][43][44][45] 

If the hypertrichosis appears to be acquired, once again the next step is to determine whether terminal hairs or lanugo hairs predominate. If terminal hairs predominate in the setting of the slow, progressive development of hypertrichosis, the patient should be screened for features suggestive of prepubertal hypertrichosis (Mediterranean or South Asian descent, familial hairiness, inverted tree pattern on the back). The patient should also be screened for symptoms of androgen excess such as the early development of axillary/pubic hair, virilization, acne, and increased androgen levels. These may suggest a diagnosis of hirsutism, as opposed to hypertrichosis. If terminal hairs predominate in the setting of rapid growth, a thorough evaluation of the patient’s drug intake, thyroid hormone levels, and nutritional status should take place. If a patient presents with the sudden appearance of acquired lanugo hairs, they should be screened for malignancy.

Treatment / Management

Laser hair removal, depilatory creams, and electrolysis are used to remove unwanted hair. The Nd:Yag laser, Alexandrite laser, and diode laser are the most efficacious hair removal lasers. Depilatory creams typically contain calcium thioglycolate and barium sulfate and are effective though they may irritate the skin.[46][47][48]

Differential Diagnosis

When considering a diagnosis of hypertrichosis, the major differential diagnosis is hirsutism. Hypertrichosis can be seen in both females and males, while hirsutism is a term used to describe male-pattern terminal hair growth in women, within androgen-dependent sites. Hirsutism is caused by increased androgens and is associated with other signs of androgen excess.

Treatment Planning

Several laser and light treatments are suitable for hair removal, depending on the Fitzpatrick skin type of the patient. 

Suitable technologies include 755 nm Alexandrite laser, 1064 nm Nd:Yag laser, diode laser, intense pulsed light (IPL), and electrolysis. [49]

Prognosis

The prognosis of hypertrichosis varies, depending on the type of hypertrichosis. Hypertrichosis associated with genetic syndromes is generally lifelong. In the setting of drug-induced hypertrichosis, it is usually reversible with discontinuation of the medication.

Deterrence and Patient Education

If the hypertrichosis has a genetic component, patients should be intimated about the risk of their children inheriting the traits.

Enhancing Healthcare Team Outcomes

Hypertrichosis can cause severe emotional distress for patients, especially those who do not have access to permanent laser hair removal or electrolysis. Self-confidence and quality of life may be extremely low for these patients secondary to societal scrutinization and bullying in patients of all ages. In cases of severe hypertrichosis, it is imperative to arrange mental health care for patients in addition to medical care to address the underlying cause of the hypertrichosis, if there is one. The outcome of patients with hypertrichosis depends on the cause. For those with inherited disorders, there is no cure and poor cosmesis is a lifelong issue. For those with acquired hypertrichosis, the outcomes are good once the primary condition is treated or the offending medication is discontinued.