Serum Androgens. In all cases of hirsutism, screening for androgen excess should include serum testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEAS).

Dexamethasone Suppression Test. An empiric administration of dexamethasone for 7 to 14 days may help exclude adrenocorticotropin hormone (ACTH)-dependent hirsutism. Dexamethasone-mediated suppression of free testosterone, DHEAS, and plasma cortisol is observed in those with congenital adrenal hyperplasia (CAH) and IH.

ACTH-Stimulation Test. ACTH at 250 µg for 30 minutes may distinguish CAH from IH, as CAH results in elevations in metabolic precursors of cortisol.

Serum Follicle-Stimulating Hormone and Prolactin. Serum follicle-stimulating hormone and prolactin help assess for ovarian failure or prolactinoma.

Diabetes Screen. To assess for insulin resistance, screen with serum glucose, HbA_1c, and lipids.

There is variability among racial and ethnic groups in the number of hair follicles per unit skin area and rate of hair growth. Therefore, the degree of body hair growth and threshold for diagnosing hirsutism differ. Black and white women have equal numbers of facial hairs, apart from the scalp, in which black individuals have fewer hair follicles on biopsy.³⁸,³⁹ In pooling data from 2 large studies of women with hyperandrogenemia, Yildiz et al³ reported that there was no significant difference in the degree of body and terminal hair growth as well as in the prevalence of hirsutism between unselected black and white women. In contrast, East Asians have less body hair, despite having insignificant differences in androgen concentration, which may be explained by low 5α-reductase activity.⁴⁰ There are limited data assessing terminal hair growth in individual populations; however, a review of studies that looked into the epidemiology of hirsutism in populations of different racial and ethnic groups highlighted distinctions in threshold for diagnosing hirsutism and in prevalence.¹ There are no universally agreed upon criteria for diagnosing hirsutism in non-Caucasian populations, but suggested parameters are discussed in the subsequent section (“Treatment”).

Hypertrichosis is defined as increased hair growth that is abnormal for the individual’s age, sex, and race, excluding male-pattern hair growth in a woman (hirsutism). The excess hair can be manifested as increased length or density and may be of lanugo, vellus, or terminal types. There are limited mechanisms that have been proposed to explain hypertrichosis such as vellus-to-terminal hair switch, change in hair growth cycle in which the follicles spend longer in anagen than normal for their location, and an increase in hair follicle density discrepant for the body site. The triggers for each of these mechanisms are unclear. Therefore, the types of hypertrichosis are often distinguished by congenital or acquired as well as localized vs generalized involvement instead of mechanism.⁴¹ Hirsutism is often thought of separately or sometimes a subclass of hypertrichosis caused by excess androgen-sensitive hair growth. In this chapter, it will be described separately owing to key distinctions from hypertrichosis.

Congenital Hypertrichosis, Localized Types. Congenital nevocellular nevi are identifiable as hair is contained within a circumscribed melanocytic lesion. Nevoid hypertrichosis can be a single circumscribed patch of terminal hair or multiple lesions that have a greater density of hair follicles. A smooth muscle hamartoma appears as a hyperpigmented patch with larger pigmented vellus hairs that may also have perifollicular papules and exhibit a pseudo-Darier sign when rubbed (contraction of follicular smooth muscle fibers). Hypertrichosis may be present in an area with an underlying neurofibroma. Hypertrichosis cubiti or excess hair present on elbows manifests in infancy, grows in childhood, and resolves in adolescence. This condition has also been reported in combination with facial asymmetry, developmental delays, and patchy hypertrichosis ipsilateral to side of face alteration.⁴² The mode of inheritance is largely unknown, with variable accounts of normal endocrine and chromosomal studies, autosomal dominant transmission with incomplete penetrance, autosomal recessive transmission, as well as de novo mutation reported.⁴³ Hemihypertrophy, in which part or all of one side of the body is enlarged, can be associated with terminal hypertrichosis of the affected side. A biopsy of a patient with hypertrichosis and hemihypertrophy showed increased hair shaft width and terminal hair follicles where vellus growth would typically be present.⁴⁴ Hemihypertrophy can be an isolated finding, but it is also associated with many syndromes that are typified by neoplastic processes. Therefore, a comprehensive workup is indicated when a patient has a diagnosis of hemihypertrophy to account for the presence of any other anomalies such as brain tumors. Hairy cutaneous malformation of the acral surfaces is a rare autosomal dominant phenomenon in which women and children present with vellus hairs on palms, soles, or both and pubertal/postpubertal males have terminal hair growth in these sites, suggesting the presence of androgen-sensitive hair follicles.⁴⁵ Tissue biopsy shows unremarkable hair follicles within increased elastic fiber content in the dermis. Spinal hypertrichosis often indicates that there is spinal dysraphism, meaning the presence of a dermal cyst or sinus or other vertebral abnormalities such as a myelomeningocele.⁴⁶ Magnetic resonance imaging is suggested for evaluation, as early surgical intervention may be beneficial in limiting the extent of neurologic damage. Anterior cervical hypertrichosis refers to the presence of hair above the laryngeal prominence and may be seen either without associated findings or in a patient with peripheral neuropathy and hallus valgus.⁴⁷ It is unclear whether these are 2 different presentations of 1 condition or 2 separate conditions.⁴¹

Congenital Hypertrichosis, Generalized Types. Congenital hypertrichosis lanuginosa is another disorder in which lanugo hair remains on the entire body after birth, apart from palms, soles, and mucous membranes.⁴⁸ Other congenital abnormalities may also be associated, such as dental anomalies. Patients with this disorder lose most of the hair during late childhood yet continue to have excess in adulthood. Congenital generalized hypertrichosis is similar; however, individuals are born with terminal hair on the face, trunk, and limbs, sparing palms, soles, and mucosa.⁴⁹ Gingival fibromatosis with hypertrichosis manifests with excess hair growth of the face, trunk, and eyebrows and gingival hyperplasia.⁵⁰ Mental retardation and seizures may also be associated. Conversely, antiepileptic therapy and cyclosporine can cause hypertrichosis and gingival hyperplasia, and therefore, medication-induced hypertrichosis and gingival hyperplasia should be considered in the differential diagnosis.⁵¹,⁵²,⁵³ Osteochondrodysplasia with hypertrichosis presents in individuals as excess hair growth that spares areas that are usually devoid of hair (glabrous) and mucous membranes.⁵⁴ Features that may
also be seen in association with this disorder are macrosomia and cardiomegaly. Hypertrichosis has also been reported anecdotally in a patient with facial anomalies and pigmentary retinopathy among other features.⁵⁵

Congenital Syndromes Associated With Hypertrichosis as a Secondary Feature. Cornelia de Lange (Brachmann de Lange) syndrome is characterized by mental retardation; thick converging eyebrows; hypertrichotic eyelashes; vellus hypertrichosis on forehead, trunk, posterior neck, sacrum, and elbows; low hairline, as well as facial and limb anomalies.⁵⁶ Hypertrichosis (Table 7.2.2) can be seen in fetuses exposed to hydantoin during the first 9 weeks of gestation (fetal hydantoin syndrome) and alcohol exposure anytime during gestation (fetal alcohol syndrome).⁵⁷ Berardinelli-Seip syndrome, autosomal recessive congenital lipoatrophic diabetes, is associated with hypertrichosis among other dermatologic manifestations such as acanthosis nigricans and xanthomas and systemic abnormalities that may be neurologic, ophthalmologic, endocrine, gastrointestinal, cardiac, renal, or reproductive.⁵⁸ Donohue syndrome is similar but more severe with growth retardation, quicker onset of insulin resistance, and greater mortality.⁵⁹,⁶⁰ Several of the mucopolysaccharidoses (MPS) have hypertrichosis as a frequent feature, and these include Hurler (MPS-I), Hunter (MPS-II), Sanfilippo (MPS-III).⁶¹,⁶² Microscopically, the hair-shaft morphology has been noted to be of irregular shapes in cross section, with the most dysmorphic hairs seen in MPS-III, and it is postulated that the hypertrichosis observed may be due to buildup of glycosaminoglycans in the skin. Stiff-skin syndrome presents with rigid skin, decreased range of motion at joints, and mild hypertrichosis.⁶³ There may be acid mucopolysaccharide deposits in between collagen fibers that can be identified, but this is an inconsistent finding.⁶³ In Winchester syndrome, patients are of short stature and have bone deformities, corneal opacifications, and thickened often hypertrichotic skin.⁶⁴,⁶⁵ The culprit biochemical defect is unknown. Patients with porphyrias have photosensitivity, due to accumulation of UV-excitable porphyrins in the skin, and are therefore prone to UV-induced damage of sun-exposed areas. These sites ultimately may become erythematous, edematous, pruritic, scarred, fibrotic, and hypertrichotic.⁶⁶ Rubinstein-Taybi syndrome is characterized by facial anomalies, keloids, digit abnormalities, hypertrichosis, short stature, and mental retardation.⁶⁷ Patients with Schinzel-Giedion syndrome may have facial anomalies; skeletal abnormalities of the skull, extremities, and ribcage; and dermatologic findings such as hypoplastic dermal ridges, seborrheic rash, and dermatophyte infection, in addition to hypertrichosis of face and limbs.⁶⁸ The Barber-Say syndrome has features of macrostomia, growth retardation, ectropion, and atrophic and hypertrichotic skin.⁶⁹ Coffin-Siris syndrome presents with facial abnormalities, digit and fingernail anomalies, mental
and growth retardation, decreased scalp hair, joint flexibility, and hypertrichosis, particularly in the lumbosacral area and eyebrows.⁷⁰ Hemimaxillofacial dysplasia is defined by facial features in which the maxilla is asymmetrically enlarged and ipsilateral facial hypertrichosis may occur.⁷¹ Other associated manifestations are hypoplastic teeth. Components of Gorlin-Chaudhry-Moss syndrome include craniofacial dysostosis, patent ductus arteriosus, hypoplasia of labia majora, dental and ophthalmologic anomalies, as well as terminal hypertrichosis on the back and extremities.⁷² In hypomelanosis of Ito, patients have hypopigmented patches following the lines of Blaschko, frequently neurologic symptoms, and occasionally hypertrichosis.⁷³ MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) syndrome may rarely manifest with terminal hypertrichosis on the lower extremities or other dermatologic signs such as scaly, pruritic diffuse erythema with reticular pigmentation.⁷⁴

Acquired Hypertrichosis. The Becker nevus typically is an acquired lesion and less commonly congenital (Table 7.2.3). It appears as an irregular pigmented patch with hypertrichosis at puberty.⁷⁵ Occasionally, patients may have a constellation of other features and therefore Becker nevus syndrome.⁷⁶ These include ipsilateral hypoplasia of the shoulder, arm, and chest and vertebral defects. In one case, a patient had ipsilateral limb hypertrophy.

Hypertrichosis can occur owing to chemically induced dermatitis, such as with psoralen application, or local inflammation in the setting of healing, as it is a common finding after orthopedic cast removal.⁷⁷,⁷⁸ Frictional areas have also been associated with focal hypertrichosis, and reported cases include occurrence in individuals who have occupational-related friction on bodily sites such as shoulders or necks of weight bearers and habitually related friction such as biting in patients with mental retardation or itching pruritic areas such as insect bites.⁷⁹,⁸⁰ Inflammation is also induced locally in thrombophlebitis, chronic osteomyelitis, and vaccination, and hypertrichosis has occurred in these contexts as well.⁸¹,⁸²

Hypertrichosis of the pinna has been reported in older men; occasionally in women; in patients with acquired immunodeficiency syndrome (AIDS), XYYY syndrome, or diabetes; or in those born to diabetic mothers.⁸³,⁸⁴,⁸⁵

Hypertrichosis singularis describes the phenomenon when one hair is unusually long, and a purported mechanism is that it may be due to a single hair follicle transitioning from vellus to terminal or arrest in anagen.⁸⁶

Trichomegaly, hypertrichosis of the eyelashes, has been reported in patients with AIDS and systemic lupus erythematosus, as well as users of latanoprost.⁸⁷,⁸⁸,⁸⁹ Users of latanoprost may also exhibit hypertrichosis of the malar areas.