Chromhidrosis

INTRODUCTION — In the normal state, sweat is colorless. The term "chromhidrosis," derived from the Greek "chroma" (colored) and "hidros" (sweat), describes the occurrence of colored sweat.

True chromhidrosis is a rare condition characterized by the secretion of colored sweat from apocrine or eccrine sweat glands. In pseudochromhidrosis, a far more common disorder, sweat becomes colored after secretion from the sweat gland. Pseudochromhidrosis results from contact between sweat and dyes, chemicals, or chromogenic bacteria on the skin.

The clinical features, diagnosis, and management of chromhidrosis and pseudochromhidrosis will be reviewed here. Other sweat disorders, including hyperhidrosis (excessive sweat) and bromhidrosis (malodorous sweat), are reviewed separately. (See "Primary focal hyperhidrosis" and "Bromhidrosis".)

CHROMHIDROSIS — In chromhidrosis, sweat glands secrete colored sweat onto the surface of the skin.

Etiology — Chromhidrosis may involve apocrine glands or eccrine glands. Apocrine glands develop after puberty and are most densely distributed in the axillae, anogenital areas, and areolae. Eccrine glands are primarily responsible for thermoregulation and are widely distributed over the body, with the highest concentration on the palms and soles. Apoeccrine glands are an intermediate type of sweat gland that exhibit features of both apocrine and eccrine glands. Whether apoeccrine glands are involved in chromhidrosis is unclear.

Apocrine chromhidrosis is most often due to the presence of lipofuscin granules within the apocrine gland that are secreted along with sweat. Lipofuscin is a yellowish pigment that is thought to be produced by the oxidation of unsaturated fatty acids. Lipofuscin is considered a histologic sign of aging and is found in the liver, kidney, neurons, and other cells; the reason for the presence of lipofuscin in apocrine sweat glands in chromhidrosis in not known [1]. The color of secreted sweat is determined by the oxidation state of the lipofuscin granules; sweat can be black, brown, blue, green, yellow, or pink [2]. The higher the state of oxidation, the darker the color appears [3].

Eccrine chromhidrosis has multiple causes. As in apocrine chromhidrosis, lipofuscin granules can be secreted by the eccrine sweat gland [4]. In addition, systemic medications, heavy metals, or other agents can be secreted in sweat causing discoloration of the sweat, such as tartrazine-coated bisacodyl [5], quinine [6], clofazimine, rifampin, silver [7], mercury, copper [8], ammonium [8], beta-carotene, and dyes such as methylene blue, fluorescein, and dyes in cranberry juice [9,10]. Hyperbilirubinemia is a rare cause of eccrine chromhidrosis [11,12]. Uremic frost, a rarely seen complication of renal failure, causes white, crystalline sweat.

A table depicts the causes and colors most commonly seen in chromidrosis (table 1).

Epidemiology — Chromhidrosis is rare. Apocrine chromhidrosis is the most common type of chromhidrosis and typically appears after puberty with maturation of the apocrine glands. Rarely, infants and children are affected [13]. Eccrine chromhidrosis can develop at any age. Chromhidrosis does not exhibit a sex predilection.

Clinical features — Patients with chromhidrosis present with the complaint of colored sweat, most often as black, brown, blue, green, or yellow stains on clothing. Dried, colored sweat also may be visible in the affected area and patients may complain of stained skin [14]. Sweat excretion may be preceded by a feeling of warmth or a "prickly sensation" [14]. Stimuli that elicit sweating, such as emotion, exercise, or heat, usually exacerbate the findings.

In accordance with the locations of apocrine glands, apocrine chromhidrosis most often occurs in the axillae. Other potential sites include the anogenital skin, areolae of the breasts, and face (especially the cheeks) (picture 1). A role for chromhidrosis in apocrine hidrocystomas of the eyelid has been proposed [15]. Eccrine chromhidrosis most often affects the palms and soles, where eccrine glands are most numerous, but can occur anywhere on the body.

Lipofuscin-associated apocrine and eccrine chromhidrosis tend to be chronic but often regress with age.

PSEUDOCHROMHIDROSIS — Pseudochromhidrosis occurs when sweat is secreted as a colorless solution and becomes colored on the surface of the skin. Pseudochromhidrosis is more common than chromhidrosis.

Etiology — Dyes, paints, or chemicals on the skin surface mix with sweat to produce a colored solution. A common example of pseudochromhidrosis is the common yellow perspiration stain on light-colored clothing; this is due to a reaction between the proteins in apocrine sweat and aluminum in antiperspirants. Application of sunless tanning agents may also result in pseudochromhidrosis at the site of application [16]. Other causes of pseudochromhidrosis are the presence of chromogenic bacteria, such as Serratia marcescens, Bacillus, Pseudomonas, or Corynebacterium, on the skin and black piedra, a cutaneous fungal infection [17,18].

A table shows the causes and colors commonly seen in pseudochromhidrosis (table 2).

Epidemiology — Pseudochromhidrosis occurs in children and adults. There does not appear to be a sex predilection [18].

Clinical features — As with chromhidrosis, patients may present with stained clothing or skin. The color of sweat in pseudochromhidrosis varies based upon the underlying cause; red, pink, blue, brown, and black sweat have been reported [18]. Pseudochromhidrosis can occur on any body site; involvement of the face, palms, or neck is most frequently reported [18].

DIAGNOSIS — The diagnosis of colored sweat involves distinguishing between chromhidrosis and pseudochromhidrosis as well as identification of the underlying cause. The diagnostic process typically requires (algorithm 1):

●Review of the patient history for risk factors for chromhidrosis and pseudochromhidrosis

●Physical examination of the affected areas and stained clothing to confirm the presence of colored sweat (the patient can be asked to exercise to induce sweating if colored sweat is not evident at the time of examination)

●Select use of diagnostic tools, such as Wood's lamp examination, skin bacterial cultures, skin biopsy, and laboratory tests

The location(s) where colored sweat occurs influences the approach to diagnosis.

Patients with apocrine distribution — Patients with involvement limited to sites of apocrine glands (eg, axillae, anogenital region, areolae of the breasts, cheeks) have either apocrine chromhidrosis or pseudochromhidrosis (algorithm 1). A history of application of dyes or dyed clothing, paints, chemicals, or other products to the affected area(s) should be obtained and compared with the time course of chromhidrosis to identify patients with pseudochromhidrosis. The site of chromhidrosis should be manually manipulated; in patients with apocrine chromhidrosis, it is often possible to manually extrude colored sweat from the apocrine glands, a finding that supports the diagnosis.

Wood's lamp examination, skin cultures, or a skin biopsy can aid in the diagnosis of apocrine chromidrosis. A Wood's lamp examination of excreted sweat is our preferred initial test and may be performed on the skin or on the stained clothing. In patients with true apocrine chromhidrosis, Wood's lamp illumination of blue, green, or yellow sweat will demonstrate yellow fluorescence. Wood's lamp examination is not reliable for apocrine chromhidrosis that manifests with darker (eg, brown or black) sweat, since fluorescence will be absent.

When the Wood's lamp examination is not helpful or feasible, culture of the affected area to identify chromogenic bacteria is an appropriate next diagnostic test. If chromogenic bacteria are identified, the patient can be diagnosed with pseudochromhidrosis. If chromogenic bacteria are not identified, a punch biopsy of skin in the affected area is typically performed. The detection of yellow-brown or orange-brown lipofuscin granules within the apocrine gland confirms a diagnosis of apocrine chromhidrosis. Examination with an ultraviolet microscope can be helpful since lipofuscin fluoresces at wavelengths of 360 to 395 nm. If lipofuscin granules are absent, the patient most likely has pseudochromhidrosis, and the clinician should revisit the patient history to search for the etiology.

Patients with nonapocrine distribution — Patients with colored sweat that is not limited to apocrine areas may have eccrine chromhidrosis secondary to drugs, toxins, systemic illness, or pseudochromhidrosis related to agents applied to the skin or chromogenic bacteria (algorithm 1). A history of application of dyes or dyed clothing, paints, chemicals, or other products to the affected area(s) should be obtained and compared with the time course of chromhidrosis. In addition, a careful medication, supplement, and exposure history should be performed to identify patients with drug- or heavy metal-induced chromhidrosis.

A review of systems and physical examination should also be performed. If symptoms or signs suggestive of liver disease are present, particularly in patients with yellow-green sweat, liver function tests are indicated to rule out hyperbilirubinemia as the cause of chromhidrosis. Screening for heavy metal toxicity is also indicated if there are findings suggestive of toxin exposure (eg, new-onset hair loss, diffuse skin discoloration).

If the cause of colored sweat remains unclear, culture of the affected area should be performed to evaluate for chromogenic bacteria; if present, the patient can be diagnosed with pseudochromhidrosis. If negative, a punch biopsy of affected skin can be performed to assess for lipofuscin-associated eccrine chromhidrosis (see 'Patients with apocrine distribution' above). If lipofuscin granules are absent, the clinician should reassess the patient history for risk factors for eccrine chromhidrosis and pseudochromhidrosis.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for chromhidrosis and pseudochromhidrosis includes alkaptonuria, hematidrosis, and disorders associated with cutaneous hyperpigmentation:

●Alkaptonuria – Alkaptonuria is an uncommon autosomal recessive disorder caused by deficient activity of homogentisic acid dioxygenase. Adults with alkaptonuria may develop brown discoloration of axillary and inguinal skin, which may be mistaken for chromhidrosis. Other manifestations of alkaptonuria include brownish or bluish pigmentation of the ear cartilage and sclerae and arthritis. The diagnosis is confirmed through measurement of homogentisic acid in the urine. (See "Disorders of tyrosine metabolism", section on 'Alkaptonuria'.)

●Hematidrosis – Hematidrosis (also known as hematohidrosis or "bloody sweat") is a rare disorder characterized by the secretion of blood from intact skin, often in association with bleeding disorders, extreme stress, or extreme fear. Sweat glands have not been definitively implicated in this condition [19]. The presence of red blood cells in the secreted liquid distinguishes hematidrosis from chromhidrosis and pseudochromhidrosis.

●Cutaneous hyperpigmentation – Occasionally, skin staining from chromhidrosis and pseudochromhidrosis may be confused with cutaneous hyperpigmentation secondary to deposition of melanin or other endogenous or exogenous pigments in the skin. The exacerbation of pigment in association with increased sweat production and the transmission of pigment to clothing distinguishes chromhidrosis and pseudochromhidrosis form these conditions. (See "Acquired hyperpigmentation disorders" and "Congenital and inherited hyperpigmentation disorders".)

TREATMENT — Apocrine and eccrine chromhidrosis secondary to the deposition of lipofuscin granules in sweat glands is a benign condition; therefore, treatment is not mandatory. However, patients often desire treatment because of the negative cosmetic effects and inconveniences associated with frequent staining of skin and clothing.

There is no clear effective treatment for lipofuscin granule-associated chromhidrosis. Topical capsaicin 0.025% cream is a reasonable initial treatment; improvement in apocrine chromhidrosis with once or twice daily application of capsaicin (0.025% or 0.1%) is documented in case reports, with responses occurring within one to two weeks [3,20,21]. The mechanism of benefit from capsaicin in chromhidrosis is not known but may relate to an inhibitory effect on acetylcholine-mediated sweat secretion [21]. Continued use of capsaicin may be necessary to maintain improvement. A burning sensation at the application site is a common side effect of capsaicin that tends to improve with increasing duration of treatment.

Botulinum toxin injections may also be effective for apocrine chromhidrosis but are more expensive than capsaicin and require a clinician trained in the procedure. Remission following this treatment is documented in case reports [22-24]. Responses may be evident within a few days after treatment and may persist for several months. Other treatments to inhibit sweating (eg, iontophoresis, oral anticholinergics, surgical removal of sweat glands, laser therapy) have also been proposed as treatment options; however, efficacy for chromhidrosis is unclear. (See "Primary focal hyperhidrosis", section on 'Treatment'.)

Patients with an identifiable underlying cause of chromhidrosis or pseudochromhidrosis may experience resolution of symptoms following elimination of the inciting factor, exposure, or illness. For example, for patients with pseudochromhidrosis secondary to chromogenic bacteria, topical or oral antibiotic therapy selected based upon the causative organism can lead to remission [18].

SUMMARY AND RECOMMENDATIONS

●Chromhidrosis is a rare disorder characterized by the secretion of colored sweat from apocrine or eccrine sweat glands. Apocrine chromhidrosis is the most common type of chromhidrosis. (See 'Chromhidrosis' above.)

●Pseudochromhidrosis occurs more frequently than chromhidrosis. In pseudochromhidrosis, sweat becomes colored after secretion from the sweat gland through contact with dyes, chemicals, or chromogenic microorganisms on the skin. (See 'Pseudochromhidrosis' above.)

●Apocrine chromhidrosis typically results from the secretion of lipofuscin granules in the apocrine glands along with sweat. Eccrine chromhidrosis has multiple causes. Examples include the secretion of lipofuscin granules from eccrine glands, exposure to medications or heavy metals that can discolor sweat, and hyperbilirubinemia. (See 'Etiology' above.)

●Patients with chromhidrosis usually present with black, brown, blue, green, or yellow sweat that may stain clothing or skin. Apocrine bromhidrosis most often involves the axilla but may also occur on anogenital skin, the areolae, and face. Eccrine chromhidrosis is most common on the palms and soles but can occur in other body areas. (See 'Clinical features' above.)

●Pseudochromhidrosis can present with a variety of colors depending on the etiology. Light yellow discoloration of clothing secondary to contact of sweat with aluminum in antiperspirants is a common presentation of pseudochromhidrosis. (See 'Clinical features' above.)

●A diagnosis of chromhidrosis and pseudochromhidrosis can usually be made through review of the patient history, physical examination, and the select use of diagnostic tools such as Wood's lamp examination and microbiologic cultures (algorithm 1). Additional laboratory tests can be helpful for ruling out underlying disease. (See 'Diagnosis' above.)

●Data on the treatment of chromhidrosis and pseudochromhidrosis are limited. For patients with apocrine chromhidrosis, we suggest topical capsaicin as initial treatment (Grade 2C). Injection of botulinum toxin into the affected area is an alternative treatment. (See 'Treatment' above.)

●Patients with an identifiable underlying cause of chromhidrosis or pseudochromhidrosis (eg, chromogenic bacteria) may experience resolution of symptoms following elimination of the inciting factor, exposure, or illness. (See 'Treatment' above.)