Chromhidrosis

Answer: Chromhidrosis

On the basis of history and physical examination, the patient was diagnosed with facial chromhidrosis. She subsequently had the following laboratory tests performed: complete blood cell count, coagulation profile, and urine for homogentisic acid. The test results were all normal. A 3-mm punch biopsy specimen was obtained from the right malar area. Histopathological examination revealed collections of ectopic apocrine glands in the deep reticular dermis. Dark cytoplasmic granules were observed in the apocrine epithelial lining. These granules were positive on periodic acid-Schiff and Oil Red O stains and were consistent with lipofuscin granules. A final diagnosis of facial apocrine chromhidrosis was made.

Figure. Right cheek showing black secretions. 

Discussion

Chromhidrosis refers to the secretion of colored sweat by apocrine or eccrine sweat glands. Chromhidrosis was first described by Yonge of Plymouth in 1709.¹ Apocrine chromhidrosis was first described in 1954 by Shelley and Hurley, who noted increased number of lipofuscin granules in apocrine glands was responsible for facial and axillary apocrine chromhidrosis.¹ Eccrine chromhidrosis occurs through eccrine excretion of water-soluble colored agents such as dyes and drugs.

The exact prevalence is not known. Suffice to say, chromhidrosis is a very rare disorder; information on this condition is limited to case reports. So far, the reported cases show a female predominance.² However, there are too few case reports to allow a meaningful conclusion to be drawn. The majority of the cases reported in the literature have been apocrine in origin. Apocrine chromhidrosis usually begins in puberty, when apocrine secretion is activated.^3,4

In most cases, chromhidrosis is idiopathic and is unrelated to diet, systemic, or metabolic abnormalities.⁵ Exacerbating factors include physical activity, increase in ambient temperature, mechanical stimulation, and emotional stress. Rarely, eccrine chromhidrosis may follow ingestion of drugs, such as bisacodyl and dyes from the quinine/imine group.^6-8

In apocrine chromhidrosis, histopathological examination of the affected area shows increased lipofuscin granules within the apocrine glands. Lipofuscin granules can be observed in the apical areas of secretory cells with hematoxylin and eosin, Oil Red O, or periodic acid-Schiff stains.^4,9 These granules autofluoresce in ultraviolet light.⁸

Clinical Manifestations 

An aura of warmth or a prickly sensation on the affected skin may precede the onset of colored sweat.^3,9 Apocrine chromhidrosis is always localized because of the restricted distribution of apocrine glands.¹⁰ The condition has most commonly been reported to occur on the face, axillae, and, to a lesser extent, breast areolae.¹⁰ The occurrence of facial apocrine chromhidrosis can be attributed to the presence of ectopic or heterotopic apocrine glands in the dermis of the affected area.² The colors of apocrine sweat vary from yellow, orange, red, green, blue, brown, to black—pending on the oxidation states of lipofuscin granules.^10,11 In general, higher states of oxidation of lipofuscin result in darker colors.¹ The colored sweat can be manually expressed by exerting pressure on the affected area.¹¹

The eccrine glands are present over the entire body surface, but are most numerous on the palms, soles, face, and axillae.¹² As such, eccrine chromhidrosis can affect any body area. The color of sweat depends on the drug or dye being absorbed in the gastrointestinal tract and the color of water-soluble agent excreted via the eccrine glands.⁶ Case reports of eccrine chromhidrosis are scarce; however, yellow, red, and blue sweat have all been described.¹¹

Diagnosis 

The diagnosis is mainly a clinical one. The diagnosis of apocrine chromhidrosis can be confirmed by the demonstration of an increased number of lipofuscin granules in chromhidrotic apocrine cells on skin biopsy.^9,11

Chromhidrosis should be differentiated from pseudochromhidrosis and alkaptonuria. Pseudochromhidrosis refers to coloration of otherwise colorless sweat on the skin surface due to exposure to an external chromogen, which may be in the form of dyed clothing, colored chemicals (such as bromophenol blue, copper salts, and quinazarin), or microrganisms (such as Cornynebacterium or Piedraia).^13,14 

Alkaptonuria is an autosomal recessive disorder that results from deficient activity of homogentisic acid dioxygenase, which converts homogentisic acid to maleylacetoacetic acid.¹⁴ The accumulation of homogentisic acid leads to pigment disposition in connective tissue and urine, which turns brown or black after standing or alkalization.¹⁴ 

Other differential diagnosis includes hematohidrosis, acne vulgaris, Pseudomonas infection, and erroneous make-up applications.¹³

Management

The condition can be cosmetically unsightly and socially embarrassing especially if it occurs in an exposed area. The psychological consequences can be considerable; low self-esteem and depression could result. 

For eccrine chromhidrosis, the prognosis is good if the offending agent can be identified and eliminated. Apocrine chromhidrosis is a chronic disorder which usually persists throughout life but tends to regress slowly with advancing age, paralleling the gradual regression of apocrine glands.^9,10

The patient should be reassured of the benign nature of the condition. If eccrine chromhidrosis results from ingestion of certain drug or dye, the offending agent should be eliminated. Otherwise, the goal of treatment is to reduce sweating, thereby reducing the embarrassment. Treatment options include topical application of a 20% alcohol solution of aluminum chloride hexahydrate (eg, Drysol), topical capsaicin cream, and botulinum toxin type A injection. Aluminum chloride hexahydrate acts by blocking the openings of the sweat ducts.¹²

Capsaicin is a white crystalline compound derived from plants of the nightshade family (Solanum).^3,9 Capsaicin works by depleting substance P levels in the unmyelinated, slow-conducting type C sensory fibers.^3,9 Presumably, substance P is the principal transmitter of nociceptive impulses from the periphery to the central nervous system.¹⁰

Botulinum toxin type A works by preventing the release of acetylcholine at the presynaptic motor neuromuscular plate, thereby effectively blocking the parasympathetic stimulation necessary for sweat production.^4,5 In addition, the toxin has been shown to inhibit substance P release.^4,5

Outcome of the Case

This patient was treated with aluminum chloride hexahydrate with satisfactory results. 

Alexander K.C. Leung, MD, is a clinical professor of pediatrics at the University of Calgary and pediatric consultant at the Alberta Children’s Hospital in Calgary, Alberta, Canada.

Benjamin Barankin, MD, is the medical director and founder of the Toronto Dermatology Centre in Toronto, Ontario, Canada.

References:

1. Shelley WB, Hurley HJ. Localized chromhidrosis: a survey. Arch Dermatol. 1954;69:449-471.

2. Wang A, Wysong A, Nord KM, et al. Chromhidrosis: a rare diagnosis requiring clinicopathologic correlation. Am J Dermatopathol. 2013 Mar 12. [Epub ahead of print]

3. Marks JG Jr. Treatment of apocrine chromhidrosis with topical capsaicin. J Am Acad Dermatol. 1989;21(2 Pt 2):418-420.

4. Tato BP, Martinez EZ, Albisua BS, et al. Facial and axillary apocrine chromhidrosis. Dermatol Online J. 2012;18(3):13.

5. Chang YC, Anderson N, Soeprono F. Bilateral facial pigmentation. Dermatol Online J. 2007;13(3):16.

6. Cilliers J, de Beer C. The case of the red lingerie-chromhidrosis revisited. Dermatology. 1999;199:149-152.

7. Hurley H, Wilkowski J. Dye clearance and eccrine sweat secretion in human skin. J Invest Dermatol. 1961;36:259-272.

8. Krishnaram AS, Bharathi S, Krishnan S. An interesting case of bisacodyl (dulcolax)-induced chromhidrosis. Indian J Dermatol Venereol Leprol. 2012;78(6):756-758.

9. Griffith JR. Isolated areolar apocrine chromhidrosis. Pediatrics. 2005;115:e239-e241.

10. Saff DM, Owens R, Kahn TA. Apocrine chromhidrosis involving the areolae in a 15-year-old amateur figure skater. Pediatr Dermatol. 1995;12(1):48-50.

11. Wyrick K, Cragun T, Russ B, et al. Atypical chromhidrosis: a case report of orange sweat. Cutis. 2008;81:167-170.

12. Leung AK, Chan PY, Choi MC. Hyperhidrosis. Int J Dermatol. 1999;38:561-567.

13. Matarasso SL. Treatment of facial chromhidrosis with botulinum toxin type A. J Am Acad Dermatol. 2005;52:89-91.

14. Yancovitz M, Anolik R, Pomeranz MK. Alkaptonuria. Dermatol Online J. 2010;16(11):6.