Continuing Education Activity

Chromhidrosis is a rare condition with a characteristic presentation of the secretion of colored sweat. This condition can further subdivide into apocrine chromhidrosis and eccrine chromhidrosis, and the treatment depends on type and cause. This activity reviews the evaluation and management of chromhidrosis and highlights the role of the healthcare team in managing patients with this condition.

Objectives:

• Describe the pathophysiology of chromhidrosis.
• Explain the common physical exam findings and test considerations for chromhidrosis.
• Identify management considerations for patients with chromhidrosis.
• Summarize the importance of collaboration and communication amongst the interdisciplinary team to improve outcomes for patients affected by chromhidrosis.

Introduction

Chromhidrosis is a rare condition with a characteristic presentation of the secretion of colored sweat and was first reported by Yonge in 1709. Chromhidrosis can subdivide into three categories: Apocrine chromhidrosis, eccrine chromhidrosis, and pseudochromhidrosis (pseudo-eccrine chromhidrosis).[1][2][3][4][5]

Apocrine chromhidrosis occurs in the areas where apocrine glands are present and are mostly limited to the anogenital and axillary areas, eyelids, ears, scalp, trunk, and areola. Normally, apocrine glands secrete scant amounts of odorless, oily fluid into the hair canal that, upon reaching the skin surface, is degraded by bacteria producing a pheromonal body odor.[6][7][2]  

Eccrine chromhidrosis may occur almost anywhere on the body as eccrine glands are distributed with varying density throughout the skin except for the ear canal, lips, prepuce, glans penis, clitoris, and labia minora. Eccrine glands are smaller than apocrine glands, secrete a dilute salty sweat composed mainly of water and electrolytes directly onto the skin surface, and are innervated by the sympathetic nervous system. They are irregularly spaced on the epidermal ridges of the pads of the digits; however, there are no pores within the furrows. They are involved in thermoregulation, protection of the skin barrier, and excretion of electrolytes.[5][2][6][7]

Pseudochromhidrosis results from the interaction of colorless eccrine sweat with other compounds, subsequently producing a colored sweat.[2]

Etiology

In 1954 Walter Shelley and Harry Hurley determined that lipofuscin granules are responsible for the pigmentation of the sweat seen in apocrine chromhidrosis. Lipofuscin is a yellow-brown pigment that is usually found in the cytoplasm of cells of various organs and is not specific to apocrine glands.[2][8] Apocrine glands of normal individuals and persons with apocrine chromhidrosis contain lipofuscin granules, the difference lies in the amount of lipofuscin present and/or the higher-than-normal state of oxidation.[9][2] Hence, apocrine chromhidrosis is considered an intrinsic process.[7] The greater the extent of lipofuscin oxidation, the darker the lipofuscin color, which can range from yellow, green, blue, black, or brown.[10][11][5][9][2] Apocrine glands are provoked by hot showers and baths, rubbing of the skin, and emotional stimuli such as pain, sexual arousal, or anxiety, which leads to the secretion of colored sweat in the case of apocrine chromhidrosis.[12][13] Substance P may also play a role in the pathogenesis, which is why capsaicin has shown to be an effective treatment in some patients.[2]

Eccrine chromhidrosis is most often caused exogenously by the coloring of clear sweat with the ingestion of water-soluble dyes such as tartrazine, heavy metals such as copper, coloring and flavoring substances in food products, and drugs such as quinines, levodopa, tartrazine-coated bisacodyl, and rifampin.[14] It is caused endogenously secondarily to hyperbilirubinemia in which patients may present with a greenish hue in a palmoplantar distribution with or without pompholyx-like lesions. [4][2][15][14][16]

Pseudochromhidrosis is an extrinsic process that occurs when the colorless sweat from eccrine glands subsequently develops color following exposure to exogenous influences like drugs that cause changes in the microflora on the skin surface.[5] Chromogenic bacteria such as Serratia marcescens, Bacillus species, and Corynebacterium species are the most common causes. Fungi, including Malassezia furfur, dyes, paints, and chemical agents such as dihydroxyacetone, have also been implicated.[3][6][4][1][5]

Epidemiology

Apocrine chromhidrosis may appear at any age but usually appears after puberty, when the apocrine secretory function begins. The disease is considered chronic, however, may regress with age as apocrine secretion diminishes.[17][2] Apocrine chromhidrosis displays no occupational or geographical predisposition and is not influenced by climatic or seasonal variation.[10][12] There is no gender predilection, but chromhidrosis has been reported in the literature more commonly in blacks, barring facial chromhidrosis, which has been reported more commonly in whites.[2] However, there are too few patients reported to draw meaningful conclusions.[18]

Histopathology

On histologic examination of a patient with apocrine chromhidrosis, the apocrine glands appear normal in morphology and size; however, the number of glands varies. Within the cytoplasm of apocrine cells, an increased number of yellow-brown lipofuscin pigments will be evident using hematoxylin-eosin staining. The lipofuscin granules are positive with oil red O and periodic acid–Schiff staining and fluoresce with nonstained paraffin-embedded sections with ultraviolet light at 360 nm.[2][9][19][12][11][4] 

Histology of eccrine chromhidrosis will appear normal, and fungi or bacteria may be present in the setting of pseudochromhidrosis.

History and Physical

Patients with chromhidrosis will present with colored sweat, with or without staining of their clothing. Some patients may describe warmth or a prickly sensation upon emotional or physical stress preceding the appearance of colored sweat.[2] The initial assessment should include a detailed history, including any new medications, started before the onset of chromhidrosis, including vitamins, supplements, and herbal medications.[16][7][3]

Evaluation

While chromhidrosis is a clinical diagnosis, further studies may be needed to ascertain the type and cause of chromhidrosis if not apparent from the history and physical examination. A Wood’s lamp will fluoresce green, blue, and yellow apocrine gland secretions yellow, while black and dark brown secretions usually do not fluoresce. Skin biopsies can be sent for hematoxylin/eosin staining and fluorescence microscopy to detect and measure lipofuscins within apocrine glands.[2][9][16][11]  

Cytological examination of secretion smears may aid in detecting lipofuscin pigment within apocrine gland cells. Spectrophotometer analysis of samples from sweat, sebum, urine, skin scrapings, and extraction samples from clothing can help to aid in the diagnosis.[16] Bacterial and fungal cultures of the skin may be an option to rule out pseudochromhidrosis.[7] Other studies may be necessary to rule out other causes of pigmentation and include complete blood cell counts to rule out a bleeding diathesis and urinary homogentisic acid level to exclude alkaptonuria.[2]

Treatment / Management

After a thorough assessment to establish the type of chromhidrosis and causality, therapy may be initiated to target the source. The treatment of apocrine chromhidrosis aims at either inducing apocrine secretion, thereby emptying the glands resulting in a temporary symptom-free period for up to 3 days, or reducing perspiration. Manual pressure can express apocrine gland contents resulting in an improved appearance for 24 to 72 hours.[16] Capsaicin, applied once or twice daily, depletes the neurons of substance P and can improve the appearance in some patients. Burning sensation at the application site is a common side effect of capsaicin. Topical aluminum chloride and injections of botulinum toxin type A have also reportedly shown benefit in patients.[9][17][2][11] The condition usually recurs after cessation of therapy.[2]

The treatment of eccrine chromhidrosis revolves around stopping or replacing the causative agent.[16]

In cases of pseudochromhidrosis, topical or systemic antimicrobials are often used to eradicate the offending microorganism. Of note, medications may have implications in altering the normal flora, allowing for chromogenic organisms to take their place.[16] Discontinuation of these medications should be a consideration in such situations.

Differential Diagnosis

The differential diagnosis of chromhidrosis includes bleeding diathesis (hematidrosis), hyperbilirubinemia, Addison’s disease, hemochromatosis, poisoning, and alkaptonuria.[19][17] Hematidrosis, or bloody sweat, is a rare condition where blood seeps from the skin and mucosa. It may occur anywhere on the body and can be associated with pain. Alkaptonuria is a rare genetic condition caused by a deficiency in functional homogentisic oxidase. Patients may present in early adulthood with darkened skin and urine, and arthritis.[13]

Prognosis

Chromhidrosis is a benign chronic condition that may regress with time. However, it may lead to significant anxiety, depression, or embarrassment requiring frequent clothing changes during the day.[19][12]

Complications

While there are no complications directly associated with chromhidrosis, there may be implications secondary to psycho-social issues.[16][19]

Deterrence and Patient Education

It is essential to inform the patient that while apocrine chromhidrosis is benign, it is considered chronic and may be present for many years, if not forever.  The treatment options are symptomatic, and when discontinued, the disease will likely recur.  Educating the patient regarding stressors and physical activity, which can increase the appearance of chromhidrosis, can be beneficial.

Patients with eccrine chromhidrosis and pseudochromhidrosis need to be informed of the responsible cause and recommend avoidance.  If the cause remains undetermined, a diary of ingested substances and a list of chemical contacts can be helpful. 

Enhancing Healthcare Team Outcomes

Chromhidrosis, while benign, can pose a diagnostic dilemma. This condition can receive treatment on an outpatient basis, but still requires the efforts of an interprofessional healthcare team. A thorough history and physical exam should be performed on every patient presenting with colored sweat to assist in making the diagnosis, finding the cause, and preventing unnecessary laboratory testing. If the diagnosis is unclear, prompt consultation with an interprofessional group of specialists may be needed. A dermatologist may be necessary to perform a skin biopsy or evaluate skin scrapings — a dermatopathologist to examine the skin biopsy for hematoxylin and eosin staining, and possibly under fluorescence light. A culture may be needed to rule out the possibility of a chromogenic microorganism causing pseudochromhidrosis. If the patient displays significant depression or anxiety related to the symptoms, consultation with a psychiatrist or a mental health counselor may be appropriate. A thorough discussion with the patient regarding the disease, potential treatment options, and the prognosis is essential as some cases are chronic and may be present for years, as is the case with apocrine chromhidrosis. Dermatology nurses educate patients and their families, perform followup, and verify compliance while keeping the clinician informed. Pharmacists review medications prescribed, check for drug-drug interactions, and also have a role in education. These interprofessional collaborations can help patients achieve optimal outcomes. [Level 5]