Bromhidrosis

Bromhidrosis, also known as osmidrosis, bromidrosis or body odor, is a common phenomenon in postpubertal individuals. In rare cases, bromhidrosis may become pathologic if it is particularly overpowering or if the bromhidrosis significantly interferes with the lives of the affected individuals. Bromhidrosis is a chronic condition in which excessive odor, usually an unpleasant one, emanates from the skin. Bromhidrosis is determined largely by apocrine gland secretion and can substantially impair a person's quality of life.

Types of glands and their functions

Human secretory glands are primarily divided into two types: apocrine and eccrine.

Eccrine glands are distributed over the entire skin surface, where they are involved in thermoregulation by means of sweat production.[1]

In contrast, apocrine glands have a limited distribution involving the axilla, genital skin, and breasts. Apocrine elements are also found in the periorbital and periauricular areas. Apocrine glands have no thermoregulatory role but are responsible for characteristic pheromonal odors. They secrete a small amount of oily fluid, which is odorless upon reaching the skin surface. The characteristic odor is due to bacterial decomposition of the oily fluid.[2, 3] Studies have shown that in comparison to controls, individuals with bromhidrosis display more numerous and larger apocrine glands.

Lastly, apoeccrine glands are sweat glands that become apparent between the ages of 8 and 14 years. They are functionally and pharmacologically distinct from apocrine glands and contribute heavily to overall axillary sweating. They develop during puberty from eccrinelike precursor glands.

Histological findings suggest that eccrine glands are dominant in the dermis.  Apocrine glands are located in the lower part of the reticular dermis and the subcutaneous tissue.  They are much larger than eccrine glands.

Control of apocrine glands

Current evidence suggests that the human apocrine gland appears to be under sympathetic nervous control with the peripheral mechanisms regulated by catecholamines. The presence of purinergic receptors within the gland also indicates the use of a secondary sudomotor pathway with nucleotide involvement in the secretory glands.[4]

Apocrine bromhidrosis

Apocrine bromhidrosis is the most prevalent form of bromhidrosis and should be differentiated from the less common eccrine bromhidrosis. Several factors contribute to the pathogenesis of apocrine bromhidrosis. Bacterial decomposition of apocrine secretions yields ammonia and short-chain fatty acids, with their characteristic strong odors. The most abundant of these acids is (E)-3-methyl-2-hexanoic acid (E-3M2H), which is brought to the skin surface bound by 2 apocrine secretion odor-binding proteins, ASOB1 and ASOB2. ASOB2 has been identified as apolipoprotein D (apoD), a known member of the lipocalin family of carrier proteins.[5, 6, 7]

Axillary bacterial florae have been shown to produce the distinctive axillary odor by transforming nonodoriferous precursors in sweat to more odoriferous volatile acids. The most common of these are E-3M2H and (RS)-3-hydroxy-3-methlyhexanoic acid (HMHA), which are released through the action of a specific zinc-dependent N -alpha-acyl-glutamine aminoacylase (N-AGA) from Corynebacterium species. This aminoacylase has been demonstrated to also release other odoriferous acids from glutamine conjugates in sweat, which may be the basis of individual body odor.[8]

Eccrine bromhidrosis

In certain circumstances, eccrine secretion, which is typically odorless, assumes an offensive aroma and causes eccrine bromhidrosis. When eccrine sweat softens keratin, bacterial degradation of the keratin yields a foul smell. Ingestion of some foods, including garlic, onion, curry, alcohol, certain drugs (eg, penicillin, bromides), and toxins may also cause eccrine bromhidrosis. Lastly, eccrine bromhidrosis may result from underlying metabolic or endogenous causes.

The role of excessive eccrine secretion, or hyperhidrosis, in the pathogenesis of bromhidrosis is unclear. Hyperhidrosis may promote the spread of apocrine sweat and contribute further to bromhidrosis by creating a moist environment, one ripe for bacterial overgrowth.[9, 10] Conversely, eccrine hyperhidrosis may cause a decrease in odor because the eccrine sweat flushes away the more odoriferous apocrine sweat.

Genetic involvement

Most patients have family members who also have bromhidrosis. An autosomal dominant inheritance pattern has been proposed in one study. Recent studies have found a strong relationship between bromhidrosis and wet ear wax associated with the single nucleotide polymorphism (SNP) rs 17822931 of the ABCC11 gene.[11, 12]

Excessive secretion from either apocrine or eccrine glands that becomes malodorous on bacterial breakdown is the predominant cause of bromhidrosis.

Inadequate hygiene and medical or dermatologic conditions associated with hyperhidrosis or overgrowth of bacteria may further contribute to its development. Examples include the following:

• Obesity

• Diabetes mellitus

• Intertrigo

• Trichomycosis axillaris

• Erythrasma

• Colonization with other bacteria, including Sphingomonas paucimobilis[13]

Bromhidrosis has been noted along with hyperhidrosis as a potential adverse effect of laser hair removal.[14, 15] Spontaneous reversal of this hyperhidrosis has been observed in 20% of patients with postlaser hyperhidrosis.[16]

Nasal foreign body is a reported cause of generalized bromhidrosis in the pediatric population.[17, 18, 19, 20, 21]

Eccrine bromhidrosis may rarely be caused by metabolic disorders, primarily disturbances in amino acid metabolism (which include phenylketonuria, trimethylaminuria [fish odor syndrome]), sweaty feet syndrome, odor of cat syndrome, isovaleric acidemia, and hypermethioninemia.

Ingestion of certain foods, drugs, or toxic materials may cause eccrine bromhidrosis.

Older medical textbooks report that offensive smells were characteristic of diseases like gout, scurvy, or typhoid, secondary to metabolite excretion in sweat.

Frequency

United States

The incidence of bromhidrosis is unclear. Its diagnosis as a medical condition is generally considered rare, but bromhidrosis is likely underreported.

International

The diagnosis of bromhidrosis is likely higher in countries where the social stigma of body odor leads more patients to seek treatment than in other countries. For example, the diagnosis of bromhidrosis may be more common in many Asian countries, where even minimal body odor is associated with personal distress and can be diagnosed as bromhidrosis, more so than in other regions of the world.

Race

Apocrine bromhidrosis is believed to be more common in patients in dark-skinned ethnic groups than in others.

Eccrine bromhidrosis occurs in persons of all races.

Sex

Bromhidrosis exhibits a male predominance, which may be a reflection of greater apocrine gland activity in men compared with women.

Age

Axillary bromhidrosis depends on apocrine function and therefore manifests exclusively after puberty. It occurs only rarely in the elderly population.

In contrast, eccrine bromhidrosis is more common than apocrine bromhidrosis during childhood, but it may occur at any age.

No morbid sequelae are known for bromhidrosis.

Patients with bromhidrosis should be encouraged to maintain an appropriate level of hygiene with the use of antibacterial soaps and antiperspirants. Bromhidrosis patients also should be aware of the odor that may arise from dried sweat on clothes.

Patients present with particularly offensive body odor that most commonly originates from the axillary region. However, the condition may also occur as genital or plantar bromhidrosis. The odor has been described as pungent, rancid, musty, or sour in character.

Bromhidrosis is a metabolic and functional disease not typically associated with any anatomic disturbance. Therefore, results of physical examination of patients with axillary bromhidrosis are usually unremarkable. The skin appears normal, except when bromhidrosis is associated with concomitant skin conditions such as erythrasma, in which case a sharply marginated erythematous macular rash is seen, or trichomycosis axillaris, in which case concretions are visible on the hairs in the affected area.

In contrast, individuals with eccrine bromhidrosis caused by bacterial degradation of keratin may have maceration and a thick mat of moist keratin on examination. This finding is most common on the plantar and intertriginous surfaces.

Several case reports in children have described a nasal foreign body as a cause of generalized bromhidrosis.[17, 18, 19, 20, 21] Therefore, examiners should conduct thorough visualization and palpation of nasal passages in pediatric patients.

Typically, the olfactory perception of the diagnostician is the only clinical tool required for diagnosis. Chromatography or spectroscopy may help identify odor-producing chemicals; however, the specific identification of odoriferous molecules is largely of academic interest and lacks diagnostic or therapeutic importance. In addition, results of chromatography or spectroscopy do not help in differentiating normal odor from odor caused by bromhidrosis. Starch iodine test can demonstrate areas of excessive sweating but would not characterize the associated malodor.

If concomitant erythrasma, a chronic bacterial infection of Corynebacterium minutissimum is suspected, the skin has a characteristic coral-red fluorescence under Wood lamp examination, and a potassium hydroxide preparation is negative for hyphae.

Gram stain preparation shows bacteria within concretions from axillary hair in cases of trichomycosis axillaris.

If an underlying metabolic disorder is suspected as a cause of odor, specific testing of urine or sweat may be indicated to detect the aberrant amino acid product.

No imaging studies are indicated for the evaluation of bromhidrosis.

Skin biopsy is rarely indicated in bromhidrosis. However, skin biopsy may be used to evaluate apocrine glands if surgical treatment options are being considered.

Evidence about histologic findings in patients with bromhidrosis is conflicting. Some research indicates that no histologic abnormalities are seen in the skin or glands of patients with apocrine bromhidrosis when compared with control subjects. A few studies have shown that the number and the size of apocrine glands is increased in bromhidrosis skin. This finding suggests increased apocrine sweating as a possible cause of this bothersome condition.[23]

Several therapeutic modalities are available to treat body odor. When a treatment method is chosen, it is important to consider the cultural implications and the degree of impairment in quality of life, as well as the patient's expectations and goals of treatment.

Medical treatments can include hygiene and topical antibacterial agents, drying agents, lasers, and botulinum toxin.

Surgical treatments can include surgical removal, superficial liposuction curettage, deep liposuction curettage, and upper thoracic sympathectomy.

Future directions

A novel microwave device that causes the apocrine and eccrine glands to fibrose has been used to treat both hyperhidrosis and bromhidrosis; the authors suggest that the results may be permanent and that the main adverse effect of inflammation is transient.[24]

Ultrasound technology may also be used to treat hyperhidrosis, and thus also has the potential to treat bromhidrosis.[25]

Hygiene and topical antibacterial agents

Conservative measures, which aim to reduce bacterial florae and maintain a dry environment, include improved hygiene and topical therapy. Hygienic measures, such as adequate washing of the axillary vault, prompt removal of sweaty clothing, and the use of topical deodorant (which covers the odor and decreases bacterial counts) are beneficial in cases of apocrine bromhidrosis. Regular shaving of axillary hair prevents the accumulation of sweat and bacteria on the hair shafts. Electrolysis might also be considered for hair removal to minimize bacterial growth.

Use of topical antibiotics, such as clindamycin, erythromycin, and benzoyl peroxide, as well as antiseptic soaps, may yield clinical benefit by limiting the growth of the contributory bacteria that decompose apocrine secretions, liberating fatty acids that have peculiar smells. Topical antibiotics, such as clindamycin and erythromycin, should only be used when other antiseptics are ineffective, because they are associated with a greater risk of bacterial resistance. Treatment of coexisting skin conditions, such as intertrigo, erythrasma, and trichomycosis axillaris, is important.

Drying agents

Measures to enhance drying and limit maceration, such as the use of antiperspirants including aluminum chloride, may improve bromhidrosis of either apocrine or eccrine origin, particularly if hyperhidrosis is a contributing factor. Antiperspirants, unlike deodorants, contain aluminum salts, which inhibit sweat production.

Iontophoresis, which disrupts sweat production, has a role in the treatment of eccrine bromhidrosis. With this method, a small electric current is passed through the skin while the affected area is placed under tap water. Typically used only for volar skin, this treatment is time intensive and should be considered only if excessive eccrine sweating contributes to the patient's body odor. Amelioration of hyperhidrosis does not reduce apocrine sweat production.

Conservative methods are ideal for mild cases. However, they do not offer a definitive cure, and results may be unsatisfactory if odor reduction is short lived and incomplete. Systemic anticholinergic agents decrease sweating, but their use can be limited by their adverse effect profile.

Lasers and botulinum toxin

For patients who desire more long-lasting treatment, a few nonsurgical options have been developed, although the data on these options are limited.

Laser

A frequency-doubled, Q-switched Nd:YAG laser (1064 nm) has been effective in axillary bromhidrosis.[26] More recently, the 1444-nm Nd:YAG laser has been used to achieve subdermal coagulation and destruction of apocrine glands, leading to effective management of bromhidrosis.[27, 28] Over 75% of patients reported satisfaction with the procedure up to 6 months afterward.[28]

Botulinum toxin

The inhibitory action of botulinum toxin A (BTX-A) to decrease sweat production by denervating eccrine sweat glands has also been applied to successfully treat axillary hyperhidrosis.[29, 30] The effect on axillary apocrine gland secretion is unknown; however, local injections of botulinum toxin A reduced axillary body odor in a small sample of healthy subjects, and 1 case of improved genital bromhidrosis after botulinum toxin A treatment is reported.[31] It is particularly effective for patients who have a strong correlation between malodor and sweating.[32] In a 2018 study of 62 adolescent patients, the use of BTX-A was rated either very good or good in 82% of patients.[33] The study used 50 U of BTX-A and provided relief of symptoms for 1 month in most patients. In some, multiple injections were required. The authors concluded that the use of BTX-A is safe and effective over long-term follow up and that patient education regarding the limitations of BTX-A and the potential for multiple injections is necessary to facilitate patient satisfaction.

Surgical treatment for axillary bromhidrosis has been used in a limited fashion in the United States; however, several surgical techniques are used more widely in Asian countries, where axillary odor causes more social and psychological distress.[34]

Clearly, surgical reduction in the number of apocrine glands diminishes apocrine secretion, and because some histologic evidence to suggest overactive apocrine sweat glands contributes to bromhidrosis, surgical techniques may be the most satisfactory methods of treatment. Surgical treatment improves the long-term management of bromhidrosis, but it is associated with an increased risk of morbidity, including scarring, surgical complications, and risk of recurrence. In recent years, new minimally invasive techniques with less morbidity have been developed. These include procedures with smaller incisions, which leave the vascular plexus as well as superficial fascia intact and may lead to satisfactory results with fewer adverse effects.[35, 36]

Surgical removal

A multitude of surgical methods have been reported to date, which can be categorized into the following 3 classic types[37, 38, 39, 40, 41, 42, 43] :

• Removing only subcutaneous cellular tissue without removing skin: In some reports, axillary superficial fascia is removed in addition to the apocrine glands, with good results.[44] In minimally invasive procedures, this fascia is left intact. One novel technique used subcutaneous curettage combined with fat trimming to create a smooth surface on the axillary skin flap while removing the apocrine glands. Ninety eight percent of subjects reported good-to-excellent results, and no significant complications occurred.[45]

• Removing skin and subcutaneous cellular tissue en bloc

• Removing skin and cellular tissue en bloc, as well as removing the subcutaneous cellular tissue of the adjacent area: This is often performed by using a shaving technique on the subcutaneous tissue.[46]

Depending on the depth of the surgical injury, regeneration of gland function over a period of years may be observed. Subcutaneous tissue removal has also been combined with carbon dioxide laser to vaporize the residual apocrine glands.[47]

Superficial liposuction curettage

The superficial liposuction curettage technique is an outpatient procedure that has the advantage of being less traumatic than open surgery. Small incisions are made in the axilla, and a suction device is inserted that removes the subcutaneous tissue. This procedure offers a smaller incision, lower complication rates, and minimal postoperative care.[48, 49, 50, 51] However, its associated recurrence rate is higher than that of open surgery, leading to decreased patient satisfaction on long-term follow-up. A similar procedure, ultrasound-assisted suction aspiration, liquefies fat and sweat glands.[52, 53, 54] This treatment has recurrence rates lower than those of traditional superficial liposuction curettage and results in similarly small scars.

Deep liposuction curettage

A refined suction-curettage technique with subdermal undermining through a miniature incision, as well as introducing scissors through the same incision for further undermining of the subcutaneous tissue, leads to a higher curative rate (87.5%) versus suction-curettage alone (33%), but it resulted in complications (13.7%) such as hematoma, epidermal cyst formation, and axillary skin necrosis.[55] The authors noted that since most of the apocrine glands reside close to the subdermal vascular plexus, the complication rate is higher. Overall, because the complications were neither severe nor permanent, they reported that their patients were happy and willing to accept the higher rate of complication for greater treatment success.

Upper thoracic sympathectomy

Upper thoracic sympathectomy has also been performed for axillary bromhidrosis, and one study in Taiwan reported a satisfaction rate of 70.6%; however, this therapeutic modality has more frequently been used for axillary and palmar hyperhidrosis.[56]

Omission of certain foods may be of value if these factors can be isolated or identified as contributory factors to the bromhidrosis. Common culprits include curry spices, onions, garlic, and alcohol.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

Bacteria have been implicated in the pathogenesis of bromhidrosis; the organisms decompose apocrine secretions, liberating fatty acids that have peculiar smells.

Clindamycin topical (Cleocin, Clindagel)

Clindamycin topical inhibits bacterial growth by binding to the 50S ribosomal subunit and blocking dissociation of peptidyl t-RNA from ribosomes, arresting RNA-dependent protein synthesis.

Erythromycin topical (Erythro-Statin 2%, Akne-mycin, Theramycin Z)

Erythromycin topical is a macrolide antimicrobial that inhibits bacterial growth by binding reversibly to the 50S ribosomal subunit and blocking dissociation of peptidyl t-RNA from ribosomes, arresting RNA-dependent protein synthesis. Use 2-4% solution.

OnabotulinumtoxinA

OnabotulinumtoxinA is known to be effective in treating hyperhidrosis. It has also been found to decrease axillary odor in a study of healthy subjects and in one case study in genital bromhidrosis.

 

Aluminum chloride topical

Aluminum chloride topical is an astringent agent used in the management of hyperhidrosis.  Its antiperspirant mechanism of action is not known, although creation of aluminum-containing casts within the sweat duct has been postulated. A solution of 20% aluminum chloride in ethyl alcohol is used.