Colour or Blood in Sweat: Let Us Know the Origin

INTRODUCTION

Colour or blood in sweat are distressing skin conditions affecting both the physical and mental health of the individual. This editorial aims to discuss and identify the cause of coloured sweat and provides an outline to approach such cases in clinical practice. These skin conditions are extremely rare and encountered only once or twice, if at all, in the life of a dermatologist. Let us imagine that in a busy dermatology outpatient clinic, a patient presents with a complaint of either colour in sweat or coloured staining of inner wear. Patients may appear psychic or uncanny to others; however, dermatologists must take the responsibility of treating them and make them understand that it is like any other treatable skin ailment. To fulfil this task, we must be well versed with the different pathophysiologies involved in these interesting skin conditions. While colour in sweat may sometimes be acceptable to patients and their families, blood in sweat is considered a phantom that has occupied the afflicted body’s soul rather than its acceptance as a disease. These odd situations may rarely be associated with an underlying systemic disease, e.g. hyperthyroidism, psychiatric disorders or may occur due to consumption of colourful food items in large amounts, e.g. cranberry juice or beetroot.

There are some case reports and review articles throwing light on the individual entities; however, all the related conditions have not been discussed together in the literature. This editorial aims to do a detailed and comparative study of these entities.

NOMENCLATURE

The presence of different colours -black, brown, blue, red, yellow, or green- in sweat is known as chromhidrosis. Chromhidrosis was first reported in 1709 by Younge. It can be apocrine or eccrine in origin.

Appearance of blood in sweat is known as haematidrosis. Compared to chromhidrosis with a largely known scientific basis, haematidrosis has primarily been described as a mythical belief rather than a true health condition, or sometimes associated with Munchausen syndrome (a psychiatric condition whereby patients present with self-inflicted injuries). Though the description of blood in sweat can be found even in old sacred books like the Bible in relation to Jesus Christ and has also been mentioned by Aristotle in the 3rd century B.C., there is no data as to when this term was first used. The first review done on this topic in 1996 threw some light on haematidrosis, but due to the unavailability of laboratory data in such cases, it was not accepted worldwide.^[1]

Chromhidrosis and haematidrosis must be differentiated from pseudo-chromhidrosis, which is the change in colour of sweat after it has been secreted on the surface of the skin.

APOCRINE CHROMHIDROSIS

Coloured sweat coming from apocrine sweat glands is known as apocrine chromohidrosis and is hence localised to regions rich in these glands, for example, anogenital area, axilla, eyelids, ears, scalp, trunk, and areola. The distribution of apocrine sweat glands is shown below in Figure 1. This sweat, which is originally odourless, develops a musky odour once degraded by the bacteria present on the skin surface.^[2-4]

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Figure 1: Distribution of apocrine glands.

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Apocrine secretions are oily, and the colour of the sweat is supposed to be due to oxidation of lipofuscin, which is a polymer contained inside lysosomes and imparts colour to the sweat on being oxidised.^[5,6] This fact was discovered by Walter Shelley and Harry Hurley in 1905. The stimuli are either emotional or psychological, such as anxiety, pain, sexual arousal, excitement, or physical stimuli like hot shower baths or rubbing of skin, etc. Apocrine chromhidrosis is more common in adult males and decreases with age.

ECCRINE CHROMHIDROSIS

In contrast to localised apocrine glands and rarely reported cases of apocrine chromhidrosis, eccrine sweat glands are ubiquitous on skin [Figure 2], and eccrine chromhidrosis is more commonly encountered in clinical practice. Eccrine chromhidrosis can be both exogenous (as in the case of intake of dyes like tartrazine coated Bisacodyl, due to drugs like rifampicin, levodopa, quinines, and flavours in foods) or endogenous (as in hyperbilirubinemia) [Figure 3].^[7,8] There is no age or sex predilection in eccrine chromhidrosis.

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Figure 2: Distribution of eccrine sweat glands.

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Figure 3: Eccrine chromhidrosis with bilirubin in sweat on the forehead (green circle)

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PSEUDO CHROMHIDROSIS

Unlike eccrine and apocrine chromhidrosis, pseudo-chromhidrosis is an extrinsic process which results from the conversion of eccrine sweat to coloured sweat on the skin surface, either due to interaction with exogenous drugs and chromogenic microbes such as Serratia marcescens (pink or red colour), Pseudomonas aeruginosa (blue-green colour), and Bacillus (blue) or Corynebacterium (brown or black). Due to the involvement of microbes, these are better recognised as infectious pseudo-chromhidrosis.^[1,9] The pigment, so produced, is believed to be a means of self-defence by the microbes. Figure 4 shows a case of a 12-year-old girl with pseudo-chromhidrosis on the face.

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Figure 4: A 12-year-old girl with pseudo-chromhidrosis after cycling.

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One study from Hiroshima reported large amounts of intracellular purple pigment (copper coproporphyrin III) in a Bacillus cereus strain.^[10,11] A few authors (Leonardo et al. and Shukla et al.) have reported brown and black pigment being produced by Corynebacterium species.^[11,12]

HAEMATOHIDROSIS

The appearance of blood in sweat is called haematohidrosis or haematidrosis. The mechanism behind this utterly odd situation is hypothesised to be vasoconstriction due to progressively increasing stress and then dilatation of thin blood vessels to the point of rupture after the stress is over. Thereafter, as sweating occurs, sweat pushes the blood towards the skin surface, releasing a mixture of blood and sweat.^[13] The rarity of this entity is responsible for only a few cases reported in the literature. Its overall presence has been found to be more in Asia. Figures 5a and 5b show a case of haematidrosis on bilateral upper limbs during an underlying stress period.

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Figure 5(a-b): Haematidrosis in the same patient on two different areas of the body at the same time.

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Moreover, its association has been seen in many psychiatric conditions like schizophrenia, necessitating its treatment in collaboration with a psychiatrist.^[14]

DIFFERENTIAL DIAGNOSIS

The differentials of coloured sweat include hematidrosis, alkaptonuria, hyperbilirubinemia, haemochromatosis, poisoning, and Addison’s disease. While the latter five can be differentiated based on biochemical findings, in the case of hematidrosis, all the blood components are seen under the microscope.

APPROACH TO A PATIENT WITH COLOURED SWEAT

The quality of life of the patients of both chromhidrosis and hematidrosis is severely affected. Hence, these conditions should not be taken lightly, and management is targeted at finding the cause, which must be eliminated. The approach to chromhidrosis has been elaborated in Table 1 and haematidrosis in Table 2.^[9,15-18]

Lipofuscin is an important cause of chromhidrosis. It is a brown substance confined not only to apocrine glands but also to other coloured organs like the liver, kidney, heart, retina, adrenals, nerve cells and ganglia. The colour of lipofuscin depends on its concentration in the cell and its oxidation. The lower the concentration, the darker the colour in apocrine sweat.

Chromhidrosis caused by topiramate deserves special mention. It inhibits the enzyme carbonic anhydrase found in both kidneys and eccrine sweat glands. and decreases aquaporin-5 expression in the skin, hence leading to altered sweat pH and hypohidrosis.^[17] Promethazine, administered to alleviate pruritus, can cause hypohidrosis and bacterial colonisation. Similarly, if ranitidine and lansoprazole are taken together, they can lead to bacterial growth on the skin, hence coloured sweat.^[18] A hot water bath, stimuli such as pain, anxiety, and emotional imbalances can trigger coloured sweat secretion from the apocrine glands.^[19] Rarely,Substance P may also play a role in the pathogenesis of apocrine chromhidrosis, as its inhibitor, capsaicin, was found to be effective in one such case.^[20]

HAEMATIDROSIS AND COMORBIDITIES

Haematidrosis is characterised by blood coming from the intact mucous membrane and skin and can be associated with pain or psychological stress. Munchausen’s syndrome (or Munchausen’s by proxy) is an important differential, as stress is a common factor for both haematidrosis and Munchausen syndrome. Munchausen syndrome is depicted by self-inflicted injuries with blood on the skin mimicking haematidrosis.

While Gilbert Octavius et al (2021),^[21] Bhattacharya et al (2013),^[22] Manonukul et al (2008),^[23] Murota et al (2020),^[24] Carvalho et al,^[25] Rossio et al (2014),^[26] did not mention any comorbidity associated with haematidrosis. Das et al reported a history of head trauma two weeks prior to the episode of haematidrosis.^[27]

Matsuoka et al (2020) reported two years history of frequent episodes (2-3 times/week) of haematidrosis in association with dissociative disorder and self -harming episodes.^[28]

Similarly, Gayal et al in 2020 reported six months history of episodes of anxiety, schizophrenia, and bleeding episodes.^[14]Further, Jagannathan et al.^[29], and Jarjour et al.(2005)^[30] have described the occurrence of epistaxis with episodes of haematidrosis, which may be due to activation of the trigeminal-vascular system followed by vasodilatation of Keisselbach’s plexus.

Based on the above findings in studies on haematidrosis, the greater the severity of stress, the higher the frequency of episodes of bleeding from skin, and rarely epistaxis, homolactic and haemoptysis also coexisted with this peculiar disease.^[21]

A careful look at Table 2 shows that stress in the form of anxiety, dissociative disorders, family issues like parental separation, medical and surgical treatments, accidents, depression, etc., is the chief cause of hematidrosis in one form or the other. Tables 1 and 2 also show that investigations required in such cases include blood parameters and coagulation profile to rule out bleeding disorders, autoimmune profile (antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide) to exclude autoimmune disorders, IgE, and Aspergillus-specific IgE to rule out allergic bronchopulmonary aspergillosis. Invasive examinations, including nasal endoscopy, laryngoscopy, bronchoalveolar lavage (BAL), upper gastrointestinal (GI) endoscopy, fibreoptic bronchoscopy (FOB), and biopsies, are rarely required to rule out local pathologies and help us to differentiate apocrine and eccrine chromhidrosis. Computed tomography (CT) scan of the paranasal sinus and thorax may rarely reveal any abnormality. The smear made from the patients’ secretion during the bleeding episode shows numerous red blood cells on microscopy in haematidrosis.

MANAGEMENT

A temporary relief can be given to the patients of apocrine chromhidrosis either by expressing the gland, or by Botulinum toxin A injections, or by capsaicin gel, which depletes the Substance P release by neurons. In case of eccrine chromhidrosis, the causative agent needs to be stopped or replaced.

The treatment of pseudo-chromhidrosis is done with oral and topical antimicrobials, e.g., azithromycin, doxycycline, clindamycin, etc., but sometimes these drugs can lead to growth of chromogenic bacteria, and hence care must be taken to stop these drugs in such cases.

Treatment of haematidrosis encompasses a combination of drugs like beta blockers and other anxiolytics and antipsychotic medicines, psychotherapy, and counselling of both patients and attendants. These cases should be better managed in collaboration with a psychiatrist.

An algorithmic approach to these unusual presentations of different colours and blood in the sweat is also mentioned in Figure 6.

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Figure 6: An algorithmic approach to a patient presenting with coloured sweating. (LFT: Liver function test, PAS: Periodic schiff.)

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PROGNOSIS

Though chromhidrosis is a benign skin condition without any complications, it carries a lot of psychosocial stress. Chromhidrosis has a good prognosis. Haematidrosis has a relatively bad prognosis due to strong myths of unearthly things involved with this condition and a strong belief prevalent in society that it can be cured only by an exorcist or a priest.

CONCLUSION

This editorial aims to raise awareness among the readers about this dermatological condition. This condition creates a lot of fear not only in the patients but also in their attendants. Many times, patients undergo a battery of unnecessary investigations. Others from low socioeconomic conditions fall prey to those practising witchcraft.

These patients require a lot of counselling, hence a psychiatrist consultation too is needed, and this should be considered henceforth.