Severe night sweating treated by oxybutynin

Abstract

Sleep hyperhidrosis is defined as profuse nocturnal sweating that disrupts sleep. Although the mechanism is unknown, some cases are secondary to hot flushes during the menopausal period, medical, mental and sleep disorders, and medication, while dysregulation of thermoregulation during sleep is suspected in primary cases. We present the case of a woman with severe primary sleep hyperhidrosis, occurring nightly for 23 years, which definitively resolved after brief treatment with oxybutynin (a muscarinic receptor-blocking anticholinergic). An ammoniacal odor in the sweat and a sensation of coldness on awakening during sweating episodes suggest that the mechanism of her night sweating was not an exacerbation of thermoregulation during the night but shares the mechanical properties of emotional/psychological sweating. This extreme case of sleep hyperhidrosis was treated with excellent efficacy and minimal side effects using oxybutynin, which could benefit other patients with nighttime discomfort.

Citation:

Dias L, Martinot C, Vaillant G, Arnulf I. Severe night sweating treated by oxybutynin. J Clin Sleep Med. 2024;20(1):169–172.

INTRODUCTION

One third of the general population reports occasional excessive nighttime sweating.¹ Severe sleep hyperhidrosis consists of excessive perspiration during the night, which disrupts sleep to the point of requiring a change of bed linens during the night.² Unlike daytime hyperhidrosis, which may be focused on the axilla, palms, sole, and craniofacial area or generalized to the whole body, sleep hyperhidrosis is most often generalized.³ There are primary cases and cases associated with various medical (lymphoma, tuberculosis, diabetes mellitus, hyperthyroidism), psychiatric (panic disorder), and sleep disorders (sleep apnea syndrome), as well as with the use of certain drugs.^1,3 Although several treatment options are available for generalized and focal hyperhidrosis, the best treatment for sleep hyperhidrosis is not known. We report the case of a woman having experienced a severe primary sleep hyperhidrosis for 23 years, which resolved after treatment with oxybutynin.

REPORT OF CASE

A 47-year-old woman was referred for difficulty in sleep initiation and severe night sweating, which had started 23 years before. Her body mass index was 22.15 kg/m². She had a history of cervicobrachial neuralgia, lumbar L3-L4 isthmic lysis, pudendal neuralgia, and regular cannabinoid consumption. She was treated with cyproterone acetate 50 mg combined with estradiol 2 mg as an oral contraception, as she was not yet menopausal.

She had difficulties initiating sleep and severe, nightly sweating but no snoring, nocturia, morning headaches, pain, or restless legs symptoms. In the polysomnography performed at home, sleep latency (17 minutes), total sleep time (378 minutes), sleep efficiency (90%), and apnea-hypopnea index (2.2 events/h) were normal. N3 sleep (16% of total sleep time) and rapid eye movement sleep (14%) were mildly reduced. Periodic leg movements were frequent (31 events/h) but not associated with arousals. The raw polysomnography performed in 2013 is no longer accessible. The interview and follow-up actigraphy were consistent with a delayed sleep-wake phase disorder. She was briefly treated with melatonin 5 mg and mianserin 10 mg (a tetracyclic antidepressant with sedative properties), which adjusted sleep delay and insomnia. She was able to stop both drugs and still sleep at an earlier time. However, severe night sweats persisted, and the patient came back 7 years after, at age 53 years, to the clinician in charge, who asked for medical advice from our hospital sleep center.

A further interview revealed that night sweats began at the age of 30 years and occurred exclusively at night. They occurred every night, with a frequency of 3 to 4 times per night; involved the trunk, limbs, and head; and caused severe soaking of sheets and pillow and awakenings (Figure 1). When she woke up at night, her body felt cold, and she smelled of ammonia from perspiration. She had to shower several times a night and change her sheets and panties. The white sheets were yellowed with perspiration. She could not share her bed with partners, as she would disturb them with her soaked body and bed, as well as with her unpleasant odor. There was no difference in sweating episodes between winter and summer; cold, neutral, or hot environment; or periods with or without cannabinoid consumption or with and without contraception. The patient was not menopausal and had regular menstrual periods on oral contraception, had no nocturnal hot flushes, and had not observed any influence of the menstrual cycle on sweating. There was no history of neoplasm or infection; no recent or distant travel to tropical countries; and no weight loss, fever, lymph nodes, pyrosis, or other gastrointestinal symptoms. Blood count, C-reactive protein, thyroid-stimulating hormone, blood glucose, blood cultures, and urinalysis were normal.

Figure 1. Photograph of the bed at night showing the shapes left by the patient body sweating during the night.

Given the long duration of night sweats, the absence of other symptoms, and a negative examination, primary sleep hyperhidrosis was diagnosed. As some of our patients with venlafaxine-induced night sweats had benefitted from treatment with oxybutynin (a drug indicated to treat overactive bladder), she was treated with 5 mg oxybutynin at bedtime. She noted complete resolution of symptoms on the first night of use. The treatment was suspended after 3 weeks because she was afraid of taking a drug for a long time, even though she had no side effects. Surprisingly, she had no more hyperhidrosis for 9 months, until a sudden and violent relapse with no obvious cause occurred. She started taking oxybutynin again, and the hyperhidrosis stopped.

DISCUSSION

Our patient experienced severe hyperhidrosis exclusively related to sleep. Profuse sweating occurred every night for 23 years, disrupting her sleep and her personal quality of life and intimacy. The condition was considered primary, as it was not associated with any medical, psychiatric or sleep disorders or with any specific medication. This difficult chronic condition had gone untreated for decades but was immediately relieved by a single nightly dose of oxybutynin, with a benefit that lasted for several months after discontinuation of the drug.

Chronic sleep hyperhidrosis was defined in the International Classification of Sleep Disorders, first edition, revised (1990–2001) as profuse sweating that occurs during sleep during more than 6 months.² The severity of the disorder could be mild (no bathing or change of clothing is required; the patient may have to turn the pillow or remove blankets), moderate (sleep is disturbed by the need to arise and wash the face or other affected body areas but no clothing change is necessary), and severe (a bath or change of clothing is required).² Our case was severe in all these domains, as her symptoms occurred nightly for 23 years and required her to change panties and sheets several times per night. She seems to represent an extreme case in the spectrum of sleep hyperhidrosis.

Daytime and nocturnal hyperhidrosis are common, with a prevalence of 4.8% in the population according to a questionnaire.⁴ It is severe in 3.4% of those questioned, but only 2.5% had told their doctor about it.⁴ The true prevalence of sleep hyperhidrosis, however, is unknown, but some cross-sectional studies in primary care settings using a questionnaire have reported values ranging from 23% to 40%, including severe cases in around 10%.¹ This high prevalence contrasts with the lack of a definition of the disorder in the International Classification of Sleep Disorders, third edition, text revision, the rarity of patients referred to sleep specialists for this reason, and here the long delay before the patient visits a sleep specialist and receives appropriate treatment. It illustrates how sleep hyperhidrosis can be overlooked, perhaps because it has no major health consequences (apart from sleep disruption) and because many doctors do not know how to treat it (no medication is indicated). In this sense, it is similar to nocturnal enuresis.

Primary hyperhidrosis is a symmetric and bilateral sweating occurring in one of the following areas: palms, soles, axillae, or craniofacial region, whereas trunk area is atypical and rare.⁵ Primary hyperhidrosis patients show a positive family history, and there is a cessation of sweating during sleep.⁵ Sleep hyperhidrosis is primary when isolated (which is a rare condition, occurring in 3% of the population) or secondary when associated with several pathologies or treatments (Table 1).^1,3 Specifically, certain sleep disorders or their treatments may be associated with night sweats, including obstructive sleep apnea syndrome (40–43%, possibly due to recurrent sympathetic discharge associated with awakenings and intermittent hypoxemia), insomnia (possibly due to sympathetic hyperexcitation), restless legs syndrome, type 1 narcolepsy, and sodium oxybate use.^3,5,6 The association with sleep disorders was ruled out by means of an interview and polysomnography in our patient. Medical and psychiatric disorders were ruled out in our patient by means of an interview and blood measurements and above all because the long duration of the condition without any other symptoms was not compatible with cancers and other severe disorders. This case was therefore a primary sleep hyperhidrosis.

Table 1.

Causes of sleep hyperhidrosis and proposed treatments.

Main Disorders Associated with Sleep Hyperhidrosis
Infectious: tuberculosis, brucellosis, bacterial pneumonia, human immunodeficiency virus, mononucleosis, cysticercosis, endocarditis Tumor: Lymphoma, leukemia, mesothelioma, inflammatory prostatic cancer, pheochromocytoma, POEMS syndrome Endocrinological/Metabolic: diabetes mellitus, hyperthyroidism, obesity, menopause, pheochromocytoma Autoimmune: giant cell arteritis, Takayasu arteritis, rheumatoid arthritis, sarcoidosis	Neurological Disorders: cervical spinal cord lesion, hypothalamic lesion, brainstem stroke, synucleinopathy, peripheral neuropathy Mental Disorders: panic disorder, anxiety disorder Sleep Disorders: sleep apnea, insomnia, restless legs syndrome, narcolepsy type 1 Miscellaneous: gastrointestinal reflux, Prinzmetal angina, environmental heat
Drug Effects on Sleep Hyperhidrosis
Reduction of night sweats	Increase of night sweats
Benzodiazepines: diazepam Anticholinergic: oxybutynin, glycopyrrolate Alpha-adrenergic agonists: clonidine Calcium channels inhibitors: diltiazem Carbonic anhydrase inhibitor: acetazolamide Immunomodulator: thalidomide Opioids: nabilone Hormonal replacement therapy	Cholinesterase inhibitors Cholinergic agents Selective serotonin and noradrenalin reuptake inhibitors antidepressants: venlafaxine, serotonin Antiviral: efavirenz Hypoglycemic agents Sodium oxybate Opioids

POEMS = polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes.

The question arises as to the mechanisms of sleep hyperhidrosis. The normal purpose of sweating is to reduce core body temperature (here during sleep) by evaporation, a process that mostly occurs during non-rapid eye movement sleep (via increased parasympathetic/sympathetic balance) and leads to normally lose 0.5 to 1 L of sweat per night.⁷ Normal sweat is odorless, whereas the odor described by the patient was rich in ammonia, suggesting that not only the eccrine sweat glands (which produce odorless sweat) but also the apoeccrine sweat glands (which produce pheromones, ie, body odor) had been further stimulated.⁸ Indeed, sweating also occurs during emotions and when gustatory heat receptors are stimulated by spicy foods.⁸ This “emotional sweating” differs from thermoregulatory sweating as it occurs in response to psychological stimuli and regardless of ambient temperature.⁹ Indeed, sweating is associated with cutaneous vasodilation when the sympathetic autonomic system aims to reduce core body temperature by evaporating sweat from the skin but with vasoconstriction during stress, leading to “cold sweats.”⁸ Psychological cold perspiration is diffuse over the body and malodorous, unlike thermoregulatory perspiration, which is odorless.^10,11 Our patient had no hot flushes and woke up sweating with a sensation of cold (a consequence and not a cause of sweating), suggesting that her hyperhidrosis was not caused by a thermoregulatory problem. Her “cold night sweats” with an ammoniacal smell could rather be an exacerbation of the emotional sweating reflex.

Hyperhidrosis results from excessive sympathetic cholinergic (muscarinic-type) activity on the eccrine and apoeccrine sweat glands.⁹ In this sense, drugs increasing cholinergic transmission (such as cholinesterase inhibitors) can trigger sleep hyperhidrosis, and drugs blocking cholinergic transmission ameliorate it (Table 1). This explains why oxybutynin, an anticholinergic drug that blocks muscarinic receptors, attenuated nocturnal sweating in our patient. Oxybutynin has potential side effects, including dry mouth, constipation, and urinary retention, which were not observed in our patient.¹² Although oxybutynin has been reported to treat daytime hyperhidrosis,¹³ its beneficial effect on sleep hyperhidrosis, as observed here, has not yet been reported to our knowledge. The initial cause of this cholinergic overstimulation is unknown. Interestingly, the beneficial effect of oxybutynin lasted for several months after its withdrawal. One wonders whether it did downregulate muscarinic receptor sensitivity, permanently resetting a normal sweat reflex. Other drugs could have been suggested to alleviate sleep hyperhidrosis (Table 1). Case reports support the use of benzodiazepines in emotional hyperhidrosis, which help patients with concomitant sleep insomnia.^12–14 Alpha-adrenergic agonists such as clonidine, thanks to a sympatholytic effect, have been used successfully in some cases of hyperhidrosis.^12–14

In conclusion, this extreme case of primary sleep hyperhidrosis illustrates the extent to which severe nocturnal sweating is neglected despite a significant impact on quality of life and demonstrates that oxybutynin, an anticholinergic generally used for overactive bladder syndrome, can be used in sleep hyperhidrosis with excellent efficacy, a good adverse side-effect profile, and a long-lasting effect.

DISCLOSURE STATEMENT

All authors have seen and approved the manuscript. Institution where work was performed: Sleep Clinic, Pitié-Salpêtrière Hospital, Paris, France. Dr. Dias was financed by the Centro Hospitalar Universitario de Sao Joao, EPE, Porto, Portugal, for her stay in the Paris Sleep Unit. The authors report no conflicts of interest.