Abstract
Background
Paroxysmal localized hyperhidrosis is a rare disorder of the central autonomic nervous system. No association between paroxysmal hyperhidrosis and severe headache has been previously described in literature.
Conclusion
Paroxysmal localized hyperhidrosis is a rare central autonomic nervous system disorder that can occur in combination with severe headache. Both the headache and paroxysmal hyperhidrosis complaints were treated effectively with clonidine in the patient described in this case-report.
Case report
A 65-year-old woman visited the outpatient clinic of the neurology department with gradually increasing complaints of excessive sweating and headaches for 2 years. There was no clear cause for the attacks, and these did not occur in clusters; however, the attacks mainly occurred in the early morning around 6 am. The attacks started from the beginning with both excessive sweating followed by attacks of headache. When presented at the neurology outpatient clinic, the patient experienced daily attacks beginning with bilaterally symmetric excessive localized sweating of the face, scalp, full neck, and upper chest simultaneously followed, after several minutes, by a progressive severe holocranial headache (numeric rating scale of seven to eight out of 10 concerning the pain intensity). Both the sweating and the headache had a mean duration of 1.5 to 2 h.
There were no identifiable triggers for the attacks (i.e. not triggered by food intake, emotional distress, physical exercise or a high ambient temperature) and they frequently started during sleep in the early morning, secondarily awaking the patient. The headache did not spread to the neck and the patient had a normal sweating pattern during exercise and a warm ambient temperature. There were no complaints of accompanying facial flushing, phono- or photophobia, vomiting, eyelid ptosis, conjunctival injection or lacrimation, nasal congestion or rhinorrhoea, palpitations or tachycardia, or a sense of restlessness. There were no other neurological complaints during the attack and patient did not have any symptoms between the attacks. Patient’s last menstruation was 10 years ago and since that moment, she did not experience any postmenopausal symptoms. There was no weight loss. The family medical history was noncontributory and the patient’s relevant prior medical history only included a supraventricular tachycardia, for which she receives treatment by the cardiologist in an outpatient setting. The patient receives the following medications: omeprazole 40 mg BID, flecainide 50 mg daily, verapamil 120 mg daily, pregabalin 150 mg two times a day (BID), and zopiclone 7.5 mg daily. She did not have any medication or dosage adjustments in the last 9 years and did not have any side effects prior to the current medical complaints. Patient was asymptomatic at the time of the neurological consultation and the general and neurological examination were both completely normal (e.g. blood pressure of 105/70 mmHg with a pulse of 70 beats/min; there were no palpable lymphomas).
Routine blood tests did not show any abnormalities (i.e. normal white blood cell count, C-reactive protein, erythrocyte sedimentation rate, electrolytes, glucose, kidney function, vitamin-B12 value, and normal thyroid function). Moreover, patient twice had a 24-h urine analysis after an attack to exclude a pheochromocytoma as a possible cause, which showed normal fractionated metanephrine and catecholamine values. Electrocardiogram, chest X-ray and abdominal ultrasound and computed tomography scans did not show any abnormalities. Hodgkin and non-Hodgkin lymphomas were excluded by the absence of lymphomas on physical examination, normal chest X-ray, normal abdominal imaging results, and absence of weight loss or fever. Moreover, a potential Pancoast lung tumour seems very unlikely because of the fact the patient already had complaints for over 2 years with a normal chest X-ray, the absence of a Horner syndrome with a normal neurological clinical examination, and the bilaterally symmetric sweating. Serum microbiological analysis for syphilis, HIV and Borrelia Burgdorferi all were negative. Additional magnetic resonance imaging scans of the brain and spinal cord also did not show any abnormalities.
A tentative diagnosis of idiopathic paroxysmal localized hyperhidrosis was made, and treatment with clonidine 0.050 mg BID was started; the dose was escalated guided by the clinical response. The patient had an excellent response and the attacks (concerning both the hyperhidrosis and the headaches) almost completely disappeared on a clonidine dosage of 0.075 mg three times a day (TID) without any side effects. The hyperhidrosis disease severity scale score (HDSS) decreased from 3 (severe complaints and a bad quality of life) initially, to 1 (no complaints and an excellent quality of life) after treatment. Follow-up at the outpatient neurological clinic after 1 year did not show any abnormalities with an ongoing excellent clinical response to treatment.
Discussion
The autonomic nervous system regulates the physiological control of the body’s core temperature, which is called thermoregulation. The lowering of the core temperature through evaporation of sweat from the skin is an important aspect of thermoregulation. Excessive sweat production that exceeds the thermoregulatory needs is called hyperhidrosis (1). Estimations concerning the prevalence of hyperhidrosis in the general population range from 1.0–4.8% (2,3).
Hyperhidrosis can be divided into generalized and focal hyperhidrosis. Generalized hyperhidrosis affects the entire body and is mostly a phenomenon secondary to an underlying endocrinologic, metabolic, neoplastic, inflammatory, infectious, or neurological disorder. Additionally, an iatrogenic cause such as drug side effects should be considered. Focal hyperhidrosis can either be secondary to a central or a peripheral neuronal damage (e.g. diabetic neuropathy or spinal injury) or primary idiopathic. Primary focal hyperhidrosis mainly involves the feet, palms, axillae and craniofacial areas. The cause of primary (idiopathic) focal hyperhidrosis is largely unknown, but it is thought to represent a complex dysfunction of the autonomic nervous system. We would like to refer to the extensive reviews for further information concerning the broad differential diagnoses of hyperhidrosis, the additional diagnostic work-up, and management options (1,4–7).
The diagnostic clinical criteria concerning the differentiation of primary from secondary hyperhidrosis causes are summarized in Table 1 (4). In a study of a single university-based population of 415 patients, 93.3% (387 patients) had primary hyperhidrosis and 6.7% (28 patients) were found to have secondary hyperhidrosis. The author concluded, based upon the study results, that the diagnostic criteria (summarized in Table 1) had a sensitivity of 99%, specificity of 82%, positive predictive value of 99%, and negative predictive value of 85% (4). The patient in the case report, described above, had complaints for over 6 months, which were excessive with secondary impairment of daily activities, therefore meeting criterion A of the diagnostic criteria. However, our patient only met three out of the seven characteristics of criterion B (impairment of daily activities, episodes occurring at least weekly, and bilateral/symmetric involvement). The patient mainly had hyperhidrosis of the face, scalp, and especially the full neck and upper chest, therefore the anatomical localization is not limited to the craniofacial areas. Moreover, involvement of the neck is very uncommon in primary hyperhidrosis (4). Also, our patient had episodes during sleep, an age of onset of 63 years, and a non-contributory family history, making it necessary to rule out a secondary cause of the hyperhidrosis (1).
Diagnostic criteria concerning the clinical differentiation of primary from secondary hyperhidrosis. Adapted from Walling (2011) (4).
Due to the high clinical suspicion of a secondary hyperhidrosis, additional laboratory tests, urinalyses and imaging studies were performed, as discussed above, which did not provide any evidence for a possible underlying disorder. Additionally, an iatrogenic cause due to a side-effect of the medication seemed very unlikely, because the patient used the same medication and medication dosages for over 9 years prior to the consultation without any side-effects. Moreover, drug-induced hyperhidrosis is mostly generalized, has a clear temporal relationship between the complaints and the start of the medication or dose adjustments, and in literature reviews there is no known relationship between the medication used by the patient and hyperhidrosis (1,4–6). Drugs can induce excessive sweating through various pathways, which are: a) Drugs that augment cholinergic transmission, b) drugs that interact with opioid receptors, or c) drugs that affect serotonin or norepinephrine transmission (5). Interestingly, however, the pharmaceutical companies that manufacture verapamil (a calcium-channel blocker) and flecainide (a cardiac sodium-channel blocker) list these side effects as very uncommon in their package inserts, as the mechanism of action of both drugs cannot directly explain excessive sweating on pharmacological grounds. Based upon the normal findings of the additional history without specific clues, the normal clinical neurological examination, and the normal findings of the diagnostic ancillary laboratory and imaging studies, it was concluded that the patient probably has a paroxysmal focal hyperhidrosis of idiopathic aetiology.
The literature on the treatment of paroxysmal localized hyperhidrosis is very scarce, and consists mainly of small case series and isolated case reports, in which patients were treated with clonidine orally with dosages up to 0.25 mg TID with a generally good response (8,9). Clonidine is an α2-adrenergic receptor agonist, which amongst other effects inhibits central noradrenergic activity at the hypothalamus by suppressing the presynaptic norepinephrine release (8). Based upon the literature referenced above, clonidine was started 0.050 mg BID and the dosage was escalated guided by the clinical response. The patient had an excellent clinical response at a clonidine dosage of 0.075 mg TID; moreover, both the headache and the hyperhidrosis attacks almost completely disappeared and there were no side effects.
The combination of headaches and ipsilateral autonomic symptoms is well known for trigeminal autonomic cephalalgias (TACs) and are thought to result, in part, from a central disinhibition of the trigeminal-autonomic reflex. However, the bilateral character of our patient’s complaints and the lack of other autonomic symptoms aside from the hyperhidrosis suggests a different underlying pathophysiological mechanism. There is, however, increasing evidence that hypothalamic involvement is important in both generating and driving both trigeminal autonomic cephalalgias (e.g. cluster headache) and migraine (10). Because of the combination of a central autonomic disorder (paroxysmal focal hyperhidrosis) and severe headaches with a diurnal pattern, one could speculate that the most likely anatomic substrate for the complaints would be the hypothalamus. In addition, central hypothalamic noradrenergic hyperactivity could potentially play a pathophysiologically important role, as clonidine (an α2-adrenergic receptor agonist) treatment was effective in our patient. This case report is the first, to our knowledge, that describes a patient with paroxysmal focal hyperhidrosis in combination with severe headache attacks.
Clinical implications
Paroxysmal localized hyperhidrosis is a rare central autonomic nervous system disorder that can occur in combination with severe headache and can be treated effectively with clonidine.
Footnotes
Ethic approval and patient consent
The patient described in this case report kindly gave verbal consent for publication. During the writing of this article, every precaution was taken to ensure patient anonymity.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.