Dysaesthetic penoscrotodynia: nomenclature,classification,diagnosis and treatment

Abstract

Male patients can present with a genital skin burning sensation that bears similarities to vulvodynia. The classification of vulvodynia by International Society for the Study of Vulvovaginal Disease of vulvodynia provides a blueprint for nomenclature and classification of Dysaesthetic penoscrotodynia (DPSD). Recognizing DPSD as generalized, localized, provoked, unprovoked and mixed will enable precise and objective communication between practitioners. Learning from research on the aetiology and management of vulvodynia can improve the care of patients suffering with DPSD. Scope remains for better acknowledgement of DPSD within the medical profession and improvement in its public profile in order to enhance patient care.

Keywords

dysaesthetic penoscrotodynia penodynia scrotodynia nomenclature classification male genital pain

INTRODUCTION

Men present with genital skin burning sensation in what otherwise is healthy skin with no clinical evidence of pathology and with no clear underlying aetiology.¹ The condition bears similarities to women presenting with vulvodynia. The impact of the complaint on the patient's physical and mental wellbeing is usually out of proportion with the physical signs, if any are present. This adds to the dilemma experienced by patients and clinicians in understanding and managing the complaint. The paucity in literature and low reporting by the medical profession perpetuates the complexity of clinical management and frustrates the progress of care. There are anecdotal publications, of single or series of case reports, which list the sporadic use of empirical treatments. The long-term use of unvetted pharmacotherapy, in patients who are otherwise healthy, should raise concern.

This article aims to review the English language literature in order to formalize a consensus for nomenclature, classification, diagnosis and treatment for DPSD. The PubMed database was searched for references listed under: male genital pain, scrotodynia, penodynia and/or peno-scroto-dynia. Genital dermatology textbooks were reviewed for articles about genital pain and the authors' observations were also listed.

AETIOLOGY

We first coined the term Dysaesthetic penoscrotodynia (DPSD)^1,2 to describe conditions of men presenting with a clear and precise complaint of genital skin burning sensation and/or pain, with no indication of physical signs or underlying recognizable disease condition. The term was used in acknowledgement of the ‘burning vulva syndrome’ and its definition later as ‘vulvodynia’.

Patients' alertness, their precise description of the pain/burning sensation, and its association with drinks and beverages have indicated plausible mechanisms of induction in some cases. The patients' reports of recovery upon abstinence of such beverages and drinks supported the association and the given explanation. In these circumstances, the male genital skin burning sensation ceased to be described as dysaesthetic, as there was a clear underlying aetiology, and the removal of the precipitating agent led to cessation of the complaint. There continue to be other groups of men with no clear underlying aetiology for their genital skin burning sensation, in whom it is safe to describe the condition as ‘dysaesthetic’.

Alcohol-induced penodynia ³ has become a prominent explanation in a subgroup of patients. Allergy to ethanol and acetic acid may give a plausible mechanism of action.^4,5 An alternative explanation is the effect of ethanol on the vanilloid receptor-1 (VR1). Ethanol was found to potentiate the response of VR1 to heat and lowers the VR1 threshold for heat activation, from ± 42°C to ±34°C. In alcohol-induced penodynia, the patient senses heat at a temperature lower than that of the body, leading to burning sensation.⁶

Caffeine-induced genital skin pain may be produced by intake of beverages containing caffeine, with cessation of the burning/pain on abstinence.⁷ The effect of caffeine on peripheral nerves is extrapolated from research. The experimental use of caffeine led to blockage of the alleviation of hyperalgesia, produced by the chronic administration of amitriptyline.⁸ In this experiment, the use of caffeine led to blockage of thermal antihyperalgesia, when amitriptyline had already intercepted and alleviated the neuropathic pain, leading to the recurrence of pain.⁹

There are emerging suggestions that the male genital skin burning could be a neurovascular phenomenon,¹⁰ as a proportion of patients described signs suggestive of vascular changes, especially on the penile glans.¹⁰ The changes were described as ranging from mild hyperaemia to bluish discolouration (i.e. cyanosis).

The red scrotum syndrome may be described in terms of vascular changes. It was first described in 1997 as a separate entity,¹¹ with burning sensation and hyperaemia of the anterior half of the scrotum that may extend to the posterior scrotum or the base of the penis. The author of this case suggested that closely related conditions of idiopathic penile and/or scrotal pain were reported by other physicians in scientific meetings.¹¹ The red scrotum syndrome was also explained in terms of erythromelalgia ¹² as both follow a cascade of severe burning pain with observation of redness and feeling of hotness. Erythromelalgia, in line with Raynaud's syndrome and acrocyanosis,¹³ is a functional vascular disorder. It is a rare condition, with paroxysms of burning sensation and redness of extremities (i.e. legs, feet and, less often, the hands) and it affects more women than men. The explanation of erythromelalgia, as peripheral microvascular arteriovenous shunting of blood leading to accumulation of metabolites and burning sensation, as an underlying cause for genital skin burning sensation seems plausible.¹⁴ The red scrotum syndrome may be explained as a phenotypic expression of localized primary erythromelalgia.¹²

The reported response of vulvodynia, DPSD and other forms of neuropathy to drugs such as tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs), selective norepinephrine re-uptake inhibitors (SNRIs) and antiepileptics, promotes a neuropathic aetiology.^15,16

Restless genital syndrome was reported recently in two men. The finding of static mechanical hyperaesthesia in the pudendal dermatomes and eliciting the genital sensation by manual examination of the dorsal nerve of penis also supports a neuropathic origin.¹⁷ The association with overactive bladder syndrome and restless legs promotes the postulation of small fibre sensory neuropathy.¹⁷ The association with ejaculation or orgasm bears similarities to the ‘restless genital syndrome’ in women. In men, it remains to be established whether it is a separate entity or a subgroup of DPSD.

The role of allergy to lotions and soaps was postulated.¹¹ The investigations of vulvodynia¹⁸ followed a similar line of thinking. It would be premature to make conclusions regarding the role of contact allergy in DPSD, as evidence points to a lack of correlation of allergy with burning mouth syndrome (i.e. stomatodynia).^19,20

Studies of the hypothalamic–pituitary–adrenal axis function in patients with chronic pain syndrome (CPS) showed significantly lower overall mean diurnal salivary cortisol concentration compared with the control group, particularly in men.²¹ The dynamics of cortisol secretion in CPS and whether it is a cause of the pain or an effect of the associated chronic stress remains to be determined.

The recent understanding of the role of acid-sensing ion channels as chemo-electrical transducers, and their involvement in somatic and visceral nociception, provides an opening into the mechanism of pain and its management.²²

NOMENCLATURE AND CLASSIFICATION

The International Society for the Study of Vulvovaginal Disease recently classified vulvodynia as generalized, localized, provoked, unprovoked and/or mixed. ²³ The classification will improve communication between physicians, in terms of objective measurement of diagnosis, clinical care, response to treatment and research.

DPSD would benefit from a similar classification, depending on the spread and distribution of the complaint. The male genital skin pain/burning may well be generalized penoscrotodynia, when the condition is described to affect most of the genital skin. Alternatively, it may be localized and described as Scrotodynia, Penodynia or Glansodynia. Physicians have similarly identified separate entities of localized vulvodynia (e.g. vestibulodynia or clitoridynia). Past case reports suggest that subgroups of patients present with complaints of localized burning and erythema in part of the organ (e.g. part of the glans). The red scrotum syndrome^11,12 could also be described in terms of localized scrotodynia when it affects the anterior scrotal skin only.

Under the proposed classification, the pain/burning sensation would also be provoked, unprovoked or mixed (i.e. provoked and unprovoked). In most published cases, patients perceived the pain as spontaneous (i.e. unprovoked), without any precipitating factor. It was also described as provoked, in the form of allodynia or hyperaesthesia, when patients described intolerance to their own underwear. Dyspareunia was also a prominent symptom, leading to the expression of coital and postcoital genital skin pain and burning sensation. In the severe cases, there was history of abstinence from sexual intercourse to avoid the pain. On examination, the patients' response to the cotton wool test was markedly positive, in the form of hyperaesthesia and/or allodynia.^1,2,10,11 It appears that most case studies refer to patients with secondary DPSD,^1,2,10,11 when the condition presented after a pain-free period. There have been no reports of primary DPSD, when the condition presented early in life.

There are clinical and practical benefits in classifying the severity of the condition into:

Severe, when the patient describes DPSD as severe enough to interfere with the daily normality of life or sexual relationships;

Moderate, when the patient describes DPSD as troublesome in general but not to the extent of interfering with daily living or sexual relationships and

Mild, when the patient perceives DPSD as a problem that is either sporadic, non-severe or both, and allows for the normality of living and sexual relationships at the best of times.

Identifying the degree of severity will exercise some influence on the use of pharmacotherapy, as many of the suggested drug treatments have side-effects. If such side-effects of drug therapy were significant and worse than the condition, the patient may understandably request the cessation of the medication.

There was a report of DPSD in conjunction with stomatodynia,²⁴ similar to both vulvodynia and stomatodynia coexisting in the same patient.²⁵

PREVALENCE

There is a noticeable paucity in literature reporting on DPSD, and publications are based on case reports. Other specialists indicated that they had observed similar patients' complaints, when the condition was presented in scientific meetings.^10,11 DPSD, like vulvodynia, would benefit from clinical recognition, patient support groups and patient educational websites.

The prevalence studies of DPSD are hampered by the relatively low interest in male genital skin conditions, as compared with the female counterpart (e.g. rare or sporadic penoscopy/male genital skin clinics, web-based patient information sites or support groups). We could not find evidence of a population survey for DPSD, as compared with several for vulvodynia.^26–29 The management of DPSD would benefit from similar studies.

The analysis of other case reports suggests that penodynia is reported more frequently than scrotodynia.^1,2,9,11 It is possible that the lack of recognition of DPSD as a clinical entity in the medical community leads to lack of diagnosis and consequently lack of referrals. It is also possible that some of the less symptomatic cases are not brought to the attention of specialists.

DIAGNOSIS

The case series are too small to withdraw dogmatic patient profiles. Most of the case reports described healthy men with no other history of physical or psychiatric conditions or treatment, and no other pattern suggestive of somatization. Understandably, the patient who reached the secondary care practitioner must have been troubled enough by DPSD to require such referral. There is an agreement between practitioners on the degree of distress exhibited by the patient.^1,2,10 Some authors subdivide patients into two age groups: the middle aged (35–50 years) and the elderly (60–70 years).¹⁰

The clinician needs to make a clear differentiation between DPSD and more common conditions of the burning pain of urethritis, the aching pain of orchalgia and penile tip referred pain from prostatitis, prostatic disease and/or deep pelvic pain. Detailed medical history in DPSD may show a link to ingestible materials (e.g. alcohol or caffeine) or contact dermatitis. The removal of the offending agent in these cases leads to recovery, which helps support the diagnosis. These should be recognized as separate clinical entities from DPSD.

Clinical findings

The condition of DPSD is diagnosed mainly on the patient's history. The patient is usually very distressed by the condition. His distress is perpetuated by the lack of understanding in a section of the medical community and inability of physicians who show interest to provide a sustainable cure. There are usually no clinical findings, unless the patient presents during an episode, when the results of vascular changes are witnessed (i.e. hyperaemia and/or cyanosis). Inspection of the genital skin does not usually identify any abnormality in these patients and the diagnosis is reached after exclusion and treatment of any other incidental or concurrent physical skin condition.

Most patients would have paid meticulous care to their genital skin hygiene and contact irritants. There is no evidence of correlation with personality or psychiatric disorders or treatment in the published cases. This does not exclude the possibility of a correlation as patients with other chronic pain syndromes may have already been under treatment for the more pronounced elements of their ailment, which may have consequently managed the underlying DPSD. There are suggestions of a correlation between chronic stress and localized provoked vulvodynia.^30,31

Pain diary

The diary aims to keep a register of type, location, severity, spread, duration and frequency of pain. The patient is encouraged to look for any provoking or precipitating factors (e.g. foods, drinks and skin applications). There should be no leading questions, to ensure an objective response. The keeping of a pain diary proves helpful³² with the following advantages:

Focuses the patient's attention to measure the frequency and duration of the condition objectively, which helps identify its severity and response to prospective treatments, if any;

Identifies any precipitating or provocative factors that proved useful in identifying correlations with contact or ingestible materials;

Helps the patient and the physician to establish whether pharmacotherapy is indicated or justifiable, as many of the drugs used for the treatment of DPSP have side-effects.

INVESTIGATIONS

The diagnosis is made on clinical history and following the exclusion of a physical condition. The patient may have had urological investigations, such pelvi-abdominal ultrasonography and/or cystoscopy, and sometimes urodynamic studies.^1,2 Investigations would have been performed already for any incidental findings, and would help in the process of exclusion of physical condition/s.

Penoscopy

The use of magnification and illumination would help to exclude lesions that may not be easily identifiable by the naked eye.

Skin biopsy

Most of the patients have no clinical evidence of underlying skin pathology. Contrary to recent suggestions, that patients presenting with vulvodynia should be submitted to genital skin biopsy as part of the diagnostic work-up,³³ there is no justification for ‘routine’ biopsies for men with DPSD. Ideologically, it is unjustifiable to perform a biopsy when the findings are expected to be within normal limits. On reflection, it seems unreasonable to offer a biopsy for what otherwise looks like normal and healthy skin, which was the case in all the published case reports^10,11 and other cases of DPSD we encounter in our practice.^2,3,7 The second practical difficulty is choosing the site of the biopsy, when there is no single area of the genital skin that looks different from the others. Thirdly, it would be difficult to justify the normality of the histological findings to the patients when the biopsy was deemed essential for diagnosis. Skin biopsy is an invasive procedure, and although rare, complications may ensue. It has a cosmetic outcome that is usually significant to men. We look forward to the expertise and reflections of other specialists to readdress this opinion.

Research into neuroreceptors has led to better understanding of the aetiology and treatment modalities (e.g. tender sites from primary vestibulodynia had increased nerve density compared with secondary and controls).³⁴ There could be ground for a similar research into DPSD with the approval of the relevant medical ethics committees.

Skin patch testing was investigated for vulvodynia and stomatodynia, with no evidence of positive correlation or advantage for the latter.^18,19 The list of allergens is too extensive to make it of practical significance in the process of investigating DPSD. The patient's observations should be encouraged in the first place by the use of a pain diary. There might be a place for skin patch testing in research studies.

TREATMENT

The published case reports of treatment modalities seem to be anecdotal, empirical and based on the accepted line of care for vulvodynia.^35–37 The interested specialist would have normally received the patient after a long history of unsuccessful attempts of investigations and/or treatments. The patients may have had systemic and/or topical antibiotics, steroids, antifungals or antivirals.

The useless effect of topical treatments was a consistent finding between authors.^1,2,10,11

Amitriptyline, gabapentin, pregabalin, carbamazepine or paroxetine have all been used with variable degrees of reported success.^2,3,7,10,11 There is also an indication of efficacy of cognitive-behavioural therapy in provoked vulvodynia,^38,39 which opens the door for a similar approach with DPSD. The current collective evidence and guidelines into the management of peripheral neuropathy suggests that tricyclic antidepressants, SSRIs/SNRIs, calcium channel alpha(2)-delta ligands (i.e. gabapentin and pregabalin) and topical lidocaine should be the considered first line therapy.^40–44

Transcutaneous electrical nerve stimulation had some encouraging results in some cases.¹⁷ Its reported success in vulvodynia deserves clinical attention as an option for non-invasive management of DPSD.⁴⁵

Unlike vestibulodynia, where there had been reports of improvement following vestibulectomy, there is no direct evidence to suggest that improvement may follow surgical intervention in DPSD. The evidence of improvement with vestibulectomy had come directly from patient follow-up studies, and indirectly from the finding of increased nerve endings and receptors in skin biopsies undertaken from patients suffering from vestibulodynia,³⁴ as compared with those who did not.

FUTURE RESEARCH

The improved understanding of vulvodynia benefited from population surveys and web questionnaires. We still need to ascertain the prevalence of DPSD in a similar manner. Clinical research on DPSD will continue to be hampered in the absence of clear recognitions by clinicians, uniformity of nomenclature and an identified pool of patients. The low literature reporting of DPSD reflects on the anecdotal management of sporadic cases, while double-blinded placebo controlled therapeutic trials are missing for the practice of evidence-based medicine.

DPSD can benefit from the research done in allied conditions and their scientific studies. The ability to measure pain objectively can further the understanding of patient problems and help to measure the effect of drug therapy.⁴⁶ The idea of erythromelalgia and microvascular arteriovenous shunting deserves further attention.^12,14

CONCLUSION

There may well be more than one underlying group of patients, explanation or mechanism of pathophysiology for DPSD. The understanding of the mechanism of induction will influence future modalities of care. Having a unified classification and nomenclature will enable more objective communication between physicians. Raising the level of understanding and recognition of DPSD, within both the medical community and the public, should further patient care in what otherwise is a frustrating condition for both patients and carers.

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