Pruritus and Pain

Pruritus and Pain

Peter J. Lynch

Libby Edwards


Pruritus (itch) is an uncomfortable sensation that provokes the urge to scratch. This does not necessarily mean that the patient is actively scratching; pruritus only provokes the urge to scratch. This depends upon the cause of itching, which exists on a spectrum, as well as the genetic and psychological makeup of the person involved. Atopic dermatitis/eczema is regularly associated with scratching; scratching produces intense pleasure, and the skin findings of atopic dermatitis are produced by the rubbing and scratching. Urticaria/hives is often associated with only modest scratching; scratching is not pleasurable, and scratching produces immediate worsening of the hives. And, aquagenic pruritus produces more of a prickling, stinging itch that generally does not induce scratching. There are several common mistakes made in describing and writing about pruritus. First, the correct spelling is pruritus, not pruritis, because this sensation does not indicate inflammation. Second, many confuse the word “itch” with the word “scratch.” One scratches his skin, one does not itch it. Pruritus specific to the anogenital region has been recently reviewed.1

Pruritus is generally classified into four groups based on neuropathophysiology: (1) pruriceptive pruritus (itching arising in the context of recognizable skin disorders); (2) neuropathic pruritus (itching occurring due to damage of neurons of the peripheral or central nervous system by orthopedic issues such as entrapment, metabolic factors such as diabetes, neurogenerative factors, infections such as herpes zoster, and malignant tumors); (3) neurogenic pruritus (itching arising as a result of central stimulation secondary to systemic disease and occurring in the absence of skin disease); and (4) psychogenic pruritus (itching arising as a result of psychological factors). However, there may be considerable overlap; psychological factors can at least exacerbate if not serve as a primary factor in each of these groups, and there seems to be interactions between the immune system and cutaneous nerves in neurogenic itching.2,3,4,5

Pruritus, of course, is a symptom, not a disease, but it is discussed below for the convenience of the clinician as though it is one condition, in the patient who presents with the complaint of itching.

Clinical Presentation

Pruriceptive itching is covered with the individual mucocutaneous disorders as they are discussed throughout this book. Neuropathic itching is localized mostly to areas outside the anogenital areas (eg, notalgia paresthetica, brachioradial pruritus), but pruritus can occur in the genital region with disorders such as postherpetic neuralgia, other small fiber neuropathies, and itching within scars as a result of reinnervation of the scar tissue. Neurogenic pruritus tends to be generalized and therefore may affect the anogenital region. This type of pruritus often occurs with medications such as opiates and with disorders such as Hodgkin lymphoma, chronic hepatobiliary diseases (especially in the presence of cholestasis), polycythemia vera, and other myeloproliferative disorders. Psychogenic pruritus occurs in patients with conditions such as obsessive-compulsive disorders and those with prurigo nodularis and delusions of parasitosis.

Regardless of cause, the presence of pruritus (especially if it is accompanied by scratching) leads to a greatly diminished quality of life (QoL), disturbance of sleep patterns, and very often leads to the development of, or worsening of, depression and anxiety.6,7 Scratching while the person is unaware of doing so is common during daytime scratching and is also common during scratching that occurs at night, especially in the lighter stages of non-REM sleep.8

Central Pathways

The peripheral C fibers terminate in the dorsal root ganglia and the itch sensation is then transmitted to neurons expressing gastrin-releasing peptide receptors (GRPRs) that cross over to the contralateral side and ascend the spinothalamic tract to the thalamus. Interestingly, there are also itch-inhibiting neurons in the spinal cord. From the thalamus, neuronal signaling is transmitted to cortical and subcortical sensory regions of the brain. Chronicity of pruritus is believed to be related to impairment of the itch-inhibitory pathways as well as to the development of central sensitization in a manner similar to that which occurs in chronic pain.


The management of pruritus is much the same for all itching, no matter whether pruriceptive, neuropathic, neurogenic, or psychogenic pruritus. The basic principles of this approach are given detailed coverage in the section on eczematous and lichenified disease (see Chapter 5). However, there are several additional modalities for use in patients with noneczematous cutaneous disorders and for pruritus occurring in the absence of skin lesions.3,8,10 In the pruriceptive group, greater emphasis can be placed on the use on both sedating and nonsedating antihistamines for urticaria and other itching disorders mediated by histamine. In the neuropathic group, the antiepileptics, pregabalin and gabapentin, can be used in the treatment of the itching that sometimes occurs with diabetic and postherpetic neuropathies. In the neurogenic group, mirtazapine, naltrexone, naloxone, aprepitant, and ultraviolet light phototherapy may be considered for the itching associated with chronic renal disease, hepatobiliary disease, polycythemia vera, leukemia, and lymphoma. In the psychogenic group, much can be gained with clinical psychological intervention as well as with placement of earlier and greater emphasis on psychotropic medications.

Anogenital Pain

Generally, patients who present with a chief complain of genital itching suffer from different diseases than those who describe primarily pain. Of course, scratching can produce pain, but those individuals usually describe pruritus as their primary symptom and report that they scratch to the point of pain. Interestingly, some patients deny the presence of pain, but rather insist they have burning, rawness, irritation, stinging, tearing, soreness, stabbing, aching, or throbbing. For the purposes of this chapter, all of these characterizations of discomfort are discussed under the umbrella of pain. Also, some people report itching that does not produce a desire to scratch; with more questioning, they sometimes describe this as a tingling, prickling, or stinging itch. These sensations are usually characterized under pain as well, since the definition of itching is an unpleasant sensation that provokes a desire to scratch.

True itching is generally not included in the same differential diagnosis as pain, although there are several exceptions, notably lichen planus and atypical pain syndromes/neuropathy. Most chronic itching with scratching results from dermatoses. Chronic superficial burning,
soreness, and pain, as distinct from pelvic pain, most often occurs from the anogenital pain syndromes vulvodynia, penodynia, scrotodynia, and anodynia, but erosive skin diseases, malignancy, neuropathy, and, in women, estrogen deficiency occur regularly (Table 13-1).

Vulvodynia, penodynia, scrotodynia, and anodynia represent chronic discomfort in the absence of relevant clinical abnormalities. Whereas there is abundant literature on vulvodynia, there is little written about male genital pain syndromes, so that most of what we know is extrapolated from experience with vulvodynia.

The evaluation of the patient with chronic anogenital pain is quite easy and straightforward, requiring only a few carefully chosen questions of history, a careful examination of the skin and, in women, a wet mount (see Table 13-2). The skin should be examined using simple magnification if needed. The patient with pain and visible erosions does not present a diagnostic dilemma. However, erosions can be subtle at times; vaginal and introital erosions can be missed in women, and fissures are overlooked easily in both men and women.

Many patients who report symptoms of burning, irritation, or rawness also report redness, and, often, edema. Men especially frequently describe texture changes or stickiness. Redness that is mild, poorly demarcated, and without scaling or thickening is frequently within the range of normal, but patients are not generally in agreement and insist that this is new for them (Figs. 13-1 and 13-2).

Those patients who have no relevant observable skin disease other than unimportant redness, no infection, and no specific neurologic abnormality fall into the category of a genital pain syndrome: vulvodynia, penodynia, scrotodynia, or anodynia. Abnormalities that do not produce pain, such as anogenital warts or Candida glabrata, are not relevant and can be disregarded. Sometimes patients have an abnormality that can cause symptoms, such as lichen sclerosus, but discomfort is not in the area of the lichen sclerosus; this person may have lichen sclerosus and vulvodynia. Also, at times, patients present with objective skin disease or infection, but their discomfort is disproportionate to the degree of skin disease noted, or pain persists after the infection or skin disease is cleared. These patients have an underlying pain syndrome that is either unassociated with the skin disease or triggered by it. For example, lichen sclerosus and lichen planus are recognized by vulvologists as initiators for the development of vulvodynia (Presented at ISSVD World Congress, Paris, 2011). Therefore, the skin disease or
infection should be controlled, but a pain syndrome can be diagnosed and treated concomitantly.

Infection, skin disease, malignancy, trauma, estrogen deficiency (in women), neuropathy and pain syndromes are the usual causes of chronic genital pain (Table 13-1).

Many clinicians and most patients initially assume that genital pain (or itching) without obvious skin findings is due to infection, including yeast, bacterial vaginosis, or sexually transmitted disease. Chronic pain almost never occurs from infection in immunocompetent patients, and negative cultures and a lack of response to antimicrobial therapy also signifies a different diagnosis. Yeast, the most common cause implicated by patients and providers, usually is a pruritic rather than painful condition, and C. albicans clears, at least briefly, with therapy. Some postulate that an inflammatory response to low levels of yeast may cause pain.11 Nonalbicans Candida is nearly always asymptomatic. Sexually transmitted diseases generally either do not cause superficial genital pain other than dysuria (gonorrhea, Chlamydia, warts) or they produce intermittent symptoms with visible skin findings (herpes simplex virus infection). However, trichomonas, particularly in women, certainly produces irritation and burning, although more often itching. These infections can be ruled out easily by molecular studies.

Irritant contact dermatitis is the most common skin disease that causes symptoms of pain with irritation, rawness, or burning. Overwashing and medications (see Chapters 5 and 10) or strong irritants such as destructive therapies for warts that cause a chemical burn are common contactants. Allergic contact dermatitis produces itching more than burning and irritation. Lichen planus is an erosive skin disease, and one of the few that causes both itching and pain (Chapter 11). The blistering diseases pemphigus vulgaris and mucous membrane pemphigoid are painful (see Chapter 10). In women, erosive vaginal skin diseases produce a purulent vaginal discharge that causes an irritating contact dermatitis in the vestibule; these include lichen planus and mucosal immunobullous diseases (see Chapter 14). Abnormalities can be visualized.

Malignancies can produce ulcerations, especially late squamous cell carcinomas and melanoma, but squamous cell carcinoma in situ (high-grade squamous intraepithelial lesion, differentiated intraepithelial neoplasia, Bowenoid papulosis, squamous cell carcinoma in situ) can produce itching or pain symptoms, as can Paget disease. These can be seen.

Trauma regularly produces pain, whether it is surgical, overlapping with irritant contact dermatitis (application of acid for treatment of anogenital warts), accidental, etc. These can be seen in the office.

Estrogen deficiency in women can produce discomfort as well, by causing thinning and dryness of the vaginal mucosa. Because the vaginal mucosa can be difficult to visualize, especially in the patient with pain, a wet mount can be crucial to rule out these vaginal diseases.

The most common specific neurologic disease causing anogenital pain is pudendal neuralgia. This can be difficult to diagnose, at least partly because there are several types and causes, and there is considerable individual variation in the anatomy and course of this nerve.10 There is no one standard evaluation and diagnostic regimen. This condition is suggested by sensory abnormalities in the saddle distribution of the pudendal nerve. There is pain or numbness of the genitalia and adjacent buttock, the proximal, medial thigh, and/or rectal area. Classically,
the pain is worst when sitting and minimized by standing or lying. The diagnosis can be implicated further by a careful physical examination, magnetic resonance imaging examination performed by specialists in this disease, and magnetic resonance neurography. Management consists of physical therapy, medications for neuropathic pain and nerve block, behavioral modifications, surgical pudendal nerve decompression, radiofrequency, and spinal cord stimulation.12 Other causes of specific neuropathic pain are uncommon and history is required for diagnosis. Postherpetic neuralgia only follows herpes zoster, not herpes simplex virus infection; the intake of all patients of one of us (LE) includes a question regarding past shingles of this area, and not one of several thousand patients with chronic pain or itching has had herpes zoster as a possible factor. And, this is an obvious diagnosis as shingles rarely occurs unnoticed. Diabetes can be associated with peripheral neuropathy, but far, far more common of the feet, and multiple sclerosis is sometimes associated with pain syndromes.

Patients with normal genital skin, to include the vagina, no specific diagnosable neuropathy, and, for women, a normal wet mount, are diagnosed as vulvodynia, penodynia, scrotodynia, penodynia, or anodynia.


Vulvodynia is defined as chronic vulvar discomfort in the absence of relevant clinical abnormalities. Rarely, discomfort extends to anal skin or even solely affects the perianal area. The discomfort is most often described as burning, stinging, rawness, irritation, aching, stabbing, soreness, or throbbing. Itching is not a prominent symptom. Although most vulvologists believe that this is a symptom rather than a specific disease, others, including me (LE), feel that this is a specific condition. Vulvodynia is common, with a great deal of data available, including characteristic epidemiology, comorbidities, and reported management strategies.

Vulvodynia is the most common cause of chronic vulvovaginal pain. This is not a diagnosis of exclusion and can be diagnosed fairly reliably by a validated questionnaire; a study reported in 2006 shows that history alone is prognostic for vulvodynia.13 Characteristic vulvar pain in the presence of recognized associated comorbidities is highly predictive of this diagnosis. Since then, we know that the finding of an abnormal pelvic floor examination confirms the diagnosis.

Vulvodynia is very, very common, although uncommonly recognized. From 10% to 28% of premenopausal women experience this at some point, but only 30%-48% sought care in one study, and fewer than 50% of those who did were given a diagnosis.14 This condition appears to occur more often in those of Hispanic background than White,14 and although recognized much less often in Black patients, this may be because of a difference in words used to describe symptoms.15 It is truly amazing that women generally are unaware of a condition this common, and experience isolation, believing that they are the only individuals suffering from this vulvar pain.

Clinical Manifestations

Vulvodynia often begins in young women, in their third and fourth decade, but occurs in all age groups, including in postmenopausal women and, rarely, in children and adolescents.16,17 A common presentation is entry dyspareunia and self-described “vaginal” burning, irritation, redness, and rawness. Usually, they categorically deny itching that produces a desire to rub and scratch, and report that they do not scratch. Patients very often also have background discomfort as well, and irritation with tampons, tight clothing, exercise, and sitting for long periods. Often, they have consulted previous clinicians who have diagnosed and treated yeast, with incomplete improvement, and many women have been treated repeatedly for yeast and bacterial vaginosis, sometimes for years, and nearly always without laboratory confirmation.

Patients with vulvodynia exhibit typical comorbidities.18 Nearly all patients with vulvodynia have a “positive review of systems” with anxiety, depression, insomnia, constipation, diarrhea, heartburn, urinary frequency, urgency, dysuria, headaches, arthralgias, and myalgias. Diagnoses including fibromyalgia, irritable bowel syndrome, migraine headaches, temporomandibular joint disorder, chronic fatigue syndrome, and interstitial cystitis are common. Many report multiple medication allergies, which are actually intolerances.

On examination, many patients are anxious and tearful. When asked to touch where they experience pain, most women indicate the vestibule, and they usually report vestibular redness and sometimes feel swelling of this area (Fig. 13-1). The clinician may also see redness, but this is usually within the realm of normal (see Chapter 1). Redness is classically around the ostia of the vestibular glands and formerly was thought to be associated with inflammation of these glands, but this is seen in some asymptomatic women as well. A significant minority of women experience discomfort in other areas of the vulva, and many report redness in other areas as well (Fig. 13-2).

If the skin is otherwise normal, the examination should include gently probing the vulva with the soft end of a cotton-tipped applicator. If the patient has pain in the vestibule with this probing, and only in the vestibule, as well as a history of pain limited to the vestibule, and a wet mount showing no infection, no inflammation, and no parabasal cells, then the diagnosis of the vestibulodynia subset of vulvodynia can be made with confidence. Previous names for this condition include the vulvar vestibulitis syndrome, vestibulitis, vestibular adenitis, and infection of the minor vestibular glands. The name has
been changed to eliminate “itis,” since clinical and histologic inflammation is lacking when compared to the normal vestibule. This is a quick and simple examination requiring no further testing. If there is discomfort to q-tip probing that extends beyond the vestibule or the patient reports that pain occurs in areas outside the vestibule, the patient has generalized vulvodynia, termed dysesthetic vulvodynia in the past. Uncommonly, patients have no pain to touch.

An examination of the pelvic floor is characteristic in women with vulvodynia. Pressure to the levator ani muscles with an inserted finger generally produces pain in addition to pressure, and asking the patient to squeeze that finger with her pelvic floor muscles produces minimal contraction and poor endurance.

Many years ago, the ISSVD divided vulvodynia into additional subsets beyond vestibulodynia and generalized vulvodynia, with the premise that different subsets had different epidemiology and different underlying etiologies. However, recent data increasingly show a lack of evidence-based information that these subsets represent distinct categories.19 However, at least distinguishing vestibulodynia from generalized vulvodynia remains crucial for at least one reason. Excision of the vestibule is a treatment of choice only for women with vestibulodynia, due to the location of the discomfort. The ISSVD, the International Society for the Study of Women’s Sexual Health, and the International Pelvic Pain Society revised the academic terminology and classification of persistent vulvar pain and vulvodynia in 2015 based on not only on location but also on the role of touch/pressure/friction (provocation), temporal onset, and pattern.20 These basically are unimportant to the clinician in the diagnosis and management of vulvodynia.

Once believed to be a chronic condition with severity that waxes and wanes, vulvodynia now is reported to be characterized by remissions and recurrences, with persistence being the exception rather than the rule.21,22 However, this is not my (LE) experience; my patients very rarely experience spontaneous remission, although waxing and waning of severity of symptoms is common. I suspect that the nature of these studies, where the patients did not seek care but rather received unsolicited surveys, selected for those with milder symptoms than those who fight their way to a specialty clinic. In addition, another study suggests that primary vulvodynia, those patients with dyspareunia since first coitus, are less likely to experience remission,23 and these patients are known to be more resistant to treatment as well.

Jan 8, 2023 | Posted by in GENERAL | Comments Off on Pruritus and Pain

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