Pruritus Ani

Introduction

Pruritus ani is a dermatological condition characterized as an unpleasant itchy or burning sensation in the perianal region. Persistent itchiness in the anal region can be a difficult condition to treat. Although it may be due to a definable perianal dermatological condition, including psoriasis, eczema and lichen sclerosis, most cases are idiopathic.

Pruritus ani is a term of Latin, which means itchy anus. Pruritus ani is a symptom, a Medline MeSH searchable diagnosis, and is also used to designate a specific condition of multiple aetiologies recognized since antiguity.

The term pruritus when used alone simply means itchy: there is no distinction between pruritus and itch (an unpleasant sensation that provokes the desire to scratch). To avoid confusion in this entry, the syndrome will always be referred to as pruritus ani.

Fungal, bacterial or parasitic infections such as pinworm and pediculosis are rare causes (except in children). Contributing factors may include excessive attempts at hygiene causing local irritation, loose stools, prolapsing haemorrhoids, and the frequent use of anorectal creams and ointments which may lead to perianal wetness with maceration of the skin and contact dermatitis. An itch and scratch cycle is then set up which can be very difficult to break.

Pruritus ani is classified as either primary or secondary. The primary form is the classic syndrome of idiopathic pruritus ani, whereas the secondary form implies an identifiable cause or a specific diagnosis.

Physiological Considerations

There are different types of itch which may respond to different forms or modalities of therapy:

1. pruritoceptive (C-fiber mediated),
2. neuropathic (e.g., Post-zoster), and
3. central or neurogenic.

Itch is a surface phenomenon mediated by unmyelinated C-fibers in the epidermis and subepidermis, these fibers may have a lower threshold for stimulation when reporting itch than when reporting pain. Itch receptors may be located more superficially than those dedicated to pain. Because receptors are superficial, innocuous, nondamaging stimuli such as wearing long fibered fabric (i.e., wool) or other minor mechanical stimuli may induce itching.

In addition to histamine, kallikrein, bradykinin, papain, and trypsin experimentally produce itching, but these substances do not respond to blockade with classic histamine antagonists such as diphenhydramine; hence, topical antithistamines are not always effective against itching. Recent studies suggest that gastrin releasing peptide receptors may, at least in part, mediate itch. This finding could explain some of the impact of H2 blockers (nonclassic antihistamines) on itch.

The phenomenon of hyperesthesia with chronic pain may have a parallel with itching; just as minimal stimulation of the skin may induce itching, scratching with subsequent injury may produce an expanding area of itchy skin. Scratching produces inadequate feedback to inhibit itching, more scratching occurs with cutaneous injury, which provides an additional stimulus to scratch in a self-defeating loop.

Substituting heat, cold, painful, or stinging stimulus for the itch by applying alcohol or pepper extract (capsaicin) may provoke an inhibitory feedback not supplied by scratching alone and lead to inhibition of the urge to scratch. Cowhage induced itching does not produce an inflammatory reaction and is mediated by different neurons than histamine-induced itching and may be the type of itching blocked by use of capsaicin.

Antidepressant medications (such as paroxetine) and anticonvulsants (gabapentin) have antipruritic effects at the central nervous system level though mechanisms of action may not be clear. Itching associated with healing probably results from the combination of histamine release, release of other kinins and prostaglandins involved in the inflammatory phase of healing, and regeneration of nerves which may be thinly myelinated in immature scars. Antihistamines, topical anti-inflammatory agents (steroids), topical anesthetics, moisturization, petrolatum, and aloe preparations (prostaglandia inhibitors) all have beneficial effects on the itching of healing wounds.

Aetiology of Pruritus

Because pruritus is a symptom that may have protean causes, it is useful to consider diagnoses which have been associated with pruritus ani. Table X1 is a list of diagnoses and conditions modified from Stamos and Hicks. Specific causes are considered below.

1. Localized Itch Syndromes

Notalgia paresthetica is a defined syndrome with itching or pain of the upper mid-back to either side of the scapular region. This has been attributed to spinal nerve damage or entrapment, although an inherited form has been described. Skin biopsies have shown increases in sensory innervations in the area of nostalgia paresthetica; other changes are seen in the biopsy which could be attributed to repeated rubbing and scratching.

Treatment by application of pepper cream (capsaicin 0.025%) has been effective. Such treatment may exacerbate the symptoms during the first week of application, but thereafter both the symptoms and the side effects of the treatment subside. Topical application of eutectic mixture of local anesthetic (EMLA) (2.5% lignocaine + 2.5% prilocaine), a topical anesthetic cream has also been effective. Dermatographism has been reported as a cause of anogenital pruritus. It is not unreasonable to propose that one aetiology of the idiopathic forms of pruritus ani may be related to dermatographism or nostalgia paresthetica, and that the skin changes are the sole result of skin trauma. The effectiveness of the anal tattooing procedures, may lend some insight into the aetiologies of idiopathic pruritus ani.

2. Fecal Contamination

Systematic, rigorous studies of anal pruritus are rare, but good evidence supports fecal contamination as one cause of symptoms. Caplan performed a study in 27 Caucasian men on whom fresh autologous feces was applied as a patch test both perianally and on the inner arm, and perianal skin was also cultured for fungi.

In ten control subjects fecal samples were collected and while the skin was spatulated, feces were not applied. The patch tested subjects (n=27) had several pH-adjusted samples applied to the skin in addition to the unadulterated samples; 12 of the 27 had a history of pruritus ani prior to being enrolled in this study. pH of the perianal skin varied from 5.0 to 7.0 and was not different between the two groups.

Five of twelve pruritus subjects (42%) grew yeast (non Candida albicans) but no dermatophytes, while 4 of 15 nonpruritus subjects (27%) grew C. albicans (3) or Geotrichum. Twelve of 27 (44%) with feces applied to the skin developed symptoms from the feces. Four of 12 (33%) of the prurtus group developed symptoms, 8 of 15 (53%) of the nonpruritus group developed symptoms, while none of the control group developed symptoms. Symptoms occurred within 1–6 h in all but one subject and were relieved by washing the skin. Only one of the 27 subjects reacted to feces on the arms patch test, suggesting that the skin in different locations reacts differently. The prompt appearance of symptoms and relief with cleansing was felt to indicate an irritant effect rather than an allergic effect.

Smith et al., in a rigorous study of 75 patients with pruritus, found that half of their patients had poorly formed stools and 41% of their patients complained of soiling from daily to several times a week. Seepage of liquid and mucous was felt to be an important factor in the aetiology of the symptoms. Coffee consumption lowered anal resting pressure in 8 of 11 patients.

Allan et al. showed that leakage during a saline infusion test occurred sooner in patients with pruritus ani than in non-pruritic controls (median leak point 600 ml vs. 1,300 ml in controls). This is consistent with findings by Farouk et al. and Eyers and Thompson who both found that the anal inhibitory reflex was more pronounced in patients with pruritus ani. Rectal distension makes these patients more prone to leak and soil, because the fall in anal pressure from baseline is greater in patients with pruritus ani.

3. Viral Infection

Condylomata accuminata is a common cause of itching, but the diagnosis is generally easy to recognize and should not be confused with idiopathic pruritus ani. Herpes syndromes are usually accompanied by pain or burning sensation rather than itching and the clinical course is accompanied by a characteristic eruption consisting of red macules, which progress to vesicles that rupture, ulcerate, and may become secondarily infected. Culture or biopsy shows specific diagnostic findings. Likewise, molluscum contagiosum produces characteristic lesions, palpable papules, 2–5 mm diameter, with central umbilication, flesh colored to slightly pink and usually clustered. HIV-associated lesions are rarely associated with chronic itching except for secondary fungal infections.

4. Fungal Infection

Smith et al. found no instances of fungal infection in their investigation of pruritus ani where each of 75 patients had scrapings and fungus cultures. In contrast, Dodi et al. found C. albicans had no relationship to pruritus (culture positive in 23% of control subjects, 26% of those with pruritus, and 28% of those without pruritus), but ten patients who cultured dermatophytes all had itching. None of these patients had exposure to steroids or antibiotics. Their conclusion was that C. albicans was saprophytic in the absence of steroids, but that dermatophytes were always pathogenic. Prolonged courses of steroids are said to enhance pathogenicity of C. albicans and to mask Candida infection.

Verbov found 7 of 47 (15%) patients with pruritus ani had itching which was attributable to Candida. In a review of his dermatologic practice (3,000) patients surveyed on the basis of their primary complaint), Pirone et al. reported that surgical treatment of anal disorders (haemorrhoids, fissure, spasm, mucosal prolapsed) eliminated Canida and dermatphyte infections in all but 3 of 23 patients who were culture positive and symptomatic with itching before surgery. Two of these three patients responded to antifungal treatment, but the third patient continued to itch.

In another study of 200 patients evaluated by colorectal surgeons and dermatologists, thrush was found in 28 (14%), only one of whom was diabetic. Fourteen patients had Candida infection after local steroid therapy, and six occurred after a course of systemic antibiotics. Only one case of dermatophyte infection was found.

Perianal dermatophyte infection, all Trichophyton rubrum, was reported to be infrequent by Alexander (four of nearly 300 cases). Topical steroids may render direct scrapings negative for hyphae, though most frequently they facilitate dermatophyte growth.

5. Bacterial Infection

Several nonsexually transmitted bacterial infections are reported to cause longstanding pruritus. Weismann et al. reported that 19 patients (16 males and 3 females) with pruritus of duration 1–20 years had beta hemolytic streptococci cultured (four also had Staphylococcus aureus) from the perianal area but not from nasal or throat swabs.

Treatment with various regimen resulted in cure of 42% and amelioration of symptoms in the rest. Erythrasma was reported to cause pruritus in 15 of 81 (18%) patients who failed to respond to routine treatment. Wood’s light fluorescence (coral pink or red in the case of Corynebacterium minutissimum) was the most reliable diagnostic test, being positive in every case, whereas cultures for C. minutissimum were positive in only 4 of 15 cases. Groin, thighs, and toes were also involved in every case and cure was achieved in all patients with erythromycin.

Smith et al. found erythrasma in only one of their 75 patients, each of whom had Wood’s light examination. C. minutissimum is probably present as normal skin flora, but moisture, diabetes, and obesity predispose to pathogenicity, which usually develops in the body folds (axillae, groin, intergluteal, inflammatory) and toe webs.

The St. Mark’s Hospital series found erythrasma in 16% of 200 cases, but in 27% of the patients who had been symptomatic for over 5 years C. minutissimum was identified. These patients had disease in more than one site, in common with other quoted series.

S. aureus has been anecdotally implicated as a cause of treatable pruritus. Intertrigo was reported in 27% of the St. Mark’s Hospital series and was highly treatable with topical agents.

Treatment of Pruritus Ani

A general strategy is presented in Table X2. Directed treatment for a specific, curable diagnosis is the ideal, and diagnostic efforts should be directed to avoid overlooking curable disease.

Many investigators have alluded to the importance of controlling seepage and fecal contamination of the skin. Diet may directly contribute to itching and it is prudent to give patients a list of potential foods implicated in itching for an elimination trial.

Patients with loose stools may benefit from the addition of fiber to absorb moisture and add bulk and improve emptying with defecation. Many patients who have tried fiber without benefit may benefit from judicious use of Immodium^® (Pfizer Inc., New York, NY) to lessen frequency and firm up stools. Questran^® (Bristol-Myers Squibb, Princeton, NJ), in varied doses, has been helpful in the practice to firm loose stools.

Environmental factors should be altered as much as possible with removal of irritants such as soaps, perfumes, dyes in clothes or wiping tissues, alcohol or witch hazel containing agents, moisture. Dove^® (Unilever, London, UK) is free of conventional soap and is the preferred bathing agent. Bidets are not common in the USA, but detachable shower heads are common and inexpensive and when equipped with long tubing and handle may be a useful item for cleansing the perianal skin and anal canal and eliminating soap residues by flushing with water in the squatting position. Subsequent drying with a hair dryer can eliminate moisture, and application of an athlete’s foot powder or barrier cream will lubricate and prevent maceration of the skin in the cleft and anal canal. Zeasorb^® (Stiefel Laboratories, Research Triangle Park, NC) is an alternate lubricating, drying agent in powder form.

Cornstarch is to be avoided because it is culture medium for yeast. Cornmeal agar is used to identify different species of yeast in the laboratory. Dilute white vinegar (one tablespoon in an 8 ounce glass of water) on a cotton ball is a cheap effective nonsoapy cleanser that can be kept at the toilet when bathing is not handy.

Burrow’s solution, 1:40 (Domeboro^® tablet one in 12 onces water or one in six ounces for 1:20) is another nonirritating cleanser that can be kept refridgerated in a plastic squeeze bottle and used in lieu of soap or plain water. Burrow’s^® may be used as an antibacterial soak for 5–15 min and then dried. Balneol^® (Alaven Pharmaceutical, Marietta, GA) is a commercially available mineral oil-based preparation that can be kept in a pocket and squeezed onto toilet paper to make a soothing cleansing agent when using public facilities.

Breaks in the skin caused by scratching or over vigorous cleansing efforts must be avoided, so an attempt to control symptoms with application of topical anesthetics, menthol, phenol, camphor, or a combination of ingredients may be appropriate. These agents may be used on combination with topical steroids, topical antifungal agents and topical antibacterials.

Doxepin (Sinequan^®, Pfizer, Inc., New York, NY – orally) is available as an effective antihistamine (Zonalon^®, DPT Laboratories, Ltd. San Antonio, TX), but orally it is 1,000 times more potent than diphenhydramine (Benadryl^®, McNEIL-PPC, Inc., Skillman, NJ) for elimination of itching and may be a useful adjunct at bed time to avoid nocturnal scratching. Doxepin possesses both anti-H1 and anti-H2 activity, a fact which may explain some of the enhanced effectiveness.

Cimetidine, in 1 g/day dose, has been reported to eliminate itching induced by lymphoma and polycythemia vera, and oral gabapentin and paroxetine have been reported to have centrally acting antipruritic effects.

Nocturnal scratching, of which the patient may be unaware, is probably a significant contributing factor in most cases of idiopathic pruritus ani. Patients who are awakened by the urge to scratch should be instructed to gently cleanse the area to eliminate any fecal seepage and reapply their steroid or barrier cream whichever is in effect at the time but not to scratch. topical capsaicin may be useful in breaking the overwhelming urge to scratch by substituting a more powerful temporary burning stiumulus.

No data exists on the influence of clothes or other formites on pruritus, but from a practical standpoint, loose underwear that allows air circulation and promotes dryness makes sense. fresh clothes laundered without perfume or fabric softeners, perhaps with the addition of a small amount of chlorine bleach to secure lowered bacterial counts should be used daily.

Patients who come to the office with acute moderate to severe changes of the skin may be treated by application of Berwick’s dye (combination of gentian violet and brilliant green) which has alcohol content and stings, often relieving the itch. The dye is dried with compressed air or a hair dryer. Benzoin tincture is applied over top of this as a barrier and dried similarly. This preparation will stay in place for several days if only water is used to cleanse and gives excellent temporary relief of symptoms and allows reepithelialization of broken skin. Berwick’s is suitable as an office-applied remedy but is generally not for home application.

Patients who have mild to moderate symptoms with minimal skin changes will often respond to topical 1% hydrocortisone cream which can be combined with menthol, 0.5–1.0%, and topical antibiotics (gentamicin, clindamycin, or bacitracin) or antifungals (clotrimazole, nystatin).

This preparation is applied at night and in the morning after bathing, being used daily until symptoms subside. Thereupon a tapering regimen is instituted, ending with substitution of a barrier cream such as Calmoseptine^® (Calmoseptine, Inc., Huntington Beach, CA) to keep the skin covered.

Elimination of the steroids and substitution of an innocuous agent to maintain attention to the hygiene is an important goal. Patients with thickened skin and chronic moderate or severe changes should be approached with higher intensity therapy, with a medium or high potency steroid for a limited, defined period of time (Table X3).

When prescribing topical steroids, the use of brand name products allows control of both the delivery vehicle and specific active steroid salt (Table X3). The choice of solution, lotion, cream, or ointment is of major therapeutic importance. For instance, betamethasone as Diprolene^® (Schering Laboratories, Kenilworth, NJ) is over 1,000 times more potent than Valisone^® (Schering Laboratories, Kenilworth, NJ) cream, with Valisone^® (Schering Laboratories, Kenilworth, NJ) ointment somewhere in between.

These differences can lead to a great deal of confusion when prescribing by generic name without spelling out every tiny detail. It is important to emphasize to patients that a high potency steroid should be used for a limited period of time, generally 4–8 weeks. When normalization of the skin has been achieved, patients are switched to a mild steroid such as hydrocortisone 1% or Locoid^® (Ferndale Laboratories, Inc., Ferndale, MI) 0.1% with tapering frequency of application down to once or twice a week or to total elimination. Patients who have frankly eroded or denuded skin may benefit from topical antibiotics. Silver sulfadiazine cream to which hydrocortisone or triamcinolone and menthol has been added may be soothing and promote regrowth of epidermis over ulcerated areas while suppressing the inflammation that can cause fissuring in the skin.

Skin atrophy is a serious problem with prolonged use of potent steroids, but each of the steroid preparations differs in its tendency to cause trouble. Creams cause comparatively greater atrophy than ointment preparations containing identical ingredients.

Newer, double-ester, nonfluorinated steroids may prove to be less atrophogenic than the older preparation, but the FDA required informational inserts for prednicarbate and mometasone furoate still quote 8 and 6% incidence of mild skin atrophy for these compounds. Macrolide topical immune modulators (tacrolimus and primecrolimus) appear to be free of the problem of skin atrophy, a fact that enhances their appeal for use on the opposed skin of the cleft.

Use of topically applied picolimus and tacrolimus has not been approved for skin diseases other than atopic dermatitis. As such, its use is off-label. Burning sensation after application has been relatively common in my experience, but tends to subside (Table X4). The FDA issued a black box warning regarding risk of lymphoma and skin cancer in 2005, but recent long-term safety data in large cohorts of patients with up to 4 years duration of treatment have not revealed an increase in either skin or internal cancer associated with topical use.

European and US use of these agents topically now approaches 17 years and anecdotally, safety has not appeared as a problem. These compounds may have some intrinsic antifungal activity as well. I (COF) have had limited but very good clinical experience with these compounds. There is currently no published data on topical macrolide use in pruritus ani. Table X5 lists the potential complications of topical steroids, which are not to be taken lightly, and are all the more important as they are preventable complications of treatment.