4.3.3 Balanitis

Balanitis is a descriptive term which refers to inflammation of the glans penis and since also the prepuce is often affected, the term balanoposthitis may be used, too. Posthitis refers to inflammation of the prepuce. Balanitis/balanoposthitis has varying aetiologies but the clinical presentation is often similar.

The most common etiology of balanoposthitis is poor hygiene and preputial dysfunction is often a contributing factor. Balanitis/ balanoposthitis is uncommon in circumcised men. Balanitis/balanoposthitis may be caused by irritation, various types of infection or cutaneous autoimmune processes (see Classification below).

The pathophysiology can be irritant, allergic, infectious, autoimmune-mediated or secondary to trauma or malignancy. Many cases of balanoposthitis are ‘intertrigo’ in nature, i.e. inflammation between two adjacent skin layers with bacterial or fungal overgrowth. Also, many skin diseases, such as erythema multiforme and immuno-bullous disorders, may affect the glans penis and genitalia.

Lichen sclerosus is an inflammatory scarring skin condition for which an autoimmune pathogenesis has been postulated. The condition occurs in all ages. It is probably responsible for many cases of phimosis in childhood. Obesity, congenital and acquired anatomical abnormalities (hypospadias), piercing and urological surgery are predisposing factors.

Pre-malignant conditions include penile intraepithelial neoplasias (PeIN): Erythroplasia of Queyrat, Bowen’s disease of the penis and Bowenoid papulosis, which are strongly associated with human papillomavirus infection and/or lichen sclerosus. All may progress to squamous cell carcinoma (SCC), the risk being greatest for Erythroplasia of Queyrat (10-40%). In immunocompromised patients the risk is increased (e.g. HIV infection, immunosuppressive medication).

Notably, SCC presenting as an irregular tender or painful ulcer or nodule may coexist with PeIN and lichen sclerosus.

The symptoms and signs vary according to the aetiology.

Candidal balanoposthitis is a common cause of balanoposthitis in children. It presents as blotchy erythema with small papules (may be eroded), or dry dull red areas with a glazed appearance with soreness and/or itch. In adults, candida may often be secondary to primary inflammatory dermatoses.

Bacterial infection presents as uniform erythema with eventual oedema and transudative or exudative preputial discharge. Anaerobic subpreputial infection typically yields a foul smelling and discharge with preputial oedema and superficial erosions, sometimes accompanied by swollen inguinal lymph nodes.

Irritant / allergic balanitis-balanoposthitis presents as mild erythema with or without pruritus. It may result from irritation such as frequent genital washing with soap, a history of atopy, or exposure to topical agents suggesting delayed hypersensitivity to e.g. common allergens (latex condoms, preservatives and fragrances) found in intimate hygiene products. Seborrheic balanitis presents with mild itch or redness. Fixed drug eruptions appear after using certain medications (tetracyclines, phenolphthalein, phenacetin, NSAIDs, barbiturates or sulfa-drugs) present as round, erythematous patches that turn dark upon healing. Vesicles may occur.

Non- specific balanoposthitis is often chronic with relapses and remissions or persistence and there is no evidence of underlying infective cause.

Lichen sclerosus presents with itching, soreness, splitting, haemorrhagic blisters, dyspareunia, problems with urination including post micturition micro-incontinence or dribbling but may also be asymptomatic. The appearance is lichenoid (lilac) balanoposthitis with white patches on the glans, often with involvement of the prepuce. There may be haemorrhagic vesicles, purpura and rarely blisters and ulceration. Tissue changes such as blunting of the coronal sulcus, destruction of the frenulum, phimosis or ‘waisting’ of the prepuce (constrictive posthitis), and meatal thickening and narrowing, often develop. In contrast with female LSA, perianal disease is rare.

Lichen planus may be asymptomatic but appears purplish with well demarcated plaques on the glans and prepuce and on the shaft of the penis, or may present as erosive or annular lesions on the mucosal surfaces. Mucosal lichen planus is often a chronic condition with remissions and exacerbations.

Psoriasis appearing on the glans presents as red scaly plaques. In the uncircumcised scaling is lost and the patches appear red and glazed. The glazed appearance resembles pre-malignant Bowen’s disease and extramammary Paget’s disease and other inflammatory conditions.

Zoon’s (plasma cell) balanitis is a disease of uncircumcised males aged 40 years or older. It presents with well-circumscribed orange-red glazed areas on the glans and the inside of the foreskin, with multiple pinpoint redder spots - “cayenne pepper spots” in a symmetrical distribution. It is thought to be due to irritation, partially caused by urine, in the context of a ‘dysfunctional prepuce’. It is generally regarded as a benign condition. Zoonoid inflammation (clinically and histologically) frequently complicates other dermatoses, including precancer and cancer, but especially lichen sclerosus.

Circinate balanitis may occur sporadically or as a sign of the post infective Reiter’s disease (triggered by urethritis or enteritis in genetically predisposed individuals). It may also occur in association with HIV infection. It has a typical appearance of greyish white areas on the glans which coalesce to form “geographical” areas with a white margin.

The premalignant lesions locate on the prepuce (45%), glans (38%) or shaft of the penis (3%).

Erythroplasia of Queyrat (PeIN of the balanopreputial epithelium) appears as red, velvety, well- circumscribed area on the glans or visceral prepuce.

Bowen’s disease (PeIN of keratinised, hair-bearing, skin) appears as scaly, discrete, erythematous patches or plaques and bowenoid papulosis, usually in younger patients than the two aforementioned, appears as firm papules to plaques, often grouped and pigmented or erythematous.

The balanitis/balanoposthitis is classified in three main groups based on the etiopathogenesis. Infective balanoposthitis may be caused by viral infections such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), fungal infections including Candida spp, and bacterial infections such as Staphylococcus spp or Streptococcus spp. Sexually transmitted infections such as Trichomonas vaginalis, syphilis and Mycoplasma genitalium may also cause balanoposthitis.

Inflammatory balanoposthitis group includes lichen sclerosus, lichen planus, psoriasis and circinate balanitis, Zoon’s balanitis, eczema (irritant allergic or seborrheic), allergic reactions (including fixed drug eruptions).

Penile intraepithelial neoplasia (PeIN) is a premalignant precursor lesion of invasive penile SCC, a SCC in situ. It includes Bowen’s disease, Bowenoid papulosis and Erythroplasia of Queyrat. In 2016, the World Health Organization (WHO) introduced a new pathological classification of PeIN based on aetiology, with two main pathways for malignant transformation, one named “undifferentiated PeIN” based on HPV-induced carcinogenesis, and the other one “differentiated PeIN” derived from inflammatory lichen sclerosus (LS) and lichen planus (LP). Transformation of a premalignant lesions transform to invasive cancer occurs in 10-30% of cases in PeIN, with the glans and inner prepuce having the highest risk. Penile cancer is rare but aggressive.

Notably, a range of skin diseases may affect the glans penis and genitalia. These include psoriasis, erythema multiforme, immuno-bullous disorders (e.g. pemphigus) and dermatitis artefacta.

The duration of symptoms, clinical appearance, hygiene habits, infectious exposures, potential allergens, and sexual practices need to be clarified before deciding which laboratory examinations to select.

Sub-preputial swab for Candida and bacterial cultures (e.g. Gardnerella vaginalis as a facultative anaerobe), urinalysis for glucose (if candidal infection suspected), Trichomonas vaginalis nucleic acid amplification test (NAAT) if a female partner has an undiagnosed vaginal discharge, full routine screening for other STIs and particularly Chlamydia trachomatis infection / non-specific urethritis if a circinate-type balanitis is present.

If ulceration is present, HSV and Treponema pallidum NAAT and/or examination for spirochaetes (see Syphilis chapter) or syphilis serology with follow up at 3 months need to be performed.

Testing for HLAB27 in case of circinate balanitis. If contact allergy is suspected, patch testing with common allergens.

A penile biopsy should be performed if features are atypical or do not resolve with treatment and if lichen sclerosus or Zoon’s plasma cell balanitis is suspected. Biopsy should be carried out by an experienced practitioner, to obtain a representative sample and to avoid unnecessary risks.

Not needed for infectious balanoposthitis patients.

In lichen sclerosus, histopathology initially shows a thickened epidermis which later becomes atrophic with follicular hyperkeratosis. In dermis, a band of hyalinisation with loss of the elastin fibres, with an underlying perivascular lymphocytic infiltrate is seen. Histological interpretation can be difficult and needs clinico-pathological correlation. A negative biopsy result does not exclude lichen sclerosus, and a positive biopsy does not necessarily exclude PeIN elsewhere.

Lichen planus histology shows irregular saw-toothed acanthosis, increased granular layer and basal cell liquefaction and a band-like dermal lymphocytic infiltrate. Biopsy may be necessary also to distinguish the glazed appearance lesions of penile psoriasis, which can look similar to pre-malignant conditions.

Fixed drug eruptions show hydropic degeneration of the basal layer and epidermal detachment and necrosis with pigmentary incontinence. Circinate balanitis shows spongiform pustules in the upper epidermis, similar to pustular psoriasis.

In Zoon’s plasma cell balanitis, epidermal thickening first occurs and is followed by epidermal atrophy (with erosions). Often mild epidermal oedema is seen with a predominantly plasma cell infiltrate in the dermis with haemosiderin deposition and extravasated red blood cells. However, a Zoonoid inflammation may complicate other dermatoses and ‘positive’ biopsy findings do not confirm the diagnosis or exclude neoplasia.

In PeIN the squamous epithelium shows dysplastic changes. PeINs are morphologically divided into four subgroups: differentiated PeIN (most prevalent), warty-basaloid, basaloid and warty morphology.

Acute balanitis is often caused by infectious agents and most balanitis cases recover with treatment. The majority of patients without an infectious etiology will respond to changes in hygiene and therapy with emollients within one to two weeks. Balanitis relapses are common in men who are not circumcised and if good hygiene, such as cleaning under the foreskin, is not practiced.

Severe balanitis may be complicated by phimosis and urinary retention. Fever and malaise may also occur. If symptoms recur or are refractory to treatment after four weeks, present with pathologic phimosis or urinary obstruction, the patient should be referred to a urologist. Balanitis has often a profound effect on the patient’s sexual life and may cause substantial psychosocial problems.

The diagnostic entity includes the following procedures and examinations: sexual history, medication, presence of phimotic and urethral discharge, urinary retention, clinical appearance of lesions, inguinal lymphadenitis, testicular status. A dermatological examination for skin diseases (like psoriasis) and history of possible contact or drug allergy (e.g. erythema fixum). If contact allergy is suspected, patch testing with common allergens needs to be performed. For laboratory and histopathological examinations, see paragraph “Laboratory” above.

Biopsy may be needed if the diagnosis is uncertain and the condition persists or to exclude a pre- malignant condition. Differential diagnosis includes some common dermatological diseases which may affect the male genitalia, such as psoriasis, lichen planus, erythema multiforme, autoimmune bullous diseases and fixed drug reaction as discussed in this chapter. Notably, syphilis lesions may resemble circinate balanitis. Artefactal dermatitis and traumatic lesions must be differentiated, too.

Predisposing factors for balanoposthitis include poor hygiene, non-retraction of the foreskin, and some medical conditions such as diabetes mellitus. Good personal hygiene, washing daily, avoiding irritants (including soap), and keeping the foreskin retracted until the glans penis is dry (risk of paraphimosis if the prepuce is tight) are recommended. Attention should be paid to risk factors for PeIN, which include lichen planus, inflammation of the glans, genital warts, obesity and immunosuppressive drugs (e.g. organ transplantation).

Treatment depends on the causative agent or condition.

Nonspecific balanoposthitis is the most common etiology in children and is due to poor hygiene. Treatment involves gentle cleaning of the area 2 to 3 times per day by retracting the foreskin and cleaning with gentle use of cotton swab. Forceful prepuce retraction should be avoided in case of phimosis. Symptoms usually resolve within five days.

Candidal balanoposthitis is treated with clotrimazole or miconazole cream, twice a day for 7-14 days. Topical imidazole with 1% hydrocortisone is a choice if marked inflammation is present. Alternatively, fluconazole 150 mg orally can be used if symptoms are severe and nystatin cream if the patient has allergy to imidazoles. Sexual partners should also be tested for candida or offered empiric anti-candidal treatment to reduce the reservoir of infection in the couple.

Aerobic bacterial balanoposthitis is usually treated topically with mupirocin cream twice a day or with clobetasone butyrate /oxytetracycline/ nystatin-cream once or twice daily for 7-10 days. Severe cases may require systemic antibiotics while awaiting culture results: flucloxacillin 500 mg x4/ d or clarithromycin 250 mg twice daily for seven days. Management of anaerobic subpreputial infection includes improved genital hygiene, topical or oral metronidazole 400-500 mg twice daily for one week. Alternatively, co- amoxiclav 375 mg three times daily for one week or clindamycin cream twice daily until resolved.

Balanoposthitis caused by HSV, Trichomonas vaginalis, Mycoplasma genitalium or syphilis is treated as per specific guidelines for these diseases.

Irritant / allergic balanitis-balanoposthitis is treated by the avoidance of precipitants like soaps, use of low-allergy products, emollients (used as a soap substitute), hydrocortisone once or twice daily until resolution of symptoms. In florid cases more potent topical steroids, combined with antifungals and/or antibiotics, or calcineurin inhibitors may be required. Follow up is not required, although recurrencies are common. Potential allergens such as latex condom use and lubricants, should be investigated and avoided.

Fixed drug eruptions are treated symptomatically with mild to moderate steroid creams, since the lesions will heal without treatment after discontinuation of the culprit drug. However, the lesions return on the same location if the culprit medication is resumed.

Balanitis due to seborrheic dermatitis is treated with topical antifungal cream with a mild to moderate steroid. Psoriasis on the penis can be treated with moderate potency topical steroids (+/- antibiotic and antifungal), emollients, calcipotriol or calcitriol (applied twice daily). Circinate balanitis is treated similarly and any underlying infection must be treated, too.

Lichen sclerosus is managed by soap-free washing, avoidance of contact with urine, barrier preparations, weight loss and removal of any genital jewellery. Topically, ultrapotent topical steroids (e.g. clobetasol proprionate) is applied twice daily for a month, then ceased and replaced with a barrier preparation. Intermittent use to maintain remission is not encouraged. Secondary bacterial or candidal infection should be treated. Alternatively, topical calcineurin inhibitors (e.g. pimecrolimus) may be used. Circumcision is indicated if topical treatment fails. Follow up is advisable, since there is risk of recurrence, urethral disease or neoplastic change.

Lichen planus may affect the genital area in addition to the skin and oral mucous membranes. Certain drugs, most frequently ACE-inhibitors, beta blockers, NSAIDs and thiazide diuretics, and biologics may cause lichen planus like eruptions. For the treatment of lichen planus, see the corresponding chapter.

Zoon’s (plasma cell) balanitis, regarded as a benign condition, is thought to be due to irritation, partially caused by urine, in the context of a ‘dysfunctional prepuce’. In therapy, good hygiene, management of underlying dermatoses, topical steroid creams and antibacterial creams (e.g. mupirocin) applied twice daily are used. Alternative topical treatments include calcineurin inhibitors (pimecrolimus twice daily, not for continuous use) and imiquimod 5% cream. Laser ablation may be used to treat individual lesions and circumcision is an alternative for recalcitrant lesions.

Premalignant penile lesions, PeIN, should be referred to specialists in dermatology and urology/ andrology. A combined, sequential approach is often needed, taking into account age, circumcision status, site/sites, comorbidities, concomitant immunosuppression and the pathogenesis (HPV and/or lichen sclerosus) and histology (differentiated or undifferentiated type). For topical therapy imiquimod 5%, fluorouracil cream 5%, fluorouracil 0.5% / salicylic acid 10% combination or podophyllotoxin 0.5% are alternatives. Local surgical excision (usually adequate and effective), cryotherapy, photodynamic therapy or laser treatment are often needed, too. Circumcision is used for balanopreputial disease, especially for uncircumcised high-risk patients (HIV, transplant recipient etc.) to avoid recurrence. Additionally, polyvalent HPV vaccination and smoking cessation are recommended. Follow up is mandatory because of the risks of field change and recurrence (up to one third of patients may harbour microinvasive disease), except for circumcised patients with Bowenoid papulosis or PeIN confined to the prepuce.

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