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Balanitis Circumscripta Plasmacellularis

Editor: Francisco J. Salazar Updated: 8/22/2023 9:04:12 AM


Balanitis circumscripta plasmacellularis, also called Zoon balanitis or plasma cell balanitis, is a chronic, idiopathic, reactive balanoposthitis that occurs in uncircumcised men and is thought to be secondary to a dysfunctional foreskin, characterized by silent symptoms and florid signs.[1] Professor Johannes Jacobus (J.J) Zoon, a Dutch dermatologist, originally described this distinctive benign penile dermatosis in 1952.[2] The dysfunctional foreskin is thought to trap heat, smegma, and moisture, predisposing the person to chronic infection and irritation. This benign condition must be differentiated from other benign conditions (eg, sexually transmitted infections, drug reactions, and other dermatoses), and it must also be discerned from erythroplasia of Queyrat, a neoplastic disease. A similar clinical condition has been described in women, named vulvitis circumscripta plasmacellularis.[3]


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The etiology of balanitis circumscripta plasmacellularis is still unclear. Researchers believe it is due to irritation from the retention of moisture, smegma, and heat in the context of a dysfunctional foreskin, as it typically does not occur in circumcised men. This retention occurs between two desquamative, secretory, hyper-colonized epithelial surfaces under inadequate hygiene conditions and repeated infection.

The 2 main contributing factors are constant exposure to high humidity and chronic irritation.[4][5] This explains why Zoon balanitis lesions go through long remissions after circumcision.[6] The foreskin may be dysfunctional due to several coexisting diseases, including lichen sclerosus, chronic nonspecific inflammation, infection, lichen planus, psoriasis, or eczema.[4][6] Other theories include chronic infection with Mycobacterium smegmatis or human papillomavirus (HPV).[7] These theories have not been validated.[8] 


Balanitis circumscripta plasmacellularis is described as an infrequent entity; however, it is probably underreported and underdiagnosed. Mallon et al reported 27 cases of balanitis circumscripta plasmacellularis among 357 patients with genital disease.[9] Pearce et al reported 26 patients out of 226 penile biopsies (10%) had balanitis circumscripta plasmacellularis, and Kumar et al reported a prevalence of 5.82%.[10][11] The condition can present at any age but is usually seen in older uncircumcised men. Unlike other inflammatory penile dermatoses, it is generally not thought to be a precursor for neoplasia.


Long-lasting erythematous lesions involving the glans or prepuce may be challenging to classify. A biopsy is required to confirm the diagnosis or to rule out other conditions such as erythroplasia of Queyrat, drug eruptions, and psoriasis.

The histopathological changes in balanitis circumscripta plasmacellularis are distinctive and include the presence of epidermal atrophy, lozenge keratinocytes with watery spongiosis, and a dense lichenoid subepidermal infiltrate composed largely of plasma cells. Plasmocytes usually exceed over 50% of all cells.[12] Erythrocyte extravasation and hemosiderin deposition are often noted, corresponding to the "cayenne pepper spots" observed clinically. Other observed histological epidermal features include epidermal thickening, parakeratosis, and acanthosis. These epidermal features progress to epidermal atrophy, spongiosis, and erosions. Late developments include lozenge keratinocytes and subepidermal clefts.[1][13]

Dermal changes include early patchy lichenoid lymphocytic dermal infiltration and some plasma cells in the papillary dermis. This infiltrate is eventually replaced with a dense band of mixed infiltrate comprised of erythrocytes, eosinophils, lymphocytes, neutrophils, and plasma cells, with more than 50% plasmocytes.[1][5] Vascular dilation with a unique characteristic orientation of individual vessels in an oblique or vertical direction is observed.[1][5] In late stages, fibrosis develops in the upper dermis along with plasma cell infiltrates, epidermal atrophy, and subepidermal clefts.[1][5]

The lack of dysplastic epithelial elements easily differentiates balanitis circumscripta plasmacellularis from malignant and premalignant lesions histologically.[1]

History and Physical

Balanitis circumscripta plasmacellularis presents as symmetrical, well-marginated, erythematous, shiny plaques with multiple pinpoint red specks known as "cayenne pepper spots," involving the glans, prepuce, or both. Vegetative, erosive, and multi-lesion variants have also been reported.

The condition is usually asymptomatic, although pruritus or burning may be present. Patients are typically older uncircumcised men. The course tends to be chronic, persisting for months to years, and is generally poorly responsive to standard topical therapy. 


At presentation, lesions typically have been present for over 3 months and are shiny and red. The lesions usually do not respond well to standard topical therapy except as noted below. No evidence of infection should be noted.

A good response to mupirocin 2% ointment has been suggested as a diagnostic aid for balanitis circumscripta plasmacellularis, but the reliability of this clinical response has not been definitively determined or verified.[14] 

Recently, dermoscopic findings in balanitis circumscripta plasmacellularis have been described in 11 patients, which include focused curved vessels (100%) in different shapes, including serpentine (100%), convoluted (45%-50%), and chalice (27.3%-25%).[15] Orange-brownish structureless areas (75%-81%), linear irregular blurry vessels (36.4%-37.5%), and dotted vessels (25%-27.3%) have been described.[15] These findings might assist in the clinical diagnosis of Zoon balanitis, distinguishing it from its primary differential diagnoses, which include:[15]

  • Erythroplasia of Queyrat, which shows scattered glomerular vessels;
  • Psoriasis, which displays regular dotted vessels and seborrheic dermatitis; and 
  • Nonspecific balanoposthitis, which typically demonstrates linear irregular unspecific blurry vessels.

The use of reflectance confocal microscopy in differentiating between balanitis and carcinoma in situ has been evaluated. Balanitis shows a nucleated honeycomb pattern and vermicular vessels, whereas carcinoma in situ shows round, nucleated cells with an atypical honeycomb pattern.[16]

As it may not be possible to diagnose balanitis circumscripta plasmacellularis by clinical examination reliably, a biopsy may be necessary for a definitive diagnosis.

Treatment / Management

First-line therapy continues to be circumcision, the only treatment modality providing long-term, complete remission. Some patients often reject procedures in this sensitive area. Other options include topical steroids or calcineurin inhibitors, mupirocin ointment, photodynamic therapy, or laser ablation, but the disease tends to relapse with any alternative treatments.

Carbon dioxide lasers and erbium:yttrium-aluminum-garnet (Er:YAG) lasers are therapies that have shown good outcomes. Carbon dioxide laser therapy has been successfully used in a defocused or "silk touch" approach where the laser head spins the beam rapidly, exposing each target for less than its thermal relaxation time.[5][17] In one study of 20 patients, Er:YAG lasers were used, focusing mostly on 3 mm.[18] The frequency employed was 8 Hz, and the impulse energy was mostly 800 mJ. In most patients, a complete re-epithelization was achieved within 10 days. During follow-up, lesions were cleared completely at 3 to 30 months.[18] No major complications, including phimosis, were found.[18] Er:YAG laser therapy offers a precise superficial ablation with low thermal injury, low risk of scarring, low pain, and rapid healing.[18](B3)

Photodynamic therapy appears effective but has not yet been well established since it's primarily based on case reports.[19] Nevertheless, it is considered a moderately effective and safe option for Zoon balanitis and has been used in refractory lesions.[19](B3)

Mupirocin 2% ointment is a topical antibiotic for traumatic skin lesions and impetigo. When applied 3 times daily for 6 to 12 weeks, complete resolution of Zoon balanitis was seen in a small number of anecdotal reports.[14][20][21] This could be explained by the possibility that Zoon balanitis is associated with bacterial colonization or super-antigen. A quick response of the lesion to mupirocin ointment therapy may be useful diagnostically as it strongly suggests balanitis circumscripta plasmacellularis and may help differentiate it from erythroplasia of Queyrat.[14] The reliability of this finding is still to be determined and verified.(B3)

Topical calcineurin inhibitors, such as tacrolimus 0.1% and 0.3% and pimecrolimus 0.1%, have been used, with complete remission after 3 to 8 weeks of therapy.[8][22] However, there is concern regarding a possible relationship between topical calcineurin inhibitors and carcinogenesis.[1][23][24] Therefore, the diagnosis should be definitively made by a biopsy to exclude any malignancy before topical calcineurin inhibitors are used.[1](B2)

The use of topical steroids in treating balanitis circumscripta plasmacellularis has been suggested, although little evidence supports their use. Tang et al reported an excellent response to a topical cream made of oxytetracycline 3%, nystatin 100,000 units/g, and clobetasone butyrate 0.05% with a complete clinical resolution observed.[25] Three of 10 patients had recurrences within 3 months after cessation of therapy but responded to a second course of clobetasone butyrate 0.05% cream. A fourth patient had 3 recurrences within 12 months, and each recurrence responded well within a few days of resuming treatment.[25] Another similar study appears to show efficacy, but even taken together, this is insufficient evidence to recommend routine topical steroid therapy for Zoon balanitis.[26](B3)

There are isolated, anecdotal reports of imiquimod 5% cream use, which appears beneficial in balanitis circumscripta plasmacellularis. Imiquimod 5% cream is thought to work by upregulating the cellular immune response. Additional studies are required to determine this treatment's optimal dosing, duration, and long-term effectiveness.[27][28](B3)

Radiation therapy, cryotherapy, superficial electrodesiccation, topical antifungals, and griseofulvin have all been proven ineffective.[1]

Differential Diagnosis

The differential diagnoses include candidiasis, contact dermatitis, fixed drug eruption, Kaposi sarcoma, herpes simplex virus, lichen planus, lichen sclerosus, pemphigus vulgaris, erythroplasia of Queyrat, psoriasis, Reiter disease, secondary syphilis, and squamous cell carcinoma. Coinfection with Candida may occur.


balanitis circumscripta plasmacellularis is considered a benign entity, although isolated cases have been associated with squamous cell carcinoma. In 1999, a case of penile carcinoma in a patient with balanitis circumscripta plasmacellularis was described by Joshi.[29] In 2001, Bunker claimed there were zoonoid changes in clinical and histological features in some cases of lichen sclerosus, lichen planus, Bowenoid papulosis, and penile cancer.[30] These zoonoid changes could suggest that Zoon balanitis might be a premalignant condition. Further studies are necessary to establish this association.


Minimal local complications of balanitis circumscripta plasmacellularis occur other than the development or persistence of localized symptoms such as discomfort, dysuria, or pruritus. The lesion may enlarge or spread over time. The main concern is the possible development of penile carcinoma due to a misdiagnosis. For that reason, it is suggested that follow-up care be instituted for at least 5 years after treatment, especially if a biopsy did not confirm the diagnosis.

Deterrence and Patient Education

Clinicians play a crucial role in educating patients about proper hygiene practices. This includes instructing uncircumcised males on how to maintain good hygiene by regularly cleaning the glans and foreskin. In addition, patients should be educated on the importance of promptly reporting any abnormal lesions or changes in coloration of the glans or foreskin to their physician or advanced practice provider.

Pearls and Other Issues

The presence of balanitis circumscripta plasmacellularis often requires proactive investigation by the clinician. Patients may be unable to retract the foreskin or adequately examine the glans due to body habitus. Consequently, it becomes the clinician's responsibility to assess this region for potential lesions and anomalies diligently. This is particularly crucial given the challenges many patients face in conducting such examinations independently.

Accurate diagnosis of this condition may necessitate a biopsy to establish certainty. While a potential correlation between a swift response to mupirocin ointment and balanitis circumscripta plasmacellularis has been suggested, the reliability of this connection remains unverified.

Enhancing Healthcare Team Outcomes

Patients with lesions on the penis may first present to their primary care provider or internist. Given that many healthcare professionals may not possess specialized knowledge of penile lesions, a prudent approach involves directing the patient to a urologist or dermatologist for a definitive workup. In this context, the primary care provider's primary role revolves around prevention, encompassing patient education concerning appropriate hygiene practices and the identification of penile lesions warranting additional scrutiny.

First-line therapy continues to be circumcision, the only treatment option providing long-term, complete remission. Other options include topical steroids, calcineurin inhibitors, mupirocin, photodynamic therapy, and laser treatment, but the disease tends to relapse with any of these alternatives.

Outcomes for balanitis circumscripta plasmacellularis with proper treatment are excellent, and progression to dermal malignancy is rare.[31]



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