Balanitis Circumscripta Plasmacellularis 

Updated: Nov 18, 2019
Author: Elizabeth U Rogozinski, MD, MS; Chief Editor: Dirk M Elston, MD 



In 1952, JJ Zoon first recognized balanitis circumscripta plasmacellularis as a chronic, idiopathic, rare, benign penile dermatosis associated with dysfunctional foreskin in uncircumcised males.[1] Balanitis circumscripta plasmacellularis is also known as Zoon balanitis and plasma cell balanitis. The differential can be broad and includes a variety of sexually transmitted infections, drug eruption, psoriasis, and others.[2] It is important to distinguish balanitis circumscripta plasmacellularis, a benign condition, from the neoplastic process erythroplasia of Queyrat, an additional differential diagnosis that often leads to the biopsy of plasma cell balanitis. While plasma cell balanitis is considered a benign entity, a small number of case reports suggest that it may be a premalignant condition, but further study is required.[3]

Immunohistologically, IgE and IgG are found to be major immunoglobulin classes in the plasma cellular infiltrate. IgM- or IgA-positive cells are either absent or present in very low numbers. Although a specific allergen has not been identified, the findings suggest that this condition could be related to immediate hypersensitivity.[4] The kappa-to-lambda ratio is variable. This suggests a nonspecific polyclonal stimulation of B cells as the basis of balanitis circumscripta plasmacellularis (plasma cell balanitis), which might be caused by a persistent infection, although this theory has yet to be proven in the literature.

While the etiology remains unclear, it is believed that plasma cell balanitis is caused by dysfunctional foreskin, as it typically does not occur in circumcised men, with few exceptions. The dysfunctional foreskin is thought to cause retention of urine and smegma, trap heat and moisture, and predispose to chronic infection leading to irritation.[2]

Other related Medscape Drugs & Diseases articles include Bowen Disease, Lichen Sclerosus et Atrophicus, Erythroplasia of Queyrat (Bowen Disease of the Glans Penis), Balanitis Xerotica Obliterans, and Balanitis in Emergency Medicine.


The etiology of balanitis circumscripta plasmacellularis (plasma cell balanitis) is unknown. It is important to note that all confirmed cases have been in uncircumcised males. It has been proposed that friction, trauma, heat, poor hygiene, chronic infection with Mycobacterium smegmatis, a reactive response to an unknown exogenous or infectious agent, an immediate hypersensitivity response mediated by IgE class antibodies, and hypospadias may be predisposing or inciting agents. No evidence suggests human papillomavirus infection in plasma cell balanitis.[5] A 2019 case-control study showed an association with smoking and poor hygiene in patients with plasma cell balanitis.[6] Numerous authors also attribute poor hygiene to the development of plasma cell balanitis.



Balanitis circumscripta plasmacellularis (plasma cell balanitis) is an uncommon entity, but it is likely underreported owing to the lack of symptoms and hesitancy to perform a biopsy on the involved region. Mallon et al studied 357 male referral patients with genital skin disease over a 120-day period.[7] Plasma cell balanitis occurred in 27 patients (~7.6%). More patients had squamous cell carcinoma, bowenoid papulosis, and Bowen disease. They noted that every patient with plasma cell balanitis, bowenoid papulosis, and nonspecific balanoposthitis had not been circumcised. Pearce and Fernando evaluated 226 patients over a 3-year period.[8] Plasma cell balanitis occurred in 26 patients (~10%). A case of plasma cell balanitis has been noted in Cotonous (Benin) in an HIV-positive man who was circumcised.[9]


Balanitis circumscripta plasmacellularis (plasma cell balanitis) affects males. Analogous lesions sharing both clinical and histologic features of balanitis circumscripta plasmacellularis (plasma cell balanitis) have been reported in women as vulvitis circumscripta plasmacellularis.


Balanitis circumscripta plasmacellularis (plasma cell balanitis) is most common in men of middle age or older, with cases reported in patients aged 20-88 years. In a 2018 report, three infants were diagnosed with clinical and dermoscopic findings consistent with plasma cell balanitis and responded to treatment consistent with the diagnosis.[10]


The prognosis is excellent if appropriate treatment is rendered.

Patient Education

For patient education resources, visit the Men's Health Center. Also, see the patient education article Foreskin Problems.




The patient, an uncircumcised male of middle age or older, usually presents with a characteristic lesion of the glans penis or prepuce, present for an average of 1-2 years before diagnosis. Symptoms are minimal, but patients may report mild pruritus or tenderness. Some patients present for evaluation because of cosmetic concerns or anxiety. Bloodstaining of the underclothes for 5 months prior to presentation has been reported in a patient with balanitis circumscripta plasmacellularis (plasma cell balanitis). In 2007, Toker et al reported on plasma cell balanitis in a circumcised man, although the study hypothesized that the initial circumcision may have been inadequately performed, supporting the etiology of a dysfunctional foreskin.[11]

Erythroplasia of Queyrat (squamous cell carcinoma in situ) of the glans penis on a background of Zoon plasma cell balanitis has been noted and can complicate the diagnosis and necessitating biopsy.[12, 13]

Physical Examination

The balanitis circumscripta plasmacellularis (plasma cell balanitis) lesion is usually a solitary, shiny, red-to-orange patch or plaque of the glans or prepuce of an uncircumcised male. The lesions may exhibit a yellowish hue with pinpoint purpuric "cayenne pepper" spotting. Erosive and vegetative variants have been reported. Bowen disease of the glans penis (erythroplasia of Queyrat) has been reported in association with plasma cell balanitis. Additionally, it is very difficult to distinguish this entity from erythroplasia of Queyrat clinically; thus, attention must be given to possible neoplastic associations with this condition and a biopsy should be considered. Plasma cell balanitis is most common on the penis in men,[14] and, in women, when it is on the vulva, it is termed vulvitis circumscripta plasmacellularis.[15]

Kumar et al studied 112 persons with a clinical diagnosis of plasma cell balanitis ranging in age from 24-70 years.[16] Most had been symptomatic for more than 12 months. Plaques manifested on the prepuce and glans in 58.92% of patients, in the prepuce only in 23.21% of patients, and on the glans only in 17.85% patients.



Diagnostic Considerations

Other considerations include the following:

  • Erosive lichen planus [17, 18]
  • Erosive balanitis
  • Solitary plasmocytoma
  • Malignant plasma cell tumors in HIV-infected patients [19]
  • Syphilis: In 2007, Babu et al noted primary syphilis presenting as balanitis. [20] Others have also noted primary syphilis being on the differential diagnosis of balanitis circumscripta plasmacellularis. [21]

Differential Diagnoses



Approach Considerations

Clinical criteria for diagnosing balanitis circumscripta plasmacellularis (plasma cell balanitis) exist and include the clinical presentation, absence/ruling-out of other diagnoses, and poor response to treatment based on the following[16] :

  • Clinical presentation: Shiny, erythematous patch or plaque on the glans, prepuce, or both for greater than 3 months duration
  • Absence of other diagnoses: Lesions suggestive of lichen planus or psoriasis elsewhere on the body, concurrent infections (herpes simplex virus, Candida, syphilis, bacteria)
  • Poor response to at least a 4-week trial of topical treatments

Laboratory Studies

The diagnosis of balanitis circumscripta plasmacellularis (plasma cell balanitis) is confirmed by distinctive histologic findings after skin biopsy.

Imaging Studies

Reflectance confocal microscopy

A 2013 study assessed the possibility of using reflectance confocal microscopy (RCM), a tool used to perform in vivo imaging, to help differentiate balanitis and carcinoma in situ (CIS) instead of using the standard of care, which is biopsy.[22] Findings used in the assessment were histologic, clinical, and RCM data. Outcome measures were overall death, disease-specific death, nodal metastasis, and local recurrence. Results indicated that RCM findings were effective in differentiating balanitis and CIS, suggesting a possible role for avoiding biopsy in the delicate area.[22] Features suggestive of a benign, inflammatory conditions like balanitis are a nucleated honeycomb pattern and vermicular vessels. CIS on RCM shows an atypical honeycomb pattern, disarranged epidermal pattern, and round, nucleated cells.[22]


Dermoscopic features can provide helpful clues in determining the diagnosis of plasma cell balanitis. Two major features exist: (1) focal or diffuse, orange-yellow structureless regions and (2) focused curved vessels. The prior represents hemosiderin deposition and the latter represents vascular dilatation or proliferation.[23] The vessels are the paramount feature to differentiate plasma cell balanitis from other differential diagnoses. Erythroplasia of Queyrat may have scattered, glomerular vessels. Psoriasis has regular dotted vessels. Nonspecific balanitis often has linear, irregular, unfocused vessels.[23]


Skin biopsy may be necessary for histologic studies.

Histologic Findings

Skin biopsy of the balanitis circumscripta plasmacellularis (plasma cell balanitis) lesion reveals very distinct changes in the epidermis and dermis.

Epidermal findings include early and late changes. Initially, there is epidermal thickening, acanthosis, and parakeratosis at the earliest stages. At the later stages of the lesion, when this entity most often undergoes biopsy, there is epidermal thinning with effacement of the rete ridges. This atrophy may be significant enough to reveal erosions or ulceration of the epidermis, often with scattered neutrophils. Diamond-shaped or lozenge keratinocytes are common, identified as elongated keratinocytes in the lower half of the stratum spinosum, parallel to the skin surface. There is also uniform spongiosis, known as "watery spongiosis." Dyskeratotic keratinocytes are not uncommon.

Dermal findings include a dense, bandlike subepidermal or lichenoid infiltrate with a predominance of plasma cells in the papillary dermis. Vascular dilatation and proliferation with erythrocyte extravasation and hemosiderin deposits with siderophages are noted frequently.

Alessi et al analyzed this condition and found that a small group of previously unclassified cases showed common clinical and histopathological features.[24] All of the patients were uncircumcised, and all had long-standing asymptomatic erythematous plaques on the balanopreputial sac. No correlation with sexual intercourse was reported. Histologically, all the specimens showed a thinned and spongiotic epithelium, a bandlike infiltrate of lymphocytes, and histiocytes. A variable number of plasma cells were present in the upper part of the submucosa. The authors concluded that these cases fell within a spectrum of inflammatory noncicatricial disorders, ranging from almost pure lymphohistiocytic forms to forms that fulfill all criteria for balanitis circumscripta plasmacellularis. They proposed the term idiopathic inflammatory noncicatricial balanoposthitis.

Weyers et al studied 45 cases of plasma cell balanitis clinically and histopathologically.[25] They noted that slight epidermal acanthosis and parakeratosis and a patchy lichenoid infiltrate of lymphocytes and some plasma cells were present in early lesions. They reported epidermal atrophy and erosions, a scattering of neutrophils in the upper epidermis, scant spongiosis, red blood cell extravasation, and a denser infiltrate with many plasma cells as late findings. Additional late changes included subepidermal clefts, ulceration, superficial dermal marked fibrosis, and a marked increase of siderophages. These findings suggest that plasma cell balanitis results from irritation or mild trauma involving scantly keratinized skin in a moist environment. Plasma cell balanitis may be found superimposed on other types of cutaneous pathology, and that can alter such histopathology.[25]

Kumar et al described four major histological features, which included (1) epidermal edema; (2) a dense upper dermal band of chronic inflammatory cells, including many plasma cells; (3) dilated capillaries and extravasated red blood cells; and (4) hemosiderin deposition.[16]

In 2010, at the University of Virginia,[26] 28 cases of Zoon-like lesions, 22 cases of lichen planus, 8 cases of plasmacytoma, and 2 cases of syphilis were reviewed. The authors tabulated 24 histologic data points including 12 epidermal and 12 dermal criteria. In Zoon-like lesions, histopathologic findings, regardless of location, included superficial cutaneous erosions and basal vacuolar alteration. Epidermal lozenge-shaped keratinocytes with dense dermal inflammatory infiltrate composed predominantly of dermal plasma cells, with scattered neutrophils and lymphocytes and upper dermal fibrosis, were often seen as well. The authors suggested the generic term idiopathic lymphoplasmacellular mucositis-dermatitis be considered to cover the lymphoplasmacellular infiltrates in the skin and mucosal surfaces.

See the image below.

Plasmacytosis mucosae of balanitis circumscripta p Plasmacytosis mucosae of balanitis circumscripta plasmacellularis (plasma cell balanitis or Zoon balanitis. Hematoxylin and eosin stain. Courtesy of Nephron, via Wikimedia Commons.


Medical Care

The first step in management should focus on good hygiene.[27]  This includes regular retraction of the foreskin and gentle cleansing of the entirety of the penis.

Several classes of medications shown to be effective in balanitis circumscripta plasmacellularis (plasma cell balanitis): topical calcineurin inhibitors (tacrolimus and pimecrolimus), topical steroids, topical imiquimod, and topical mupirocin.

Topical tacrolimus 0.03-0.1% ointment twice daily has been reported to be useful for plasma cell balanitis in multiple studies.[28, 29, 30] In 2008, Virgili et al reported in a comparative analysis of subjective, objective, and histopathological data that topical tacrolimus was less effective in treating plasma cell vulvitis compared with plasma cell balanitis in men.[31]

Bardazzi et al evaluated pimecrolimus 1% cream twice daily for treating resistant plasma cell balanitis in two patients.[32] One patient had complete regression of the lesion after 2 months of therapy, and the other had great improvement of the lesion but a hyperpigmented patch persisted on the glans. Similarly, Stinco et al in 2009 noted a series of three patients with plasma cell balanitis refractory to several treatments with steroids and antifungals and twice-daily pimecrolimus 1%.[33] Of the three, one had complete resolution, one responded but relapsed after treatment was stopped, and the last had a partial response but stopped treatment because of adverse drug effects.

Topical moderately potent steroids steroids have been effective alone or in combination with topical antibiotics. Tang et al described clinical response within 3-12 weeks with clobetasol butyrate 0.05% cream, nystatin 100,000 units/g, and oxytetracycline 3%.[34] Yoganathan et al described only 50% response to saline compresses with a variety of combination steroid preparations.[35]

Nasca et al described a 43-year-old, uncircumcised, white, diabetic man with a 4-year history of plasma cell balanitis that was unresponsive to topical steroid therapy.[36] He experienced a clinical but not histological cure after 16 weeks of imiquimod 5% three times weekly, with multiple periods without therapy for several days' duration owing to an adverse cutaneous reaction. An additional study showed complete resolution after 12 weeks of imiquimod 5% three times weekly without interruption.[37]

Fusidic acid cream 2% has been reported as effective in disease suppression and curative in some patients.[38] Topical agents including antibacterials, gentian violet, and antifungal agents have been used with only limited success in patients with plasma cell balanitis and are not curative. Intralesional interferon-alfa was found to be helpful in treatment of the vulvar analog of plasma cell balanitis.[39] Griseofulvin therapy and oral tetracycline have been tried without success.

Surgical Care

The treatment of choice for balanitis circumscripta plasmacellularis (plasma cell balanitis) is circumcision, which usually is curative.[40, 41, 42, 43] Patients must be informed that circumcision is the current criterion standard for the treatment of this disorder. The carbon dioxide laser has been used successfully in ablation of plasma cell balanitis lesions.[44] Retamar et al treated five patients with a carbon dioxide laser,[45] and three were free from disease years later. Radiotherapy and electrodesiccation have been used with less than optimal results. Other treatment options include photodynamic therapy[46] and the ablative YAG laser.[47] The 2103 European Guidelines are firm that circumcision is the definitive treatment for plasma cell balanitis.[27] It was also noted again in 2014 that plasma cell balanitis is not an infection.[48]

Palminteri et al noted that in selected cases of benign, premalignant, or malignant penile lesions (including those related to plasma cell balanitis),[49] glans resurfacing or reconstruction can ensure a normal-appearing and functional penis, without jeopardizing cancer control.


Consultation with a urologist may be helpful.



Medication Summary

Topical tacrolimus ointment has been reported to be useful for plasma cell balanitis in multiple studies.[28, 29, 30]

Topical Calcineurin Inhibitors

Class Summary

Topical tacrolimus inhibits calcineurin, which is related to stimulation by interleukin 2 of T cells. As such, it is an anti-inflammatory agent.

Tacrolimus ointment 0.1% or 0.03% (Protopic)

Topical tacrolimus ointment inhibits calcineurin, which is related to stimulation by interleukin 2 of T cells. As such, it is an anti-inflammatory agent.