Penile Pemphigus FREE

PEMPHIGUS VULGARIS (PV) is an autoimmune mucocutaneous blistering disease.¹ Most patients have mucosal involvement during the course of the disease.¹ The mucosa of the oral cavity is most frequently involved. Involvement of the conjunctiva, nasal mucosa, pharynx, larynx, epiglottis, esophagus, vagina, and anal canal has been reported.¹ There are few reports^{2 - 6} documenting the involvement of the penile skin.

This report describes the involvement of penile skin in patients with PV and provides a long-term follow-up.

Twelve patients with PV who had penile involvement are described. This information was collected from their medical records and by direct personal interviews and physical examination. The diagnosis of PV was established based on histological features and confirmed by direct immunofluorescence.¹ Titers of pemphigus antibody were determined by indirect immunofluorescence using monkey esophagus as substrate.¹

The following information was noted for each patient: (1) the age at onset of PV, (2) the clinical distribution of disease as percentage of body surface area, (3) the characterization and distribution of penile erosions (patients were examined for involvement of the urethral mucosa), (4) the duration of penile erosions, (5) the time for resolution of penile erosions, (6) the total length of follow-up since the onset of PV, and (7) the presence of sequelae secondary to the involvement of penile erosions. The patients were advised to refrain from sexual activity and from allowing water from showers to directly impact penile skin.

For each patient, a urinalysis and a urine culture were done. In addition, a culture was taken from the involved penile skin for bacteria, viruses, and fungi.

The systemic treatment given to each patient was noted. The doses of prednisone and immunosuppressive agents were those used in conventional therapy of PV.⁷

The following topical therapy was used. A small towel (washcloth) or gauze wrap was soaked in a 1:40 dilution of Burow solution.⁸ It was then squeezed, and only a single layer was wrapped around the sites of involvement.⁸ Bundling or multiple wrappings were avoided. The moist cloth was left in contact with affected skin for 7 to 10 minutes.⁸ Patients were advised to wait 5 to 7 minutes and then apply a topical corticosteroid cream of mild to moderate potency and avoid ointments and high-potency topical corticosteroid preparations.⁸ These corticosteroid creams included 2.5% hydrocortisone or 0.25% triamcinolone creams. Patients were advised to perform this topical care 3 times daily. The frequency of topical care was reduced to twice daily as healing progressed, and then reduced to once daily until healing or reepithelialization was complete. Patients with extensive skin involvement were advised to soak in a bathtub and underwent topical therapy as previously described.⁸ Patients who had limited skin disease and took showers were advised not to allow the shower stream to impact the penile skin because it was perceived that the high impact of the shower stream would have the effect of a Nikolsky sign. Patients were also asked not to aggressively scrub dry but rather to towel dry by gently patting.

Twelve patients with PV who had involvement of the penile skin are described. (1) The age at onset of PV ranged from 36 to 72 years (mean, 56.5 years). (2) Of the 12 patients, 10 had involvement of the scalp, face, upper torso, and upper extremities. These 10 patients had approximately 10% to 30% body surface area involvement. Two patients did not have any skin involvement. Eleven patients had oral involvement, and 2 had involvement of the esophagus. Involvement of the larynx, epiglottis, and conjunctiva was seen in one patient each. The antibody titers varied from 1:40 to 1:5260. (3) All 12 patients were circumcised. In 5 patients, only the glans of the penis was involved. In 3 patients, only the shaft was involved. In 2 patients, the shaft, corona, and glans were involved. The distribution of these erosions was observed to be only on the proximal glans and the distal part of the shaft. Representative clinical disease in 4 patients is presented in Figure 1. Involvement of urethral mucosa was not observed in any of the patients. (4) The duration of PV before the institution of systemic therapy was 2.9 to 5.5 months (mean, 4.0 months). (5) The duration of the penile erosions after systemic therapy varied from 1.4 to 8.3 months (mean, 3.5 months). (6) The total duration of follow-up was 2.8 to 5.9 years (mean, 4.5 years). All the patients showed a positive clinical response to therapy. (7) During the follow-up, no sequelae secondary to penile involvement were observed. All patients refrained from all types of sexual activity as advised. Penile lesions did not relapse.

Herein, we have described 12 patients with PV with penile involvement. Ten patients had 10% to 30% of cutaneous surface involvement along with mucosal disease. Only 2 patients had PV localized to the oral mucosa. Autoantibodies typical of pemphigus were detected in the serum samples of all 12. Lesions of the glans occurred more frequently compared with those of the shaft and the corona. The duration of lesions differed according to the anatomic distribution. Lesions of the shaft alone resolved in the shortest time (range, 1.4-3.1 months; mean, 1.8 months) compared with those of the glans, which took the longest (range, 1.6-8.3 months; mean, 4.3 months) to resolve. Penile lesions of the shaft, corona, and glans vs the glans and the shaft resolved in the same time (range, 1.6-6.0 months; mean, 3.7 months).

The response of penile skin to systemic therapy in these patients appears to be at the same rate as the response of the skin on other sites of the body (data not presented). All patients were treated with prednisone. In 9 of the 12, immunosuppressive agents were used. Of the 12, 6 were treated with intravenous immunoglobulin because of (1) lack of response to the conventional treatment with prednisone and immunosuppressive agents and/or (2) development of significant adverse effects from such treatments. All the patients received topical care and systemic therapy. We recognize that since patients were treated with systemic and topical therapy, the benefits of topical therapy alone cannot be isolated and objectively evaluated. In all 12 patients, recurrence of penile lesions was not observed during a relatively long follow-up. This could also be a reflection of the clinical course of the disease, or due to the fact that these patients had been advised to avoid skin trauma, such as sexual activity, and other factors that can prolong or exacerbate penile pemphigus. Controls in whom sexual activity was not discontinued would have provided an opportunity to identify this factor's contribution to the permanent resolution of lesions.

Repeated cultures showed expected normal cutaneous flora, probably a consequence of the extensive and aggressive topical therapy used.

Because a tissue diagnosis was established by biopsies of other mucosal sites and/or skin, biopsy of the penile skin to establish a diagnosis was unnecessary. The response to therapy provided additional evidence that the lesions were due to PV.

None of the patients had symptoms of urethral involvement. Urethra examination did not reveal involvement of the meatus. A urinalysis showed no abnormalities with red or white blood cells and casts, and the result of the urine culture was also negative. The lack of urethral involvement could be because the urethral mucosa consists of a columnar epithelium. Most of the urethral mucosa is derived from the embryonic endoderm layer; therefore, it is possible that it may lack desmogleins 1 and 3, present in the skin and other mucosal tissues derived from the ectoderm.⁹

The distal portion of the urethra, lining the navicular fossa, is derived from the ectoderm.⁹ Its lack of involvement might indicate a low density of pemphigus antigen. Sison-Fonacier and Bystryn¹⁰ have reported regional variations of the pemphigus antigen, with the concentration of the antigen severalfold higher on the skin of the axilla, scalp, and buccal mucosa compared with other tested sites. The concentration of these antigens was concluded to be directly proportional to the frequency of anatomic distribution of PV lesions.¹⁰ Desmoglein 3 is probably present in the distal urethral epithelium. However, this is probably a "privileged" site and not involved in the disease process in our patients. Sison-Fonacier and Bystryn did not study the density of pemphigus antigen(s) on normal human penile skin compared with other sites. Therefore, no concrete or definitive conclusions can be made to explain the rarity of penile involvement in pemphigus.

Descriptions of pemphigus of the penile skin are scarce in the reported literature with only 5 such cases having been reported.^{2 - 6} Patients' ages ranged from 32 to 67 years; 4 had PV and 1 had pemphigus vegetans.^{2 - 6} Three patients had pemphigus lesions on other areas of the body; 2 just had penile involvement. The anatomic distribution of erosions in these 2 patients was on the glans, and 1 only on the shaft.^{2 - 4} In 2 patients, the details of the anatomic distribution of the erosions were not provided.^{5 - 6} Four patients were treated with high doses of corticosteroids and immunosuppressive agents.^{2 - 5} One patient was successfully treated with intravenous immunoglobulin since the erosions were nonresponsive to prednisone and conventional therapy.⁶ Two of the patients with penile pemphigus died.^{3 ,5}

None of the patients in the literature were documented to have pemphigus foliaceus. All of our 12 patients had PV. We realize that the small sample size of the study does not permit formation of any objective conclusion. However, a recent study¹¹ demonstrated that neonatal foreskin is protected against pemphigus foliaceus antibody because of the presence of desmoglein 3 and its ability to compensate for any damage to desmoglein 1. Whether such a state exists in adult skin on the penis is not known.

Accepted for publication January 31, 2001.

Corresponding author: A. Razzaque Ahmed, MD, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Ave, Room I-217, Boston, MA 02115 (e-mail: razzaque_ahmed@hms.harvard.edu).