Cutaneous warts are a very common reason for consultation in the everyday practice of dermatologists. Although multiple therapies are available, none of them guarantees improvement and cutaneous warts can become a recalcitrant, disabling, medical problem. Regarding this issue Dr. Megan N. Landis and collaborators have just published their personal experience with a 59-year-old, otherwise healthy lady, who suffered from recalcitrant plantar warts. The lesions had been present for 5 years, and they had been treated with multiple consecutive treatments without success: liquid nitrogen cryotherapy, topical imiquimod 5%, 40% salicylic acid, pulsed dye laser, oral cimetidine, topical tretinoin 0.025%, occlusion by 40% salicylic acid and intralesional bleomycin 1% injections. Based on isolated previous reports Dr.  Megan N. Landis et al decided to administer 3 doses of the recombinant quadrivalent human papillomavirus vaccine types (6,11,16 and 18)  at 0,2, and 6 months (from July 2010 to January 2011). By April 2011 the lesions had completely resolved.

Of course, the authors underline the possibility of spontaneous resolution. However, HPV vaccines may play a role when managing recalcitrant warts in which other therapies do not show efficacy. Certainly, clinical trials are needed to study the issue in depth in terms of efficacy and safety, and to define which patients should be treated.

Do you have a personal experience in this field?.

Recalcitrant plantar warts treated with recombinant quadrivalent human papillomavirus vaccine.

In the last August issue of the Archives of Dermatology Dr. Cristián Vera-Kellet and co-workers have published a very interesting paper focusing on a highly topical subject: Interferon-γ release assays (IGRAs), and their usefulness in dermatology. Indeed, IGRAs have become lately a complement to the tuberculin skin test (TST) in the diagnosis of tuberculosis infection (TB). IGRAs measure responses to the Mycobacterium-specific antigens and they are characterized by their high specificity for Mycobacterium tuberculosis (MT) infection. IGRAs are currently being used as a method to increase specificity in TB diagnosis, mainly in BCG (bacille Calmette-Guérin)-vaccinated individuals, and to increase sensitivity, mainly in immunocompromised patients.

Usefulness of Interferon-γ release assays in the diagnosis of erythema induratum.

Vera-Kellet C, Peters L, Elwood K, Dutz JP.

Arch Dermatol. 2011 Aug;147(8):949-52. PMID: 21844454

Erythema induratum (EI), Bazin disease, is a good example of a cutaneous condition in which MT is very rarely documented by culture or staining procedures. Dr. Vera-Kellet and collaborators communicate in their paper the clinical courses of 5 patients presenting with skin lesions and biopsy findings very suggestive of EI, positive TST and previous TB or BCG vaccination. The authors support EI diagnosis by means of positive IGRAs and response of skin lesions with antiTB therapy. Based on their experience the authors remind us some interesting points:

1. Previous BCG vaccination can result in confounding TST interpretation. IGRAs do not yield false-positive results in patients exposed to BCG or to Mycobacterium avium. Therefore, they are currently being used as the method to test for TB in patients vaccinated against BCG.
2. IGRAs are not useful when dealing with infections caused by Mycobacterium marinum and Mycobacterium kansasii, atypical mycobacterioses, and trying to distinguish them from TB, due to antigen similarities between these organisms.
3. IGRAs may be used in the future to confirm response to therapy and relapses.

In conclusion, Dr. Vera-Kellet et al underline the fact that IGRAs are becoming a new complementary tool in the identification of occult TB, a field of growing concern in the times of tumor necrosis factors inhibitor therapies. In addition, the authors highlight the potential advantages in supporting EI diagnosis in patients with a prior BCG or TB exposure.   

Cutaneous and mucosal warts are a very common dermatological disorder. Their management can be challenging due to the frequent lack of efficacy of standard therapies and significant rate of recurrences. It has already been documented in literature that the intralesional injection of microbial antigens can activate cell-mediated immune responses against human papillomaviruses (HPV), resulting in warts resolution. Recently, Dr. K. H. Kim and co-workers have published a paper in the Archives of Dermatology regarding the efficacy, security and immunologic mechanisms implicated in the treatment of common warts with Candida antigen injections:

Phase 1 clinical trial of intralesional injection of Candida antigen for the treatment of warts.

Kim KH, Horn TD, Pharis J, Kincannon J, Jones R, O’Bryan K, Myers J, Nakagawa M.

Archives of Dermatology. 2010 Dec;146(12):1431-3. PMID: 21173332

The authors intend to deal with the immunologic mechanisms behind Candida injection immunotherapy in depth.

18 patients suffering from at least 2 skin, nongenital, nonfacial warts were enrolled from February 2007 to May 2009. Every patient was treated with an intralesional injection of 0.3 mL of Candida antigen in the largest wart, and then retreated every 3 weeks. Immunologic responses were measured by means of an ex vivo interferon gamma-enzyme-linked immunospot (IFN-γ ELISPOT) assay.

11 patients completed the study protocol. A total resolution of the treated warts was observed in 9 patients (82%), a partial resolution in 1 patient (9%), and an absence of response in 1 patient (9%). 4 injections were needed to observe complete resolution as a median. 6 out of 8 patients (75%) presented with total healing of the first distant untreated warts. Adverse events were limited to pain and erythema at the injection site.

(IFN-γ ELISPOT) assay was performed in 10 patients. 60% of them (6/10) showed a positive response to HPV-57 L1-peptide-(380-412). No responses were found to the Candida antigen. Interestingly, 6 out of 9 patients with positive clinical evolution had a positive response to the L1-peptide. The patient that showed a total absence of response had negative results.

In conclusion, the authors underline the following learning points:

1-      Injections of Candida antigen seem to be safe and can cause important improvement of viral warts by promoting anti-HPV T cell responses.

2-      All of the patients showing immune response to HPV-57 L1-peptide-(380-412), the most frequent one identified, presented with improvement of their warts. Dr. Kim and co-workers suggest that L1-specific T cells may be implicated in wart healing.

3-      Dr. Kim and collaborators propose to incorporate HPV-57 L1-peptide-(380-412) with Candida antigen and to study the combination as a new treatment option for warts.

Of course, the study is limited by the small number of patients enrolled and the absence of a placebo group. Further studies are needed to better define the role of HPV-57 L1-specific T cells.