Severity of human papillomavirus (HPV) infections in immunosuppressed organ transplant recipients (OTRs) is often aggravated, causing physical and psychologic discomfort and increased risk of skin carcinogenesis in these patients, and treatment is often frustrating and ineffective.
Cidofovir (CDV), (S)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cytosine, is an antiviral nucleotide analog with potent effect on DNA viruses including herpesvirus, poxvirus, polyomavirus, and papillomavirus (1, 2). It is licensed for intravenous use in the treatment of cytomegalovirus chorioretinitis in AIDS patients. Reports indicate a promising effect on HPV-induced lesions from intravenous, intralesional, and topical treatment, in normal subjects, immunocompromised, and OTR patients (3). Lack of clinical trials and suspicion of nephrotoxicity has, however, limited its use.
A 13-year-old boy, receiving a renal transplant 2 years earlier, was referred with a history of warts on both hands, debuting shortly after the transplantation. The patient received dual immunosuppressive therapy with mycophenolate mofetil and tacrolimus and was previously treated with thymoglobulin as an induction agent.
Initial treatments of the warts included over-the-counter keratinolytics, cryotherapy, curettage, and topical imiquimod 5% (under surveillance of graft function). None had any effect after 6 months. The warts gradually worsened, and the boy was socially isolated and harassed at school.
Clinical examination revealed a massive “glove-like” affection of classical verrucae on both hands (Fig. 1). After informed consent from the patient and his parents, the patient was scheduled for surgical (curettage) and carbon dioxide laser debulking under general anesthesia followed by topical treatment with CDV.
CDV (1%) was compounded locally from Vistide 75 mg/mL, mixed with propylene glycol, beeswax, sodium lauryl sulfate, cetostearylalcohol, and cleansed water. Light debridement was carried out before each CDV cycle. Each session consisted of 2-hour application of CDV 1% gel directly onto lesions with a 3-mm margin under occlusive dressing, followed by rinsing. The session was repeated daily for 5 days, followed by 9 days pause and clinical evaluation. This cycle was repeated.
Treatment response was remarkable with total clearance of the warts in 4 weeks. Neither local nor systemic adverse events were observed. No changes of glomerular or tubular functions were observed during the ensuing 32 months. Three years after the combined debulking and CDV treatment, no recurrence has been observed.
Our case report demonstrates CDV as an effective and well-tolerated supplementary treatment of recalcitrant, massive warts in an OTR child. Our patient suffered from both psychosocial stress at school and mild functional impairment because of the severity of his infection. Furthermore, HPV infection is believed to increase the risk of squamous cell carcinoma in immunocompromised patients, leading to an increased morbidity and mortality rate in this population (4), which strengthens the need for preventive measures such as vaccines and an effective treatment against overt HPV manifestations.
Recently, reports on CDV treatment of HPV-induced cutaneous warts on the hands and feet in immunocompetent as well as immunocompromised adult and pediatric populations have emerged (5–8). One study involving seven children receiving topical 1% CDV gel on warts on hands and feet included two immunocompromised patients, although one of which failed to clear all lesions (6).
Generally, CDV treatment is well tolerated with most of the adverse effects being described as local discomfort or mild malaise. However, in one patient with chronic renal failure, acute deterioration was observed after topical CDV treatment (9). CDV is known to be potentially nephrotoxic, inducing dose-related caspase-3–driven apoptosis in renal proximal tubular cells (10). This serious side effect should not be neglected with topical treatment modalities, especially on damaged skin and mucous membranes. Consequently, all CDV-treated patients should be followed up closely including monitoring renal (allograft) function. Methods to accurately measure CDV plasma levels are well underway and are likely to see more widespread use in the future (11).
It seems that topical CDV in combination with curettage is a promising modality in the treatment of cutaneous HPV infections and may become an important treatment option in immunocompromised patients or recalcitrant cases, although there is need for further studies to investigate therapeutic efficacy, safety, and cost-benefit of CDV.
Henrik H. Kralund1
Henrik F. Lorentzen1
1 Department of Dermatology and Allergy Centre
Odense University Hospital
2 Department of Nephrology
Odense University Hospital
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