Stalwart approach to stall wart.

Sir,

Immunosuppression is a common feature encountered in palliative care owing to the disease per se and/or the therapy and there is a plethora of adverse effects associated with it. We throw light on a relatively under-rated complication condylomata acuminata and would like to share our clinical experience. A 37-year-old female with a history of allograft kidney transplantation 6 years ago, receiving prednisone and mycophenolate mofetil (later switched to azathioprine), presented with small perianal warty growths from 6 months that have now become confluent and extruding. Local examination revealed a 6×4 cm cauliflower like warty, malodourous growth with an irregular rough keratotic surface in the perianal region [Figure 1]. A biopsy of the lesion was done which showed typical human papilloma virus (HPV) affliction changes with clear vacuolization of prickle cells (koilocytosis), elongation of rete pegs, marked acanthosis, hyperkeratosis, and increased mitotic activity. The diagnosis of condylomata acuminata (CA) was confirmed. The dose of immunosuppressive drugs was decreased and patient was switched to sirolimus. She was started on topical imiquimod (5%) and over the follow up period of 4 weeks, the warty growth showed modest deterioration in size and symptoms.

Figure 1

A cauliflower like warty growth with an irregular rough keratotic surface in the perianal region (condyloma acuminatum)

The HPV serotypes 16 and 18 confer high risk for CA and are most commonly associated with squamous cell carcinoma. The prevalence of CA is higher in the immunosupressed with lower CD4 count (<200 cells/ μL)[1] being one of the important risk factors. There is an increased propensity of cancers of the vulva, vagina, penis and anus, as well as cancers of esophageal, buccal cavity, nonmelanoma skin, lung, bladder, and Hodgkin and non-Hodgkin lymphoma.[2]

Locally, the hallmarks of immunosuppression, such as increased cellular interleukin-10 production, decreased expression of transporter associated with antigen presentation, CD40, and carbonic anhydrase IX, decreased dendritic cell counts, and increased T-regulatory cell infiltration are seen. Forkhead box-P3+ (FOXP3+) regulatory T cells with suppressive function have been shown to accumulate in large warts with high expression of IL-10 and TGF-β1 and low expression of IL-2 and IFN-γ. The chemotaxis of CCL17 and CCL22, derived from Langerhans cells and macrophages in warts, governs such accumulation. The depletion FOXP3+ T cells heightens the responsiveness of wart-infiltrating T cells (both in vitro and in vivo).[3] Human beta-defensin (hBD-2 and hBD-3) expression is significantly upregulated in HPV-associated anal skin lesions.

Low-dose cyclophosphamide post-laser therapy of CA has shown to deplete T regulatory cells and enhance the function of HPV-specific T cells and NK cells in the periphery. Cryotherapy, intralesional interferon, and topical 5% imiquimod coupled with surgical excision have shown promise. Cidofovir with it antiviral, antiproliferative properties and its ability to induce apoptosis improves severe recurrent HPV-induced lesions.[4]

Photodynamic therapy and topical ammonium trichloro (dioxoethylene-O, O) tellurate (AS101) 15% w/w cream[5] have shown benefit. A quadrivalent HPV (6/11/16/18) vaccine decreased the incidence of genital HPV-induced lesions in women.

CA is an entity of a considerable significance that clinicians dealing with the immunosupressed in palliative care could encounter and adequate management can curb the complications.