Interferon alfa-2b in the management of recurrent conjunctival papillomatosis
Abstract
Conjunctival papillomatosis (CP) is a diffuse and multicentric variant of benign conjunctival papillomas. It is commonly (5%–45%) associated with alfa (α) genus of human papillomavirus (HPV) type 6 and 11 (in children) and type 16, 18, and 33 (in adults), the formers having a low risk for malignant transformation. The infants acquire HPV during delivery while in adults, it spreads through “self-inoculation.”[1] Histologically, these are benign squamous epithelial tumors showing acanthosis of keratinizing or nonkeratinizing epithelium mixed with few goblet and mixed inflammatory cells.[12]
Few clinical features (extralimbal location) and histological markers (presence of goblet cells, no elastosis, and nonkeratinizing epithelium) may point toward its viral etiology.[1] They are larger, multiple and have greater tendency to recur in children as compared to their adult counterparts.[3] The pediatric variant of conjunctival papillomas generally requires surgical intervention secondary to their multifocal, exuberant, and fulminant nature. Recently, literature reports the adjunctive use of interferon alfa-2b (INFα-2b) in topical or local injection form, to prevent recurrences of CP.[456] We report a case of unilateral, diffuse, recurrent CP successfully managed using multimodal therapy (surgical excision, cryotherapy, and local INF therapy) in a child with lamellar ichthyosis.
Case Report
A 2-year-old boy presented to us with a reddish fleshy mass protruding from the inner side of the left eye for 8 months. He underwent an incisional biopsy at a local dispensary 2 months ago, following which there was an increase in the size of mass, spontaneous bleeding episodes, and epiphora. He was a diagnosed patient of classical lamellar ichthyosis and was using skin emollients.
On local examination, a 15 mm × 12 mm, strawberry-like polypoidal mass was observed in the left caruncular region [Fig. 1a]. The left inferior orbital sulcus was full medially, with hemorrhagic matting of eyelashes. The inferior fornix revealed multiple, gelatinous, frond-like lesions originating from both forniceal and tarsal conjunctiva, along its entire length [Fig. 1b and c]. The caruncular mass mechanically obstructed both normal appearing lacrimal puncta. The mucocutaneous junction of eyelid was normal. The child was not cooperative for superior bulbar, palpebral, and forniceal conjunctival examination. Rest of ocular examination was within normal limits.
A clinical diagnosis of diffuse, multifocal CP was made, and topical fortified eye drops of INFα-2b (Injection Zavinex, Zydus Cadila, India) was started QID (1 million IU/1 ml). The child was kept under regular weekly follow-up for 6 weeks, but there was no mass reduction. However, the mass vascularity and spontaneous bleeding episodes reduced markedly after the topical treatment.
In view of no reduction in mass size, a near-total surgical excision of the papillomas with cryo application at each site (2 “freeze-thaw-freeze” cycles) was performed under general anesthesia. Intraoperatively, similar lesions were noted at the superior tarsal and forniceal conjunctiva [Fig. 2a and b]. The gelatinous exophytic masses were excised with Westcott scissors, keeping its blades flush with the conjunctival surface. After cryo application, total 1 ml (3 million IU) of INFα-2b was injected subconjunctivally at multiple sites [Fig. 2c and d]. No abnormal pigmentation or feeder vessel was identified. The inferior conjunctiva and caruncle appeared to be the tumor epicenter.
The histopathology of excised mass revealed multiple pedunculated papillomatous figures with central core of fibrovascular tissue covered by nonkeratinizing epithelium. There was no cellular atypia, and nuclear-cytoplasmic ratio was normal, ruling out any evidence of malignancy. None of the papillomas showed inverted type of configuration. Hence, the final diagnosis was benign CP. Postoperatively, topical 0.5% moxifloxacin (QID) and 1% carboxymethyl cellulose (2 hourly) were prescribed along with topical fortified INFα-2b (1 IU/ml QID) eye drops. In the 1st postoperative week, the child had mild eyelid edema and nasal subconjunctival hemorrhage [Fig. 3a and b]. Topical steroid ointment (HS) was prescribed for 1 week to reduce cryotherapy-induced inflammation. Topical INFα-2b and carboxymethyl cellulose were continued for 12 weeks and then stopped. No oral treatment was given to the child. At 14-month follow-up, the child is symptom-free (no epiphora and spontaneous bleeding episodes), and there are no signs of local recurrence [Fig. 3c and d].
Discussion
The INFs are naturally produced glycoprotein molecules in our body secondary to viral infections and tumors. Of late, these molecules have been employed with significant success in various human diseases, including CP, an uncommon ophthalmological condition. In children, due to the diffuse, multicentric nature, and inferior fornix predilection, the topical fortified INFα-2b eye drops has a potential role. This drug has shown satisfactory results in primary and recurrent CP cases.[367]
In the past, many drugs such as oral cimetidine, 5-fluorouracil, mitomycin-C, local INFα-2b (topical or injection), and long-acting pegIFNα-2b have been used in the management of primary and recurrent CP. All these therapeutic agents mainly played the role of an adjunct to the surgical intervention than isolated therapeutic agents.[378] No-touch technique, excisional biopsy ± cryotherapy, is the surgery of choice. Surgical debulking not only provides instant relief but also reduces the viral load which is rather a difficult job for a short-acting, fortified drug such as INFα-2b. Hence, it is a good option in management armamentarium of surgeon handling recurrent cases. Even after these treatment modalities, the recurrence rate exists between 6% and 27%, more in pediatric CP.[3]
Kaliki et al. have described specific clinical tumor details which might be helpful in monitoring the treatment response, for example, tumor epicenter location (clockwise and quadrant wise), basal dimensions and thickness (in millimeters), configuration, pigmentation, and vascularity (intrinsic and feeder vessels).[3] On PubMed search with keywords - ichthyosis and CP, only single case report in literature is available from year 1988 though no association has been established.[9]
In our patient with classical lamellar ichthyosis and unilateral recurrent CP, the topical INFα-2b eye drops mildly reduced the tumor vascularity which probably eliminated spontaneous bleeding but did not show any regression in tumor size. CP showed remission after near-total surgical excision and cryotherapy along with local subconjunctival injection of INFα-2b. This was supplemented with topical INFα-2b eye drops in postoperative period. We postulate that the postoperative topical INFα-2b eye drops prevent the dislodged viruses to establish and form a nidus at other conjunctival sites, which might lead to multifocal recurrences specifically in pediatric CP.
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Conflicts of interest
There are no conflicts of interest.
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