Oral Acyclovir and Intralesional Interferon Injections for Treatment of Giant Pyogenic Granuloma–Like Lesions in an Immunocompromised Patient With Human Orf | Allergy and Clinical Immunology | JAMA Dermatology | JAMA Network
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September 2015

Oral Acyclovir and Intralesional Interferon Injections for Treatment of Giant Pyogenic Granuloma–Like Lesions in an Immunocompromised Patient With Human Orf

Author Affiliations
  • 1Department of Dermatology, Peking University First Hospital, Beijing, China
  • 2Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China
  • 3Research Center for Medical Mycology, Peking University, Beijing, China
JAMA Dermatol. 2015;151(9):1032-1034. doi:10.1001/jamadermatol.2015.0760

Orf is a zoonotic infection caused by a parapoxvirus and is widespread in sheep and goats. Human orf, characterized by self-limiting purulent skin lesions at inoculation sites, is caused by contact with infected animals. In immunocompromised patients, orf often exhibits atypical, multifocal, persistent, giant lesions, making treatment frustrating.

Report of a Case

A man in his 40s presented with a 3-month history of 3 rapidly enlarging lesions that developed at the sites of injuries sustained while working with livestock. He had a history of transplantation 3 years earlier and had been taking tacrolimus since that time to avoid rejection. Physical examination revealed 2 exophytic large granulomas on his left thumb (Figure 1A) and forearm (2 × 3 and 3 × 5 cm, respectively) and a red exudative papule on his right forefinger. Histopathologic analysis revealed acanthosis with ballooning degeneration and eosinophilic inclusions (Figure 2A and B) in some keratinocytes as well as abundant blood vessels in the dermis. Transmission electron microscopy showed numerous oval viral particles in degenerated keratinocytes (Figure 2C). Polymerase chain reaction analysis using specific primers described previously1 followed by Sanger sequencing confirmed the diagnosis of human orf.

Figure 1.  Clinical Images of the Thumb Lesion Before and After Treatment
Clinical Images of the Thumb Lesion Before and After Treatment

A, A 2 × 3-cm erosive tumor with bloody crusts developed at the site of an accidental syringe stick on the left thumb. B, Complete resolution of the giant orf tumor after combination treatment with oral acyclovir and intralesional interferon injections left black dots, scars, and crusts.

Figure 2.  Histological Features of Biopsy Specimens From Left Thumb Lesion
Histological Features of Biopsy Specimens From Left Thumb Lesion

A, Acanthosis and ballooning degeneration of keratinocytes and abundant blood vessels with edema and inflammation seen in the dermis (hematoxylin-eosin, original magnification ×100). B, Eosinophilic virus inclusions (arrowheads) found in degenerated keratinocytes (hematoxylin-eosin, original magnification ×400). C, Transmission electron microscopy shows a large amount of viral particles with major axes over 200 nm found in degenerated keratinocytes.

The patient was treated with oral acyclovir, 400 mg every 6 hours, and intralesional interferon alpha-2b injection, 1.5 million IU/wk. Two weeks after the commencement of treatment, remarkable shrinkage of lesions with reduced hemorrhage and exudation were noted. Weekly interferon injections were discontinued at the end of week 6, when all the lesions were resolved, leaving small black scars with crusts (Figure 1B). Acyclovir was given for a further 3 weeks to prevent viral relapse, which has often been documented in orf infection in immunocompromised patients.2 At 1-year follow-up, there were no signs of relapse.


Human orf is a self-limiting disease and usually subsides within 4 to 12 weeks with scarring.3 However, immunocompromised patients are prone to large and refractory orf tumors.2-5 Such rare, atypical forms of orf are frequently associated with the use of posttransplantation immunosuppressants,3,6 such as glucocorticoids, cyclosporine, and tacrolimus. Clinically, the patients often present with pyogenic granuloma like lesions,3,6 as noted in our case.

Treatment of giant orf tumors in immunocompromised individuals typically relies on surgical excision, which is often followed by rapid postoperative recurrence.2,3 To spare patients unnecessary surgeries, a number of topical medications such as idoxuridine,3 cidofovir,4 and imiquimod5,6 have been documented. Among them, imiquimod cream alone or as an adjuvant with surgery appears to have lower recurrence rates, making it the most commonly used topical treatment in recent years.

In the present case, our new, nonsurgical, combined antiviral strategy was based on the following information: (1) Both idoxuridine and acyclovir are nucleoside analogues that competitively inhibit viral DNA polymerases; thus they are used as common antiviral drugs for treatment of different herpesvirus infections. (2) Interferon alpha, in addition to its well-known antiviral properties, has strong antiproliferative and antiangiogenic effects by downregulating vascular endothelial growth factor, which makes it a strong candidate to treat our patient with highly vascularized orf tumors. In view of this information, we started treating the patient with the experimental combined therapy of oral acyclovir and intralesional interferon alpha-2b.

This strategy is minimally invasive and has mild adverse effects. Our patient experienced only low-grade (<38°C), manageable fever at the first night of each injection. Furthermore, the combined therapy took only 6 weeks to completely clear the lesions—one of the shortest recovery periods reported to date (compare several recent imiquimod cream studies, which have reported complete resolution within 6-17 weeks5,6). Nevertheless, further follow-up will be important to find possible signs of orf relapse. More studies are required to confirm the actual effectiveness of acyclovir to inhibit orf virus.

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Article Information

Corresponding Author: Zhimiao Lin, MD, Department of Dermatology, Peking University First Hospital, 8 Xishiku St, Xicheng District, Beijing 100034, China (zhimiaolin@bjmu.edu.cn).

Published Online: May 6, 2015. doi:10.1001/jamadermatol.2015.0760.

Author Contributions: Authors Ran and Lee contributed equally to this report.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by grant YETP0069 from the Beijing Higher Education Young Elite Teacher Project (Dr Lin).

Role of the Funder/Sponsor: The Beijing Higher Education Young Elite Teacher Project had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We are grateful to the patient for participation in this study.

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