Herpes vegetans, an atypical herpes lesion in HIV patient: A case report.

Herpes vegetans is a rare form of Herpes simplex virus (HSV) infection in immunocompromised patients that clinically presents as a verrucous and hypertrophic lesion. In this case, we present a 36-year-old man with exophytic verrucous masses in the genital area that was initially suspected as a malignancy. Difficulty to properly diagnose the patient resulted in a few failed attempts at treating the lesion. After excluding other differential diagnoses, the atypical lesion proved to be caused by vegetative herpes infection due to a good response to HSV therapy. Reevaluation of biopsy also showed signs of HSV etiology. Atypical presentation of herpes simplex in immunocompromised patients still proves to be a challenge to diagnose and treat. Proper clinical identification and workup are needed to diagnose and to choose proper regiments. ©Copyright: the Author(s).

Introduction

Herpes simplex virus (HSV) infection is a common infection worldwide, it is caused by 2 types of viruses. HSV Type 1 (HSV-1) infections manifest as mucocutaneous infections, mostly associated with orofacial disease. Meanwhile, HSV Type 2 (HSV-2) is usually associated with genital infections. HSV-2 infections are closely related to extensive genital lesions in different stages of evolution, including vesicles, pustules, and erythematous ulcers that require 2 to 3 weeks to resolve.[1] The global prevalence of HSV-2 infections among persons aged 14-49 years old is 11.9%, which increased especially among patients with co-HIV infection.[2,3]

All manifestations of HSV in an immunocompetent host can be seen in an immunocompromised host, but they are more severe, more extensive, more difficult to treat, and highly recurrent. One uncommon form of chronic HSV infection, verrucous HSV or herpes vegetans, occurs both in patients with advanced AIDS and wellcontrolled HIV.[1] In this variant, the presentation of genital herpes is atypical, which includes chronic ulcerations, papular eruptions, verrucous lesions which are hyperkeratotic, and eroded vegetating plaques that can continue for long periods.[1,4] In this report, we present a case of atypical herpes lesions in HIV that initially mimics malignancy.

Case Report

A 36-year-old man presented with multiple nodules and ulcers on his glans and shaft penis, and pubic area for 4 months prior. He was referred from other dermatologist with squamous cell carcinoma based on fine needle aspiration biopsy (FNAB). The nodules began to spread and formed ulcerations. A thin white layer on top of the wound was developed. The patient was diagnosed with HIV 6 months before the examination and started antiretroviral (ARV) therapy around that period. He had been diagnosed with genital herpes before. The patient also had been taking Itraconazole for one week to treat his tinea corporis. There was a positive history of malignancy in his family, a distant relative of his had bladder cancer. On clinical examination, there were multiple erythematous plaques, nodules, and exophytic verrucous masses which were superficially eroded and covered with slough (Figure 1a). These lesions were found on the penile glans, shaft, and pubic area. The rest of the dermatological and systemic examination was normal. We suspected squamous cell carcinoma with differential diagnosis of condyloma lata, bowenoid papulosis, extramammary Paget’s, and condyloma acuminata.

A 5 mm punch biopsy was performed, which revealed acanthotic epidermis, spongiosis, exocytosis of neutrophils and lymphocytes, and basal layer vacuolization. There were perivascular inflammatory infiltrates composed of lymphocytes, neutrophils, eosinophils, and plasma cells in the superficial and deep dermal layer. Although the histopathological presence of dense inflammatory cells and numerous plasma cells leans toward syphilis, the serologic tests (VDRL and TPHA) showed negative results. Further workup of HPV-genotyping showed positive HPV-DNA but none of the 33 subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 81, 82, 6, 11, 26, 40, 42, 43, 44, 54, 55, 57, 61, 70, 71, 72, and 84). Based on these findings, we still cannot rule out the possibility of malignancy.

One month later, the lesions were exudative and painful. With further discussion, the diagnosis was established as atypical condiloma lata on HIV undergoing ARV therapy. The patient was given two doses of 2,4 million units benzathine penicillin injection with a week interval in between. A wet NaCl 0,9% compress was also recommended. After one week, the verrucous lesion slightly improved but was still wet and itchy.

Four months later, the patient presented again with complaints of new lesions of plaque, nodules, vesicles, and erosion covered with slough and pus at the penile shaft and glans (Figure 1b,c). In the last four months, the patient had sought a second opinion and was given podophyllin tincture and valacyclovir. The lesions dried and were excised. We reviewed the previous biopsy. The tissue showed ulceration, spongiosis, multinucleated giant cells with peripheral rimming, perivascular inflammanb-UVB phototherapy was associated. In May 2019, the psoriasis had further worsened with a PASI of 13. We therefore decided to start a therapy with DMF, recently available in Italy, at increasing dosage as per drug data sheet.

To date, the patient is taking DMF 600mg/day, with good tolerability and complete clinical resolution of psoriasis.

Discussion

Chronic plaque psoriasis is the most common form of psoriasis, affecting about 90% of patients. Nowadays, as a consequence of a better understanding of the pathogenetic mechanisms of the disease, many therapeutic options have become available[2]. Nevertheless, finding the right therapy, especially in complex patients, can still be a challenging task. In moderate to severe psoriasis, the use of systemic therapy is recommended.

In some European countries, fumaric acid esters (FAEs) such as FumadermR, a combination of DMF and monoethyl fumarate salts, have been used for years as a systemic therapy for psoriasis.[3] In this combination, DMF is believed to be the primary active ingredient and responsible for efficacy in the treatment of psoriasis. Therefore in 2017, the European Medicines Agency (EMA) approved SkilarenceR, a new oral formulation of DMF for the treatment of adults with moderate-to-severe chronic plaque psoriasis in need of systemic medical therapy.[2] The safety profile and efficacy of DMF were investigated by the BRIDGE trial,[4] whereas other previous studies had already investigated the efficacy of FAEs in the treatment of psoriasis.[3]

In our patient’s case, the existence of important comorbidities limiting the therapeutic range and the failure of multiple therapies have made the management of his psoriasis particularly complex.

Moreover, the treatment of psoriasis in patients with cancer history is especially difficult: malignancy represents at least a relative contraindication to the use of immunosuppressive drugs such as methotrexate or cyclosporine, while the use of biologics is generally considered with caution in patients that have been cancerfree for at least 5 years.[5] Data in the literature appear to indicate an increased risk of certain malignancies in patients with psoriasis, especially lymphohematopoietic, head and neck, and gastrointestinal tract cancers. There is also an increased risk of nonmelanoma skin cancers (NMSC), possibly as a result of prior therapies such as p-UVA phototherapy or cyclosporine. With regard to biologic drugs, some studies suggest a possible increased risk of NMSC in subjects treated with anti-TNF alpha, while there are no reports about the other molecules.[6] However, there is a lack of long-term safety data regarding newer biologic agents, which leads to a very cautious use of them in patients with a history of cancer. This also tends to cause patients to be managed with topical therapies that are less effective in moderate-severe psoriasis, with a detriment of quality of life.

In this multifaceted scenario, DMF could represent a valid therapeutic choice in terms of safety. In our experience, in fact, DMF is an effective treatment option, generally well tolerated, with few side effects that recede by adjusting the dose or by discontinuation of the drug.

Conclusions

This case is of interest because in patients with many comorbidities, there is a tendency to use only topical therapies or phototherapy even in cases of moderatesevere psoriasis, with deterioration in the patient’s quality of life. Thus, DMF is a valid and safe therapeutic option in patients requiring systemic therapy either as a first line or in case of previous unsuccessful treatments.